DIFFERENTIAL DIAGNOSIS AND

MEDICAL THERAPEUTICS
A Treatise on Clinical Medicine
DIFFERENTIAL DIAGNOSIS AND
MEDICAL THERAPEUTICS
A Treatise on Clinical Medicine
SECOND EDITION

P Siva Rama Krishna Rao

BSc MD FICP (India) FIAMS (India) FIMSA (India)
FCCP (USA) FICA (NY) FRSM (London)
Senior Consultant Physician
Formerly Professor and Head
Department of Medicine
Andhra Medical College
First Physician
King George Hospital
Additional Director of Medical Education
Visakhapatnam, Andhra Pradesh, India

Foreword
David R London

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Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

© 2010, Jaypee Brothers Medical Publishers

All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or
by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author
and the publisher.

This book has been published in good faith that the material provided by author is original. Every effort is made to ensure
accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of
any dispute, all legal matters are to be settled under Delhi jurisdiction only.

First Edition: 2000

Second Edition: 2010

ISBN 978-93-80704-95-1

Typeset at JPBMP typesetting unit

Printed at
 To
My Dear Wife, Children, Grandchildren
and
Great Grandchildren
 Foreword to the First Edition

It gives me great pleasure to write a foreword to Common Clinical Challenges—A Treatise

on Maladies and Remedies. The approach adopted by the author should be a great help to
those faced with the management of medical emergencies. The idea of taking symptom
complexes and then describing the diagnostic possibilities with guides to management
both of the disease itself and of the symptoms that is occasions will be valuable to all who
have to deal with problems of this sort.
The demand placed on the medical profession is ever-increasing for a variety of
reasons; the complexity of medical practice steadily increases as more and more diagnostic
and therapeutic possibilities become available, and as populations age so the incidents of
disease increase. Added to these are, on the one hand ever-increasing consumer demand
while, on the other, governments attempt to hold down health care costs. All this means that doctors simply have to raise
their game. This requires a process of continuing professional development to keep up to date and to ensure that
professional performance is kept to an acceptable level. Included in this process is continuing medical education that
nowadays can be derived from a variety of modalities including distance learning. However, despite electronic means of
communication and the visual display unit (VDU), most people find the printed word still the best way of assimilating new
information and Dr P Siva Rama Krishna Rao’s book is an excellent example of this.
My hope is that it will valuable to all who have to deal with the clinical differential diagnosis that he has identified. It
should be of particular use to general practitioners, accident and emergency physicians and indeed all those who encoun-
ter this aspect of medicine. It is the sort of book that should be present not only on the shelf at home and in libraries but
also at all sites where emergency medicine is practised.

David R London
Registrar
Royal College of Physicians of London
United Kingdom
 Preface to the Second Edition

The force that has driven me to bring out yet another edition single-handedly, is the appreciation
supported by encouraging comments from various Professors of Medicine from different corners
within the country and outside as well, apart from the reviews of the reputed Journals.
Owing to the change of the publisher, much time is lost since the first edition of this book
was published. So much so more than the usual amount of revision has been necessitated.
The whole gamut of medicine is covered while discussing all thirty-six challenges with easy
flow for easy uptake.
This book is principally intended for medical students and house-officers to comprehend
what is perceived by them in the wards, besides for those preparing for higher examinations.
The quantity of information furnished is qualitative with essential fast facts. The complexity of clinical medicine is
simplified with a lucid, updated, expanded, account, maintaining the uniform problem-based unique approach, while
retaining the introductory basic concepts of symptom complexes. Two new Appendices are added—one on “Toxicol-
ogy” and the other on “HIV/AIDS”.
I sincerely hope that it will be an invaluable aid to both students (under- and postgraduate) and practitioners to
accomplish clear medical insight and enable one to strike at the diagnosis even while listening to the patient, as the doctor
is taken from bed-to-text unlike from conventional text-to-bed to face such problem-oriented challenges.

P Siva Rama Krishna Rao

 Preface to the First Edition

This book on Common Clinical Challenges—A Treatise on Maladies and Remedies is an expo-
sition of common medical encounters in day practice, by an author with varied experience of
about five decades, right from the days of clinical student of medicine, house officer, postgraduate
student, tutor, assistant professor, professor/head Department of Medical Institutions. The
active involvement in the training programmes for undergraduates and postgraduates and committed
patient care although these years continuously are rich contributing factors in this endeavour.
This manual is a practical clinical guide to diagnosis and principles of treatment of some of
the age old medical problems. The overall emphasis is on clinical access to these problems and
the importance of fundamental clinical skills of history-taking and systemic problem-oriented
physical examination in search of a correct diagnosis is highlighted. In addition, a sensible order
of investigations to be adopted during the diagnostic work-up is detailed, instead of indulging in the endless array of
investigations.
The pattern followed for each symptom runs through basic fundamental concepts, appended causes, essentials of
diseases therein, clinical approach with illustrations wherever necessary, diagnostic flow charts followed by symptom-
atic as well as specific treatment. The student burdened with his ever-crowded curriculum or the practitioner anxious to
keep abreast of the times may find it useful as it is easily readable and assimilable. The guiding principle throughout this
endeavour is to inculcate knowledgeable medical practice enabling the growth of the Doctor’s clinical acumen and
competence to establish an early diagnosis confidently, after which an effective treatment can be instituted.
This is not a textbook of description of diseases to bestow theoretical knowledge, but an attempt to bridge the gap
between theory and practice of medicine and reinforce the ability to apply the knowledge coherently to various clinical
situations. As a matter of fact, any book is likely to become out of date within few years as theory-cum-practice of
medicine is ever-changing and advancing. In such a live science and art of medicine, new concepts and technical
innovations demand voluminous output of information and explanation. Such information has been freely drawn from
many related books and for that matter my own colleagues in various specialities.
The idea of writing such a symptom-oriented approach book is a real challenge, to one who has spent most of his life
in the practice of medicine facing ever so many specific problem areas. I hope all the thirty-six symptoms, specially
identified in relation to day-to-day practice of general medicine, some of which even poorly understood, are presented
with lucidity, in a practical and clinically useful manner, for medical personnel at any stage ranging from an examination
going students to a practitioner or even a matured physician for that matter.
Solid 2500 hours or so are bestowed to bring out this treatise, fulfilling the desired aim of this book. Suggestions
offered to further improve the style and pattern of presentation in subsequent editions will be gracefully acknowledged.

P Siva Rama Krishna Rao

 Acknowledgements

I would like to acknowledge my gratitude to the following Institutions and individuals for their invaluable assistance:
King George Hospital and Andhra Medical College, Visakhapatnam—Department of Cardiology, Department of
Endocrinology and Diabetology, Department of Gastroenterology, Department of Nephrology and Department of Neurology.
Visakhapatnam Port Trust Golden Jubilee Hospital—Dr B Satyanarayana (Chief Medical Officer), Dr GV Suryanarayana
Rao (Deputy Chief Medical Officer) and Dr ML Kasturi (General Physician) who particularly assisted in collection of
some of the illustrations—Dr A Ranga Rao (General Surgeon), Dr PV Rao (Orthopaedic Surgeon) and Dr PK Bhaskara
Rao (Dermatologist).
Bharat Heavy Plates and Vessels Hospital, Visakhapatnam—Dr PS Krupakar (Chief Medical Officer) Dr S Subba Rao
(Deputy Chief Medical Officer), Dr BK Arunabala (Gynaecologist), Dr BK Satyanarayana and Dr K Subrahamanyam
(Medical Officers).
Visakhapatnam Steel Plant Hospital—Dr C Harendra (Consultant ENT Surgeon).
Apollo Hospital, Hyderabad—Dr K Saratchandra (Cardiologist).
Though most of the illustrative material of clinical photographs, radiology and imaging, ECGs, ECHOs, colour
Doppler, isotope scannings, endoscopic pictures, etc. are all personal collections from patient’s records and other sources.
I must particularly thank Dr G Saigopal, Professor of Cardiology and Cardiologist and Dr E Pedaveera Raju, Professor of
Gastroenterology and Gastroenterologist, Andhra Medical College, Visakhapatnam and Dr Vaheesan, VITA diagnostics
Ltd, MR and CT Imaging Centre, Visakhapatnam, who have readily lent some of the illustrations.
I with also to thank Professor DV Krishna Rao, Department of Physics, Andhra University and Professor A Appa
Rao, Department of Computer Sciences, Andhra University for Rendering Photographic Services for offering computer
services in the preparation of flow charts and Dr (Mrs) CH Suguna for assisting drawing of line diagrams.
I am particularly grateful to V Sree Rama Murty for secretarial work throughout the preparation of the primer, but for
whose help probably this gigantic attempt would not have been possible.
I must specially thank Jaypee Brothers Medical Publishers (P) Ltd for having recognised the merits of the presented
material and to have come forward enthusiastically for publishing and for cooperating patiently throughout this period in
bringing out this edition.
 Book Reviews from Distinguished Professors and Journals on
Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Congratulations on your wonderful book Prof BM Hegde

Vice-Chancellor, Manipal Academy of Higher
Education (MAHE), Manipal, Karnataka, India
You have done a good job, presenting clinical Dr V Thiruvengadam
problems in an analytical manner. Former Professor and Head
Department of Medicine
Madras Medical College, Chennai, India
A much needed book in these days of investigations and Dr V Parameshara
invasive medicine. First of its kind published in India—an Consulting Physician and Cardiologist
excellent piece of work. Former President of Association of
Physicians of India (API)
I am sure, the book will be useful for the clinicians Dr Sukumar Mukherjee
in practice in our country. Former Professor and Head
Department of Medicine, Kolkata
President, Association of Physicians of India (API)
I am certain that it is useful book with all your fifty Dr P Krishnam Raju
years of experience distilled into it. Professor of Cardiology, Hyderabad
Organising Secretary, CSI 2001
It is exciting. Congratulations! Dr Manatosh Panja
Professor of Cardiology, Kolkata
Former President of Cardiological Society of
India Association of Physicians of India (API)
Your effort has seen the light of day. You deserve Dr KV Krishna Das
congratulations of this book. Former Professor and Head
Department of Medicine, Trivandrum
Kerala, India
Long felt need…. Dr AK Das
Professor of Medicine and Dean
Jawaharlal Institute of Postgraduate Medical
Education and Research (JIPMER)
Puducherry, India
Former President of Association of Physicians of
India (API)
Problem oriented approach of 36 symptom complexes Dr (Mrs) Sachdev
discussed analytically with good coverage. Former Professor of Medicine
Lady Hardinge Medical College
New Delhi, India
It is a valuable edition in day-to-day clinical practices and Professor Rameshwar L
a good reference for the clinicians of all ranks in their Bang Faculty of Medicine
career endeavour. Kuwait University, Kuwait
xvi Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

The book is responsible for my success in the postgraduate Dr S Udaya

examination (MD—Medicine) along with my friends Nizam’s Institute of Medical Sciences
Hyderabad, Andhra Pradesh, India
It is an excellent and elaborate analysis of the common Dr PD Gulati
symptoms encountered in clinical practice. Editor
Journal of International Medical Sciences
Academy
The book is an honest effort of Senior Medical Teacher to Dr Madhuchand Kan
place on record his experience and judgement in dealing Reviewer, Journal of Indian Medical Association
with various symptom complexes. A practical clinical November 2001
book—will be a useful companion to Medical Practitioners
as well as medical students and even health care
professionals.
Professor Rao with teaching experience of three decades Dr PS Shankar
is successful in providing a clinical guide to diagnosis and Editor
principles of treatment of the listed 36 medical problems. Medicine Update—December 2001
The book is highly recommended to the Medical students
and practitioners. Congratulations!
There is a crying need for a book that deals with day-to- Dr VR Joshi, Emeritus
day Maladies a practitioner faces. Dr Rao has single Editor
handedly produced an important clinical companion. The Journal of Association of Physicians of India
contents reflect amply the depth and width of author’s June 2002
knowledge and clinical skills. The book has its worth as a
ready recknor.
The approach adopted by the author, one of the eminent Professor MV Nagaraj
teachers of our time has proved to be of great help to Reviewer
those with management of common clinical problems British Medical Journal
including medical emergencies. The book is very useful South Asia Edition – June 2002
to all the medical students both undergraduates and
postgraduates, specialists and practicing doctors.
The author has discussed each symptom in fairly good Dr Hariharasubramanian
deal using easy language. To decide on diagnosis and Reviewer
management from the symptoms presented requires in- The Antiseptic—January 2003
depth understanding and in this context, the treatise is
most welcome.
 Contents

1. Acute Abdominal Pain ....................................... 1 Genetic 64

Causes of Acute Abdominal Pain 1 Allergic 65
– Intra-abdominal 2 Paradoxical 65
– Abdominal 5 Factitious 65
– Extra-abdominal 6 Clinical Approach 65
– Psychogenic 7 Treatment of Chronic Diarrhoea 68
Clinical Approach 7
Specific Treatment for Specific Diseases 68
Treatment of Acute Abdominal Pain 12
Specific Treatment for Specific Diseases 12 5. Coma ................................................................... 74
Causes of Coma 75
2. Bleeding Disorders ............................................ 19
– Neurological 75
Classification of Haemorrhagic Disorders 21
– Coagulation Defects 22 – Metabolic 78
– Platelet Defects 24 – Endocrinal 80
– Capillary Endothelium Defects 27 – Tropical 80
Clinical Approach 29 – Toxicological 81
Treatment of Bleeding Disorders 31 – Haematological 82
Specific Treatment for Specific Diseases 32 – Psychiatric 82
3. Chest Pain .......................................................... 39 Clinical Approach 82
Causes of Chest Pain 39 Treatment of Coma 86
– Chest 39 Specific Measures for Specific Causes 87
– Abdomen (Alimentary Affections) 45 6. Cyanosis ............................................................. 94
– Endocrinal 46 Causes of Cyanosis 96
– Psychogenic 46
– Central Cyanosis 96
Clinical Approach 47
– Peripheral Cyanosis 99
Treatment of Chest Pain 49
Clinical Approach 100
Specific Treatment of Specific Causes 49
Treatment of Cyanosis 102
4. Chronic Diarrhoea ............................................ 57 Specific Treatment for Specific Diseases 104
Causes 58
– Inflammatory Diarrhoea 58 7. Dyspepsia .......................................................... 108
– Malabsorption Syndrome and Protein Losing Causes of Chronic Dyspepsia 108
Enteropathy 60 Acute Dyspepsia 108
Neoplasms 62 Alimentary 108
Deficiency States 63 Extra-alimentary 111
Endocrinal and Metabolic 63 Nonorganic 111
Post-Gastrointestinal Surgery 64 Clinical Approach 112
Drugs 64 Treatment of Dyspepsia 113
Functional Colonopathies 64 Specific Treatment for Specific Diseases 113
xviii Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

8. Dysphagia ......................................................... 119 12. Goitre ................................................................ 192

Causes of Dysphagia 119 Causes of Goitre 192
– Stage One 119 – Nontoxic Goitre 193
– Stage Two 121 – Toxic Goitre 194
– Stage Three 122 – Thyroiditis 196
– Stage Four 123 – Benign Neoplastic Nodules 197
Clinical Approach 124
– Malignant Neoplastic Nodules (Malignant
Treatment of Dysphagia 127 Goitre) 197
Specific Treatment for Specific Diseases 127
Clinical Approach 198
9. Dyspnoea .......................................................... 132 Diagnostic Strategy at a Glance 201
Mechanisms of Dyspnoea 133 Treatment of Goitre 201
Causes of Dyspnoea 133
13. Gynaecomastia ................................................. 206
– Cardiovascular 133
– Pulmonary 136 Causes of Gynaecomastia 206
– Alimentary Affections 142 – Physiological Gynaecomastia 206
– Neurological 142 – Pathological Gynaecomastia 206
– Metabolic 142 – Pharmacological (Drugs) 209
– Psychogenic 143 Clinical Approach 209
Clinical Approach 143 Treatment of Gynaecomastia 211
Treatment of Dyspnoea 146 Specific Treatment for Specific Causes 211
Specific Treatment for Specific Diseases 146
14. Haematemesis and Melaena .......................... 216
10. Epileptic Seizures ............................................ 155 Causes of Haematemesis 216
Aetiological Classification of Epileptic Seizures 155 Causes of Melaena 219
International Classification of Epileptic Seizures 156 – Haematemesis 219
Clinical Presentation 160
– Melaena 220
Clinical Approach 163
Clinical Approach 221
Treatment of Epileptic Seizures 167
Treatment of Haematemesis and Melaena 223
Specific Treatment of Specific Diseases 168
Specific Treatment for Specific Diseases 224
11. Fatigue .............................................................. 174
Causes of Fatigue 174 15. Haematuria ...................................................... 230
– Haematological 174 Causes of Haematuria 230
– Metabolic and Endocrinal 177 Local Urinary Tract Diseases 230
– Malnutrition 178 General (Systemic) Diseases 238
– Infections and Inflammatory Disorders 178 Clinical Approach 240
– Neoplasia 178 Treatment of Haematuria 244
– Cardiovascular Disorders 178 Specific Treatment for Specific Diseases 244
– Respiratory Disease 178
16. Haemoptysis ..................................................... 250
– Gastrointestinal Disorders 178
Causes of Haemoptysis 250
– Neurological Diseases 179
– Respiratory 251
– Psychogenic 179
– Asthenic Syndromes 180 – Cardiac 253
– Drugs 180 – Vascular 253
Clinical Approach 180 – Bleeding Diathesis 254
Treatment of Fatigue 183 Clinical Approach 254
Specific Treatment for Specific Diseases 183 Treatment of Haemoptysis 256
 Contents xix

17. Headache .......................................................... 261 Causes of Obesity 330

Causes of Headache 261 – Simple Obesity (Primary) 330
– Vascular Headache 261 – Endocrinal Obesity (Secondary) 330
– Musculoskeletal 263 – Congenital Disorders 332
– Neuritides 264 – Disorders of Adipose Tissue (Lipodystrophies) 332
– Meningeal 264 Drugs 332
– Space Occupying Lesions 264 Complications of Obesity 332
– Altered CSF Flow 265 Clinical Approach 333
– Trauma (Head Injury) 265 Treatment of Obesity 334
– Referred Pain (Reflex Headache) 265
22. Oedema ............................................................ 339
– Anoxaemia 265
Pathogenesis 339
– Psychogenic 266
Causes of Oedema 340
Clinical Approach 266
– Pathological Oedema 340
Treatment of Headache 268
– Physiological Oedema 344
Specific Treatment of Specific Diseases 268
Clinical Approach 344
18. Impotence ......................................................... 275 Treatment of Oedema 346
Anatomical and Physiological Basis of Male Sexual Specific Treatment for Specific Diseases 346
Dysfunction 275
23. Oliguria ............................................................ 352
Causes of Erectile Impotence 276
– Physiological 277 Acute Renal Failure 352
– Pharmacological 277 Causes of Oliguria 353
– Pathological 277 Clinical Essence 354
Clinical Approach 280 Clinical Discussion 355
Treatment of Impotence 282 Clinical Approach 357
Treatment of Oliguria 359
19. Jaundice ............................................................ 287
Metabolism of Bilirubin 287 24. Pain in the Extremities ................................... 364
Classification and Causes of Jaundice 289 Pain in the Upper Extremities 364
– Haemolytic Jaundice 289 Pain in the Lower Extremities 364
– Hepatocellular Jaundice 293 Mechanism of Pain 364
– Obstructive Jaundice 297 – Cutaneous 366
Clinical Approach 299 – Locomotor 366
Treatment of Jaundice 304 – Lymphovascular 368
– Neurological 368
20. Low Backache .................................................. 311
– Referred Pain (from viscrea) 369
Causes of Backache 311
Clinical Approach 369
Spinal Cord and Roots 312
Treatment of Pain in the Extremities 371
Lesions of the Vertebral Column 312
Soft Tissue and Joints 318 25. Palpitations ....................................................... 376
Referred Pain 319 Causes of Palpitations 376
Psychogenic 320 Pathological 377
Clinical Approach 320 Clinical Approach 383
Treatment of Low Backache 322 Treatment of Palpitations 386
Specific Therapy for Specific Diseases 323 26. Paraplegia ......................................................... 391
21. Obesity .............................................................. 328 Causes of Paraplegia 391
Types of Obesity 329 Spastic Paraplegias 392
xx Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Flaccid Paraplegias 396 – Granulomas 472

Clinical Approach 400 – Liver Cirrhosis 473
Treatment of Paraplegia 401 – Hypersensitivity of Drugs 473
Specific Treatment for Specific Diseases 402 – Haematological 473
27. Polyarthritis ..................................................... 408 Others Causes 474
Causes of Oligo and Polyarthritis 409 Clinical Apporach 474
Causes of Monoarthritis 410 Treatment of Pyrexia of Unknown Origin (PUO) 477
Inflammatory Arthrititis (Infectious or Immuno- Specific Treatment for Specific Diseases 478
logical) 410 31. Rashes .............................................................. 483
Degenerative (Mechanical) 417 Causes of Rashes (Generalised Eruptions) 484
Metabolic 418 – Infections 485
Less Common Arthritides 419
– Immunologic 490
Clinical Approach 420
– HLA Related Diseases (Genetic components in-
Treatment of Polyarthritis 423 volved in Autoimmunity) 490
Specific Treatment for Specific Diseases 424 – Tumours 491
28. Polyuria ............................................................ 431 – Drug Eruptions 491
Causes of Polyuria with High Specific Gravity 432 – Idiopathic 491
Causes of Polyuria with Low Specific Gravity 432 Clinical Approach 491
– Diabetes Mellitus 432 Treatment of Rashes 494
– Hypercalcaemia and Hypercalciuria (Calcium Specific Treatment for Specific Diseases 495
Diabetes) 437
32. Shock ................................................................ 501
– Renal Dysfunction 438
Pathophysiology of Shock 501
– Diabetes Insipidus 439
Classification and Causes 502
– Primary Polydipsia 439
Clinical Features of Shock 503
– Hypokalaemia 439
Specific Types of Shock 504
Clinical Approach 439
Treatment of Polyuria 443 Clinical Approach 506
Specific Treatment for Specific Diseases 443 Treatment of Shock 508
33. Syncope ............................................................. 514
29. Pruritus ............................................................ 449
Aetiopathogenesis 514
Causes of Pruritus 450
– Itching Dermatoses (With Obvious Skin Lesions— Types of Syncope 514
usually Localised) 451 Clinical Approach 517
– Itching Dermatoses (Without Obvious Skin Treatment of Syncope 519
Lesions—Generalised) 455 Specific Treatment for Specific Causes 520
Clinical Approach 457 34. Vertigo and Dizziness ...................................... 525
Treatment of Pruritus 459 Causes of Vertigo 525
Specific Treatment 460 Causes of Dizziness 526
30. Pyrexia of Unknown Origin ........................... 468 Vertigo 527
Causes of Pyrexia of Unknown Origin 468 Dizziness 529
– Infections 469 Clinical Approach 530
– Neoplastic (Malignant or Benign) 471 Treatment of Vertigo and Dizziness 534
– Connective Tissues Disorders 471 Specific Treatment for Specific Diseases 535
– Vascular Diseases 472 Treatment of General Medical Disorders 537
 Contents xxi

35. Vomiting ........................................................... 540 Clinical Approach 556

Causes of Vomiting 540 Treatment of Weight Loss 558
– Central Causes 540
Specific Treatment of Underlying Causes 558
– Reflex Causes 542
Clinical Approach 543
APPENDICES
Treatment of Vomiting 546
Specific Treatment for Specific Diseases 546 APPENDIX I: Laboratory Reference Values ..... 565
36. Weight Loss ..................................................... 551 APPENDIX II: Function Tests of
Causes of Weight Loss 552 Diverse Organs ............................................. 572
– Gastrointestinal 552 APPENDIX III: Toxicology (Specific Poisons) 583
– Endocrine and Metabolic 554
APPENDIX IV: HIV/AIDS ................................ 586
– Cardiopulmonary 554
– Renal 554 Suggested Reading ............................................. 591
– Infect/Immunological 554 Index .................................................................. 593
– Malignant Neoplasms 554
– Substance (Drugs and Alcohol) Abuse 555 Note: Algorithms for decision-making detailed at the end
– Psychogenic 556 of individual chapters.
 List of Illustrations

1. Radiogram of small bowel obstruction 36. Gastroscopic view of duodenal ulcer

2. Ultrasound scan of cholelithiasis 37. Barium radiograph of gastric carcinoma
3. Ultrasound scan of renal calculus 38. Abdominal CT scan of polycystic kidney
4. Ultrasound scan of acute pancreatitis 39. Microscopic appearance of urinary deposits
5. Diagram of coagulation pathway 40. Skiagram chest of bilateral pulmonary tuberculosis
6. Clinical photograph of vascular purpura 41. Skiagram chest of lung abscess (RT)
7. Electrophoretogram in health and disease 42. Skiagram chest of carcinoma bronchus (RT)
8. Diagram of coronary circulation 43. Thoracic CT scan of bronchogenic carcinoma (LT)
9. Electrocardiogram of subendocardial infarction 44. Magnetic resonance angiography showing microan-
10. Electrocardiographic patterns of acute myocardial eurysm of the left internal carotid artery
infarction 45. Cranial CT scan of meningioma (LT)
11. Echocardiogram of mitral value prolapse 46. Cranial CT scan of glioma of corpus collosum
12. Radiogram of Peptic ulcer perforation 47. Clinical photograph of hypogonadotrophic hypogo-
13. Electrocardiogram of exercise induced ischaemia nadism before and after treatment
14. Myocardial perfusion scintigraphy with thallium 48. Normal bile pigment metabolism
15. Diagram of developmental stages of Entamoeba 49. Ultrasound scan of the amoebic abscess of the liver
histolytica 50. Abdominal CT scan of cholangiocarcinoma
16. Barium enema roentgenogram of ulcerative colitis 51. Diagram of biliary tract
17. Diagram of normal metabolism of bile salts 52. Endoscopic retrograde cholangiopancreatography
18. Diagram of carotid-vertebral-arteries and circle of (ERCP) of choledochal cyst as compared to normal
Willis ERCP
19. Cranial CT Scan of intracerebral haemorrhage and 53. Abdominal CT scan of carcinoma of the pancreas
cerebral infarction 54. Diagram of root compression due to disc prolapse
20. Diagram of normal and abnormal pupils 55. Diagram of lumbosacral spine showing disc prolapse
21. Skiagram chest of Fallot’s tetralogy 56. MRI of the lumbosacral spine showing disc prolapse
22. Colour flow Doppler of ventricular septal defect 57. Radiogram of osoteoarthritis of lumbar spine
23. Radiogram of pancreatic calculi (Calcification) 58. Radiogram of skull in multiple myeloma
24. Diagram of normal swallowing mechanism 59. Diagram of pathophysiology of oedema
25. Radiogram of carinoma of the oesophagus 60. Clinical photograph of periorbital oedema due to
26. Skiagram chest of emphysematous bulla dermatomyositis.
27. Spiral CT showing interstitial lung disease 61. Diagram of cervicobrachial plexus
28. Skiagram chest of pleural effusion (RT) 62. Radiograph of cervical spondylosis
29. Diagram of spirogram in health and disease 63. Diagram of thoracic outlet and sites of compression
30. Photograph or Wright’s peak expiratory flowmeter 64. Radiograms of bilateral cervical ribs and surgical re-
31. Cranial CT scans of tuberculoma and neurocysticer- moval of the offending left rib
cosis 65. Diagram of conduction of cardiac impulse
32. Diagram of microscopic appearance of abnormal 66. ECG patterns of extrasystoles
blood cells 67. Electrocardiogram of atrial fibrillation
33. Thyroid scintiscan of nodular goitre 68. Electrocardiogram of atrial flutter
34. Clinical photograph of adolescent gynaecomastia 69. Electrocardiograms of supraventricular
35. Endoscopic view of oesophageal variceal bleeding tachycardias
xxiv Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
70. Diagram of cross-section of spinal cord
71. MRI of intramedullary ependymoma
72. Diagram of sagittal view of knee joint
73. Skiagram of hand in rheumatoid arthritis
74. Diagram of LE cell phenomenon
75. Arthroscopic view of villonodular synovitis of knee
76. Diagram of structure of nephron
77. Diagram of blood glucose curves in oral GTT
78. Ophthalmoscopic appearances of diabetic retino-
pathy
79. Intravenous pyelogram showing dilatation of pelvis
and calyces of left kidney with megaureter
80. Diagram of action times of different insulins
81. Clinical photograph of lipodystrophy of right deltoid
with insulin therapy
82. Diagram of structure of normal skin
83. Clinical photograph of papular urticaria
84. Electrocardiogram patterns of pulmonar embolism
85. Electrocardiogram of partial heart block
86. Electrocardiogram of complete heart block
87. Electrocardiograms of ventricular tachycardia and fi-
brillation
88. Electrocardiograms of risk sinus syndrome before
and after pacing
89. Diagram of labyrinth and vestibular pathways
90. Diagram of caloric responses in health and disease.
 Chapter
1 Acute Abdominal Pain
Abdominal pain of sudden onset is a challenging task in
clinical practice, as early diagnosis and prompt relief, without
clouding the picture and loss of precious time, are the principal
responsibilities of any clinician. Acute abdomen connotes
acute illness of short duration with clinical features confining
to the abdomen predominantly. This may be of abdominal or
extra-abdominal origin. The acute abdomen need not always
find its way to the surgical wards since certain medical
conditions may simulate the same very much. Usually, it is
associated with vomiting with or without shock.
Three different types of pain are involved in the spectrum
of abdominal pain, i.e.
i. Visceral
ii. Somatic
iii. Referred.
The pain arising from hollow or solid viscera is termed
visceral or splanchnic. It tends to be deep, diffuse and full
(solid organ) or colicky (hollow organ) with poor localisation.
Pain originating in the abdominal wall and parietal peritoneum
is called somatic pain, which is well localised and sharp.
Referred pain is one in which visceral disease gives rise to
localised pain, apparently superficial, usually away from the
site of the diseased viscus and often dermatomic.
The mechanism of abdominal pain is:
a. Parietal due to inflammation
b. Visceral due to obstruction and/or with inflammation
c. Muscular (smooth muscle spasm)
d. Vascular (ischaemia, haemorrhage)
e. Referred pain and
f. Psychogenic pain (functional).
The inflammation or ischaemia lowers the pain threshold
by releasing some chemicals like bradykinin, histamine,
prostaglandins, serotonin and lactic acid. The other stimulus
includes increased tension in the wall of the viscus due to
distension or contraction.
The painful impulses are mediated over somatic nerves
supplying the parietal peritoneum or visceral afferent nerves
accompanying the abdominal sympathetic nerve fibres.
Pain may be referred to the abdomen due to disease of
thorax or genitalia or spine, since the visceral sympathetic
nerve fibres share the neural pathway, with the somatic nerve
fibres arising from the same spinal segment. A careful
analysis of abdominal pain and the sequential events of the
episode form the diagnostic pathway, to arrive at a correct
diagnosis in the majority of cases.
CAUSES OF ACUTE ABDOMINAL PAIN
In order to obtain a clear insight, the causes can be grouped
as: (i) intra-abdominal, (ii) abdominal, (iii) extra-abdominal,
(iv) psychogenic (Table 1.1).
Table 1.1: Aetiological classification of acute abdominal pain
I. Intra-abdominal
Pain may arise from peritoneum, viscera or mesentery due to:
1. Inflammations
2. Mechanical (obstructive colics) or
3. Vascular disturbances
1. Inflammations
A. Peritoneal: Acute peritonitis: Infective or perforative
B. Visceral
a. Hollow organs
i. Gastroduodenal (peptic ulcer)
ii. Biliary tract (biliary colic, acute cholecystitis,
cholangitis)
iii. Intestinal (acute appendicitis, acute gastroenteritis,
diverticulitis, colitis, intestinal colic).
b. Solid organs
i. Pancreatic (acute pancreatitis)
ii. Renal (acute pyelonephritis)
c. Pelvic organs: Pelvic inflammatory disease (PID)
C. Mesentery: Acute mesenteric lymphadenitis
Contd...
 2 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Contd... Palpation reveals board like muscular rigidity, tenderness

2. Mechanical and rebound tenderness (peritonism). Auscultation may
A. Visceral reveal absent bowel sounds. Progressive abdominal
a. Hollow organs distension, ileus and shock may follow. Plain X-ray of
i. Intestinal (intestinal obstruction) the abdomen in an erect position reveals air under the
ii. Biliary tract (biliary obstruction) diaphragm. In addition, distension of both bowels, with
iii. Ureteral (ureteric colic)
fluid levels or fluid between the loops of the bowel giving
b. Solid organs: Renal (pelvi-ureteric junction, Dietl’s
crisis) a thickened appearance, may be present. Secondary
c. Pelvic organs peritonitis due to a ruptured viscus from peptic ulcer is
i. Torsion of the ovarian cyst acute in onset, localised peritonitis may develop
ii. Ectopic pregnancy gradually to generalised peritonitis if it is due to infection
B. Mesentery: Omental torsion like appendicitis or diverticulitis, or salpingitis.
3. Vascular Trauma or systemic lupus erythematosis or acute
A. Ischaemic mesenteric vascular occlusion are the other causes of
i. Mesenteric (angina, infarction)
peritonitis.
ii. Splenic (infarction)
iii. Hepatic (Budd-Chiari) Visceral
iv. Sickle cell crisis • Peptic ulcer, biliary colic, acute cholecystitis and
B. Bleeding cholangitis (Refer to Chapter ‘Chest Pain Dyspepsia,
i. Ruptured ectopic pregnancy
Haematemesis and Jaundice’).
ii. Ruptured graafian follicle (Mittelschmerz)
iii. Ruptured spleen Acute appendicitis: This is one of the most common causes
iv. Ruptured mesentery of acute abdomen. There is a typical history of central
v. Ruptured aortic aneurysm abdominal pain of short duration with nausea or vomiting
II. Abdominal and mild rise of temperature. The pain may be colicky in
1. Bornholm’s disease
character and may be followed by a shift to right iliac fossa.
2. Nerve entrapment
3. Haematoma of rectus sheath It gets sharply localised and causes discomfort on coughing
4. Abdominal hernias or moving. Well localised tenderness to one finger and slight
5. Referred pain. muscular rigidity are elicitable over MacBurney’s point.
III. Extra-abdominal Cough, tenderness, rebound tenderness, tachycardia,
1. Cardiopulmonary (Acute myocardial infarction, pneumonia, obturator test (pain is elicited when right hip is flexed and
diaphragmatic pleurisy, Pneumothorax, mediastinal internally rotated) and neutrophil leucocytosis are valuable
emphysema) for arriving at a diagnosis. The pain is poorly localised and
2. Neurological (herpes zoster, radiculitis, spinal lesions, e.g.
may not shift if the appendix is retrocaecal (loin) or pelvic
tabes)
3. Genital (torsion of the testicle) or retroileal. Abdominal X-rays are helpful in these atypical
4. Metabolic (diabetic ketoacidosis, acute porphyria, C’L Esterase cases. Localised air-fluid levels or increased soft tissue
inhibitor deficiency) density in the right iliac region is seen in 50% of the cases
5. Alcohol, drugs and metals (lead poisoning) of early appendicitis. Ultrasound examination of the
6. Hip joint disease abdomen is also of immense value in diagnosing appendi-
IV. Psychogenic citis. Any delay in the diagnosis leads to complications like
gangrene, perforation, peritonitis/abscess.
INTRA-ABDOMINAL Acute gastroenteritis: Acute gastroenteritis generally
presents as profuse watery diarrhoea and vomiting with
• Inflammations fever. There may be acute abdominal pain localised
Peritoneal especially in Salmonella gastroenteritis due to intestinal
• Acute peritonitis: It is characterised by severe abdominal inflammation and colic. The other common pathogens are
pain with the conspicuous presence of a quiet picture enteric viruses, and Shigella and staphylococcal food
and absence of any restlessness. Vomiting with or poisoning. In severe cases, there may be dehydration,
without fever and diminished respiratory excursions of prostration and collapse.
the abdominal wall are the other presenting features. Diverticulitis (Refer to Chapter ‘Chronic Diarrhoea’).
 Acute Abdominal Pain
Colitis: It may be general or localised to one segment
involving the mucous membrane and submucous tissue.
In acute colitis, there may be diarrhoea with blood and
mucus, and paroxysms of colicky pain. This may be a result
of specific infections of the bowels from food, water or septic
foci or due to toxaemias like uraemia or acute exacerbations
of amoebic colitis.
Intestinal colic: Intestinal colic may produce severe
intermittent abdominal pain due to tension or spasm of the
smooth muscle. This is colicky in nature with freedom from
pain between the attacks. It can be due to inflammation as
seen in acute enteritis, or due to intestinal obstruction or
lead poisoning or as a functional disturbance in spastic colon.
Acute pancreatitis (Refer to Chapter ‘Chest Pain’).
Acute pyelonephritis: It is characterised by a sudden onset
of pain in the loin radiating down to the iliac fossa and
hypogastic region. Fever with rigor, urinary symptoms (like
dysuria, strangury and frequency) and tenderness in the renal
angle are the striking features. It is due to acute inflammation
of the parenchyma and pelvis in the kidney as well, due to
infections like E. coli with or without obstruction of the
urinary tract. The diagnosis can be confirmed by urinalysis
particularly the microscopic examination, which reveals
numerous pus cells, few red cells and epithelial cells with
or without motile bacteria.
Pelvic inflammatory disease (PID): Acute pelvic inflammatory
disease may present as lower abdominal pain sometimes
severe cramp like, particularly, in either or both the iliac
fossa as in salpingitis, fever, vaginal discharge, dyspareunia
and urinary symptoms. On examination there is adnexal
tenderness, tenderness on cervical motion or rebound
tenderness of the lower abdomen. Inflammatory mass may
be found on pelvic examination. There may be a past history
of menstrual irregularities or abortion. PID is due to the
ascending spread of organisms from the genitalia or
endogenous species in the genital tract. The diagnosis is
confirmed by obtaining cultures from the fallopian tubes,
cul-de-sac and endocervix at laparoscopy or a sonogram.
Mesentery
• Acute mesenteric lymphadenitis: It is characterised by
diffuse abdominal pain with tenderness in the lower right
quadrant and fever due to enlarged lymphadenitis at the
root of the mesentery. The exact site of pain cannot be
indicated and the point of maximum tenderness varies
from time to time. Leucocytosis with relative
lymphocytosis may be present. It is usually nonspecific
and filariasis may be the causative factor. Children and
3
young adults are usually affected and it has to be
differentiated carefully from acute appendicitis.
• Mechanical
Visceral
• Intestinal obstruction: The failure to facilitate the onward
passage of the intestinal contents is called intestinal
obstruction. A distinction must be made between the
obstruction of mechanical origin (dynamic) and paralysis
of the intestinal muscle (paralytic ileus) (i.e.) Peristalsis
is absent or it may be present in non-propulsive form
e.g. mesenteric vascular occlusion or Pseudo-obstruction
(adynamic). Intestinal obstruction can occur either in
the small intestine or large intestine. The obstruction
may be at one point (simple) or at two points (closed
loop).
Mechanical, nonstrangulating obstruction of the
small intestine results in central abdominal pain, which
is colicky at the outset and tends to become constant
few hours later, particularly in the low small bowel
obstruction. This is followed by vomiting, the frequency
and faeculent nature of which depends on the level of
obstruction. In higher obstruction of the small bowel,
vomiting is an early feature which may be profuse and
not faeculent. Constipation and ostipation with failure
to pass gas per rectum is present if there is complete
obstruction and sometimes it may be preceded by
diarrhoea. Visible peristalsis may be seen in thin
individuals especially during colicky episodes.
Abdominal distension is minimal in higher obstruction
and more in lower obstruction. Mild tenderness may be
elicited. A palpable mass due to tense fluid in the loop is
suggestive of closed loop strangulated obstruction.
Auscultation may reveal rush of bowel sounds
(peristaltic activity). Signs of dehydration and
hypovolaemia may set in due to absorbed toxins and
sequestration of large volume of fluid in obstructed
bowel.
Strangulation is suspected when shock appears
during the course of obstruction. Previous cramping pain
assumes continuous character. High fever and peritonism
may develop. Most of the strangulations occur in the
closed loop variety.
X-rays of the abdomen in supine as well as upright
positions show ladder like pattern of distended small
bowel loops with air fluid levels (Fig. 1.1). There will
be no gas in the colon in nonstrangulating obstruction.
A widened space between the dilated bowel loops due
to intraperitoneal fluid is seen in simple obstruction and
 4 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 1.1: Plain X-ray of the abdomen in erect position showing
distended small intestine loops with fluid levels—small bowel
obstruction
strangulation as well. Loops due to intraperitoneal fluid
and thumb printing, absence of mucosal pattern and gas
within the bowel wall may be seen in strangulation.
Large bowel obstruction also presents as above but
for its slow onset, pain of less intensity in the lower
abdomen, delayed vomiting with faeculent odour and
significant marked distension. Obstipation and
continuous abdominal pain of severe intensity suggest
strangulation and a tender mass may be palpable in
closed loop strangulation.
Abdominal X-rays, in colonic obstruction, may
show distension with gas proximal to the block, and
without gas in the rectum. If the ioeocaecal valve is
incompetent, it may appear like a small bowel
obstruction.
The common causes of small intestinal obstruction are:
a. Adhesions due to previous operations
b. Internal and external hernias
c. Intussusception
d. Occlusion of superior mesenteric artery;
e. Mesenteric panniculitis
The common causes of large intestinal obstruction are:
a. Carcinoma of the bowel
b. Diverticulitis
c. Volvulus
d. Occlusion of inferior mesenteric artery
Paralytic ileus: It is characterised by absence of colicky
abdominal pain and bowel sounds. Abdomen is
distended and vomiting is frequent. Peritonism may be
present. It accompanies inflammatory abdominal
condition (intraperitoneal sepsis), postoperative periods,
intestinal ischaemia or associated with low cardiac
output states.
Plain X-ray shows dilated colon and the gas is present
throughout the bowel including rectum.
• Biliary obstruction (Refer to Chapter ‘Chest Pain’).
• Ureteric colic (Renal pain): In renal colic, the pain
radiates from the loin to the groin and testicle or labia.
There will be restlessness, groaning in agony, sweating
and vomiting. The intensity reaches the peak in 30
minutes and usually subsides within two hours. This is
usually due to stone in the pelvi-ureteric junctions or
ureter or vesicoureteric junction. Sometimes, this may
be an inaugural symptom of acute pyelonephritis. Urine
may show plenty of red blood cells and crystals (oxalate)
or pus cells and protein.
• Dietl’s crises: They are characterised by severe pain
down the ureter radiating to the back and are uncommon.
Fever with rigors, nausea or vomiting, haematuria and
shock may be the associated features. There may be a
history of constant dragging pain due to a movable
kidney with a traction on the renal plexus. The crises
are due to kinking of the ureter. A floating kidney usually
feels larger and its shape with the easy mobility are highly
suggestive.
• Torsion of the ovarian cyst: Any severe abdominal pain
in a known patient of ovarian cyst should suggest torsion
of the ovarian cyst. Pelvic examination may not be
helpful because of marked tenderness. Nevertheless, it
may be palpable during pelvic examination under
anaesthesia.
• Ectopic pregnancy (Vide infra.)
Mesentery
Omental torsion: Torsion of the omentum occurs when it
gets caught up in the opening of a hernia or fixed by
adhesions with consequential twist and impaired blood
supply. It is characterised by severe abdominal pain and
tenderness over the affected area with nausea and vomiting.
The twisted omentum may be felt as a mass on palpation.
• Vascular
Ischaemic
• Mesenteric angina (Chronic intestinal ischaemia):
This is an uncommon cause of abdominal pain. If
superior mesenteric artery is stenosed, it is termed as
 Acute Abdominal Pain
intestinal angina and if two or more major arteries are
affected, it is known as abdominal angina. However, this
has to be considered in aged patients who have evidence
of atherosclerosis with angina pectoris or intermittent
claudication. The pain starts at the mid-umbilical region
30 minutes after food and persists for two hours. There
may be diarrhoea and loss of weight. Only angiographic
demonstration of more than 50% of narrowing of the
major arteries will be diagnostic.
• Mesenteric infarction: Severe abrupt onset of colicky
and progressively constant pain located in periumbilical
area with minimal abdominal signs is the inaugural
symptom in the early stage. Fever, bloody diarrhoea,
bleeding per rectum, tenderness and blood in the
nasogastric tube aspirates or vomitus may develop due
to infarction. In addition, signs of intestinal obstruction
may follow and eventually generalised peritonitis with
hypovolaemic shock occurs. Previous history of
abdominal angina may be forthcoming. The mesenteric
infarction occurs in the superior mesenteric artery with
small bowel obstruction or inferior mesenteric artery
with large bowel obstruction and may be due to
myocardial infarction or atrial fibrillation. Raised
phosphate concentration in the serum of peritoneal fluid
is suggestive. X-rays show thumb printing in the lumen
of the colon due to mucosal oedema. Intramural gas or
gas in the portal venous system may occur late.
• Splenic infarction: Infarction of the spleen may be
aseptic or septic. The pain is attributed to perisplenitis.
The septic infarction may lead to splenic abscess which
may burst giving rise to generalised peritonitis.
• Budd-Chiari syndrome: It is suspected when there is
sudden pain over the liver with vomiting, tender
hepatomegaly and ascites (with rapid filling after
paracentesis). Absence of hepatojugular reflux is highly
suggestive.
• Sickle cell crisis: The painful crisis like abdominal crisis
(biliary colic) or chest (pulmonary infarction), localised
(bones and joints) may occur in sickle cell anaemia due
to microinfarcts as a result of vaso-occlusive process.
(Biliary colic may also be due to possible cholelithiasis).
The crisis consists or severe, sudden abdominal pain of
chest or joints, sometimes associated with fever. The
tender rigid abdomen may be mistaken for a surgical
illness. The presence of normal bowel sounds, absence
of rebound tenderness and demonstration of sickling are
diagnostic. Crisis can also be from marrow aplasia due
to parvo viruses or sequestration wherein rapid enlarge-
ment of liver and spleen occur due to trapped RBCs.
5
Bleeding
• Ruptured ectopic pregnancy: Ectopic implantation is
tubal in majority of the cases. Acute severe lower
quadrant pain of sudden onset is the usual presentation
in a woman with history of amenorrhoea or recent
menstrual irregularity. Vaginal bleeding with or without
passage of decidual tissue and a tender palpable
pelvimass outside the uterus are the cardinal features.
The important complications are haemorrhage and
shock. Plain X-ray of the abdomen may reveal a pelvic
mass and culdocentesis demonstrates haemoperitoneum.
• Ruptured graafian follicle: Sudden onset of severe pain
in the middle of the menstrual cycle in a young female,
apparently not looking ill with no gastrointestinal
symptoms, is suggestive of rupture of the graafian
follicle. The pain sequence is characteristic in being
severe initially and fading gradually (Mittelschmerz).
• Ruptured spleen: The acute abdominal pain in the left
upper quadrant or referred pain to the left shoulder or
cervical region (Kehr’s sign) due to diaphragmatic
irritation usually elcited by palpating left quadrant or by
adopting Trendlenberg decubitus. Tenderness over the
9th and 10th ribs or increased splenic dullness or
abdominal distension may be present. Hypovolaemic
shock may be associated. There is usually, a history of
abdominal trauma. Plain X-ray of the abdomen may
show medial displacement of the gastric air bubble or
inferior displacement of the transverse colon.
• Ruptured mesentery: Haemorrhage may be due to
spontaneous rupture of the mesenteric arteries leading
to haemorrhage in the peritoneal cavity (mesenteric
apoplexy). The characteristic picture will be the sudden
onset of diffuse abdominal pain followed by hypoten-
sion. There is diffuse tenderness and distension due to
peritoneal irritation and free fluid in the peritoneal cavity.
• Ruptured aortic aneurysm: Aorta may increase in length
or diameter or both and the resulting aneurysm may be
painful or even rupture. Severe abdominal pain radiating
to the legs together with features of shock may appear.
Femoral pulses may be absent and an expansile pulsating
swelling may be seen in the abdomen. A loud continuous
murmur is heard if it has ruptured into inferior vena cava.
If the rupture occurs into retroperitoneal tissues,
manifestations due to loss of blood may be mild initially.
ABDOMINAL
• Bornholm disease (Refer to Chapter ‘Chest Pain’).
• Nerve entrapment: A nerve can be entrapped by a
nonabsorbable suture and may cause pain in the
 6 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
abdominal wall like causalgia. Hyperaesthesia of the skin
over the dermatome is highly suggestive.
• Haematoma of rectus sheath: Haematoma in the rectus
sheath may usually appear as a swelling in the lower
quadrant due to trauma or anticoagulants or bleeding
diathesis. Sudden abdominal pain with nausea and
vomiting are the presenting features. A tender mass can
be palpated which becomes more distinct on raising the
head. Ultrasound examination helps localisation.
• Abdominal hernias: A protrusion of the intra-abdominal
tissue through a defect in the abdominal wall includes
inguinal hernia, femoral hernia, umbilical hernia or
epigastric hernia (Fatty hernia of the linea alba) or
incisional hernia (ventral) and Spigelian hernia. This
hernial mass is made up of outer coverings of skin, etc.
a peritoneal sac and any viscus. The neck of the sac is
narrow which may endanger strangulation of the
protruding bowel. In all cases of abdominal pain, careful
inspection and palpation of the hernial orifices, umbilical
area, linea alba above the umbilicus, incisional areas
and lateral border of the rectus muscle may become
imperative.
• Referred pain: Any visceral pain may be referred to
superficial areas of the abdomen away from the affected
viscus or area. The classical examples are myocardial
infarction, diaphragmatic pleurisy or spinal lesions or
diseases of hip joint and genitalia. Pain is referred to
cutaneous root areas which are innervated by the same
segments supplying the painful viscus. It may or may
not be associated with cutaneous hyperalgesia.
EXTRA-ABDOMINAL
Cardiopulmonary
Acute myocardial infarction, pneumonia, diaphragmatic
pleurisy, pneumothorax, and mediastinal emphysema. (Refer
to Chapter ‘Chest Pain’).
Neurological
Pain arising from posterior roots is of lancinating or burning
character and precipitated by body movements or coughing.
It is caused by inflammation in herpes zoster (preceding the
eruption or postherpetic neuralgia) or compression in spinal
tumours or disc prolapse or degeneration in tabes dorsalis.
The gastric crisis in tabes is uncommon now and characte-
rised by attacks of epigastric pain of short duration
associated with vomiting which is due to increased motility
and muscle spasm of the viscus.
Genital
Torsion of the testicle: Testicular pain is so sudden that the
patient is unable to walk. On examination, the scrotum is
enlarged with rubor. Testis is elevated, transversely placed
and exquisitely tender. The duration influences the speed
of infarction and so, it has to be recognised early enough to
save the testis. Four hours is the said limit after which the
testis is damaged irreversibly.
Metabolic
In any obscure abdominal pain, the metabolic causes may
have to be entertained.
Diabetic ketoacidosis: Abdominal pain may be present with
vomiting and abdominal rigidity especially in children.
The pain may be shifting with variable intensity and is
attributed to dryness of the endothelial surfaces. Examina-
tion of urine for sugar and acetone will clinch the diagnosis.
Acute intermittent porphyria: Acute colicky abdominal pain
with vomiting and constipation may accompany porphyria,
which is rather uncommon. Examination of the urine will
help in the diagnosis by the presence of elevated
porphobilinogen (PBG). The urine turns deep red on
standing and PBG is detected by Ehrlich’s Reagent which
forms a red complex that cannot be extracted with butanol.
Rare genetic disease due to (autosomal dominant conditions)
error in haem biosynthesis.
C’l Esterase inhibitor deficiency: This deficiency may be
associated with attacks of severe abdominal pain with
angioneurotic oedema. This hereditary angio-oedema is an
autosomal dominant condition and is suggested by the family
history, attacks of laryngeal oedema besides colicky
episodes. Urticarial lesions may or may not be present.
Sometimes, this deficiency may be seen with
lymphoproliferative disorders. Diagnosis is confirmed by
low serum levels of CI inhibitor and C4 levels.
Alcohol, Drugs and Metals
Alcohol and drugs have been incriminated in the
development of pancreatitis. Heavy alcoholic bouts may
precipitate acute pancreatitis. Chronic alcoholism may result
in atrophy of the acini due to obstruction by the proteinacious
plugs in the small duct. Antimetabolite drugs like L-
Asparginase are associated with pancreatitis.
Lead poisoning: It can result in crampy diffuse abdominal
pain accompanied by vomiting and constipation probably
due to effect of lead on smooth muscle. Diagnosis of lead
poisoning is confirmed by:
 Acute Abdominal Pain
i. Occupation history
ii. Punctate basophilic stippling of the red cells
iii. Associated features of anaemia and wrist drop (lead
palsy)
iv. Increased levels of corpoporphyrin or, delta-amino
levulinic acid or lead concentrations.
Hip Joint Disease
Certain diseases (acute bursitis) of the hip joint may produce
pain radiating into the lower quadrant but the examination
of the hip joint helps to clarify the diagnosis.
Psychogenic
Sometimes abdominal pain may be perceived without any
obvious cause especially in emotionally disturbed young
females or hysterics. Psychogenic pain varies erratically in
intensity and location without any specific character. There
are no associated features of vomiting and constipation or
tenderness or spasm of the abdominal musculature. On the
other hand, features of conversion reaction or dissociation
reaction may be perceptible. Nevertheless, psychogenic pain
is not entertained in acute abdomen unless organic causes
are eliminated with absolute concrete evidences.
Some malingerers travel from place to place seeking
hospital admissions by picturesque acts of illness in whom
multiple laparotomy scars may provide the clue. This is a
classical example of Munchausen syndrome of malingering.
CLINICAL APPROACH
Acute abdomen is a temple of surprise and the clinician’s
primary responsibility is to assess the extent of critical illness
and decide whether possibility of any immediate surgery,
without undue delay, is necessary. For this, careful history,
which by itself reflects underlying pathology and critical
physical examination to determine the direction of
investigations, so as to arrive at a correct diagnosis, should
be endeavoured.
Analysis of Pain
Is pain associated with shock or not is an important
observation before analysing the pain?
Location
Enquiry must be made regarding the site of the pain initially
and any shift of the pain thereafter. This depends on the
organs involved in general:
a. Epigastric: Perforated peptic ulcer, acute pancreatitis,
acute myocardial infarction.
7
b. Right Upper Quadrant: Acute Cholecystitis, biliary
colic, initial stage of acute appendicitis (retrocaecal),
pancreatitis, pneumothorax.
c. Right Lower Quadrant: Acute appendicitis, intestinal
obstruction, renal colic, salpingitis, ruptured ectopic
pregnancy.
d. Umbilical or periumbilical: In affections of small
intestine.
e. Left Upper Quadrant: Pancreatitis, renal pain, splenic
infarction or rupture, acute myocardial infarction.
f. Left Lower Quadrant: Obstructive lesions of the colon,
diverticulitis, renal colic, ectopic pregnancy.
Well localised pain implies inflammation of the
peritoneum in relation to the area affected (vide supra).
Poorly localised or diffuse pain is suggestive of acute
peritonitis, mesenteric vascular occlusion, sickle cell crisis
and intestinal obstruction.
Character
a. Colicky intermittent pain suggestive of spasm or
obstruction and arises usually from a hollow viscus.
The pain is not aggravated by movement. The classical
examples are intestinal colic (acute enteritis, intestinal
obstruction, lead poisoning), biliary (Fig. 1.2) and
ureteric, colics.
b. Gnawing pain suggestive of ulcer.
c. Excruciating pain suggestive of infarction or rupture.
Intensity
a. Is it severe and constant? e.g. mesenteric vascular
occlusion.
b. Is it agonising with intervals of remission (colicky)?
Fig. 1.2: Ultrasound scan of the abdomen showing
cholelithiasis
 8 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
c. Does the intense pain suddenly disappear sponta-
neously? e.g. rupture of a hollow viscus.
d. Is the pain slight to begin with and steadily increasing
in severity? e.g. peritonitis.
Duration
a. If duration is brief—suggestive of colics.
b. If present for more than six hours—invariably
suggestive of surgical problems like inflammations
or neoplasms.
Radiation
Pain from gallbladder disease may be radiated to right tip
of the shoulder or inferior angle of scapula. Renal colic may
arise from back and travels through lumbar region and is
radiated to the testicle or labia (Fig. 1.3).
In pancreatitis, pain radiates to the back (Fig. 1.4).
Aggravating Factors
a. Fatty food may initiate biliary colic.
b. Heavy meal may herald acute pancreatitis.
c. Movement aggravates pain in peritonitis.
d. Pain is aggravated during menstruation in PID.
Relieving Factors
a. Epigastric pain present in the lying position and
relieved by sitting, is suggestive of pancreatitis.
b. Hypogastric pain associated with diseases of sigmoid
colon may be relieved by passing motion or flatus.
Fig. 1.3: Ultrasound scan of the abdomen showing
calculus in the left kidney
Fig. 1.4: Ultrasound scan of the abdomen showing swollen
pancreas and ill defined peripancreatic fat planes in the region
of the body and tail, suggestive of acute pancreatitis
Associated Symptoms
a. Pain with shock occurs in perforative peritonitis, acute
pancreatitis, acute intestinal obstruction, acute
enteritis, internal haemorrhage (ruptured ectopic
pregnancy or solid viscera due to trauma or aneurysm),
mesenteric vascular occlusion, torsion of the ovarian
cyst, and acute myocardial infarction.
b. Restlessness is present in colics whereas the patient
is very quiet, because of possible pain during any
movement in peritonitis.
c. Nausea and vomiting accompany most cases of acute
abdomen. The frequency of vomiting; the amount of
vomits and its colour; faeculent character; time of onset
of vomiting in relation to pain (occuring early in high
obstructions and late in the low obstructions, preceding
onset of pain as in enteritis; or pain preceding vomiting
by few hours as in appendicitis).
d. Bowel function: If the bowels have not moved for two
days and no gas has been expelled (obstipation), it is
suggestive of obstruction. If a feeling of constipation
and the need for enema is felt, it is suggestive of classic
or retrocaecal appendicitis (gas stoppage sign). If
diarrhoea is associated, it is a manifestation of acute
enteritis or in the early stages of machanical obstruc-
tion. If it is bloody diarrhoea, it is ischaemic colitis.
e. Dysuria or haematuria in renal colic.
f. Pyrexia: Fever is not usually high in appendicitis.
Chills and high fever may be due to infections of renal
or biliary tract.
 Acute Abdominal Pain
Clues from History
a. Any past history of indigestion, peptic ulcer disease,
dysentery, jaundice, gallstones, haematemesis and
melaena, haematochezia or diabetes mellitus.
b. Drug history
c. Alcohol ingestion
d. Trauma
e. Menstrual history
Physical Examination
Age and sex
If the acute abdomen is seen in a child then it is intussuscep-
tion; adolescent, (appendicitis) middle age, (cholecystitis
or diverticulitis) and old age (neoplasms).
Acute abdomen in women usually may be of gynaecolo-
gical origin.
General Examination
a. Decubits: Gnawing or rolling in the bed (colic); hip
flexed (PID).
b. Facies: Anxious looks or agonising appearance or
Hippocratic facies.
c. Skin: Pallor, sweat or signs of dehyderation.
d. Any jaundice or anaemia.
e. Vital data
1. Pulse: Rate and volume of all peripheral pulses.
2. Respiration: Whether it is abdomino-thoracic with
normal excursions or purely thoracic (peritonitis)
or any decrease in any phase of respiration.
3. BP: Hypotension suggestive of shock.
4. Temperature: Fevers are associated with
inflammatory causes.
Examination of the Abdomen
a. Inspection of any operation scars.
b. Movement of the abdomen (immobile in peritonitis).
c. Contour: Retracted or distended abdomen. If retracted,
then suggestive of peritonitis and scaphoid perforated
duodenal ulcer; if distened, epigastric (pyloric
obstruction); central, (small intestine obstruction) and
flanks, (colon obstruction).
d. Visible peristalsis
1. Gastric peristalsis: In pyloric stenosis, peristaltic
waves travel left to right and the dilated stomach
is at a lower position than normal.
2. Small intestine peristalsis: Waves are central in
position and there are to and fro movements.
9
3. Large bowel instruction: The visible peristalsis is
less and the colonic distensions is seen in
transverse colon with right to left movement.
Palpation: Ask the patient to point out the area of
maximum pain. Examine the hernial orifices both inguinal
and femoral canals. By gentle palpation, note for tenderness
or rigidity or any mass in the abdomen. Gaurding may be
encountered, which is voluntary or involuntary, and the latter
is due to peritoneal inflammation or perforation of viscus.
If rebound tenderness is elicited (by exerting pressure with
the hand over the painful region and suddenly releasing the
pressure when sharp pain is felt), it is suggestive of
inflammation of viscus or perietal peritoneum. Coughing
may also elicit rebound tenderness without the need for
palpating hand. Well localised tenderness may be felt by
one finger palpation.
Hyperaesthesia and hyperalgesia of the skin in the
original area or segmental area of referred pain may be
elicited by superficial palpation. Masses can be detected by
deep palpation.
If both rigidity and tenderness are present, it is suggestive
of peritonitis. If only tenderness is present without rigidity,
it is suggestive of inflammation of the intestines, e.g.
gastroenteritis without peritonitis.
Percussion: Gentle indirect percussion with the first over
the anterior chest wall on either side elicits sharp pain if
there is inflammation between diaphragm and liver or
diaphragm and stomach or diaphragm and spleen.
Obliteration of liver dullness is suggestive of perforation.
Presence of free fluid is detected by shifting dullness. If the
percussion note is resonant, it is suggestive of obstruction.
Auscultation: If the peristaltic sounds are absent even
after auscultating for three minutes (silent abdomen), it
indicates diffuse peritonitis. Intermittent peristaltic tinkling
sounds with free intervals, synchronising with episodes of
pain (noisy abdomen), are suggestive of mechanical
intestinal obstruction.
Abnormal peristaltic sounds not synchronising with pain
is seen in gastroenteritis. A succussion splash is heard over
the abdomen in pyloric obstruction which may have to be
differentiated from the splashing sound observed in normal
individuals after a meal.
Special Signs
a. Cullen’s sign: Faint blue discolouration around the
umbillicus due to haemoperitoneum.
b. Grey-Turner’s sign: Brownish green discolouration in
the loins in certain cases of pancreatitis.
 10 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
c. Murphy’s sign: Palpation of right upper quadrant during
deep inspiration may hold up the breathing if there is
inflammation of the gallbladder.
d. Boas sign: Area of hyperaesthesia in infrascapular area
in gallbladder disease.
e. Courvoiseer’s sign: Distended palpable gallbladder
due to compression of common bile duct.
f. Iliopsoas sign: If the pain is elicited when the patient’s
thigh is flexed against the resistance of the examiner’s
hand, it is suggestive of inflammation of Iliopsoas
muscle.
g. Obturator sign: When the thigh is flexed to right angle
and rotated internally or externally, it may produce
pain if there is strangulated small bowl in the obturator
canal or sometimes in pelvic inflammation or
appendicitis.
Rectal and pelvic examination: Rectal examination must
invariably be done to elicit any tenderness of pelvic perito-
neum due to peritonitis, or a ballooning feeling obstruction
or pelvic abscess. Vaginal examination is helpful to assess
the state of pelvic peritoneum or ectopic pregnancy. So is
the importance of examination of scrotum.
Examination of chest: This must be carefully examined
for diagnosing intrathoracic causes, producing upper
abdominal pain like pleurisy or cardiovascular degenerative
disorders.
Examination of CNS: Careful inspection for tenderness
over the spinal column is beneficial to diagnose abdominal
pain due to vertebral disease and nerve roots. Sometimes
hypersensitivity can be elicited in the back and front of the
trunk in certain situations of irritation of peritoneum.
Reviewing the changes or progress of the clinical
features often, during the course of the abdominal episode
may be rewarding.
Investigations
Urine
a. Albuminuria and cellular deposits like pus cells and
RBCs suggest urinary tract infection or RBCs alone
Nephrolithiasis.
b. Urine is allowed to stand for six hours and if it darkens,
it indicates porphyria.
c. If sugar and acetone are present, suspect diabetic
ketosis as a cause of abdominal pain.
d. Bile pigments and urobilinogen in urine indicate
hepatobiliary disease.
Motion
a. Intestinal parasites like roundworm ova and EH Cysts
may be present.
b. Presence of blood and white blood corpuscles may be
due to Salmonella enterocolitis.
c. Faecal lipase is high in acute inflammations of
pancreas.
d. Occult blood may be seen in cases of haemorrhage
with perforation.
Blood
a. High haematocrit values suggest dehyderation and low
values indicate existing anaemia or bleeding.
b. Leucocyte count may be helpful especially in the
progressively rising count which indicates progress
of the infective process. Polymorphonuclear leuco-
cytes suggests appendicitis whereas low count with a
relative lymphocytosis may be seen in viral
gastroenteritis.
c. Low RBC and haemoglobin percentage suggest
bleeding.
d. ESR is raised in infections.
e. Sickle cell preparations: Sickling suggests haemolytic
crisis.
f. Electrolytes: Serum sodium and potassium may
indicate the amount of the fluid loss.
g. Serum bilirubin (both direct and indirect): if indicated.
h. Blood sugar.
i. Blood urea and serum creatinine.
j. Enzymes.
i. In acute pancreatitis, serum amylase is elevated
due to sudden release into the bloodstream which
is normally earmarked for the duodenum. This is
also seen in bowel perforation or obstruction or
perforation of peptic ulcer.
ii. SGOT raised in obstruction of common bile duct
with cholangitis and early cardiac infarction.
iii. LDH and CPK raised in cardiac infarction.
iv. CL esterase.
k. Ratio of renal clearance of amylase and creatinine is
elevated in acute pancreatitis (normal 1 to 4%).
It is calculated as:Cam /Ccr Ratio = Urine amylase/
Serum amylase × Serum creatinine / Urine creatinine
×100%
l. Night blood for microfilaria or QBC for M.F. may be
useful to diagnose mesenteric lymphadenitis.
 Acute Abdominal Pain
Peritoneal fluid
a. Test for blood and pus.
b. Elevated amylase levels are highly diagnostic of acute
pancreatitis.
Radiology
A. Plain films of the abdomen
a. Erect position: Presence of abnormal gas shadows or
gas-fluid levels are highly diagnostic.
(Normally gas is present in the fundus of the stomach
and throughout the large bowel, although it may be
visible in the small bowel occasionally).
i. Gas beneath the diaphragm is seen in perforation
of peptic ulcer. If present underneath both the
diaphragm, it is suggestive of colonic perforation.
ii. Dilated loops of small bowel with horizontal fluid
levels, without gas or much less than normal, in
the large intestine are suggestive of small bowel
obstruction.
iii. Presence of gas proximal to the block and no gas
seen in the rectum is suggestive of colonic
obstruction.
iv. Marked dilatation and rotation of sigmoid or
caecum are suggestive of volvulus.
v. Distension of both small and large bowels
(including the rectum) with copious gas or
retention of large amounts of gas and fluid in the
dilated loops of the small and large bowels, and
absence of ‘J’ loops (as compared to presence of
the same in obstruction) are characteristic of a
dynamic ileus.
vi. Abnormal opaque shadows (gallstones, renal
calculi, pancreatic calcification or calcified
faecolith as seen in acute appendicitis) may be
encountered.
vii. Obliteration of psoas shadow indicates retro-
peritoneal haematoma or abscess.
b. Supine abdominal X-ray: Look for shifting fluid levels.
c. Left lateral decubitus film: Shows minimum amount
of air in the peritoneal cavity. This X-ray is particularly
useful if the patient is unable to remain in the erect
position for minimum 10 minutes which in necessary
to demonstrate air under the diaphragm.
B. Contrast films
a. If biliary pathology is suspected, oral cholecystogram
or cholangiogram or Endoscopic Retrograde Cholangio
Pancreatography (ERCP) may be undertaken.
11
b. ERCP is also useful for pancreatic pathology (should
not be done in acute pancreatitis).
c. If renal cause is suspected, IV pyelogram, may be
done.
d. In gastrointestinal pathology
i. Barium meal (avoided in intestinal obstruction)
is performed.
ii. Barium enema (avoided in perforation and
peritonitis) done, when colonic obstruction is
suspected, to identify the type and location. A
patent appendix rules out acute appendicitis.
Barium enema has to be done cautiously since
the dangers of perforating an inflammatory lesion
like diverticulitis or appendicitis or changing a
partial colonic obstruction to complete obstruc-
tion, exist.
iii. Gastrografin (nonbarium radio-opaque substance)
may be useful to diagnose upper gastrointestinal
tract pathology
C. Skiagram chest PA view and lateral views are useful
particularly in acute abdomen due to extra- abdominal
causes.
D. X-ray of the spine at the suspected level (if necessary)
is done.
ECG
ECG should be taken to rule out myocardial infarction as a
cause of acute abdomen.
Special Investigations
a. Ultrasound scanning is useful in gallstone, close loop
obstruction and intussusception. Focussed high resolution
ultrasound useful for appendicitis, diverticulitis.
b. CT scanning is useful in acute pancreatitis or its compli-
cations, localisation of abscesses or detecting abdominal
injuries like lacerations or subcapsular haematomas.
c. Radionuclides scanning is not routinely done. It may
help in localising intra-abdominal abscess.
d. Endoscopy (upper GI endoscopy or lower GI endo-
scopy), sigmoidoscopy or colonoscopy should be
reserved for discriminatory use.
e. Culdocentesis and culdoscopy.
f. Angiograms are useful in diagnosing subcapsular rupture
of a solid organ or site of obstruction or bleeding in
mesenteric vessels (not done routinely).
The clinician must exclude nonsurgical conditions
arising from systemic diseases, be it thoracic or abdominal.
 12 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
If no definite diagnosis is established, laparotomy may be
the only tool for the ultimate diagnosis. Of course, this has
to be undertaken only when ‘wait and see’ policy for an
optimum period does not yield any positive inference.
TREATMENT OF ACUTE ABDOMINAL PAIN
Successful treatment of acute abdominal pain depends
entirely on precise diagnosis, a real challenge, since the list
of both surgical and nonsurgical conditions is long, be it
intra-abdominal or extra-abdominal. Most often an overlap
of pain characteristics is encountered. It is further
compounded either by a medical condition mimicking as
“acute abdomen” or by its critical catastrophic nature. Hence,
the clinician must be alert in identifying the origin of noxious
stimulus for pain which may be due to inflammation, spasm,
obstruction, or perforation/rupture. Other associated features
also contribute substantially to the analysis of pain; be it
arising de novo or transgressing from a chronic low type to
an acute intense type.
• Immediate Management
1. When the diagnosis is in doubt, it is rewarding “to
look and see, than to wait and see”; reexamine the
abdomen and observe for any progression of symp-
toms, without risking undue delay. Simultaneously,
appropriate radiological investigation or ultrasound
examination may be undertaken.
2. The opinion of the surgical colleague shall be sought
to assess the real need for any immediate surgical
intervention, preferably after eliminating medical
conditions (avoid unnecessary delay in operation or
unjustifiable surgery, which is equally harmful).
3. Since many acute abdominal conditions are associated
with fluid and electrolyte imbalances, appropriate
intravenous fluid therapy is instituted, monitoring
haemodynamic status. It is better not to give anything
orally. Pass nasogastric tube (“Drip and Suck”).
4. Shock, if present, is treated with inotropic agents when
volume replacement fails to restore adequate
circulation. (Vital signs are to be monitored. Refer to
Chapter ‘Shock’).
5. Analgesics: Narcotic analgesics must be withheld,
pending diagnosis, since the valuable diagnostic signs
may be masked, delaying the necessary therapy.
Analgesics without sedation may be considered.
However, the pitfall of disappearance of pain,
worsening the disease and endangering patient’s life
must be kept mind while offering symptomatic relief
for pain. The temptation is better resisted.
6. Antispasmodics: If the pain is due to colic and if
severe, suitable antispasmodics like atropine, propan
the line, hyoscine, dicylomine, drotaverine are
beneficial. It should be borne in mind that disappear-
ance of pain may mislead the clinician and in the
meanwhile, the disease may worsen.
7. If acid peptic disease is suspected, antacids, H2
receptor antagonists, proton pump inhibitors and/or
anticholinergics may be considered.
8. Nasogastric tube is inserted for decompression so as
to prevent any further distension or aspiration
pneumonia during anaesthesia. Fluid aspirated
continuously must be measured for purposes of
optimum fluid administration. (In paralytic ileus fluid
is yellow and of less quantity, i.e. I- 2 L/d as against
intestinal obstruction it is dark brown or black and or
more quantity. It is to be managed with appropriate
fluid and electrolyte replacement).
9. If any history of constipation is forthcoming, flatus
tube is passed or soap and water enema considered.
No purgatives shall be given.
10. Antibiotics: They are better withheld till diagnosis is
fairly settled, since they may conceal the true
perspective of the disease or even its complications.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
Intra-abdominal
Inflammations
Acute peritonitis: Treatment of peritonitis depends upon
whether it is primary (spontaneous) which is rare, or
secondary to acute infection or perforation of viscus, and
includes control of infection, correction of fluid imbalance,
restoring, normal intestinal motility and maintaining
nutrition.
a. Preoperative supportive measures are:
i. Bed rest in Fowler position.
ii. Start appropriate fluid therapy immediately
(normal saline and/or Ringer lactate); parenteral
feeding may be required.
iii. Associated shock should be combated (oxygen
therapy with or without inotropic agents).
iv. Nasogastric suction to be done. Nothing is given
by mouth. Oral intake is allowed only when
suction is discontinued.
v. Establish adequate urinary output (fluid
requirements are to be estimated from the urinary
output and nasogastric aspirations).
 Acute Abdominal Pain
vi. Effective antibiotics are initiated as soon as the
diagnosis is made (blood cultures may be obtained
and type-specific antibiotic better administered).
vii. Analgesics: Narcotic analgesics like morphine are
valuable once diagnosis is definite.
viii. If paralytic ileus is persistent, intestinal decomp-
ression is done by Miller-Abbott’s tube. (The long
intestinal tube is pushed into small bowel-
duodenum).
b. Operative: Surgical removal of the source of contami-
nation like inflamed appendix, perforated bowel or
gallbladder, together with peritoneal toilet and lavage.
Intestinal decompression may be employed.
The sequel of peritonitis is localised abscess
formation at the primary site either in the subphrenic
or pelvic region which is treated by surgical drainage;
supplemented with appropriate antibiotics and
metronidazole parenterally.
c. Postoperative: Necessary preoperative measures must
be continued. Blood transfusion may be required for
anaemia.
Peptic ulcer (Refer to Chapters ‘Dyspepsia and Haematemesis’)
Treatment of perforation of peptic ulcer includes insertion
of nasogastric tube and emptying the stomach, antibiotics,
combating shock are the nonsurgical measures. Laparotomy
and simple closure is routine measure hitherto. But
vagotomy and gastroenterostomy or partial gastrectomy are
preferred when general condition is good in the absence of
purulent peritonitis.
Biliary tract
a. Biliary colic
i. Anticholinergic drugs like dicyclomine hydro-
chloride relieve smooth muscle spasm.
ii. Narcotic analgesics (morphine - 10 mg i.m.) may
be required, though they cause spasm of the
sphincter of oddi which can be countered by
simultaneous administration of atropine (0.6 mg
i.m.). Pentazocine (30 mg) or buprenorphine (0.3
mg) are other parenteral alternatives.
iii. Low fat diet.
b. Acute cholecystitis
i. Bed rest.
ii. Nasogastric suction especially if the vomiting
persists.
iii. Pain is relieved using analgesics (morphine or
pentazocine).
iv. Maintain fluid balance.
v. Antibiotics (cephalosporin and metronidazole).
13
vi. Prompt cholecystectomy is undertaken if the pain
and tenderness spread with tachycardia, otherwise
an elective cholecystectomy planned after
complete recovery usually 2-3 months later.
c. Cholangitis
i. Appropriate antibiotics are chosen.
ii. Biliary drainage may be attempted (Refer to
Chapter ‘Jaundice’).
Intestinal
a. Acute appendicitis
i. Appendectomy is the treatment of choice, though
early cases recover spontaneously with or without
antibiotics.
ii. Nasogastric suction prevents distension of the
stomach.
iii. Fluids are given if necessary.
iv. Antibiotics and analgesics are withheld preferably
before operation though they are mandatory at the
time of surgery and thereafter.
v. If appendicular mass is present without other
abdominal signs, conservative treatment is
preferred.
vi. Surgical intervention is necessary when pulse rate
rises, pain spreads and gastric aspirations are
copious.
b. Acute gastroenteritis
i. Fluid replacement and appropriate antibiotics like
ciprofloxacin are administered.
ii. Loperamide is beneficial in controlling diarrhoea.
iii. If any food poisoning is suspected, stomach wsh
is given and the contents are to be kept for
analysis.
c. Diverticulitis
i. High fibre diet with bran and bulky laxatives help
constipation.
ii. Treatment of acute diverticulitis includes bed rest,
nasogastric suction (nothing by mouth), intra-
venous fluids, antibiotics like cefuroxime, and
metronidazole and antispasmodics. If severe,
blood transfusion may be needed.
iii. If unresponsive surgery is undertaken (colectomy
and end to end anastomosis).
iv. If obstructive features or any complications occur
after the acute attack, elective surgery is indicated.
d. Colitis
i. Treatment of acute catarrhal colitis is same as
acute gastroenteritis.
 14 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
ii. Ischaemic colitis may subside with conservative
management.
iii. Surgery may be necessary in a few cases, if
peritonitis or stricture develops.
e. Intestinal colic: Since the colic is due to distension
and spasm of the bowel, antispasmodics like
dicyclomine or atropine relieve the spasm and the
distension by passing a flatus tube. Apart from this,
the underlying cause of the intestinal colic (ranging
from improper diet to intestinal obstruction) must be
carefully explored and treated accordingly.
Acute pancreatitis
a. Relieving pain and combating impending shock are
the essentials of treatment depending on mild or
fulminant nature.
b. Pain is relieved with narcotic analgesics like pethidine
or pentazocin.
c. Morphine is better avoided since it causes spasm of
sphincter of oddi.
d. Oral feeds are to be withheld at least for 48 hours.
e. Nasogastic suction is done till distension subsides and
peristalsis returns (also eliminates vomiting).
f. Shock is managed as detailed in Chapter—Shock.
g. Early oxygen supplementation controls hypoxia. If
shock lung (acute respiratory distress syndrome)
results, mechanical ventilation and Positive End-
Expiratory Pressure (PEEP) must be established.
h. Antibiotics administered to prevent secondary
infection as well as H2 receptor antagonists for stress
ulceration.
i. Intravenous calcium gluconate is given if
hypocalcaemia and tetany occur.
ii. Parenteral nutrition may be required to avoid
secretory stimulation in prolonged illness.
iii. Peritoneal lavage with catheters used for
peritoneal dialysis may not be of much value.
iv. Surgery is necessary for pancreatic abscess,
extensive necrosis or rapidly enlarging pancreatic
pseudocyst (fluid usually in lesser sac).
i. Aprotinin (70 mg slowly IV for 10 minutes
followed by 28 mg very 4 hours for 2 days).
(This is an inhibitor of proteolytic enzymes as
well as plasmin).
Pyelonephritis (Refer to Chapter—Haematuria).
Pelvic inflammatory disease: The preferred regimen of
ceftriaxone 2 g IV 12 hourly (or equivalent of cephalosporin)
followed by doxycyline (100 mg b. d. for two weeks) relieves
symptoms caused by commonly incriminated organisms like
N gonorrhoeae, chlamydia and preserves the tubal function.
Alternative choice is clindamycin (900 mg IV 8th hourly)
and gentamycin (1.5 mg/kg 8 hourly) followed by
doxycycline (100 mg b.d. for two weeks).
Surgery is necessary for ruptured tube-ovarian abscess
or drainage of the pelvic mass pointing to cul-de-sac.
Acute mesenteric lymphadenitis: Short bouts of periumbilical
pain lasting few minutes may be relieved by bed rest. Most
of these infections mimic appendicitis. If operation is
performed, inflamed lymph nodes and bowel are apparent.
Some prefer to do appendectomy under such circumstances.
If it is due to filariasis, treat with diethylcarbamazine, and
antibiotics.
Mechanical (Colics—Obstruction and acute
distension)
Intestinal obstruction: Treatment of intestinal obstruction
includes decompression by gastrointestinal suction,
replacement of fluid and electrolytes and supplementing with
antibiotics before relieving the obstruction surgically. Small
intestine obstruction and paralytic ileus can be managed
conservatively (nasogastric decompression till flatus is
passed) in the initial stages at least, whereas strangulation
and large bowel obstruction need immediate surgery. If the
small intestine is strangulated, blood-stained fluid in the
peritoneal cavity is removed by suction, and the strangulated
segment is resected followed by anastomosis.
Pyridostigmine (60-240 mg tds) is useful in paralytic ileus.
If the obstruction is in the large intestine (usually due to
malignancy), appropriate surgical measures depending on
the site of obstruction and general condition of the patient,
either hemicolectomy, ileotransverse enterostomy or left iliac
colostomy, are to be undertaken.
Sigmoid volvulus is treated by sigmoidoscopy and a soft
rubber tube is coaxed into the twisted loop to deflate the
gut, failing which deflations is attempted after laparotomy
followed by resection and end to end anastomosis.
Biliary obstruction (symptomatic cholelithiasis) Sympto-
matic treatment is indicated with antispasmodics and
narcotic analgesics for biliary colic. Administer antibiotics
if cholangitis is associated. If the biliary colic is recurrent,
surgery is imperative (cholecystectomy and choledo-
chostomy if necessary and endoscopic papillotomy with
calculus extraction).
 Acute Abdominal Pain
Gallstone induced pancreatitis or gallstone ileus due to
stone ulcerating into the gut and obstructing is treated
appropriately (Refer to Chapter ‘Jaundice’).
Medical dissolution with Ursodeoxy Cholic acid (8-15
mg/kg/24 h orally for 2 years) recommended for small
stones, which are radiolucent, and noncalcified.
Lithotripsy is not favoured because of high recurrence.
• Ureteric colic: Renal colic and Dietl’s crisis (Refer to
Chapter ‘Haematuria’).
• Torsion of the ovarian cyst: Appropriate incision is made
and the cyst removed. When ruptured ovarian cyst leads
to peritonitis, it may be treated accordingly.
• Ruptured graafian follicle: Symptomatic treatment with
analgesics suffice, if there is no evidence of associated
pathology.
• Ectopic pregnancy: Haemorrhagic shock associated with
ruptured tubal pregnancy is combated by blood
transfusion besides surgery. Attempts must be made to
control haemorrhage by salpingectomy or salpingostomy
(removal of the products of conception and ligating
bleeding points). However, excision of the implanted
ovum and preservation of tube indicated in unruptured
tubal pregnancy or tubal abortion.
• Omental torsion: Treatment of omental torsion includes
ligating the pedicle above the twist and removal of the
mass. Bacterial peritonitis which may follow is treated
appropriately.
Vascular
• Mesenteric angina and infarction: Mesenteric angina
(abdominal angina) due to chronic intestinal ischaemia
is rare and treatment is symptomatic.
When the diagnosis is obvious at laparotomy,
superior mesenteric embolectomy is attempted or the
artery is re-anastomosed to the aorta along with resection
of the affected bowel. Blood transfusion may be given
and anticoagulants may be started one day after opera-
tion. In case intestinal obstruction occurs, treat
accordingly. Occlusion of inferior mesenteric artery leads
to ischaemic colitis (vide supra).
• Splenic infarction: Bed rest and sedation may suffice.
If a septic infarct results in an abscess, splenectomy is
required.
• Budd-Chiari syndrome: Streptokinase followed by
anticoagulants indicated. If it is infective in origin,
appropriate antibiotics must be administered. A meso-
atrial shunt may be considered in a blocked inferior vena
cava. However, peritoneal-jugular shunt for ascites or
15
porta-caval anastomosis or mesocaval shunt for portal
hypertension recommended. Liver transplantation may
be required in progressive hepatic failure.
• Sickle cell crisis: Pain associated with infarction crisis
in sickle cell anaemia is relieved by narcotic analgesics
followed by nonaddictive analgesics. Dehydration is
corrected which may also help to relieve pain. Antibiotics
administered in the presence of infection. Mesenteric
infarction may be treated as above. Pulmonary micro-
embolism and pseudo-toxaemia syndrome (the hazards
of associated pregnancy) may require heparin therapy.
Urgent blood transfusion may be needed in Aplastic
crisis, and exchange transfusion in sequestration.
• Ruptured ectopic pregnancy (Vide supra)
• Ruptured graafian follicle (Vide supra)
• Ruptured spleen: Treatment consists of resuscitation,
immediate laparotomy and splenectomy.
• Ruptured mesentery (Mesenteric apoplexy): Immediate
laparotomy, locating the site of bleeding and ligating
the bleeding artery is imperative. Resection of the
segments of bowel may be required, if its blood supply
is impaired.
• Ruptured aortic aneurysm: Immediate laparotomy is
mandatory. Aorta proximal to aneurysm is taken control off,
to stop bleeding. Replace the aneurysmal segment with a
prosthesis.
Abdominal
• Bornholm disease: Epidemic myalgia due ot coxsackie
B virus infection is treated with analgesics and NSAIDs
(rarely requires narcotic analgesics).
• Nerve entrapment: It may necessitate exploration and
mobilisation of the nerve.
• Haematoma of rectus sheath: Locate and evacuate the
haematoma.
• Abdominal hernias: Appropriate operative treatment is
undertaken (herniotomy, herniorrhaphy).
• Referred Pain
a. Myocardial infarction (Refer to Chapter ‘Chest
Pain’).
b. Diaphragmatic pleurisy (Refer to Chapter ‘Chest
Pain’).
c. Spinal lesions and hip joint disease (Refer to Chapter
‘Low Backache’).
Extra-abdominal
• Cardiopulmonary (Refer to Chapter ‘Chest Pain’).
• Neurological (Refer to Chapter ‘Low Backache’).
16 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Acute Abdominal Pain 17
 18 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Torsion of the testicle Untwist the testis gently in the
right direction till pain is relieved. If unsuccessful,
exploration of the scrotum and fixation of the testis is to
be done without risking delay. If the testis is not viable,
orchidectomy is to be done.
• Metabolic
a. Diabetic ketoacidosis: (Refer to Chapter ‘Coma’).
b. Acute porphyria: Treatment includes infusion of
glucose 30 g/h and correction of electrolyte
imbalance. If unresponsive within two days,
haematin is infused twice a day for about four days
(4 mg/kg body weight). Nausea, pain, seizures are
controlled appropriately. Tachycardia and hyper-
tension treated with Propranolol. The precipitating
factors are better avoided.
c. C’1 esterase inhibitor deficiency: It is treated either
by danazol which raises the inhibitor levels or with
epsilon aminocaproic acid which decreases plasmin
activity.
• Alcohol drugs and metals
a. Acute Pancreatitis (Vide supra):
b. Lead poisoning treatment consists of:
i. Fluids: Maintain fluid balance to ensure adequate
urine flow.
ii. Chelation therapy: Calcium sodium edetate (25
mg/kg twice daily IV in saline) and dimercaprol
(3 mg/kg IM every four hours) for five days.
Interrupt for two days and repeat for another five
days if necessary. This may be followed by oral
D-penicillamine (up to 500 mg/d) for about 1-2
months.
iii. Symptomatic treatment for convulsions with
diazepam, and cerebral oedema with dexa-
methasone and mannitol.
iv. Remove permanently from exposure to lead.
• Hip joint disease—Acute bursitis Rest, hot fomentations
and avoidance of pressure are helpful for inflammation.
Needle puncture may be done and purulent infections
demand incision and drainage whereas tuberculosis
needs excision and antibuterculous treatment.
Psychogenic
After eliminating confidently the organic causes of
abdominal pain by a comprehensive examination, psychiat-
ric assessment is to be done. Appropriate psychotherapy
behavioural therapy, systemic desensitisation and physical
drug therapy with anxiolytic drugs are instituted. This may
be supplemented by educating the patient about his illness
and dealing with psychosocial problems.
 Chapter
Bleeding Disorders
2
Bleeding may be localised or generalised. The localised
bleeding may be from a local lesion of any of the viscera
with or without any abnormality of haemostasis. Generalised
bleeding from more than one site is usually due to a
haemostatic defect and is characterised by prolonged nature,
disproportionate to the injury or surgery; or occurring
spontaneously into the skin and/or mucous membrane.
Purpura is bleeding into the skin and/or mucous
membrane and does not blanch on pressure. The pin head
size haemorrhagic spots are known as petechiae. The large
purpuric haemorrhages are known as ecchymoses. Bruises
are larger areas of bleeding and occur subcutaneously (Refer
to Chapter ‘Rashes’).
NORMAL HAEMOSTASIS
Normal haemostasis consists of the following:
a. Immediate active contraction of the smooth muscle of
the vessel wall (vascular factor).
b. Plugging due to platelets aggregation (platelet factor).
c. Fibrin formation by the soluble clotting factors present
in the blood (coagulation).
d. Certain extravascular factors like tissue tension by the
escaped blood and the support of the vessels also play a
secondary role in the normal haemostatic mechanism.
• Vascular Factor
The contraction of the capillaries is a normal reflex
vasoconstriction in response to injury. Further, serotonin
released from platelets cause contraction of small
vessels. This event and plugging by platelets offer time
for coagulation to occur.
• Platelets
Adequate number of platelets play an important role in
the haemostatic mechanism at several stages.
Thromboxane A-2 and serotonin in platelets and
prostacycline (PGI-2) in endothelial cells are generated
which affect the activation and release of platelets.
Prostacyclin inhibits thromboxane and the balance
between these two is the actual deciding factor for the
extent of platelet aggregation. They provide phospho-
lipid substance in which coagulation reaction proceeds
by the formation of thromboplastin and thrombin.
This thrombin and adenosine diphosphate (ADP)
act as stimuli for the platelet aggregation. The final
product of coagulation of blood (fibrin) and coalesced
platelets help in plugging of the bleeding points in the
vessels. Besides this mechanical role, they maintain the
resistance of capillary endothelium to injury.
• Coagulation
The mechanism of coagulation consists of:
a. Coagulation system (fibrin formation)
b. Coagulation inhibitory system (antithrombin)
c. Fibrinolytic system (digestion of fibrin; both
intravascular deposits namely thrombin and
extravascular fibrin in the haemostatic plugs).
Coagulation System
The key step in coagulation is fibrin formation (from
fibrinogen by thrombin), followed by cross linking of fibrin
polymers to form a stable clot.
Formation of prothrombinase, i.e. Prothrombin activa-
tor: Sequence of reactions encompasses extrinsic and
intrinsic systems, by activating Factor-X (i.e. Stuart-power)
by two different Pathways of coagulation cascade
converging in Factor X which catalyses conversion of
prothrombin to thrombin.
Extrinsic Pathway
i. Tissue factor (i.e. tissue thromboplastin or Factor III)
which is released from the damaged cells, activates
 20 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Factor-X in the presence of Factor IV (calcium) and
Factor VII (proconvertin) resulting in activated factor
(Xa).
ii. Activated Factor X complexes (Xa) with phos-
pholipids and Factor V form prothrombinase or
extrinsic prothrombin activator.
[Extrinsic pathway. Clotting Factors like III, IV and
VII activate factor X to form activated Factor -(Xa)].
Intrinsic Pathway
i. The inactive coagulation Factor XII (Hageman) is
motivated by contact of blood (platelets) with a foreign
surface like skin or collagen.
ii. Activated Factor XII (XII a) activates Factor XI
(plasma thromboplastin antecedent PTA) in the
presence of prekallikrein, and kininogen.
iii. Activated Factor XI (XI a) activates Factor IX
(Christmas factor or plasma thromboplastin
component PTC) in the presence of calcium.
iv. Activated Factor IX (IX a) converts Factor X into
activated Factor X (X a) in the presence of Factor VIII
(antihaemophilic globulin), calcium, Factor III and
platelet phospholipid.
v. Activated Factor X (Xa) combines with Factor V and
phospholipids (platelet or tissue) to form prothrom-
binase, i.e. intrinsic prothrombin activator (like the
final step in extrinsic pathway).
[Intrinsic pathway: Contact-platelets—clotting Factors
(VIII, IX, XI, XII) activate Factor X to form activate
Factors Xa].
Formation of thrombin: Prothrombin (Factor II) is converted
into thrombin (Factor IIa) by the action of prothrombinase
in the presence of calcium. (Factor IV) and Factor V
(Proaccelerin).
Formation of fibrin: Fibrinogen (Factor I) is converted into
fibrin by the action of thrombin in the presence of calcium.
Formation of insoluble (crosslinked) Fibrin (Fibrin clot) The
fibrin becomes insoluble fibrin by the action of Factor XIII
(fibrin stabilising factor). The stable clot consists of aggrega-
ted platelets, blood cells and fibrin as well (Fig. 2.1).
NB: Blood coagulation factors are: Factor I (fibrinogen);
Factor II (prothrombin); Factor III (tissue thromboplastin;
tissue factor) Factor IV (calcium); Factor V (proaccelerin);
Factor VI (activated Factor V); Factor VII (proconvertin);
Factor VIII (antihaemophilic- VIII C, i.e. clotting and VIII
RAG, i.e. antigenic); Factor IX (Christmas or plasma
thromboplastin component); Factor X (Stuart-Power); Factor
XI (plasma thromboplastin antecedent-PTA); Factor XII
Fig. 2.1: Simplified diagram of coagulation
(Hageman); Factor XIII (fibrin stabilising factor).
Coagulation Inhibitory System
(Prevention of blood clotting in the intravascular system, i.e.
anticoagulants). There are several mechanisms in the
circulation to maintain the fluidity of the blood in addition to
the coagulation factors described above. This consists of
cellular component and a humoral component. The former
which includes liver and reticuloendothelial system,
specifically removes only the activated clotting factors and
fibrin. The humoral component consists of (I) antithrombin
III (AT III which is alpha 2-globulin) and alpha 2 macro-
globulin which specifically inactivate the activated clotting
factors. Recently, an inhibitor (like AT III) has been identified
and designated as heparin cofactor II (HC II), which acts
against thrombin as well as (II) fibrinolytic system (Vide infra).
Fibrinolytic System
The humoral component which also includes the fibrinolytic
system facilitates the dissolution of fibrin. Plasmin is the
principle enzyme of the fibrinolytic system which is formed
by activation of plasminogen (Beta-globulin synthesised in
the liver) through certain naturally occuring tissue
plasminogen activators provided by the damaged cells in the
wall of the blood vessels (process stimulated by formation of
fibrin) and Factor XII as well. Plasmin is not normally found
in the blood stream since it is rapidly inactivated by
antiplasmins. Plasmin not only digests fibrin but also digests
clotting Factors I, V and VIII resulting in fibrinogen as well
as fibrinogen degradation products (FDPs). D-dimers
contained in FDPs are released into the plasma. The
fibronogenolysis is prevented by alpha-2 globulin which
rapidly inactivates plasmin. So there is localised lysis of fibrin
in the thrombus without affecting circulating fibrinogen due
to antiplasmins and alpha 2 globulin. Thus fibrin formation
 Bleeding Disorders 21

may be prevented by fibrinolytic system and coagulation B. Acquired

inhibitors (AT III) in the circulation. a. Bone marrow defect
However, in certain pathological conditions, tissue i. Marrow infiltration
1. Lymphoma
plasminogen activator is released into the blood stream in
2. Leukaemia
large amounts, resulting in ‘hyperplasminaemic state’
3. Myeloma
leading to abnormal bleeding because 4. Aplastic anaemia (marrow failure)
a. fibrin in the plugs is digested, 5. Myelosclerosis
b. factors IV and VIII in plasma are also digested, and ii. Marrow depression
c. the breakdown products of fibrinogen and fibrin 1. Drugs and radiation
digestion act as anticoagulants. 2. Infections
iii. Maturation defect: Megaloblastic anaemias
CLASSIFICATION OF HAEMORRHAGIC DISORDERS b. Splenic defect: Hypersplenism (Banti’s disease)
c. Decreased survival of platelets—(Accelerated destruction)
Haemorrhagic disorders are classified aetiologically in Immunological and nonimmunological.
Table 2.1. i. Immunological
1. Autoimmune (autoantibody induced) mechanism
Table 2.1: Aetiological classification of haemorrhagic disorders may be: Idiopathic Thrombocytopenic Purpura (ITP)
Systemic Lupus Erythematosis and Drugs
I. Coagulation Defects 2. Allo Antibodies (Isoimmune)—post-blood trans
Coagulopathies (Defective clotting mechanisms)
fusion
1. Congenital
ii. Nonimmunological:
a. Haemophilia
b. Von Willebrand’s disease (Vascular haemophilia or 1. Infections
pseudohaemophilia) 2. Disseminated intravascular coagulation (DIC)
c. Christmas disease 3. Thrombotic thrombocytopenic purpura
d. Fibrinogen deficiency 4. Haemorrhage and Massive Transfusion
e. Deficiency of Factors XI and XIII (and other factors like (Dilutional coagulopathy)
V, VII, X, XII) 5. Haemolytic uraemia syndrome
2. Acquired 6. Myeloproliferative disorders
a. Vitamin K deficiency 2. Thrombocytosis: Causes
b. Fibrinogen deficiency A. Physiological
c. Excessive fibrinolysis (Primary) B. Pathological (Primary and Secondary)
d. Disseminated intravascular coagulation (DIC) 3. Thrombasthenia: Causes
e. Circulating anticoagulants A. Congenital
f. Liver disease affecting Factors II, V, VII, IX, X B. Acquired
II. Platelet Defects
III. Capilliary Endothelium Defects
1. Thrombocytopaenia (quantitative)
Vascular Purpuras (Nonthrombocytopenic): Causes
2. Thrombocythaemia and thrombocytosis
3. Thrombasthenia (Thrombocytopathy-qualitative abnormal A. Congenital
platelet function) a. Hereditary haemorrhagic telangiectasia
1. Thrombocytopaenia: Causes b. Hereditary capillary fragility
A. Congenital c. Ehlers-Danlos syndrome
a. Bone marrow defect B. Acquired
i. Marrow infiltration: Hereditary disorder like Marble a. Symptomatic purpuras
bone disease (Osteopetrosis) i. Infections
ii. Marrow depression: Fanconi’s anaemia ii. Drugs
iii. Maturation defect: Wiskott-Aldrich syndrome iii. Scurvy
b. Splenic defect: Gaucher’s disease iv. Uraemia
c. Decreased survival of platelets due to intrinsic platelet v. Steroids and Cushing’s disease
defects vi. Dysproteinaemia (Hyperviscosity)
i. Bernard-Soulier syndrome b. Anaphylactoid: Henoch-Schönlein purpura
ii. Von Willebrand’s disease (Vascular haemophilia or c. Autoerythrocyte sensitisation
pseudohaemophilia) d. Purpura simplex (simple easy bruising)
iii. Glanzmann’s disease e. Senile purpura (involutional purpura)
iv. Storage pool deficiency f. Necrotising vasculitis
 22 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
I. Coagulation Defects
Congenital
Haemophilia (Haemophilia A) It is manifested almost
exclusively in males and transmitted by females only,
according to the Law of Nasse (i.e. sex linked recessive
deficiency of Factor VIII). The bleeding tendency occurs in
early life and persists life long. The bleeding is not severe
but slow and prolonged for days or weeks. Some trauma is
necessary for initiation of bleeding into soft tissues or any
organ or joint. There is no purpura. Haematoma may form
in the deep subcutaneous or intramuscular tissues due to
extravasation of blood. Haemorrhage into the joint cavity
is recurrent in severe haemophilia and never occurs in mild
haemophilia. The joints which are affected are knees and
elbows (Refer to Chapter ‘Polyarthritis’). Anaemia may be
present depending on the degree of bleeding.
Diagnosis is confirmed by
i. Family history of bleeding in male relatives
ii. Prolonged coagulation time
iii. Normal bleeding time
iv. Prolonged partial thromboplastin time
v. Deficiency of antihaemophilic factor-Factor VIII.
Plasma may contain little antihaemophilic factor (5 to
40% of the normal 50 to 150%).
Von Willebrand’s disease (Vascular haemophilia) It is a
hereditary bleeding disorder transmitted as an autosomal
dominant trait. There is deficiency of Von Willebrand-protein
which acts as plasma carrier of Factor VIII complex, and
deemed to be synthesised in the endothelial cells. This Von
Willebrand’s factor is necessary for platelet adherence, i.e.
dual abnormalities with platelet adherence defect and
coagulation defect due to Factor VIII deficiency. Capillaries,
when injured, fail to contract which results in prolonged
bleeding time. The symptoms include easy bruising,
epistaxis, prolonged bleeding for about 36 h after tooth
extraction or minor trauma. Haemarthroses are rare. Purpura
may be present.
The diagnosis is established by
i. Presence of family history
ii. Prolonged bleeding time with normal platelet count
iii. Clotting time is usually normal unless deficiency of
Factor VIII is more severe
iv. Factor VIII less than 50% (both VIII C and VIII RAG
are low)
v. Positive capillary resistance test
vi. Von Willebrand’s Factor (VBF) is reduced (normal
10 mg/l)
Christmas disease (Haemophilia B) It is a sex-linked recessive
disease simulating haemophilia. However Factor IX is
deficient. Thromboplastin generation test detects the
deficiency of Christmas disease. This fascinating name is
that of the first English family in whom it was observed at
Christmas.
Fibrinogen deficiency It is a hereditary disorder with an
autosomal recessive character. Bleeding tendency resembles
that of haemophilia without haemarthroses. Both sexes are
affected. Diagnosis is confirmed by
i. Absence of fibrinogen content
ii. Prolonged clotting time
iii. Prolonged one stage prothrombin time
iv. Prolonged thrombin time
Deficiency of factor XI Clinically it resembles the mild form
of haemophilia.
Deficiency of factor XIII (Fibrin stabilising factor deficiency)
The bleeding tendency from umbilicus, keloid formation
after minor injuries and recurrent abortions in early
pregnancy are the characteristic features. It is inherited as
autosomal recessive trait and appears in both sexes or in
males only.
Diagnosis is confirmed by
i. The stability of the blood clot in 5M urea or monochlor
acetic acid solutions (1%)
ii. Quantitative assay of Factor XIII activator
Acquired
Vitamin K deficiency This fat soluble vitamin is necessary
for synthesis of prothrombin, Factor VII, Factor IX and
Factor X in the liver. It may be due to
i. Deficient intake of Vitamin K containing foods as in
malnutrition
ii. Deficient absorption due to lack of bile salts as in
obstructive jaundice or malabsorption syndrome
(steatorrhoea)
iii. Deficient utilisation of Vitamin K in liver parenchymal
diseases
iv. Drugs decreased bacterial flora in the bowel due to
oral antibiotics; oral anticoagulant drugs like
dicoumarol antagonising the action of Vitamin K.
v. Haemorrhagic disease of the new born which occurs
in the few days of life due to a defect of synthesis of
Vitamin K or functional immaturity of the liver or
drugs like oral anticoagulants, oral anticonvulsants and
aspirin.
 Bleeding Disorders
During pregnancy there may be bleeding from the mouth,
nose, urinary tract or into the viscera. Diagnosis is confirmed
by prolonged one stage prothrombin time.
Fibrinogen deficiency It may be due to impaired synthesis
as in hepatitis or with certain drugs like L-asparaginase and
accelerated proteolytic activity. It occurs most often in late
stages of pregnancy due to entry of thromboplastin
substances from the placenta.
Diagnosis is confirmed by
i. Reduction of fibrinogen content in the blood
ii. Prolonged clotting time
Fibrinolysis (primary) A bleeding state may result from an
increased plasma fibrinolysis activity due to liver disease
or septicaemia or disseminated carcinoma. This primary
fibrinolysis has to be differentiated from DIC with secondary
fibrinolysis.
Diagnosis is confirmed by
1. The tests for plasma fibrinolytic activity are positive,
increased fibrin degradation products. (D-Dimer is not
increased in primary fibrinolysis).
2. Demonstration of lysis of a clot, from a normal subject
by the patient’s plasma.
3. The platelet count is normal and schistocytes absent
unlike DIC.
4. Fibrinogen content is reduced.
5. Prolongation of thrombin time, prothrombin time and
partial thromboplastin time.
6. Fibrinogen breakdown products are present in significant
titre.
Disseminated intravascular coagulation (DIC) Disseminated
intravascular coagulation is a result of intravascular activa-
tion of coagulation system In various clinical set-ups. So it
is a systemic thrombo-haemorrhagic disorder, i.e. activation
of clotting and fibrinolytic pathways with thrombin and
plasmin generation respectively leading to thrombosis and
bleeding.
Pathophysiology The fibrin deposits in microcirculation lead
to consumption of clotting factors and platelets to such a
degree that their concentrations in the plasma are lowered
resulting in diffuse bleeding. Further, fibrin degradation
products may act as anticoagulants which also account for
bleeding. The fibrin strands slice the circulating RBCs and
cause haemolysis with formation of schistocytes (fragmented
RBCs). This is usually seen in subacute DIC situations and
this is termed as microangiopathic haemolytic anaemia.
Apart from release of plasminogen activators like urokinase
and excess fibrinolysis secondary to tissue trauma and
formation of fibrin degradation products, ischaemic tissue
23
damage occurs consequent to localised occlusive thrombus
or deposition of fibrin in the small blood vessels, i.e.
intravascular coagulation.
The causes of DIC are
i. Septicaemia (particularly gram-negative organisms)
or any shock with hypovolaemia
ii. Obstetrical accidents (ante partum haemorrhage or
amniotic fluid embolism)
iii. Prostatic carcinoma, or neoplasms of other organs, or
acute promyelocytic leukaemia
iv. Cardiothoracic surgery, prostatecomy; release of
thromboplastins
v. Extensive burns
vi. Haemolytic uraemic syndrome (vascular damage)
vii. Trauma
The clinical features of DIC essentially include features
of the precipitating primary conditions with or without
shock. Bleeding which is the common presentation of acute
DIC may be localised (from venepuncture sites or at the
site of operation) or may be generalised with purpura or
ecchymoses or visceral bleeding.
Thrombosis is another clinical feature of acute DIC
resulting in damage of certain organs like kidney leading to
renal failure or brain with thrombotic manifestations.
Diagnosis is confirmed by
i. Prolonged thrombin time, prolonged prothrombin
time, prolonged partial thromboplastin time and
prolonged clotting time.
ii. Decreased platelet count, decreased fibrinogen
content, and decreased Antithrombin III.
iii. Blood may not clot in a test tube (If formed, it is a
flimsy, friable small clot. If the clot is demonstrated it
is suggestive of depletion of fibrinogen in the primary
process and not fibrinolysis).
iv. The fibrin and fibrinogen breakdown products
detected in significant titres including D-Dimer levels.
v. Blood smear shows schistocytes (Fragmented Red
Blood cells)
vi. Plasma fibrinolytic activity tests are negative (i.e.
euglobulin lysis time, dilute plasma clot lysis, and
fibrin plate assay).
Circulating anticoagulants and anticoagulant drugs
These are antibodies to specific clotting factors like Factors
V, VIII, IX, X, XI, XII. Other forms of circulating anticoagu-
lants are antibodies developed against prothrombin activator
and occur in conditions like SLE and dysproteinemia and
rheumatoid arthritis. They may be encountered also in
pregnancy when bleeding occurs few weeks after delivery
and may recur in the subsequent pregnancies. Clinical
 24 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
features are suggestive of congenital deficiency of the said
factors. Bruising is common than severe bleeding or it may
resemble haemophilic type of bleeding. Lab tests reveal a
prolonged clotting time, prothrombin time and partial
thromboplastin time. Anticoagulant drugs like heparin
activate antithrombin III and warfarin acts as a Vitamin K
antagonist. Haemorrhage may be a complication.
Liver disease In liver disease, haemostasis is frequently
impaired due to
i. Defective synthesis of clotting Factors I, II, V, VII,
IX, X, XI
ii. Thrombocytopenia due to congestive splenomegaly
iii. Increased fibrinolytic activity due to defective
synthesis of plasminogen and antiplasmins as well as
impaired clearance of plasminogen activators from the
blood stream
Diagnosis is confirmed by
i. Low fibrinogen levels
ii. Prolonged prothrombin time and thrombin clotting
time
iii. Increased partial thromboplastin time
iv. Reduced platelet count
II. Platelet Defects
Platelet defects may be due to
1. Altered number of platelets (quantitative) either
decreased (100000/c.mm) or increased (400000/c.mm),
normal platelet count being 1,50,000–4,00,000 thousand/
c.mm
2. Altered function of the platelets (qualitative)
A low platelet count (thrombocytopenia) may be of
varied aetiology, secondary to a bone marrow defect, or
splenic defect or intrinsic platelet defects with decreased
survival which may be of inherited or acquired origin.
Causes of Thrombocytopenia (Quantitative)
Usually due to either decreased production (marrow failure/
disorders; B12/folate deficiency) or decreased survival
(DIC,SLE, ITP, TTP, viruses) or platelet aggregation
(heparin).
Congenital
1. Bone marrow defect
a. Marrow infiltration: Marble Bone Disease (osteopetrosis)
It is a congenital disorder characterised by anaemia,
splenomegaly, increased density of bones and fractures
with minor trauma. It is due to narrowing of the marrow
cavity by encroachment of bone with thickened cortices.
b. Marrow depression: Fanconi’s anaemia It is characte-
rised by hypoplastic anaemia with neutropenia,
thrombocytopenia and multiple congenital anomalies
like hypoplastic thumbs or radii, hypoplasia of the
kidney, testicular hypoplasia.
c. Maturation defect: Wiskott-Aldrich syndrome In
Wiskott-Aldrich Syndrome there are normal or increased
megakaryocytes but because of defective maturation
there is dysthrombopoiesis. This is also usually asso-
ciated with eczema and immunological abnormalities.
2. Splenic defect (Gaucher’s Disease) It is characterised by
accumulation of nitrogen containing cerebroside (kerasin)
in the reticulo-endothelial cells. Clinical features are
hepatosplenomegaly with or without lymphadenopathy;
skeletal changes (like generalised rarefaction with cortical
thinning and spontaneous fractures and club-shaped
widening of the lower ends of the femora); brownish
pigmentation of the skin specially in the face and exposed
areas; eye changes (yellow thickening of conjunctiva at
angles); and bleeding tendencies.
Blood changes like anaemia, leucopenia, thrombo-
cytopenia are due to hypersplenism and marrow infiltration.
Diagnosis is confirmed by demonstrating Gaucher’s cell
(kerasin containing cell) in bone marrow or liver.
3. Decreased survival of platelets due to intrinsic platelet
defects (Defective adhesion and defective aggregation)
a. Bernard Soulier syndrome (giant platelet) Though the
platelet count is normal, the bleeding time may be
prolonged due to malfunction of the platelets like defective
adhesion due to abnormal platelet membrane glycoprotein.
b. Von Willebrand’s disease (vascular haemophilia): (Vide
supra.)
c. Glanzmann’s disease: Though the platelets are normal
in number they do not aggregate properly in response to
ADP or other aggregating agents like collagen and
epinephrin. Bleeding time is prolonged and clot
retraction is defective or absent. Clinically there is
tendency for bruising after minor injury or epistaxis or
menorrhagia. It is an autosomal recessive disorder.
d. Storage pool deficiency This is also a functional defect
of the platelets with defective storage pool of ADP or
defective ADP release. Drugs like aspirin or phenyl
butazone or indomethacin may inhibit platelet function.
Platelet aggregation is abnormal to ADP and absent to
collagen and epinephrin. Bleeding time is less prolonged
than Glanzmann’s disease and clot retraction is normal.
 Bleeding Disorders
Acquired
1. Bone marrow defect
Marrow infiltration
a. Lymphoma: Lymphomas (malignancy of lymphoid
tissue) can be grouped as (i) Hodgkin’s lymphoma and
(ii) non-Hodgkin’s lymphoma (Lymphocytic
Lymphomas).
Hodgkin’s lymphoma is classified as (i) nodular
sclerosing, (ii) lymphocytic predominant, (iii) lympho-
cytic depleted, and (iv) mixed cellularity.
Non-Hodgkin’s lymphoma is classified as
i. Nodular type: Lymphocytic, histiocytic and mixed.
ii. Diffuse type: Lymphocytic, histiocytic, mixed,
lymphoblastic, and undifferentiated.
(Burkitt’s lymphoma is small noncleaved B-cell
neoplasm)
They may inflitrate the bone marrow resulting in
localised bone pain and blood changes (like anaemia
and lymphopenia with moderate thrombocytopenia).
Hodgkin’s disease is clinically diagnosed by charac-
teristic painless discrete rubery lymphadenopathy with
hepatosplenomegaly and Pel-Ebstein type of fever.
However, clinical staging is done to facilitate therapy, i.e.
Stage-I (single region usually one side of the neck); Stage-
II (two regions); Stage-III (above and below diaphragm
limited to lymph nodes and spleen); and Stage-IV
(widespread involving bone marrow, liver and lung).
b. Leukaemia: Acute leukemia with bleeding tendencies
and necrotic ulcers in the mouth or pharynx with hepato-
splenomegaly, lymphadenopathy and characteristic
blood changes (leucocytosis and increased percentage
of predominant primitive cells and thrombocytopenia).
Acute lymphoblastic leukaemia is divided into three
types (L1, L2, and L3) whereas acute myeloid leukaemia
is divided into seven types (M1, M2, M3, M4, M5, M6
and M7) by microscopic appearance.
Chronic myeloid leukaemia is characterised by
massive splenomegaly and marked leucocytosis with 80
to 90 percent of granular series of which myelocytes
form 20 to 50% (> 95% have Philadelphia chromosome).
Prognosis is bad in those without pH. Chronic lymphatic
leukaemia is characterised by prominent cervical axillary
or inguinal lymphadenopathy and leucocytosis with 80
to 90% of lymphocytes.
c. Myeloma: (Refer to Chapters ‘Polyuria, Oliguria’ and
‘Low Backache’).
d. Aplastic anaemia Secondary aplastic anaemia may be
due to drugs, X-rays exposure, carcinoma (bone marrow
25
infiltration by secondary metastases from primary
tumours of the breast, prostate and thyroid) and result
in characteristic haematological changes (normocytic
normochromic anaemia, granulopenia with necrotic
ulcers and thrombocytopenia with purpura and free
haemorrhages). Primary aplstic anaemia is rare.
e. Myelosclerosis There is hardening of the bone marrow
due to excessive production of fibrous tissue
(myelofibrosis and osteosclerosis). Since the normal
blood forming elements of the marrow are replaced by
fibrous tissue, myeloid metaplasia (extramedullary
haemopoiesis in the spleen and liver) occurs. It may
involve precursors of white cells and red cells precursors
as well as megakaryocytes. Hepatosplenomegaly with
leukoerythroblastic anaemia are the characteristic
features. Bleeding tendency due to thrombocytopenia
is common in the later stages.
Marrow Depression
a. Drugs and radiation:
i. Toxic depression of the marrow is caused by cytotoxic
agents, gold, chloramphenicol and sulphonamides.
ii. Specific defect on the megakaryocytes with impair-
ment of platelet formation may occur with aspirin and
NSAIDS.
iii. Hypersensitive reaction may occur when the drug acts
as primary antigen with subsequent formation of
antigen antibody complex, which is absorbed on the
platelet membrane resulting in immunological platelet
destruction, e.g. quinidine, quinine, carbamazapine,
methyldopa, chlorpropamide. Bleeding occurs after
hours or days of consuming the last dose. The
haemorrhage is severe with or without constitutional
symptoms, after any hypersensitive reaction.
Sensitivity can be demonstrated by the complement
fixation test.
iv. Exposure to X-rays and radioactive substances
including luminous paint may also affect the marrow.
b. Infections: Certain infections due to viruses, rickettsial
or bacteria and/or septicaemia may result in
thrombocytopenia during the acute or recovery stage.
Maturation defect
• Megaloblastic Anaemias
In vitamin B12 deficiency or folic acid deficiency or both
deficiencies, there is ineffective thrombopoiesis although
the number of megakaryocytes is normal in the bone
marrow. It may be associated with symptomless
thrombocytopenia, besides megaloblastic anaemia as
such.
 26 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
2. Splenic defect
• Hypersplenism (Banti’s disease):
In hypersplenism, there is massive splenomegaly and
reduction of white cell count, red cell count or platelet
count singly or incombination due to either abnormal
sequestration and destruction of cells in the splenic pulp
or by inhibiting the release of mature cells from the
marrow by splenic hormone. Bone marrow may be
essentially normal. The classical example is Banti’s
syndrome where there is portal hypertension with
anaemia, leucopenia and occasional thrombocytopenia,
i.e. Pancytopenia.
3. Decreased survival of platelets
• Immunological (Antibody mechanism)
a. Autoimmune (autoantibody induced) mechanism
i. Idiopathic thrombocytopenic purpura (ITP): It
exists in two forms—acute self-limiting type
(following an infection within preceding three
weeks) and chronic recurrent type.
The predominant sign is purpura over the
neck, chest and limbs with or without bleeding
from the mucosal membranes or internal organs.
(Bleeding can occur if the platelet count is less
than 100000/c.mm.). The bleeding is usually
confined to one site only. Mild splenomegaly
may be present in about 10 per cent of cases.
The platelets may be reduced even up to 10,000
c.mm. (although morphologically normal) when
bleeding may be associated with severe
haemorrhage. Spontaneous bleeding is unusual
unless the count is less than 20000/cmm.
Bleeding time is prolonged. Clot retraction is
poor. Cloting time is normal. The bone marrow
shows either normal or increased number of
megakaryocytes which appear abnormal with
20 per cent activity as compared to 70 per cent
in the normal marrow. Platelet antibodies are
found in vitro and antibody is an immuno-
globulin-G which sensitises the platelets. Hence
it is termed as “Acute Immune Thrombocyto-
penia”. The disease is usually a chronic one with
remissions and relapses.
ii. Systemic lupus erythematosus (SLE): Thrombo-
cytopenia may occur in SLE in about 10 per
cent of cases due to platelet autoantibodies. This
autoimmune thrombocytopenia may also occur
due to drugs, Coombs’ positive haemolytic
anaemia, chronic lymphatic leukaemia and
lymphoma.
iii. Drugs (Vide supra).
b. Isoimmune (alloantibodies)
Postblood transfusion following massive transfusion
or extracorporeal circulation, platelet alloantibodies
may develop in the patient from sensitisation to
antigen in transfused platelets. This may occur in
women one week after transfusion and may persist
for six weeks.
• Nonimmunological
a. Infections Marrow suppression is caused directly
by the infective agent or toxin resulting in thrombo-
cytopenia.
b. Disseminated intravascular coagulation (DIC) (Vide
supra).
c. Thrombotic thrombocytopenic purpura: It is a rare
fatal disease characterised by thrombocytopenia
purpura, rapidly developing haemolytic anaemia,
fever, fluctuating neurological disturbances (Fits) and
renal failure. It may occur in association with
collagen diseases and the manifestations are due to
intravascular thrombi without damage to vessel wall
or inflammation. The diagnostic feature is presence
of severely fragmented red blood cells in the
peripheral blood smear.
d. Haemorrhage and massive transfusion (dilutional
coagulopathy): Following massive transfusions or
exchange transfusions, excess bleeding may occur
due to decreased number of competent platelets
consequent to poor survival in the stored blood that
is transfused.
e. Haemolytic uraemic syndrome: It is characterised
by microangiopathic haemolytic anaemia, thrombo-
cytopenia and acute renal failure. It may be preceded
by abdominal pain and bloody diarrhoea. Occlusion
of small vessels occurs due to fibrin deposition.
Thrombotic thrombocytopenic purpura is differen-
tiated by absence of fever and neurological manifes-
tations. It is associated with bacterial or viral
gastroenteritis.
f. Myeloproliferative disorders: These are characte-
rised by proliferation of one or more stem cells in
the haemopoietic cell line in the bone marrow
(chronic myeloid leukaemia, polycythemia vera,
thrombocythaemia) and sometimes in the liver or
spleen (myeloid metaplasia or myelofibrosis). In
these diseases, platelet function may be impaired due
to intrinsic platelet defects.
Thus thrombocytopenia may result from (i) decrea-
sed production (marrow infiltration, depression or
defects) and (ii) Increased destruction (hyper-
 Bleeding Disorders 27

splenism, autoimmune mechanism like ITP or
nonimmunological like overconsumption DIC).
Causes of Thrombocytosis and Thrombocythaemia
(Quantitative)
Platelet count is more than 400000/cmm. It may be primary
(haemorrhagic thrombocythaemia) or secondary. Primary
thrombocytosis (as seen in myeloproliferative disorders may
occur alone, or as part of polycythaemia and chronic myeloid
leukaemia) may be complicated by spontaneous bleeding
and/or thrombosis. The increased platelet count is sustained
and may be more than 800000/cmm. and haemoglobin
percentage is reduced. Secondary thrombocytosis may occur
after splenectomy, surgery, haemorrhage, chronic
inflammatory disease (osteomyelitis), malignancy
(carcinoma or lymphoma), iron deficiency and display of
drugs like cytotoxic agents. The increased platelet count is
transient and rarely causes haemostatic episodes. So is the
case with thrombocytosis due to physiological causes like
exercise or parturition, i.e. platelet count rise is < 1000 ×
109 /L whereas in thrombocythaemia it is markedly raised
> 1000 × 109 /L.
Causes of Thrombocytopathy/
Thrombasthenia (Qualitative)
The causes can be (i) congenital (Glanzmann’s disease, Von
Willebrand’s disease, ADP release dysfunction-vide supra)
and (ii) acquired (drugs like aspirin, NSAIDs, amytriptyline,
amantidine, carbenicillin; uraemia; paraproteinaemias and
DIC). Prolonged bleeding time with normal platelet count
offer the clue.
arterioles and blanch on pressure. They bleed easily because
of thinness and the bleeding may be prolonged due to poor
contractility. Family history may be forthcoming.
Hereditary capillary fragility This is inherited as a Mendelian
dominant affecting both sexes. There is defective morpho-
logy and contractility of the small vessels of skin and mucous
membranes. Bleeding may occur spontaneously or following
surgery or injury. There is neither abnormality of the platelets
nor coagulation mechanism. However, the abnormal finding
is prolonged bleeding time. Examination under the capilliary
microscope may reveal capillaries abnormal in shape and
reaction.
Ehlers-Danlos syndrome
Refer to Chapter ‘Polyarthritis’.
Acquired
Symptomatic purpuras
• Infections: Purpuras may occur in many severe infections
like meningococcal septicaemia or subacute bacterial
endocarditis. Sometimes the bleeding into the skin
spreads and progresses in wavy pattern leaving some
areas unaffected (purpura fulminans).
• Drugs: Penicillin, aspirin, and sulphonamides are some
of the examples where purpura can occur due to
idiosyncrasy (Fig. 2.2).

III. Capilliary Endothelium Defects

Vascular purpuras (Nonthrombocytopenic) Easy Bruising
Vascular purpuras are primarily due to the disorders of small
blood vessels (vasculitides) or secondary to altered fragility
of vessels consequent to disorders of supporting structures
in the skin. In this group the capillary walls are injured due
to allergy or direct effect of infections or chemicals (drugs,
metabolic products like in uraemia or cholaemia) or scurvy.

Congenital
Hereditary haemorrhagic telangiectasia (Osler-Weber-
Rendu Syndrome) It is an autosomal dominant entity and
both sexes are affected. Telangiectases are present in the
skin especially of the face, hands and mucous membrane of Fig. 2.2: Purpuric spots over the limbs due to drug
nose and mouth. They are due to dilation of capillaries and idiosyncrasy (vascular purpura)
 28 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

• Scurvy: It is due to increased capillary fragility conse-

quent to defective form of intercellular substance of the
capillary walls. Vitamin C is essential for the formation
of hydroxyproline. Bleeding may occur in the skin
(perifollicular purpura) or in the calf muscles resulting
induration and tenderness. There may be associated
hyperkeratosis of the skin and hypertrophy of gums.
• Uraemia: Bleeding occurs into the skin or GI tract or as
epistaxis. There is a dual mechanism of capillary
endothelial defect and defective function of platelet
(adhesiveness and aggregation by ADP are impaired).
Bleeding time is prolonged.
• Steroids and Cushing’s syndrome: Haemorrhagic skin
manifestations like ecchymoses occur in Cushing’s
disease and after administration of corticosteroids due
to vascular defect. The supporting structures in the skin
may be affected, making the vessels abnormally fragile.
• Dysproteinaemia: An abnormality of the plasma
proteins like cryoglobulinaemia or macroglobulinaemia
or multiple myeloma may result in purpura due to
damage of the vessel walls by the proteins and anoxia Fig. 2.3: Serum protein electrophoresis—Electrophoretogram
of the capillaries due to hyperviscosity. Hyperviscosity (a) Normal, (b) Increased γ-globulin in multiple myeloma and
can be caused also by hyperfibrinogenemia, polycy- macroglobulinaemia
thaemia vera and leukaemia. In mixed cryoglobuli-
naemia, purpura may occur and arthralgia and nephritis lesions whereas Schönlein purpura is seen in adults
may be associated. Electrophoresis may reveal the characterised by periarticular effusions and swollen joints.
gamma-globulin peak (Fig. 2.3). Autoerythrocyte sensitisation: It usually manifests as tender
Clotting of blood in the syringe is suggestive of ecchymosis and persists for a week or so. They occur in
cryoglobulinaemia and paper electrophoresis may clinch the crops on the extremities especially in legs over severe weeks.
diagnosis of the other two. Visceral bleeding, gastrointestinal bleeding, haematuria and
menorrhagia may be associated. Emotional disturbances
Anaphylactoid: The various types of anaphylactoid purpura
associated with injury possibly make the subject become
are the consequences of an allergic reaction which may also
sensitive to the red cells of their own extravasated blood.
include urticaria or angioneurotic oedema. Acute nephritis
Blood examination reveals no abnormality.
may be a complication.
Purpura simplex: It is a mild purpura encountered in healthy
Henoch-Schönlein purpura (HSP): Purpura over the buttocks
individuals particularly young women. Small haemorrhagic
or extensor surfaces of the limbs is due to cutaneous
spots or superficial painless bruises appear on the limbs or
vasculitis. Polyarthralgia, colicky abdominal pain and
elsewhere in the body without any trauma. They appear in
haematuria accompanied by albuminuria or localised
crops and disappear within a week or two. It carries no
oedema of the dorsum of the hand or around eye are the
significance. Hereditary factors, stress, and drugs like aspirin
characteristic clinical manifestations. Although
are incriminated. All laboratory tests are normal.
streptococcal infection of the throat with bacterial
hypersensitivity and food or drug allergies are associated, Senile purpura: It is seen in elderly people as large irregular
exact aetiological relationship is not established. areas with a clear cut margin on the extensor surfaces of the
Diagnosis is confirmed by Hess test and absence of blood arms. The skin is inelastic and moves freely over the
changes (normal platelet count). The presence of IgA underlying tissues. It is due to atrophy of the structures
deposits in the blood vessels of the skin is contributory. supporting the blood vessels and hence the vessels easily
Henoch purpura is seen in children characterised by visceral rupture.
 Bleeding Disorders 29

Necrotising vasculitis: Inflammation and necrosis involve Table 2.2: Differential diagnosis
small vessels (arterioles, venules and capillaries) and of haemorrhagic disorders
extravasation of blood occurs. Purpuric areas appear raised Distinct features Disorders of Disorders of platelets
and tender. Fever, arthralgia, abdominal pain, renal coagulation and vessels (purpuric
involvement are the other clinical features like Henoch- disorders)
Schonlein purpura. Infections, drugs, SLE or mixed 1. Sex predominance Male Female
cryoglobulinaemia are implicated with this hypersensitivity 2. Family history Positive Negative
vasculitis (Type III reaction). 3. Petechiae Rare Characteristic
To sum up, purpura can be caused by (i) disorders of 4. Ecchymoses Solitary Small and multiple
clotting constituents like hypoprothrombinaemia or 5. Haematoma Characteristic Rare
fibrinogenopenia, (ii) platelet defects, (iii) disorders of vessel 6. Haemarthrosis Common Rare
wall, and (iv) hereditary disorders of connective tissue (due 7. Site of bleeding Skin, Skin,
to abnormal interaction of platelets with collagen and Mucous membrane, Mucous membrane,
weakness of vessel wall). Viscera Central nervous system
Haematuria
CLINICAL APPROACH 8. Precipitating Post mild trauma Spontaneous
Precise diagnosis of bleeding is essentially based on clinical factors Spontaneous Trauma
evidence whether 9. Time sequence Delayed and Immediate and
1. Bleeding is due to haemorrhagic diathesis (bleeding from of bleeding prolonged short duration
more than one site; bleeding out of proportion to injury; 10. Blood loss Minimal by oozing Profuse and more
and spontaneous bleeding into the skin or mucous 11. PT Normal or Normal
membrane or deeper tissues) or due to any local lesion prolonged
in a haemostatically normal subject. 12. PTT Prolonged Normal
2. If so, what is the defective haemostatic mechanism
(coagulation defect, or platelet defect or capillary defect)
(Table 2.2)? i. Time sequence of bleeding: Bleeding is minimal and
3. What is the underlying specific bleeding disorder? delayed after a trauma and oozing persists or shows a
4. Is the bleeding merely from a localised lesion like GI tendency to rebleed even after initial haemostasis,
tract without any bleeding diathesis? whereas bleeding is profuse, immediate and of short
duration without tendency to rebleed when once
History haemorrhage is controlled. Diffuse spontaneous bleeding
a. Age of onset: In haemophilia, bleeding tendency from any area associated with any systemic disease
develops in early life. indicates DIC (Vide supra).
b. Sex: Coagulation defects usually seen in males whereas j. Any constitutional symptoms like fever.
platelets or capillary defects seen in females. k. Precipitating factors: Venipuncture, trauma or surgery.
c. Family history: Positive history in a close relative may
suggest coagulation defects. Physical Examination
d. History of ingestion of drugs like anticoagulants. It depends essentially on the urgency arising out of extent
e. Any evidence of presence of systemic disorder of bleeding whether the subject is having hypovolaemia or
associated with abnormal haemostasis (causes: Vide impending threat of shock or critical bleeding episodes like
supra). central nervous system bleeding leading to coma (related to
f. Any history of previous attacks of bleeding, e.g. the amount and duration of blood loss).
following dental extraction.
g. Site of bleeding: Visceral or muscular after trauma, General Examination
indicate coagulation defects whereas petechiae or
ecchymoses occurring spontaneously in the skin or 1. Appearance
mucous membranes indicate platelet or capillary defects. a. Bleeding into the skin
h. Type of bleeding: Localised or generalised (generalised i. Petechiae: Small types present usually over the
is rare in vascular abnormalities). ankles (usually due to increased fragility of the
 30 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

vessels due to thrombocytopenia and vascular
purpuras but rare in coagulation disorders).
ii. Purpuric lesions in HSP are distributed over legs,
buttocks, and arms which appear raised, accom-
panied by erythema, unlike thrombocytopenic
purpura.
iii. Ecchymoses: In coagulation defects, ecchymosis
is solitary due to bleeding from relatively large
vessel, whereas in other purpuras ecchymoses are
small and multiple.
b. Bleeding into subcutaneous tissues: Haematoma is
caracteristic of coagulation defects and rare in others.
c. Bleeding into the mucous membrane (oral cavity);
any purpura over the buccal mucosa; or
haemorrhagic bullae due to thrombocytopenia; or
telangiectasia underneath the tongue (Hereditary
haemorrhagic telangiectasia).
d. Nose: Epistaxis may be due to haemostatic disorder
or hypertension or any local cause.
e. Eyes: Any haemorrhages in the conjunctiva or fundi
(fundal haemorrhages seen not only in
thrombocytopenia but also in hypertension, diabetes
mellitus).
f. Bleeding into the joints: Any swelling and tenderness
of a joint (Haemarthrosis) suggests deficiency of
Factor VIII or IX, and rare in others.
2. Pressure response: Usually ineffective in coagulation
disorders whereas effective in others.
3. Any abnormal elasticity of the skin and
hyperextensibility of the joints (ED Syndrome).
4. Any lymphadenopathy (leukaemia or lymphoma).
5. Any spider angiomas or palmar erythema (chronic liver
disease).
6. Vital data: temperature, pulse, blood pressure and
respirations.
7. Hess’s test: Vide infra.
Systemic Examination
1. Abdomen: Any dilated abdominal veins or hepatomegaly
or splenomegaly (may be due to thrombocytopenia itself
or any haematological malignancy).
2. Evidence of any visceral haemorrhage (common in
coagulation defects) or haemorrhage in the central
nervous system (common in platelet disorders).
3. Any other evidence of underlying coexisting disorders
accounting for haemostatic abnormality.
Investigations
Blood Examination (Table 2.3)
a. Blood counts and peripheral blood smear
i. Platelet count and morphology (normal I platelet for
10-20 RBCs) 150000-400000/cmm. Diminished in
Thrombocytopenic purpura and DIC.
ii. Red cell count and morphology (schistocytes with
thrombocytopenia indicate DIC; target cells, etc.).
iii. White cell count and morphology (abnormal white
blood cells indicate leukaemia).
b. Platelet function tests:
i. Bleeding time: Prolonged in thrombocytopenic
purpura. However, bleeding time is prolonged with
a normal platelet count in Von Willebrand’s disease,

Table 2.3: Laboratory investigations in common haemorrhagic diseases

Common haemorrhagic diseases Platelet BT PT PTT CT TCT FDPs CRT

count
Haemophilia and Christmas disease N N N P P N N N
Von Willebrand’s disease N P N or P P N or P N N N
Fibrinogenopenia N or D N or P P P P P I N or P
Hypoprothrombinaemia N N P P N N N N or P
DIC D N or P N or P N or P No clot N or P I No clot
Thrombocytopenic purpura D P N N N N N P
Thrombasthenia N P N N N N N P
Vascular purpuras N N N N N N N N

N.B: D = Decreased; I = Increased; N = Normal; P = Prolonged; BT = Bleeding time; PT = Prothrombin time; PTT = Partial thromboplastin
time; CT = Clotting time; CRT = Clot retraction time; TCT = Thrombin clotting time; FDPs = Fibrin degradation products
 Bleeding Disorders 31

thrombasthenia, cirrhosis, uraemia, dysprotein- d. Other blood tests

aemias. Aspirin (Normal value: 1-9 minutes IVY i. Haemoglobin percentage and haematocrit value to
method). assess the degree of anaemia. Haematocrit above
ii. Clot retraction time (screens defect in platelet 50% increases viscosity with risk of thrombosis.
function): It is prolonged in thrombocythaemia, ii. ESR.
hypoprothrombinaemia, fibrinogenopenia (apparent
in 60 min, complete within 24 hours, usually in 2 h). Capillary Resistance Test (Hess Test)
iii. Platelet aggregation: Response of platelets to ADP
Sphygmomanometer cuff is inflated to midway between
and other aggregating agents.
systolic and diastolic blood pressures or 100 mmHg and
c. Coagulation screening tests
kept for 10 min. The skin over the forearm in a circle of
i. Clotting time: Prolonged in haemophilia, fibrino-
3 cm diameter is examined after deflating the cuff. Normally,
genopenia, heparin therapy, (Normal value
not more than 2-3 haemorrhagic spots are seen. When the
8-18 min).
capillary resistance is decreased, i.e. increased fragility, a
ii. Prothrombin time: Prolonged in hypoprothrom-
number of small haemorrhagic spots are found in vascular
binaemia, liver disease, with warfarin or DIC and
purpura or thrombocytopenia and negative in clotting
indicates a deficiency of one or more extrinsic factors defects.
as it reflects defects in extrinsic clotting system
(normal value not more than 2s longer than control;
Bone Marrow Examination
control time 11 to 15s). International normalised ratio
(INR) 0.9-1.2. This examination is conducted for the evidence of
iii. Partial thromboplastin time: Prolonged in Factor I i. Presence or absence of megakaryocytes in normal
deficiency (fibrinogen), Factor II deficiency number
(prothrombin), Factor V deficiency (proaccelerin), ii. Leukaemia
Factor VII deficiency (proconvertin), Factor VIII iii. Presence of aplasia
deficiency (antihaemophilic factors), Factor IX iv. Infiltration by carcinoma cells
deficiency (Christmas factor), Factor X deficiency v. Appearance of myelofibrosis
(Stuart-power), DIC and with heparin. It reflects
defects in intrinsic clotting system. Normal value— Further Investigations
68-82s).
i. Protein electrophoresis
iv. Thrombin clotting time (the time taken by the plasma
ii. LE Cell and ANF Tests
to clot after addition of thrombin): Prolonged in
iii. Radiological skeletal survey
hypofibrinogenaemia, or with heparin therapy
iv. Any other appropriate tests pertaining to underlying
(Normal value—13 to 17s).
systemic conditions.
v. Fibrinogen concentration: Decreased in congenital
Though the list of investigations appears long, most often
fibrinogenopenia and DIC. (normal value: 160–415
simple tests like platelet count, bleeding and clotting time,
mg/100 ml).
prothrombin time, partial thromboplastin time serve as
vi. Fibrin degradation products: Increased in DIC
primary screening and are of immense value for diagnosis.
(Normal value 2-8 ug/ml).
However if these tests are normal, it suggests vascular
vii. Euglobulin clot lysis time: Prolonged in fibrinolysis
purpuras or Factors XI and XIII deficiencies. Other tests
(Normal value 2-6 h).
like clot retraction time, thrombin clotting time, fibrinogen
viii. Individual factors assays: Normal coagulation screen
content and Hess’s test, are undoubtedly contributory.
with bleeding history may require the assayss. Single
factor deficiency indicates inherited defect whereas
TREATMENT OF BLEEDING DISORDERS
deficiency of multiple factors suggests an acquired
lesion (Normal value ranges from 50-200%). The clinician must determine the actual component (platelet,
ix. Thromboplastin generation test: It is abnormal in coagulation and vascular defects including connective tissue
haemophilia, Christmas disease and Factors X, XI, support of the capillaries) of the normal haemostatic
XII deficiencies. It particularly defines whether machanism that is affected whenever confronted with a case
Factor VIII or IX is missing. It is not routinely done, of bleeding disorder (purpura, bruising, epistaxis, gum
as individual factor assays are available. bleeding, haemarthrosis, haematemesis, haematuria,
 32 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
haemoptysis and soft tissue bleeds). Further presence of
any associated local or general pathology must be looked
for. The urgency involved in the case of bleeding is to be
assessed, before implementing the therapeutic modalities.
The etiology of the specific haemorrhagic disorder must
also be deciphered to institute specific therapy.
SYMPTOMATIC TREATMENT
It consists of rest, local pressure, haemostatics and
immobilisation.
1. Bruises: Heparin with benzyl nicotinate ointment is to
be applied twice daily.
2. Epistaxis (nosebleed)
i. Ensure sitting upright position with head tilted
downward.
ii. Pinch the nose for 5-10 min.
iii. Apply ice pack to the nose.
iv. Adrenaline 1 in 1000 may be packed into the nostril
or nasal cavity tightly (avoid adrenaline in
hypertension).
v. Cauterise bleeding point.
vi. Pass Foley’s catheter and inflate the bulb (useful for
posterior epistaxis).
vii. Consider ligation of specific arteries like ethmoidal.
viii. Arrange blood transfusion, if necessary.
3. Gum bleeding:
i. Mouth gargles with povidone-iodine or Condy’s
solution help to maintain good oral hygiene.
ii. Encourage massage of the gums.
iii. Apply glycerine-borax, or 1-2 drops of choline
salicylate with cetrimide locally.
iv. Vitamin-C 100-500 mg/d useful.
v. Antibiotics administered, if necessary.
4. Haemarthrosis:
i. Elevate the involved extremity and apply ice bags.
ii. Immobilise the joint for 24 h in plaster splint.
iii. Corticosteroids beneficial, if synovitis picture
develops.
iv. Avoid aspiration, unless the swelling becomes
substantial.
v. Encourage muscle exercises and active movements
of joints, once the swelling subsides.
5. Haematemesis
6. Haematuria
7. Haemoptysis
} (Refer respective Chapters).
8. Soft tissue bleeds: Haematoma needs no active treatment.
Antibiotics may be given. Drainage is considered if
infected.
However, retropharyngeal haematoma or haemorrhage
into the floor of the mouth or gastrocnemius haematoma
needs prompt treatment.
NB: Recombinant factor VII a (100 mg/kg dose) controls
bleeding rapidly.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
1. Coagulation Defects
Congenital
Haemophilia A: Replace Factor VIII by IV infusion of Factor
VIII concentrate, prepared from plasma (treated by heat or
chemicals to prevent transmission of viruses) or
cryoprecipitate, or fresh frozen plasma (keeping in mind
possible allergic reactions), so as to raise the plasma level
to 50 per cent. Resistance to therapy may be due to develop-
ment of antibodies.
If minor surgery is to be undertaken, single infusion of
Factor VIII may suffice, whereas mjor surgery needs infusion
twice daily for about two weeks.
Desmopressin (a vasopressin analogue not derived from
blood) is an alternative (0.3 µg/kg in 50 ml saline over half
an hour twice daily) for mild haemophilia and to cover minor
surgery.
Danazol is promising when given daily for two weeks
(600 mg/d) at an interval of three months as an intermittent
therapy.
Epsilon Aminocaproic acid (EACA)-4g IV 4th hourly
for one week, is a valuable adjunct therapy in surgical
procedures which is a fibrinolysis inhibitor.
Von Willebrand’s disease (vascular haemophilia) If the
bleeding site is accessible symptomatic therapy with
thrombin-soaked gelfoam controls the bleeding. The low
Factor VIII level is corrected only by cryoprecipitate, since
Factor VIII concentrate may contain only little Von
Willebrand’s factor. Desmopressin is beneficial for minor
episodes.
Christmas disease (haemophilia B): Factor IX concentrate
may be infused like Factor VIII for haemophilia A. (It
contains also Factors II, VII and X.) Fresh frozen plasma
may be used.
Fibrinogen deficiency: Treatment includes cryoprecipitate
or fresh whole blood (less than 12 h old) or plasma
transfusion.
Deficiency of factor XIII: Fresh blood or plasma is given, if
replacement therapy is indicated.
 Bleeding Disorders
Acquired
Vitamin-K deficiency: Vitamin K1 (10-15 mg) given
parenterally for active bleeding. Synthetic analogue like
menadione is given orally for hypoprothrombinaemia
without bleeding.
Fibrinogen deficiency: Underlying cause to be identified and
corrected (Vide supra).
Primary Fibrinolysis
i. Replace the affected clotting factors (Factors I, V and
VIII) by administration of fresh whole blood, fresh
frozen plasma or fibrinogen.
ii. Antifibrinolytic therapy is given with epsilon
aminocaproic acid (5 g IV followed by 1 g hourly for
8 h not exceeding 30 g/d).
iii. Treat the underlying disorder.
Disseminated Intravascular Coagulation (DIC)
i. Treat the precipitating factors like shock or sepsis.
ii. If the bleeding is predominant fresh whole blood or
fresh frozen plasma or cryoprecipitate or platelet rich
plasma must be given to replace coagulation factors
and platelets. Fibrinogen (5-10 g IV infusion) may by
considered keeping in mind the possibility of hepatitis.
Antithrombin III (11 units/kg IV) may help replace-
ment besides potentiating action of heparin.
iii. Low molecular weight heparin (100 units/kg/SC or
Heparin (5000 units 6th hourly SC or 20000 units IV
continuous infusion over 24 h.
Administered, if there is (a) intravascular thrombo-
sis damaging vital organs, (b) microangiopathic
haemolytic anaemia (c) ongoing defibrination with
persistent bleeding, in spite of replacement therapy
or (d) chronic DIC. However, it is contraindicated if
thrombocytopenia is severe, oral anticoagulants are
not effective in inhibiting clotting process unlike
heparin in chronic DIC. (Low dose heparin before
chemotherapy may prevent DIC in promyelocytic
leukaemia).
iv. Clotting time and platelet count monitored every 12
hours till haemostatic parameters maintained without
replacement. (Most of the patients can be managed
with replacement without heparin).
v. EACA is considered only when fibrinolysis continues,
despite replacement or when there is doubt whether
fibrinolysis is primary or secondary to DIC. However,
for DIC, it is not administered unless heparin is given
first, lest DIC should fatally aggravate with fatal
thrombosis.
33
vi. Tranexamic acid is about ten times more potent than
EACA.
Circulating anticoagulants
i. Treatment is unsatisfactory as it may require massive
doses of particular factor to overcome the inhibitor.
(Majority of them interfere with thromboplastin
formation.)
ii. Whole blood transfusion is beneficial.
iii. Prednisolone with cyclophosphamide may be tried.
iv. Occasionally infusion of Factor IX concentrate is
helpful.
Liver disease
i. Underlying haemorrhagic defect is to be assessed.
ii. Vitamin K IV (50 mg for 4-5 days) given.
iii. Fresh plasma infusion.
iv. Concentrates of Factors II, VII, IX, and X are
beneficial especially in reversible liver disease, with
coagulation defect.
v. Platelet concentrates are administered in severe
thrombocytopenia.
vi. EACA is necessary if fibrinolytic activity is increased.
2. Platelet Defects
Platelet defects are more often acquired rather than
congenital. They may be affected quantitatively (decreased
or increased) or qualitatively (normal count with disordered
function).
Thrombocytopenia
It may be due to (a) decreased production (bone marrow
infiltration or depression or maturation defect), (b) increased
destruction or consumption (hypersplenism, immune
idiopathic thrombocytopenic purpura, or secondary to drugs,
disease or after a ordinary blood transfusion; or
overconsumption DIC, or thrombotic thrombocytopenic
purpura or massive blood transfusion).
Treatment of thrombocytopenia, in general, consists of
treating the underlying cause. Platelet transfusion are
indicated only in severe bleeding cases.
Bone marrow defects (Decreased production)
a. Bone Marrow Infiltrations
Congenital
Marble bone disease (Osteopetrosis) High dose of calcitriol
may be beneficial. Bone marrow transplant may be
considered.
 34 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Acquired
• Lymphoma (Refer to Chapter ‘Pyrexia of Unknown
Origin’).
• Leukaemia Treatment of acute leukaemia includes
supportive care with transfusions (of red cells,
granulocytes and platelets) and/or prevention and
treatment of infections.
1. Acute lymphatic leukaemia
i. Remission is induced with five drug chemo-
therapy cyclophosphamide (1.2 g/M2 IV on 1st
day along with vincristine (2mg iv. on days 1, 8,
15, 22), prednisolone 60 mg/M2 /d for three
weeks), daunorubicin (45 mg/M2/d IV on days 1,
2 and 3), L-asparaginase (6000 U/M2SC twice a
week during the first three weeks).
ii. Consolidation phase of therapy includes IV
cyclophosphamide and vincristine along with SC
cytarabine (100 mg/M2 every 12 h on day 8 for
six doses). Plus oral 6-mercaptopurine (60 mg/
M2 daily for next 8 weeks.
Cranial irradiation with weekly injections of
intrathecal methotrexate (15 mg) for five weeks
is effective for central nervous system
prophylaxis.
iii. Maintenance therapy includes oral 6-mercapto-
purine daily and weekly oral methotrexate (20 mg/
M2) for five weeks.
iv. Late intensification treatment is done with IV
doxorubicin weekly (30 mg/M2) plus weekly
vincristine (2 mg) IV together with daily
dexamethasone (10 mg/M2) for three weeks.
v. Final phase of treatment is employed with IV
cyclophosphamide (1 g/M2 ) plus cytarabine
(75 mg/M2 SC eight doses) along with oral
6-thioguanine (60 mg/M2 daily for two weeks).
vi. For adults, same treatment as above is indicated
but maintenance therapy is prolonged for two
years with daily 6-mercaptopurine and weekly
methotrexate orally plus monthly pulses of
vincristine with five days of prednisolone therapy.
vii. Bone marrow transplantation is considered
especially in younger groups, if necessary.
2. Acute myeloid leukaemia
i. Remission induction regimen includes cytarabine
(100 mg/M2/d for seven days) and daunorubicin
(50 mg/M2/d for three days) both are given by
continuous IV infusion with or without
6-thioguanine (60 mg/M2/d).
After finishing one week induction therapy, bone
marrow examination is done and second induction
course may be entertained if the marrow is
cellular. If hypocellular, repeat marrow exami-
nation weekly for further therapy.
ii. Consolidation therapy includes three courses of
cytarabine and daunorubicin as above, alternating
with high dose of cytarabine every 12 h for eight
doses (each course begins within one week of
recovery).
iii. After the completion of consolidation sequence,
no maintenance therapy is preferred and in case a
relapse occurs, remission is induced as above.
iv. Bone marrow transplantation is considered
especially in younger groups, if necessary.
v. Recurrence is treated with hydroxy urea and
palliative treatment or intensive remission therapy.
3. Chronic lymphatic leukaemia
i. Chlorambucil (0.08–0.12 mg/kg/d) or cyclophos-
phamide (50-100 mg/M2/d orally) form the initial
therapy. Prednisolone (30-60 mg/M2/d) may be
combined.
ii. Combination therapy is indicated in advanced
disease, i.e. cyclophosphamide (800 mg/M2 on
day 1 of every month i.v.) plus vincristine (1 mg/
M2/d on day 1 of every month i.v.) and predni-
solone (40 mg/M2 on days 1 to 5 every month
orally) with or without doxorubicin (25 mg/ M2
on day 1 of every month.) IV immunoglobulin
infusion (400 mg/kg every three weeks) may
mitigate bacterial infections. Fludarabine useful .
4. Chronic myeloid leukaemia
i. Chemotherapy with busulphan (2-8 mg/d) or
hydroxyurea (1-3 g/d) is effective and the dose of
either drug should be reduced as white blood cell
count falls.
ii. Combination therapy includes cytarabine,
6-thiogunaine and doxorubicin. Blast crisis may
be treated with, acute leukaemia therapeutic
programmes, though refractory.
iii. Splenectomy or splenic radiation is not effective.
iv. Interferon-gamma suppresses Philadelphia
chromosome positive cells. Interferon-alpha (9
million units daily s.c.) may result in complete
haematological remission in 70-80 per cent of
cases.
v. Imatinib Mesylate 300 mg/d is superior and useful
in chronic phase. 600-800 mg/d advocated in
accelerated and blast crisis stages.
 Bleeding Disorders
vi. Imatinib may be combined with interferon,
Arabinoside cytocine to overcome resistance to
Imatinib.
vii. Bone marrow transplantation may be beneficial
in some patients. Allogeneic stem cell transplant
is curative.
• Myeloma
a. General measures:
i. Maintain adequate urine output and ambulation
(high fluid intake of three litres advocated if there
is no renal impairment).
ii. Analgesics may be given to control pain.
iii. Anaemia may be treated with blood transfusions.
b. Specific measures:
i. Induction is facilitated by chemotherapy, i.e.
pulses of oral melphalan (7 mg/M2/day) and oral
cyclophosphamide (125 mg/M2/d) plus predni-
solone (40 mg/M2/d) for four days given together
every 4-6 weeks. Vincristine (1 mg IV every four
weeks) may be added, till the paraprotein,
haemoglobin beta microglobulin levels are stable
with clinical improvement for at least three
months. If unresponsive, vincristine, doxorubicin
(adriamycin) (30 mg/M2) and dexamethasone
(20 mg/M2) combination may be valuable; or
improved combination of chemotherapeutic drugs
such as melphalan day 1 to 4, prednisolone, for
1 to 7 days; vincristine together with cyclophos-
phamide (300 mg/M2) are given IV on day 1; and
the cycle is repeated every five weeks; which
schedule appears to yield survival rates of 8-10
years.
Thalidomide plus Dexamethasone is emerging as
promising induction therapy and stem cell
transplantation as consolidation therapy.
ii. Maintenance therapy is facilitated by interferon-
alpha 2a or 2b (3 million units/M2, SC three times
a week). Chemotherapy may be repeated if relapse
occurs.
iii. Thalidomide or bortezomib useful for relapse/
refractory cases.
iv. Radiotherapy is useful for localised problems.
v. Supportive therapy for complications, i.e.
hypercalcaemia (Refer to Chapter—Polyuria).
Hyperuricaemia, hyperviscosity, renal failure,
compression myelitis, intercurrent infections, may
be instituted. Biphosphonates reduce bony
complications. Erythropoietin useful for anaemia.
35
• Aplastic anaemia (Refer to Chapter ‘Fatigue’).
• Myelosclerosis (Myelofibrosis): Androgenic steroids like
testosterone ethanate (600 mg weekly or nandrolone
decanoate (2 mg/kg/week IM) or oxymetholone (2.5 mg/
kg/d orally) may be useful, to correct anaemias apart
from blood transfusions. For haemolytic anaemia
prednisolone or splenectomy considered. Busulphan
tried for painful enlargement of the spleen. Blast crisis
may be treated with mercaptopurine.
Bone Marrow Depression
Congenital
Fanconi’s anaemia: Testosterone and corticosteroids useful.
Bone marrow transplantation may be considered.
Acquired
Drugs and radiation: Withdraw the offending drug.
Corticosteroids may be administered. If necessary, blood
transfusion or platelet transfusion may be considered.
Infections: Treat appropriately infections causing secondary
thrombocytopenia apart from using steroids and
transfusions, as necessary.
Maturation Defect
Congenital
Wiskott-Aldrich syndrome: Bone marrow transplantation is
recommended. If it is not possible, splenectomy considered.
Penicillin cover is suggested after surgery.
Acquired
Megaloblastic anaemia: (Refer to Chapter ‘Fatigue’).
Splenic Defect (Sequestration)
Congenital
Gaucher’s: Treatment is supportive. Splenectomy is
indicated if hypersplenism occurs. Bone marrow
transplantation may be considered. Enzyme (glucosyl
cerebroside) replacement therapy is encouraging.
Acquired
Hypersplenism (Banti’s disease): Portal hypertension may
be relieved by surgical methods like porta-caval or lieno-
renal shunts. Splenectomy is undertaken, if hypersplenism
causes symptoms, due to reduced cell counts, i.e.
thrombocytopenia with spontaneous haemorrhage, severe
anaemia with sequestration of red cells in the spleen,
neutropenia with recurrent infections.
 36 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Decreased Survival of Platelets
(Increased Destruction/Consumption)
Congenital
• Bernard Soulier syndrome: Normal platelet transfusion
is usually effective in the early periods, since the life
span of transfused platelet becomes limited later on.
• Glanzmann’s disease (Thrombasthenia): Platelet
transfusion is considered, if necessary. Aspirin is better
avoided. Epsilon aminocaproic acid may be useful in
some cases (vide infra).
• Storage pool deficiency: There is no specific treatment.
Platelet transfusion may be of value.
Von willebrand’s disease (Vide supra)
Acquired
• Immune thrombocytopenic purpura (Idiopathic or
primary) (ITP): Acute ITP which occurs in children
with mild bleeding requires no specific treatment. If the
bleeding is moderate to severe, specific therapy is
indicated, i.e.
i. Prednisolone (1-2 mg/kg/d) in divided doses till
platelet count returns to normal, after which the
dose is gradually decreased.
ii. In situations like severe bleeding, surgery, delivery
time, IV immunoglobulin (400 mg/kg/d) for 3-5
days is beneficial as platelet count is raised, though
not sustained.
iii. Alternative drugs considered are danazol—an
impeded androgen (400-800 mg/d); cyclopho-
sphamide (50-100 mg/d); azathioprine (3 mg/kg/
d). During immunosuppression an adequate
antibiotic cover is necessary.
iv. IV vinblastine (10 mg) or vincristine (2 mg) once
weekly for 4-6 weeks given if prednisolone
requirements are more.
v. Platelet transfusion therapy is indicated only in
severe cases during splenectomy, since immune
destruction of transfused platelets occurs.
vi. Splenectomy is indicated if unresponsive to steroid
therapy, with life threatening bleeding or relapses
(2 or 3 times) or if the thrombocytopenia is of more
than one year duration (chronic ITP).
vii. Plasmapheresis with or without Staphylococcus
protein A column is considered in chronic ITP.
• Secondary Thrombocytopenia
i. Drug/Infection induced immune thrombocytopenia:
Drugs like quinidine-quinine, sulphonamides;
heparin are withdrawn immediately. Corticosteroids
may ameliorate bleeding. Active haemorrhage may
be treated with blood/platelet transfusion despite
destruction of transfused platelets. HIV and other
viruses or bacterial infections, if incriminated, are
treated appropriately. Similarly other diseases like
SLE and lymphomas may be dealt with accordingly.
ii. Post-transfusion purpura (Isoimmune): Post-
transfusion purpura developing one week after
blood transfusion (Anti-PLA1 antibodies develop
on exposure to PLA1 platelet antigen by transfusion
or pregnancy) is treated with plasmapheresis or IV
gammaglobulin for 3-5 days.
iii. DIC: (Vide supra).
iv. Thrombotic thrombocytopenic purpura (TTP):
Plasmapheresis is life saving and initiated imme-
diately. If it is not available, fresh frozen plasma
(6 units) infused daily. If unresponsive, IV immuno-
globulins or steroids or immunosuppression are the
other options to be considered.
v. Massive blood transfusion (secondary to dilution):
Transfusion of platelets is considered for thrombo-
cytopenia (if platelet count falls below 60000/mm3
or microvascular haemorrhage occurs) secondary
to massive transfusion, i.e. more than 12 units.
vi. Haemolytic uraemia syndrome: Treatment includes
dialysis for acute renal failure and careful use of
blood transfusions for anaemia are the essentials
of therapy.
vii. Myeloproliferative disorders: Chronic myeloid
leukaemia and myelofibrosis (vide supra).
• Thrombocytosis
Primary thrombocytosis (thrombocythaemia) is treated
by administration of p32 (3 to 4 millicuries) or
hydroxyurea.
Or plasmapheresis. Busulphan or Melphalan is also
beneficial. Recently Anagrelide (1 mg/d) is effective.
Splenectomy is contraindicated.
Secondary Thrombocytosis: Underlying cause is treated.
• Thrombocytopathy/Thrombasthenia (Qualitative Platelet
Defects)
The platelets may be small or large or fail to
aggregate with ADP (Thrombasthenia) or platelet
phospholipid (Platelet factor 3) availability is impaired
(Thrombocytopathy). The treatment is symptomatic.
Platelet transfusion therapy is undertaken if indicated.
Therapy for the acquired qualitative defects is directed
at the underlying disorder.
Bleeding Disorders 37
 38 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
3. Capillary Endothelial Defects
Vascular Defects (Vascular Purpuras)
Congenital
Hereditary haemorrhagic telangiectasia: Local pressure and
symptomatic treatment with topical haemostatics may be
tried in the accessible areas. Laser therapy may prevent
bleeding from single lesions. Multiple bleeding points may
lead to chronic iron deficiency when parenteral iron is
preferred. If the bleeding is severe, blood transfusion may
be required.
Hereditary capillary fragility: Apart from symptomatic
measures, effective local haemostasis is essential in surgical
procedures. Adrenocorticosteroids may be tried. Effective
surgery can be undertaken during the phase of normal
bleeding time.
Ehlers-Danlos syndrome: Except avoiding trauma there is
no effective treatment. Symptomatic measures may be
undertaken if necessary.
Acquired
Symptomatic purpuras
i. Infections: Appropriate antibiotics to be administered.
ii. Drugs: Purpura subsides within a week after
withdrawing the drug.
iii. Scurvy: Adequate Vitamin-C (500 mg twice daily)
clears the purpura within 1-2 days.
iv. Uraemia: (Refer to Chapters ‘Oliguria’ and ‘Polyuria’).
v. Steroids and Cushing’s disease: Withdrawal of steroids
results in clearance of purpuras.
Treatment of Cusing’s disease includes adrenalectomy
(bilateral for cortical hyperplasia or unilateral for
adrenal tumour) with or without putuitary irradiation.
Selective removal of ACTH secreting pituitary
microadenoma is indicated, if necessary.
vi. Dysproteinaemia: Removal of paraproteins by
plasmapheresis or specific chemotherapy of the
primary disease, controls haemorrhagic episodes.
Henoch-Schönlein purpura (Anaphylactoid purpura): It is a
self-limiting disease. However, corticosteroids are useful
specially for joint involvement and soft tissue swelling or
abdominal manifestations rather than cutaneous or renal
involvement, which is treated as per crescentic glomerulo-
nephritis. (Refer Chapter ‘Haematuria’).
Autoerythrocyte sensitisation: Corticosteroids may effect
relief temporarily. Any associated psychological component
may be treated.
Purpura simplex (Simple easy bruising): It calls for no
treatment. Reassurance and withdrawal of any precipitating
events advocated.
Senile purpura (Involutional purpura): There is no effective
treatment. Shearing strain to the skin may be avoided.
Necrotising vasculitis: This heterogeneous disorder is
treated with the combination of prednisolone (1 mg/kg body
weight) and oral cyclophosphamide (1-3 mg/kg/d.). The
former is tapered over 1-3 months and the latter is continued
at least for three months or longer, till the disease process is
controlled.
 Chapter
Chest Pain
3
The unpleasant perception of pain is one of the earliest
warnings of morbidity. The exact stimulus for pain may vary,
e.g. accumulation of excess of metabolites in the heart
muscle as in angina. The pain in angina arises in the nerve
fibres within the heart muscle. The pain impulses are
conducted through the sympathetic nerves, travel through
the ganglia, enter the spinal cord by way of white rami
communicantis, ascend along the spinothalamic tract of the
cord and reach the thalamic region of the brain. The intensity
of pain may vary from individual to individual. Patients with
a high pain threshold will have less pain and vice versa. All
chest pains need not necessarily be of serious import.
However, it should be kept in mind that all chest pains
are due to an underlying serious disease unless there is an
overwhelming evidence to the contrary. The physician’s
responsibility is great since the diagnosis depends entirely
on the interpretation of this subjective symptom, with that
elusive quality of clinical judgement.
CAUSES OF CHEST PAIN
The causes of pain in the chest can be grouped on the basis
of anatomical origin—the chest or abdomen or otherwise
(Table 3.1).
CHEST
Cardiac
• Myocardial Ischaemia
This is caused by the narrowing or spasm of the coronary
vessels (right, left, circumflex and anterior descending)
(Fig. 3.1) due to atherosclerosis in a majority of cases.
Relative increase in myocardial oxygen demand may be seen
in anaemia or valvular disease or thyrotoxicosis. Sometimes,
ischaemia can be produced by leutic aortitis or paroxysmal
tachycardia.
The three clinical syndromes recognised included under
ischaemic heart disease (IHD) are:
1. Angina pectoris: Diagnosis of angina pectoris depends
on eliciting accurate history. Angina pectoris means
compression of the chest. The pain is characteristically
retrosternal, radiating upwards towards the neck or
downwards towards the epigastrium or sidewards towards
the left arm, occasionally to the right or back of the chest.
The patient complains of a constriction or squeezing or
feeling of tightness, lasting for not more than few minutes
(less than 5 minutes and rarely 15 minutes), often related to
an effort (during or after) and relieved by rest or nitrates.
The duration of pain is usually never less than 30 seconds.
The pain is described as stabbing coming in sharp jabs.
Irregular pain, increasing from time to time or momentary
in duration is probably not angina.
The term ‘stable angina’ denotes pain which continues
for several weeks without significant change in the
frequency or duration. One should also always note the
potential risk factors (like obesity, hypertension, diabetes,
smoking, high LDL and low HDL fractions of cholesterol,
a positive family history, Type-A personality and sedentary
occupation) which may be of predictive value in arriving at
a conclusion.
In the majority of cases there may not be any physical
signs. However, two important signs may be sought viz.
atrial gallop rhythm (4th sound) or paradoxical splitting of
the second sound.
The ECG is usually normal at rest but RS-T depression
of more than 1 mm may be present which confirms the
diagnosis. This electrocardiographic appearance may also
be produced during exercise. Radioisotope scanning of the
myocardium with Thallium-201 may delineate ischaemic
areas that develop during the exercise.
 40 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 3.1: Aetiological classification of chest pain Other useful investigations are Holter Monitoring
(dynamic ECG) and coronary angiography.
A. Chest
1. Cardiac
A variant of this condition is described by Prinz Metal
*a. Myocardial ischaemia in which the pain may occur in a cyclic or recurrent pattern
b. Pericarditis and pericardial effusion (*Cardiac at rest usually at the same time of the day—often at night.
tamponade) The ECG shows raised ST segment. This is due to coronary
c. Tachyarrhythmias spasm and may be associated with a high frequency of
d. Mitral valve prolapse arrhythmias.
e. Hypertrophic obstructive cardiomyopathy
f. Aortitis 2. Unstable (Pre-infarction) angina: There will be
g. Aneurysms
prolonged cardiac pain lasting 30 minutes or more occurring
i. Aortic aneurysm
*ii. Dissecting aneurysm
at rest or minimal exertion without evidence of myocardial
h. Chronic pulmonary hypertension necrosis. It is of new onset manifesting in a crescendo
2. Pulmonary fashion—increasing angina over a short period of time (days
*a. Pulmonary embolism or weeks) and refractory to nitrates. There is an increased
b. Pleurisy risk of developing infarction. The ECG reveals ST-T changes
c. Pneumonia
without actual evolutionary QRS complex. Serum cardiac
d. Spontaneous pneumothorax—*Tension pneumothorax
e. Bronchogenic carcinoma
markers (enzymes) are not elevated. Unstable angina also
3. Mediastinal includes a postmyocardial angina, resting prandial nocturnal
a. New growths angina or a worsening stable angina (change in severity or
b. Mediastinal emphysema frequency of chest pain).
4. Oesophageal (Vide Infra)
5. Musculoskeletal 3. Myocardial infarction: It is always due to the occlusion
a. Costochondritis (Tietze’s Syndrome) of the coronary arteries. The pain is that of angina often
b. Xiphoidalgia without a precipitating cause like exercise and lasts even
c. Spondylitis
for hours varying, from a feeling of tightness to extreme
d. Pleurodynia
e. Subacromial Bursitis agony. Associated symptoms like breathlessness, restless-
f. Left periarthritis of the shoulder joint ness, sweating and vomiting are obvious. Rarely, it may be
g. Trauma painless in which case it may manifest as syncope or
6. Neurovascular unexplained left heart failure.
a. Herpes zoster On examination, there is slight elevation of jugular
b. Thoracic outlet compression syndrome
venous pressure. The pulse may be feeble or irregular. There
c. Hyperabduction syndrome
d. Mondor disease
is a tendency for the blood pressure to fall. Auscultation
may reveal atrial gallop or diastolic gallop, paradoxical
B. Abdomen (Alimentary affections)
1. Acute indigestion splitting of second sound or a pericardial rub on 2nd or 3rd
2. Gastric or colonic distension day or a systolic murmur due to papillary muscle
3. Oesophageal dysfunction.
a. Oesophageal motility disorders: Spasm The cardinal complications are
b. Hiatus hernia and reflux oesophagitis a. Cardiac failure
*c. Oesophageal rupture
*4. Perforated peptic ulcer
b. Cardiogenic shock
*5. Acute pancreatitis c. Cardiac arrhythmias
6. Cholelithiasis d. Thromboembolism
C. Endocrinal e. Rupture of the ventricular septum or heart.
1. Mammary dysplasia The important prognostic indicators are left ventricular
2. Mastitis functional status and extent of the coronary heart disease.
D. Psychogenic The ECG shows
1. Acute anxiety a. Deep symmetrical inverted T waves without
2. Chronic anxiety (Da Costa’s syndrome or effort syndrome) Q waves, is labelled as subendocardial or nontrans-
*Life-threatening causes. mural infarction (Fig. 3.2).
 Chest Pain
Fig. 3.1: Coronary circulation
Fig. 3.2: Subendocardial infarction—Deep symmetrical
inverted T waves in percardial leads with ST depression in
standard and pericardial leads and absent Q waves
b. Prominent or monophasic Q waves with elevated ST
segments followed by inverted T waves: evidence
of through and through (transmural) infarction.
41
i. Changes localised to L1 aVL, V 1 to V 6—
extensive anterior myocardial infarction
(depending on the extent).
ii. Changes localised to V1 to V 4 without or
indefinite characteristic changes in standard
limb leads—ateroseptal infarction (V 1-V 2
septal) and V3-V4 (anterior).
iii. Changes localised to L1, aVL, V 3 to V6—
anterio-lateral infarction L 1, aVL, V 5 -V 6
(lateral) and L1, aVL (high lateral) and V3-V4
(anterior).
iv. Changes localised to L2, L3 and aVF—inferior
infarction.
v. Changes like prominent R wave with ST
depression and upright T waves localised to
V1 to V3—posterior infarction.
vi. Changes such as prominent R wave with ST
depression and upright T waves localised to
V1 to V3 besides prominent Q waves with ST
 42 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 3.3: A: Anterior infarction, B: Anteroseptal infarction,
C: Anterolateral infarction, D: Inferior infarction, E: Posterior
infarction, F: Posterolateral infarction (A and B = LAD; D = RCA;
E = RCA or circumflex and Lateral = circumflex are the culprit
vessels)
elevation and associated T wave changes in V5
and V6—posterolateral infarction (Fig. 3.3).
vii. Isolated right ventricle myocardial infarction
shows changes such as ST elevation in V3R;
V 4 R (may be associated with inferior
myocardial infarction), i.e. RCA involved.
ECG may remain normal in case of small myocardial
infarction for 48 hours.
The increased values of CK or CK-MB (i.e.) CK-MB
> 6% of total CK or CK-MB > 16 IU/L within 48 hours and
SGOT within four days indicate myocardial necrosis. LDH
levels may remain elevated upto 10 days. Troponin-T levels
are elevated within 6-12 hours (>0.01). Normal (< 0.01).
Echocardiography may demonstrate dyskinetic areas of
damaged ventricular wall.
Acute coronary syndrome consists of unstable angina (Non
S-T elevation) and AMI (non S-T elevation myocardial
infarction (NSTEMI) or non Q wave myocardial infarction
and S-T elevation (STEMI) OR Q Wave myocardial
infarction).
If ischaemia is severe enough with typical S-T change
or Q wave and the increased levels of cardiac markers, then
AMI is established. Otherwise unstable angina is to be
entertained. It results from inflammation and disruption of
atherosclerotic plane with subsequent thrombosis.
• Pericarditis and Pericardial Effusion
The pain is felt in the sternal region and to the left radiating
to the neck, shoulders, aggravated by deep breathing,
coughing, swallowing, movements of the chest wall and in
recumbent position. It is relieved by sitting up and leaning
forward. The characteristic physical sign is the presence of
friction rub. ECG shows ST elevation which is concave
upwards with upright T waves, unlike that of myocardial
infarction which has an upward convexity with initial upright
T becoming inverted in 48 hours.The diagnosis can be
complete if the cause is determined, which includes
connective tissue disorders, infections like tuberculosis,
acute myocardial infarction, postmyocardial infarction
(Dressler’s) and uraemia. Signs of inspiratory swelling of
neck veins, pulsus paradoxus, and distant heart sounds
suggest associated pericardial effusion. ECG shows low
voltage QRS and T waves. QT interval is not prolonged as
in congestive cardiac failure. ECHO confirms the diagnosis.
Rising jugular venous pressure and fall of systolic pressure
indicate cardiac tamponade. (Acute cardiac compression due
to increased intrapericardial pressure).
Constrictive pericarditis may follow any type of
pericarditis (the commonest is tuberculosis). Clinical
features are that of mainly right heart failure with severe
ascites, pulses paradoxus, loud third sound, hepato-
splenomegaly. X-ray shows small heart.
 Chest Pain
Fig. 3.4: 2D echo showing buckling of the two leaflets in the
left atrium in systole, diagnostic of mitral valve prolapse
• Tachyarrhythmias
Refer to Chapter ‘Palpitations’.
• Mitral Valve Prolapse
This lesion is associated with dyspnoea and palpitations.
The pain is variable, has no clear-cut diagnostic feature and
is not usually of ischaemic origin. There is a midsystolic
nonejection click and a late systolic murmur. ECG shows
an inconstant T wave inversion in L3 and AVF. Diagnosis
can be confirmed by ECHO (Fig. 3.4).
Progressive mitral regurgitation may occur.
Hypertrophic obstructive cardiomyopathy Angina,
dyspnoea, palpitations or syncope are usually complained.
Physical examination reveals sharply rising jerky
peripheral pulse, a prominent ‘a’ wave in jugular venous
pulse, a double apical impulse, a paradoxical splitting of
the second heart sound, a third sound and ejection systolic
murmur along the left sternal border or at the apex.
The ECG shows left ventricular hypertrophy with
abnormal deep broad Q waves stimulating old myocardial
infarction. ECHO reveals a disproportionate hypertrophy
of the ventricular septum with a systolic anterior motion
(SAM) of the anterior mitral leaflet of mitral valve. Diastolic
filling pressure raised
• Aortitis
Leutic history may be forthcoming. Pain is usually localised
and not related to exertion. Auscultation reveals an aortic
43
systolic murmur with a loud bell-like second sound with
evidence of dilatation of ascending aorta.
• Aneurysms (Dilatation of artery >1.5 times compared
to adjacent normal segment)
Aortic aneurysm: Aortic aneurysm is not a common entity
now. Aneurysm of the ascending aorta is known as the
aneurysm of physical signs in contrast to that of the arch of
aorta which is termed as aneurysm of symptoms. The former
shows a visible pulsating mass in the first or second right
interspace. A systolic thrill and murmur, a loud second sound,
are often present. Other symptoms and signs result from
pressure on the mediastinal structures causing hoarseness of
the voice (recurrent laryngeal), cough and stridor (trachea),
dysphagia (oesophagus), collapse of the lung (left bronchus),
tracheal tug due to depression of the main bronchus, inequality
of the pulses (innominate artery occlusion), oedema of the
face and neck and venous engorgement of the upper half of
the body (superior vena cava).
Dissecting aneurysm: This is also uncommon. The pain is
very severe at the very onset, radiating to the back, neck
and abdomen and sometimes lower limbs in an elderly
person with hypertension.
Unless shock is present, BP is maintained and may be
different in the two arms. Evidence of occlusion of an artery
may be appreciated like the disappearance of the peripheral
pulse, hemiparesis, blindness in one eye, etc. Aortic
regurgitation if developed is a valuable diagnostic feature.
Widening of aortic shadow on radiography may be seen.
Diagnosis is confirmed by ECHO or aortography.
• Chronic Pulmonary Hypertension
Substernal pain due to decreased cardiac output is also seen
in chronic pulmonary hypertension as seen in mitral stenosis
or Eisenmenger’s syndrome. The characteristic signs like
cyanosis, parasternal heave, a loud second sound, an ejection
systolic murmur and an early diastolic murmur in the
pulmonary area, a pansystolic murmur in the tricuspid area,
and an apical murmur of the underlying heart disease will
help diagnosis. Chronic thromboembolic obstruction of
major pulmonary arteries; as a consequence of acute
pulmonary embolism is a lurking cause.
Pulmonary
• Pulmonary Embolism (Acute Cor Pulmonale)
The diagnosis is easy, in case, there is sudden onset of central
chest pain, breathlessness, cyanosis, shock, unexplained
 44 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
fever and tachycardia. If infarction occurs, there will be
associated features of pleuritic pain and haemoptysis. Pleural
friction rub and signs of consolidation may be present. The
cardiac signs include raised jugular pressure, invariably loud
P2, systolic murmur and gallop rhythm.
If a terminal artery is occluded, findings may be minimal
or absent. In a medium size artery occlusion, pulmonary
symptoms and signs and X-ray densities occur, whereas in
a large artery occlusion, predominant cardiac signs appear.
Pulmonary embolism is due to cardiac causes or deep
venous thrombosis. It occurs usually in congestive cardiac
failure, postmyocardial infarction, prolonged recumbency,
postoperative period (10th day usually), and due to the use
of oral contraceptives. ECG shows Q3 and T3 type with T
inversions in V1 to V4 (AVF does not show abnormal Q
waves), right axis deviation with prominent S1 waves and
clockwise rotation or may be normal. Chest radiography
shows dilation of one of the main branches of the pulmonary
artery (plump hilum) with unusual translucency in the lung.
Dilatation of one of the main branches of the pulmonary
artery, radiolucent density in the lung, and elevated
diaphragm are frequent findings on radiography or may be
normal. Elevated LDH and bilirubin level with normal
SGOT is of some diagnostic value. However, reduced
arterial blood gases, pulmonary angiography, and lung
scanning will confirm the diagnosis. Plasma D-Dimer level
increased (> 500 ng/ml).
Severe PAH and RV dysfunction (RVF) must be
investigated for chronic pulmonary embolism.
• Pleurisy
The pain is sharp and stabbing in nature and increasing on
inspiration. The characteristic physical sign of pleural rub
is heard during inspiration and expiration. Holding the breath
in expiration relieves the pain and pleural rub disappears. It
is usually due to infection or infarction.
• Pneumonia
History of high fever, pleuritic pain and physical signs of
consolidation like dull note, bronchial breath sounds and
fine crepitations will confirm the diagnosis.
• Bronchogenic Carcinoma
Refer chapter Haemoptysis
• Spontaneous Pneumothorax
This is distinguished by abrupt onset of pain with dyspnoea,
deviation of the trachea to the opposite side, diminished
movements, a hyperresonant percussion note on the affected
side. Valvular type (tension pneumothorax) allows trapping
of air during inspiration and prevents escaping of air during
expiration. Large amounts of air may be trapped during bouts
of cough resulting in increasing dyspnoea and even
asphyxia. Chest X-ray shows the sharp edge of the collapsed
lung and the air between this and the chest wall collection
is seen as translucent area without any lung markings.
Mediastinal (Chest)
• New Growths
The symptoms and signs of the mediastinal tumours
essentially depend on the pressure on the neighbouring
structures like phrenic nerve resulting in diaphragmatic
paralysis, sympathetic trunk resulting in Horner’s syndrome,
pericardial rub or effusion (Pericardium) and others as
described in aortic aneurysm.
• Mediastinal Emphysema
There is abrupt onset of pain in the chest radiating to the
arms and neck besides dyspnoea. The diagnosis is easily
made by the characteristic signs of loud crunching, crackling
sounds over the sternum and associated subcutaneous
emphysema. Lateral view of the skiagram chest taken at
full expiration reveals air in the anterior mediastinum
(retrosternal area).
Oesophageal (Chest)
Vide infra.
Musculoskeletal
• Costochondritis (Tietze’s Syndrome)
Pressure over the costo-chondral junctions and especially
on the left fourth rib reveals tenderness, pain in costal
cartilage is exaggerated by movements, or coughing.
• Xiphoidalgia
Xiphoidalgia is a similar entity involving the xiphisternum.
• Spondylitis
Cervical spondylosis is one of the common, often
unrecognised causes of chest pain referred to the precordium
and left arm due to degeneration of the synovial
intervertebral joints and ligaments. It is recognised by
 Chest Pain
restricted movements of the neck in all directions. X-ray of
cervical spine shows narrowing of disc spaces and
osteophytes.
Ankylosing spondylitis may cause diffuse pain in the
anterior chest wall with tenderness over the sternum or
cartilages.
• Pleurodynia
The pain is identical to that of pleurisy and caused by group
B-Coxsackie. Virus Fever, headache, and myalgia are
associated features.
• Subacromial Bursitis and Periarthritis of
Left Shoulder Joint
The pain is present over the shoulder region and also in the
arm and anterior chest wall. The left shoulder is involved.
The pain is likely to be interpreted as angina. The pain is
exaggerated by elevating or rotating the arm. The movement
is also limited.
• Trauma
The fractured rib can be localised by physical examination.
Gentle pressure over the sternum may make the pain worse.
A slipping rib cartilage may also cause chest pain. Usually
cartilages of 8th, 9th, and 10th ribs are involved having been
displaced by fracture.
Neurovascular (Chest)
• Herpes Zoster
The pain along the intercostal region is burning or shooting
in character and loated in the corresponding dermatome.
There will be an area of hyperalgesia. The pain is not affected
by breathing. The development of rash later confirms the
diagnosis.
• Thoracic Outlet Compression Syndrome
Compression of the lower trunk of brachial plexus by the
cervical rib or between the clavicle and first rib or getting
stretched as it passes over the first rib causes pain (scalenus
anterior syndrome). The pain is sharp and felt in the
precordium or arm, radiating to the 4th or 5th finger. It is
associated with numbness and tingling. Objective
neurological signs and local tenderness can be elicited. Hand
may be cold or radial pulse may be absent if subclavian
artery is compressed.
45
• Hyperabduction Syndrome
This is characterised by pain in the upper limb with
paresthesia and a feeling of numbness in the hand and
fingers. Objective vasculr signs may be present. It is due to
constriction of the subclavian artery and brachial plexus by
the hyperabduction of the arm during sleep or trauma.
• Mondor Disease
There is a pleuritic type of pain provoked by raising the
arm. It is due to phlebitis of subcutaneous and anterior
thoracic veins. The vein can be palpated as a tender cord.
ABDOMEN (ALIMENTARY AFFECTIONS)
• Acute Indigestion
The pain is not retrosternal. It is not radiating, marked
dyspeptic symptoms are expressed. More often, angina is
regarded as acute indigestion and vice versa. Hence, a
careful approach in delineating one from the other is highly
desirable.
• Gastric or Colonic Distension
Gastric distension due to aerophagy or other causes can
cause substernal pain. Similarly pain may be felt in the left
hypochondrium and precordial region radiating to the left
arm, due to distension of the splenic flexure of the colon,
irritable colon, or chronic amoebiasis.
• Oesophageal
Oesophageal motility disorders The pain is central, with a
feeling of tightness and radiates down both arms. It is
periodic, like intestinal colic without relation to effort but
associated with swallowing (Odynophagia). Diagnosis is
confirmed by traditional barium swallow or oesophageal
manometry or provocative tests or scintigraphic
measurement of oesophageal transit.
Reflux oesophagitis Incompetence of cardiac sphincter
facilitates repeated regurgitation of gastric juice. Sliding
hiatus hernia may be present. The pain is felt in the midline
of the chest, radiating to the jaw or shoulder or back due to
oesophageal spasm. Heart burn, pyrosis or cough are
characteristic. The pain is related to food, aggravated while
bending forward or in the recumbent position and relieved
by sitting upright or with antacids. Gastro-oesophageal
reflux oesophagitis is established by oesophagoscopy and
 46 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
distal biopsy; 24th pH monitoring; or Bernstein’s test
(reproduction of heart burn on N/10 HCl instillation and
not on saline).
Oesophageal rupture
There is sudden substernal pain following violent vomiting
or retching. Shock develops rapidly. Haematemesis may
occur. X-ray shows Naclerio’s sign (air in V or triangular
shape in the thorax below the dome of left diaphragm
posterio-medially), pneumomediastinum, hydrothorax or
hydropneumothorax. It is confirmed by radiopaque contrast
study.
• Perforated Peptic Ulcer
Past history of relationship of pain to food is obvious. The
most striking feature is severe pain accompanied by
vomiting, pallor and sweating. It can be timed accurately.
The rigidity of the abdomen and obliteration of the liver
dullness to percussion and absent intestinal sounds on
auscultation are very helpful diagnostic features. The
X-ray taken in the vertical position reveals gas under the
diaphragm (Refer Fig. 1.1).
• Acute Pancreatitis
Profound shock may be present. Past history of occasional
attacks of dyspepsia or alcoholic excess associated with pain
in the back will be forthcoming. This is distinguished by
sudden attacks of agonising pain in the epigastrium. It
radiates to the sternum, back or either of the shoulders,
worsens in supine or prone position and is relieved by
drawing knees to the chest. Periumbilical discoloration
(Cullen’s sign) or at flanks (Grey Turner’s sign), rigid
abdomen, jaundice may be present. Ultrasound scanning is
Fig. 3.5: X-ray of chest in upright position showing free air
under the diaphragm—Peptic ulcer perforation
of immense value. (See Fig 1. 4). LDH may be raised
(> 600 IU/L) whereas calcium levels fall. Rising levels of
serum amylase during the first 48 h will be of high diagnostic
value.
Alcoholic bouts, gallstones, mumps are important
causes. Acute Respiratory Distress syndrome. Acute renal
failure are early complications. Later after one week,
Pseudocyst or abscess may result.
• Cholelithiasis and Cholecystitis (Biliary Colic)
A sudden pain is felt in epigastrium which gradually
increases in a wave-like manner. It is frequently agonising
and referred to the front of the right chest, back or shoulder.
Fever, vomiting, positive Murphy’s sign indicate associated
acute cholecystitis. Past history of dyspepsia related to food
and precipitated by faulty or fried foods is often encountered.
Cholecystography or scanning of the abdomen will help the
diagnosis. (Refer Fig. 1.2).
ENDOCRINAL
Mammary Dysplasia; Mastitis
Pain in the left mammary region often calls attention to
lumps in the breast on both sides. The discomfort is said to
increase in premenstrual period. Cyclic breast pain and
fluctuation in the size of lumps will be the differentiating
features.
PSYCHOGENIC
Acute Anxiety
Most often a woman complains of precordial pain with
palpitations, dyspnoea, dizziness and angor animi. The
absence of objective evidence of organic disease and the
psychological background in the clinical set up are important
distinguishing features.
Chronic Anxiety (Da Costa’s Syndrome)
It is characterised by a dull ache or sharp, stabbing pain
increasing from time to time momentarily in the region of
the apex or inframammary area, often unrelated to an effort.
Sometimes, it may occur after exertion but not at all during
exertion. Dyspnoea may occur at rest with inability to take
a satisfactory breath. The other reatures of the syndrome
are palpitations, easy fatigability, dizziness, psychic
symptoms like depression, phobia and hypochondric
elements, tachycardia, cold and moist palms. The pain is
not relieved by nitroglycerine. The diagnosis is confirmed
 Chest Pain
by mere exclusion of organic heart disease and also
supporting clinical data. The ECG is usually normal but in
some, inversion of T wave is seen in L2, L3 precordial leads.
Very often, T waves are normal in recumbent position and
abnormal in the upright position. The breath holding test is
usually positive, i.e. breath cannot be held for more than 30
seconds. The duration of breath holding after
hyperventilation, divided by the duration of breath holding
before fast breathing, which is termed as hyperventilation
index, is always less than 1.3 (Normal > 1.3).
CLINICAL APPROACH
Careful evaluation implies delineation of the nature of pain
(cardiac or noncardiac), recording precise history, meticu-
lous physical examination and appropriate investigations.
History
The nature of pain can be evaluated based on the following
features elicited by history:
a. Site: Anterior chest pain can be either in the centre of
the chest or in its lateral aspects. The central chest pain
may be retrosternal or precordium or inframammary. The
lateral chest pain includes all tissues of the lateral chest
wall.
b. Character: The pain may be in the nature of mild
discomfort or extreme agony. The pain which is
strangling, compressing or constricting is highly
suggestive of angina. Dull ache is common in myalgia,
pricking or stabbing pain in psychoneurosis, and sharp
catching pain in pleurisy.
c. Duration: If the pain is severe, sustained without
fluctuations, and of brief duration lasting for about
5 minutes, it is highly suggestive of angina. If it is more
prolonged and persistent, it may be a myocardial
infarction. The duration is usually less than 30 seconds
in functional chest pain.
d. Radiation: The central chest pain usually indicates pain
originating from heart or oesophagus. The pain radiates
to the left shoulder, arm, wrist, neck, jaws and
epigastrium.
e. Provoking and relieving factors: If the pain is
precipitated by exercise or emotions or extremes of
temperature, and made better by stopping exercise or
relieved by sublingual nitrates, it is angina. If it is
aggravated by breathing, twisting movements of the
muscles in the chest wall and swallowing, and relieved
by leaning forward, it is pericarditis.
47
If the pain increases on inspiration, disappears on
expiration and breathing is restricted, it is pleurisy.
If the pain is precipitated by food, lying flat, or bending
forward, and made better by sitting from the supine position
and relieved by antacids, it is suggestive of reflux
oesophagitis.
Similarly, pain occurring one hour after food and relieved
by antacids is peptic ulcer.
If pain is associated with sweating or dyspnoea or
dizziness, it is likely to be due to a cardiac lesion. If
associated with nausea or vomiting or indigestion, it is likely
to be of gastric origin or heart itself. If pain is precipitated
by hot or cold drinks or induced by swallowing or associated
with heart burn or dysphagia it is of oesophageal aetiology.
Sighing and palpitations indicate anxiety.
Physical Examination
Inspection of neck veins and examining the radial pulse are
contributory. Palpate the chest wall over the costochondral
junctions, ribs and muscles for identifying areas of
tenderness or hyperasthesia to exclude local and superficial
lesions.
Similarly look for any periumbilical discoloration and
rigidity of the abdomen. Palpate for any areas of tenderness
in the epigastrium and other areas.
Check the percussion of the chest wall for any areas of
hyper resonance or obliteration of normal dullness.
Auscultate precordium for paradoxical splitting of the
second heart sound or third sound presence, or murmurs or
friction rubs or crunching sounds and abdomen also for
intestinal sounds.
Investigations
ECG
a. ECG: Resting ECG for any ST depression.
b. Stress test (for those with good left ventricular function):
ST depression, down sloping, or horizontal is significant
(Fig. 3.6).
Figs 3.6A and B: Exercise-induced ischaemic changes—
Marked ST depression A: At rest, B: After exercise
 48 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

X-ray
a. Chest
i. Pleuropulmonary disease
ii. Cardiac silhoutte
iii. Rib lesions
b. Cervical spine for spondylitic changes
c. Abdomen
i. Cholelithiasis
ii. Any gas shadow undermeath the diaphragm
d. Barium swallow and GI Radiography.

Haematology
a. RBC and Hb%
b. ESR
c. CRP

Enzyme Study
i. Myocardial infarction-
a. SGOT-raised during 1 to 3 days
b. LDH-raised during 2 to 7 days
c. CPK and CK-MB-raised. During 1 to 3 days
ii. Acute Pancreatitis-
a. Serum Amylase Raised
Lipid Profile: Increased LDL and LP(a) Levels increase
risk for CAD
a. Serum total cholesterol and its fractions (LDL, HDL,
VLDL)
b. LDL/HDL ratio and TC/HDL.
c. Triglycerides
d. Lipoprotein a-LP (a) Measurement is useful in
normolipidaemic patients as high levels (> 30 mg/dl)
impart increased risk for coronary artery disease.
e. Apolipoproteins (APO A-1 and APoB).
Cardiac markers of myocardial damage: Troponin-T
May rise after 6 hours and remain elevated for one week.
Neopterin as a marker for acute coronary syndrome and
MI.
Special Tests
a. Echo cardiography and Stress Echo
b. Nuclear imaging
i. Radionuclide angiography (for those with poor left
ventricular function)
Fig. 3.7: Myocardial perfusion scintigraphy with thallium
T 1-201 2.5 mCi shows reversible perfusion abnormality
(ischaemia) in apex, septum, anterior wall (LAD territory)
ii. Thallium scintigraphy (Fig. 3.7)
iii. Positron emission tomography (PET)
iv. Radionuclide ventriculography (RNVG)
c. Coronory arteriography (For those having positive
exercise test and good left ventricular function especially
in patients selected for coronary surgery)
d. Multislice computed tomography (MSCT) for assessing
coronary artery stenosis.
e. Ultrasound examination of abdomen for evidence of
pancreatitis.
f. Endoscopy for ascertaining any oeasophago-
gastroduodenal pathology.
g. Lung scan for confirming pulmonary embolism.
h. D-dimer (< 500 ng/ml is normal).
Therapeutic Trial
Sublingual isosorbide dinitrate or nitroglycerine relieves
angina in less than two min. Delayed relief in 5-10 min. is
not compatible with angina and may be due to oesophageal
spasm or biliary colic, since nitrates affect generalised
smooth muscle relaxation.
From this scheme of examination one can reasonably
deduce the anatomical site affected, and its possible
mechanism.
 Chest Pain
TREATMENT OF CHEST PAIN
The management of chest pain depends on the assessment
of the possible cause, whether it is cardiac or noncardiac.
The clinician must be aware that an incorrect diagnosis of
angina pectoris may lead to unnecessary psychological and
other problems. Failure to recognise myocardial ischaemia,
on the other hand, may lead to dangerous consequences.
Hence, this challenging diagnostic problem must be
diligently tackled, exercising all knowledge at command.
Nevertheless, it must be realised that the severity of pain
may not always correlate with the seriousness of the
underlying disease and there may be dual aetiology of pain
(both noncardiac and cardiac origin). Most often,
observation pays dividends.
Symptomatic Relief
a. ECG is a clinching accomplice. If this primary
investigation does not throw any light and if central chest
pain is suspected to be due to angina on clinical grounds,
the initial management consists of administration of
sublingual glyceryl trinitrate (0.25-0.5 mg) which yields
desired result dramatically within two minutes. Delayed
relief may be due to oesophageal spasm. Sublingual
isosorbide dinitrate (2.5-10 mg) is the other alternative
with relatively slow onset and longer duration of action.
b. If the pain is presumed to be noncardiac (oesophageal),
reflux suppressants and antacids may yield results.
c. Analgesics and NSAIDs may be beneficial for
musculoskeletal pains.
d. Lateral chest pain (pleuritic pain) may be relieved by
restricting chest movements with strapping after
expiration.
e. Functional overlay in association with the above causes,
should not mask the underlying serious organic disease,
and mislead.
f. However, functional causes like neurocirculatory
asthenia may respond to tranquilisers like diazepam
(5 mg bd).
g. If the chest pain is of abdominal origin, surgical treatment
may be contemplated in consultation with a surgical
colleague.
SPECIFIC TREATMENT FOR SPECIFIC CAUSES
Chest
Cardiac Causes
1. Myocardial ischaemia
• Angina Pectoris—Stable angina
A. Identify and correct risk factors.
49
a. Nitrates
i. Sublingual nitrates—(Vide supra).
ii. Long acting nitrates—Isosorbide mononitrate
orally 10-60 mg 8th hourly (start with the
lowest dose). If the pain does not respond to
3-4 tablets and lasts for > 20 min, it is
suggestive of an evolving infarction.
iii. Glyceryl trinitrate (not > 2-10 mg/h should be
used). Since it has a short duration of action, it
can be given percutaneously as an ointment
(5-10 mg twice daily).
b. Beta blockers: Atenolol 25-100 mg once a day
(titrated to resting heart rate of 60. Contra-
indicated in bronchospasm or heart failure).
c. Calcium antagnoists
i. Diltiazem (30-90 mg tds)
ii. Nifedipine (10-40 mg tds)
iii. Verapamil (80 mg tds)—not to be used along
with beta blockers.
d. Potassium channel openers/activators nicorandil
(5-10 mg) bd.
e. Trimetazidine (20 mg tds)
B. Surgical measures—(Vide infra).
• Variant angina pectoris—Prinzmetal’s angina
a. Nitrates yield prompt results—Sublingual or IV
nitroglycerine abolish attacks. Long acting
nitrates prevent attacks.
b. Calcium antagonists effective in preventing
coronary spasm of variant angina.
c. A combination of nitrates and calcium
antagnoists is the mainstay of therapy. After 6-
10 months of therapy, gradual tapering may be
contemplated.
d. Prazosin (alpha adrenoreceptor blocker) may be
beneficial.
e. Beta blockers—the response is variable and it
may be detrimental in some cases.
f. Aspirin is not indicated in Prinzmetal’s angina
as the severity of the ischaemic attacks may
accelerate.
g. Percutaneous transluminal coronary angioplasty
(PTCA) may be helpful.
• Unstable angina
a. Bed rest and sedation as needed
b. Aspirin 150-300 mg daily or Clopidigrel 75 mg daily
or both or platelet GP II b/III a receptor blockers
may reduce risk of propagation to myocardial
infarction.
50 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
c. Triple anti-anginal drugs-Nitrates and beta blockers
initially and if patient is adequately betablocked add
long acting-slow releasing nondihydropyridine
calcium channel blockers (Non-DHPCCB) like
diltiazem to further improve the outcome. (Short
acting DHPCCB like Nifedipine is not advocated:
nor monotherapy with CCB). Potassium channel
blockers can be considered, if required. Metabolic
modulation with trimetazidine is a new edition to
control the angina.
d. If pain persists, consider
i. Anticoagulants lest progression to acute
myocardial infarction should occur, i.e. IV
heparin 1000 units 6th hourly for two days
which inactivates thrombin (PTT must be kept
between 60 and 80 seconds), i.e. (more anti
thrombin and less anti-xa activity) or preferably
low molecular weight heparin, e.g. enoxaparin
1 mg/kg/s. c twice daily for 3 to 5 days which
inactivate more-xa (i.e.) and less antithrombin
activity contributes to less haemorrhagic effects
and does not need any PTT monitoring. It is
followed by oral anticoagulants-warfarin 5 mg
bd for 6 months (PT must not exceed 2.5 times
normal or INR not to exceed 2.
ii. Intravenous nitrates (isosorbide dinitrate 1-2
mg/h) or glyceryl trinitrate 10-20 µg / mt IV or
modified release (buccal) glyceryl trinitrate
2.5 mg 4th hourly may be administered.
e. If pain settles, measures as for myocardial infarction
may be undertaken, if indicated.
f. If refractory, unstable angina warrants coronary
angiography and revascularisation measures (i) intra-
aortic balloon counterpulsation (used for stabilisation
before angioplasty. Now rarely used because of
modern procedures) (ii) under optimal conditions
Percutaneous transluminal coronary angioplasty
(PTCA) followed by stenting with the use of drug
eluting stent sirolimus (Rapamycin) or Paclitaxel
(Taxol) and GP II b/III a inhibitors with or without
low molecular weight heparin to improve results and
prevent restenosis (GP II b/III a inhibitors preferably
indicated before and during angioplasty if troponin
levels are raised) (iii) Coronary artery bypass grafting
(CABG) especially if there is left main coronary
artery stenosis or many severe stenoses. Intracoro-
nary radiation may reduce neointimal proliferation.
Revascularisation measures are not indicated in low
risk patients, i.e. no provocable ischaemia, LVEF
> 50%; low treadmill score (>5) and normal cardiac
markers. (iv) Gene therapy may offer a solution if
the vessels are not suitable for revascularisation.
g. Thrombolytic therapy is not indicated without
persistent ST elevations or new LBBB.
h. Lipid lowering drugs like statins.
i. High dose of statins indicated for pacification of
ruptured atheromatous plaque.
j. Folic acid and ACE inhibitors improve endothelial
function (ACEI Prevents ventricular remodelling)
k. Precipitating factors may be corrected.
Acute Myocardial Infarction
Aim to treat all three components of thrombus (i.e.) fibrin,
platelets and thrombin, with fibrinolytics, antiplatelets and
antithrombin agents (Heparin) apart from dealing with
ischaemic insult to myocardium and the likely complica-
tions.
1. Prehospital care
a. General measures
i. Bed rest.
ii. Liquid diet for 24 hours; then soft low calorie
diet.
iii. Stool softeners— dioctyl sodium sulfosuccinate
(100 mg daily) to facilitate easy bowel movement.
iv. Keep vigil on vital signs.
b. Pharmacological intervention
i. Control pain and anxiety with
• morphine (4-8 mg) or parenteral diazepam
(5-10 mg),
• sublingual nitrate (if the systolic blood
pressure is above 100), or
• oxygenation—2 to 4 litres per minute.
ii. IV life line with 5 per cent dextrose at the rate of
10 ml per hour.
2. Intensive coronary care units (hospital care)
a. General measures as above
b. Continuous cardiac monitoring
c. Reduction of cardiac work and infarction size
(improvement in myocardial oxygen supply-demand
relationship) with
i. Beta blockers—Metoprolol (50 mg for one day
later increased to 50 mg twice a day) is given
provided there is no heart failure, hypotension
or bradycardia.
ii. Nitrates—Nitroglycerine may be administered IV
with an initial infusion rate of 5-10 µg/min with
increments of 5-10 µg every 5-10 min avoiding
 Chest Pain
hypotension (Not < 100 mg/Hg) or tachycardia,
i.e. 2-10 mg/h till the mean arterial blood pressure
decreases by 10 per cent in normotensives and
30% in hypertensives and at any rate not less than
90 mm Hg; and an increase in the heart rate by
10 beats/min and not exceed 110 beats/min.
Alternatively, it may be given sublingually
(0.3-0.6 mg), although hazardous. Though there
is no clear evidence of either benefit or harm with
the routine use of nitrates, it may be considered,
for recurrent or persistent ischaemic pain or in
the presence of left ventricular failure.
iii. Calcium antagonists—Diltiazem (30-60 mg
q.i.d.) is beneficial if given preferably 72 h later,
as it decreases the incidence of reinfarction in
non Q wave MI. However, nifedipine is not
recommended as it may be detrimental.
iv. ACE inhibitors attenuate ventricular remodelling
and decrease fatality. Ramipril considered
preferably on the 3rd day (2.5 mg bd)
d. Re-establishment of blood flow in the affected artery.
(Reperfusions)
i. Thromobolytic/fibrinolytic therapy (contrain-
dicated in bleeding episodes). Streptokinase (SK)
(stimulates activation of endogenous plasmino-
gen to plasmin) is preferred over urokinase. SK
administered (1.5 million units in 100 ml of saline
within 3-6 hrs of onset of pain over one hour).
Anisoylated plasmingen streptokinase activity
complex (APSAC) also contain the same foreign
bacterial protein as in streptokinase. Reombinant
tissue plasminogen activator (rt-PA) (i.e.)
Alteplase is an alternative (1 mg/kg of which
10 mg is given as bolus and the remaining as
infusion over a period of 1 hour), which converts
fibrin bound plasminogen in the clot only thereby
minimising risk of bleeding and without antibody
response of hypotension and not in the circulation
as with streptokinase. Combination of SK and
rt-PA may provide higher patency rates and lower
reocclusion rates. However, when reocclusion
develops following SK, urokinase is considered
since SK cannot be readministered for 3-6
months. (not used in acute coronary syndrome).
Other tissue plasminogen activators are Reteplase
(r-PA) and Tenecteplase (TNK-tPA).
ii. Postlytic strategy—Coronary angiography and
PTCA or emergency CABG if PTCA is unsuitable
(considered only when thrombolytic therapy
51
fails or contra-indicated). If pain is uncontrolled
with continuing ST elevation rethrombolysis is to
be entertained. ABCIXIMAB (Antiplatelet)
Recommended (IV infusion) prior to PTCA.
iii. Angioplasty may replace thrombolytic therapy
for acute myocardial infarction in coming years.
e. Antithrombotic therapy (Inhibits clot formation and
propagation). Thrombolytic therapy is considered
antithrombotic because of thrombolysis effect.
i. Antiplatelet drugs: Low dose of aspirin (75-125
mg/d) when given right from the beginning is of
high utility in reducing the fatality rate and
continued in the post-infarction period to prevent
reinfarction. Clopidogrel (75 mg/d) or preferably
both aspirin and clopidogrel given within 24
hours of onset of symptoms of acute myocardial
infarction. Glycoprotein II b/III a receptor
antagonists; monoclonal antibodies against this
receptor, i.e. abciximab and nonmonoclonal
antibodies, i.e. eptifibatide and tirotiban IV only
(as they are not effective orally) used only in high
risk individuals especially when they undergo
angioplasty.
ii. Anticoagulants: Inspite of inconclusive evalua-
tion for several decades unfractioned heparin
(10000 units followed by 1000 units/h IV and
monitored to maintain the clotting time and PTT
at 1.5 times normal) increases overall patency
rates by preventing early reocclusion when
administered after 4-6 hrs of thrombolytic therapy
during the first 24 hours in patients with high
risk of embolism or large anterior infarcts. After
five days of therapy, it may be continued SC.
Alternatively heparin (5000 units bd or tds given
SC after 12 hrs of thrombolytic therapy till two
days prior to discharge from the hospital)
unequivocably diminishes the incidence of mural
thrombus following AMI. It is especially
indicated in immobile patients with a risk of
venous thrombosis or documented embolic
episode.
Low molecular weight heparin (LMWH) given
sc has a better bioavailability than sc unfractioned
heparin. (Vide supra). Heparin is mostly an
indirect thrombin inhibitor through its increasing
inhibitory effect of antithrombin III, i.e. more AT
activity with less neutralising factor xa, whereas
LMWH action is just contrary. Even in-patients
not eligible for thrombolytic therapy, heparin or
52 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
LMWH is of proven benefit. FondaParinux
Sodium 2.5 mg (Parenteral) is a synthetic
selective factor Xa inhibitor.
This is followed by long term warfarin therapy,
after discharge from the hospital, in extensive
anterior infarction with special indications like
thrombophlebitis or systemic thromboembolism
or mural thrombus in the left ventricle (as
detected by echocardiography) and severe heart
failure.
iii. Low dose of aspirin and oral anticoagulation
results in better outcome if INR is kept 2.
f. Direct thrombin inhibitor: Hirudin/hirudin peptides-
Hirugens or hirulling; (derived from medicinal leech
and synthetic analogues) does not need antithrombin
III unlike heparin. Bivalirudin, synthetic analogue
of hirudin seems to be yielding better results as
compared to heparin.
Thus all the three components of thrombus, i.e. fibrin,
platelets and thrombin are being tackled now.
g. Magnesium therapy though there is no established
protocol to magnesium (Mg) administration the total
dose recommended may be 20-90 mmol IV over a
period of 24-72 hrs. Hypotension and heart block
are to be carefully monitored during magnesium
sulphate infusion. Oral magnesium hydroxide
(15 mmol/d (is advocated for 1 year to control
arrhythmias and coronary spasm).
h. Treatment of complications of AMI
i. Cardiac arrhythmias—(Refer to Chapter
‘Palpitations’).
ii. Cardiogenic shock (Pump failure with or without
pulmonary oedema).
• 100 per cent oxygen.
• Correction of fluid and electrolyte imbalance
and/or arrhythmias if any.
• Vasopressors—dopamine, dobutamine or
amrinone.
• Vasodilators—useful if pulmonary capillary
wedge pressure is > 20 mm Hg, i.e. pulmo-
nary oedema treated with either nitroglycerine
10 µg/min and increased by 10 µg every five
minutes or sodium nitroprusside 10 µg/min
as IV infusion is titrated to maintain the
PCWP at 15-18 mm Hg and systolic blood
pressure at > 90 mm Hg.
• Thrombolysis for early perfusion.
• Intraaortic balloon pump—useful if patient
does not recover rapidly.
• Angioplasty or surgery for mechanical
complications (ruptures) result in salvage of
few patients.
iii. Cardiac failure
• Left ventricular failure—(Refer to Chapter
‘Dyspnoea’).
• Congestive heart failure—(Refer to Chapter
‘Oedema’). May behave like congestive
cardiomyopathy.
iv. Right ventricular infarction: Tachypnoea, basal
crepitions, unexplained hypotension are highly
suggestive. ST segment elevation in V4R lead is
specific. The haemodynamic disturbance is
improved by plasma volume expanders. Arterial
vasodilators considered if LVF is present.
v. Postinfarction angina: Angina occurring within
the first 10 days of infarction may be treated as
for unstable angina. Postinfarct extension must
be differentiated from postinfarction angina by
the re-elevation of CK-MB after initial rise.
However, such patients should be considered for
coronary angiography and require either
angioplasty or bypass surgery.
vi. Mechanical complications
• Medical therapy for rupture of
interventricular septum or papillary muscle
includes vasodilators (IV nitroprusside 10 µg/
min and titrated to maintain systolic pressure
at 100 mm Hg). Intraaortic balloon pump may
be necessary to maintain cardiac output.
Surgical correction is deferred for 4-6 months
if the patient is stable. Otherwise immediate
surgical repair attempted, as for the rupture
of the free wall of the left ventricle.
• Left ventricular aneurysm—Heart failure or
angina or ventricular tachyarrhythmias treated
appropriately. If medical management fails,
surgical aneurysmectomy is considered and
the success rate depends upon the contractile
ability of the nonaneurysmal portion.
vii. Thromboembolism:
• Deep venous thrombolism—(Refer to Chapter
‘Oedema’).
• Pulmonary embolism—(Vide infra.)
• Cerebral embolism—(Refer to Chapter
‘Coma’).
viii. Pericarditis: It may occur between the first day
and six weeks after the infarction. Dressler’s
syndrome (pericarditis and fever with or without
 Chest Pain
pneumonitis) may subside spontaneously or
improve with indomethacin or corticosteroids.
Anticoagulants are contraindicated.
3. Rehabilitation: The patient can be allowed ambulation
within a week and discharged after 10 days, provided
there are no complications. Physical activity is gradually
stepped up and facilitated to return to work after 6 weeks.
This schedule may be adjusted as per the course of the
disease and complications.
4. Prognostic stratification: Patients with an uncomplicated
clinical course must undergo diagnostic studies to assess
the future cardiac events. Routine coronary angiography
is not indicated in every case. Others with complicated
hospitalisation are considered high risk. Decreased left
ventricular ejection fraction (< 45%), myocardial
ischaemia and ventricular arrhythmias are the predictors
of increased risk. The former two warrant coronary
angiography, whereas arrhythmias require exercise
testing, provided left ventricular function is adequate.
Assessment of ischaemic threshold, i.e. the product of
heart rate and blood pressure is more of predictive value
than anatomic documentation.
5. Revascularisation: If symptoms are limited, treadmill
exercise test (to a heart rate of 120/min.) done after 4-6
weeks of infarction, reveals either exercise induced fall
in blood pressure or residual ischaemia at risk of
recurrent infarction coronary artery bypass graft
(elective) is recommended. Transmyocardial laser
revascularisation is promising.
6. Prevention of reinfarction: Apart from primary
prevention, i.e. risk factors like dyslipidaemia etc., the
recurrence, i.e. secondary prevention is facilitated by
long-term therapy with beta blockers and ACE
inhibitors for 2 years with or without dilitazem,
antiplatelet therapy, statins, anticoagulants (if there are
specific therapeutic indications), adequate exercise
within one’s limits and advice against primary risk
factors assure better prospects. Tertiary prevention, i.e.
arrhythmia’s and LV dysfunction with appropriate
antiarrhythmic agents and ACE inhibitors respectively,
can be achieved.
Acute Coronary Syndrome
Inhibition of clot formation and propagation is to be aimed
with antithrombotics, i.e. anticoagulants and antiplatelets.
Thrombolytic therapy is contra-indicated in unstable angina.
Plaque stabilisation (reduced propensity to plaque rupture
and thrombosis) is achieved by life style modification, lipid
lowering therapy and possible long term antibiotic treatment.
53
2. Pericarditis and pericardial effusion (Cardiac tampo-
nade): Treatment is predominantly directed towards the
underlying cause. Pain relievers may be prescribed for
symptomatic relief (aspirin-600 mg 6th hourly or
indomethacin-25 mg tds). Prednisolone is considered (10
mg 6th hourly, then tapered over several weeks as needed)
if the pain is resistant to analgesics. Prolonged intractable
or recurrent pain unresponsive to cortisone may require
pericardiectomy.
Paracentesis of the pericardial effusion is beneficial both
for diagnostic and symptomatic relief.
Cardiac tamponade (rising venous pressure and falling
arterial pressure and distant heart sounds) requires
immediate pericardiocentesis. If it recurs, pericardial cavity
is drained for a day or two, through a pericardial catheter.
Constrictive pericarditis is treated mainly by surgical
excision of pericardium.
3. Tachyarrhythmias
Refer to Chapter ‘Palpitations’.
4. Mitral valve prolapse—If symptomatic, beta blocker is
the drug of choice. Phenytoin is beneficial if Q-T is
prolonged. Endocarditis prophylaxis is recommended for
those with the characteristic systolic murmur only and not
mere presence of midsystolic click. Mitral valve replacement
may be required in severe mitral regurgitation, unresponsive
to medical treatment. Antiocoagulants are considered if
history of embolisation is forthcoming.
5. Hypertrophic obstructive cardiomyopathy
(Refer to Chapter ‘Syncope’)
6. Aortitis: Benzathine penicillin 2.4 million units/week
for three weeks is recommended. If allergic to penicillin,
terramycin or erythromycin (500 mg 6th hourly for one
month) is given. Monitor whether the VDRL titre levels are
lowered.
7. Aneurysms
• Aortic Aneurysm: Surgical excision may be done if the
aneurysm is more than 7 cm in diameter or diseased
aorta may be replaced with a prosthetic graft. With re-
implantation of branches or revascularise the branches
from ascending aorta first and then aneurysm excluded
using a stent graft. Associated regurgitation may require
prosthetic replacement of the aortic valve. Leutic
coronary artery disease requires endarterectomy at the
arterial orifice, or bypass surgery.
• Dissecting Aneurysm: Medical therapy consists of
maintaining systolic blood pressure below 120 mm Hg
with sodium nitroprusside, if necessary, followed by oral
 54 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
antihypertensives (Beta blockers, methyldopa and
nifedipine). Immediate surgical repair is considered for
ascending aortic dissection unlike descending aortic
dissection which is stabilised medically. However, the
latter requires surgery only when pain recurs or extension
of the dissection occurs as evidenced by expanded
mediastinum on serial skiagrams or CT scans.
8. Chronic pulmonary hypertension—Pulmonary thrombo
endarterectomy is definitive treatment for chronic pulmonary
hypertension. Treat underlying condition and heart failure
(Refer to Chpater ‘Oedema’).
Pulmonary Causes
1. Pulmonary embolism: It is aimed at the restoration of
adequate tissue oxygenation and prevention of further
emboli.
a. Give oxygen (to maintain PO2 > 70 mm Hg) even
upto 100 per cent oxygen.
b. Administer suitable analgesics for relief of pain.
c. Treat shock if present with colloid infusion and if
necessary dobutamine.
d. Anticoagulants—Heparin IV 10000 units given
immediately followed by IV infusion of 1000 units
per hour with the dose adjusted to give partial
thromboplastin time of 1.5 to 2 times normal. Low
molecular weight heparin or Fonda Parinux is
considered nowadays After 7-10 days, warfarin is
given orally (10 mg a day for three months).
e. Thrombolytic therapy if it is massive (Streptokinase
250000 units IV over 30 minutes and 100000 units
every hour for 1-3 days).
f. Surgery—Embolectomy or interruption of inferior
vena cava, if necessary entertained.
g. Prevention: Compression stockings, correction of
risk factors, thrombophilic tendency insert IVC filter.
2. Pleurisy: If the lateral chest pain is due to pleurisy,
restrict chest movements by strapping the affected side
preferably in expiration starting from two inches from the
vertebrae on the sound side and extending over the sternum
on to the sound side. Mild analgesics may be necessary.
Caution is exercised in using opiates. The underlying cause
must be treated.
3. Pneumonia
a. Effective antibiotic treatment promptly depending on the
causative organism is the mainstay of therapy. If seriously
ill, the conventional ampicillin treatment should be
augmented with cloxacillin as well as gentamicin
parenterally or 3rd generation cephalosporins or any
other appropriate combination of antibiotics. Oral
therapy can be substituted when fever subsides and
improves clinically. Total course of treatment should be
1-2 weeks.
b. Associated pleuritic pain is treated (vide supra).
c. Supportive therapy may be given with parenteral fluids,
corticosteroids and oxygen as needed.
d. Watch for complications like peripheral circulatory
failure or adult respiratory distress syndrome and treat
appropriately.
4. Spontaneous pneumothorax: If the pain is due to
spontaneous pneumothorax, treatment depends on the
amount of air leak and the intrapleural pressure.
If the pneumothorax is small, no treatment is necessary.
Spontaneous recovery occurs in 3-4 weeks. If tuberculous
aetiology is suspected, specific chemotherapy is given.
Sometimes aspiration through a needle and syringe
connected to a three-way tap and underwater seal system
may be necessitated (till cough occurs).
If the intrapleural pressure is more (tension pneumo-
thorax) intercostal catheter is connected to an underwater-
seal system in which a wide-bore plastic cannula is
connected to a tube the end of which is placed under water
in a bottle. It is kept till the bubbling stops for 24 h while
monitoring the expansion of the lung.
In recurrent cases, chemical pleurodesis (instilling an
irritant like kaolin to make surfaces adherent) or thoracic
surgery (parietal pleurectomy at thoracotomy) may be
considered.
5. Bronchogenic carcinoma: Refer to Chapter ‘Haemoptysis’.
MEDIASTINAL CAUSES
1. New growths: Beingn tumours are better removed
surgically lest the compression symptoms should occur.
Malignant tumours are subjected to a combination of
radiotherapy and chemotherapy. Treatment of lymphomas
is detailed under ‘PUO’ and leukaemias under ‘Bleeding
diathesis’.
2. Mediastinal emphysema: No treatment is usually
necessary. A prompt search should be made for the
underlying cause and should be corrected. An emergency
tracheostomy is required if the symptoms are progressive
as in a perforated intrathoracic oesophagus.
 Chest Pain
Oesophageal Causes
1. Oesophageal spasm: (Refer to Chapter ‘Dysphagia’).
2. Hiatus hernia and reflux oesophagitis: (Refer to Chapter
‘Dysphagia’).
3. Oesophageal rupture: Immediate thoracotomy to repair
the perforation is imperative if patient’s condition permits.
Effective antibiotics should be employed. If time (more than
12 h) has elapsed, bypassing the perforated area by cervical
oesophagostomy and gastrostomy is life saving. Pleural
space may be drained, if necessary. The final surgical repair
can be undertaken later.
Musculoskeletal Causes
Musculoskeletal pains are mitigated by analgesics, NSAIDs
and muscle relaxants.
Treatment of cervical spondylosis is detailed under
Chapter—Pain in the Extremities.
Neurovascular Causes
1. Herpes zoster: (Refer to Chapter ‘Rashes’).
2. Thoracic outlet compression syndrome: (Refer to
Chapter ‘Pain in the Extremities’).
3. Hyperabduction syndrome: Avoid hyperabduction of the
arm or postural strain. Overhead use of the extremities
should be discouraged. If symptoms persist, the first thoracic
rib is resected and the pectoralis minor attachment is
released.
4. Mondor disease: The treatment of thrombophlebitis is
described under Chapter Pain in the Extremities.
Abdominal
• Acute indigestion (Refer to Chapter ‘Dyspepsia’).
• Gastric or Colonic Distension (Refer to Chapter
‘Dyspepsia’).
• Oesophageal (Vide supra).
• Perforated Peptic Ulcer: (Refer to Chapter ‘Acute
Abdominal Pain’).
55
• Acute Pancreatitis: (Refer to Chapter ‘Acute Abdominal
Pain’).
• Cholelithiasis and Cholecystitis: (Refer to Chapter
‘Acute Abdominal Pain’).
Endocrinal
1. Mammary dysplasia: Primarily the diagnosis of mammary
dysplasia must be established by biopsy. Breast pain is
mitigated by wearing brassiere, offering support and
protection from possible trauma. If a cyst is present, the
fluid is to be evacuated and subjected to cytologic
examination. If the follow up of the patient reveals any
atypical mass, biopsy is done without delay, since the risk
of breast cancer is twice that of normal woman.
2. Mastitis: Mastitis due to mammary dysplasia is treated
as above. Treatment of puerperal mastitis consists of
suppression of lactation (hormones/bromocriptine for those
who do not wish to suckle their infants from the beginning
or mechanical inhibition for those who wish to wean the
baby), continued support to the breast, antibiotics and
analgesics. If abscess occurs, incision and drainage is
required.
Breast hygiene is maintained.
Psychogenic
1. Acute Anxiety
(Refer to Chapter ‘Fatigue’).
2. Chronic Anxiety (Da Costa’s Syndrome)
The increased sympathetic drive to the heart and vascular
bed with significant symptoms and without any evidence
of coronary artery disease as such may require propranolol
in some cases. Psychological counselling analgesics and/or
tranquilisers and lucid explanation of the benign nature of
the complaint are contributory. In those with long standing
psychoneurotic cardiac ill health, the management is
predominantly psychological and behavioural therapies, and
the reassurance that there is no organic disease of the heart
may be helpful.
56 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Chronic Diarrhoea
4
Diarrhoea is a term derived from Greek dia means through
and rhein means to flow. Diarrhoea connotes frequent rapid
evacuation of unformed stool with abnormal high fluid
content (liquid stool) or frequent passage of normal stool.
Increased frequency, consistency (liquidity) and volume
(weight) are the essential factors in ascertaining true
diarrhoea. Normally the average daily weight of the stool is
200 gm, or less of which water constitutes about 70% (upto
350 gm in Indians). Diarrhoea can be of acute onset
persisting for a period of 1 to 3 days or may be chronic
lasting for > 4 weeks continuously or intermittently.
PHYSIOLOGY
The primary function of colon is absorption of water and
all soluble constituents of the chyme reaching the caecum.
After completion of the digestion process, the liquid effluent
from the ileum (about one litre) is converted into solid matter
in the colon and the undigestible residue, i.e. faeces, is stored
in the pelvic colon. Normally, the large bowel has got the
capacity to absorb six litres of water and 800 mg of sodium
by means of deep segmentation movements caused by the
activity of the muscularis mucosae. The principal absorption
sites are ascending and transverse colon. Its function is also
influenced by the failure of the small intestine to absorb the
seven litres of daily gut secretions and also the nature of the
unabsorbed products like bile salts, sugars and fats.
The propulsion of the food contents from the duodenum
to rectum is accomplished by peristalic contractions, the
principal stimulus for which is the gastrocolic reflex. During
defaecation, the contents of the pelvic colon along with any
residue higher up in the descending colon pass into the empty
rectum. The distended walls of the rectum facilitate its
contraction and simultaneous reflex relaxation of the
sphincter, resulting in evacuation of the rectum. However,
the final control of defaecation is voluntary which can be
augmented or prevented by the contraction of the abdominal
muscles and pelvic floor muscles respectively.
PATHOPHYSIOLOGY
Chronic Diarrhoea is chracterised pathophysiologically as
1. Inflammatory 2. Osmotic 3. Secretory 4. Dysmotility
5. Fatty acids 6. Factitial.
The pathogenesis of diarrhoea is essentially due to the
excessive amount of fluid coming from the small intestine
to the colon due to (i) mucosal injury and (ii) inadequacy of
the small intestine. The mechanisms involved are
multifactorial.
1. Increased secretion of electrolytes and/or decreased
absorption of electrolytes result in secretory diarrhoea
with increased volume of faecal fluid rich in sodium
and potassium, e.g. cholera or pancreatic tumours
secreting vasoactive intestinal polypeptides or excess
of bile Salts and fatty acids as in malabsorption
syndrome, Inflammatory Bowel Disease, Zollinger-
Ellison syndrome, Thyrotoxicosis, malignant carcinoid.
2. Increased secretion of electrolytes and impaired colonic
absorption with outpouring of necrotic mucosa and fluid
from the inflamed colon, leads to exudative diarrhoea,
e.g. amoebiasis and shigellosis. Presence of polymorphs,
pus and blood in the stool may be characteristic unlike
in secretory diarrhoea.
3. Presence of nonabsorbable substances (like magnesium
containing laxatives or glucose due to transport failure
or lactose in lactose deficiency) in gut exert osmotic
effect causing decreased absorption of water and sodium
leading to osmotic diarrhoea where the osmolality is
greater than the sum of concentration of sodium and
potassium. These sugars undergo fermentation to lactic
 58 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

acid by colonic bacteria and lower the pH which Table 4.1: Aetiological classification of chronic diarrhoea
increases the frequency of defaecation ex disaccharidase 1. Inflammatory Diarrhoea (Infectious or noninfectious)
deficiency, lactulose therapy and malabsorption. A. Specific
4. Decreased absorptive surface due to either mucosal a. Tuberculosis
damage or resections as in malabsorptive states. b. Amoebiasis and Giardiasis
5. Altered intestinal motility with decreased contact time c. Yersinea enterocolitica
between small bowel mucosal surface and its contents, d. Human immunodeficiency virus (HIV)
e. Cryptosporidium parvum (fungal)
for necessary adequate absorption, as in (a) hyper-
B. Non-specific
thyroidism, (b) primary motility abnormality with a. Ulcerative colitis
premature emptying of the colon like irritable bowel b. Diverticulitis
syndrome Or diabetic diarrhoea (c) reduced peristalsis c. Crohn’s disease
leading to bacterial overgrowth and (d) post GI Surgery, C. Postradiation
neoplasms like maligant carcinoid and medullary 2. Malabsorption Syndrome and Protein Losing Enteropathy
carcinoma of thyroid. 3. Neoplasms
6. Bacterial overgrowth due to diminished motility can give a. Carcinoid tumour
b. Colonic carcinoma
raise to chronic diarrhoea due to (a) deconjugation of
c. Zollinger-Ellison syndrome
bile saits with impaired micelle formation and fat d. Lymphomas
malabsorption (b) mucosal lesions and (c) consumption 4. Deficiency States
of B12 or other nutrients. a. Pellagra
7. Excessive colonic secretions occur in rectal villous b. Globulin
adenomas distal to the principal sites of absorption. c. Achlorhydria
N. B. In many clinical entities, one or more of the factors 5. Endocrinal and Metabolic
described above may play a part. Watery diarrhoea is either a. Hyperthyroidism
osmotic or secretory diarrhoea and may be from either small b. Diabetes mellitus
c. Chronic uraemia
or large bowel.
d. Endometriosis
e. Amyloidosis
AETIOLOGY (CAUSES) f. Pancreatic cholera syndrome
6. Post G.I. Surgery
Table 4.1 presents an aetiological classification of diarrhoea.
a. Gastrectomy
b. Vagotomy
1. Inflammatory Diarrhoea c. Afferent loop syndrome
(Inflammatory Bowel Diosrders) d. Intestinal resections
7. Drugs
a. Prolonged use of purgatives
Specific b. Hypotensive drugs—methyldopa, reserpine
Tuberculosis Intestinal tuberculosis may be primary due to c. Magnesium in antacids
infection with bovine strain or secondary to pulmonary d. Antibiotics like broad-spectrum antibiotics, lincomycin,
tuberculosis (human strain). The presenting feature is the clindamycin, neomycin (adverse reaction is malabsorption
cramping or dull pain in the lower right quadrant most often instead of diarrhoea or colitis)
after food and associated with weight loss and diarrhoea or 8. Functional Colonopathies
a. Irritable bowel syndrome
a tender palpable mass in the ileocaecal region. The
b. Nervous diarrhoea
diagnosis is confirmed by evidence of pulmonary
9. Genetic
tuberculosis or narrow stream of barium in the small bowel a. Abetalipoproteinaemia
or triangular appearance with base towards caecum. There b. Chloridorrhoea
are the characteristic radiological changes supported by stool c. Hartnup disease
culture for mycotuberculosis or animal inoculation or d. Hypogammaglobulinaemia
histological evidence of tuberculosis. e. Disaccharidase deficiency, e.g. lactasee
10. Allergic
Amoebiasis This is one of the most common conditions
11. Paradoxical
causing chronic diarrhoeas in tropics. Intestinal amoebiasis
12. Factitious
is usually characterised by onset of afebrile, offensive,
 Chronic Diarrhoea
Fig. 4.1: Motile (trophozoite or vegetative) and resting (cystic) stages of development of Entamoeba histolytica
voluminous stool intermingled with blood and mucus. Lower
abdominal pain and impaired digestion may lead to
considerable loss of weight. Tenesmus is unusual.
Abdominal examination may reveal a thickened, tender
colon specially in the caecum and sigmoid and in some cases
associated tender hepatomegaly may be elicited due to
associated amoebic hepatitis.
Diagnosis is confirmed by identifying the different
phases of Entamoeba histolytica with or without Charcot-
Leyden Crystals in the stool, which is acidic in reaction
(Fig. 4.1).
Sigmoidoscopy may show painless oval shaped yellow
ulcers with underlined edges from the lesions surrounded
by zones of hyperaemia and normal intervening mucosa and
superficial depression of the mucosa representing healed
ulcers. During instrumentation, it is better to take some
material directly from the ulcers for confirmatory micro-
scopic examination for parasites.
59
Barium examination may reveal filling defects of the
caecum and ascending colon with deficient haustrations or
a small irregular caecum with incompetent ileocaecal valve
as seen by the flow of the barium from the caecum into the
ileum.
Serological test with purified antigens may be positive.
The serodiagnosis tests in vogue are indirect haemaggluti-
nation test, indirect immunoflourescence, latex agglutina-
tion, counterimmuno-electrophoresis, ELISA, gel diffusion
and precipitation.
Giardiasis (Vide Infra)
Yersinia: Yersinia pseudo tuberculosis and enterocolitica are
associated with chronic diarrhoeal diseases with mesen-
terical as well as cervical adenitis. There may be asymmetri-
cal polyarthritis with or without erythema nodosum, uvetis,
glomerulonephritis, pyomyositis, terminal ileitis. Diagnosis
is confirmed by culture of the stool or lymph node biopsy.
 60 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

The antibody titre higher than 1 in 160 ranging upto even 1

in 10,240 are diagnostic.
HIV
(Refer to Chapter ‘Pyrexia of Unknown Origin’).
Cryptosporidium Parvum: Fungal infection causing diarrhoea
in AIDS patients. Oocyst excretion can be quantified. It may
be self-limiting depending on CD4 count.

Non-specific
Inflammatory bowel disease includes ulcerative colitis and
Crohn’s disease.
Ulcerative colitis: This is characterised by recurrent attacks
of diarrhoea with blood and mucus and abdominal pain
preceding defaecation. There may be generalised wasting
with associated nutritional deficiencies. Tenderness over the
left iliac fossa may be elicited with or without colonic
distension. Hectic temperature with toxaemia is related to Fig. 4.2: Barium enema roentgenogram showing colon with
the severity of the disease. The diarrhoea may become loss of haustrations with fine serrations over bowel margins
persistent when chronic changes occur in the colon leading representing small ulcers and multiple irregular densities within
to failure of its functions of absorption and as a storehouse the lumen indicating pseudopolyps (severe ulceration),
diagnostic of ulcerative colitis
of food residue.
The diagnosis can be confirmed by proctoscopy or Post Radiation
sigmoidoscopy which shows congestion of mucosa through-
out with tendency of contact bleeding, small ulcers, granu- Small Bowel Mucosa Involvement may result in Diarrhoea/
larity or hyperplastic colon with a polypoid appearance. Steatorrhoea and GI Malabsorption.
Radiology may reveal no abnormality if rectum alone is
2. Malabsorption Syndrome and
involved or mucosal lesions showing granular ulcerations or
Protein Losing Enteropathy
shortening and narrowing of colon with loss of haustrations,
pseudopolyps and a shaggy outline due to ulcer craters. Malabsorption Syndrome
Radiological examination reveals varying appearances
Malabsorption syndrome may be maldigestion or
related to underlying pathological changes (Fig. 4.2).
malabsorption and is associated with abdominal pain,
Crohn’s disease distension, diarrhoea with bulky pale offensive stool
(Refer Chapter ‘Pyrexia of Unknown origin’). (steatorrhoea); nutritional deficiencies, both vitamins and
minerals and anaemia with hypoproteinaemia and loss of
Diverticulitis: A diverticulum is an outpouching of the gut
weight and pigmentation of the skin. It is a chronic failure
wall. Inflammation of the diverticula of the colon produces
of absorptive function of small intestine due to damage of
pain in the left iliac fossa or lower abdomen associated with
the rapidly dividing intestinal mucosal cells, resulting in
tenderness and vomiting. Gross blood in the stool or severe
disturbances of enterocyte population. The causes leading
rectal haemorrhage may occur as inaugural symptom in some
to this malabsorption are innumerable.
cases. History of alternating constipation and diarrhoea may
be forthcoming. Rectal examination may be negative. Impaired digestion
Plain X-ray of the abdomen may show pattern of ileus A. Gastrogenous (inadequate mixing)
or partial colonic obstruction. Barium enema which is done a. Gastrojejunostomy
at a later date may show diverticula with narrowing and b. Gastrectomy
irregularity in the colon or pericolic or intramural abscess c. Vagotomy
with spasms or fistula to the urinary bladder which will be The probable mechanism of malabsorption is due to
seen filled with barium. gastric contents rapidly entering the jejunum without
 Chronic Diarrhoea 61

bile and pancreatic secretions. The consequent increased

fluid content in the intestines results in diarrhoea due to
the osmotic action of the food.
B. Pancreatogenous (Pancreatic insufficiency)
a. Chronic pancreatitis (Refer to Chapter ‘Dyspepsia’).
b. Tumours of the pancreas, e.g. Zollinger-Ellison
syndrome.
c. Mucoviscidosis (fibrocystic disease of the pancreas).
The pancreatic exocrine insufficiency is usually due to
chronic alcoholism or protein calorie malnutrition and
the pancreatic lipase deficiency is responsible for the
steatorrhoea.
In Zollinger-Ellison Syndrome, the hyperchlorhydria
due to the gastrin secreting adenoma inactivates the
pancreatic lipase. Also the precipitation of bile acids at
low pH and consequent decrease of bile salts in the
lumen, leads to decreased absorption of fatty acids (vide
infra).
Cystic fibrosis is an inherited disease characterised Fig. 4.3: Normal metabolism of bile salts
by thick secretions from the mucus glands leading to
bronchial obstruction or pancreatic duct obstruction
resulting in respiratory infections or pancreatic insuffi- Impaired absorption
ciency. Foul fatty stool, recurrent bronchopneumonia, A. Primary absorptive disorders of small bowel mucosa.
failure to thrive are the consequent clinical a. Inflammatory
manifestations. The obstruction of the intestines in i. Tropical sprue and nontropical sprue (coeliac
neonates may present as meconium ileus. In older disease)
children, bronchiectasis and diabetes mellitus may be ii. Parasitic infections, e.g. Giardiasis, Diphyllo-
present. Diagnosis is confirmed by sweat test which bothriasis, strongyloidiasis
shows elevated sodium concentration (> 60 mmol/L). iii. Intestinal tuberculosis (vide supra)
C. Enterogenous (Bile salt deficiency) iv. Crohn’s disease (vide supra)
a. Cholestasis (intrahepatic and extrahepatic) b. Infiltrative
b. Abnormal intestinal flora (blind loop syndrome) i. Lymphomas
c. Drugs like neomycin precipitate bile salts ii. Scleroderma
iii. Amyloidosis (vide infra)
Primary bile salts are conjugated in the liver with glycine
and taurine. These conjugated bile salts are essential for • Inflammatory:
emulsification of fats and facilitate its digestion by Tropical sprue is the classical example of malabsorption
lipases and micelles formation. Thereafter, the bile salts syndrome. It is due to coliform organisms and its toxins
are reabsorbed in the ileum and transported back into leading to shortened and thickened villi (villous atrophy)
the liver (Fig. 4.3). with infiltration of mononuclear cells causing jejunitis.
In conditions where there is stasis in the small Nontropical sprue is mucosal sensitivity to gluten
intestine (due to postoperative blind loops or blind (a protein found in the wheat, barley, oat and rye). The
structures or Jejunal diverticula or autonomic neuropathy possible mechanism is a direct toxic effect by gliadin
in diabetes mellitus), bacterial overgrowth with sub- (polypeptide component of gluten) as a result of an antigen
sequent mucosal invasion occurs in the small intestine, antibody reaction at the mucosa. The HLA B8 antigen is
which causes deconjugation of bile salts leading to associated with such immunological reactions leading to
steatorrhoea. The organisms utilize vitamin B12 resulting production of antigliadin antibodies with subsequent villous
in its deficiency (blind or stagnant loop syndrome). This damage in jejunum and malabsorption of the nutrients
is diagnosed by 14CO2 breath test. resulting in protean manifestations. Malignancies,
 62 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
lymphoma myopathies are complications. The damage to
the intestinal mucosal cells can also occur due to cytotoxic
drugs or disseminated maligancies. The term coeliac
syndrome is introduced to embrace these conditions.
Parasitic infections like giardiasis may produce
steatorrhoea due to failure of absorption of fat and excretion
of bile due to mechanical effects of the parasites on the
intestines.
• Infiltrative
i. Lymphomas—Diffuse involvement of the small
intestinal mucosa by the lymphoms and such other
infiltrations may be due to affection of the intestinal
wall with lymphatic obstruction and diminished
arterial blood supply leading to stasis and bacterial
overgrowth. There may be abdominal pain and fever
with hepatosplenomegaly and lymphadenopathy and
abdominal masses. IgG is increased.
ii. Scleroderma—In Scleroderma, intestinal involve-
ment leads to impaired motility which may result in
steatorrhoea.
B. Secondary absorptive defects
a. Surface Inadequacy
i. Intestinal resections (intestinal hurry)
ii. Jejuno ileal bypass
b. Inadequate flow of lymph or blood
i. Whipple’s disease
ii. Lymphangiectasia
iii. Mesenteric arterial insufficiency
iv. Congestive heart failure
• Surface inadequacy: Resection of small intestine or
juejuno ileal bypass may lead to inadequate bowel
surface with consequent malabsorption diarrhoea and
steatorrhoea (small bowel syndrome).
• Inadequate flow of lymph or blood: Whipple’s disease
is a rare disease characterised by loss of weight,
steatorrhoea with abdominal pain and arthralgia. This is
associated with lymphatic obstruction. This is confirmed
by demonstrating macrophages in the lamina propria and
dilated lymphatics with blunt villi.
Intestinal lymphangiectasis is characterised by
hypoproteinaemia (due to protein losing enteropathy),
oedema, steatorrhoea or diarrhoea, chylous effusions and
lymphocytopenia. Oedema may be asymmetrical. The
congenital hypoplastic lymphatic system leads to
obstruction of lymph flow with consequent dilated
lymphatic vessels in the small intestine and mesentery.
Oedema is due to increased intestinal lymphatic pressure
with consequent leakage of lymph into the intestinal
lumen. There is hypogammaglobulinaemia as well as
decreased albumin.
Steatorrhoea is rarely described in congestive heart
failure and superior mesenteric arterial insufficiency due
to mucosal congestion and oedema or impaired blood
flow with consequent mucosal hypoxia.
Protein Losing Enteropathy
The metabolism of plasma protein is intimately associated
with gastrointestinal tract. Normally 70 g of fat and 50 g of
albumin are present in the 1500 cc of lymph that flows
through thoracic duct and about 10 to 20 per cent of the
total turnover of the albumin may be lost in intestines. In
certain pathological conditions, the loss of protein is more
and the disorders may be gastrogenous or enterogenous or
may be associated with certain cardiac disorders. The
mechanism of loss is due to inflamed mucosa or altered
structure of the mucosal cell or due to rupture of dilated
lymphatic vessels.
3. Neoplasms
Carcinoid Tumour
Carcinoid tumours arise from argentaffin cells of the
appendix or ileum or other areas of gastrointestinal tract or
from gallbladder or bronchus. The clinical features are
grouped as carcinoid syndrome and features may be
intermittent or occur late, i.e.
a. Culaneous: Spontaneous or provoked flushing by
alcohol, coffee, plantains or drugs, erythema,
telangiectasia.
b. Gastrointestinal: Increased intestinal motility leading to
diarrhoea; abdominal pain due to intestinal cramps or
hepatic metastasis; appendicitis or small bowel
obstruction due to the tumour itself.
c. Cardiac: Tricuspid incompetence or pulmonary stenosis.
d. Pulmonary: Bronchospasm.
e. Nutritional: Sometimes pellagra and hypoproteinaemia
with oedema may result due to diversion of excessive
tryptophan into hydroxylation pathway leaving behind
less amounts for formation of nicotinic acid and protein.
f. Endocrinal: Occasionally, due to ectopic production of
ACTH by tumour, Cushing syndrome may be seen.
Diagnosis is confirmed by urine excretion of more than
15 mg of 5-hydroxyindoleacetic acid in 24 h. Qualitative
test is considered to be positive when Ehrlich’s Aldehyde
reagent gives a blue colour, which occurs if its excretion
 Chronic Diarrhoea
exceeds 25 mg per day. In some cases 5-hydroxytryptophan
and 5-hydroxytryptamine (serotonin) may be sought by
paper chromatography of urine.
Colonic Carcinoma
This is suspected in males above 50 years who present
themselves with a dull or coliky pain and altered bowel habit
like diarrhoea or constipation or both alternating. Presence
of blood and mucus in the stool is not uncommon in the
lesions of rectum or rectosigmoid.
Sigmoidoscopy or colonoscopy and barium enema
(appears as a fixed filling defect with an ‘apple core’
appearance, loss of mucosal pattern and ‘hooks’ at the
margins of the lesion) are most valuable diagnostic
investigations. Carcino Embryonic Antigen (CEA) may be
found in the blood.
Zollinger-Ellison Syndrome (Gastrinoma)
This is an uncommon disease with peptic ulceration and/or
diarrhoea occasionally steatorrhoea. The non-beta islet cell
tumour of the pancreas (gastrinoma) or hyperplasia or
extrapancreatic tumours produce gastrin which is
responsible for hypersecretion of gastric acid resulting in
peptic ulceration. The diarrhoea is due to increased volume
of acid pouring into the upper small intestine causing direct
injury to the intestinal mucosa. Gastrin can also produce
diarrhoea by reducing intestinal absorption of water and
electrolytes, which is probably the mechanism where
diarrhoea may be present without peptic ulceration (about
10%). A positive secretin test (increase of 200 pg per ml
over fasting serum gastrin levels within 10 minutes following
IV secretin), high gastrin levels (> 1000 pg/ml) and high
acid output, strikingly increased gastric folds on endoscopy
or radiology are diagnostic. CT scanning may help tumour
localisation.
Lymphomas
Vide supra.
4. Deficiency States
Pellagra
Normally one mg of nicotinic acid is formed from 60 mg of
essential amino acid tryptophan. Nicotinic acid deficiency
leads to pellagra which depends on the dietary proteins and
vitamins. Endemic pellagra is seen in maize eaters, since
maize contains low nicotinic acid and high leucine content.
63
Leucine inhibits the synthesis of nicotinic acid. Pellagra is
characterised by symmetrical dermatitis on the exposed
parts, dementia and diarrhoea. The other concomitant
features are stomatitis, glossitis and vaginitis. The diarrhoea
is due to inflammation of the mucosa of the gastrointestinal
tract. It may be secondary to carcinoid syndrome or Hartnup
disease. The latter is an inherited disease and consists of
intermittent symptoms of pellagra depending on the
metabolic demands for tryptophan. Associated constant renal
aminoaciduria is diagnostic since this is absent in classical
nutritional pellagra.
Globulin Deficiency
Hypo or agammaglobulinaemia of inherited or acquired type
may be associated with malabsorption. Some may exhibit
selective deficiency of IgA which fraction predominates in
intestinal mucosa. Intestinal biopsy reveals nontropical
sprue like changes and mononuclear infiltrates. Culture of
intestinal fluid may show anaerobic bacteria.
Achlorhydria
Hydrochloric acid is secreted normally by parietal cells of
the gastric mucosa. Secretory variations are related to types
of personalities and diseases. The free hydrochloric acid of
the gastric juice is an effective germicide and maintains the
pH of small intestine thus preventing bacterial invasion from
the colon. Achlorhydria may allow organisms swallowed to
reach the small intestine and gastric emptying time may
become rapid, leading to diarrhoea. (Refer to Chapter
‘Dyspepsia’).
5. Endocrinal and Metabolic
Hyperthyroidism
In hyperthyroidism, the increased circulations of thyroid
hormone may cause increased frequency of bowel
movements and produce noninfective diarrhoea. Thyroid
enlargement with associated tachycardia even during sleep,
tremors, weight loss, eye signs and hyperkinetic circulation
are diagnostic. It is confirmed by elevated T3 and T4 levels
(Refer to Chapter ‘Goitre’).
Diabetes Mellitus
In diabetes mellitus, autonomic neuropathy may result in
diarrhoea (specially nocturnal) and gastroparesis. There may
be associated features of autonomic dysfunction in the
cardiovascular system leading to postural hypotension or
 64 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
genitourinary system leading to erectile impotence and
bladder disturbances. Pancreatic insufficiency or bacterial
overgrowth in small intestine with blind loops may also
account for diarrhoea.
This may be confirmed by
a. Raised blood sugar levels
b. Measuring variations of the heart rate during postural
changes and deep breathing
c. Hand grip test
d. Estimation of valsalva ratio (during valsalva
manoeuvre, if ECG is taken the ratio of longest pulse
interval and shortest pulse interval will be normally
more than 1.5).
Chronic Uraemia
The failure to excrete waste products (especially by products
of protein metabolism) and maintain water and electrolyte
balance, leads to acidosis, azotaemia resulting in certain
gastrointestinal symptoms like anorexia, nausea, vomiting,
diarrhoea and ulcerations in gastrointestinal tract. The other
biochemical and haematological abnormalities with
consequent clinical features and hypertension are
proportional to the deterioration in renal function. (Refer
Chapter ‘Polyuria’).
Endometriosis
The abberant growth of endometrium outside the uterus
(endometriosis) may involve small intestine, sigmoid colon
or rectum due to bowel invasion by endometrium tissues
after entering the peritoneal cavity via fallopian tubes. Pelvic
examination may reveal a tender nodule in the cul-de-sac.
X-ray contrast studies may show the delineation of the
colonic endometriosis with an intact mucosa.
Amyloidosis
Amyloid which is composed of proteins derived from light
chains of immunoglobulin and a circulating serum protein
may be deposited in the gastrointestinal tract or other tissues
of the body secondary to chronic infections or inflammatory
diseases like rheumatoid arthritis or primary without any
existing disease. The multisystem involvement leading to
proteinuria, hepatosplenomegaly, cardiomyopathy, bleeding
tendencies, diarrhoea. Macroglossia and peripheral
neuropathy should make one to suspect amyloidosis. Biopsy
studies of the rectum or gum or affected organ and
demonstration of amyloid are diagnostic. (Positive staining
with congo Red and appearance of apple-green birefringence
in polarized light).
Pancreatic Cholera
(VIP—Vasoactive Intestinal Polypeptide)
It is a rare entity associated with islet cell tumours, severe
watery diarrhoea (more than 1 litre per day) with loss of
electrolytes like hypokalaemia (more than 300 m eq per day)
and achlorhydria. During diarrhoeal remission, though
serum potassium is normal, gastric acid remains low.
6. Post-gastrointestinal Surgery
Gastrojejunostomy (Vide Malabsorption—Gastrogenous).
Gastrectomy (Vide Malabsorption—Gastrogenous).
Vagotomy (Vide Malabsorption—Gastrogenous).
Afferent (Blind) Loop Syndrome (Vide Malabsorption-Bile
salt deficiency).
Small intestinal resection (Vide Malabsorption-Surface
inadequacy).
7. Drugs
Drugs like purgatives, antibiotics (lincomycin, clindamycin,
tetracycline, ampicillin, neomycin), magnesium containing
antacids, hypotensives, and cytotoxics can result in osmotic
or secretory diarrhoea.
8. Functional Colonopathies
Irritable Bowel Syndrome
Refer to Chapter ‘Dyspepsia’.
Nervous Diarrhoea
This occurs as postprandial diarrhoea in highly strung
individuals or during anxiety states and emotional upsets.
There is no previous history of peptic ulcer surgery;
the physical and endoscopic examinations are essentially
normal.
9. Genetic
Abetalipoproteinaemia
It is seen in early childhood with symptoms of steatorrhoea,
ataxia, neuropathy, retinitis pigmentosa and acanthocytosis.
The lipid levels are low (50 mg of cholesterol, absence of
VLDL and LDL and less than 10 mg of triglycerides). The
underlying mechanism is defective synthesis of apoprotein
‘B’.
Chloridorrhoea
In congenital chloridorrhoea, the child passes large watery
stools instead of meconium even before feeding is started.
 Chronic Diarrhoea
Stool, contains more chloride (> 100 m eq/L). The normal
value is 50-70 meq/L. This is an inherited defect of chloride
absorption in distal ileum and colon. Hypokalemia,
hypochloremia, abdominal distension due to paralytic ileus
and volvulus are the diagnostic cardinal features.
Hartnup Disease
Vide supra pellagra
Hypogammaglobulinaemia
Malabsorption of fats, D-xylose and vitamin B 12 is
associated with hypogammaglobulinaemia. Diarrhoea and
steatorrhoea may worsen with bacterial infections of the
small bowel or parasitic infections like giardiasis. There
appears selective deficiency of immunoglobulin ‘A’, which
is present not only in the intestinal mucosa but also in the
gastrointestinal secretions. The immunoglobulin is usually
below 5 mg per dl (normal Ig A: 90 to 325 mg per dl). It
may be of acquired origin too.
Disaccharidase Deficiency
The classical example of lactase deficiency may be of genetic
or acquired origin due to infections of the intestinal tract
like bacterial, rotavirus and giardiasis. It is associated with
symptoms of lactose intolerance. Lactose sugar is the main
constituent of milk. Symptoms like abdominal distension
and diarrhoea, following ingestion of milk are usually seen
in adolescence period in such cases. This may be due to
failure of hydrolysis and absorption of lactose due to lactase
deficiency. The unabsorbed lactose is fermented by colonic
bacteria to lactic acid and fatty acids. Stool lactic acid is
more than 1000 mg daily (normally stool contains 30-40
mg daily). The consequent lowered pH increases the
frequency of defaecation resulting in diarrhoea. The
diagnosis is confirmed by lactose tolerance test or breath
hydrogen test.
10. Allergic
Milk allergy syndrome is due to milk protein like B
lactoglobulin or casein of the bovine milk. This is usually
noticed after weaning from the breast fed period. Symptoms
like vomiting, abdominal distension, watery diarrhoea,
abdominal colic, failure to thrive and wheezing appear. The
symptoms subside after stopping milk and recur within 48h
after reintroduction. The challenge test by giving milk
protein fractions only will confirm allergy. Serum and the
stool may show antibodies to milk protein fractions. This
65
has to be differentiated from intolerance to lactose in milk
which can be detected by lactose tolerance test (Vide infra).
11. Paradoxical (Spurious diarrhoea)
This is seen in constipated individuals. The diarrhoea is due
to fluid faecal contents being expelled after passing around
the hard impacted faeces. Digital examination reveals the
faecal rocks.
12. Factitious
Factitious diarrhoea may explain some unexplained
diarrhoea. Self-administration of laxatives covertly alone
or with diuretics to feign diarrhoeal illness (Munchausen
syndrome).
CLINICAL APPROACH
History (listening to patient)
The primary method of enquiry into the cases of chronic
diarrhoea is to assess
1. Whether it is several incomplete attempts of evacuation
of well-formed stools (pseudo diarrhoea) or increased
fluid collections being evacuated past the faecal
impaction as in chronic constipation (paradoxical
overflow diarrhoea) or faecal incontinence or profuse
watery stool with or without blood and mucus.
2. Is the diarrhoea alternating with constipation? e.g.
carcinoma of the colon and diverticulitis.
3. Is the diarrhoea occurring soon after ingestion of foods
(lienteric diarrhoea) which may be seen in gastrogenous
diarrhoea or lactose intolerance or allergic states.
4. Does diarrhoea stop after fasting for 1 or 2 days
(osmotic) or not (secretory)? (Of course the patient
should be maintained on intravenous saline and
dextrose.)
5. Is the diarrhoea related to menstrual periods, as in
endometriosis?
6. Crampy abdominal pain or distension with a past
history of dysentery and/or diarrhoea is suggestive of
amoebiasis and intestinal tuberculosis.
7. Any tenesmus (recurrent painful urge to defaecate)? If
any tenesmus is present, it is always suggestive of
diseases of rectum, e.g. ulcerative colitis. If pelvic pain
is relieved by defaecation large bowel is to be blamed
whereas the periumbilical or right iliac fossa not
relieved by defaecation small bowel is blamed.
8. History of fever, anaemia, weight loss—which may
indicate the chronic illness like intestinal tuberculosis.
 66 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
9. History of drug ingestion or any systemic illness or
ulcer dyspepsia or flushings or any previous surgical
interference.
10. Description of faeces
a. Volume—Voluminous, offensive and pale frothy,
e.g. steatorrhoea. If the stool is consistently large,
it is likely to be small intestinal or proximal colonic
in origin and if it is small in quantity with mucus, it
is of descending colonic origin. In pancreatic
cholera, it is more than 1 litre and in irritable bowel
syndrome it is < 1/2 litre per day.
b. Colour—Pale stool may be due to lack of bile in
the intestine or abnormal high fat content or rapid
passage in the intestine.
c. Odour—Offensive as in sprue or jaundice and
odourless as in cholera; like semen in amoebic stool.
d. Nature of Stool—Watery or semisolid or slimy stool
due to mucus or blood as occurs in ulcerative
tumour or ulcerative colitis. Blood and mucus
mixed with fluid faecal material or mucus or
mucous casts (1 to 6 inches) as in irritable bowel
syndrome.
Physical Examination (looking at patient)
A complete general examination and systemic physical
examination is imperative.
General Examination
It is for the evidence of
1. Anaemia and/or nutritional deficiencies
2. Cutaneous manifestations
3. Lymphadenopathy
4. Goitre
5. Arthritis
6. Weight loss or
7. Fever
Systemic Examination
1. Abdomen for evidence of
a. Tenderness over the right or left iliac fossa
b. Hepatomegaly
c. Other abdominal masses like rolled up omentum
d. Ascites
e. Rectal examination
2. Chest for any evidence of cavity in the lungs
3. Neurological examination for evidence of peripheral
neuropathy or long tract lesions.
Investigations
All cases of chronic diarrhoea require studies, beyond history
and physical examination pursued at the very initial
encounter.
1. Stool
a. Naked eye or macroscopic
b. Microscopic examination for
i. Ova and cysts
ii. Occult blood
iii. Faecal leukocyte study—One or two drops of
Loffler’s methylene blue are added to a fleck of
stool on a glass slide. After gentle mixing, a cover
slip is placed over it and examined as wet mount
preparation. If 10 cells per high power field are
identified on a minimum of 5 fields, it is said to
be positive. In 90 per cent of patients with
bacterial diarrhoea, it is positive whereas in 95
per cent of viral infections or giardiasis, it is
negative. If irritable bowel syndrome suspected,
it is better to obtain mucosal smear and stained
for pus (i.e. leucocytes) when it is invariably
negative.
c. Faecal pH. Chemical detection of unconjugated bile
acids, fat with sudan stain, phenolphthalein abuse
(shows pink colour after alkalinisation).
d. Stool cultures for enteric pathogens including
campylobacter.
e. Stool electrolytes and osmolality—In secretory
diarrhoea, electrolytes entirely account for osmolality
whereas in osmotic diarrhoea, electolytes and
osmotically active substances as well account.
(normal faecal osmolality 375 m Osmol.).
Formula: [290–(2 × Na + K concentrations)] yields
osmotic gap. If it is > 125 mOsm/kg it is osmotic
diarrhoea and < 50 it is secretory diarrhoea or
deranged motility.
2. Blood
a. Haematological—Full Blood Counts and ESR
b. Biochemical
i. Serum proteins
ii. Postprandial blood sugar
iii. Serum creatinine
iv. Serum cholesterol and triglycerides
v. Serum thyroxine levels
vi. Immunoglobulins (if indicated)
c. HIV
d. Serological test (vide p 62)
3. Urine
a. Albumin and deposits
b. 5-Hydroxy indole acetic acid if carcinoid suspected.
 Chronic Diarrhoea
4. Endoscopy (Sigmoidoscopy and Colonoscopy). Video
capsule enteroscopy of small bowel.
It is abnormal especially when the stool contains
pus or blood or parasites and normal in malabsorption
syndromes.
5. Gastric acid analysis
6. Radiology
a. Chest X-ray for any evidence of pulmonary
tuberculosis
b. Plain X-ray abdomen for any pancreatic calcification
c. Barium studies
i. Barium meal and follow through—which may
show structural defects or flocculation in the
small intestine due to excess secretion of mucus.
If a non-flocculable barium sulphate is used, the
dilated small intestine with striking transverse
folds may be seen. Jejunal segment may be
present in intestinal lymphoma.
ii. Barium enema—preferably instant enema.
7. Ultrasound of the abdomen
8. CT scan of abdomen.
Additional Investigations
1. Absorption tests
a. Carbohydrates
i. Glucose Tolerance Test (GTT)—In pancreatic
diarrhoea, it is either normal or diabetic type,
whereas it is flat in idiopathic steatorrhoea.
ii. Lactose Tolerance Test—One quarter of milk
(50 g of lactose) when given orally, the blood
glucose levels will rise. Normally the rise is
25 mg and above over the fasting levels. In lactase
deficiency, the glucose level rise will be less than
20 mg/100 ml and onset of cramps and diarrhoea
is the clinical indicator.
iii. Xylose Absorption Test—25 gm of D-xylose is
given orally and about 6 g is excreted in the urine
in five hours time normally, if the kidney function
is good and the subject is not elderly.
b. Fats—Estimation of 72 h faecal fat excretion. Normal
fat is less than 6 g per day.
c. Proteins—Faecal nitrogen excretion is less than 3 g
in 24 h. (1 g of nitrogen = 6.5 g of protein)
d. Vitamins (Schilling test)—1 microgram of radio-
active (cobalt labelled) Vitamin B12 is given orally
and two hours later 1000 micrograms of non-labelled
B12 is given parenterally. Normally more than 7 per
cent of the administered dose should be excreted in
67
urine in 24 h. An abnormal test indicates pathology
of the distal small intestine since B12 is absorbed in
the distal ileum.
e. Minerals (calcium)—Serum calcium may be
decreased in steatorrhoeas and normal in pancreatic
diarrhoea.
2. Breath tests (for Bacterial Overgrowth)
a. Hydrogen breath test—After 50 g of lactose, the
excretion of hydrogen in the breath can be measured by
gas chromatography. Breath hydrogen excretion rises
in lactase deficiency since colonic bacteria converts
unabsorbed lactose to hydrogen.
b. Bile acid breath test—14C glycine cholatge or 14C
cholyglycine may be given orally—when less than 1 per
cent of dose is excreted as 14CO2 in four hours time.
Increased excretion is seen with bacterial overgrowth
or bile acid malabsorption.
c. 14 CTriolein breath test—When triolein is given,
normally 3.5 per cent of the dose and above is excreted
as breath 14 CO 2 per hour. It is decreased in the
malabsorption or maldigestive disorders.
3. Endoscopy
Small intestine visualised with capsule endoscopy and
double balloon enteroscopy.
4. Pancreatic function tests
a. Secretin Test Supported by Lundh Test Meal—Direct
stimulation of the pancreas with secretin given IV (one
unit per kilogram) and analyse the duodenal contents
especially the bicarbonate concentration. Normally the
volume of panreatic juice and bicarbonate content
increased but in pancreative disease IV secretin has no
such effect and bicarbonate concentration is diminished
(i.e.) less than 80 m Eq/l). Lundh test meal may increase
enzyme output.
b. PABA Test (Para Amino Benzoic Acid Test)—Benzoyl
tyrozyl amino benzoic acid is given orally when it is
hydrolysed by chymotrypsin in the small intestine
liberating PABA. This is absorbed/excreted in the urine.
If this PABA in the urine is low, it is suggestive of
pancreatic insufficiency.
c. ERCP (Endoscopic Retrograde Cholangio Pancreato-
graphy)
5. Selective testing for gastrin, VIP carcinoembryonic
antigen (CEA).
 68 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
6. Biopsy studies
a. Intestinal mucosal biopsy for lactase activity at the
ligament of Treitz.
b. Jejunal biopsy and culture of the jejunal juice—Crossby
capsule is swallowed at the end of the tube, which is
directed to the jejunum under fluoroscopy and fired by
suction down the tube. The small bowel biopsy material
is held between the jaws. If the culture of the jejunal
juice shows over 105 organisms, it is suggestive of
bacterial overgrowth in the blind loops or other
conditions of intestinal stasis.
c. Rectal biopsy—Instead of normal finger-like villi, there
may be ridges or convolutions (partial atrophy) or flat
cobblestones appearance (subtotal atrophy).
7. Radiology—Indium III Scanning.
With autologous leucocytes may show localisation and
extent of activity of the inflammatory bowel disease.
8. Radioimmune assay — To test for hormone secreting
tumours of the gastrointestinal tract.
TREATMENT OF CHRONIC DIARRHOEA
Management approach to chronic diarrhoea demands an
enquiry as to whether it is
a. Infectious type (secretory)
b. Noninfectious type
i. Nonspecific inflammatory bowel diseases
(Exudative)
ii. Altered intestinal motility (Endocrinal or post-
vagotomy or cathartic abuse)
iii. Colonic tumours (Secretory)
iv. Functional
c. Malabsorption states (Osmotic)
This can be ascertained by a proper evaluation.
Management includes symptomatic therapy and treatment
of specific diseases.
Symptomatic Therapy
1. Fluid and electrolyte replacement (Na-K; HCO3–) is
indicated when fluid loss is more than 1 litre per day.
Oral hydration is considered, since sodium and glucose
facilitate the integrity of cotransport mechanism of small
intestine.
2. Diet and Nutrition
i. Bland diet, low in residue in general
ii. Glucose and saline mixtures orally; dilute milk, tea,
whey (defatted dried milk in steatorrhoea)
iii. Coarse roughage, root vegetables, avoid bananas in
ulcerative or malignant disease of the alimentary tract
or intestinal carbohydrate dyspepsia.
iv. Low carbohydrate diet in fermentative diarrhoea
(carbohydrates escaping digestion) or fatty
diarrhoeas (fats escaping digestion). Replace with
fat soluble vitamins.
v. Gluten free diet (exclusion of wheat, barley, oats and
rye) indicated in coeliac disease. Similarly
elimination of dietary lactose for lactase deficiency.
vi. High protein diet in steatorrhoea or ulcerative colitis
and low protein diet in putrefactive diarrhoea
(proteins escaping digestion)
vii. Low fat diet and protein diet in chronic pancreatitis.
3. Provide supplements of vitamins and minerals as
necessary.
4. Antidiarrhoeal agents (Avoid in Inflammatory bowel
disease since toxic megacolon may be precipitated).
a. Binding osmotically active substances is aimed with
Kaolin-Pectin—15-30 ml (four times daily or after
liquid bowel movements as necessary).
b. Decreasing bowel motility
i. Diphenoxylate—2.5 mg 3 to 4 times daily
ii. Loperamide—2 mg 4 times or after each liquid
bowel movement, to a maximum of 8 mg
iii. Racecadotril 100 mg tds.
iv. Opiates—codein phosphate (3-60 mg tds); opium
(0.08 ml tds) (opiates contraindicated in
infectious or inflammatory bowel diseses)
5. Anticholinergics antispasmodics—hyoscine-N-
butybrom (10 mg); dicyclomine (10 mg), clidinium (2.5
mg)
6. Tranquilisers—Chlordiazepoxide (5-10 mg)
7. Digestants—Supplements of enzymes; pancreatic
extracts
8. Treatment of perianal discomforts
i. Seitz bath for 10 min. may be soothing
ii. Tenesmus is relieved with ointments like cinchocaine
1.1 per cent or lidocaine 5 per cent inserted by an
applicator.
Specific Treatment for Specific Diseases
1. Inflammatory
Infectious (Specific)
• Protozoal
• Amoebiasis Treated with
i. Metronidazole (400-800 mg tds) for 7-10 days; or
 Chronic Diarrhoea
ii. Tinidazole (1.2 g per day for 7-10 days); or
ornidazole (500 mg bd for 7 days); or
iii. Occasionally dehydroemetine (30-60 mg im for 1
week) or 20 mg b.d orally followed by
iv. Diloxamide furoate (500 mg tds for 10 days); or
v. Diiodohydroxyquinoline (650 mg tds for 20 days);
vi. Tetracycline—0.5 g 6-hourly for 10 days given along
with above drugs (as it is not directly amoebicidal)
may prevent relapse.
• Giardiasis Tinidazole (2 g single dose) repeated after
one week.
• Intestinal Tuberculosis
a. Drugs—3 or 4 drugs mentioned underneath given
for 6-9 months.
i. Rifampicin (10-20 mg/kg/day)
ii. Isoniazid (300 mg/day)
iii. Pyrazinamide (20-35 mg/kg/day—maximum 2 g
per day)
iv. Streptomycin (1 gm daily im)
v. Ethambutol (15 mg/kg/day up to 1 gm per day)
b. Surgical intervention if stenosis or marked
diminution of bowel occurs.
• Yersina: Ciprofloxacin (500 mg b. d. for 5 days orally)
HIV– (Refer Chapter ‘Pyrexia of Unknown origin’)
Cryptosporidium parvum-paromomycin is
recommended (1 gm bd)
Noninfectious (Nonspecific)
• Inflammatory bowel disease
(Some include ulcerative colitis and Crohn’s disease only
as inflammatory bowel disease in the restricted
connotation).
a. Ulcerative colitis. Treatment includes supportive
measures, systemic therapy and surgery, if necessary.
• Supportive measures—Maintaining nutrition, (if
necessary, parenteral nutrition through central venous
route); correction of fluid and electrolyte balance
especially hypokalaemia; anaemia and secondary
infection treated accordingly.
• Systemic therapy
i. Glucocorticoids—(oral 40-60 mg per day for
3-6 weeks; topical—with suppositorries for
proctitis or enemas for colitis; intravenous—in
severe disease, hydrocortisone 100-200 mg IV
6th hourly).
ii. ACTH intravenous drip (120 units per day) is
preferred in the nascent attack.
iii. Sulphasalazine—2 to 4 g per day orally for one
year.
69
iv. Mesalazine—1 to 2 g per day orally or as enema
(4 g per 60 ml) may be useful to maintain the
remission.
v. Azathioprine (derivative of 6-mercaptopurine) or
6-mercaptopurine (2.5 mg/kg) may spare the
steroid (anticholingergics and opiates are
contraindicated).
• Surgery (for nonresponsive cases)—Procto-
colectomy and ileostomy or ileorectal anastomosis
iloeostomy or ileorectal anastomosis.
b. Crohn’s disease
i. Drugs—Antidiarrhoeals, Cortico steroids,
sulphasalazine, immunosuppressants and metro-
nidazole if persistent. Anti-tumour necrosis
antibodies therapy (Infliximb)
ii. Surgery—Minimal resection for fistulas,
strictures or intractability.
c. Diverticulitis
i. Drugs—Methyl cellulose (1 teapoons in water);
metronidazole and ampicillin
ii. Surgery—resection.
d. Postradiation: Symptomatic
2. Malabsorption Syndrome and Protein Losing
Enteropathy (Diarrhoeal/Steatorrhoeal)
Gastrointestinal malabsorption can be broadly grouped as:
(A) Defective Secretions. (B) Small bowel mucosal
disorders. (C) Intestinal hurry.
A. Defective Secretions
i. Bile salt deficiency
a. Obstructive jaundice (Refer to Chapter ‘Jaundice’).
b. Stagnant (blind) loop syndrome- treated with
oxytetracycline orally (I g per day in divided
doses for I week) and repeated every 2 months
and / or Metronidazole (400 mg tds. for one
week). Surgery advocated if necessary. (Refer to
Chapter ‘Weight Loss’).
c. Intestinal resection (Vide infra)
ii. Enzyme Deficiency
a. Chronic Pancreatitis (Pancreatic enzyme
deficiency). Treated with pancreatic extracts
containing lipase (1000 units per meal), protease
and amylase; antacids and H 2 receptor
antagonists prevent inactivation of pancreatic
extracts by hydrochloric acid; insist on alcohol
abstinence and low fat diet with vitamins A and
D; judicious use of anagesics before meal.
 70 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Surgery is indicated for unremitting pain
(Pancreatic duct drained into small intestine or
pancreatectomy).
b. Zollinger-Ellison syndrome- omeprazole in larger
doses than for duodenal ulcer preferably given
continuously, with supplements of lipase. If
unresponsive, total gastrectomy advocated.
c. Lactase deficiency- Restrict or eliminate dietary
lactose. (Vide infra).
B. Small Bowel Syndromes
i. Inflammatory
a. Tropical sprue-treated with tetracycline (250 mg
6th hourly for 4 weeks) and folic acid (5 mg/
day)
b. Coeliac disease-strict gluten-free diet is of
immense value vitamin and mineral deficiencies
and hypoproteinaemia (due to impaired amino
acid absorption) are corrected if necessary.
c. Fistulae (Crohn’s disease, stagnant loops)-(Vide
supra).
d. Intestinal tuberculosis- (Vide supra).
e. Radiation enteritis- (Vide supra).
f. Parasitic Infestations
• Giardiasis- (Vide supra)
• Diphyllobothrium latum (Albendazole 400
mg single dose daily for 3 days to be repeated
at 14 days interval for a total of three cycles,
with supplements of B12)
• Strongyloidiarsis – Albendazole (400 mg for
3 days).
g. Blind loop syndrome (Vide Supra)
ii. Infiltrations
a. Whipple’s disease (Tetracycline 1 gm per day for
one year or penicillamine 250 mg per day
gradually increased upto 1 gm)
b. Lymphoma—Surgery, radiotherapy and
chemotherapy. (Refer to Chapter ‘PUO’)
c. Scleroderma (Refer — polyarthritis)
d. Ischaemic Colitis—Symptomatic treatment and
surgery if stricture or peritonitis develops.
C. Intestinal Hurry:
i. Postgastrectomy: Dumping syndrome
Diarrhoea, sweating and fainting after eating may
occur. Late dumping occurs after 1 or 3 hours after
taking food due to hypoglycemia, which is relieved,
by taking glucose. More proteins and less glucose
in meals will be helpful and improve with time.
ii. Postvagatomy
Loperamide is effective.
iii. Postsurgical (GI tract)
Intestinal resection leading to diarrhoea/steatorrhoea is
treated with H2 receptor antagonists and a simple diet to
reduce the gastrointestinal secretions. Cholestyramine (4 mg
with meal) prevents cathartic effect by binding bile acids in
the intestine. Supplements of vitamins and minerals are
complimentary.
Protein losing enteropathy
Diagnosis is confirmed by measuring faecal clearance of
chromium labelled albumin after IV administration.
Adequate nutritional support and symptomatic treatment for
oedema while discerning the underlying cause is advocated.
3. Neoplasms
a. Vipoma and carcinoid tumour are treated surgically.
However, somatostatin 50 mg subcutaneously appears
promising in carcinold tumour (Refer to Chapter
‘Pruritus’). Somatostatin analogues (Octreotide
0.1 mg tds) counters peripheral effects by blocking
release of tumour mediators. Loperamide or
cyproheptidine to control diarrhoea and ketanserin for
flushing may be beneficial. Octreotide is beneficial for
vipoma, if surgery is not possible.
b. Colonic carcinoma-Adenocarcinoma, which is common,
needs surgical intervention. Postoperative intravenous
infusion of 5-fluorouracil via hepatic vein/intraportal
plus levamisole or folinic acid for one year is
recommended. Radiotherapy useful in cancer rectum.
c. Zollinger-Ellison Syndrome) (Refer to Chapters
‘Haematemesis and Melaena’).
d. Lymphomas (Refer Chapter ‘Pyrexia of Unknown
Origin’).
4. Deficiency States
a. Pellagra Nicotinamide 100 mg is administered 4
hourly. Dosage may be decreased after one week. In
addition, Vitamin B complex is added to maintain
the equilibrium with other components. The diet
should be rich in proteins and vitamins. Avoid cereals
like maize. Symptomatic treatment for diarrhoea and
dermatitis may be instituted.
Secondary pellagra is to be treated appropriately.
b. Globulin- (Vide infra)
c. Achlorhydria-Treat the underlying cause. Associated
features like flatulence, anaemia, and diarrhoea are
treated symptomatically.
 Chronic Diarrhoea
5. Endocrinal and Metabolic
a. Hyperthyroidism (Refer to Chapter ‘Goitre’)
b. Diabetes mellitus (Refer to Chapter ‘Polyuria’).
Diarrhoea due to diabetic autonomic neuropathy or
pancreatic insufficiency is treated with loperamide (6-8
mg/d orally). Clonidine may be beneficial.
c. Chronic uraemia (Refer to Chapter ‘Polyuria’)
d. Endometriosis—Danazol (10-15 mg/kg body weight per
day) induces ovarian suppression and resolution of
endometriosis. The other alternative is administration
of gonadotropin releasing hormone GnRH which
suppresses FSH and LH with consequent resolution of
endometriosis. Laparoscopic laser electrocoagulation or
surgery are other therapeutic approaches.
e. Amyloidosis—if once amyloid is deposited, rarely it
regresses. Supportive measures are provided, as there is
no specific therapy. Colchicine may be useful in
preventing acute attacks in familial mediterranean fever.
The role of dimethylsulphoxide is being assessed.
However, the underlying cause of amyloidosis may be
treated.
f. Pancreatic cholera syndrome (Vipoma-Islet cell tumour).
(Vide supra).
6. Post Gastrointestinal (GI) Surgery
Loperamide (6-8 mg/d) or codein (90-180 mg/d) may be
tried (Vide supra).
7. Drugs
Withdrawal of the offending drug and if necessary
symptomatic treatment indicated.
8. Functional Colonopathies
a. Irritable bowel syndrome (Refer to Chapter ‘Dyspepsia’)
b. Nervous diarrhoea—Drugs reducing activity of
gastrocolic reflex like propantheline may be useful.
Codeine or loperamide is effective. Tranquiliser is added
half an hour before each meal if necessary. Diarrhoea is
not influenced by dietary measures.
9. Genetic
a. Abetalipoproteinaemia—The inherited biochemical
defect of an inability to transport absorbed triglyceride
71
into portal circulation with absent chylomicron and VLDL
formation is treated with medium chain triglycerides and
a low fat diet.
b. Chloridorrhoea-The treatment includes parenteral
administration of fluids consisting of sodium and
potassium chlorides to replace the loss of chlorides. 10
mmols of chlorides/kg/d may be necessary. Once
hydration is corrected, oral replacement may be done
for 3-4 weeks. As the weight gains, the outlook improves.
c. Hartnup disease-This inborn error of metabolism, in
which tryptophan absorption is impaired, responds to
nicotinamide.
d. Hypogammaglobulinaemia-It is treated with
immunoglobulin injection consisting mainly of IgG
(monthly parenterally 100 mg/kg).
e. Disaccharidase deficiency-Stopping lactose ingestion is
all that is required, i.e. milk is contraindicated. However,
soybean milk or arrow root can be used. Costly lactose
free proprietary milk preparations are alternatives.
Associated overwhelming infections may be treated with
appropriate antibiotics though, in general, lactase
deficiencies are worsened by antibiotics.
10. Allergic
Avoid incriminating agents like milk protein or any other
dietary factor.
11. Paradoxical
Appropriate measures like-fibre diet, plenty of water,
abdominal exercises, and education may be encouraged
instead of strong laxatives or purgatives. However, liquid
paraffin alone or with hydrophillic colloids like agar may
be given as a substitute for purgatives. Mild laxatives like
senna or bisacodyl can be considered for long continued
constipation.
12. Factitious
Feigning illness with the hope of gaining hospital admission
through deception should be detected, and the pattern of
social maladjustment, due to low socioeconomic status is
to be rectified.
72 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Chronic Diarrhoea 73
 Chapter
Coma
5
The term coma is derived from Greek ‘KOMA’ meaning
“deep sleep” and in fact denotes brain failure. It is defined
as a state of prolonged unconsciousness, unreceptiveness
and unresponsiveness. Consciousness is awareness of the
environment and of the self which is associated with cortical
activity and dependent on ascending reticular activating
system of the brainstem and thalamus. This system of
Magoun is like a pacemaker keeping the cerebral cortex in
a state of varying wakefulness. The reticular formation which
extends from lower border of the pons to ventromedial
thalamus receives collateral fibres from sensory pathways
and cortex as well and in turn sends fibres to the cortex for
alerting.
PATHOPHYSIOLOGY
Disturbance of consciousness may be due to structural or
metabolic abnormalities of both cerebral cortices, thalamus
or brainstem particularly midbrain. In the former,
macroscopically visual lesions are demostrable whereas in
the latter, no visible lesion is present except a possible
microscopic demonstration of cellular change. Coma is
generally not produced by lesions of one cerebral
hemisphere only, unless the other cerebral hemisphere or
secondarily involvement of the brainstem also occurs.
The pathophysiological mechanisms by which
consciousness is disturbed essentially are
1. Structural (compressive, destructive, occlusive)
2. Metabolic (Hypo or hyperglycaemia, hepatic or uraemic
encephalopathy)
Structural
These lesions can be classified as follows:
1. Supratentorial lesions (Extracerebral and intracerebral
lesions)—Result in focal signs like hemiplegia, conjugate
ocular deviation opposite to hemiplegic side.
a. Laterally extending mass lesions result in herniation
of medial part of the temporal lobe through the
opening of the tentorium, compressing the third nerve
and lateral midbrain with consequent ipsilateral
dilatation of the pupil and external ophthalmoplegia,
ipsilateral hemiplegia and later decerebrate posture.
b. Medially extending mass lesions result in small
pupils (1 to 3 mm); all eye movements except upward
conjugate deviation present (demonstrated by Doll’s
head phenomenon) and hemiplegia. Later small
pupils become dilated and fixed (3 to 5 mm), eye
movements impaired, Cheyne-Stokes respirations
followed by hyperventilation, bilateral decerebrate
rigidity and quadriplegia occur. The absence of eye
movements along with ataxic respirations set in, as
further spread occurs to medulla.
2. Infratentorial lesions—Hemiplegia with conjugate
deviation towards the hemiplegic side with ophthalmo-
plegia like adduction failure on the side of the lesion
and paralysis of cranial nerves, pupillary changes with
loss of light reflex, absent oculovestibular reflex and
bizarre respirations noticed.
Metabolic
Specific metabolic and toxic states interfere with the
metabolism of both cerebral cortices and brainstem leading
to altered states of consciousness. This is attributed to
reduced cerebral blood flow and metabolic activity, due to
insufficiency of coenzymes, substrate and oxygen (below
20 ml per 100 g of brain tissue per min. as compared to the
normal cerebral blood flow of 55 ml per 100 g per min).
This is characterised by diffuse neurological signs (usually
no localising signs) hyper or hypoventilation, equal pupils
reacting to light normally, intact eye movements and
involuntary movements (like tremor and asterixis).
 Coma
Oculovestibular reflex is preserved. Coma is gradual in onset
unlike structural lesions and precedes motor signs which,
when present, are symmetrical.
The altered states of consciousness can develop (a)
rapidly or acutely (coma); (b) insidiously as a chronic
process (dementia).
GRADING OF COMA
The loss of consciousness can be graded as
a. drowsiness
b. stupor and
c. coma
depending upon the degree of arousal or loss of reflex
activity.
It is assessed by (i) Motor response to pain or commands
(6 points) (ii) Verbal response to questions (5 points)
(iii) Eye opening in response to pain or shouts (4 points).
The minimum is 3 points out of 15 is scored in coma
(Glasgow coma scale). Reflex activity may be an additional
feature for assessment.
Drowsiness (Somnolence)
Consciousness is impaired and there is an element of
confused cloudy state or imperceptiveness (inattention and
incoherence of thinking). The subject may obey commands
and responds to questions and stimuli easily (withdraws the
limb to avoid the stimulus).
Simple conversation is possible for a short period with
a degree of disorientation or random inappropriate speech,
without a conversational flow. Spontaneous eye opening is
appreciable.
Stupor
It is a state where one can be roused by strong vigorous
stimuli with some motor response to pinprick and cannot
answer questions. The speech may be incomprehensible with
low inarticulate sounds. Eyes are opened to verbal
commands or painful stimuli. Nevertheless, the subject sinks
back to a state of unresponsiveness immediately reflexes
remain unaltered.
Coma
In coma, one cannot be roused by pressure or painful stimuli
or spoken commands. There is no motor response or verbal
response. The patient cannot utter any words. The eyes
appear closed and fail to open in response to painful stimuli
75
or verbal commands. The loss of reflex activity such as
absence of reflexes occurs and the vital reflexes (coughing,
breathing and vasomotor control) finally disappear as the
coma deepens. All these stages may be appreciated either
in the evolving coma or its recovery.
CAUSES OF COMA
The causes of coma can best be grouped in Table 5.1.
1. Neurological Causes
Cerebrovascular Lesions
This is the commonest cause of coma in clinical practice.
The conditions likely to produce these lesions result from
cerebral haemorrhage, subarachnoid haemorrhage, cerebral
thrombosis, cerebral embolism and hypertensive
encephalopathy (Figs 5.1 to 5.3).
In a case of apoplexy or stroke due to vascular lesion
(haemorrhage, thrombosis or embolism), the onset is abrupt
occurring during excitement or physical exertion in a case
of haemorrhage or embolism, whereas in thrombosis the
onset will be gradual occurring in sleep. The presence of
unilateral signs like hemiplegia is a common feature in all
the three episodes. To know which side is paralysed, one
has to examine for the flaccidity of the limbs, conjugate
deviation of the eyes, flattened nasolabial fold and loss of
corneal reflex on the side opposite to the lesion. Pupils are
unequal (large pupil on the side of the lesion). In spite of
loss of consciousness spontaneous withdrawal of the limbs
of the nonparalysed side to pin prick may be present in some
cases. An evidence of hypertension or atherosclerosis or
acute infection may be present. The rise in blood pressure
may be due to a hypertensive response or long standing
hypertension per se. The former lasts for few days to one
week after the accident. This point is to be borne in mind
while displaying antihypertensive drugs. In severe cases,
coma is deep, breathing is stertorous, cyanosed and the skin
is cold with profuse sweating.
The localisation of the lesion is possible
a. Hemiplegia to the opposite side of the lesion and eyes
as well as the head deviated towards the lesion (cerebral
hemisphere) usually middle cerebral artery and
occasionally anterior cerebral artery are involved.
b. Hemiplegia and deviation of eyes opposite to the side
of the lesion (thalamus-posterior communicating,
anterior choroidal, middle cerebral, Posterior cerebral
or posterior choroidal) or pons just above the sixth
nucleus.
 76 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 5.1: Aetiological classification of coma

F. Metals
1. Neurological a. Arsenic
A. Cerebrovascular lesions b. Lead
a. Cerebrovascular accidents 6. Haematological
i. Cerebral haemorrhage A. Hyperviscosity syndrome
ii. Subarachnoid haemorrhage B. Bleeding disorder
iii. Cerebral Thrombosis C. Thrombophilia
iv. Cerebral Embolism
7. Psychiatric
b. Hypertensive encephalopathy
A. Depressive psychiatric states
c. Cerebral venous thrombosis
d. Epidural or subdural haemorrhage B. Hysteria
B. Meningitis and encephalitis
C. Space occupying lesions
D. Head injury
E. Epilepsy-postictal
2. Metabolic
A. Diabetic acidosis, hyperosmolar nonketoacidotic coma, lactic
acidosis
B. Hypoglycaemia
C. Uraemia
D. Hepatocellular failure
E. Porphyria
F. Electrolyte disorders
a. Hyper and hyponatraemia, hyper and hypocalcaemia
b. Metabolic alkalosis, acidosis
c. Respiratory acidosis (hypoxia, hypercapnia)
3. Endocrinal
A. Hypothyroidism (Hypothermia)
B. Hypopituitarism (Hypothermia)
C. Suprarenal cortical failure
4. Tropical
A. Infections
a. Parasitic
i. Cerebral malaria
ii. Filarial encephalitis
iii. (Rare) Toxoplasmosis
b. Typhoid fever
c. (Complicated) Cholera
B. Heat hyperpyrexia
C. Wernicke’s encephalopathy
5. Toxicological
A. Sedatives and tranquilisers
a. Barbiturates
b. Diazepam Fig. 5.1: Carotid-vertebral arteries and circle of Willis
c. Phenothiazines
B. Narcotic
a. Opium c. Paralysis of the 3rd nerve on the side of lesion with
b. Morphine hemiplegia on the opposite side- (Mid brain)-crossed
c. Pethidine hemiplegia (Weber’s syndrome). Posterior communi-
C. Aspirin and salicylates cating artery involved.
D. Alcohol d. Bilateral flaccid paralysis with sensory loss on both sides,
E. Carbon monoxide
pin point pupils, no oculocephalic or oculovestibular
 Coma
Fig. 5.2: CT scan showing intracerebral haemorrhage in the
region of caudate nucleus and anterior limb of the internal
capsule on the left side extending into ipsilateral temporal lobe
with grade-2 midline shift
Fig. 5.3: CT scan showing hypodense lesion in the posterior
part of the left temperoparietal region suggestive of infarct in
the left middle cerebral artery territory
reflex, hyperpyrexia, i.e. quadriplegia. Facial paralysis
of lower motor neurone type on one side and hemiplegia
on the opposite side- (Pons) Crossed hemiplegia
(Foville’s syndrome). Paramedian or lateral branches of
Basilar artery are incriminated respectively.
77
e. Ataxic respirations, fixed dilated pupils, falling blood
pressure, quadriplegia crossed hemiplegia, i.e. unilateral
paralysis of half of the tongue on one side with
hemiplegia to the opposite side postural sensibility may
occur (medulla) (Paramedian branches) vertebral artery
is involved.
f. Acute ataxia, nystagmus, vomiting (Cerebellum-superior
and inferior cerebellar arteries involved)
g. Hemi or quadriplegia, uni. or bilateral sensory symptoms,
cerebellar symptoms, drop attacks, diplopia, dizziness,
dysarthria, dysphagia. (cerebellum and brain stem).
Vertebrobasilar circulation involved.
In case of thrombosis vascular causes like athero-
sclerosis, arteritis or carotid artery stenosis; haematalogical
causes like anaemia, sickling, thrombocytosis, erythro-
cytosis, thrombophilia; and metabolic causes like hyper-
lipidiemia or diabetes mellitus are incriminated.
In case of embolism, there is evidence for the source
either in the heart or in the calf muscles.
In case of cerebral haemorrhage, hypertension, trauma or
rupture of aneurysm may be accountable.
In case of subarachnoid haemorrhage, onset is sudden
with intense headache and signs of meningeal irritation, focal
signs like cranial nerve paralysis or hemiplegia are usually
seen in the young adults due to rupture of a congenital berry
aneurysm. CSF will be under increased pressure and is
uniformly blood stained like intracerebral haemorrhage
rupturing into the surface of the brain or into the ventricles.
The supernatant fluid, after centrifuging, shows
xanthochromia. Ophthalmoscopic examination may reveal
subhyaloid haemorrhage extending from disc margin or
small retinal haemorrhages or sometimes papilloedema.
Arteriography is obligatory, if X-ray skull shows
calcification in the wall of aneurysm or when surgery is
contemplated. CT scan is confirmatory.
Unconsciousness with fits associated with hypertension
is usually termed as hypertensive encephalopathy in which
transient cerebral symptoms like hemiplegia, blindness and
papilledoema are noticed.
Cerebral venous thrombosis may occur usually in
postpartum periods resulting in coma with neurological
signs, thrombocytosis and hyperfibrinogenaemia. In
pyogenic sinus thrombosis, headache, vomiting with
drowsiness deepening into stupor or coma or sometimes
convulsions are the presenting manifestations. Bilateral
corticospinal lesions may be confined to the lower limbs or
unilateral focal symptoms may be present (Intracranial
venous sinuses receive blood from the cerebral veins and
drain into internal jugular vein).
 78 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

The epidural haemorrhage is usually due to injury of Head Injury

the temporal or parietal fractures with the involvement of
In case of traumatic accidents, the external injury may be
middle meningeal vessels. This may be misdiagnosed due
seen or blood in the external orifices like ears or nostrils or
to failure to identify the lucid interval (between unconscious-
blood in the subconjuctiva may be noticed. Examination of
ness immediately after injury and later developing
the skull may show fracture. Pupillary changes are highly
unconsciousness again.) Coma progresses during the course
characteristic and unconsciousness is progressive, following
of a week associated with seizures, hemiplegia and dilated
a lucid interval. The so called Hutchinson’s pupil, i.e. pupil
pupil on the side of hematoma. CSF may be clear or blood
on the opposite side of the lesion is normal in stage 1 and 2;
coloured.
in stage 3 it is dilated and reacts to light; in stage 4 widely
In subdural haemorrhage, the consciousness level
dilated and insensitive. On the same side of the lesion, in
always fluctuates. Intellectual retardation, personality
stage 1 there is a small pupil; in stage 2 moderately dilated,
changes, unsteadiness, headache may be discernable signs
in stage 3 widely dilated with no reaction to light; and in
of increased intracranial pressure, unequal pupils, slowly
stage 4 widely dilated and insensitive. These changes are
evolving stroke, localising neurological signs depend upon
supposed to be due to initial irritation and subsequent
the focal brain damage. It may be usually due to an injury
paralysis of the third nerve by subtentorial herniation of
which may be trivial especially in the elderly. The interval
hippocampal gyrus.
between the injury and signs may be even upto two or three
months.
Epilepsy
CSF is bloody in acute cases and xanthochromic in
chronic cases. Either history of previous epileptic attacks or scars or bitten
tongue may suggest the cause of coma as postepileptic which
Meningitis and Encephalitis usually lasts for about an hour, though status epilepticus
may be followed by prolonged coma. Post-epileptic stupor
In meningitis and encephalitis, the onset may be acute or may also be unusually prolonged in elderly patients, with
subacute before losing consciousness. The patient complains symptomatic epilepsy.
of severe headache with fever for several hours prior to the
onset of coma with signs of meningitis like kernigs or
2. Metabolic Causes
Brudzinski’s sign. The CSF, reveals pleocytosis, increased
protein and low sugar. In encephalitis, the signs are those Diabetic acidosis
of fever, fits, with or without focal signs. Not only there is
Refer to Chapter ‘Shock’
diffuse damage to the brain but also in certain cases damage
to the spinal cord is present. CSF examination shows
increased protein and normal sugar in addition to
Hyperosmolar Nonketotic Diabetic Coma
pleocytosis. It presents itself with marked dehydration and
hyperglycaemia in an elderly maturity-onset diabetic. The
Space Occupying Lesions osmolality is more then 340 mmol/kg and glucose may be
even 1000 mg percent. Focal neurological signs like
In space occupying lesions (intracranial tumour or abscess),
Jacksonian seizure, transient hemiplegia and clouding of
the loss of consciousness is insidious and gradual in onset,
consciousness or stupor may accompany coma. Prerenal
although rapid loss of consciousness is known to occur
uraemia with raised blood urea or creatinine and mild
occasionally when haemorrhage occurs in a tumour. A
metabolic acidosis may be present. Free fatty acid levels
history of throbbing type of headache more during the night
are low with nonketone bodies unlike in ketoacidosis.
and in the early morning, projectile vomiting and failing
vision will be invariably forthcoming. Signs of focal cerebral
compression are often helpful, if they are present, or
Lactic Acidosis
pulmonary symptoms like those of suppurative diseases or This results usually whenever oxygenation of the tissues is
bronchogenic carcinoma or history of previous head injury inadequate as in any case of circulatory collapse but it can
and ophthalmoscopic examination showing papilloedema also occur without apparent tissue hypoxia, e.g. drugs like
may help to diagnose a case of space occupying lesion. phenformin for thiamine deficiency. It usually presents as
(Refer to Chapter ‘Headache’) nausea, vomiting, restlessness and Kussmaul type of
 Coma
respirations. It is suspected when only acidosis actually
exists with elevated lactate. The pH is low and plsma
bicarbonate is reduced. Anion gap is more (i.e. [Na+] – [Cl–
– HCO3–] which is normally about 12 mmol/L.
Hypoglycaemia
Correspondingly opposite to the diabetic ketosis, is
hypoglycaemia which has to be borne in mind. The history
of having taken more insulin or oral hypoglycemic drugs
than necessary, altered behaviour or altered consciousness,
tremors, sweating, moist skin, shallow respirations, normal
blood pressure, dilated pupils, increased deep reflexes, and
fits help its recognition and the low blood sugar (less than
40 mg%) clinches the diagnosis. Hypoglycaemia may also
be due to islet cell tumour of the pancreas, nonpancreatic
tumours, Addison’s disease and hypopituitarism, chronic
alcoholism (fasting hypoglycaemia), or following
gastrointestinal surgery, (postprandial hypoglycaemia), or
prolonged exercise or liver failure.
If insulin does not suppress C-peptide, it is diagnostic
of insulinoma. If insulin levels are low, nonpancreatic
neoplasms or endocrinal or alcohol causes are to be
suspected. Insulin may be high in autoimmune hypogly-
caemia (insulin autoantibodies).
Uraemia
Uraemic coma may occur in either acute or chronic renal
failure especially in renal destructive lesions. Headache,
drowsiness, insomina, anorexia and vomiting are early
symptoms. Later, generalised convulsions precede coma.
Dry skin, hissing respirations and hiccups are other features.
Blood urea and serum creatinine are raised. However, urine
with fixed specific gravity (i.e. 1010) albumin, casts and
associated high blood pressure help in the diagnosis of this
condition. Common causes of uraemia are prerenal (shock),
renal (glomerulo and pyelonephritis, hypertension, diabetes
mellitus), and postrenal (stones, enlarged prostate) (Refer
to Chapter ‘Polyuria’).
Hepatocellular Failure
In case of hepatocellular failure, onset of encephalopathy
may be sudden [Grade 1 = Irritability, Euphoria, untidiness;
Grade 2 = Confusion, drowsiness, psychiatric changes;
Grade 3 = Stupor (rousable); Grade 4 = Coma] with or
without cerebral oedema. Psychiatric changes, e.g.
behaviour disorders, noisy delirium, flapping tremor
reminiscent of beating of wings of birds (tremors at the wrist
79
joints and metacarpophalangeal joints), the muscular
twitchings will be invariably noticed before the patient
becomes comatosed. A history of gastrointestinal
haemorrhage, diuretics and rapid removal of ascitic fluid
may be forthcoming. Jaundice and/or evidence of portal
hypertension may be staring. The peculiar aromatic amine
smell (Foeter hepaticus), erythema in palms and arterial
spiders and biochemical abnormalities like excess ammonia
and transminases clinch the diagnosis. Apart from ascities,
encephalopathy, haemorrhages, hypoglycaemia, infections
are oliver problems. It is most frequently associated with
acute virus hepatitis and cirrhosis of liver.
Porphyria
It is a very uncommon cause of coma and may be precipitated
after administration of barbiturates in acute porphyrias.
Increased excretion of aminolaevulinic acid and porpho-
bilinogen in the urine is diagnostic. (Refer to Chapter ‘Acute
Abdominal Pain’).
Electrolyte Disorders
i. Hyponatraemia: Water intoxication where excessive
water intake (in conditions like renal failures,
congestive heart failure and cirrhosis of liver) or
inappropriate secretion of ADH reduce the serum
(< 125 mmol/L), osmolality (<260 mmol/kg), and
raised sodium levels in urine (> 20 mmol/L) result in
mental confusion, coma and convulsions.
ii. Hypernatraemia: It may cause impaired consciousness
like drowsiness or delirium. It is usually due to more
water loss than sodium, as occurs in diabetes insipidus
or excess of IV saline administration primary
aldosteronism.
iii. Hypercalcaemia: It may be increased in parathyroid
tumors, malignancies, sarcoidosis and this may cause
impaired consciousness. Estimation of serum calcium
levels may be helpful.
iv. Hypocalcaemia: Impaired consciousness may
occur in severe cases of hypocalcaemia, e.g. below
4 m/Eq/L if the serum albumin is normal. (the level of
serum calcium varies with level of serum albumin, i.e.
for each 1 gm/1 decrease of albumin, there is
0.8 mg percent decrease in the serum calcium). It is
associated with hypoparathyroidism, chronic nephritis,
steatorrhoea or alkalosis.
v. Metabolic alkalosis: It is due to prolonged vomiting
and may produce stupor. The sodium bicarbonate is
raised to 35 mEq/L.
 80 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
vi. Metabolic acidosis (Vide supra—Diabetic Coma and
Uraemic Coma.)
vii. Respiratory acidosis: When there is disturbed alveolar
ventilation as in chronic asthma and emphysema, there
is increase in PCO2 (Hypercapnia) and carbonic acid
concentration in blood and the pH is reduced. The
administration of oxygen may correct existing hypoxia
but decrease the respiratory drive (which depends only
on hypoxic stimulus since ventilatory response to
carbondioxide is lost) and increase carbondioxide
retention (Hypercapnia)-precipitating headache and
coma (carbondioxide intoxication). Apart from this,
anoxic anoxia, anaemic anoxia due to haemoglobin
deficiency or ischaemic anoxia due to arterial disease
or cardiac standstill may result in loss of consciousness
(after six seconds of total circulatory standstill) and
(permanent damage to the brain occurs after 8 min. of
total ischaemia or 15 min of diffuse ischaemia). See
Chapter on ‘Cyanosis”
3. Endocrinal Causes
Hypothyroidism
Refer to Chapter ‘Goitre’.
Hypopituitarism
Coma is due to hypoglycaemia, hypotension, and
hypothermia with superimposed features of hypopituitarism.
Hypothermia results from either hypopituitarism or
hypothyroidism or exposure to severe cold climates. The
patient will be having temperature lower than 96°F,
sometimes falling to even 80°F in the former two, without
atmospheric influences. In addition to this, the signs of
deficiency of thyroid and pituitary are present. This is a rare
occurrence.
Suprarenal Cortical Failure
Coma is difficult to diagnose, if it is due to stress. Never-
theless, in patients suffering from Addison’s disease, the
cause of Addisonian crisis (shock) may be obvious.
4. Tropical Infections
Parasitic Infections
Cerebral malaria: This was one of the common causes of
coma in the past, the incidence of which has since
considerably come down. However, it is worthwhile to keep
it in mind in all cases of unconsciousness especially when
associated with fever in the tropics. In some cases, there
may be neurological deficiencies like paralysis of the limbs
or psychiatric disturbances. On examination, a spleen may
be palpable in addition to the modified superficial and deep
reflexes. Complications likely are black water fever, DIC,
acute renal failure, respiratory distress, circulatory collapse,
apart from hepatic damage hypoglycaemia, anaemia CSF
shows increased cells protein and lactate (> 25 mg/dl carries
bad prognosis). The blood slide invariably contains
Plasmodium falciparum malaria parasites. Dipstick method
(Parasight—F) is of immense help.
Filarial encephalitis: This is an interesting clinical picture
due to filariasis. It is presumed that the adult or considerable
collection of microfilariae invade the subarachnoid space,
cerebral vessels or the substance of the brain. Hitherto,
filarial manifestations were essentially those of the lymphatic
system involvement. Probably this is one of its kind where
filariasis produced a picture of encephalitis, with
involvement of the lymphatics elsewhere in the body.
Microfilariae may be seen in the peripheral blood or CSF.
Toxoplasmosis is a protozoal infection. The clinical features
include lymphadenopathy and multiple organ involvement.
Disturbed consciousness may be seen due to meningo-
encephalitis.
Pneumonitis, myocarditis and fever with maculopapular
rash are other features.
Trypanosomiasis (Refer to Chapter ‘Rashes’).
Typhoid Fever
Coma, of course, due to typhoid fever is noticed during the
third week of the illness. Usually it is mentioned as typhoid
state. This condition also is gradually waning due to the
powerful specific antibiotics.
Cholera
There is, invariably, history of cholera forthcoming or the
patient may have the onset of painless diarrhoea and
vomiting and may collapse; and when this collapsed stage
is prolonged, the patient develops typhoid-state-like picture.
Coma may result from acute renal failure due to excessive
loss of fluid from the gut.
Heat Hyperpyrexia
Refer to Chapter ‘Shock’.
 Coma
Wernicke’s Encephalopathy
In this uncommon entity, the patient exhibits ophthalmo-
plegias in addition to the clouding of consciousness. The
other accompanying features are lapses in recent memory
and confabulation, disorientation of space and time, limb
ataxia and polyneuropathy; before stupor steps in. It is
caused by thiamine deficiency which affects midbrain and
hypothalamus.
5. Toxicological Causes
Sedatives and Tranquillisers
Of all the sedatives, barbiturates are the most common lot
for the purposes of poisoning. The history and cold, dry
skin may be the directing factors. The patient is deeply
comatosed with subnormal temperature initially, raised pulse
rate, shallow rapid respirations, small fixed pupils,
diminished refexes and low blood pressure. In severe cases,
respirations are slow and shallow. Pupils are dilated.
Barbiturate concentration in blood is usually more than
8 mg/100 ml in unconsciousness cases. During recovery,
abnormal behaviour may be seen. Alcohol is incriminated,
most often in barbiturate poisoning.
Benzodiazepines (diazepam) cause bradycardia, hypotension,
depressed respirations, apart from impaired consciousness.
Phenothiazines may exhibit hypotension, Parkinsonian
symptoms, tremors, depressed respirations, cardiac
arrhythmias, hypothermia besides impaired consciousness.
The fatal dose is 50 mg/kg body weight.
Narcotics (Morphine and Opium)
The patient will become compatosed prior to which he might
have had euphoria, vomiting, dizziness and sleepiness.
Respirations are depressed with respirations at 2 to 4 per
min. Pupils are constricted not reacting to light, pulse will
be slow, sweating is considerable and the skin appears warm
in spite of low temperature due to peripheral vasodilatation.
A fatal dose by ingestion is 0.3 to 1.4 g while parenteral
dose is 0.1 g or more.
Aspirin and Salicylates
Salicylate poisoning is usually caused by ingestion of aspirin.
Hyperpnoea, coma and sweating, spontaneous bleeding due
to hypoprothrombinaemia are noticed in addition to the
presence of ketone bodies in the urine. Loss of carbon
dioxide results in a fall of carbon dioxide content of the
serum leading to respiratory alkalosis. Hypokalaemia and
81
dehydration are the imminent dangers during the stage. This
may be followed by metabolic acidosis. The ferric chloride
test aids the diagnosis. The fatal dose is said to be 150 mg/kg.
Alcohol
Ethyl alcohol (Ethanol): Consumption of alcoholic drinks
is very much on increase. Alcoholic intoxication depends
on the rapidity of ingestion and absorption. Four stages are
described—excitation, hypnosis, narcosis and asphyxia.
When blood concentration exceeds 100 mg per cent
excitation; exceeds 200 mg per cent—intoxication; exceeds
300 mg per cent—stupor or coma and stertor are noticed.
Other clinical features are congested conjunctiva, profuse
sweating, bounding pulse and dilated pupils, respiratory
depression and fits (due to hypoglycaemia). In severe cases,
the pupils are small, which become dilated when the patient
is shaken up without being roused, and again they become
small if left still. This Macewen’s pupil is characteristic of
this condition and it is not seen in either head injury or
apoplexy. Above all, the smell of alcohol is obvious. It may
be combined with other poisons or may be associated with
head injury. Blood alcohol level of 500 mg per cent is fatal.
Methyl alcohol (Methanol): It is more toxic than ethyl alcohol
due to the formation of toxic metabolites of formaldehyde
and formic acid. After 12 to 24 hours, headache,
photophobia, dilated pupils, initial visual disturbances
followed by progressive loss of vision (due to optic atrophy)
acidotic respirations and coma occur. The consumption is
usually in the form of methylated spirits varnish and metal
polish. Fatal dose is 30 to 60 ml. Irreversible blindness may
result with 15 ml.
Carbon Monoxide
It occurs on exposure to charcoal fires, slow combustion
stoves, exhaust fumes of automobiles or fumes of blast
furnaces. Carbon monoxide combines with haemoglobin to
form carboxyhaemoglobin which causes tissue anoxia.
Headache, vomiting, giddiness, collapse and coma are the
usual manifestations. Conjunctiva congested, pupils dilated
and fixed, breathing stertorous, and a cherry red appearance
are other features. A diluted sample of blood appears pink
and not yellow as in normals.
Metals
Arsenic: In acute arsenical poisoning, the symptoms appear
within one hour after ingestion or delayed up to 12 hours if
the stomach is full. Diarrhoea and vomiting, abdominal pain,
 82 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
cramps, restlessness and stupor develop. The fatal dose is
2 g of arsenic.
Lead: Lead poisoning may occur by ingestion or by
inhalation of dust fumes. Colicky pain, vomiting, dark stools
due to lead sulphide, oliguria, stupor and coma are the
clinical manifestations. The minimum lethal dose is 5 g of
absorbed lead.
6. Haematological Causes
Hyperviscosity Syndrome
Refer Chapter on ‘Bleeding Disorders’.
Bleeding Disorder
(Refer Chapter on ‘Bleeding Disorders’).
Thrombophilia: It is a coagulopathy resulting in thrombosis.
Inherited thrombophilia is caused by activated protein C or
S resistance and deficiency of antithrombin III or protein
C or S. Acquired thrombophilia is caused by antiphos-
pholipid syndrome and oral pill (progesterones). Treat with
heparin or AT III cryoprecipitate. Avoiding pill and aspirin
or warfarin are preventive measures.
7. Psychiatric Causes
Depressive Psychiatric States
Stupor occurs in schizophrenia (catatonia) or melancholia.
The diagnosis is based on presence of other psychiatric
features and absence of organic signs, supported by typical
history.
Hysteria
Usually the patient is a woman having psychological
conflicts. The attacks have a purpose. The patient is
apparently comatosed. On examination, resistance is offered
by the patient at every stage; e.g., when eyelids are opened;
in addition to the resistance being met with, a striking rolling
of the eye balls noticed. Pupils are equal and reactive.
Neurological examination is normal including oculovesti-
bular response. Oculocephalic reflexes may be
unpredictable. Motor tone is inconsistent or normal. The
plantar responses is flexor. Respirations may assume
character of hyperventilation or eupnoea. Also examination
of other systems reveal no physical abnormality. EEG
showing normal alpha activity, inhibited by eye opening and
other stimuli, is likely to be psychogenic.
Organic brain syndrome may present with psychiatric
features and whether they are true psychiatric in origin or
not, can be diagnosed by a careful process of exclusion of
organic disease or psychometric testing or projection tests
like TAT (Thematic Apperception Test). Nevertheless, one
has to bear in mind a coexisting organic disease, although
the features are highly suggestive of psychogenic
unresponsiveness.
CLINICAL APPROACH
The first step in the approach of a coma case, is to
differentiate whether the mental torpor and prostration is
due to:
1. Shock
2. Paroxysmal transient loss of consciousness as in syncope
or akinetic seizures.
3. Sleep disturbances such as narcolepsy, or hypersomnia
4. Mere lack of speech and action yet awake (motionless,
mindless, wakefullness) as in akinetic mutism.
5. Global paralysis of all the musculature with
unresponsiveness, yet receptive as in locked-in syndrome
6. Transient global amnesia or
7. Confusion (the content of consciousness, i.e. the material
used for communication and inner thought processes is
mixed up). Drowsiness-level of consciousness is
invariably associated with confusion whereas the
confusion, though accompanied by inattentiveness, is
not necessarily associated with drowsiness or merely
prolonged loss of consciousness (classical coma). Stupor
is unresponsiveness but arousable with difficulty.
8. Delirium (acute confusional state): Impaired conscious-
ness, disorientation, changed behaviour (agitation)
disturbed perception (visual hallucinations).
The next step is to strike at the cause of coma whether
neurological, metabolic or any other cause for which relevant
data from a relative/witness; a quick methodical, systematic
physical examination, immediate investigations of the body
fluids are imperative.
History
Method of enquiry includes the following:
1. Last known to be well
2. Since when ill—whether coma is superimposed on a
previous illness or occurs spontaneously
3. Nature of symptoms and behaviour before coma
4. Duration of coma
5. Onset—gradual or sudden
6. Any fits observed
7. Past medical history (Diabetes mellitus, hypertension,
fever fits, headache, depression)
8. Alcohol indulgence
 Coma
9. Head injury
10. Present drug history and occupational history.
Physical Examination
General Examination
1. A survey of the surroundings of the patient, e.g. bottle
of sleeping tablets.
2. Survey of the patient
a. Assess level of consciousness—Stationary, changing
or deepening
b. Posture (depends on damage to cerebral, midbrain
or pontine structures)
i. Decorticate rigidity (flexed upper limbs and
extended lower limbs) indicates damage to
contralateral hemisphere.
ii. Decrebrate rigidity (all four limbs rigidly
extended with neck retraction and arched back)
indicates damage to diencephalon or midbrain.
iii. Flaccidity of all limbs indicates pontine lesions.
c. State of hydration
d. Skin
i. Colour—Any cyanosis
ii. Scars of injections, e.g. insulin
iii. Texture—Dry thick skin (myxoedema)
e. Odour of breath—Alcohol, acetone
f. Type of breathing—It may be regular or periodic or
ataxic (irregular) and may have a localising value in
coma. Rate and depth of respirations are usually
informative.
i. Hyperventilation—Rapid and deep, hyperpnoea
occurs usually in lesions of brainstem tegmentum
and metabolic acidosis.
ii. Hypoventilation—Depressant drugs
iii. Hyperpnoea alternating with apnoea—This
Cheyne-Stokes respiration is suggestive of
central cerebral or high brainstem lesions.
iv. Apneustic breathing—There is a pause after a
full inspiration or it may consist of inspiratory
pauses alternating with expiratory pauses or
pauses at the end of respiratory cycles. It is
suggestive of mid or caudal pontine lesions.
v. Ataxic breathing—It is a completely irregular
pattern wherein both deep and shallow
respirations occur randomly. It is suggestive of
lesions of dorso medial part of the medulla.
Biot’s respiration of meningitis is a classical
example.
83
g. Look for any focus of infection in middle ear or
abscess elsewhere.
h. Vital data
i. Pulse—Pulse rate may be reduced though volume
is full in increased intracranial pressure. The
frequent cause being cerebral oedema.
ii. Blood pressure—may be raised as a hypertensive
response to subarachnoid haemorrhage or such
episodes. This lasts only for few days—up to one
week and should not be mistaken for long
standing hypertension.
iii. Respirations—Eupnoea or abnormal (vide
supra).
iv. Temperature—Hyperthermia or hypothermia.
Systemic Examination
1. Examination of the head and neck
a. Look for any injury to the skull as indicated by cuts
or tenderness or depressed fractures; discoloured skin
behind the ear is present in skull fractures (Battle
sign).
b. Any injury to the neck or any neck rigidity (may be
absent in deep coma though meningitis is present).
Avoid Doll’s manoeuvre in neck injury. Do not move
the head unless the cervical spine is not injured.
c. Feel for carotid pulsations on both sides to eliminate
carotid stenosis with hemiplegia (Moniz syndrome).
2. Any asymmetry of the face: Paralysed cheek puffs out
with each expiration.
3. Nostrils and ears: For any evidence of bleeding or
leakage of CSF in fractures of the base of the skull.
4. Lips: Discoloured as in carbon monoxide poisoning or
burns around the mouth in corrosive poisons.
5. Tongue: Dry as in diabetic coma or bitten as in epilepsy.
6. Eyes:
a. Yellow colour of the conjunctiva or any subconjunc-
tival haemorrhage.
b. Tension of the eyeball—Reduced in diabetic coma.
c. Ocular movements and gaze abnormalities.
i. Looks straight ahead in diffuse or bilateral lesions
of the cerebrum or roving eye movements (slow,
conjugate, usually horizontal movements) occur
when cerebral hemispheres are damaged.
ii. Conjugate deviation of the eyes along with the
head towards the side of the lesion if it is due to
a lesion in one of the cerebral hemispheres
(syringing the ears with ice cold water may
correct this deviation if the brainstem is intact).
84 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

iii. Conjugate deviation to the opposite side of the

lesion if it is in the pons.
iv. Conjugate deviation downwards in midbrain
lesion.
v. Ocular bobbing (involuntary brisk conjugate
downward movement and slow upward
movement) seen in bilaterl pontine haemorrhage.
vi. Ocular dipping is reverse to ocular bobbing (slow
downward and quick upward movement) seen
in diffuse anoxia, cerebral dmage.
vii. Oculocephalic reflex: Oculocephalic movements
on head rotation (Doll’s eye movements) (normal
if eyes stay looking at the same point when the
head is turned either laterally or vertically)
conjugate ocular movements occur at the
opposite direction of moving the head laterally
or vertically. This is absent in brainstem lesions
and can be elicited in the cerebral hemisphere
Fig. 5.4: Normal and abnormal pupils
dysfunction. (Eyes roll as turning head).
viii. Oculovestibular reflex (caloric response): By distal to nucleus on the side of the lesion like
instilling 50 cc of ice cold water slowly into the intracranial haemorrhage or tentorial
external auditory canal, produces rapid nysta-
herniation.
gmus towards nonirrigated ear and conjugate
b. Ipsilateral Horner’s syndrome may be due to
deviation towards the irrigated ear. This caloric
a hypothalamic disease or a lateral medullary
response is also absent in brainstem lesions.
lesion.
d. Pupils—The size (small pupil—1 to 3 mm; dilated
mid position—3 to 5 mm) symmetry and reaction to c. Ipsilateral small pupil on the side of occluded
light of the pupil offer localising value. Rough carotid artery.
measurement of the pupil is possible in relation to v. Unequal, irregular pupils—Irregular unequal
the diameter of cornea which is about 10.5 mm, if medium sized fixed pupils suggest nuclear
the pupilometry is not available (Fig. 5.4). midbrain lesions.
i. Small reactive pupils (which may be pin-point) vi. Hutchison’s pupil—(Vide supra)
suggest pontine tegmental lesions. Diencephalic e. Corneal reflex—Lost on the side opposite to the
lesions, metabolic encephalopathy and drugs like lesion.
morphine. (Size of pin point pupil is < 1 mm). f. Ophthalmoscopic examination for any papilloedema.
ii. Regular, equal medium sized pupils with no
7. Facial Reflexes: The blink reflex (contraction of the
reaction to light suggestive of midbrain tectal
palpebral orbicularis oculi produced by tactile stimuli)
lesions.
and glabellar tap reflex absent in coma. Normally tapping
iii. Dilated pupils
over the glabella (just above bridge of the nose) results
a. Bilateral dilated (mid position) fixed lesions
in blinking which seizes after few taps unlike in
suggest midbrain lesions, Cerebral anoxia or
parkinsonism.
drugs like atropine.
b. Bilateral pupillary dilatation during neck 8. Limbs
flexion suggest uncal herniation. a. These should be raised and allowed to be dropped
iv. Unequal and regular pupils (pathologically and observation must be keenly made whether they
dilated or constricted) are falling equally fast or equally slowly on both
a. Ipsilateral pupillarly dilatation with no sides. Normal side may fall slowly.
response to light on the side of the lesion is b. Flaccidity present or not (paralysed side is flaccid
due to compression of the 3rd cranial nerve initially).
 Coma
c. Painful stimuli applied and note whether the
movement is elicited equally on both sides or not,
i.e. movement of withdrawal present on the
nonparalysed side when the patient is not deeply
comatosed.
d. Reflexes
i. Extensor plantar response when present on one
side may help localisation (extensor plantar is
present on both sides in deep coma).
ii. Deep reflexes to be elicited. If it shows any
difference it helps localisation.
iii. Incidentally look for any fracture of the limbs.
N.B: Dictum in absence of focal or localising signs with
normal pupils, is mostly likely to be of metabolic origin.
9. Chest
a. Lung—look for any signs of bronchiectasis or lung
absecess which may result in cerebral abscess
producing loss of consciousness or chronic bronchial
asthma with possible carbondioxide retention.
b. Heart—any left ventricular enlargement to be noticed
as shown by a downward and outward heaving apex
beat and also any cause like mitral stenosis or
auricular fibrillation or bacterial endocarditis, which
may result in coma due to cerebrovascular accident.
10. Abdomen
a. Evidence of ascites with dilated veins over the
abdominal wall and hepatosplenomegaly or
polycystic kidney.
b. Examination of genitalia for maligancy or any
tumour in the abdomen, if present may help to think
of metastases in the brain producing loss of
consciousness.
c. Retention of urine present or not.
d. Rectal examination for any prostate enlargement.
Investigations
Immediate investigations such as (i) urine for sugar and
acetone, (ii) blood (urea and sugar and for malarial
parasities) (iii) CSF analysis are absolutely imperative. They
need not be extensive, at least initially, although other
appropriate tests as per index of the suspicion can be
entertained.
1. Body fluids
a. Catheterise for urine and look for
i. Albumin and deposits
ii. Sugar
iii. Acetone (Rothera’s test) and aceto acetic acid
(Ferric Chloride test), if present, may give an
indication of severity of ketosis (sometimes sugar
85
may be present during cerebrovascular accidents
which should not be mistaken for diabetic coma
unless acetone also is present),
iv. Bile pigments.
b. CSF—Lumbar puncture is a must, for any coma
case, unless there is a contraindication like posterior
fossa tumour.
i. Pressure and colour to be noted.
ii. Fluid may be kept for 24 h for any web formation
or in a bloody CSF; see whether the CSF is
equally blood stained throughout and whether the
supernatant fluid is yellow or colourless. If it is
colourless, the bloody CSF is due to trauma. If it
is yellow, it is subarachnoid haemorrhage or
intracerebral haemorrhage communicating with
the ventricles.
iii. Cell count and smear from the fluid may be taken
for organisms with Gram’s stain or Ziehl-Neelsen
stain if possible.
iv. Biochemistry—For proteins Pandy’s reagent
(solution of carbolic acid) is useful. Half ml of
Pandy’s reagent when added to one drop of CSF,
on the presence of turbidity indicates high
protein. For sugar, 1 ml of CSF with 1/4 ml of
Fehling’s solutions to be boiled. Normally it is
dicolourised. If blue still, sugar content is reduced
in the CSF.
c. A study of vomitus, if it is available or stomach
contents with a gastric tube is to be collected and
preserved.
d. Blood
i. Blood smear for malarial parasite quantitative
buffer coat examination (QBC).
ii. Blood chemistry
a. Blood sugar
b. Blood urea and serum creatinine
c. Serum bilirubin
d. Serum electrolytes (sodium, potassium,
calcium and sodium bicarbonate)
e. Serum osmolality =
Blood Sugar in mg % Blood Urea
[2Na + K] + +
18 2.8
(For every 100 mg % rise in sugar 1.6 mEq
of sodium is reduced.)
f. Arterial blood gases (pH, PO2, PCO2)
iii. Haematocrit values and complete blood count
iv. Blood coagulation profile
v. Blood cultures
 86 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
2. Radiology
Initially (a) Skull X-ray (b) Chest X-ray
Later (a) CT Scanning (b) MRI scanning (c) Cerebral
or MRI angiography, if necessary.
3. EEG
a. Metabolic comas may show slow and symmetrical
waves 1 to 3 whereas normally there are 8 to 13.
b. Structural—supratentorial lesions show slow activity
more on one side of the lesion or focal spike and
sharp waves continuously in epilepsy.
c. EEG is flat or isoelectric for 60 min. at an amplitude
of 50 µv/cm in brain death syndrome (it is due to
irreversible structural damage with ischaemia and
hypoxia of the brain, and diagnosed by
i. Nonfunctioning of the brain for at least 12 h
ii. Spontaneous respirations are absent (apnoea)
iii. Absence of brainstem reflexes and voluntary
movements
iv. No history of displaying CNS depressants or
hypothermia
v. EEG
vi. Circulation and purely spinal reflex responses
may be retained. Cardiopulmonary function
maintained with ventilatory assistance.
4. ECG
5. Evoked potentials: Measurement of cerebral evoked
potentials gives information about the functional status
at higher levels.
6. Drug screen: In spite of a systematized approach,
diagnosis may be apparently uncertain at times, when
poisoning may be the most probable underlying cause.
However, a constant vigil, monitoring the depth of coma
and changing state of consciousness, the state of pupils,
the type of respirations, motor and reflex responses, and
posture may be rewarding, since passage of time may
unravel the diagnosis ultimately.
TREATMENT OF COMA
The unawareness of self and environment with neural
unresponsiveness, calls for the quick reflexes of the
clinician, to adopt necessary emergency measures and
simultaneously unearth the underlying cause whether it is
intracranial (structural) or extracranial (metabolic). The
sequence of events leading to the altered level of
consciousness and its content, the pattern of respiration or
circulation and the presence of neurological deficits, are
highly contributory to the diagnostic exercise. If there is no
specific identifiable cause for this ubiquitous entity,
toxicological (poisons) aetiology may be better presumed
for purposes of management.
Symptomatic Treatment
(To maintain the life till specific diagnosis is made and
measures instituted)
Emergency Measures
(Given Precedence Over Diagnostic Effort)
a. Maintain optimum ventilation
i. Keep the patient on one side with head well extended
ii. Pull the tongue forwards with fingers or forceps
iii. Clear the airways by aspiration or suction
iv. Keep an oropharyngeal airway to keep the air passage
patent
v. Endotracheal intubation if necessary and trach-
eaostomy contemplated if intubation is imperative
for more then three weeks.
vi. Oxygen may be administered by nasal catheter or
otherwise as indicated.
b. Ensure good circulation—Treat promptly any existing
shock or impending shock with IV fluids and
vasopressors so as to maintain the systolic blood pressure
> 100 mm of Hg. (Refer to Chapter ‘Shock’).
General Measures
a. Monitor vital signs and biochemical parameters
continuously.
b. Change the position of the patient every one or two hours
to prevent aspiration pneumonia, or skin ulcerations.
c. Instil methyl cellulose or normal saline drops or eye
bandage to prevent corneal ulceration.
d. Oral hygiene needs special care.
e. Foley catheter or condom drainage is required if the
patient fails to void or when coma persists long.
f. Bowels evacuated regularly by suppository or enema.
g. Fluid and nutrition must be maintained either
parenterally or through nasogastric tube.
h. Gastric aspiration may be done and the aspirate
preserved.
i. If the content of consciousness is altered (confusion)
with agitation, small doses of diazepam considered
(avoid sedatives).
Empirical Measures
a. Prophylactic antibiotics considered.
b. Intravenous glucose—Administer 50 ml of 50 per cent
glucose (if the patient is alcoholic, thiamine is given
prior to glucose), after drawing blood sample for sugar
estimation.
c. Reduce raised intracranial pressure. If it is raised
>20 mm Hg, it is usefully associated with cerebral
oedema.
 Coma
i. Position—Patient’s head is elevated 45° to facilitate
venous drainage (avoid supine and neck flexed
position).
ii. Drugs
• Mannitol (0.5–1 g/kg every 4-6 hrs as necessary)
• Glycerol (10% in 500 ml of 5% dextrose or 15
ml 6th hourly through gastric tube).
• Frusemide (40-80 mg IV) can be alternated with
mannitol
• Thiopental IV infusion s 500-mg/200 ml. BP to
be monitored as BP may fall.
iii. Hyperventilation—Controlled hyperventilation (by
paralysing and ventilating) lowers intracranial
pressure (ICP) if PaCO2 is maintained at 30 mm of
Hg (normal = 40 mm of Hg) especially in head
injuries.
iv. Barbiturates—High doses IV therapy is effective to
lower ICP but needs expertise.
v. CSF drainage—CSF is removed from the vntricle
through an intraventricular catheter used to measure
intracranial pressure.
vi. Burr holes—Neurosurgical decompression with burr
hole made on the side, where the pupil is dilated.
Specific Measures for Specific Causes
Neurological
Cerebrovascular Lesions
1. Cerebrovascular Accidents
• Cerebral haemorrhage: The treatment consists of
general supportive measures and minimising cerebral
oedema (vide supra). Surgical evacuation is
controversial. Evacuation of moderate haemorrhages
close to the cortical areas appears to be no way better
then conservative treatment. Basal ganglia sites and
cerebellar hemisphere are easy to drain. However,
cerebellar haemorrhage with threatening secondary
brainstem compression is an absolute indication for
surgical intervention, and is life saving.
• Subarachnoid haemorrhage: The treatment consists
of supportive measures as above. Careful reduction
of high blood pressure-prevents repeated ruptures.
(Diastolic pressure to be reduced not more than
100 mmHg). However, hypotension may exacerbate
vasospasm. Nimodipine (60 mg every four hours for
3 weeks) is effective in the treatment of vasospasm
and ischaemic damage. Rebleeding or second
haemorrhages may occur after two weeks of the
initial bleed. So, surgery of clipping aneurysm or
87
endovascular therapy with coils may be performed
before this period or after the vasospasm settles
(usually 10 days after the ictus). Antifibrinolytics like
aminocaproic acid (inhibits plasminogen activator/
plasmin) or Tranexamic acid (inhibits activation of
plasminogen and inhibits plasmin) or aprotinin
(inhibitor of plasmin) are helpful in the prevention
of second bleed. Drowsiness with hemiplegia carries
bad prognosis esp in the first month.
• Thrombosis and embolism (Ischaemic strokes).
a. Supportive therapy
i. Monitor vital signs, blood pressure, blood
sugar, intravascular volume and oxygenation
besides reducing vasogenic cerebral oedema
with dexamethasone and/or mannitol.
ii. Low molecular weight dextran with normal
saline is useful.
iii. Blood pressure should not be lowered as it may
further impair perfusion as cerebral
autoregulation is affected.
iv. Nil by mouth if gag reflex is absent.
b. Medical therapy
i. Thrombolytic therapy—IV recombinant tissue
plasminogen activator (r TPA) in the first 1½-
3h (less than 0.85 mg/kg) yields encouraging
results, if there are no contra indications.
ii. Calcium channel antagonists—Nimodipine is
started within 24 h of stroke (120 mg a day in
divided doses for four weeks) as it improves
the ischaemic deficit and neural rescue.
iii. Anticoagulants—They are administered in
cardioembolic strokes, or stroke-in evolution
for impairing thrombogenesis and not for
dissolving the thrombus. Heparin 5000-10,000
units started within 48h or preferably low
molecular weight heparin like enoxaparin
(20 mg bd). After 5 days, long term oral
anticoagulation is done with warfarin (10–15
mg/d for six months to one or two years) while
monitoring prothrombin time. (immediate
coagulation). It is advisable to exclude haemor-
rhagic conversion by reimaging after three
days. Some prefer to give warfarin after 14 days
of onset without heparin (delayed anticoagula-
tion). Low molecular weight heparin prefered.
iv. Blocking glutamate—This neurotransmitter
released after ischaemic stroke promotes
calcium entry, and neurotoxicity. Results of
 88 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
pharmacological blockade (Lubeluzole) are
encouraging.
v. Antiplatelet aggregation drugs—Aspirin
(50-75 mg/day) recommended. Recently
Ticlopidine is replaced by Clopidogrel (75-150
mg/day).
vi. Vasodilators which held the sway once are no
more used. However, pentoxiphyline is used
in view of its haemorrheological properties.
vii. Increased intracranial pressure and vasogenic
cerebral oedema must be lowered with
Mannitol (20% 5 ml/kg IV) over 15 minutes
or Dexamethasone (4 mg IV/6h/day).
viii. Clomethiazole attempts at repolarisation to
protect cells (GABA antagonists).
ix. Supplemental therapy with piracetam IV
200 mg to restore neuronal energy; H2 blockers
(Parenteral) to prevent stress ulcers and
neuroprotectors (Nimodipine, Lubeluzoe
Citicoline) are beneficial.
x. Defibrogenating enzymes ANCROD within
3 hours for five days useful.
xi. Treat the underlying causes like diabetes
mellitus or anaemia or dehydration. For
homocystinuria oral pyridoxine 25-500 mg/d
recommended.
c. Surgical therapy includes carotid endarterectomy for
carotid stroke and surgical removal of infarcted
cerebellar tissue, for basilar occlusive disease.
d. Physiotherapy is better started right from the
beginning for appreciable results.
e. For prevention of attacks, correcting the risk factors,
antiplatelet therapy for secondary prevention and
warfarin in selected cases may be beneficial. That
Ramipril reduces stroke incidence in high
cardiovascular risk patients through mechanisms
independent of lowering blood pressure is
documented in both primary and secondary
prevention whereas Aspirin is documented in
secondary prophylaxis of stroke.
2. Hypertensive Encephalopathy: Lowering the high blood
pressure, treating the vasospasm, reducing cerebral
oedema and controlling convulsions are indicated.
3. Cerebral Venous Thrombosis: Treat with antibiotics and
anticoagulants, reduce intracranial pressure and control
focal seizures. Papilloedema is monitored to prevent loss
of vision.
Head injury/Epidural or subdural haemorrhage: Prompt
neurosurgical management is sought for. Treat systemic
injuries and metabolic derangements. Insist on good
respiratory care. Lower the increased intracranial pressure
(normal pressure is below 15 mm Hg). Detect haematomas
by CT scanning and plan surgical removal, besides adopting
general measures (vide supra).
Meningitis (Refer to Chapter ‘Headache’)
Viral encephalitis Supportive therapy (general nursing care,
maintaining fluid balance and nutrition, controlling
intracranial pressure and seizures, bestowing respiratory
care, etc.) enables recovery most often regardless of the
specific virus infection. However, specific therapy with
acyclovir (10 mg/kg IV lasting for one hour t.d.s. for about
7 to 10 days) is recommended for herpes simplex infection.
Space Occupying Lesions (Refer to Chapter ‘Headache’)
Epilepsy (Refer to Chapter ‘Epileptic Seizures’).
Metabolic
1. Acute Metabolic Complications of Diabetes Mellitus
i. Diabetic ketoacidosis: This life threatening compli-
cation is promptly managed by administering plain
(soluble) or unmodified insulin; replacing fluid;
monitoring electrolytes and treating associated
infection with antibiotics besides general care of a coma
patient and monitoring biochemical parameters.
a. Plain insulin—If the peripheral circulation is
adequate, unmodified (purified) insulin i.m., or else
continuous IV infusion (with controlled rate
infusion system preferably) is given every hour
(O. I. unit/kg/h) when blood glucose is > 250 mg
per cent. If the blood sugar does not fall by 2 h or
at the anticipated rate of 5-10 per cent every hour,
the dose may be doubled (monitor glucose hourly).
When once the patient is able to take feeds orally,
it is better to give insulin s.c. 4th hourly and the
daily s.c. dose should not be less than IV dose given
in the previous 24 h. (The long acting depot insulin
must not be given).
b. Fluids—The fluid loss is usually equal to 10-45
per cent of the body weight and the sodium deficit
is 400-800 mEq. The volume depletion is corrected
by administering 1 litre of normal saline IV within
half an hour to one hour and the remaining deficit
(calculated from the percentage of dehydration in
relation to body weight) is made up by giving half
 Coma
the amounts in the first 8 h and the other half in
next 16 h.
Acidosis (PH<7% or respiratory rate >36/min) is
combated with IV sodium bicarbonate (1ml/kg/ of
8.4% over one hour) and resulting hypokalaemia
carefully corrected (vide infra).
Avoid rapid correction of dehydration or acidosis
to prevent cerebral oedema or tissue hypoxia.
If blood sugar falls below 250 mg per cent, normal
saline must be replaced with 5 per cent dextrose
infusion (to prevent late cerebral oedema and
possible hypoglycaemia), and adjust the insulin
dose as required.
It is better that the total fluid replacement dose not
exceed 6 litres in the course of 24 h.
Several hours of glucose and insulin together, may
be necessary to normalise plasma ketone concen-
tration and arterial blood pH (i.e. disappearance of
acetone in the urine and return of normal breathing),
during which period hypokalaemia results, which
has to be treated (vide infra).
Plasma expanders may be considered if shock
persists. (If blood pressure does not respond to
volume replacement, silent myocardial infarction
or septicaemia may be present.)
c. Electrolytes—Potassium: (The net deficiency is
usually 300-600 mEq). Since fatal hypokalaemia
is a threat in the process of correction of
ketoacidosis as above, potassium supplementation
is necessary preferably from second hour onwards.
(Monitor potassium two hourly.) If potassium is
< 5 mEq/L, give potassium chloride (10-20 mEq/
h.) in the first 24 h by adding to saline infusion and
not as a bolus. (1 g = 13 mEq.)
Sodium: While correcting sodium deficit hyper-
natraemia is avoided.
Phosphate: Requires replacement when the serum
level is below 1 mg per cent.
Bicarbonate: It is advisable to administer about half
the calculated amount of bicarbonate requirement
due to possible hypokalaemia, tissue hypoxia, and
paradoxical cerebral acidosis impairing
consciousness. (Bicarbonate requirement = Base
deficit, i.e. 25 - measured HCO3 in mEq/L × 0.3 ×
body weight in kg).
Generally 50 mEq of sodium bicarbonate is given
IV over 30 min. (1 ml of 7.5% NaHCO3 solution
contains 1 mEq). It may be repeated till pH reaches
89
7.2. Potassium chloride (10 mEq) may be given
along with bicarbonate unless potassium is high.
d. Antibiotics—Appropriate antibiotics are given to
combat associated infection.
e. Watch for complications like aspiration pneumonia
due to gastroparesis and dilatation (gastric
decompression with nasogastric suction helpful) or
acute tubular necrosis or myocardial infarction or
venous thrombosis or cerebral oedema.
f. Heparin (5000 units s.c. t.d.s.) may be given if the
coma is prolonged or in elderly patients to prevent
vascular complications.
g. During the recovery period, small quantities of oral
feedings (if tolerated) are given initially. One-half
to one third of their previous insulin dosage is
administered s.c.
h. Prevention—Correction of precipitating factors is
the vital aspect of prevention of ketoacidosis.
ii. Hyperosmolar nonketoacidotic coma
a. Half the dose of insulin preferred (0.5/kg/h).
b. Half normal saline (0.45%) is administered, and
rate of flow is regulated (preferably as per central
venous pressure) over 48 hours or better with
normal saline at half the rate used in diabetic
ketoacidosis.
c. Hyperosmolality should not be lowered rapidly, i.e.
not more than 10 mosm in 4 h, lest cerebral oedema
should occur.
d. Potassium may be supplemented, if necessary.
e. Dopamine infusion given, if required.
f. Heparin 5000 units s.c. twice daily considered in
high risk cases to prevent thromboembolic events.
iii. Hypoglycaemia: As a complication of treatment (vide
infra).
iv. Lactic acidosis: Sodium bicarbonate intravenously is
given to raise the pH to 7.2. Insulin and glucose are
also administered in cases of lactic acidosis due to
diabetes mellitus with septicaemia or biguanide
therapy. In nondiabetic cases, oxygen therapy is
necessary besides treating the underlying cause. Blood
transfusion may be helpful if hypotension persists.
2. Hypoglycaemia: Minor episodes are corrected easily by
ingestion of readily absorbable carbohydrates. In others,
of 50 ml intravenous glucose 50 per cent may be
required. If necessary, dexamethasone IV 4 mg every
4 h is given. Glucagon 1 mg i.m. may be given which
may be repeated after 10 min (not indicated in
 90 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
hypoglycaemia due to sulphonylmeas). Repeated
episodes are to be watched carefully before resuming
regular treatment for diabetes mellitus in decreased
doses. In postprandial hypoglycaemia many small meals
or slowly absorbed carbohydrate like high fibre, complex
carbohydrates given. Other cases of hypoglycaemia, if
any, are evaluated and managed accordingly.
3. Uraemia (Refer to Chapters ‘Oliguria and Polyuria’).
4. Hepatocellular Failure (Refer to Chapter ‘Jaundice’).
5. Porphyria: (Refer to Chapter ‘Acute Abdominal Pain’).
6. Electrolyte Disorders
a. Hypernatraemia—Normalise serum osmolality by
replacing water orally or 5 per cent dextrose in water
slowly to prevent cerebral oedema. (The fall of
sodium may be 10-12 mEq/L/d).
Hypovolaemic hypernatraemia is treated with
isotonic saline till volume is restored followed by
half normal saline carefully.
Hypervolaemia hypernatraemia is treated with
isotonic saline till volume is restored followed by
half normal saline carefully.
b. Hyponatraemia—The underlying cause must be
identified and treated. In hypovolaemic hyponatra-
emia, normal saline is administered apart from
correcting mineralocorticosteroid deficiency, if
present.
In hypervolaemic hyponatraemia, water must be
curtailed (1 litre per day) and if circulatory
impairment is present or ADH is increased frusemide
is given concomitantly with hypertonic saline (1.8%)
at 70 mEqNa.
In syndrome of inappropriate ADH secretion
(SIADH), i.e. euvolaemic hyponatraemia, water must
be restricted apart from inducing nephrogenic
diabetes insipidus with democlocyline (250 mg. tds).
The target of sodium levels should be about 130 mEq/
L. The rise should be 12 mEq in 24 h lest central
pontine myelinolysis should occur (From <
125 mEq/L).
c. Metabolic alkalosis—Sodium chloride is adminis-
tered to replace the chloride deficit. Potassium
chloride is supplemented if hypokalaemia is present.
In severe alkalosis, ammonium chloride is necessary.
If diuretics are incriminated, acetazolamide is
substituted to induce sodium bicarbonate excretion.
The underlying cause must be corrected. (Refer to
Chapter ‘Vomiting’).
d. Metabolic acidosis—Calculate HCO3 deficit and
replace as 8.4% sodium bicarbonate (contains one
mEq/ml) 50-100 mEq/ml IV given apart from
correcting underlying metabolic deficit appropriately,
e.g. shock.
e. Respiratory acidosis—Ventilation must be improved
by pulmonary toilet and reversing bronchospasm.
Paradoxical respiratory motion, neurological and
cardiovascular dyfunction need mechanical
ventilation. Intubation is necessary in acute cases.
(Vide supra) Refer to Chapters ‘Cyanosis’ and
‘Dyspnoea’.
f. Hypocalcaemia (Refer to Chapter ‘Epileptic
seizures’).
g. Hypercaleaemi (Refer to Chapter ‘Polyuria’).
Endocrinal
Hypothyroidism—Myxoedema Coma
T3 (100 µ IV) is given bolus and subsequently 20 µ 8h hourly
till improvement occurs, i.e. 2 or 3 days followed by oral
thyroxine (50 µg) per 24 h. Appropriate IV fluids (normal
saline) is administered. Treat infection and heart failure, if
present, appropriately. Warm blankets for hypothermia and
IV hydrocortisone (100 mg 8th hourly), if pituitary
hypothyroidism present, and dextrose for hypoglycaemia
considered.
Hypopituitarism (Hypothermia)
Hydrocortisone sodium succinate (100 mg 6th hourly IV is
given to begin with and then only T3 (10 µg b.d.) orally is
commenced.
Suprarenal Cortical Failure
One litre of 5 per cent dextrose saline is given in the first
hour; continue fluids slowly as determined by clinical
assessment. Hydrocortisone sodium succinate (100 mg IV
6th hourly) is given for 72 h and followed by oral steroids
(fludrocortisone). Hypoglycaemia may be corrected.
Associated infection treated with antibiotics. Biochemical
parameters like cortisol are to be monitored.
Tropical
1. Infections
Cerebral Malaria
a. Reduce parasitaemia by IV saline infusion of quinine
(10 mg/kg 8th hourly up to 5-100 doses) till conscious-
ness is restored; followed by oral quinine (650 mg tds.
 Coma
for 4-7 days); or chloroquine (5 mg/kg IV infusion o.d.
or b.d. up to 1-5 doses) followed by oral chloroquine
(600 mg base followed by 300 mg after 6 h on the 1st
day and 300 mg/d for next two days) or artesunate
(120 mg on 1st day followed by 60 mg daily for next
four days parenterally). In severe cases, additional 60 mg
is given on 1st day 6 hours after first dose (artesunate is
very effective). Oral pamaquine (45 mg) is better given
on the 3rd or 4th day. That chloroquine resistance is
common is to be kept in mind when pyrimethamine plus
sulfadoxine 3 tablets may be considered. Tetracycline
250 mg 6 hrly for one week is given (if there is resistance
to Pyrimethamine + sulfadoxine) along with quinine.
b. Treat dehydration and shock by fluid replacement and
if necessary with appropriate drugs. (dopamine and
dexamethasone).
c. Treat cerebral oedema with dexamethasone (4 mg 4th
hourly IV).
d. Treat convulsions, if any, with diazepam (0.2 mg/kg body
weight IV to be repeated every 4 h if necessary).
e. General care of coma and hyperpyrexia instituted.
Filarial encephalitis: It is rare. Treatment is symptomatic,
apart from diethylcarbamazine. (Refer to Chapter ‘Rashes’).
Toxoplasmosis: Treatment includes pyrimethamine (100 mg
b.d. for two days, then 25-50 mg/24), sulpdiazine (75 mg/
kg/d in divided doses) and folinic acid (10-20 mg/d) for
one month. Spiramycin (1 mg t.d.s.) or clindamycin (1 mg
twice daily) are also recommended.
Typhoid fever: (Refer to Chapter ‘P.U.O.’)
Cholera: Tetracycline (250 mg 6th hourly for three days),
correct replacement of water and electrolytes (normal saline,
potassium chloride and sodium bicarbonate or sodium
lactate) and chlorpromazine (25 mg 6th hourly to decrease
the intestinal secretion and thereby fluid loss) form the
mainstay of treatment. (Refer to Chapters ‘Vomiting and
Oliguria’).
Heat hyperpyrexia: Supporting vital organ system and
lowering body temperature are the objects of therapy.
91
Remove the patient to a cool shady place. Remove all
clothing. Sprinkle cold water (15°C) to keep the skin wet
and fan the body to promote heat loss. Ice water is not
advisable. Lower the body temperature to 39°C. Maintain
blood pressure and urine output with IV fluids. Airway is to
be maintained and oxygen given, if necessary. Watch for
complications like acute circulatory failure, acute renal
failure or disseminated intravascular coagulation and treat
accordingly.
Wernicke’s Encephalopathy
Prompt administration of thiamine parenterally (50 mg/24h
IV followed by 50 mg i.m. daily for a week) is indicated
and improvement is appreciated within 2-3 days IV glucose
may be administered if necessary and vitamins B
supplemented, which can be continued subsequently for
several days.
• Toxicological (Refer—Appendix III)
• Haematological (vide supra)
• Psychiatric
a. Patients with major depressive disorder need
pharmacotherapy with second generation anti-
depressants like fluoxetine.
Electroshock therapy is indicated in life threatening
depression. Psychotherapeutic strategy may be
adopted subsequently.
b. Hysteria—After ruling out organic causes, if hysteria
is diagnosed, abreactive therapies with carbon
dioxide inhalations or drugs like methyl
amphetamine sulphate (30-60 mg IV) or sodium
pentothal (100-200 mg) or under the influence of
hypnosis may be beneficial.
Placebo therapy may be helpful sometimes.
Subsequently the disturbiong or precipitating factors
for emotional trauma are to be corrected. Adaptablity
and psychotherapy may facilitate coping with the
social network.
92 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Coma 93
 Chapter
Cyanosis
6
Cyanosis is bluish discolouration of the skin and mucous
membrane. It is due to excess of reduced haemoglobin in
the red cells of the blood (>5 g %) circulating within the
small blood vessels, of the respective regions.
Normally, there is about 15 g of haemoglobin per
100 cc of blood and 1 g of haemoglobin combines with
1.33 cc of oxygen, i.e. the blood has an oxygen capacity of
20 volumes per cent. Actually, arterial blood contains
19 volumes per cent of oxygen or 95 per cent saturated with
oxygen, i.e. 14.25 g of oxyhaemoglobin and 1 volume
percentage of oxygen unsaturation, i.e. 0.75 g of reduced
haemoglobin. Venous blood contains 14 volumes percentage
oxygen or 70 per cent saturated with oxygen, i.e. 10.5 g of
oxyhaemoglobin and 6 volumes of oxygen unsaturation, i.e.
4.5 g of reduced haemoglobin. The average of arterial and
venous oxygen unsaturation is taken as capillary
unsaturation, i.e.
0.75 + 4.5 1 vol% + 6 vol %
= 2.6 g% or
2 2
= 3.5 volumes %
Haemoglobin is normally 100 per cent saturated with a
PaO2 (partial pressure of oxygen in the arterial blood) of 90
mm of Hg. If the PaO2 falls, the saturation of haemoglobin
with oxygen also falls. Cyanosis is detectable when
saturation of haemoglobin with oxygen is less than 66-2/3
per cent or when capillary oxygen unsaturation is more than
7 volumes per cent, which represents reduced haemoglobin
of 5 g per cent. It is to be emphasised that PaO2 and arterial
oxygen saturation are different from saturation of
haemoglobin with oxygen. (PaO2 of blood depends on PaO2
of inspired air, i.e. 160 mm Hg).
It is also seen when the blood has other haemoglobin
abnormalities like (a) methaemoglobin (1.5 g or 10% of
total haemoglobin), or (b) sulfhaemoglobin (0.5 g) are
present in the blood.
In polycythaemia, where the haemoglobin content is
high, central cyanosis appears, even at normal oxygen
saturation, since the increased red cells have proportionately
increased amounts of reduced haemoglobin. Conversely in
anaemia, extreme oxygen unsaturation is necessary for
cyanosis to occur and when the total haemoglobin is less
than 1/3rd of the normal, i.e. less than 5 g per cent, cyanosis
cannot appear, even though all the haemoglobin is in reduced
form, since the total amount is still less than the critical
level of 5 g per cent.
Generally, cyanosis can be divided into central and
peripheral.
CENTRAL CYANOSIS
This is detected in both skin (nose, cheeks and fingers) and
mucous membranes inside the mouth (especially tongue and
the inner side of the lips, cheeks and palate) and conjunctiva.
There is always cyanosis at the periphery. It is usually
associated with clubing and polycythaemia (blue hands and
blue tongue). The cyanosed extremities are warm unlike in
peripheral cyanosis. The presence of central cyanosis
indicates that the PaO2 is about 50 mm of Hg or below and
the arterial oxygen saturation below the critical level of 85
per cent, with normal haemoglobin. The degree of cyanosis
increases with exercise as vascular resistance is reduced and
exercising muscles extract more oxygen.
PERIPHERAL CYANOSIS
This is bluish discolouration of the skin of the ears, nose,
outer side of the lips, cheeks as well as hands, feet and digits.
The extremities are cold. There is no cyanosis in the mucous
membrane of the oral cavity or underneath the tongue nor
 Cyanosis
clubing present (blue hands only). The intensity of cyanosis
depends upon the thickness of the overlying skin and the
status of the capillaries and venules of the skin as well as
subpapillary venous plexuses, i.e. if the skin is thin and
contains more number of dilated capillaries and venules,
the intensity is more. Peripheral cyanosis is always
associated with central cyanosis but may occur per se even
without it, with normal oxygen saturation.
OTHER CLINICAL TYPES OF CYANOSIS
Mixed Cyanosis
It, can be seen in conditions where the causes of both types
of central and peripheral cyanosis exist like left ventricular
failure which is partly central (pulmonary) and partly
peripheral (decreased peripheral circulation) or cor
pulmonale where the lung lesion tends to produce central
cyanosis and the associated right sided heart failure tends
to produce peripheral cyanosis.
Differential Cyanosis
This cyanosis is confined either to the lower extremities
with no cyanosis of the arms and faces in patent ductus
arteriosus or upper half of the body with no cyanosis of the
legs as in transposition of the great vessels.
Acrocyanosis
It is a vasospastic disorder with cyanosis of hands and feet
which may be cold. There is excessive sweating and pain is
absent. Cyanosis disappears on warming. It is uncommon
and not associated with any underlying disease.
Erythrocyanosis
It is charactrised by bluish-red discolouration of the legs.
The feet feel cold. Burning and itching are the accompanying
features. It is a vasomotor disorder, seen in young women
in cold weather.
MECHANISM OF CYANOSIS
The mode of production of cyanosis is multifactorial and
variable depending on whether it is central or peripheral.
Though the degree of saturation of haemoglobin with
oxygen is ultimately the deciding factor for its presence,
hypoxia or arterial oxygen unsaturation is yet another key
factor. Cyanosis may not always be a reliable guide for the
degree of hypoxaemia.
95
Central Cyanosis
Central cyanosis is due to (a) hypoxia or (b) haemoglobin
abnormalities.
Hypoxia
1. Inadequate oxygenation of blood in the lungs from
a. unequal ventilation/perfusion as in chronic obs-
tructive pulmonary disease or pulmonary embolism.
b. impaired diffusion due to either decreased total area
of alveolar walls for diffusion as in emphysema or
alveolar capillary diffusion defect as in diffuse
pulmonary fibrosis or pulmonary oedema.
c. low inspired PO2 as at high altitudes (normal PO2 of
inspired air is 160 mm of Hg).
2. Free admixture of venous and arterial blood as in right
to left shunt as in cyanotic congenital heart disease. The
arterial oxygen saturation usually falls below 85 per cent.
Haemoglobin Abnormalities
Diminished oxygen carrying capacity of the blood due to
replacement of the oxygen ion of the oxyhaemoglobin as
seen in (a) methaemoglobinaemia and (b) sulfha-
emoglobinaemia; account for cyanosis (enterogenous or
pigmentary cyanosis). The arterial oxygen saturation is
normal in these entities.
Peripheral Cyanosis
Peripheral Cyanosis is due to (a) vasoconstriction or (b)
vascular obstruction.
Vasoconstriction
Peripheral cyanosis is due to excessive extraction of oxygen
by tissues from existing inadequate relese of oxygen in the
tissues consequent to slow and diminished circulation
through the peripheral vascular beds (poor perfusion of
tissues and increased capillary deoxygenation). The
vasoconstriction may be either due to reduced cardiac output
as in congestive heart failure or shock or arteriospastic
disorders (exposure to extreme cold and Raynaud’s
phenomenon). The arterial oxygen saturation is normal but
the venous oxygen saturation falls from 70 per cent and the
normal difference between arterial and venous oxygen
saturation, which is 25 per cent, exceeds.
Vascular Obstruction of Arteries or Veins
In venous thrombosis, cyanosis occurs due to stagnation of
blood flow with dilated subpapillary venous plexuses. In
 96 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

acute arterial obstruction, cyanosis occurs due to a sudden Table 6.1: Aetiological classification of cyanosis
fall in the mean pressure in the distal arteries leading to
I. Central Cyanosis
decreased tissue PO2. Its intesity depends on the collateral 1. Congenital Heart Diseases
arterial potential. a. Fallot’s tetralogy
The colour of the skin and mucous membrane may not b. Pulmonary stenosis with ASD
be always blue as in polycythaemia where the cyanotic hue c. Eisenmenger’s syndrome
may be modified with red of the oxyhaemoglobin and the d. Atresias
blue of reduced haemoglobin giving a purplish or plum- i. Pulmonary atresia
coloured appearance. ii. Tricuspid atresia
e. Transposition
i. Transposition of the great vessels
CAUSES OF CYANOSIS ii. Transposition of the pulmonary veins
Aetiological classification of cyanosis is given in Table 6.1. f. Ebstein’s anomaly
g. Truncus arteriosus
2. Pulmonary Causes (Refer chapters Dyspnoea, and chest pain)
Central Cyanosis a. Obstruction of the airways
1. Congenital Heart Diseases i. Laryngeal obstruction
ii. Bronchial obstruction with collapse
Fallot’s tetralogy This is the most common congenital iii. Chronic obstructive pulmonary disease (Due to chronic
cyanotic heart disease. The anatomic abnormalities are bronchitis and/or emphysema)
ventricular septal defect, pulmonary stenosis, dextroposition b. Pulmonary fibrosis
of the aorta, right ventricular hypertrophy. The symptoms c. Pulmonary oedema
d. Extensive pneumonia
exhibited are dyspnoea, central cyanosis, and clubing.
e. Acute respiratory distress syndrome
Exertion and cry spells increase the cyanosis and may result f. Pulmonary arteriovenous fistula
in syncopal attacks or convulsions. Dyspnoea relieved by g. Massive pulmonary embolism
squatting or knee-chest position (orthostatic dyspnoea) due h. High altitudes (low inspired PO2)
to improved arterial oxygenation. Auscultation of heart 3. Haemoglobin abnormalities
reveals systolic murmur in the 3rd left intercostal space with a. Methaemoglobinaemia
a single second sound of the aortic component. X-ray of the b. Sulfhaemoglobinaemia
c. Kansas haemoglobin
4. Polycythaemia
II. Peripheral Cyanosis
1. Decreased cardiac output
a. Shock
b. Heart failure
2. Obstructions
a. Venous
b. Arterial
3. Raynaud’s phenomenon
• Central cyanosis
4. Causes

chest may show coeur-en-sabot configuration of heart and

Fig. 6.1: X-ray of the chest showing rounded left lower cardiac
contour with the apex elevated and blunted giving rise to Coeur-
en-sabot (like wooden shoe) configuration, diagnostic of Fallot’s
tetralogy
oligemic lung fields (Fig. 6.1). ECG shows evidence of right
ventricular hypertrophy.
Pulmonary stenosis with ASD This entity is suspected when
clinical features of Atrial Septal Defect (ASD) are associated
with a pronounced thrill in the 2nd intercostal space. When
there is elevated pressure in the right ventricle, hypertrophy
occurs and causes less distensibility with consequent shunt,
resulting in central cyanosis. The signs are a harsh prolonged
 Cyanosis
systolic murmur with a thrill and right ventricular heave.
X-ray shows cardiomegaly and the pulmonary vessels are
small, though the main artery is dilated (poststenotic
dilatation due to valvular stenosis). ECG shows right
ventricular hypertrophy and prominent P waves.
Eisenmenger’s syndrome This condition results from reversed
shunt due to increased pulmonary hypertension after
prolonged period of existence of ventricular septal defect
(Eisenmenger’s complex), atrial septal defect and patent
ductus arteriosus, i.e. the left-right shunt without cyanosis
changes to right-left shunt with cyanosis. The symptoms are
cyanosis, clubbing, and dyspnoea. A prominent ‘a’ wave in
the neck, pulmonary element of second sound accentuation,
faint systolic murmur and diastolic murmur in pulmonary area,
are the usual elicitable physical findings.
Ventricular septal defect (VSD) The characteristic pansystolic
murmur with the thrill in the 3rd and 4th intercostal space
and accentuated second sound with a close split are
diagnostic. Other evidences of pulmonary hypertension like
right ventricular heave, an ejection systolic murmur, early
diastolic murmur of pulmonary incompetence may be
present. The X-ray shows pulmonary plethora, dilatation of
pulmonary artery and biventricular hypertrophy. ECG may
show evidence of biventricular hypertrophy. When
Eisenmenger’s reaction occurs, the pansystolic murmur may
disappear. Second sound becomes single. X-ray shows
diminished pulmonary vascular markings and ECG shows
absence of Q in V6 and secondary R wave in V1.
Atrial septal defect (ASD) In uncomplicated ASD, the
ejection systolic murmur is heard in the left upper sternal
border with a loud and widely split fixed second sound, due
to prolongation of right ventricular systole and already
overfilled chamber’s inability to fill further on inspiration.
Pulmonary hypertension complicating ASD may be recogni-
sed by pulmonary diastolic murmur due to pulmonary
incompetence and a high pitched pulmonary ejection click.
In some, a mid diastolic murmur may be present over
tricuspid area due to torrential tricuspid blood flow. The
X-ray shows prominent pulmonary artery and branches,
enlarged right ventricle. The ECG shows incomplete right
bundle branch block with right axis deviation. When
reversed shunt occurs, a giant ‘a’ wave, considerable right
ventricular lift, right atrial gallop and an obviously split
second sound which does not widen on inspiration are
diagnostic. X-ray shows right atrium and right ventricle
enlargement with a dilated right pulmonary artery. ECG
shows conspicuous Pulmonale and right ventricular
preponderance.
97
Patent ductus arteriosus (PDA) The cyanosis is prominent
in the lower half of the body due to unoxygenated blood
from the pulmonary artery reaching the descending aorta
(differential cyanosis). The machinery continuous murmur
of the PDA in the left second intercostal space getting louder
on expiration, disappears and a loud systolic murmur and
occasionally a diastolic murmur may be heard, in pulmonary
hypertension with reversed shunt. The second pulmonic
sound is split, which widens normally during inspiration.
X-ray of the chest shows enlarged left ventricle, dilated
pulmonary artery and pulmonary plethora in an
uncomplicated case. With reversed shunt, an abnormal
convexity between the aortic knuckle and pulmonary arc is
seen, with diminished peripheral vascular markings. ECG
shows evidence of left ventricular preponderance when
shunt is large enough, otherwise it may be normal. With
reversed shunt, ECG may also show right ventricular
preponderance besides good Q waves in leads V5 and V6.
Atresias
Pulmonary atresia (Single outflow tract): This is rare and
usually associated with other anomalies like ASD, PDA or
VSD which keep up the passage of blood. It is characterised
by a loud systolic murmur or a continuous murmur in the
left subclavicular region or bilateral, due to dilatation of
the bronchial arteries coming from dextraposed aorta. The
second sound is not split and loud. X-ray shows clear lung
fields with concave pulmonary conus.
Tricuspid atresia This is rare and there is no communication
between right atrium and right ventricle. Hence, there will
be an associated atrial septal defect or ventricular septal
defect. A systolic murmur in the left sternal border with a
split second sound is present. X-ray shows enlarged heart
with a concavity in the region of the pulmonary conus. ECG
reveals left axis deviation and conspicuous pulmonale.
Transposition
Transposition of the great vessels Here the aorta arises from
right ventricle and pulmonary artery arises from left
ventricle. It is usually associated with ASD, VSD or PDA
to maintain the circulation. Cyanosis is prominent, from birth
and when PDA is associated, the cyanosis is more in the
upper half of the body due to more oxygenated blood in the
left ventricle communicated through transposed pulmonary
artery and PDA into the aorta (differential cyanosis). In about
1/3rd of cases, there is no murmur. In others, the charac-
teristic murmurs from the coexisting defects and single
second sound due to improper transmission of the pulmonary
 98 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
component are identified. There is an evidence of marked
right ventricular hypertrophy. X-ray shows cardiomegaly
and it is egg-shaped with the narrow end at the apex. ECG
shows right axis deviation and right ventricular hypertrophy.
Transposition of the pulmonary veins In this situation, the
pulmonary vins drain into the right atrium instead of left.
There is midsystolic murmur along the left sternal border
with widely split second sound unaltered by respiration and
an ejection click. There is cardiomegaly with parasternal
lift.
X-ray shows cardiac silhoutte with figure ‘8’ appearance
due to enlarged supra cardiac shadow. ECG shows peaked
P waves with right axis deviation and right ventricular
hypertrophy.
Ebstein’s anomaly There is a downward displacement of the
posterior and medial cusps of the tricuspid valve into the
right ventricle far below the annulus fibrous, from where
normally the leaflet arises. The anterior cusp may be the
only functioning part of the valve. The portion of the right
ventricle above the valve behaves like right atrium (atrialised
right ventricle). There is associated atrial septal defect. The
cyanosis may be of late onset. The heart is quiet and enlarged
due to large right atrium, as right ventricle is relatively small.
A pansystolic murmur in the lower end of the sternum and a
scratchy diastolic murmur in 3rd left space may be heard.
The second heart sound is widely split. X-ray shows a
balloon-shaped heart with a concave pulmonary artery
salient and clear lungs. ECG shows right bundle branch
block, tall ‘P’ waves and prolonged PR interval.
Truncus arteriosus This is very rare and there is a failure of
development of the septum between the aorta and the
pulmonary artery; so much so a single vessel arises from
both the ventricles with a single quadri cuspid valve. A large
VSD is invariable. Pansystolic murmur and a thrill is present
in the 3rd and 4th intercostal spaces with a loud single second
sound. There is cardiomegaly with a parasternal lift.
X-ray shows cardiomegaly, conspicuous ascending aorta,
absent pulmonary arc, with marked pulmonary plethora.
ECG shows evidence of biventricular hypertrophy and right
atrial hypertrophy.
N.B: The etiology of congenital heart diseases is complex,
as the congenital cardiovascular malformations are not
inherited as such but seem to result from an interplay
between genetic and environmental factors, which ultimately
interfere with the normal embryonic development. A single
gene mutation or chromosomal aberrations on one hand and
virus infections like rubella or abuse of alcohol and
teratogenic drugs on the other, are incriminated.
2. Pulmonary Causes
Central Cyanosis due to respiratory diseases associated with
impaired pulmonary function either from alveolar
hyperventilation and /or overperfused (ventricular perfusion
mismatch) or diffusion defects across alveolar membrane
(inadequate gas exchange) result in hypoxaemia and
hypercapnia.
Pulmonary arteriovenous fistula: It may be congenital or
acquired. The cyanosis, which depends on the size of fistula,
is caused by the shunting of unoxygenated blood from the
pulmonary artery into the pulmonary veins. Clinical features
like clubbing, dyspnoea, syncopal attacks may be seen and
mistaken for a cyanotic congenital heart disease. A
continuous murmur may be heard over the fistula in either
of the lower lobes. There may be cardiomegaly. It is often
associated with hereditary haemorrhagic telangiectasia
wherein epitaxis is common and haemoptysis occurs only
in a small percentage of cases.
Chest X-ray shows nodular densities, with branches into
the vascular markings of the lung. The size of the densities
may increase with valsalva manoeuvre or decrease with
Muller’s.
High altitudes Central cyanosis due to diminished arterial
oxygen saturation, can occur at higher altitudes depending
upon the oxygen tension of the inspired air, which is directly
proportional to oxygen tension of the arterial blood, i.e. the
higher the altitude higher the percentage of reduced
haemoglobin.
At high altitudes, the atmospheric pressure is lower than
the normal 760 mm of Hg and so its 21 per cent of oxygen
becomes lower than the normal 160 mm of Hg. This low
inspired PO2 leads to a fall in the partial pressure of oxygen
in the arterial blood (PaO2). The lower the PaO2 of arterial
blood, the lower the saturation of haemoglobin with oxygen,
and the consequent higher reduced haemoglobin, leading
to cyanosis.
All other conditions causing cyanosis due to impaired
pulmonary function are discussed in Chapters ‘Dyspnoea’
and ‘Chest Pain’.
3. Haemoglobin Abnormalities
Methaemoglobinaemia Normally, methaemoglobinaemia,
which is formed by the oxidation of haemoglobin, is reduced
enzymatically by methaemoglobin reductase. When this
enzyme is deficient or when the haemoglobin variant (M
haemoglobin) with less oxygen affinity is present, hereditary
methaemoglobinaemia results. On the other hand, consump-
tion of water with excess of nitrites or drugs like phenacetin,
 Cyanosis
pamaquine, dapsone, sulphonamides or contact with aniline
dyes which act as oxidising agents produce acquired
methaemoglobinaemia. Normally less than one per cent of
methaemoglobin is present. If it exceeds 10 per cent
(1.5 g), cyanosis occurs. If it exceeds 35 per cent, symptoms
like headache, breathlessness and weakness occur in
addition. If it exceeds 70 per cent, it is incompatible with
life.
This is suspected clinically whenever there is central
cyanosis without any evidence of underlying cardiac or
pulmonary disease and also if the blood remains brown when
it is mixed in a test tube, despite exposure to air (if the
cyanosis is due to low arterial oxygen saturation, the blood
sample changes to red colour when mixed with air). It is
further confirmed by spectroscopic examination of
1 : 100 dilution of blood and the band is seen at 630 mm
which disappears on adding a reducing agent.
Sulphaemoglobinaemia The sulphaemoglobin band at 620-
630 nm is not decreased by addition of the cyanide. Cyanosis
occurs if it exceeds 10 g/dl.
Kansas haemoglobin Mutant haemoglobin (Kansas
haemoglobin) with low affinity for oxygen causes lowered
arterial oxygen saturation and central cyanosis.
4. Polycythaemia
It means literally ‘too many cells’. The increase in the
number of circulating red blood cells may be:
Absolute or true polycythaemia (RBC mass ↑)
a. Primary (polycythaemia rubra vera) is a myelo-
proliferative disorder with increased WBC and
platelet count and also splenomegaly.
b. Secondary to hypoxia renal disease (hyper-
nephroma), cerebellar vascular tumours, congenital
haemoglobinopathies, cigarette smoking, or attitude,
wherein the red cell count as well as the haemoglobin
increase without leucocytosis, thrombocytosis, or
splenomegaly. Erythropoietin, which is released from
the kidney, in hypoxia or the inappropriate
erythropoietin stinulates the red cell production.
Relative polycythaemia or pseudoerythrocytosis (Plasma
volume decreased)
a. Decreased plasma volume occurs secondary to
dehydration (persistent vomiting or diarrhoea)
wherein red cell count and haemoglobin percentage
increase, the haematocrit rises from normal 52-54
per cent and the total red cell mass remains normal.
99
b. Decreased plasma volume without apparent
dehydration (Gaisbock’s syndrome) seen in the
obese, smokers, those under stress, and hypertension.
In polycythaemia rubra vera, symptoms like headache,
dizziness, pruritus and fatigue may be complained.
Examination shows a dusky red and cyanotic facies.
Hypertension may be present in 50 per cent of cases. As
haematocrit values rise, viscosity also rises, when
polycythaemia is more pronounced with consequent
diminished flow of blood and a tendency towards vascular
occlusions. This hyperviscosity may also impair the oxygen
transport with consequent increased work for the heart
leading to heart failure. The actual red cell mass is
unequivocally increased (upper normal limit 35 ml/kg)
besides an increase in all the three cellular elements of blood.
The cyanosis in polycythaemia is due to (a) increased
red cells with proportionately increased reduced haemo-
globin and (b) reduced rate of blood flow consequent to
increased viscosity; in spite of a normal arterial oxygen
saturation.
Peripheral Cyanosis
1. Decreased Cardiac Output
Shock Peripheral cyanosis occurs in shock. (Refer to Chapter
‘Shock’).
Heart Failure
a. Left heart failure—Peripheral cyanosis may occur along
with cold extremities, sweating, sinus tachycardia due
to adrenergic activity. The dyspnoea is more pronounced
and out of proportion to cyanosis (Refer to Chapter
‘Dyspnoea’).
b. Congestive heart failure—Cyanosis occurs due to low
cardiac output and consequent compensatory
vasoconstriction leading to reduced inflow of blood
through the skin and reduced oxygen tension in the
capillary bed at the venous end. Congestive heart failure
with systemic congestion usually occurs in mitral
stenosis, cardiomyopathy, hyperkinetic circulatory states
or after left heart failure. Massive pulmonary embolism
or severe pulmonary stenosis results in right ventricular
failure per se (Refer to Chapter ‘Oedema’).
2. Obstructions
Venous Obstruction This type of obstruction in a limb
produces stagnation of blood flow and the venous
hypertension dilates sub-papillary venous plexuses resulting
in cyanosis (Refer to Chapter ‘Oedema’).
 100 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Arterial Obstruction When there is sudden arterial obstruction
in an extremity, the limb becomes cold, pale and painful
with numbness and slight cyanosis. The pulses are absent,
distal to the occlusion. The common causes are embolism
(valvular diseases of the heart, atrial fibrillation, myocardial
infarction) or thrombosis (atherosclerosis obliterans, injury
to the arterial wall, collagen diseases, dysproteinaemias, and
myeloproliferative diseases) Refer to Chapter ‘Pain’ in the
extremities.
3. Raynaud’s Phenomenon
It is due to tonic contraction of the digital arteries inter-
mittently and the vasospasm is considered to be an abnormal
activity of the vasoconstrictor nerve fibres. It is precipitated
by exposure to cold and consists of parasthesiae and colour
changes. When there is no obvious specific cause, it is
primary (Raynaud’s disease) or it is secondary to
i. Occlusive arterial disese
ii. Collagen vascular disease
iii. Thoracic outlet syndrome
iv. Occupational where the upper extremities are exposed
to high frequency vibrations
v. Haematological abnormalities like cryoglobulins and
dysproteinaemias
vi. Drugs like ergot or propranolol
Raynaud’s disease is more common in emotional women
and occurs between teenage and menopause. It is due to
extreme sensitivity to cold and appears to be an exaggerated
physiological constrictor response. The symptoms are
bilateral, symmetrical and confined to the fingers more often
than toes. Paresthesiae like tingling or numbness or burning
are more common than pain. The triphasic colour response
occurs in sequence white-blue-red. The pallor occurs when
the digits are bloodless, the cyanosis is due to sluggish flow
of excessive deoxygenated blood and redness is a rebound
effect due to pronounced vasodilatation after the spasm
(Reactive hyperaemia).
Raynaud’s phenomenon secondary to any underlying
disease and presenting as a part of the clinical picture, is
suspected when the onset is abrupt and unilateral, with
associated features of the ongoing disease process in men.
Although there are no pathological changes initially,
endarteritis obliterans occurs with or without thrombosis.
Ischaemic changes in the skin of the digits and ultimately
ulceration or gangrene (dead fingers) result from the
prolonged asphyxia.
CLINICAL APPROACH
It is imperative to confirm whether the bluish discolouration
is true cyanosis or not. The usual pitfalls are
i. A pigmented tongue can be mistaken for cyanosis. The
former is confined to certain areas of the tongue only.
ii. The bluish skin can result from argyria due to
deposition of silver salts. This colour does not blanch
on pressure unlike cyanosis.
iii. The discolouration of the lips may be mistaken for
cyanosis in chronic smokers.
The next step is to determine the type of cyanosis—
whether it is central, peripheral or mixed.
History
a. Age
i. Childhood—Congenital heart disease
ii. Old age—Corpulmonale
b. Duration of the cyanosis (present from birth in cyanotic
congenital cyanotic heat disease or some acyanotic
congenital heart diseases may develop cyanosis later,
i.e. cyanose tardive)
c. Factors responsible for intensifying cyanosis (capillary
status, thickness of the skin, exercise)
d. Any indulgence of drugs or chemicals like phenacetin.
e. Presence of dyspnoea or cough (presence of cyanosis
without dyspnoea is usually pigmentary cyanosis)
Physical Examination
General Examination
a. Oral cavity—Dorsum and underneath surface of the
tongue, inner side of the lips and cheeks
b. Hands and feet
i. Warm (in Corpulmonale) or cold (in shock);
ii. Cyanosis
iii. Clubbing—If present, it is highly suggestive of
congenital heart disease or respiratory disease.
However, clubing is not present in conditions where
central cyanosis occurs all in a sudden or in
peripheral cyanosis.
c. Oedema—Over the ankles (early oedema) or localised
to the legs or generalised.
d. Vital data—Especially palpating all the peripheral
pulses.
Systemic Examination
a. Cardiovascular system—look for cardiomegaly
(character of apical impulse—left ventricular type or
right ventricular type), altered heart sounds, murmurs,
or evidence of heart failure.
b. Respiratory system—Is expansion of the chest normal.
Any tracheal deviation? Any altered percussion note or
breath sounds? Type of adventitious sounds?
 Cyanosis 101

c. Abdomen—Any hepatomegaly? If so, is it tender? Look

for hepatojugular reflux or evidence of ascites.

Bedide Manoeuvres
a. If the cyanosis disappears after massaging or warming,
it is very likely to be peripheral cyanosis.
b. Administration of 100 per cent oxygen may relieve the
cyanosis, if it is of pulmonary origin and not in cardiac
disorders. In emphasema, oxygen has to be administered
carefully to avoid CO2 narcosis.
c. If there is no evidence of cardiac or respiratory disorders
and if the cyanosis is of recent onset, it is likely to be
methaemoglobinaemia in which condition
administration of methylene blue may reduce the
intensity of cyanosis.

Investigations
Fig. 6.2: Colour flow Doppler showing a high velocity ventricular
They are essential primarily to elucidate the underlying septal defect jet and tricuspid regurgitation (For colour version
cause. see Plate 1)

Radiography Pulse oximetry: Useful to detect hypoxaemia. It will assess

X-ray of the chest which may show pulmonary or cardiac peripheral haemoglobin saturation with oxygen
disorder. (Oxyhaemoglobin saturation of <90% is abnormal).

ECG Haematology
This is to know which chamber hypertrophy is present. a. Complete blood count (WBC, DC, RBC, HB%,
platelets)
Echocardiography (2D or colour) b. ESR
c. LE Cell
It reveals the exact underlying cardiac anomaly (Fig. 6.2).
Spectroscopic
Circulation Time
Examination of the blood for abnormal types of
Arm to tongue time is fast in congenital heart disease with
haemoglobin.
shunt (3-5 s) or prolonged in left ventricular failure (28 s)
(normal 9-18 s).
Electrophoresis
Doppler Test a. Immunoelectrophoresis and cryoglobulins in serum
b. Haemoglobin electrophoresis
If necessary, to assess the circulatory status in the limb.
Second Level Studies (If necessary)
Spirometry
1. Cardiac catheterisation
For any evidence of obstructive or restrictive ventilatory
2. Angiocardiography and arteriography
defects
3. Bronchoscopy
4. CAT scans—Chest
Measurement of Blood Gas Tensions
5. Radioisotope study of red cell mass may discriminate
PaO2 and PaCO2 (PaO2 is low in central cyanosis and PaCO2 between decreased plasma volume and increased red
is low in hyperventilation or raised in hypoventilation). cells.
 102 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
6. 2, 3-Diphosphoglycerate (DPG) in RBC. They are
elevated in hypoxia (The affinity of haemoglobin for
oxygen is influenced by 2, 3-DPG in red cells, i.e.
important for the haemoglobin function).
TREATMENT OF CYANOSIS
Cyanosis is the hallmark of arterial hypoxaemia (i.e.) when
arterial oxygen tension (PaO 2) falls to 50 mm Hg or
saturation of blood falls below 80% (normal Pao2 is 80-100
mmHg and arterial oxygen saturation is 95-99%). The bluish
discoloration depends on whether it is due to (a) inadequate
pulmonary oxygenation (pulmonary lesions, pulmonary
heart disease, ventilatory disorders without pulmonary
pathology like sleep apnoea, neuromuscular disorders,
obesity); (b) increased deoxygenation of capillary blood
(circulatory or heart failure); Pulse oxymetry is useful to
detect hypoxaemia. It assesses peripheral haemoglobin
saturation with oxygen. (Oxyhaemoglobin saturation of <
90% is abnormal). (c) cardiovascular shunts (congenital
heart disease); or (d) reduced oxygen capacity (haemoglobin
abnormalities—methaemoglobinaemia, anaemia). The
administration of oxygen is vital in all hypoxaemic situations
(resting, exertional or nocturnal) while probing for the
underlying cause.
Oxygen Therapy
It is administered by oronasal devices (nasal catheter, nasal
cannula, different types of masks like BLB or venturi) or
occasionally tent or chamber and recently transtracheal
cannula. It is given in low or high concentrations at specified
flow rates depending upon CO2 retention. In acute lung
pathology per se high concentration of oxygen is
administered, preferably humidified to prevent drying of
secretions of respiratory tract. (A flow rate of 4-6 L/mt yields
a concentration of 60% reasonably whereas 6-10 L/mt yields
100 per cent oxygen.) A low concentration of oxygen given
at 1-2 L/mt yielding a concentration of 24-28 per cent
improves the survival rate in chronic retention of CO2, as in
chronic obstructive pulmonary disease (COPD).
(Intermittent administration of O2 in patients with CO2
retention is dangerous). These endeavours are to maintain
oxygen tension of >60 mm Hg or >90 per cent of oxygen
saturation monitored by pulse oximetry. It is advisable to
give oxygen continuously till the acute phase is recovered
(should not be stopped abruptly). Long term domicillary
oxygen supplementation judiciously in chronic hypoxia is
of established value.
Adverse effects of prolonged high concentration of
oxygen are acute respiratory distress syndrome, pulmonary
oedema and consolidation. In premature infants retrolental
fibroplasia and blindness are documented.
If PaO2 does not improve, Positive pressure ventilation
with continuous positive airway pressure (CPAP) through
fitting mask or tracheal intubations and mechanical
ventilation may have to be adopted. If still does not improve
add positive end expiratory pressure (PEEP) in 2 cm of water
increments to maximum of 20 cms of water, failing which
extracorporeal membrane oxygenation (ECMO) considered.
Respiratory Failure
This may be acute or chronic resulting from either an acute
problem or a chronic problem with /without exacerbations.
It occurs when gas exchange is not adequate resulting in
hypoxia, i. e. Pao2 is <8 kpa. (Normal II - 13 kpa). I kpa is:
76 mmHg or when ventilation is inadequate resulting in
hypercapnia (i. e.) paco2>6.5 kpa. There are 2 types of
respiratory failure (I) Acute hypoxaemic respiratory failure
(Type I) (2) Acute ventilatory failure or acute hypercapnic
respiratory failure (Type II), i. e. hypoxia with hypercapnia.
It results from. (a) Obstruction in the upper airways. (b)
Paralysis of the respiratory muscles and (c) lung diseases
affecting gas exchange. The former two lead to hypercapnia,
i. e. rise in arterial Paco2>50 mmhg and hypoxaemia <60
mmhg (Type II) whereas the third cause leads to hypoxaemia
essentially with normal or low. Paco2 (Type I).
Treatment of Acute Type-I Respiratory Failure
1. Treat the underlying cause like pneumonia, acute asthma
pulmonary oedema, and ARDS.
2. Oxygen therapy to correct hypoxia. (>35%).
3. Treat the infection with appropriate antibiotics.
4. a. Maintain patent airways by pharmacotherapy with
bronchodilators like salbutamol (nebulization) or
xanthine, expectorants with mucolytics and
hydrocortisone.
b. Postural drainage and suction
5. Respiratory stimulants like doxapram given if the patient
becomes drowsy and not tachypnoele or exhausled or
prethcamide (225 mg amp).
6. Treat the coexisting conditions like shock, anaemia,
hypokalaemia or hypophosphataemia.
7. Sedatives and tranquilliser are contraindicated.
8. Mechanical ventilation if needed.
 Cyanosis
Treatment of Acute Type-II Respiratory Failure
1. Supplement oxygen starting with low concentrations and
increasing as needed to correct hypoxia (too much
oxygen contraindicated if associated with COPD).
Controlled low oxygen (24-28%).
2. Treat the underlying cause like obstruction of airways
by foreign body, paralysis of respiratory muscles due to
CNS lesions, narcotic poisoning with naloxone or acute
severe asthma.
3. Maintain the patent airways by Pharmacotherapy or
suction.
4. If respiratory acidosis is severe, sodium bicarbonate IV
can be given.
5. Respiratory stimulants given if the patient becomes
drowsy.
6. Mechanical ventilation or tracheostomy to be considered.
Tracheal intubation and volume controlled ventilation
adopted if paco2 is rising (Acute Co 2 retention). If
improves, synchronised intermittent mandatory
ventilation (SIMV) introduced as prelude to weaning
and extubation.
Treatment of Chronic Type-I Respiratory Failure
Treat the underlying cause like
1. Pulmonary interstitial fibrosis and R-L intracardiac
shunts (Refer to Chapter ‘Dyspnoea’). Interstitial fibrosis
needs immunosuppressents like corticosteroids or
azathioprine.
2. Controlled low oxygen (24%-28%).
3. Mechanical ventilation or tracheostomy.
Treatment of Chronic Type-II Respiratory Failure
Treat underlying cause like
i. Chronic pulmonary diseases like chronic obstructive
pulmonary diseases (COPD which includes chronic
Bronchitis Obliterative Bronchititis chronic Asthma
and emphysema).
(Corpulmonale is the term applied to hypertrophy of
the right ventricle with or without cardiac failure
secondary to chronic hypoxaemia).
ii. Ventilatory disorders which include neuromuscular
entities like polio; kyphoscoliosis, Ankylosing
spondylitis, obstructive sleep apnoea (intermittent
recurrent closure of the pharyngeal airway leading to
apnoea during sleep associated with loud snoring).
COPD is managed with (a) Bronchodilators-nebulised
salbutamol (2.5 mg) or Ipratropium bromide (20 ug each)
103
6th hourly inhalations or theophylline oral or parenteral
(considered if inhaled treatments have failed).
a. appropriate antibiotics for respiratory infections
(existing) or to prevent the same.
b. Corticosteroids inhalations (beclomethasone, budesone,
fluticosone) with or without long acting beta
adrenoceptor agonists like salmeterol. In certain cases
short course of oral corticosteroid therapy may be given
for a week or two as needed especially in acute
exacerbations.
c. Symptomatic cough expectorant mixtures with
mucolytics and enough hydration to clear secretions.
d. Acetazolamide is beneficial in CO2 retention as it
facilitates renal excretion of bicarbonate.
e. Controlled low concentrations of domicilliary oxygen
(1-2 l/min for 15 hours a day-24%) to keep PaO 2
>60 mmHg on long term basis. No oxygen is required if
PaO2 is>60 mmHg (SaO2-90%) except during flights.
Excess of oxygen may accelerate hypoventilation due
to interference with anoxic reflexes (decrease respiratory
drive and increase PaCO2) (Usually long-term oxygen
therapy prescribed, if PaO2 mm Hg and FEV1 < 1.5L).
f. Avoid bronchial irritation by dusty atmosphere and
smoking or remove the triggers so as to prevent
exacerbation/progression.
g. Encourage chest physiotherapy (Breathing exercises,
relaxation of cervical muscles and clearing secretions if
necessary with suction).
Ventilatory disorders (hypoventilation with normal lungs).
a. Obstructive sleep apnoea is treated with nasal continuous
positive airway pressure (CPAP) during sleep
(Encourage sleeping in the lateral position) avoiding
alcoholic excess, reducing overweight. Tonsillectomy,
uvulopalato pharyngoplasty or tracheostomy rarely
needed.
b. Neuromuscular entities and kyphoscoliosis- noninvasive
ventilation with negative pressure ventilators (Cuirass-
type) help rest the respiratory muscles at night may be
helpful.
Treat respiratory failure
a. Respiratory stimulants- doxapram as IV infusion
(1-4 mg/min) given if respiratory acidosis is profound,
i.e. PaCO2 continues to rise. (This is not indicated in
neurological disorders or drug overdosage or tachypnoea
or patient when exhausted).
N.B: Sodium bicarbonate may be harmful in chronic
hypercapnia (Carbondioxide retention) due to removal
of the low pH stimulus.
 104 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Noninvasive ventilatory support like nasal intermittent
positive pressure ventilation (NIPPV) with nasal or
facemask is of value. Invasive mechanical ventilation
not indicated.
Treat coincident cardiac failure with loop diuretics,
vasodilators judiciously (reduces pulmonary hypertension),
phelbotomy (if haematocrit is>65%). Digoxin is considered
only when atrial tachyarrhythmia or concomitant left
venticular failure occurs.
Treatment of Acute on Chronic Respiratory Failure
1. Treat precipitating conditions in acute on chronic
ventilatory failure like infections, retained secretions or
pneumothorax or narcotic overdosage
2. Oxygen Therapy
3. Drugs: Bronchodilators, corticosteroids and antibiotics
4. Nasal positive pressure ventilation is of immense value.
Invasive mechanical ventilation indicated only if PaO2
<40 mm, severe acidosis pH < 7.25, and PaCO2> 60 mm.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
Pulmonary Causes
Obstruction of the Airways
Laryngeal obstruction The management depends upon the
underlying cause. Though laryngeal obstruction due to
inflammatory causes does not produce cyanosis, other causes
like foreign body (leading to acute asphyxia accompanied
by cyanosis) demand prompt measures for the relief of
obstruction and prevention of a possible catastrophe.
Turning the child head downwards and vigorously squeezing
the chest may facilitate expulsion of the foreign body.
However, in adults, Heimlich manoeuver (compressing the
upper abdomen forcibly with a quick upward thrust) may
be necessary. The foreign body may be removed by
laryngoscopy. In a dreaded emergency, tracheostomy is
performed without delay.
Bronchial obstruction with collapse Pulmonary function is
not impaired unless the main bronchus is involved, with
fall in respiratory reserve. The treatment depends upon the
cause of bronchial obstruction. Bronchoscopic examination
and extraction of the obstructive factor through the
bronchoscope is the mainstay of treatment.
Chronic Obstructive Pulmonary Disease (Vide supra)
Pulmonary fibrosis (Vide supra)
Pulmonary oedema (Refer to Chapter ‘Dyspnoea’)
Extensive pneumonia The treatment consists of effective
antibiotics in optimum doses preferably a combination
(ampicillin and gentamicin or ceftazidime or Meropenem)
in seriously ill patients, for 7-10 days. Oxygen is adminis-
tered in hypoxaemia.
Pulmonary arteriovenous fistula Pregnancy compresses the
fistula when the murmur disappears and cyanosis decreases
by reducing the venoarterial mixing. The cure may be
effected by resection or lobectomy.
Massive pulmonary embolism (Refer to Chapter ‘Chest
Pain’).
High altitudes Those patients who develop clinical features
while ascending too quickly are treated by taking them down
by about 1000 metres rapidly and by administering oxygen.
Acetazolamide may facilitate increased ventilation by
causing metabolic acidosis.
Complications like venous thrombosis, pulmonary
oedema, and cerebral oedema, are appropriately treated, i.e.
adequate hydration and exercise prevents increased viscosity
of blood and possible thromboembolic episode. Frusemide
for pulmonary oedema and dexamethasone for cerebral
oedema may be required.
Hypoxaemic Spells (Congenital Heart Disease)
1. Decubitus—knee-chest position
2. Forty per cent humidified oxygen
3. Sodium bicarbonate to correct metabolic acidosis
4. Vasopressors like methoxamine, an alpha agonist, is
useful as it increases the systemic vascular resistance
leading to increased pulmonary blood flow
5. Treat heart failure, if present
6. Surgical correction.
Methaemoglobinaemia
i. Methylene blue solution (0.1 to 0.2 ml/kg, i.e. 1-2 mg/
kg IV) and repeat every 15 minutes if necessary (In
G6PD, there is no response).
ii. If ingestion of drugs is responsible, gastric lavage,
repeat doses of altered charcoal are instituted. Treat
coma, hypotension or seizures accordingly if they
occur.
Polycythaemia
To reduce the RBC mass to normal levels
i. Repeated phlebotomy (500 ml at one time every 3-6
months).
Cyanosis 105
106 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Cyanosis
ii. P32 radiotherapy (3-5 millicuries when the effect is seen
only after 4 months).
iii. Chemotherapy—Hydroxy urea 500-1500 mg/d orally
is preferred. Anagrelide substituted or added when
hydroxy urea is not tolerated, although Anagrelide is
not a preferred initial agent.
Alkylating agents are not recommended with as
conversion to acute leukaemia is encountered.
iv. If hyperuricaemia occurs allopurinol is recommended.
v. About 20 per cent of patients may progress to
myelofibrosis or about 5 per cent to acute leukaemia.
Circulatory Failure (Decreased cardiac output)
i. Acute Circulatory failure—(Refer to Chapter ‘Shock’).
107
ii. Heart Failure—(Vide supra, and refer to Chapter
‘Oedema’).
Vascular Obstructions
i. Venous—(Refer to Chapter ‘Pain in the Extremities’)
ii. Arterial—(Refer to Chapter ‘Pain in the Extremities’)
Raynaud’s Phenomenon (Local cyanosis)
Immersion of the patient’s hand in hot water for 10 min.
turns the skin colour pink in Raynaud’s disease whereas in
heart failure, it remains blue. In the former, nifedipine
(5 mg 8th hourly) may be helpful. Isoxsuprine or Xanthinol
Nicotinate are other alternatives. Exposure to cold, smoking,
vasoconstrictor drugs or betablockers should be avoided.
 108 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Chapter

Dyspepsia
7
Dyspepsia is a term derived from Greek which connotes Table 7.1: Classification of dyspepsia
imperfect digestion (peptein = to digest). This indigestion
I. Morphological
is expressed in clinical practice as
a. Actual organic lesions with structural changes (organic)
1. Distress after ingestion of food in the form of epigastric b. Without any organic lesion (functional)
discomfort or sense of fullness; or even pain and inability
to complete a normal size meal. II. Clinical
2. Accumulation of gas—belchings (eructation); audible 1. Alimentary
i. Upper gastrointestinal dyspepsia
borborygmi or passing wind
– Ulcer dyspepsia (organic)
3. Heartburn and acid regurgitation
– Non-ulcer dyspepsia (functional)
4. Dull abdominal aches ii. Lower gastrointestinal dyspepsia
5. Disturbed appetite a. Flatulence
6. Nausea b. Intestinal parasites
These manifestations may occur irregularly and in c. Food intolerance
different patterns from time to time under stressful iii. Hepatobiliary dyspepsia
conditions. It may be acute in onset or chronic (recurrent), iv. Pancreatic
i.e. more than three months duration. 2. Extra-alimentary (vide infra)
Dyspepsia once defined as “the remorse of a guilty
stomach” hardly lending itself for precise evaluation, is no
more valid now. It may be acid dyspepsia or alcoholic a. Errors in diet
gastritis with faulty function of the stomach or gastro- b. Overwork and undue worry or anxiety
intestinal faulty function of both stomach and intestines; or c. Alcohol ingestion
hepatobiliary due to liver disease with insufficient bile d. Drugs
secretion; or extraalimentary origin like cardiac. The presenting symptoms are a feeling of epigastric
oppression or dull-ache nausea and vomiting, loss of
CLASSIFICATION appetite, constipation and headache. Sometimes, these acute
Dyspepsia is better classified in Table 7.1. dyspeptic symptoms are encountered in acute gastritis,
migraine or angina.
CAUSES OF CHRONIC DYSPEPSIA
CHRONIC DYSPEPSIA
Aetiological classification of dyspepsia has been better
discussed in Table 7.2. Alimentary
ACUTE DYSPEPSIA Oesophagus
Acute Dyspepsia is the sudden disturbance of digestion in Gastrooesophageal reflux disease (Refer to Chapter ‘Chest
an otherwise normal person which is due to: Pain’).
 Dyspepsia 109

Table 7.2: Aetiology of chronic dyspepsia carbohydrates and proteins leads to flatulence. This is usually
I. Alimentary
associated with excess of mucus. Achlorhydria is seen in
i. Oesophagus: Gastrooesophageal reflux disease chronic gastritis, gastric ulcer, carcinoma of the stomach,
a. Hiatus hernia pernicious anaemia, and sprue syndrome.
b. Oesophagitis
ii. Gastric
Gastric Flatulence Gastric flatulence produces a sensation
a. Gastritis of fullness and discomfort in the epigastrium. If the stomach
b. Gastric ulcer is free of fluid, the gas passes into the intestine and if there
c. Carcinoma of the stomach is fluid trap or pyloroduodenal obstruction, the gas may be
d. Achlorhydria eructated through oesophagus. It may also be associated
e. Gastric flatulence with palpitations and dyspnoea. Gastric flatulence may be
iii. Duodenum caused by:
a. Duodenitis and Moynihan disease
a. Bacterial activity in achlorhydria
b. Duodenal ulcer
iv. Intestinal b. Aerophagy (swallowing of air)
a. Intestinal flatulence c. Impaired absorption of gas, e.g. congestive heart failure,
b. Intestinal parasites (chronic intestinal amoebiasis; cirrhosis of liver
giardiasis; stronglyloidosis) d. Defective elimination due to oesophageal spasm
c. Sprue syndrome—Tropical and non-tropical Large amounts of air in the gastric fundus are seen in
v. Appendix: Chronic appendicitis X-rays.
vi. Hepatobiliary
a. Chronic cholecystitis
b. Fatty infiltration and early cirrhosis
Duodenum
vii. Pancreatic: Chronic pancreatitis Duodenitis and Moynihan Disease (Vide infra)
viii. Food intolerance Duodenal Ulcer (Refer to Chapter ‘Haematemesis’).
II. Extra-alimentary
a. Congestive heart failure Instestinal
b. Ischaemic heart disease
c. Uraemia Intestinal Flatulence About 3-4 litres of carbon dioxide is
d. Chronic infections like pulmonary tuberculosis formed in the small intestine from the interaction between
e. Anaemia acid gastric juice and alkaline pancreatic secretions. Gas is
III. Nonorganic
also formed in the large bowel due to fermentation of
a. Nonulcer dyspepsia (functional dyspepsia) and Moynihan carbohydrates and putrefaction of proteins which escape
disease digestion in the small intestine or ingestion of legumes which
b. Irritable bowel syndrome contain large quantities of nonabsorable sugars. The gas
Dyspepsia may be either acute or chronic.
diffuses across the gut in either direction maintaining
equilibrium and gets expelled from the bowel or absorbed
through portal blood stream with consequent detoxication
in the liver and excretion through lungs. If the gas is
Gastric
odourless, it may de due to nitrogen from the swallowed air
Gastritis or carbon dioxide by the fermentation of the carbohydrates.
Gastric ulcer (Refer to Chapter If the gas is foul smelling, it is due to putrefaction of proteins.
Carcinoma of the stomach ‘Haematemesis’) This intestinal flatulence may give rise to a feeling of
discomfort and fullness in the lower abdomen. Presence of
Achlorhydria The gastric secretion of hydrochloric acid is
gas does not cause pain by itself, but pain is complained of
formed by the parietal cells and is under the influence of
due to gut contractions or trapping of gas into intestinal
nervous and chemical stimuli. The psychic stimulation of
loops or bowel distension or irritation of mucous membrane
secretion is through the vagus nerve. The important chemical
by organic acid.
stimuli are histamine and hormones like gastrin. The absence
of hydrochloric acid in the gastric juice leads to rapid gastric Intestinal parasites
emptying time and facilitates organisms to reach the small • Intestinal amoebiasis: Recurrent abdominal pain with
intestine. The fermenting action of the bacteria on flatulent dyspepsia and a history of past or present
 110 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
diarrhoea or desentery is one of the most common
presentations of dyspepsia in tropics.There may be
distension of the splenic flexure of the colon with
abdominal fullness and the pressure pain radiating to
left side of the chest. Physical examination often reveals
tenderness of the colon paticularly the caecum and
sigmoid with or without hepatomegaly. The diagnosis
is always confirmed by repeated examinations of motion
for entamoeba histolytica and charcot-leyden crystals.
Sigmoidoscopic examination may reveal typical amoebic
ulcers with normal intervening mucosa.
• Intestinal giardiasis: Giardiasis intestinalis may be the
other intestinal parasite leading to periodic attacks of
diarrhoea with dyspepsia. Confirmation of the diagnosis
is made by motion examination for cysts and flagellates.
• Strongyloidiasis: It is caused by Strongyloides
stercoralis. In severe infections epigastric pain, flatulence
and change in bowel habits may be observed, besides
transitory cutaneous eruptions and pulmonary symptoms.
Diagnosis is confimed by finding rhabditiform larvae in
the stool.
• Sprue syndrome: (Refer to Chapter ‘Chronic Diarrhoea’).
Appendix
Chronic Appendicitis
Chronic appendicitis occurs as recurrent attacks of subacute
appendicitis. The principal symptoms being digestive
disturbance and chronic recurrent abdominal pain in the right
iliac fossa or right loin or right hypochondrium, occuring
after food without typical time relationship of peptic ulcer.
The pain may be aggravated by physical exertion. Barium
X-ray may be helpful in diagnosing kinked long appendix.
There may be diarrhoea when appendix is adherent to
rectum.
Hepatobiliary
Chronic Cholecystitis is usually (90%) associated with
gallstones and the remaining (10%) may be of non-calculous
origin like typhoid cholecystitis. Abdominal distension or
discomfort in the epigastrium especially after a fatty meal
and a dull ache in the right hypochondrium, right scapular
region and epigastrium, are the usual presenting symptoms.
Physical examination shows tenderness in the above
mentioned areas and a positive Murphy’s sign and
occasionally palpable gallblader. Cholecystography may be
diagnostic which shows absence of normal contractions of
the gallbladder. Ultrasound examination of the abdomen is
highly contributory.
Fatty infiltration of the liver and early cirrhosis Fatty
infiltration of the liver occurs in those who consume more
carbohydrates and alcohol and less proteins. A feeling of
discomfort with associated symptoms of alcoholic
oesophagitis and gastritis like morning nausea and retching,
vomiting of small quantities of alkaline watery fluid and
bile stained mucus are usually complained of. When
cirrhosis develops with portal obstruction, there is increased
congestion of gastric and intestinal mucous membrane
leading to excess secretion of mucus, besides deficient
absorption of gas resulting in gastric and intestinal
flatulence, which may be the earliest sign of portal
congestion.
A firm smooth surfaced and sometimes tender
hepatomegaly is the characteristic physical finding in fatty
infiltration whereas in cirrhosis liver it is nontender with an
irregular surface, which may shrink as the disease
progresses. (Refer to Chapter ‘Jaundice’)
Pancreatic
Chronic Pancreatitis There will be digestive disturbances
leading to chronic diarrhoea with excess of fat and
undigested muscle fibres in the stool and chronic abdominal
pain in the epigastrium or left hypochrondrium or lumbar
region. Hyperglycaemia, loss of weight and painless
obstructive jaundice are other manifestations. There may
be no striking clinical features at all. It is due to repeated
attacks of acute or subacute pancreatitis or penetration of
chronic duodenal ulcer into the pancreas or associated
chronic inflammation of the biliary tract. Secretin test and
presence of calcareous shadows in the region of pancreas
on roentgenogram (Fig. 7.1) and diabetic type of glucose
tolerance curve are contributory.
Food Intolerance
It means an inability to put up with the particular food
without any ill effect. The reasons may be immunological
or psychological. IgE-mediated reactions are the only
immunological responses to the food. Psychological
response is characterised by the individual’s false belief that
they suffer from food allergy, to which they may attribute
symptoms, which are not identical with the classical allergic
disorders. The IgE mediated food allergy depends on the
level of specific IgE sensitisation of each organ and on the
amount of food ingested. Different organs are involved with
different foods. The gastrointestinal tract is affected usually
with low levels of sensitisation with symptoms of epigastric
pain, bloating, diarrhoea or vomiting, besides tingling and
 Dyspepsia
Fig. 7.1: Plain X-ray of the abdomen showing pancreatic
calcification consistent with chronic pancreatitis
itching of the lips. Most of these immunologically mediated
food allergic patients may react to encapsulated food
provocations. Nevertheless the only available valid evidence
of hypersensitivity is doubleblind feeding.
Extra-alimentary
• Congestive Heart Failure (Refer to Chapter ‘Fatigue’).
• Ischaemic Heart Disease (Refer to Chapter ‘Chest Pain’).
• Uraemia (Refer to Chapter ‘Coma’).
• Chronic Infections like Pulmonary Tuberculosis (Refer
to Chapter ‘Haemoptysis’).
• Anaemia (Refer to Chapter ‘Palpitations’).
Nonorganic
Nonulcer Dyspepsia (Functional or Nervous Dyspepsia)
Dyspepsia without an ulcer or any discerniable anatomic
pathologic lesion is nonulcer dyspepsia and encountered in
patients twice as often as peptic ulcer. However, symptoms
simulating peptic ulcer are present in nonulcer dyspepsia
and no ulcer is found on evaluation. Hence it is termed as
nonulcer (functional) dyspepsia. The term nervous dyspepsia
is yet another synonym described since gastrointestinal
symptoms are closely associated with emotional state.
It may present as a typical ulcer type without any ulcer
or atypically. The obvious clinical feature is a sense of
wellbeing alternating with a feeling of vague abdominal
discomfort, not amounting to actual pain without constant
111
relationship to either food or time. This may be influenced
by fatigability, worry, changes of environment. The other
features are frequent belchings with anorexia, constipation
and sensation of fullness even after small quantities of food
without receptive relaxation of the stomach. Nausea and
vomiting may occur. In addition, features like emotional
instabilities with anxieties and depressions and phobias of
imaginary diseases are striking manifestations. Physical
examination may show tense abdominal muscle and diffuse
tenderness variable in positions may be appreciable.
Radiological examination may reveal altered gastric
emptying time or may be essentially normal. There are no
structural abnormalities and endoscopic studies are negative.
Pathogenesis: Primary motility disturbance appears to be a
distinct possibility. The disordered gastroduodenal motility
results in delayed gastric emptying which is presumed to be
mediated hormonally by circulating concentrations of gastric
hormones and impaired release of motilin. The incriminating
factor of stress alters the motility besides vascularity and
secretion. Duodenogastric reflux or gastric acid appears to
be noncontributory. Genetic and environmental factors play
minimal role. The important entities to be excluded are
peptic ulcer, gastric carcinoma, aerophagy, gastro-
oesophageal reflux, biliary tract disease, chronic pancreatitis
and irritable bowel syndrome.
Moynihan Disease
Nonulcer dyspepsia may be associated with duodenitis
without duodenal ulcer. Spiro coined a term Moynihan’s
disease, which constitutes a triad of nonulcer dyspepsia,
duodenitis and duodenal ulceration, to focus apparent
relationship among these diseases. The proposed stages are
a physiologic phase of acid hypersecretion, a symptomatic
stage and an ulceration stage. It is observed that macroscopic
duodenitis ultimately develops a duodenal ulcer between
2-4 years, in about 40 per cent of cases. Similarly, patients
with nonulcer dyspepsia may develop a peptic ulcer in 40
per cent of hospital-based population, and 3 per cent in
general population. Though this hypothesis appears
attaractive, the evidence of Moynihan’s disease as an
important contribution to nonulcer dyspepsia is inconclusive
since most dyspeptic patients are normochlorhydric without
erosive duodenitis and typical discriminative ulcer
symptoms.
Irritable Bowel Syndrome
It is a diffuse disorder of smooth muscle of the colon and
the motility is influenced by stress or specific food
 112 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
intolerance. Abdominal distension; constant or recurrent
crampy lower abdominal discomfort or pain commonly in
either iliac fossae or both, relieved by defaecation;
disordered bowel habit, i.e. constipation (spastic colon),
diarrhoea with onset of pain or alternating constipation with
diarrhoea or a feeling of incomplete evacuation and mucus
per rectum are the cardinal presentations. There is no blood
in the stool. Constitutional symptoms are strikingly absent
and the presenting symptoms are long standing without
being progressive. Associated symptoms like fatigue, early
satiety, heart burn and urinary frequency may be present.
The discomfort or the pain extends over the entire course
of signoid colon spreading over either to precordial region
or left iliac fossa.
There is increased sensitivity to visceral pain (Visceral
hypersensitivity), which may be triggered by infections and
it is cited as a major factor in the pathophysiology where
the mechanism involved includes psychosocial factors and
altered sensorimotor function of gut due to peripheral and
central sensitisation of visceral afferents. The diarrhoea is
acute or recurrent; watery and nonbleeding without systemic
illness, due to accelerated transit of the intestinal contents.
The disorder is seen usually in adults (30-40 yrs) with
neurosis or hypochondriasis. During the attacks, scybalous
stools are passed with large amounts of mucus. The bowel
rhythm is normal between the episodes.
Physical examination may show a hard pencil type of
gut in the left iliac fossa. Rectal examination is normal.
Signoidoscopic examination may reveal extreme motility
of contraction and relaxation and pouring of mucus. Barium
enema shows variation in the colonic outline with spasm
and narrowing (especially sigmoid) and exaggerated haustra.
Diagnosis is made by exclusion of other causes with similar
clinical features. No organic pathology can be established
in irritable bowel syndrome.
CLINICAL APPROACH
History
1. History of type of diet and dietary habits (chronic
gastritis); history of alcoholism and smoking, analysis
of the type of work and personality trait (duodenal ulcer).
2. Evaluation of predominant symptoms
a. Analysing nature of pain and its location: Is it chronic
abdominal pain or vague discomfort, e.g. intestinal
flatulence may give rise to vague discomfort in the
lower abdomen due to gaseous distension. Chronic
cholecystitis may have dull pain or discomfort in the
epigastrium or right upper quadrant or right back.
b. Relationship to food: Early postprandial pain
suggests oesophageal or gastric disorders and late
onset (four hours after) pain is suggestive of duodenal
ulcer or pancreatic insufficiency.
c. Aggravated after food in cholecystitis or pancreatitis
d. Relieved by antacids or food in duodenal ulcer
e. Radiation: Radiates to the back in chronic
pancreatitis
f. Nausea and vomiting: Morning nausea and vomiting
in chronic gastritis
g. Haematemesis and melaena: Peptic ulcer or cirrhosis
or hypertrophic gastritis (Menetrier’s)
h. Heartburn: Duodenal ulcer, hiatus hernia
i. Water brash: Gastritis, duodenal ulcer
j. Flatulence: Chronic amoebiasis, chronic cholecystitis
k. Anorexia: Common in early cirrhosis and carcinoma
of the stomach
l. Associated with headache: Recurrent attacks of
dyspepsia with headache in migraine
m. Associated psychoneurotic features like anxiety or
emotional lability
3. Bowel movements
a. Constipation: Duodenal ulcer or chronic chole-
cystitis, irritable bowel syndrome (IBS)
b. Diarrhoea: Chronic pancreatitis, chronic amoebiasis
c. Alternating bowel habit in irritable bowel syndrome
4. Duration of symptoms: Short duration usually in
malignancy, uraemia. Long duration in duodenal ulcer
and chronic cholecystitis.
Physical Examination
Though useful rarely for diagnosing specific alimentary
disorders, it helps to delineate extra-alimentary conditions.
General Survey
a. Depressed or anxious facies (nervous dyspepsia)
b. Alcoholic facies (alcoholic gastritis or early cirhosis)
c. Obesity, fat female forty ( gallbladder dyspepsia)
d. Generalised wasting in pulmonary tuberculosis or
malignancy
Examination of tongue: Dry tongue with brownish fur
suggestive of uraemia.
Oral sepsis: Any dental caries or other evidences of poor
oral hygiene.
Examination of chest: For any evidence of pulmonary
tuberculosis, or hypertensive or valvular disease of heart.
Examination of abdomen: For any gaseous distention
(flatulence) or tenderness in either iliac fossae (amoebiasis)
 Dyspepsia
or organomegaly like hepatomegaly (in early cirrhosis or
congestive heart failure), visible peristalsis, e.g. pyloric
obstruction.
Pointing sign: Accurate localisation of pain with finger or
fingers is a positive sign of peptic ulcer. In practice, musculo
skeletal pain due to spasm of the abdominal or intercostal
muscles or peripheral neural enterapment at rectus sheath
border may stimulate the dyspeptic symptoms. Paraspinous
tenderness or spasm and segmental distribution of pain may
be contributory for the diagnosis.
Investigations
Investigations (Based on clinical suspicion to begin with)
1. Clinical pathology/microbiology
a. Stool examination for evidence of intestinal parasites
or undigested food or occult blood
b. Blood examination-RBC, Haemoglobin, ESR
c. Test for H. Pylori
2. Biochemical
a. Blood urea, serum creatinine
b. Gastric analysis-FTM
c. Liver function test like GGT and AG ratio
d. Absorption studies of small bowel function B12’
xylose, glucose
e. Pancreatic function tests
i Serum calcium and blood glucose
ii Secretin test and fat analysis of the stool*
f. Lactose tolerance tests*
3. Radiological
a. Plain X-ray of the abdomen for any calculi
b. Barium meal series for peptic ulcer
c. Barium enema for irritable bowel syndrome
d. Oral cholecystogram for chronic cholecystitis
4. ECG (Exercise testing)
5. Ultrasonic Exam
For calculous cholecystitis or for pancreatic calcification
6. CT Scan*
7. Endoscopic Examination*
a. Oesophago-gastroduodenoscopy
b. Sigmoidoscopy
c. Colonoscopy
d. Endoscopic retrograde cholangio-pancreatography
(ERCP) for illustrating biliary tree and pancreatic
ducts
8. Radiotelemetry*
*Investigations at a later stage
113
Treatment of Dyspepsia
The clinician envisages the treatment of dyspepsia (variety
of alimentary symptoms) on the basis of its origin, whether
it is an organic event, nonorganic tumult or iatrogenic.
Treatment of symptoms constituting dyspepsia are
detailed (Vide infra).
1. Organic event
a. Alimentary disease like reflux oesophagitis, ulcer
dyspepsia, gastritis, gastric carcinoma, small bowel
syndromes, cholecystitis and pancreatitis
b. Consequent to systemic (extra-alimentary) disease
like congestive heart failure, etc.
2. Non-organic tumult
a. Non-ulcer dyspepsia
b. Irritable bowel syndrome
3. Iatrogenic drugs
Specific Treatment for Specific Diseases
Alimentary
Oesophageal
Gastrooesophageal reflux (Reflux oesophagitis) (Refer to
Chapter ‘Haematemesis’)
Hiatus hernia (Refer to Chapter ‘Haematemesis’)
Gastric
Ulcer dyspepsia (Peptic ulcer) Aim of the treatment is to
promote healing and prevent recurrences.
1. General measures like abstinence from alcohol, smoking,
caffeine, beverages, spices and indiscriminate use of
NSAIDS, increase the rate of healing. Frequent small
meals during waking hours without spicy diet and fried
foods (balanced diet) are advocated. Certain foods like
cabbage, egg yolk and milk contain a protective factor
(gefarnate) which promotes healing of peptic ulcer.
2. Specific drug treatment: (Antacids, antisecretory drugs,
coating agents and other drugs)
a. Drugs to counter act acid secretion
• Antacids (to neutralize gastric acid)—combi-
nation of calcium carbonate (150-200 mg)
magnesium hydroxide (150-300 mg), and alumi-
nium hydroxide (300-400 mg) or megaldrate
(hydroxy magnesium aluminate 400-800 mg.)
administered one hour after meal and reinforced
after three hours, if necessary.
 114 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Gastric acid inhibitors (to inhibit acid secretion)
i. H2 receptor antagonists like cimetidine (400-800
mg) ranitidine (150-300 mg); famotidine (20-40
mg); and roxatidine (75-150 mg) 4-8 weeks.
It is prescribed in lower doses twice daily or
higher dose once daily at night. Long-term
maintenance treatment with minimal dose may
be imperative to prevent ulcer relapse.
ii. Proton pump inhibitors (inhibit hydrogen-
potassium ATPase in parietal cell) like
Omeprazole (10-20 mg/d); lansoprazole
(30 mg/d): Pantoprazole (40 mg/d);
Esomeprazole (20-40 mg/d) or Rabeprazole (20
mg/d) for 4-8 weeks.
iii. Muscarine receptor blockers - (atropine (0.5-1
mg tid), Probanthine (15 mg tid) pirenzepine (50
mg bd) inhibit both acid and motility.
iv. Gastrin receptor blockers - Proglumide and
somatostatin (octreotide) are not included in the
usual therapeutic protocol.
v. Prostaglandin E2 - Interferes with generation of
cyclic AMP to parietal cells (Vide infra).
b. Drugs to enhance mucosal defence.
i. Coating agents (to protect ulcers)
• Sucralfate (polyaluminium hydroxide salt of
sucrose sulphate)-Dose is 1 gm four times a
day one hour before food and at bed time (not
given within 30 min of antacids since acid is
needed for itsa adherence to the ulcer).
• Colloidal bismuth (tripotassium dicitrate
bismuthate)-Dose is 240 mg twice daily half
an hour before meals (useful in resistant ulcers
and reducing recurrences).
ii. Mucosal protectors
• Liquorice extracts (carbenoxolone - synthetic
derivative of glycyrrhizinic acid) - Dose is
50 mg 6th hourly.
• Prostaglandin (PG E 1 and E 2 misoprostil
200 ug four times daily and enprostil 35 ug
four times daily) serve as antisecretory and
cytoprotective agents.
iii. Mucosal regenerators
• Plaunotol (Not included in the usual
therapeutic protocol).
Adjunct Therapy
i. Antimicrobials for Helicobactor pylori associated
ulcers (Vide infra).
ii. Local anaesthetics: Oxethazine (10-20 mg four times
a day), Lignocaine viscous 2% (100-200 mg).
iii. Antiflatulents: Simethicone (50-100 mg) methyl-
polysiloxane (25-50 mg tid).
iv. Antispasmodies: Atropine, probanthine, dicyclomine
(10-20 mg tid); hyoscine-N-butylbromide (10-20 mg
tid), Drotaverine (40-80 mg tid).
v. Antidopaminergics: Metoclopramide 10 mg;
domperidone 10 mg tid.
vi. Antidepressants (to control psycho-visceral compo-
nent): Tricyclic compounds doxepin (25-50 mg),
amitriptyline (25-50 mg/d).
However, treatment of gastric ulcer differs from
duodenal ulcer (small doses of antacids, antidopaminergics
without anticholinergics) since acid hypersecretion and rapid
gastric emptying do not pose a problem.
The array of drugs mentioned above and their doses
should be judiciously chosen, for the pharmacotherapy of
peptic ulcer.
Prevention and treatment of ulcer relapses Incidence of
relapse is 80 percent within one year regardless of the drug
used and duration of initial therapy, with possible exception
of bismuth, which is associated with lower relapse rates in
one year.
a. Predictors of ulcer relapse
i. Offending factors like smoking, NSAIDs
continuously.
ii. Prior ulcer complications like bleeding.
iii. Presence of Helicobacter pylori.
iv. Family history of ulcer disease.
b. Intermittent therapy: When symptomatic relapses occur
(< 4/year), full dose monotherapy (H 2 receptor
antagonist) is given for six weeks. Sucralfate is an
acceptable alternative.
c. Maintenance therapy: If symptomatic relapses are
frequent (> 4/year) and in the presence of history of
complications or refractory ulceration, half dose of H2
receptor antagonist is continously administered, when
one year relapse rate is reduced from 80 to 20 percent.
Long term (9 years) controlled maintenance trials with
H2 receptor antagonist to date appear safe and effective.
Relapse rates and complications appear lower, than after
one year therapy as against theoretical risks of gastric
carcinoma, which is yet to be proved. At this stage, the
choice is between long-term therapy and surgery. It may
be given life long in elderly patients or subject with any
cardiorespiratory or hepatorenal impairment who are not
suitable for surgery. Colloidal bismuth compounds,
 Dyspepsia
omeprazole, carbenoxolone, sucralfate, pirenzepine, and
misoprostol are not recommended for maintenance
therapy.
d. Prevention: Apart from eliminating offending factors,
prevention of relapse is further improved by eradicating
H. pylori infection with concomitant triple therapy
consisting of tripotassium dicitrato bismuthate-240 mg
bd (which also resolves the accompanying inflamma-
tion) amoxycillin (500 mg 6th hourly) and metronidazole
(400 mg tid) for two weeks. (Though about 80 per cent
of cases are treated effectively, recurrence rate of H.
pylori infections can still be high). Other combinations
are proton pump inhibitors like omeprazole, antibiotics
like clarithromycin or amoxycillin and tinidiazole or PPI
like Esomeprazole plus Amoxycillin and Clarithromycin.
Triple therapy with one acid suppress ant and two
antibiotics is ideal.
Refractory ulcers Nonhealing is due to (a) non-compliance
of treatment, (b) presence of H. pylori, (c) Zollinger-Ellison
syndrome. (Besides increased acid output, steatorrhoea
occasionally occurs since the lipase is inactivated with
precipitation of bile acids. More than 60 per cent of tumours
are malignant and 30 per cent are associated with multiple
endocrine adenomata Type I (Refer to Chapter ‘Chronic
Diarrhoea’).
In such cases, therapeutic options include (a) continuing
the same drug at the same or higher dose, (b) adding second
agent like doxepin, (c) switching over to different class of
agents like omperazole (d) eradicating H. pylori infection,
(e) treating Zollinger-Ellison syndrome (Refer to Chapter
Haematemesis), (f) surgery.
Indications for surgery
a. Ulcer relapses even after several courses of medical
therapy or if breakthrough relapses occur, or when the
ulcer fails to heal at all interfering with the activities in
life, despite medical therapy.
b. Refractory ulcers inclusive of Zollinger-Ellison
syndrome.
c. When gastric ulcer fails to heal in 15 weeks or turns
malignant.
d. Prior complications like (i) haemorrhage, (ii) perforation
and (iii) ulcer leading to gastric outlet obstruction or
hour-glass stomach due to fibrosis.
Surgical treatment
a. Surgery for duodenal ulcer
i. Vagotomy plus gastroduodenostomy or
gastrojejunostomy
115
ii. Vagotomy and pyloroplasty
iii. Parietal cell vagotomy
iv. Gastrectomy
b. Surgery for gastric ulcer
i. Subtotal gastrectomy
Chronic gastritis Bismuth compounds (Tri-potassium di-
citrate bismuthate) 240 mg twice daily for antral gastritis;
and antacids for symptomatic relief.
Carcinoma of the stomach Gastrectomy or tumour resection
and chemotherapy, if necessary. (Refer to Chapter ‘Weight
Loss’).
Achlorhydria (Refer to Chapter ‘Chronic Diarrhoea’)
Gastric flatulence The treatment of excessive production
of gas in the stomach due to fermentation or putrefaction,
consists of correction of the underlying cause like
achlorhydria associated with gastric stasis, consequent to
either malignant or nonmalignant pyloric obstruction.
If it is due to aerophagy, the patient is explained about
the cause of his eructation or belching trouble. The
underlying causes like emotional factors, congestive heart
failure, etc., interfering with the absorption of the gas, are
to be corrected.
Duodenum
Duodenitis and Moynihan disease Antacids may be
beneficial, H2 receptor antagonists may be considered, if
necessary.
Duodenal ulcer Vide supra
Intestinal
Intestinal flatulence The colonic gas resulting from bacterial
action on carbohydrates and proteins, which escaped
digestion, causes fullness with discomfort or pain. In such
cases, restriction of diet rich in starch or proteins, prevents
excess production of gas. Besides, substances like activated
charcoal facilitating absorption of gas may be beneficial.
Digestive enzymes (diastase; pancreatin, amylase, lipase and
protease and bile constituents) and antiflatulents
(dimethicone) are of considerable value.
Intestinal parasites
a. Chronic intestinal amoebiasis (Refer to Chapter ‘Chronic
Diarrhoea’)
b. Giardiasis (Refer to Chapter ‘Chronic Diarrhoea’)
c. Strongyloidosis (Refer to Chapter ‘Chronic Diarrhoea’)
 116 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Sprue syndrome
(Refer to Chapter ‘Chronic Diarrhoea’)
Appendix
Chronic Appendicitis
The treatment consists of appendectomy.
Hepatobiliary
Chronic cholecystitis The treatment consists of cholecy-
stectomy invariably. If associated with gallstones, the
surgical removal or medical dissolution of gallstones with
bile acids (7.5 mg/kg of Chenodeoxycholic acid and 7.5
mg/kg ursodeoxycholic acid daily) is indicated. Stones in
the common bile duct require endoscopic sphincterectomy
and stone extraction. Non-invasive treatment of extracorpo-
real shock wave lithotripsy is another therapeutic approach.
Free biliary tree is to be ensured subsequently. Analgesics
for biliary colic and antibiotics like cefotaxime, metroni-
dazole for associated cholangitis may be required before
surgery.
Fatty Infiltration of Liver (Steatosis) The treatment consists
of eliminating the offending factors like alcohol or
nonalcoholic causes (obesity, diabetes mellitus). Adequate
nutrition for the former and appropriate management for
the latter group may be necessary. Essential phospholipids
(active principle diglyceride esters of choline phosphoric
acid containing excess of unsaturated fatty acids
predominantly linoleic acid linolenic acid and oleic acid)
are beneficial.
Cirrhosis: (Refer to Chapter ‘Oedema’).
Pancreatic
Chronic pancreatitis: Refer to Chapter ‘Chronic Diarrhoea’
Food Intolerance
Different elimination diets may be tried in alleviating food
intolerance.
Extra-alimentary (Consequent to Systemic Diseases)
Appropriate treatment is instituted accordingly.
Non-organic
Non-ulcer Dyspepsia
(Functional or Nervous Dyspepsia)
a. Assurance and reassurance
b. Discourage cigarette smoking and alcohol
c. Small ‘preferred’ meals frequently.
d. Drugs
i. Antacids may be helpful.
ii. H 2 receptor antagonists if nocturnal pain is
disturbing.
iii. Antidopaminergics for nausea and vomiting.
iv. Antiflatulents for bloating.
v. Pirenzepine or dicyclomine—occasionally helpful.
e. Psychotherapy for adjusting underlying psychological
factors.
Irritable Bowel Syndrome
a. Assurance and reassurance.
b. Diet—Increased roughage content.
c. Constipation—Bulk laxatives, i.e. psyllium (Isapgol) 5-
10 gm; methyl cellulose 1-4 gm. Avoid chemical
laxatives.
d. Diarrhoea—loperamide (6 mg/d) or codein (30 mg tds).
e. Pain—Dicyclomine (10 mg tds), mebeverine (135 mg
three or four times daily before meals).
f. Motility control—Cisapride (10 mg tds) relieves
distension and corrects intestinal dysmotility. Mosapride
(2.5-5 mg tds) and itopride (50 mg tds) are alternatives.
g. Antidepressants tricyclic compounds (amitryptyline 25-
75 mg/d).
h. Hypnotherapy and psychotherapy.
i. TENS (Transcutaneous Electrical Nerve Stimulation) to
control intractable abdominal pain.
j. Focus on ion channels involved in nociception
(TRPV1—Transient Receptor Potential Vanilloid
Receptor 1 and P2X) offers promise.
Dyspepsia 117
118 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Dysphagia
8
Dysphagia, the term means difficulty in swallowing solids
or liquids and a feeling of sticking of food either in the
upper, middle or lower portions of oesophagus. This
difficulty may be a consequence of (i) painful lesions, (ii)
neurological causes, or (iii) mechanical obstructions at the
oropharyngeal or oesphageal levels, (iv) motility disorders.
The act of swallowing consists of four stages and is a
continuous process, initiated voluntarily and completed by
sequence of (Involuntary) reflexes (Fig. 8.1).
1. Voluntary—Propulsion of food from mouth to pharynx,
through oropharyngeal isthumus.
Fig. 8.1: Normal swallowing mechanism (initiated
voluntarily and completed involuntary/reflex)
2. a. Reflex closure of nasal, oral laryngeal openings into
pharynx, together with pharyngeal peristaltic waves
and elevation of larynx to make way for the bolus.
b. Opening of pharyngo-oesophageal sphincter (upper
oesophageal sphincter).
3. Transmission of food down the oesophagus up to closed
cardiac sphincter by involuntary peristaltic contraction.
4. Opening of the cardiac sphincter.
CAUSES OF DYSPHAGIA
Causes of dysphagia are enlisted in Table 8.1.
Stage One
1. Stomatitis
Stomatitis or inflammation of the mouth is due to the
following causes.
Nutritional deficiencies (Riboflavin, nicotinic acid, Folic acid)
Fiery tongue with ulcers on the sides and lips as well as oral
mucosa and palate, present.
Infections
i. Bacteria (Fusiform bacilli)
ii. Viral (Herpes simplex, Behçet’s syndrome)
iii. Fungus (Candida)
iv. Spirochetes (Vincent’s)
Ulcers with ragged necrotic margins may be found in
the gums, inner side of the cheeks and fauses (vincent
angina). Herpetic stomatitis appears as crops of painful
vesicles which burst subsequently. In Candida infections
(thrush) white sloughs cover the superficial ulcers which
can be detached easily.
Aphthous stomatitis: The aphthae consist of small vesicles
which rupture within 24th forming ulcers. They are
 120 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 8.1: Causes of dysphagia or septic teeth. The mucous membrance is red and dry and
1. Stage One tongue is swollen and furred.
a. Oral lesions like stomatitis; carcinoma
Allergic stomatitis: It may be due to allergic reaction to
b. Sjögren’s syndrome
c. Acute pharyngitis chemicals in the toothpaste, drugs (like antibiotics or
d. Acute tonsillitis or quinsy (Peritonsillar abscess) sulphonamides (Stevens-Johnson syndrome), gold therapy
e. Retropharyngeal abscess or cytotoxics.
f. Pharyngo-oesophageal pouch or diverticulum
g. Cervical spondylitis with anterior osteophytes Blood dyscrasis: Necrotic ulcers in the mouth or pharynx or
2. Stage Two
soft palate are found, in acute leukaemia or agranulocytosis.
A. Plummer-Vinson syndrome Sometimes, ulcerative stomatitis may be associated with
B. Neuromuscular disorders genital ulcers or cutaneous lesions.
a. i. Bulbar paralysis (poliomyelitis; vascular lesions like
posterior inferior cerebellar artery thrombosis and 2. Carcinomatous Ulcer
motor neurone disease)
ii. Faucial diphtheria Epithelioma is usually present over the side of the tongue
iii. Tetanus or upper or under surface or in the floor of the mouth. The
b. Some cases of Parkinson’s disease ulcer appears irregular with raised, everted edges and
c. i. Myasthenia gravis
surrounding induration. Multiple ulcerations or fissure
ii Dermatomyositis
d. Globus hysterieus
carcinoma with leukoplakia are not uncommon.
3. Stage Three
A. Extrinsic compressions 3. Sjögren’s Syndrome
a. Thyroid enlargement - Intrathoracic Dryness of the mouth and eyes, enlarged salivary glands,
b. Mediastinal tumours
c. Aneurysm of Aorta
and arthritis may present as dysphagia due to interference
d. Aberantright subclavian artery (Dysphagia lusoria) with the oral phase of swallowing.
e. Left atrial enlargement
B. Intrinsic causes 4. Acute Pharyngitis
a. Congenital: Diverticula
b. Inflammations It is an infective inflammation of the pharynx associated
i. Reflux oesophagitis with coryza and fever.The discomfort varies from feeling
ii Corrosive oesophagitis of a lump in the throat to dysphagia.The pharynx and palate
iii Candidiasis are red with swollen mucosa. Sometimes, the infections
c. Motility disturbances
spreads to the submandibular space with cellulitis of the
i. Diffuse oesophageal spasm
ii. Nut cracker oesophagus floor of the mouth, extending downwards into the neck
iii. Hypertensive lower oesophageal sphincter (Ludwig’s angina).
iv. Achalasia cardia
v. Lower oesophageal rings 5. Acute Tonsillitis or Quinsy (Peritonsillar Abscess)
d. Scleroderma
e. Neoplasmas: Carcinoma of the oesophagus The onset is sudden with sore throat and fever. The tonsils
f. Oesophageal stricture are swollen with redness and exudate in the crypts. This
4. Stage Four secretion may become confluent over the tonsils. It is almost
a. Hiatus hernia always due to bacterial infections like streptococci.
b. Carcinoma of the fundus of the stomach Quinsy is a complication of acute tonsillitis when
c. Chronic volvulus of stomach infection spreads to the pertiosillar space between the
tonsillar capsule and constrictor pharyngeous muscle. Acute
pain radiating from one side of the throat up to the ear and
extremely painful and of recurrent nature and associated
neck, difficulty in swallowing and high temperature are the
with emotional upsets or inflammatory bowel disease or
presenting symptoms. As the patient cannot open the mouth
Behçet’s syndrome erythema multiforme.
widely, examination may become difficult. However, with
Catarrhal stomatitis: It is secondary to excessive smoking good light, a deep red swelling is seen bulging the affected
or alcohol consumption of spicy food or ill fitting dentures side of the soft palate forwards and pushing the uvula to the
 Dysphagia
opposite side. The abscess is usually situated above and
external to the affected tonsil which lies hidden. The cervical
glands are enlarged and tender.
6. Retropharyngeal Abscess
(Refer to Chapter ‘Dyspnoea’).
7. Pharyngeal Pouch or Zemker’s Diverticulum
The pharyngeal pouch is formed between upper divison of
the cricopharyngeous and the lower divison of
cricopharyngeous which forms cricopharyngeal sphincter
guarding the upper end of the oesophagus (cricopharyngeous
is part of inferior constrictor muscles of the pharynx
dominating in the sphincter mechanism, sphincter is
normally in tonic contraction). A small pouch produces a
feeling of lump in the throat. A bigger pouch will result in
true dysphagia. During a meal the pouch gets filled with
food, overflowing into the pharynx or larynx causing
regurgitation or coughing bouts respectively. A bulging may
be noticed in the neck which may gurgle on swallowing
fluids. A barium swallow confirms the diagnosis.
8. Cervical Spondylitis with Anterior Oesteophytes
(Refer to Chapter ‘Pain in the Extremities’).
Stage Two
1. Plummer-Vinson Syndrome (Sideropenic Dysphagia)
It consists of difficulty in swallowing solids (sticking in the
throat immediately on swallowing) and iron deficiency
anaemia (epithelial changes with glossitis, stomatitis and
koilonychia), usually seen in middle aged women. Serum
iron is low with consequent raised iron binding capacity.
There is a web of mucosal fold at the cricopharyngeal area
besides atrophic changes of the mucosa in the mouth and
upper oesophagus. This atrophy of pharyngeal mucosa may
result in loss of sensibility, disturbing the reflex action of
the second stage of swallowing. A small percentage of
patients may develop postcricoid carcinoma. The diagnosis
is confirmed by a barium swallow and/ or oesophagoscopy
which may reveal the characteristic web (seen in barium
swallow as an anterior indentation over the upper end of
the oesophagus at cricoid cartilage level) and by the
associated haematological abnormalities. An autoimmune
basis is presumed in view of the atrophy of the mucous
membrance.
121
2. Neuromuscular Disorders
Dysphagia may occur due to paralysis of muscles associated
with the first and second stages of swallowing.
Bulbar paralysis: This occurs due to the involvement of the
nucleus ambiguous. This may be acute as in bulbar
poliomyelitis with inability to swallow and cough leading
to regurgitation of fluids through the nose and accumulation
of secretions in the pharynx , causing respiratory obstruction.
This acute bulbar paralysis also occurs in vascular lesions
like thrombosis of the posterior inferior cerebellar artery
resulting in vertigo, dysphagia, ipsilateral paralysis of the
soft palate, and signs of paralysis of cervical sympathetic
fibres (Horner’s syndrome) along with contralateral
hemianalgesia from the neck.
Progressive bulbar paralysis: This type of paralysis in motor
neurone disease involving the palate shortly after the tongue
and the lips results in dysphagia and dysarthria. In pseudo
bulbar palsy weak bulbar muscles and small spastic tongue
lead to dysphagia and dysarthria, as compared to wasted
tongue with fibrilation in progressive bulbar paralysis.
Faucial diphtheria: It is rare now, and results in pharyngeal
paralysis with dysphagia and paralysis of the soft palate with
regurgitation during the second week.
Tetanus: The exotoxins after reaching the anterior roots of
spinal cord via the peripheral nerves induce spasms and
dysphagia may occur early due to spasm of muscles of
deglutition.
Parkinson’s disease (Refer Chapter ‘Fatigue’).
Myasthenia gravis: The cardinal symptom is abnormal
muscular fatiguability. Though occur muscle are involved
characteristically, the weakness of the muscles concerned
with the first and second stage of swallowing may result in
difficulty to swallow. This simple upper dysphagia may be
intensified as the day advances.
Dermatomyositis: In this, the weakness of the pharyngeal
muscles may account for dysphagia. Evidence of disease
elsewheremay be obviously present (Refer to Chapter
‘Polyarthritis’).
In dysphagia, due to neuromuscular causes, the difficulty
arises with the liquids (which require more rapid action)
and solids to a lesser extent (needing powerful action) than
semisolid soft foods.
Globus hystericus: The patient is usually a woman with a
hysterical personality. The usual complaint is persistent
 122 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
sensation of a lump the throat rather than difficulty or
discomfort during swallowing. This sensation is due to
spasm of the upper oesophageal sphincter or referred
sensation from swallowed air in lower oesophagus. It is an
expression of some emotional disturbance associated with
psychological causes. Sometimes, this engenders phobia
leading to an obession of inability to swallow.
Stage Three
Mechanical Obstruction of Oesophagus
The oesophagus or gullet is about 25 cm long and begins
opposite the cricoid cartilage at 6th cervical vertebra level
as a continuation of pharynx and ends at the 9th thoracic
spine level. Oesophageal dysphagia may result from
a. Extrinsic compressions by structures located in relation
to the oesophagus like mediastinal tumours or vascular
anomalies
b. Intrinsic pathology of oesophagus like strictures and
foreign bodies.
Extrinsic Causes
Thyroid enlargement—Intrathoracic (Refer to Chapter
‘Goitre’).
Mediastinal tumours (Lymphomas, metastates, thymoma)
may involve structures like trachea, superior vena cava or
recurrent laryngeal nerve before a mobile structure like
oesophagus is compressed causing dysphagia.
The vascular causes like aortic aneurysm (Refer to
Chapter ‘Chest Pain’) or aberant right subclavianartery
arising from the left side of the aorta traversing posterior to
the oesophagus may compress, resulting in mid-oesophageal
dysphagia.
Dysphagia lusoria connotes difficultyin swallowing due
to vascular anomalies.
Left Atrial Enlargement
It occurs mostly posteriorly and later to the right, assuming
huge size sometimes (giant left atrium). The classical
example is mitral valvular disease. Radiology is of immense
value in the diagnosis. The posterior enlargement is
appreciated in the right anterior oblique view with barium
swallow, when diminished retrocardiac space and posterior
displacement of the barium filled oesophagus, are seen. The
enlargement left atrium may cause straightening of the left
border in the posteroanterior view. Giant left atrium appears
as a distinct density within the cardiac shadow extending
beyond the right atrial border in PA view (a double right
cardiac contour with upper half by the left atrium and lower
half by the right atrium may be formed or sometimes the
entire right border by the left atrium). The left atrium
enlargement is also confirmed by the ECG which shows
wide and notched P waves in L1 L2,A VL,A VR leads.
Dysphagia is rarely a presenting symptom, due to pressure
on oesophagus by an enlarged left atrium.
Intrinsic Causes
Oesophageal diverticula: Diverticula may develop from the
anterior wall of the mid-oesophagus by the traction due to
adhesions between inflamed hilar glands and oesophagus.
Sometimes epiphrenic type, congenital in origin may be
present proximal to hiatus. Though they are asymptomatic,
dysphagia, coughing episodes, a pulling sensation on the
trachea during swallowing, and retrosternal discomfort are
presenting features.
When inflammation occurs it may cause narrowing of
the lumen. Generally, it is an incidental radiological finding
in a barium study.
Epiphrenic type may result in dysphagia. A sensation of
pressure in the lower oesophagus after a meal or substernal
pain, and intermittent vomiting are the usual manifestations.
Oesophagitis or localised mediastinitis may develop. Typical
radiological apparance of the pouch may be demonstrated
by barium swallow.
Inflammations reflux oesophagitis: Reflux of acid peptic juice
into the lower part of the oesophagus results in inflammation
or oesophagus, due to incompetent lower oesophageal
sphincter as seen in hiatus hernia, pregnancy or obesity
(Refer to Chapter ‘Chest Pain’).
Corrosive oesophagitis: Similarly oesophagitis may occur
from swallowing of corrosives which most often may lead
to oesophageal stenosis.
Barrett’s oesophagus: It represents healing of oesophagitis
by replacing the normal squamous epithelium with columnar
epithelium. Dysphagia or pyrosis and radiographic evidence
of discreet ulcer of the gullet or a stricture, are suggestive,
but confirmed by endoscopy and biopsy.
Candidiasis Refer to Chapter ‘Pyrexia of Unknown Origin’.
Primary oesophageal dysmotilities (Motility disturbances)
i. Diffuse oesophageal spasm (corkscrew oesophagus):
Oesophageal spasm results in intermittent dysphagia
for liquids and solids and gets aggravated by ingestion
of cold liquids or angina like retrosternal pain. The
 Dysphagia
pain may be spontaneous or can occur with swallowing.
The tertiary contractions are irregular and of
nonpropulsive nature. This may be due to reflux
oesophagitis, obstruction at the cardia, diabetic
neuropathy, aging or functional. The barium swallow
picture shows different contours of lower oesophagus
with multiple areas of segmental spasm described as
crockscrew or curling due to disordered motility.
Manometric results show repetitive contractions
spontaneously with deglutition, which are mostly
nonperistaltic. The pressure of the lower oesophageal
sphincter may be normal or high(more than 45 mmHg).
ii. Nut cracker oesophagus: The motility is regular and
peristaltic but of longer duration and higher amplitude
than normal. This is said to be an early form of diffuse
oesophageal spasm.
iii. Achalasia cardia: It is due to decreased peristalsis and
obstruction at the lower part of the distal oesophagus.
The degeneration of ganglion cells of the Auerbach’s
plexus with paucity of cells in the wall of the
oesophagus and lower sphincter results in motor
disorder of the smooth muscles of oesophagus, with
failure of complete relaxation of the cardiac sphincter
(relaxation normally occurs with each peristalsis). The
consequent absence of peristaltic activity and increased
pressure in the lower oesophageal sphincter with absent
relaxation, lead to difficulty in swallowing of both
liquids and solids. The dysphagia may be intermittent
initially with sensation of food sticking or fullness at
the xiphoid cartilage level. Continued oesophageal
dilatation (megaoesophagus) results in increased
hydrostatic pressure which overcomes the high
sphincter pressure and facilitates the passage of food
into the stomach as the patient learns to drink more
fluids forcibly and quickly. The other symptoms include
regurgitation, retrosternal pain, independent of
swallowing, recurrent aspiration pneumonia or weight
loss. The diagnosis is confirmed by the characteristic
radiological appearances which show absence of
propulsive waves with dilated oesophagus and beak
like narrowing of the distal oesophagus 1 to 3 cm long
just above the diaphragm. Oesophageal manometry
demonstrates increased intraoesophageal pressure and
incomplete relaxation of the hypertensive lower
oesophageal sphincter. Endoscopy with pre-endoscopic
aspiration and lavage is mandatory.
iv. Lower oesophageal rings (Schatzki’s rings): A
classical ring is 4 mm or less in thickness and is covered
by squamous epithelium on the upper side and
123
columnar epithelium on the lower side. Some of them
are mucosal in nature. When the transverse diameter
of the ring is less than 12 mm, dysphagia occurs.
Dysphagia may be intermittent initially and becomes
continuous later. It may be associated with oesophagitis
and odynophagia (pain during deglutition). Fiberoptic
endoscopy demonstrates the rings.
Scleroderma: The lower oesophagus is usually involved and
is associated with loss of peristalsis and sphincter tone.
Dysphagia is more often due to peptic stricture resulting
from accompanying reflux oesophagitis rather than by
abnormalities of motility of oesophagus. The other
characteristic clinical features enable the diagnosis. (Refer
to Chapter ‘Polyarthritis’.)
Neoplasms—carcinoma of the oesophagus: The most
common initial complaint is dysphagia of gradual onset for
solid foods with increasing severity. Later inability to
swallow liquids and regurgitation of food occurs due to
stenosis. About of coughing following the ingestion of food,
retrosternal pain or back pain, (due to spasm or spread of
the tumour through the wall of the oesophagus) and loss of
weight are the other accompanying features. Aspiration
pneumonia or fistula into the trachea or bronchus or
metastatic cervical lymphadenopathy may be encountered.
Most of the tumours are squamous cell types although half
the cases may be adenocarcinomas in the lower end, and occur
either in the upper, middle or lower third, of the oesophagus.
It may be associated with Barrett’s ulcer, Plummer-Vinson
syndrome, achalasia, benign strictures and smoking.
The diagnosis is confirmed by demonstrating an irregular
outline of the wall of the oesophagus with a characteristic
rat tail narrowing and hold up of the barium above
(Fig. 8.2). Sometimes luminal defects may be present.
Fiberoptic oesophagoscopy with biopsy and brushings are
mandatory. CT scan of oesophagus can delineate extra-
oesophageal extension.
Oesophageal stricture: It is either due to inflammation as in
longstanding oesophagitis (bengin) or carcinoma of the
oesophagus. The dysphagia is progressive leading to weight
loss.
Stage Four
Hiatus Hernia
Hiatus hernia is herniation of intra-abdominal oesophagus
and part of the stomach into the thorax through oesophageal
hiatus in the diaphragm. There are three type of hiatus hernia.
 124 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 8.2: X-ray examination with a thickened barium swallow
showing concentrically narrowed lumen of the lower third of
the oesophagus diagnostic of carcinoma of the oesophagus
Congenital short oesophagus: It is very rare. The stomach
is drawn up into the thorax due to shortening of oesophagus.
Sliding hernia (Oesophagogastric): This type is more common.
A portion of the stomach with cardia and intra-abdominal
oesophagus herniate directly into the chest. This may be due
to delay in the descent of the stomach or being drawn up into
the chest by short oesophagus which is placed above the
diaphragm. Sometimes, the oesophagus may become
shortened due to scarring from chronic oesophagitis. The
stomach may actually slide freely in and out of the thorax
with postural changes or after a large meal. The cardiac
sphincter is often incompetent and free regurgitation of the
acid peptic juice occurs resulting in reflux oesophagitis. Heart-
burn after food or recumbency, regurgitation of bitter tasting
fluid into the mouth and dysphagia due to inflammatory
oedema are the common manifestations.
Rolling hernia (Paraoesophageal): A portion of the fundus
of the stomach passes through the diaphragmatic opening
alongside the oesophagus with the cardia being intact and
competent below the diaphragm. This type is less common
and seen in obese people. Reflux oesophagitis does not occur
although a complaint of substernal discomfort or gaseous
eructations may be forthcoming. Dysphagia, if present, is
due to mechanical obstruction. (Refer to Chapter ‘Chest
Pain’.)
Carcinoma of the Fundus of the Stomach
Anorexia, postprandial pain, vomiting, and weight loss
appear before dysphagia. But in some cases dysphagia may
be the only earliest symptom like that of a growth in the
lower end of the oesophagus. The tumour may be felt on
palpitation towards left of the midline and appears as though
descending from left costal margin. Radiology is diagnostic
as the outline formed by the gas under the diaphragm is
irregular in shape and reduced in size and growth may be
seen through gas bubble.
Chronic volvulus of stomach: May be asymptomatic or noisy
gastric peristalsis (relieved by lying down), intermittent
crampy pain, dysphagia may occur in chronic rotation
(volvulus).
CLINICAL APPROACH
To evaluate dysphagia, interrogation with relevant questions,
based on the knowledge of underlying pathophysiology of
deglutition, is very pertinent. The difficulty in swallowing
may range from, local discomfort in the throat or food
sticking during swallowing to actual hold up of the food,
arising either from disease or dysfunction.
History
• Age and sex: Achalasia is more common in 3rd decade.
The post cricoid web with iron deficiency anaemia may
be seen in women in the 3rd and 4th decades. Reflux
oesophagitis and hiatus hernia are more common in
females and carcinoma of the oesophagus in men in the
5th decade.
• Onset: It is acute in vascular lesions or gradual as in
malignancy. One has to find whether it is intermittent or
constant right from the beginning. Oesophageal
dysphagia due to primary dysmotilities tend to be
intermittent whereas mechanical obstructive lesions
produce constant and progressive dysphagia.
• Relation to type of food:
a. Difficulty in swallowing solids alone may be
suggestive of mechanical defects with partial
obstruction.
b. If the difficulty is more for fluids than solids or both
from the onset, it indicates achalasia.
c. Difficulty to swallow solids initially progressing to
semisolids and liquids finally, is characterstics of
complete obstruction.
d. Difficulty to swallow liquids fast is of neurological
origin.
 Dysphagia
• Site and type of distress: Is it painful or painless? Lesions
of the mouth and pharynx may be usually associated
with pain. Similarly, hiatus hernia with oesophagitis may
have pain in the substernal region. Gagging type of
distress is more common in oropharyngeal dysphagia
as against sensation of food sticking in the oesophageal
dysphagia, which may be in the upper, middle or lower
oesophageal portions.
• Time of occurrence of dysphagia:
a. If synchronous with the passage of bolus, suspect
oropharyngeal lesions.
b. If difficulty is with the commencement of deglutition,
laryngeal or cervical oesophageal lesions are likely.
c. Five seconds after deglutition, oesophageal lesions
likely.
d. Fifteen seconds after deglutition, suggestive of lower
oesophageal lesions.
• Influencing factors: Effect of posture, types of food, and
emotional upsets are the usual precipitating factors (hot
drinks or alcohol make benign stricture worse). Antacids
may alleviate dysphagia.
• Associated symptoms:
a. Hoarseness—If present, the lesion may be in the
larynx or may extend to recurrent laryngeal nerve.
b. Cough—If cough and dysphagia are associated
together, it may be due to tracheal or mid—
oesophageal compression. If cough occurs with each
swallow, it is suggestive of ineffective closure of the
larynx. If it occurs little later after swallowing, it is
suggestive of pharyngeal pouch or achalasia, due to
regurgitation and entry of contents into larynx
initially, with subsequent aspiration pneumonia.
c. Nasal regurgitation and nasal twang—Suggest bulbar
paralysis.
d. Dysphagia—if associated suggestive of progressive
or pseudo bulbar palsy.
e. Foetor or halitosis—May be due to oesophageal
pouch or carcinoma.
f. Vomiting—In achlasia or oesophageal diverticula,
regurgitation of food into the mouth after swallowing
may occur. Vomiting is suggestive of total obstruction
of oesophagus and haematemesis may occur due to
oesophagitis or a mural growth.
g. Pain—May be spontaneous as in epigastric region
in achalasia, or substernal region (burning in
oesophagitis; angina like in hiatus hernia.)
Odynophagia (discomfort or pain induced by
swallowing) as in diffuse oesophageal spasm.
125
Physical Examination
General Examination
a. Anaemia and koilonychia as in Plummer-Vinson
syndrome
b. Weight loss
c. Cervical lymphadenopathy-Indicates advanced stage of
disease
d. Examination of hands for features of scleroderma
Local Examination
a. Mouth and throat for stomatitis, carcinoma of the tongue,
pharyngitis or tonsillitis.
b. Movements of the neck for cervical spondylitis.
c. Ask the patient to swallow some water and observe
i. Swallowing efforts (with ease or difficulty)
ii. Any bulging in the neck which gurgles on drinking
iii. Nasal regurgitation.
iv. Regurgitation into the mouth, or regurgitating on
bending or turning the head.
d. Without water ask the patient to swallow as many times
as possible for 10 seconds. (Normal swallowing
accomplishes 3 to 5 swallows).
e. Examination of the larynx for evidence of pooling of
saliva or residual bolus in the pyriform fossa or paralysis
of the vocal cord. This can be detected by indirect
laryngoscopy.Vocal cord dysfunction impairs protective
coughing reflex and fails to clear the bolus from the
airway effectively or the bolus may directly pass into
the trachea.
Systemic Examination
a. Chest for any evidence of
i Mediastinal growth (superior vena cava obstruction,
symphathetic trunk involvement, atelactasis,
D-Espine’s sign), or
ii. Cardiac lesions like aneurysm of aorta or mitral
stenosis.
b. Abdomen—Palpate for any epigastric tenderness or
mass.
c. CNS for evidence of motor neurone disease, or
myasthenia gravis. A careful assessment of symmetrical
movement of motor activity and strength of the lips, jaw
and tongue must be done by examining V, VII, IX, X,
and XII cranial nerves.
Investigations
1. Haematology—Full blood counts to be done(if necessary
serum iron and iron binding capacity).
 126 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
2. If indicated thyroid function tests.
3. Blood urea and electrolytes if vomiting is a prominent
feature.
4. Radiology (only method to identify oesophageal disease
due to paucity of external signs).
a. Barium swallow: In achalasia, disordered peristasis
and obstruction of cardia with oesophageal dilatation.
In cancer oesophagus, the radiogram shows the
position of the growth with the irregular long luminal
defect and a dilated oesophagus containing barium
and food residue, above the obstruction. In dysphagia
lusoria, a rectangular notch may be found in the
posterior part of the upper oesophagus in right
anterior oblique position. A double contrast oeso-
phagogram is useful.
b. Trendelenburg’s position: Barium swallow study in
this position is useful to decide whether mchanical
obstruction or dismotility exists. Absence of
paristalsis is indicated when the barium continues to
remain in the oesophagus till the position is tilted
upright. Narrowing of the lumen or intraluminal
pathology if present, further evaluation is to be done
by endoscopic and biopsy studies to differentiate
inflammatory and malignant lesions (Radio-opaque
solid marshmallow is prefered since dysphagia is
usually for solids initially).
c. Fluoroscopy: To visualise barium flow and the
peristalsis as the bolus moves downwads.
d. Videofluroscopy can depict the oropharynx and the
passage of bolus to the oesophagus and also detect
lesions like oesophageal rings and mucosal defects.
e. X-ray of the chest to detect aneurysm or mediastinal
tumours. (Benign tumours show circumscribed
opacity whereas malignant tumours show ill-defined
lesion or widened mediastinal shadow). Sometimes,
hiatus hernia may be suggested by the presence of
gas-filled portion of the stomach above the level of
the diaphragm especially in the lateral views, since
the cardiac shadow may obliterate hernial shadow
in the anteroposterior view.
5. Endoscopy: Fiberoptic oesophagoscopy, gastroscopy.
6. Biopsy of the lesions for exfoliative cytological
examinations to assess the severity of oesophagitis and
rule out ulcers, strictures and malignancies.
Special Investigations
As traditional barium swallow may not be very helpful in
diagnosing gastro-oesophageal reflux disease and
oesophageal motility disorders, following special investiga-
tions may be entertained.
a. Tests to diagnose gastro-oesophageal reflux: One needs
to do this test, if endoscopy and histology establish
oesophagitis.
i. 24 h pH monitoring: A pH probe is kept 5 cm above
lower oesophageal sphincter and a 24 h record is
analysed. The test is said to be positive, if the total
number of reflux episodes are more than four lasting
longer than 5 min and less than 50 min each.
ii. Bernstein test—Saline and N/10 hydrochloric acid
instilled alternatively through a Ryle’s tube in
oesophagus about 30 cms from nares. If the heart
burn is reproduced on acid instillation and not
produced with saline, it is diagnostic that the
symptoms are due to gastro-oesophageal reflux
disease. This is a sensitive test (88%) and less
cumbersome.
b. Tests to diagnose dysmotility
i. Manometric studies: Intraluminal pressures are
measured at various sites by external transducers
attached to catheters positioned in the oesophagus
and continously perfused with water. Absence of
peristalsis in the lower 2/3rd of oesophagus and an
increased lower oesophageal sphincter pressure more
than 45 mm of Hg is suggestive of achalasia.
Simultaneous contractions of lower 2/3rds of
oesophagus (prolonged duration of a contraction of
more than 6s) with intermittent normal peristalsis
and high resting pressure of lower oesophageal
sphincter of more than 50 mm of Hg is diagnostic of
diffuse oesophageal spasm. Manometric evaluation
is useful especially when X-ray study and endoscopy
are noncontributory and also to detect motor
disorders.
ii. Provocative test: Pain is provocated with edropho-
nium (80 ug/kg IV bolus followed by ten 5 ml
swallows spreading over 5 min). Though it is useful
in the diagnosis of oesophageal motility disturbances
it is better to exclude coronary artery disease before
undertaking this test.
c. Ultrasound: Submental imaging by holding the
transducer beneath the chin and rotating it to 90°
facilitates to understand the dynamics of swallowing.
d. Scintigraphy: Radionuclide scanning during the inges-
tion of radioactive bolus coupled with videofluoroscopy
offers valuable information on the movement of the
bolus.
 Dysphagia
e. CT: May be used to detect brain lesions accounting for
dysphagia.
f. MRI if necessary.
TREATMENT OF DYSPHAGIA
The categories of causes of dysphagia, be it oral, pharyngeal
or oesophageal, must be initially screened to detect whether
it is of neuromuscular origin or mechanical narrowing,
motility disorder before executing the actual therapeutic
modalitis. The following enquiries are imperative in this
endeavour, besides other interrogations (vide supra).
1. Is it a true dysphagia occuring within 15 seconds ? or
pseudo dysphagia occuring much later ?
2. Is it continuous or intermittent ?
3. Is it more for liquids than solids ?
4. Is it associated with pain or any other symptom ?
Symptomatic Treatment
Relief is offered in the meanwhile as per the needs.
1. If the dysphagia is more for liquids, soft solid food may
be given. Similarly if the dysphagia is more for solids,
liquids are to be given.
2. Encourage proper chewing before swallowing. If the
mastication is painful due to oral lesions, analgesic
lozenges and/or antiseptic mouth gargles like povidone-
iodine may be prescribed.
3. Ryle’s tube feeding is beneficial for dysphagia of
neurological origin (pharyngeal dysphagia).
4. Total parenteral nutrition may be required in some cases.
5. Laryngeal spill over may give rise to respiratory
symptoms like bronchitis which is treated with codein,
pholcodein with or without antibiotics. Bronchodilators
may be added if there is airflow obstruction.
6. Gastrostomy may be undertaken to facilitate feeding if
there is progressive loss of weight.
7. Cricopharyngeal myotomy (external division of
cricopharyngeal muscle) in neuromuscular disorders, as
in motor neurone disease may be beneficial.
Specific Treatment for Specific Disease
Stage One: Disorders of Voluntary Propulsion
(Oral/Oropharyngeal)
Stomatitis
a. Nutritional deficiencies are corrected with riboflavin,
nicotinic acid, folic acid and vitamin B12.
b. Fusiform bacilli causing ulcerative stomatitis respond
to metronidazole (400 mg t.d.s for 4 to 7 days) or
spirocheates with penicillin.
127
Candidiasis is treated with nystatin tablets (5,00,000
units 6th hourly for 4 days) or kept in the mouth as long
as possible . Gentian violet, (1% aqueous solution) may
be applied locally. Fluconazole (150 mg single dose)
may be consodered.
Herpes simplex is treated with acyclovir.
c. Aphthous stomatitis is treated with hydrocortisone
hemisuccinate lozenges (2.5 mg t.d.s.) with or without
anaesthetic lozenges. Mouth washes may be
supplemented. Vermisol (50 mg b.d. for 3 days and
repeated twice at intervals of 2 weeks) is beneficial.
d. Other forms of stomatitis are treated appropriately.
Oral carcinomas: Treatment includes radiation therapy,
surgical resection or both.
Xerostomia: Use of chewing gums and acidulated sweets
help stimulation of salivary secretion. Dehydration or
Sjögrens may be treated accordingly (Refer polyartnritis).
Acute pharyngitis: Antibiotics are indicated if necessary.
(Throat swabs may be taken). Ludwig’s angina which is
rare nowdays needs incision and drainage.
Tonsillitis: Complete bed rest, appropriate antibiotics like
appropriate penicillins or erythromycin for about 5-7 days
administered. Lozenges are not routinely prescribed.
In quinsy if pain persists in spite of treatment, it indicates
peritonsillar pus formation, which has to be opened.
Retropharyngeal abscess: Acute abcess is to be opened and
drained.
Pharyngeal diverticulum: Treatment includes diverti-
culectomy and myotomy of the cricopharynges muscle.
Cervical spondylosis: Conservative treatment with
analgesics and cervical collar indicated. (Refer to Chapter
‘Vertigo’.)
Stage Two
Pharyngeal dysphagia
• Plummer-Vinson syndrome: The associated anaemia
should be treated with iron, Vitamin B complex and well
balanced diet may be supplemented (Refer to Chapter
‘Fatigue’).
• Bulbar paralysis: (Refer to Chapter Paraplegia—
Poliomyelitis).
• Diptheria: Nowadays it is rare. It is managed by
administering antitoxin 20,000-40,000 units IM after
testing for hypersensitivity. Benzyl pencillin (600 mg
every 6th for 7 days) or erythromycin (500 mg 6th hourly
for 7 days) is given.
 128 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Tetanus: Prevention is all the more important. If risk is
suspected 250 units of human tetanus immunoglobulin
and also tetanus toxoid should be given. The later is
repeated twice after 1 month and 6th months. Treatment
includes administering antitoxin 3000 units IV (after
testing) and 3000-10,000 units of human tetanus
immunoglobulin i. m., besides benzyl penicillin (600
mg 6th hourly), surgical wound care, enough hydration
and nutrition. Muscle spasms should be controlled with
IV diazepam (10 mg 6th hourly). Total daily dose may
be up to 120 mg, when respiratory assistance is usually
necessary (artificial ventilation). The other drug used is
pentothal (2 to 4 g day for two days). The risk of asphyxia
is combated by tracheostomy to prevent spasm of the
glottis.
• Myasthenia gravis (Refer to Chapter ‘Paraplegia’).
• Dermatomyositis (Refer to Chapter ‘Paraplegin’).
• Globus hystericus: The underlying psychological
disturbance must be evaluated and alleviated by
reassurance. Anxiolytics may be of value.
Stage Three
Oesophageal dysphagia (Motility or Obstructive Disorders)
Extrinsic
• Thyroid enlargement (Refer to Chapter ‘Goitre’).
• Mediastinal tumours: Surgical exploration provides
histologic diagnosis and a possible surgical cure. The
treatment of malignant tumours includes surgical
removal combined with radiotherapy and/or
chemotherapy. Some malignant tumours respond very
well to radiotherapy alone by reducing its size but the
improvement may be temporary.
• Aneurysm of aorta: Thoracic aneurysm is better treated
conservatively unless progressive distension is evident,
since surgical correction carries a high mortality.
• Dysphagia lusoria: Dysphagia due to oesophageal
compression (at the level of 3rd dorsal vertebra) by the
abnormal vascular (vascular rings) or other structures is
relieved by severance of the affecting structure.
• Left atrial enlargement: The underlying cause of left
atrial enlargement is to be identified and treated
accordingly.
Intrinsic
• Oesophageal diverticula: The treatment consists of
removal of diverticulum in more severe cases.
Cricopharyngeal myotomy for upper diverticulum may
be helpful. Correction of motor abnormalities of the
oesophageal sphincters prevents dysphagia, progressive
regurgitation and aspiration.
• Reflux oesophagitis: H2 blockers, Omperzole (PPI) and
antacids are initially given. Metoclopramide (5-10 mg
6th hourly) may be added, if necessary. A clear 4h
interval is necessary between dinner and bed time. Head
of the bed is better kept elevated. Smoking and alcohol
are to be avoided (Refer to Chapter ‘Chest Pain’).
The other causes of oesophagitis like Candida
albicans treated with nystatin (1-3 million units 6th
hourly), flucanazole (100 mg/d for 2 wks) and herpetic
infections with acyclovir (200-400 mg five times a day).
• Corrosive oesophagitis: It is treated symptomatically,
neutralize appropriately, besides supplementing with
demulcents and analgesics.
• Motility disturbances:
a. Disorders associated with oesophageal spasm. The
treatment consists of minimising contractions by
means of acid suppression, sublingual nitrogycerine
(0.4 mg) or nifedipine (10-20 mg before meals) or
dicyclomine (10 mg). Effective specially for
hypertensive.
Lower oesophageal sphincter (LES). If unresponsive,
oesophageal dilatation or myotomy is considered.
b. Achalasia cardia: Pneumatic dilatation of the lower
oesophageal sphincter is advocated. if it is not
possible or unresponsive, Heller’s operation (cutting
of the anterior circular muscle above the LES) is
considered. Early achalasia may be given a trial with
calcium channel blockers, or nitrates. Dicyclomine
hydrochloride (10 mg tds) or propantheline
(10 mg tds) may be helpful.
c. Lower oesophageal rings: Bougienage offers relief.
• Scleroderma: The therapy includes acid suppression and
metoclopramide. Optimum luminal diameter is to be
maintained by dilatations as often as necessary. (Refer
to Chapter ‘Polyarthritis’.)
• Carcinoma of the oesophagus: High voltage radio-
therapy is preferred for upper and middle portion of the
oesophagus. However, for the lower third, oesophago-
gastrectomy is advocated. In some cases, preoperative
radiotherapy followed by surgery is presumed to enhance
the results. Palliation (bougies, endoscopic insertion of
a tube through the growth for feeding or laser therapy)
is adopted in unsuitable cases.
• Oesophagal stricture: The treatment consists of bougien-
age as frequently as possible. If unsatisfactory, surgical
treatment like oesophagectomy or endoscopic insertion
of tube is considered.
Dysphagia 129
130 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Dysphagia 131

Stage Four radical gastrectomy may be necessary. Adjunct therapy with

cytotoxic drugs increases survival rate.
Hiatus hernia: Medical therapy with esomeprazole (40 mg
Chronic volvulus of stomach: If it is associated with
morning and 20 mg at bed time); Alginic acid (200 to 500
Paraoesophageal hiatus hernia (organo-axial volvulus) repair
mg b.d.), Itopride (150 mg/day) suffices for sliding hernia.
of hernia and anterior gastropexy is undertaken. If it is due
If unresponsive, surgical correction may be necessary as in
to eventration of diaphragm (mesenterio-axial volvulus)
paraesophageal hernia.
gastrocolic ligament is divided to restore normal position
Carcinoma of the fundus of the stomach: Subtotal radical or of stomach (as colon rises) and fostan it by gastropexy.
 Chapter
Dyspnoea
9
Dyspnoea is an awareness of breathing associated with
distress. This subjective feeling of uncomfortable breathing
induces an increased respiratory effort disproportionate to
the physical stimulus. Normally breathing is without any
conscious effort. The increased respiratory effort
experienced by normal people on vigorous exercise is
proportional to the physical activity without any distress as
such. Mild dyspnoea is a symptom whereas severe dyspnoea
exhibits objective evidence of increased effort of muscles
of respiration and accessory muscles. The dyspnoea which
develops on exertion or at rest is usually organic, whereas
dyspnoea which occurs only at rest and is absent on exertion
is suggestive of functional origin. The difficulty in breathing
may be felt during inspiration due to obstruction of the upper
airways (inspiratory dyspnoea) or it may be felt during
expiration due to obstruction of the lower airways
(expiratory dyspnoea). It is sometimes seen in both
inspiration and expiration as in air hunger or metabolic
acidosis (renal asthma). This acidotic breathing, which
appears laboured, may not be accompanied by dyspnoea.
The onset of dyspnoea may be sudden or gradual. It may
be continuous or paroxysmal. Generally acute dyspnoea may
occur all of a sudden which may be continuous or
paroxysmal, whereas the chronic form will be slowly
progressive and continuous.
A. Dyspnoea is graded according to functional capacity for
cardiac patients (New York Heart Association NYHA):
Grade I—No limitation of ordinary physical activity.
Grade II—Ordinary physical activity slightly limited by
dyspnoea.
Grade III—Considerable limitation of physical activity
and comfortable at rest.
Grade IV—Severe limitation of activity and dyspnoea
is present at rest.
B. The special types of dyspnoea are:
• Orthopnoea: Dyspnoea which occurs in recumbency
and is relieved by assuming upright position. It is
suggestive of left heart failure, critical mitral stenosis,
sometimes bronchial asthma and bilateral
diaphragmatic paralysis (instant orthopnoea).
• Paroxysmal Nocturnal Dyspnoea: Dyspnoea occurs
suddenly during night with a feeling of suffocation
making the patient get out of the bed to seek more
air near a window. It is followed by repetitive cough,
wheezing and restlessness (cardiac asthma). It is due
to interstitial pulmonary oedema secondary to
subacute or chronic cases of left ventricular failure.
In severe attacks of cardiac asthma patient may notice
bubbling in the chest and may produce copious,
frothy blood-stained sputum (pulmonary oedema—
a manifestation of alveolar oedema). In chronic
pulmonary disease which awakens the patient during
night, the cough precedes dyspnoea unlike left
ventricular failure.
Dyspnoea may present with progressive severity as
(a) exertional dyspnoea, (b) orthopnoea, (c)
paroxysmal nocturnal dyspnoea, (d) breathlessness
at rest, and (e) acute pulmonary oedema. This
sequence is particularly significant in cardiac
subjects.
• Trepopnoea: Dyspnoea occurring only in either of
the lateral position.
• Platypnoea: Dyspnoea which occurs in upright
position.
C. Dyspnoea may have to be differentiated from
1. Cheyne-Stokes respiration encountered in heart
failure or neurological disorders which awaken the
patient at night during the hyperventilation phase of
 Dyspnoea
the periodic stimulation. The patient may complain
of dyspnoea, which may be mistaken for paroxysmal
nocturnal dyspnoea.
2. Tachypnoea which connotes increased rate of
respiration.
3. Hyperpnoea where the volume of ventilation is
increased with less or absent subjective distress (like
sighing respirations which are long drawn at frequent
intervals due to psychogenic impulses).
4. Sleep apnoea syndrome in which the patients develop
upper airways obstruction when they go to sleep and
thus desaturate, because of the narrow and floppy
airways. These apnoeas are terminated by brief
arousals. The cycle of arousal and apnoea continues
throughout the night.
MECHANISMS OF DYSPNOEA
Different mechanisms operate in different clinical settings
like
1. Airway obstruction
2. Decreased lung volumes
3. Decreased lung compliance, i.e. elastic properties of the
lung and chest wall
4. Pulmonary embolism
5. Elevated left atrial pressures
6. Neuromuscular weakness.
The consequent (a) defective ventilation, (b) ventilation
perfusion imbalance and (c) impaired exchange of gases in
the lungs, disturb the blood gas tension (reduced PO2,
increased PCO2 and low arterial pH) and increase the
respiratory effort.
Hypoxia (< PO2) occurs in (1) under-ventilation or
altered distribution of ventilation, (2) impaired diffusion,
(3) ventilation perfusion mismatching when the ventilation
is low in relation to perfusion, (4) cardiac shunts, (5) anaemia
when oxygen capacity of the blood is reduced and
(6) breathing air with poor oxygen as in high altitudes.
Hypercapnia (>PCO2) occurs in conditions associated
with (1) under-ventilation and (2) low ventilation perfusion
ratio. This rise in PCO2 further aggravates hypoxaemia.
In addition to the respiratory acidosis where the PCO2
and the carbonic acid concentration of the blood increase
with fall in pH, a metabolic acidosis occurs, as in diabetic
ketosis or uraemia, due to production or ingestion of acids
other than carbonic acid or reduction of concentration of
bicarbonate with fall of pH. This high concentration of
hydrogen ions (low pH) stimulates the respiratory centre.
Thus the work of breathing is influenced by
133
a. Chemical stimulation: When hypoxia, hypercapnia and
low pH occur, they stimulate the aortic and carotid
chemoreceptors as well as the respiratory centres in the
brainstem. The PCO2 and pH changes may also affect
the central chemoreceptors in the medulla which
contribute to increased dyspnoea.
b. Pulmonary receptor stimulation: The compliance of the
lung is reduced in restrictive lung diseases or cardiac
diseases with dilation of pulmonary veins and capillaries
due to increased flow or pressure. This stimulates the
local pulmonary stretch receptors and juxta pulmonary
capillary or receptors. This results in exaggerated vagal
reflexes of Hering-Breuer, which limit the inspiration,
as each receptor has its afferent pathway through vagus.
Other pathways concerned with dyspnoea constitute
afferent somatic nerves from the respiratory muscles and
afferent fibres in the phrenic nerves to the higher cortical
centres.
c. Reduced vital capacity due to mechanical hindrances to
respiration like pleural effusion, ascites, gross obesity,
and flatulence.
d. Theory of length tension inappropriateness: This theory
holds, that misalignment of muscle spindles in the
respiratory muscles leads to a sensation of insufficient
breath as there is disturbance of relationship between
the force required for lung expansion and the amount of
expansion that is achieved, i.e. the force required is
inappropriately large in relation to the volume achieved
(length/tension relationship).
e. Increased airway resistance as in (a) bronchial narrowing
due to encroachment of the lumen by mucus or oedema
and increased bronchial smooth muscle tone as in asthma
or (b) loss of lung parenchyma with consequent loss of
support by traction for the airways as in emphysema.
These factors invariably increase the work of breathing
to facilitate movement of air along the airways.
CAUSES OF DYSPNOEA (TABLE 9.1)
I. Cardiovascular
Acute
Left heart failure: One of the most common causes of
dyspnoea is left heart failure. The earliest symptom is
exertional dyspnoea and feeling of distress in supine position
which gets relieved by raising the head with pillows
(orthopnoea). A change in the number of pillows needed
serves as an index of the cardiac status like exertional
dyspnoea in relation to physical activity. During recumbency,
 134 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 9.1: Causes of dyspnoea

Causes Acute dyspnoea (rapid onset) Chronic dyspnoea (progressive or recurrent)

1. Cardiovascular i. Left heart failure i. Congenital heart disease

ii. Left atrial myxoma and ball valve thrombus ii. Valvular heart disease
iii. Pericardial temponade iii. Congestive heart failure
2. Pulmonary i. Tracheal i. Tumours
(a) Obstruction in the ii. Laryngeal ii. Fibrotic stenosis due to post-tracheostomy
upper airways or intubation
(b) Obstruction to lower i. Bronchial asthma i. Chronic bronchitis
airway ii. Ytopivsl rodinophilis ii. chronic asthma
iii. Collapse of teh lung iii. Emphysema
iv. ARDS
(c) Restrictive lung disease i. Spntaneous pneumothorax i. Fibrosis
ii. Diaphragmatic paralysis (both ii. Pneumoconiosis
Hemidiaphragm) iii. Pulmonary alveolar proteinosis
iii. Extrinsic allergic alveolitis iv. Fibrosing alveolitis
v. Sarcoidosis
vi. Diaphragmatic paralysis
vii. Pleural effusions
(d) Infections Aspiration pneumonia Pulmonary tuberculosis
(e) Vascular occlusion Pulmonary embolism Recurrent pulmonary embolisms
(f) Chest wall Trauma Restricted chest movements (e.g. Ankylosing
spondylitis)
(g) High altitudes Acute mountain sickness Chronic mountain sickness (monges disease)
3. Alimentary affections i. Flatulence Hiatus hernia
ii. Retropharyngeal abscess
4. Neurological i. Poliomyelitis Myasthenia
ii. Rabies
iii. Tabetic crises
5. Metabolic i. Diabetic ketoacidosis Renal insufficiency
ii. Renal insufficiency
iii. Certain poisons (methyl alcohol)
6. Psychogenic i. Anxiety state Neuro circulatory asthenia (Da Costa’s
ii. Hyper-ventilation syndrome syndrome)

there is reduced pooling of blood in the periphery and the
blood volume of the thoracic compartment increases. The
failing left ventricle cannot effectively pump the extra
volume of blood and the consequent pulmonary congestion
accounts for dyspnoea. Mechanical interference by elevated
diaphragm also affects the pulmonary ventilation in
recumbency.
The attacks of paroxysmal dyspnoea occurring at night
are probably due to normal nocturnal depression of the
respiratory centre and reduced adrenergic support of the left
ventricular function during sleep in addition to the factors
operating in orthopnoea. The associated bronchospasm
caused by congestion of bronchial mucosa accounts for the
alternate name of cardiac asthma. The abrupt onset of
dyspnoea may last longer, up to 30 min even to get relief in
the upright decubitus unlike immediate relief in orthopnoea.
The acute pulmonary oedema is the severest form of
breathlessness and differs from others in the rapid
development of pulmonary capillary hypertension.
Normally, the pulmonary capillary pressure is 8 mmHg.
When the pulmonary capillary pressure exceeds the plasma
colloid osmotic pressure of 28 mmHg, pulmonary oedema
occurs. This is due to increase in the rate of flow of interstitial
(20 mmHg) and alveolar (25 mmHg) liquid content
exceeding the rate of removal of the same. The former is
related to the functional capacity of lymphatics and the
 Dyspnoea
consequent increased flow of lymph in the lung. The
increased capillary permeability also results in exudation
into the alveoli.
Besides the abrupt severe dyspnoea, there is cough with
expectoration of watery frothy blood-stained sputum. The
patient looks anxious and restless with profuse sweating
and central cyanosis. The distended neck veins, tachypnoea,
noisy respirations or Cheyne-Stokes breathing, tachycardia,
pulsus alternans, cardiomegaly, triple rhythm, crackles and
wheezes are highly diagnostic. The blood pressure may be
raised unless there is cardiogenic shock. Other evidences
of underlying causative conditions like hypertension or
valvular disease (mitral or aortic stenosis) or coronary
disease may be forthcoming.
Differentiation from bronchial asthma may be
occasionally difficult.
The diagnosis may be clinched by
a. the history of previous similar attacks,
b. extreme expiratory difficulty,
c. absence of profuse sweating, cyanosis and signs of heart
disease,
d. presence of hyperresonant and hyperexpanded chest with
more high pitched musical wheezes,
e. X-ray of the chest, and
f. ECG.
The X-ray of the chest in pulmonary oedema shows:
• Diffuse hazy appearance in lower zones (due to oedema
in the interstitial perivascular tissues and accentuated
lung markings of branches of pulmonary vessels)
• Kerley lines (due to oedematous interlobular septa)
• Butterfly like density around the hilum (due to
intermingling of air filled alveoli with fluid filled alveoli)
• Pleural effusions (right side or bilateral)
• Azygos vein and superior vena cava appear enlarged
and the upper lobe pulmonary veins distended
• Enlargement of heart and its individual chambers
ECG shows sinus tachycardia, chamber hypertrophy (left
atrial or left ventricular) or ischaemic changes.
Left Atrial Myxoma and Ball-Valve Thrombus
Myxoma when mobile and pedunculated, may obstruct,
mitral valve, acute or intermittent dyspnoea, related to
particular position of the body, is out of proportion to
physical findings. A loud split first sound, pansystolic and
diastolic murmurs at the apex, absence of short PR interval
are highly suggestive. ECHO is confirmatory. Free or
pedunculated ball-valve thrombosis in the left atrium may
135
obstruct the mitral orifice and result in sudden development
of severe dyspnoea or syncope or angina or sudden fatality.
Pericardial tamponade: The three clinical features that are
diagnostic of cardiac tamponade due to intrapericardial
haemorrhage are (i) rising venous pressure, (ii) falling
arterial pressure, and (iii) a small quiet heart.
If the tamponade develops slowly the subject appears
acutely ill and dyspnoea is the usual complaint with or
without chest pain. The severe hypotension may not be
present. However, pulsus paradoxus is a constant
manifestation of cardiac tamponade. Other features are
tachycardia, tachypnoea, muffled heart sounds and
hepatomegaly.
Chronic
Congenital heart disease
a. In Fallot’s tetralogy, there is a steep fall in the arterial
oxygen saturation. This poorly oxygenated blood efects
the metabolism of tissues which in turn become
anaerobic with consequent metabolic acidosis. This
hypoxaemia and anaerobic muscle metabolism produce
dyspnoea which is relieved by squatting since it improves
arterial oxygen saturation, by reducing the volume of
desaturated femoral blood returning to the right heart.
The diagnosis of Fallot’s tetralogy is made by the
presence of cyanosis and clubbing, a loud systolic
murmur in the second left intercostal space witha soft,
single pulmonic second sound and evidence of right
ventricular hypertrophy.
X-ray of the chest confirms the diagnosis with the
‘coeur en sabot’ (the apex appears blunt and lifted above
the diaphragm) and oligaemic lung fields.
ECG shows Pulmonale and moderate right ventricular
hypertrophy. T waves are upright and rarely inverted in
right ventricular leads.
b. In severe pulmonary stenosis, dyspnoea is due to
insufficient response of cardiac output to exercise. A
loud systolic murmur is the pulmonary area with a
muffled pulmonary second sound and right ventricular
hypertrophy are diagnostic.
Radiograph shows prominence of main pulmonary artery
(poststenotic dilatation) and light pulmonary vascular
markings.
Valvular heart disease: In mitral stenosis, the dyspnoea is
due to the increased rigidity of the lungs caused by changes
in the interstitial tissue with consequent reduction of the
vital capacity. All the four grades of dyspnoea are
 136 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
encountered depending on the pulmonary congestion and
the elevated left atrial pressures. The characteristic
middiastolic murmur with apical presystolic accentuation
with a loud first sound (closing snap) and an opening snap
are highly diagnostic.
In mitral incompetence, the dyspnoea is caused by
pulmonary venous congestion as in mitral stenosis,
aggravated further by a later event of left ventricular failure.
Apical pansystolic murmur conducted towards the axilla
with a muffled first sound and left ventricular enlargement
are highly diagnostic.
In aortic valvular disease, the effort intolerance is
attributed to left ventricular failure. A rough basal ejection
systolic murmur conducted to the neck with a muffled
second sound and a left ventricular hypertrophy are diag-
nostic of aortic stenosis, whereas an early diastolic murmur
either in the aortic or Erb’s area, Duroziez’s sign, Corrigan’s
sign, Hill’s sign, water hammer pulse and left ventricular
enlargement are diagnostic criteria for aortic incompetence.
Congestive heart failure Congestive cardiac failure is
chronic heart failure. The congestion may be both in
pulmonary and peripheral circulation. Usually it is secondary
to left ventricular failure. Sometimes, it may be a pure right
heart failure due to chronic cor pulmonale or a congenital
heart disease and congestion present in systemic and portal
venous system.
Dyspnoea is atributed to
i. Possible persistence of preexisting pulmonary
congestion
ii Presence of a primary pulmonary disease
iii Low cardiac output with poor blood flow in the tissues
iv. Peripheral venous stasis resulting in reduction of
oxygen tension and hypoxia or increased lactic acid in
the blood
v. Interference with distensability of lungs due to
hydrothorax or ascites
Congestive heart failure is diagnosed by the presence of
raised venous pressure, tachycardia, tender hepatomegaly
and peripheral oedema and signs of right ventricular or
combined ventricular enlargement due to underlying heart
disease. The valsalva’s manoeuvre may be of value since
there is no overshoot as seen in normal persons.However,
square wave effect is typical due to rise in all facets of
pressures without affecting the pulse rate and volume.
Hyperkinetic circulatory states The classical example is
anaemia wherein the dyspnoea is due to decreased
haemoglobin with reduced amount of oxygen in the arterial
blood and consequent hypoxaemia and anaerobic muscle
metabolism. The principle compensatory mechanism for the
diminished oxygen supply in anaemia are (i) red cell DPG
(a product of red cell glycolysis, 2, 3-Diphosphoglycerate)
is increased which facilitates increased delivery in the tissue;
(ii) increased cardiac output; (iii) increased circulation
speed; and (iv) increased plasma volume with slightly
diminished total blood volume.
If the anaemia is prolonged and/or severe, congestive
heart failure may result which by itself will acount for
dyspnoea (Refer to Chapter ‘Fatigue’).
II. Pulmonary
Acute
1. Obstruction in the Upper Airways: Obstruction in the
trachea or larynx is an acute emergency. The trachea is
obstructed by a foreign body or by malignant thyroid or
glands. The larynx may be obstructed by severe laryngitis
(diphtheritic) or angioneurotic oedema, laryngismus
stridulus due to hypocalcaemia or foreign body or bilateral
abductor paralysis.
The clinical picture is suggestive of acute asphyxia with
the patient struggling for breath with violent insipiratory
efforts and indrawing of the intercostal spaces and lower
ribs on both sides. This inspiratory dyspnoea may be
accompanied by cyanosis. The breathing is noisy with harsh
crowing sound predominantly during inspiration (stridor).
2. Obstruction of Lower Airways: This is discussed as
follow:
Bronchial asthma It is a mucosal inflammatory disease of
small airways in the lungs with increased responsiveness to
multiple stimuli in which obstruction is episodic and
reversible in the typical acute bronchchial asthma. The attack
consists of feeling of tightness in the chest, dysponea, cough
with difficulty to expectorate and apprehension. The
paroxysms of dysponea are sudden in onset and mainly
expiratory in character in contrast to short inspirations.
vesicular breath sounds with prolongd expiration, rhonchi
and expiratory wheezes are heard. It is either acute or
chronic. The former is not a daily feature and may be mild
(intermittent or persisent) or severe. The latter is peristent
(moderate or severe) and a daily feature.
If the attack is severe, the additional features of
perspiration, use of accessory muscles of respiration,
tachypnoea, orthopnoea, monosyllabic speech, tachycardia
(more than 120), pulsus paradoxus, reduced or absent breath
 Dyspnoea
sounds with numerous high pitched musical rhonchi and
audible wheezing are discernible. When intense dyspnoea
persists for longer duration (over 24 hours), it is termed as
status asthmaticus. If respiratory rate is >30/min bradycardia
and /or hypotension cyanosed, confused it is life-threatening.
If PaCO2 is >50 mm Hg it is a near fatal asthma.
In chronic bronchial asthma, the dyspnoea is less intense
and mostly related to exertion. The wheeze is slight or low
grade and these symptoms of airway obstruction occur with
less conspicuous paroxysmal character. The intermittent
exacerbations are due to inter current respiratory infections
with cough and mucoid sputum. The various irritants acting
on the bronchial mucosa superimposed by the infection or
mucosal oedema due to adverse atmospheric conditions may
be responsible for the exacerbations of chronic bronchitis,
which often complicates chronic bronchial asthma.
Etiopathogenesis: In clinical practice, asthma can be as
extrinsic on intrinsic. In the former, the attacks are related
to allergens like dust, drugs, danders, family history of
asthma (genetic), whereas in the latter attacks are usually
related to infections like sinusitis, bronchitis, tuberculosis
aspergillosis, colds with a nasal polyp, exercise, environ-
mental or psychogenic stress acting as triggering factors.
Rarely drugs, polyarteritis nodosa or carcinoid syndrome
may be aetiological factors. The underlying mechanism of
the reversible airway obstruction is related to bronchospasm
due to hypertrophy contraction of the airway smooth muscle
and inflammatory swelling of the bronchial wall with
intraluminal hyper-secretions of mucus. This bronchial
narrowing (caused by degradation of mast cells releasing
prostglandin-D2 histamine, leukotrienes as well as cytokines
released by bronchial epithelial cells contributing to the
ongoing inflammation) increases the respiratory effort by
enhancing the resistance to air flow in the airways interfering
with pulmonary ventilation.
The bronchial hyper reactivity is attributed to various
immuno pathological and biochemical mechanisms in
various types of asthma.
a. Mast cell activation: When specific allergens form
bridges between adjacent IgE molecules on the surface
of lung mast cell, mediators are released which cause
broncho constriction.
Prostaglandin D 2 (PGD 2 ) and slow reacting
substance of anaphylaxis (SRS-A) (leukotrienes) form
these mediators, concerned in the pathogenesis.
Histamine produced by mast cells cause broncho
constriction as well as mucosal oedema due to increased
microvascular permeability.
137
b. Platelet activating factor: IgE and endotoxin generate
the platelet activating factor by macrophages and
eosinophils which produce inflammatory sequelae. This
in turn diminish the threshold to the activating stimuli
and hypertrophy of the smooth muscle. This concept
accounts for the exacerbations of symptoms of asthma.
c. Epithelial cells: Airway epithelial cell damage produced
by several stimuli release leukotrienes and hydro-
xyelcosatetraenoic acid (HETE). The damage also
deprives the protective relaxant factor and exposes the
afferent nerves which may be triggered and contribute
to the constriction and mucus secretion.
Airway cooling: The pathogenesis of bronchoconstriction
is also attributed to airway cooling as a consequense of body
cooling (as occurs in nocturnal asthma) or respiratory heat
loss as in exercise induced asthma or inhalation of
cold air.
Autonomic neurogenic reflexes: The mediators stimulate the
afferent nerves (irritant receptors and bronchial c-Fibre
endings) in the airways and produce the reflex effects of
bronchospasm through efferent vagal pathways.
Thus bronchial hyper responsiveness results from
(a) contraction of the smooth muscle, (b) Mucus secretions
from submucosal gland epithelium, (c) Mucosal swelling
inflammation (i.e.) oedema due to increased vascular
permeability and release of chemical mediators from the
inflammatory cells interacting with autonomic innervation
of airways.
Evaluation: A peak flowmeter is a valuable tool for an
asthmatic to assess the pulmonary status. The patient is asked
to blow out a single and forceful breath after a full inspiration
through the mouth piece of the flowmeter. The peak flow
rate can be recorded on the dial. Reduced Peak Expiratory
Flow Rate (PEFR) can be significantly elevated after a
bronchodilator unlike in emphysema. If the PEFR can not
be elevated above 100 L per min. with treatment, it indicates
a risk of ventilatory failure.
FEV1
Reduction of ratio (<70%)
FVC
(FEV1 Forced expiratory volume in one second
FVC Forced vital capacity)
and reduced PaO2 are diagnostic. If the PaCO2 is raised, it
indicates marked severity. Diffusion capacity (DLCO) is
normal or increased.
X-ray of the chest shows no abnormality except the
underlying infections if any. In others, it may show
emphysema or pneumothorax.
 138 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Blood examination shows eosinophilia (5 to 20%) and
the sputum examination may show eosinophilia cells and a
compact cluster of bronchial columnar epithelial cells (creola
bodies).
Skin test may help to identify the atopic asthmatics and
the specific allergens.
Obliterative bronchiolitis (OB) More than 90% cases are post
infectious and some are due to collagen vascular disease,
accounting for airflow limitation like COPD. OB is as
common as COPD and an important cause of pulmonary
hypertension as well as cor pulmonale.
Mosaic attenuation with worsening on expiratory scan
on HRCT thorax is diagnostic.
Tropical eosinophilia (Refer to Chapter ‘Haemoptysis’)
Emphysema: Chronic obstructive pulmonary disease
(COPD) include chronic bronchitis (Refer Chapter
“Haemoptysis”) and emphysema. The latter results
commonly from smoking and rarely due to α1-Antitrysin
deficiency. In emphysema, air spaces are dilated due to
destruction of their walls which causes obstruction by
decreasing elastic recoil of the lungs. In a chronic obstructive
pulmonary disease, the dyspnoea is insidious in onset with
exacerbation due to infections, exposure to cold air and high
humidity. Chest is of barrel shape, with decreased excursions
of the diaphragm. The percussion note is hyper resonant
with decreased breath sounds and scattered wheezes
throughout. Liver dullness and superficial cardiac dullness
are obliterated. There may be evidence of right heart failure,
pulmonary hypertension and right ventricular hypertrophy
(cor pulmonale). The features of COPD depend upon Type-
A (emphysematous) and Type-B (bronchial). The former is
relatively quiet on examination of chest, unlike the latter.
X-ray of the chest shows hyperinflation with low and flat
diaphragm and regional attenuation of vessels or bullae with
enlargement of the main pulmonary artery and right ventricle
(Fig. 9.1), usually there is no reversibility, after inhaled
salbutamol in COPD (i.e) 15% improvement in FEV1.
Pulmonary function tests reveal:
a. Reduced FEV1 (if it is between 1.2 and 1.5 litres-
exertional dyspnoea and if less than 1 litre, Cor
pulmonale will be present),
b. Reduced PEFR (does not improve significantly with
bronchodilators),
FEV1
c. ratio reduced (< 70%)
FVC
d. PO2 is reduced and PCO2 is normal (Pink Puffers), in
Type-A (Pink Puffers) and
e. PCO2 is raised and PO2 is low in Type-B (Blue Bloaers).
Fig. 9.1: X-ray of the chest showing emphysematous bulla
on the left side after inhaled salbutamol in COPD
Collapse of the lung
When a sudden massive collaspe of the lung due to
obstruction occurs, there is severe dyspnoea, tachycardia,
tachypnoea, and cyanosis. The breath sounds and vocal
resonance are diminished without any accompaniments and
with a tracheal shift to the affected side. The development
of such symptoms within 48h of an operation is almost
always due to collapse. If the obstruction of a major bronchus
is partial, the major complaint is dyspnoea, increasing on
exertion. The breath sounds may be high pitched bronchial.
coarse crepitations and bronchophony present. A foreign
body, bronchial carcinoma, enlarged hilar lymph nodes, and
viscid secretions are some of the causes for pulmonary
atelectasis.
X-ray chest shows a homogenous opacity, with a shift
of the mediastinum to the side of the lesion and elevated
diaphragm.
Acute respiratory distress syndrome (Shock Lung) - ARDS
ARDS is an acute respiratory insufficiency following events
like sepsis, shock, oxygen toxicity, over hydration, surgery,
trauma, fat embolism.
It is due do diffuse injury to the alveolar capillary
membrane with consequent increased permeability of
endothelium of pulmonary capillaries and epithelium of
alveolar wall. This result in pulmonary oedema which is
otherwise called noncardiogenic oedema i.e. water in the
lungs increases without any increase in hydrostatic forces.
In the early stage, there is hyperventilation, increased
respiratory frequency and respiratory alkalosis. Few fine
 Dyspnoea
crepitations may be audible. X-ray chest may be normal in
this stage. PaO2 and PaCO2 are reduced with increased
alveolar arterial gradient. Rapid onset of respiratory failure
leads to increased dyspnoea with tachypnoea, tachycardia,
cyanosis and disorientation. Crepitations are prominent
throughout the lung fields. Refractory hypoxaemia with ratio
of PaO2: FiO2 < 200 mmHg; pulmonary capillary wedge
pressure of less than 19 mmHg. Total thoracic compliance
<30 mL/cm H 2O; (stiff lungs) are diagnostic criteria.
Hypocapnia and respiratory alkalaemia are present in the
evolving stage. Hypercapnia may result ultimately due to
inadequate alveolar ventilation. If the disease lasts for more
than 10 days, fibrosing alveolitis will set in. X-ray chest
shows evenly distributed puffy densities in lung fields
suggestive of interstitial pulmonary oedema.
Less Severe form Constitutes Acute Lung Injury.
Chronic
•
•
•
Chronic asthma
Obliterative bronchitis
Chronic bronchitis
} Vide Supra
• Emphysema
3. Acute Restrictive Lung Disease
• Spontaneous pneumothorax
(Refer to Chapter ‘Chest Pain’)
• Extrinsic alergic alveolitis (vide infra)
Diaphragmatic paralysis
Unilateral diaphragmatic paralysis usually is asymptomatic,
but patient may complain of dyspnoea in the supine position.
It is usually due to a tumour in the mediastinum or trauma.
In bilateral paralysis, dyspnoea is usually severe in the supine
position. This is due to neurological disorders like
poliomyelitis or mediastinal lesions or cervical cord injury.
Diaphragmatic paralysis can be clinically diagnosed by
Litten’s sign, Hoover’s sign, and tidal percussion. The
associated features of mediastinal tumour or neurological
disease can also be elicited. It can be confirmed by
fluoroscopy wherein paradoxical movements of the
diaphragm can be observed.
Chronic pulmonary fibrosis
Fibrosis may replace the lung parenchyma due to infections
or may be focal due to inhalation of certain types of dust or
confined to the alveolar walls as in fibrosing alveolitis (vide
infra). Dyspnoea on exertion is progressive, spread over a
period of 10 years, which may become severe and
incapacitating. Breathing appears restricted with decreased
expansion. Physical signs like clubbing, flat chest on one
139
side (asymmetrical) tracheal shift to the affected side, dull
note, coarse crepitations with altered breath sounds
(diminished vasicular or low pitched bronchial) may offer
clues.
X-ray examination shows scoliosis to the opposite side
with contraction of the rib spaces and shift of the trachea
and mediastinum to the side of the opacity with or without
small radiolucencies. The diaphragm is pulled up on the
affected side.
Occupational lung diseases These may be due to exposure
of
a. Organic dust like mouldy hay, cotton dust, sugar cane
dust, etc. causing extrinsic allergic alveolitis or
asthma
b. Mineral dust like exposure to coal dust, silica,
asbestos and iron-oxide causing pneumoconiosis
c. Irritant gases, fumes and other chemicals like
ammonia, chlorine, acid fumes, fumes of various
metals and paraquat—causing occupational asthma
Extrinsic allergic alveolitis (Hypersensitivity Pneumonitis)
Inhalation of organic dust may give rise to Type-3 allergic
reaction in the alveoli and bronchioles. The clinical features
appear suddenly 4 to 6 h after exposure. These features are
dyspnoea, dry cough, fever with fine inspiratory crepitations
and little wheeze, usually in the lung bases. The symptoms
subside in 2 to 3 days time. After repeated acute attacks,
fibrosis may occur with progressively increasing dyspnoea,
clubbing and persistent fine crepitations throughout the lung
field.
X-ray of the chest shows diffuse haze or bilateral miliary
shadows. After repeated attacks, honeycomb appearance or
pulmonary fibrosis may be present.
IgA and IgG are raised. Precipitins specific to the
offending antigen are present in majority of cases. Lung
function tests shows restrictive pattern.
Pneumoconiosis This term simply means ‘dusty lung”. It is
defined as the accumulation of dust (an aerosol composed
of solid inanimate particles) in the lungs and tissue reaction
to its presence. The inhaled dust particles are conveyed by
macrophages from the mucosa of the airways to scattered
lymphoid tissue in the lungs which in turn results in fibrosis
in the course of years of prolonged exposure. The common
types are coalminer’s pneumoconiosis, silicosis (quarry
workers, metal grinders), asbestosis (asbestos cement and
insulation workers), siderosis (iron foundry workers).
Dyspnoea on exertion over a period of 10 years with
varying severity, cough with expectoration due to associated
bronchitis (sputum may be black in coal miners, and may
 140 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

show asbestos bodies in asbestosis), and physical signs of

fibrosis are the characteristics features. General health may
be maintained unless tuberculosis or congestive cardiac
failure supervene.
X-ray of the chest shows small, discrete and nodular
opacities in both the lungs which increase in size
progressively in the early stages of silicosis. Subsequently
opacities become large and irregular with fibrosis and
enlarged hilar glands may show typical egg-shell
calcification. In asbestosis, linear shadows and pleural
involvement (thickening and bilateral calcification) are the
characteristic radiological features. Evidence of broncho-
genic carcinoma, which is a complication, may be
appreciated radiologically.
Occupational asthma It is usually related to exposure to air-
borne dust or gases and fumes, which induce Type-1
hypersensitivity reaction. The airway narrowing occurs
immediately after exposure to the allergen with the same Fig. 9.2: High resolution computed tomography (HRCT) or
material. This casual relationship is usually associated with helical (spiral). CT of the lungs showing interlobular septal
predisposing factors of atopy. Physical signs of rhonchi will thickening, honey-combing and traction bronchiectasis charac-
be striking. Eosinophilia is common. IgE is raised. Skin teristic of interstitial lung disease, one of the causes of which is
test with appropriate extracts may be useful in identifying fibrosing alveolitis
the offending agent. Pulmonary function tests may show
obstructive pattern specially measurements before and after nodular opacities like pulmonary oedema. Sputum shows
a work shift. The common causes of occupational asthma periodic acid schiff (PAS) positive lipid rich proteinaceous
are grain dust, plants, insect proteins, animal products, drugs, material.
irritant gases and chemicals.
Fibrosing alveolitis It is progressive fibrosis of alveolar walls
Irritant gases and chemicals not only give rise to
with interstitial cellular exudate. It is crytopgenic and only
occupational asthma (due to immunological sensitisation
in few cases, the causes can be found such as viral
with IgE antibodies or activation or the alternative pathway
pneumonia, drugs like cyclophosphamide, extrinsic allergic
of complement or direct action like anticholinesterases,
alveolitis, collagen diseases or shock lung. Exertional
example, insecticides) but also pulmonary oedema.
dyspnoea, dry cough without wheeze, clubbing, cyanosis
Acute chemical inflammations of the respiratory tract
and crepitations (fine and inspiratory) are the typical
can occur in certain industrial exposures to ammonia in the
features.
fertiliser industry. Acid fumes like in steel industry, metal
X-ray of the chest shows diffuse bilateral basal nodular/
fumes in welding or foundries and polymerisation processes
reticular shadows and honey comb pattern. Immuno-
in plastic industry can produce fever (characterised by chills
globulins and ESR are raised. Lung function tests
and sweating). Ingestion of paraquat in the agricultural sector
demonstrate restrictive pattern. Spiral CT is diagnostic
results in cough, with expectoration dyspnoea and
(Fig. 9.2).
pulmonary oedema. Other chemicals like nitrogen oxide in
the rocket fuel industry, chloride in chemical industries, Sarcoidosis (Refer to Chapter ‘Pyrexia of Unknown Origin’)
phosgene in welding and plastics and cadmium fumes Interstitial lung disease is a chronic inflammation of
provoke less acute response resulting in dyspnoea. respiratory tract (lower) and subsequent fibrosis of granulo-
matous process affecting interstium (loose connective tissue
Pulmonary alveolar proteinosis This is known for its rarity.
throughout lung) and alveolar spaces and includes disorders
Clinical features will be exertional dyspnoea, cough with
caused by dust; drugs; infections; malignancy or connective
viscid sputum, prolonged fever and weight loss. Various
tissue disease and idiopathic.
atmospheric pollutants have been incriminated in its
aetiopathogenesis. X-ray of the chest shows patchy confluent Diaphragmatic paralysis (Vide supra).
 Dyspnoea
Fig. 9.3: X-ray of chest showing dense uniform opacity in the
lower and lateral parts of the right haemothorax merging above
and medially into the translucency of the lung, suggestive of
pleural effusion
Pleural Effusion
A large pleural effusion or bilateral effusions may present
as dyspnoea progressing over a period of few weeks. The
tell-tale physical signs of shift of the mediastinum to the
opposite side, stony dullness, vocal resonance and
diminished breath sounds will be diagnostic of pleural
effusion.
The X-ray chest shows obliteration of the normal costo
phrenic angle in a small effusion. The homogenous shadow
with a concave border extends upwards to the axilla or the
haemithorax may be completely obscured as the effusion
becomes large enough (Fig. 9.3). Aspiration of the fluid from
the pleural cavity will be absolutely diagnostic.
4. Infections
Aspiration pneumonia
Aspiration pneumonia may be due to aspiration of infective
material
a. from preexisting suppurative conditions of the
respiratory tract, e.g. sinusitis,
b. during unconsciousness or laryngeal paralysis,
c. inadequate expectoration, and
d. from aspiration of gastric acid leading to acute broncho-
pneumonia/postoperative suppurative pneumonia and
lung abscess or aspiration pneumonitis (Mendelson
syndrome).
141
Suppurative pneumonia and lung abscess (Refer to Chapter
‘Haemoptysis’)
Aspiration Pneumonitis (Mendelson Syndrome)
This syndrome is due to aspiration of gastric contents,
dyspnoea, cyanosis and hypotension may develop as in
pulmonary oedema.
• Pulmonary tuberculosis (Refer to Chapter ‘Haemoptysis’)
5. Vascular Occlusion
• Pulmonary Embolism (Refer to Chapter ‘Chest Pain’)
• Recurrent Pulmonary Embolism (Refer to Chapter
‘Chest Pain’)
6. Chest wall
• Trauma (Mediastinal Emphysema) (Refer to Chapter
‘Chest Pain’)
Restricted chest movements The conditions of the chest
wall like kyphoscoliosis can cause impairment of ventilation
resulting in dyspnoea, so is the case with extreme obesity
wherein dyspnoea may be due to increased respiratory effort
due to adipose tissue around the chest and abdomen with
elevated diaphragm. On the same analogy, pregnancy may
account for obstruction to free breathing. Nevertheless, other
mechanisms of dyspnoea due to underlying cardiovascular
disorders or hyperkinetic circulatory states in pregnancy
should not be overlooked. Ankylosing spondylitis is another
entity wherein the restricted chest movements may give rise
to increased respiratory effort due to increasing stiffness of
the spine with involvement of the costovertebral joints (Refer
to Chapter ‘Low Backache’)
7. High altitudes
Acute mountain sickness This occurs when unacclimatised
persons ascend rapidly to higher altitudes. Dyspnoea,
headache, gastrointestinal disturbances, impaired
judgement, and tachycardia may appear. These features are
attributed to increased ventilation stimulated by hypoxia
resulting in hypocapnia and respiratory alkalosis. Acute
pulmonary oedema may result when persons ascend rapidly
to altitude higher than 9000 feet. The alveolar PO2 decreases
as the altitude increases. The lower the PO2 the greater are
the cerebral disturbances including unconsciousness.
Chronic mountain sickness (Monge’s disease) This occurs
in persons living at altitudes over 14,000 feet for some years.
Dyspnoea, cyanosis, cough, headache, dizziness,
erythrocytosis with high haemoglobin levels of 20 g per
cent are the clinical manifestations. At a later stage,
 142 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
hypertension and tendency to thrombosis due to high
viscosity of the blood may result.
III. Alimentary Affections
Flatulence
(Refer to Chapter ‘Dyspepsia’)
Retropharyngeal Abscess
This occurs due to the involvement of retropharyngeal lymph
glands, complication of laryngitis in children, suppurative
parotitis or injury to the posterior pharyngeal wall. Dyspnoea
is related to posture (being absent in the lying position and
present in the sitting position). In addition there may be
dysphagia with a feeling of lump in the throat or sometimes
progressive airway obstruction as the abscess progresses.
The voice is changed assuming that of a cry of a duck. This
may be seen as a rounded swelling on inspection of the
posterior pharyngeal wall. X-ray confirms the diagnosis.
Hiatus Hernia
(Refer to Chapter ‘Chest Pain’)
IV. Neurological
Poliomyelitis
In acute stage of poliomyelitis, the involvement of the
anterior horn cells of the grey matter of spinal cord or motor
nuclei of the brainstem may result in dyspnoea. Weakness
of the intercostal muscles and diaphragm may lead to
diminished chest expansion, prominent accessory muscles
and short spans of speech. The patient cannot count up to
60 in one breath unlike normal persons. In bulbar polio,
impairment of swallowing and coughing may lead to
regurgitation of fluids through nose and rattling sounds in
the throat. The respirations are dysrhythmic. When the
secretions accumulate in the pharynx, respiratory obstruction
may be caused (Refer to Chapter ‘Weak Legs’).
Rabies
In rabies, nuclear lesions involving the vagus (nucleus
ambiguous) may result in bilateral abductor paralysis leading
to dyspnoea, although the pharyngeal spasm evoked by
offering a glass of water is highly characteristic.
Tabes Dorsalis (Tabetic Crises)
Laryngeal crises consist of attacks of dyspnoea associated
with cough and stridor. The bilateral abductor paraylsis of
the larynx due to nuclear lesion involving the vagus is the
underlying mechanism. This entity is very rare now.
Myasthenia
Refer to Chapter ‘Weak Legs’
V. Metabolic
Metabolic Acidosis
Low HCO3– and Low pH (increased H+ ions) are charac-
teristic. Changes in HCO3 are termed metabolic acidosis
and changes in CO2 are termed respiratory acidosis.
Metabolic acidosis may be either increased anion gap
acidosis due to increased organic acids or normal anion gap
acidosis due to loss of HCO3 or ingestion of H ions.
(Hyperchloraemic acidosis), e.g. diarrhoea. Hyperventilation
with deep and sighing respirations (Kussmal’s) due to
metabolic acidosis may give rise to breathlessness. But this
is too minor a complaint for the obvious illnesses detailed
below, which belong to increased anion gap acidosis (i. e.
Renal Failure, DM, hypoxia).
Diabetes Mellitus with Ketoacidosis
Wherein the production of β-hydroxy-butyric acid and
acetoacetic acid is so great, that the body cannot cope up
with their oxidation. (Refer to Chapters Coma and Shock).
Renal Insufficiency
Where the kidney fails to
a. generate enough bicarbonate ions from carbonic acid
normally produced in the tubules to neutralise the normal
amounts of 40 to 80 m Eq of acid produced in the urine.
b. secrete enough H ions from carbonic acid in exchange
for filtered sodium resulting in loss of sodium in the
urine.
c. excrete phosphate and sulphate which are strong acid
ions. Sodium which is to neutralise them, is lost in the
urine because of limited H secretion for exchange with
the sodium in the tubules.
d. secrete enough ammonia to buffer the H ions. Hence,
the H ions are increased, i.e. fall of pH, which stimulates
the respiratory centre. Associated hypertension and
anaemia may further contribute to dyspnoea in chronic
renal parenchymal diseases. (Refer to Chapters ‘Oliguria
and Polyuria’).
Poisons (Refer Appendix III)
Outbreaks to methyl alcohol poisoning occur when spurious
alcoholic drinks are contaminated with methyl alcohol.
 Dyspnoea
Acidosis is a striking feature since methyl alcohol is partly
oxidised to formaldehyde and formic acid. The accumulation
of organic acid accounts for metabolic acidosis. The other
common feature is progressive loss of vision with concentric
constriction of the visual fields.
This metabolic acidosis is characterised by reduced
bicarbonate, reduced pH and reduced PCO2 secondary to
hyperventilation, consequent to respiratory stimulation. This
abnormality can also occur in diarrhoea, ingestion of acid
salts, which belong to normal anion gap acidosis (Refer
appendix III).
VI. Psychogenic
Anxiety State
The outstanding feature is anxiety with accompanying
feeling of unpleasent happenings and undue inner tension.
This may lead to somatic symptoms like dyspnoea, dizziness
or fine tremors, palpitations and accelerated activity of the
sympathetic nervous system which may be obvious on
physical examination.
Hyperventilation syndrome This may be due to lesions of
the central nervous system, salicylate poisoning or metabolic
acidosis. Anxiety and over breathing spontaneously are
conspicuous. The fall in PCO2 results in decreased cerebral
blood flow leading to blurred vision and fainting attacks.
Consequent respiratory alkalosis may lead to paraesthesiae
and tetany.
Neurocirculatory asthenia (Da Costa’s Syndrome) (Refer to
Chapter ‘Chest Pain’)
CLINICAL APPROACH
The clinician must ascertain whether the vague description
of breathlessness does really fall in the spectrum of
dyspnoea. If so, a systemic approach of meticulous history,
physical examination and relevant investigations have to
be undertaken to decipher the actual underlying clinical
setting of a cardiac or respiratory disease or anaemia, etc.
History
a. Mode of onset—sudden (asthma or ARDS or pulmonary
embolism) or progressive (emphysema).
b. Time of onset—nocturnal or anytime?
If nocturnal—is it associated with cough. If cough
precedes dyspnoea, it is more likely to be of respiratory
origin.
143
c. Character of breathlessness—inspiratory type (upper
airways) or expiratory type (lower airways) or is it a
mere difficulty in taking a deep breath (psychogenic).
d. Relation to exercise—occurring at rest or on exertion?
If it is on exertion, elicit exercise capacity on level
grounds and inclined grounds.
Is it during exertion or after exertion?
Grade of dyspnoea to be ascertained.
e. Relation to posture
i. Comfortable in sitting position than lying (cardiac)
ii. Comfortable on lying position than sitting
(orthostatic hypotension or myxoma)
f. Periodicity and duration—is it recurrent (bronchial
asthma) or continuous. If continuous, how long—days
or weeks (effusion); months (emphysema or fibrosis).
g. Associated symptoms—Pain, fever, cough, wheeze
h. Predisposing factors like
i. Hypertension
ii. Coronary artery heart disease
iii. Recurrent upper respiratory infection
iv. History of tuberculosis
v. Obesity
vi. Exposure to dusts or allergens
vii. Smoking
viii. Recent surgery or trauma
Physical Examination
General Examination
To look for
a. Decubitus for comfortable breathing
b. Anaemia
c. Cyanosis
d. Clubbing
e. Oedema
f. Leg veins
Vital data like respiratory rate, pulse, temperature, blood
pressure and type of respiration, pulse ratio should be
collected.
Systemic Examination
Respiratory system
1. Inspection and palpation
a. Shape of the chest and its movements
b. Use of accessory muscles and restriction of the
intercostal spaces
c. Respiratory rhythm like Cheyne-Stokes
 144 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
d. Palpation of chest for any alterations, mediastinal
shift or asymmetrical movements or tenderness or
vocal fremitus alterations
e. Measurement of chest expansion
2. Percussion: Any areas of dullness or obliteration of
normal areas of dullness
3. Auscultation:
a. Breath sounds—if bronchial (low pitched)
suggestive of cavity; if vesicular with prolonged
expiration suggestive of airway obstruction.
If absent suggestive of pneumothorax or effusion.
If diminished vesicular suggestive of emphysema.
b. Adventitious sounds—basal, fine inspiratory
crepitations are characteristic of pulmonary oedema.
Coarse crepitations are suggestive of fibrosing alveolitis.
Rhonchi and wheezing are present in obstructive airways.
Cardiovascular System
1. Inspection and palpation
a. Inspection of neck veins
b. Position of apex beat
c. Thrills
2. Percussion: Any cardiomegaly
3. Auscultation: Any gallop rhythm and murmurs
Abdomen: Is abdomen distended? If so, is it due to flatus,
or fluid or fat or foetus or faeces.
Neurological Examination
This is done espicially for (a)10th cranial nerve (b) motor
system (c) spine for evidence of curvatures and spondylitis.
Investigations
1. Haematology:TC, DC, ESR, RBC, and Hb
2. Examination of sputum
a. Naked eye apparance
i. Odour—foul chracter indicates infection
with anaerobes or other bacilli.
ii. Quantity—small amounts of sticky
secretions at the end of asthmatic attacks.
iii. Chracter—is it watery and frothy.
Is it mucoid or mucopurulent or purulent?
Is it blood—stained or blackish?
Is there any formation of 3 layers?
b. Microscopic examination: For
i. Bacterial (AFB)
ii. Eosinophils and Charcot-Leyden crystals;
> 20 per cent eosinophils suggest atopic
disease
iii. Malignant cells
iv. Elastic tissue
c. Cultures
3. Urinalysis
Including for acetone.
4. Biochemistry
Blood urea, sugar and serum creatinine.
5. Radiology
Chest X-ray may show
a. Mottled appearance, flat diaphragm, radio-
lucency, pneumothorax, pleural effusions or
collapse
b. Enlargement of the heart, prominent pulmonary
conus
6. ECG
7. Circulation Time: Arm to tongue circulation time is
increased by 4 or more seconds in left heart failure
and decreased in high output heart failure (normal value
10 to 16 s).
8. Pulmonary Function Tests
There are two types of pulmonary function tests.
a. Spirometric tests
b. Blood gases
Spirometric Tests (Spirometry)
a. Forced vital capacity: This is the maximum
volume of air expelled by a forceful and fast
expiration following a full inspiration (normal
values 3 to 6 litres). A reduced forced vital
capacity is characteristic of any pathology which
restricts the expansion of the lung (like
pulmonary fibrosis, ankylosing spondylitis or
myasthenia gravis) and obstruction of airways.
b. Forced expiratory volume from a position of full
inspiration in the first second (FEV1) should be
greater than 75 per cent of the vital capacity. It is
greatly reduced in asthma and if it is less than 1
litre after a bronchodilator, respiratory failure is
likely to set in.
c. FEV1 percentage (i.e.) FEV1/FVC = Normally >
70 per cent. If it is below 70 per cent, it is
suggestive of obstruction of airways. If it is more
than 70 per cent, it is a restrictive disease.
Interfering with expansion though actual FEV1/
FVC may be normal or high. If it improves after
a bronchodilator, the obstruction is said to be
reversible as in asthma (i.e. FEV1/FVC ratio
increased but not in COPD. This percentage is
 Dyspnoea
A = Normal FEV1/FVC (i.e.) 3.5/4.5 = 78%
B = Restrictive FEV1/FVC (i.e.) 2.0/2.5 = 80%
C = Obstructive FEV1/FVC (i.e.) 1/2 = 50%
Fig. 9.4: Spirogram showing normal pattern; restrictive
and obstructive ventilatory defects
assessed at bed side by placing a stethoscope
over trachea. If forced expiration time is >6 s, it
is < 60 per cent (normally the time taken for
expiration after maximum inspiration is 4 s) (Fig.
9.4).
d. Peak expiratory flow rate (PEFR)—Measure-
ment of flow rate at the beginning of maximum
forced expiration by wright’s peak flowmeter also
gives a clue to the changes in airways (Fig. 9.5).
The normal range is highly variable (380 to 700
litres per min). Respiratory failure is likely to
occur if the reading is less than 100 litres per
min after a bronchodilator.
e. Lung volumes
i. Residual volume (the amount of air present
in the lungs at the end of a maximal
expiration)
ii. Total lung capacity (the volume of air present
in the lung at the end of a maximal
inspiration)
The residual volume and the ratio of “residual
volume to the total lung capacity” are increased
in obstructive lung disease (normal ratio is 30 to
35%).
f. Vitalograph: It is a graphic record of Forced
expiratory volume against time. From this forced
expiratory volume in one second and FVC are
measured.
145
Fig. 9.5: Wright’s Peak Expiratory Flowmeter: Peak expiratory
flow rate is proportionately variable with height, age and sex:
The more the height, the more the flow rate; peak expiratory
flow is the ‘highest’ during 25-40 years and relatively more in
men than in women. (Values of PEF, up to 100 L/min in men
and 85 L/min in women, less than predicted value, are
considered to be within normal limits)
Blood Gases (Arterial): (PCO2 reflects ventilation and
PO2 reflects gas exchange or shunts)
a. PCO2—Normal range is 36 to 44 mmHg (5 to 6
kPa).
Low arterial PCO2 (30 mmHg or 4 kPa) and
normal PO2 in hyperventilation and
High PCO2 (> 50 mmHg or 6.7 kPa) and low
PO2 in ventilatory failure encountered.
Normal or low PCO 2 and low PO2 indicate
anoxia due to ‘stiff lungs’ or cardiac shunts.
b. PO2—Normal arterial PO2 is 80 to 110 mmHg
(11 to 15 kPa).
Low arterial PO2 (below 60 mmHg or 8 kPa) is
due to (i) hypoventilation (ii) inadequate pulmo-
nary gas exchange (mismatched perfusion and
ventilation; diminished diffusing capacity or
transfer factor) like pulmonary fibrosis, emphy-
sema, pulmonary oedema, and recurrent
pulmonary embolism; and (iii) right to left cardiac
shunts.
c. pH and HCO3 (low pH and low HCO3 indicate
metabolic acidosis).
9. Treadmill Test
10. Echocardiography: Especially useful when both
cardiac and respiratory diseases coexist.
Further Investigations
1. CT Scanning or HRCT
2. Tomogram and bronchography following bronchoscopy
3. Biopsy studies—Pleural, transbronchial, through
fibreoptic bronchoscope, percutaneous aspiration and
lung biopsy.
4. Pulmonary angiography
5. Lung scans—Gamma-emitting radionuclides produce
images which demonstrate parenchymal disease. It is
particularly diagnostic in pulmonary embolism.
 146 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
6. Gallium scan indicates activity and extent of inflamma-
tory process. In sarcoidosis increased uptake in lacrimal
and salivary glands (Panda sign) and increased uptake
in mediastinum and hilar nodes (Lambda sign) is specific.
TREATMENT OF DYSPNOEA
Diligent evaluation of the underlying mechanism of
dyspnoea, i.e. dys (hard) and pnoea (breathing) is the primary
endeavour in its management, since the etiology is
multifactorial (physiological, pathological or psychogenic).
The acute mode of onset is more alarming than chronic and
it is a medical emergency. It is usually of cardiovascular or
respiratory origin which may be proportionate to exertion
unlike metabolic cause (acidosis). The presence of striking
neurological signs makes central dyspnoea (neurological)
obvious. Any history of flatulence or evidence of hiatus
hernia elucidates alimentary basis.
In practice, the clinician must differentiate cardiac
asthma from bronchial asthma before designing correct
protocol of treatment.
Symptomatic Treatment
a. Decubitus—Make the patient sit up with a back rest
dangling the legs over the side of the bed if preferred.
b. Administer oxygen at 5 litres/min via nasal prongs so as
to maintain PaO2 at more than 60 mm Hg (make sure
that there is no respiratory failure as oxygen may abolish
the hypoxic drive).
c. Aminophylline 5 mg/kg body weight in 20 ml of 5
percent dextrose IV over 20 minutes.
d. Tranquilisers—Opiates are contraindicated in bronchial
asthma as they depress the respiratory centre. However,
diazepam or promethazine may be considered in smaller
doses.
e. Antiflatulents (methylpolysiloxane and simethicone)
with or without antacids may be beneficial if the
dyspnoea is of alimentary origin.
f. Set up IV line for therapeutic and diagnostic purposes
(arterial blood gases, creatinine and sugar).
g. Obtain ECG so as not to miss any myocardial infarction.
h. Arrange skiagram chest.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
1. Cardiovascular
Acute
Cardiogenic pulmonary oedema (Left heart failure) Assump-
tion of upright sitting position, frusemide (40-80 mg IV),
morphine (2-4 mg IV slowly and in mild cases subcuta-
neously) and high concentration of oxygen (if there is no
pre-existing lung disease) are the important initial steps.
Rapid digitalisation and aminophylline IV slowly are
additional therapies tried judiciously. If these measures are
inadequate, vasodilators may be given to reduce the after
load with glyceryl trinitrate intravenously (10-200 ug/min)
or sublingually (0.5-1 mg every five minutes for 20 min).
Sodium nitroprusside (20-30 ug/min) is the other alternative
provided the systolic blood pressure is > 100 mm Hg.
In cases of low cardiac output and low systolic pressure,
inotropic agents like dopamine or dobutamine are indicated.
Alternatively, 100 ml of saline may be given every 15 min
IV (If the facilities are available to monitor pulmonary
capillary wedge pressure to keep it at 15 mm Hg. When
PCW is > 20 mm Hg, vasodilators are indicated and if < 10,
saline is indicated.) Rotating tourniquets are beneficial
(blood pressure cuffs are placed around three extremities;
the cuffs are inflated midway between systolic and diastolic
pressure and are rotated every 15 minutes). If condition is
worsening, venesection (removal of 250 ml) and intubation
may be required.
Noncardiogenic pulmonary oedema Apart from oxygen
therapy, loop diuretics, and inotropic agents (aiming at stable
blood pressure and good urine output), the underlying cause
is treated. Mechanical ventilation and positive end-
expiratory pressure may be required if the condition worsens
(vide Treatment of Adult Respiratory Distress Syndrome).
Atrial myxoma Excision of the tumour preferably fossa
ovalis region and subsequent repair of the resultant defect
of the atrial septum, is the treatment adopted.
Ball valve thrombus Thrombus forming in the left atrium
with predilection to embolic episodes when associated with
mitral stenosis/atrial fibrillation, may result in ball valve
thrombus. Prophylactic anticoagulant therapy may be
beneficial. Surgical treatment is recommended particularly
in the presence of embolisation and when the mitral orifice
is < 1.2 cm2. If echocardiography reveals a large spherical
mass in the left atrium, be it as free floating ball thrombus
or not, an emergency surgery is indicated since there is a
high risk of arterial embolism or obstruction to mitral orifice.
Pericardial tamponade (Refer to Chapters ‘Chest Pain and
Syncope’)
Chronic
• Congenital heart disease (Refer to Chapter ‘Cyanosis’)
• Valvular heart disease (Refer to Chapters ‘Haemoptysis
and Syncope’)
 Dyspnoea
• Congestive heart failure (Refer to Chapter ‘Oedema’)
• Hyperkinetic circulatory states (Refer to Chapter
‘Fatigue’)
2. Pulmonary
Obstruction in the upper airways
• Acute tracheal or laryngeal obstruction: In acute upper
airway obstruction, due to a foreign body in a conscious
patient (upright position) or unconscious patient (lying
position) Heimlich’s manoeuvre is life saving. If
unsuccessful, tracheostomy or removal by direct
laryngoscopy or bronchoscopy must be undertaken
immediately.
Acute laryngeal oedema may be treated by sucking
ice or applying ice bag over the neck initially.
Angioneurotic oedema may be treated with adrenaline,
antihistamine and corticosteroids as required.
Tracheostomy may be considered before the respiratory
embarrassment becomes severe.
• Chronic obstruction of upper airways: The treatment
depends upon the cause of obstruction. Large benign
tumours may require laryngotomy for adequate excision.
For malignant tumours, external irradiation and surgical
excision may be done. Extensive tumours require not
only surgical excision but en block neck node resection.
Post-tracheostomy stenosis may be treated appropriately.
Obstruction to Lower Airways
Acute
Bronchial asthma
A. Acute mild/moderate attack (Eliminate Trigger Factors)
a. Bronchodilators: Oral long acting beta-agonies like
bambuterol (10 mg od) or sustained release of
salbutamol or terbutaline long acting inhaled beta-
agonists like salmeterol (50 ug b d) and formeterol
(12-24 ug b d ) also can be considered. The R isomer
of beta agonist (R albuterol, i.e. levalbuterol in doses
of 0.63 mg –1. 25 mg offers more efficatious control
(The S isomer of beta agonist has no benefit).
i. Short acting beta-adrenergic agonists (salbutamol
or Levosalbutamol and terbutaline—2nd genera-
tion) may be given orally or by metered dose
inhaler or by nebuliser every 4 h. Other beta-
adrenergics are isoprenaline, orciprenaline (1st
generation) and Formoterol (3rd generation).
ii. Methyl xanthines (aminophylline)—orally or
parenterally. Doxofylline is safe.
147
iii. Anticholinergics (ipratropium bromide—
inhalation 20 µg/dose or nebuliser) (250 µg/ml).
Tiotropinm bromide designed for once daily
usage.
b. Anti-inflammatory drugs
i. Corticosteroid aerosol may not be beneficial in
acute attack. Systemic corticosteroids (short
term) may be necessary when others fail. Inhaled
corticosteroids such as Budesonide, Fluticasone,
Beclamethasone and mometasone are effective
in reducing airway inflammation.
ii. Cromolyn (inhaled)
c. Anti-infective drugs—antibiotics are useful when
there is associated infection like sinusitis.
d. Mucolytics.
e. Antihistamines may be beneficial when hay fever
accompanies asthma.
f. Long term management
i. Antileukotrienes like montelukast 10 mg /d or
zafirlukast 20 mg b d are useful in preventing
asthmatic attacks.
ii. Sodium chromoglycate inhalations (1-5 mg
metered inhalation dose 2 metered puffs every 6
hours
iii. Allergen Immunotherapy (hyposensitisation)
iv. Identify trigger factors and deal accordingly
g. Inhaler devices
i. Pressurised metered dose inhalers (MDI) and dry
powder inhalers (DPI)
ii. Spacer devices
iii. Nebulisers are in vogue using the desired
medication like beta agonists or steroids
B. Acute severe attack—Status Asthmaticus
a. Give oxygen in high doses. 40%-60% and maintain
PaO2 > 60 mmhg (helium + oxygen useful).
b. Hydrocortisone sodium succinate 200 mg IV 4-8
hourly or methyl prednisolone 60 mg IV 4-8 hourly
until improvement.
c. Aminophylline- 250 mg IV slowly over 20 munutes.
d. Salbutamol 250 ug s. c. administered. (Continuous
flow nebulisation of salbutamol usually translates to
about 1. 5 to 10 mg of drug over one hour.
Ipratropium (0. 5 mg) may be added every 6 hrs)
e. Adrenaline 0. 3 to 0. 5 ml 1 in 1000 s. c. given
cautiously if deemed necessary.
f. Adequate hydration with 5 per cent dextrose saline
g. Appropriate antibiotics
h. If the condition improves, stop parenteral
hydrocortisone and switch over to oral prednisolone
 148 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(40 mg per day) and taper off over 1-2 weeks.
Similarly, theophylliae and salbutanol can be given
orally.
i. Magnesium sulphate intravenously (2 gm over 20
min).
j. Anxiolytics and hypnotics contraindicated unless
patient is intubated.
k. If respiratory acidosis occurs (condition deteriorates),
give controlled low concentration oxygen to avoid
carbon dioxide narcosis. Sodium bicarbonate intra-
venously may be beneficial. Respiratory stimulants
(doxapram 1-4 mg/min by IV infusion) may be given,
if PaCO2 continues to rise.
i. If the condition worsens further (i.e.) PaO2 is <6.5
kPa, PaCO2 >6.5 kPa, (One kPa = 7.6 mmHg),
pH <7.3 and systolic blood pressure < 90 mmHg),
mechanical ventilation - intermittent positive
pressure ventilation is provided through a cuffed
endotracheal tube.
ii. Extubate if there is appreciable relief (usually
after 3 days)
iii. Noninvasive positive pressure ventilation
(NIPPV) is also employed for patients requiring
mechanical ventilation in selected cases.
However, NIPPV should not be used as a
substitute to avoid endotracheal intubation.
C. Chronic Asthma
a. Such patients are kept reasonably well with
bronchodilator drugs (vide supra).
b. Immunomodulators
i. Corticosteroids – Beclomethasone inhalations
(50-100 µg/per inhalation 2-4 times daily) with
or without occasional short courses of
prednisolone. This is replaced by Budesonide
(100-200 µg twice daily) and 1 mg of Budesonide
is equal to 17 mg of oral prednisolone.
Fluticasone propionate (100-250 µg twice daily)
is promising.
ii. Prevent release of mediators from mast cells by
regular inhalation of sodium cromoglycate (5-
10 mg from metered dose inhalor 3-4 times/day).
Nedocronil sodium by inhalation or ketotifen (1-
2 mg twice daily) orally is said to have a similar
mode of action.
c. Combination of long acting bronchodilators and
steroid inhalations are used if necessary e.g.
Salmeterol (50 µg) and Fluticasone propionate
(125-250 µg) Rotacaps twice daily. The other long
acting beta 2 agonists is formeterol which is
combined with Budosonide. Recently monetasone
inhalations are employed.
d. Antileukotrienes (Montelukast 10 mg once daily) are
used in stable asthma to advantage.
e. Antihistamines used cautiously (avoiding possible
inspisation of secretions) may be helpful.
f. Educate the patient to avoid allergens. Skin testing
may identify the allergens and hyposensitisation with
extracts of allergens may be of some value.
g. Immunotherapy progressed from whole allergen
immunotherapy to modified allergen molecules or
fragments thereof or peptides derived from the
allergen. Recombinent or synthetic hypoallergenic
derivatives are introduced.
h. Eliminate triggering factors like emotional
disturbances, drugs like aspirin or propranolol, air
pollution, smoking and intriasic factors like chronic
bronchitis.
i. Breathing exercises may be encouraged.
In practice, an ideal working formula can be
recommended as follows:
Acute Asthma
i. Mild intermittent cases (< 2 times a week) - steroid puffs
twice daily suffice. Salbutamol (short acting) inhalations
may be supplemented, if necessary.
ii. Mild persistent cases (> 2 times a week) - Long acting
beta 2 agonists with steroid puffs may be beneficial.
Albuterol or ipratropium may be employed in some
cases.
iii. Severe (vide supra)
Chronic Asthma
i. Moderate persistent cases:
a. Low dose steroid inhalations (fluticasone 50-200
mcg) with long acting bronchodilators (Salmeterol).
b. Low dose steroid inhalations with antileukotrienes.
c. Low dose steroid inhalations with theophylline.
d. Ipratropium (20-40 mcg 3 to 4 times a day) or
tiotropium (18 mcg once daily) inhalations may be
added along with steroids, if necessary.]
ii. Severe persistent (severe i.e. acute exacerbations on
chronic)
a. High dose steroid with long acting bronchodilator
inhalations;
b. Cromolyn sodium or nedocromil sodium
inhalations;
c. Appropriate antibiotics;
 Dyspnoea
d. Oral steroids (Steroid resistant cases may need
methotrexate or cyclosporine).
e. Methotraxate may be added so as to reduce steroid
dosage.
f. Monoclonal anti igE antibody is beneficial in
patients with chronic corticosteroid dependent
asthma.
• Tropical eosinophilia
Symptomatic treatment for cough and wheezing is
indicated apart from specific therapy (Refer to Chapter
‘Haemoptysis’).
• Collapse of the lung
a. Postoperative collapse may be prevented by
hyperventilation and early ambulation after surgery.
b. When once the collapse occurs, facilitate cough and
restore ventilation to the collapsed lung by rolling
the patient from side to side, which can be repeated
every 4 hours. Expectoration may be further
promoted by stimulant expectorants. Blow bottles
and similar devices are beneficial.
c. Postural drainage and percussion over the affected
lung may be helpful to dislodge the mucus (patient
is postured with the affected side uppermost).
d. Administer oxygen.
e. Antibiotics are given for secondary infections
consequent to occlusion.
f. Intermittent positive pressure breathing may be
adopted if necessary.
g. Bronchoscopy may be required not only to determine
the cause but also to remove the offending obstructive
factor like foreign body.
• Acute Respiratory Distress Syndrome (ARDS) (Shock
Lung)
a. The initial therapy is oxygen administration so as to
maintain oxygen delivery to tissues with arterial Pao2,
more than 60 mmHg or with continuous positive
airway pressures when breathing spontaneously
(CPAP). Inhaled nitric oxide increases oxygenation.
b. Fluid balance to be maintained (keeping the
pulmonary capillary wedge pressure between 8-10
mm Hg (since higher pressure may predispose to
pulmonary oedema) preferably by restricting the
fluids to 20-25 ml/kg body weight/d with crystalloid
solutions or packed red blood cells, if necessary
(Colloid solutions may predispose to pulmonary
oedema).
c. Dopamine (2-10 µg/kg/min as IV infusion) or
Dobutamine.
149
d. Steroids—Hydrocortisone (100 mg 6th hourly IV).
e. Treat underlying conditions like sepsis appropriately
with suitable antibiotics.
f. Pentoxyfylline may be beneficial.
g. Nutritional support with lipid preparations.
h. Apart from haemodynamic stabilisation and treating
the underlying cause, respiratory support with
mechanical ventilation and positive end-expiratory
pressure (PEEP) is indicated if the disease woersens
(side affects of PEEP, reduction in cardiac output,
pneumothorax/pneumomediastium/subcutaneous
emphysema to be monitored). Weaning from the
ventilator by using a T-tube is considered when the
rate of intermittent mandatory ventilation is 2-5
breaths per min and also indices of pulmonary
function are satisfactory. Inverse ratio ventilation is
useful i.e. more time spent in inspiration than
expiration. Protective lung ventilation, (low tidal
volumes), high frequency jet ventilation, high
frequency oscillatory ventilation, liquid ventilation
are other alternative strategies adopted to
conventional mechanical ventilation.
i. Treat complications like left ventricular failure,
pneumothrax, secondary infections and bronchial
obstruction caused by tracheostomy or endotracheal
tube, GI bleeding and pulmonary embolism and renal
failure.
Chronic
• Chronic asthma (Vide supra)
• Obliterative bronchiolitis: Treat like COPD (Refer to
Chapter ‘Cyanosis’).
• Chronic bronchitis (Refer to Chapter ‘Haemoptysis’).
• Chronic asthma (Vide supra.)
• Emphysema Since most of the patients have associated
chronic bronchitis with bronchospasm, the principles of
treatment are the same as that of chronic bronchitis/
chronic asthma. Bronchodilators like salbutamol with
or without anticholinergics (Ipratropium) to relieve
spasm; (Prethcamide 100 mg tid orally in mild cases
helpful) mucolytic agents to mobilise secretions,
antibiotics for infection are the primary modes of
treatment. If unrelieved, steroids may be beneficial. For
long term use, Tiotropium (18 µg once daily) by
inhalation preferred to ineffectives steroids. Low flow
home oxygen therapy twice a day for one hour each and
postural drainage and breathing exercises are helpful.
Surgical excision is indicated for giant bulla or if
pneumothorax is recurrent.
 150 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
If the disease progresses, respiratory failure may occur,
which requires appropriate treatment (refer to Chapter
‘Cyanosis’). Complications like congestive heart failure
(chronic cor pulmonale—refer to Chapter ‘Cyanosis’)
and pneumothorax (refer to Chapter ‘Chest Pain’) may
be treated accordingly.
Acute exacerbation’s are to be prevented. If occurs
oxygen therapy, (estimating arterial blood gases to ensure
appropriate oxygen and carbon dioxide levels),
nebulized salbutamol and ipratropium, steroids,
antibiotics may be administered ventilatory support with
noninvasive intermittent positive ventilation indicated,
if patient is tired, (pH< 7.35 and PaCO2 > 45 mm).
Impending acute respiratory failure is treated with
invasive mechanical ventilation criteria include life
threatening: hypoxaemia i.e. PaO2 <40 mmHg, severe
hypercapnia (PaCO2>60 mmHg) and sever acidosis
(arterial blood pH < 7.25.)
• Restrictive Lung Disease
Acute
• Spontaneous pneumothorax (Refer to Chapter ‘Chest
Pain’).
• Diaphragmatic paralysis In general, the treatment
consists of treating the condition causing paralysis.
• Extrinsic allergic alveolitis Avoid exposure to allergens.
In acute cases, administer prednisolone 40 mg/d until
symptoms are controlled, after which it may be reduced
gradually over a week and then continued for about six
weeks.
Chronic
• Fibrosis: Removal of the causuative agent is mandatory.
Prednisolone (40 mg/d) is beneficial to control the
inflammatory process for about six weeks. If there is no
improvement clinically taper steroids over a week. If
improvement occurs, continue discriminately.
Immunosuppressant drugs may be considered wherever
necessary like azathioprine.
• Pneumoconiosis: Exposure to respirable dusts should
be avoided as no treatment influences the clinical course
of the disease once it develops. Symptomatic therapy
includes antibiotics, bronchodilators, supplementation
with oxygen and diuretics, if right heart failure exists.
• Hypersensitivity pneumonitis or extrinsic allergic
alveolitis caused by sensitivity to inhalation of organic
dust may be treated with prednisolone (40-60 mg/d) till
the symptoms improve and then taper over a period of
four weeks.
• Pulmonary alveolar proteinosis: Removal of the protein
lipid content filling the alveoli,with lung lavage under
general anaesthesia improves pulmonary function.
• Fibrosing alveolitis (Vide supra-Fibrosis)
• Sarcoidosis: The treatment includes prednisolone
20-40 mg/d and tapering it to lowest effective dose of
7.5 mg/d for 9-10 months).
Methotrexate (5-10 mg/week) or chlorambucil (8 mg/
d) is beneficial in steroid failure causes (Refer to Chapter
‘Pyrexia of Unknown Origin’).
• Diaphragmatic paralysis: Since the vital capacity is
severaly reduced in the supine position, a rocking bed
during nights is helpful. However, when phrenic nerves
are intact, electrical pacing of those nerves is found to
be successful.
• Pleural effusion: Thoracocentesis is better performed
in all cases of pleural effusions for effective management
based on the type of fluid aspirated. If it is a transudate,
the underlying cause must be treated. If it is an exudate,
it may be postpneumonic effusion, i.e protein content is
> 30 g/l (3 gm%) and cytology reveals neutrophils in
community acquired pneumonia whereas lymphocytes
indicate TB (vide infra) or post-primary tuberculous
effusion (Refer to Chapter ‘Haemoptysis’).
In the early stage of collection of pus (empyema) due to
nontuberculous organisms, antibiotic to which the causative
organism is sensitive, should be given parenterally or orally.
Pus may be aspirated on alternative days or continuous
closed drainge through an intercostal tube connected to a
water-seal drain.
At a later stage, when the pus becomes thick in
consistence, rib resection and drainage or resection of the
empyema sac is indicated. If the lung is not able to re-expand
sufficiently, resection of the empyema with decortication
of the lung supplemented by thoracoplasty, if necessary, is
performed.
If the empyema is of tuberculous entiology, effective
antituberculous treatment should be undertaken coupled
with repeated aspirations.At a later stage. when the
pulmonary lesion is controlled adequately, resection of the
empyema sac may be considered. Postresectional empyema
may require myoplasty with muscle flap closure or
decortication or thoracoplasty.
If the fluid is haemorrhagic, a primary tumour in the
pleura or a primary bronchial growth must be confirmed
appropriately and frequent aspirations with intrapleural
administration of cytotoxic drugs or radiotherapy may be
employed. The other causes of haemothorax like injury or
rupture of aneurysm or rarely tuberculosis itself, may be
appropriately treated.
 Dyspnoea
If the fluid is milky, the treatment depends upon the
primary condition like tubercuosis or malignant growth and
aspiration is not advisable unless it causes respiratory
embarrassment.
Infections
Acute
Aspiration pneumonia: The clinical entities of aspiration
pneumonia consequent to the factors enumerated (vide
supra) like
a. Acute bronchopneumonia is treated effectively with
suitable antibiotics.
b. Hypostatic pneumonia with frequent changing of
positions and breathing exersises besides antibiotics.
c. Postoperative pneumonia with effective evacuation of
the bronchial secretions by postural coughing or through
a bronchoscope, antibiotics and oxygen, if necessary.
d. Suppurative pneumonia (lung abscess ) with prolonged
antibiotic treatment for about 4-6 weeks and drainage
or surgical resection rarely. Adjacent suppurative process
like sinusitis, if any, must be managed effectively with
appropriate antibiotics, intransal vasoconstrictors and
adequate sinus drainge, to avoid extention of the
organisms into the lung by inhalation.
e. Mendelson syndrome is treated with antibiotics:
clearance of aspirated material by coughing or nasotra-
cheal suction or bronchoscopy: oxygen or endotracheal
intubation and artificial ventilation to achieve PaO2 >
60 mmHg. and hydrocortisone (endotracheal tube and
IV as well).
Chronic
Pulmonary tuberculosis (Refer to Chapter ‘Haemoptysis’).
Vascular Occlusion
Acute
Pulmonary embolism (Refer to Chapter ‘Chest Pain’)
Chronic
Recurrent pulmonary embolism Effective prophylaxis with
anticoagulants should be considered for moderate risk
patients for recurrent venous thromboembolism.
Interruption of inferior vena cava is indicated for recurrent
pulmonary embolism despite anticoagulants or when
anticoagulants are contraindicated.
151
Chest Wall
Acute
Trauma Though the chest injuries are associated with pain
invariably, blunt thoracic injury may cause dyspnoea due to
haemothrax (Refer to Chapter ‘Chest Pain’) or
pneumothorax (vide supra), or air may enter mediastinum
through an open neck wound (Mediastinal emphysema-
(Refer to Chapter ‘Chest Pain’).
Chronic
Restricted chest movements (Refer to Chapters ‘Obesity and
Backache’).
High Altitude
Acute
Mountain sickness The administration of oxygen relieves
acute symptoms. If pulmonary oedema occurs, bed rest in
semifolwer position and continuous oxygen administration
at 6-8 L/h enables recovery within two days. If unresponsive,
diuretics and rapid digitalisation is recommended and patient
should be moved to lower altitude as early as possible.
Prevention of pulmonary oedema is facilitated by appro-
priate physical conditioning before travel, gradual ascent
and rest for 1 or 2 days after reaching high altitudes.
Chronic
Mountain sickness The symptoms of alveolar
hypoventilation and raised carbon dioxide tension associated
with chronic cor pulmonale can subside after shifting the
patient to sea level when the pulmonary artery pressure
usually falls abruptly.
3. Alimentary Affections
Acute
Flatulence (Refer to Chapter ‘Dyspepsia’)
Retropharyngeal abcess Early treatment consists of anti-
biotics and general supportive care. Incision and drainage
are required if fluctuation occurs. General anaesthesia is
better avoided lest dangerous laryngeal obstruction and
aspiration should occur. If inevitable, tracheostomy under
general anaesthesia may be undertaken.
Chronic
Hiatus hernia (Refer to Chapter ‘Chest Pain’)
 152 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
4. Neurological
Acute
Poliomyelitis (Refer to Chapter ‘Weak Legs’)
Rabies: The rare paralytic from of rabies may be associated
with dyspnoea or dysphagia. Prophylaxis is all important
since rabies is invariably fatal. Postexposure treatment
consists of active immunisation with successive doses of
vaccine as early as possible. It may be vaccine derived from
animals infected with virus (Nerve tissue vaccine - semple
vaccine). Later on, tissue culture vaccine (replaced semple
vaccine) prepared in chick embryo free from brain tissue is
preferred (chick embryo vaccine). Further, a still safer
vaccine is introduced wherein the inactivated virus is grown
in the human diploid cell strain(HDCV vaccine), the dosage
schedule of which is 1 ml IM on days 0, 3, 7, 14 and 28.
Vero cell live vaccine (0.5 ml on days as schedule for
HDCV) from kidneys of monkeys is another new one. The
bite itself should be treated with soap and water or quaternary
ammonium compounds or 70% alcohol or cauterisation. The
wound should never be sutured. Passive immunisation with
rabies immunoglobulin 20 i.u/kg (50% around the wound
and 50% in the buttock) may be combined. If it is not a
available within 24 h equine rabies antiserum (40 i.u/kg)
can be used as an alternative, after testing for sensitivity.
Interferon may be used to infiltrate the wound
intramuscularly.
Treatment is symptomatic if clinical rabies actually
develops.
The most beneficial preventive approach under normal
cicumstances is, avoiding stray dogs in general and
immunisation of household dogs and cats and active
immunisation of persons at high risk of exposure like
veterinarians.
Tabes dorsalis (Tabetic crises)
a. Antileutic treatment must be given. (Refer to Chapter
‘Paraplegia’)
b. Laryngeal crises are usually relieved by inhalation of
amylnitrite. Bilateral abductor paralysis may necessitate
tracheostomy. Other tabetic crises are ameliorated with
analgesics, and/or antispasmodics.
c. Other associated features are treated appropriately, i.e.
easing pains with carbamazepine or steroids;
perforating ulcer with protective dressings and systemic
antibiotics; atonic bladder with instructions to pass
urine at 4-hourly intervals and damaged joints with
elastic support.
Chronic
Mysthenia (Refer to Chapter ‘Paraplegia’)
5. Metabolic
Metabolic Acidosis
Acute
Diabetic ketoacidosis (Refer to Chapter ‘Coma’)
Renal insufficiency (Refer to Chapters ‘Oliguria and
Polyuria’)
Methyl alcohol poisoning (Refer to Chapter ‘Coma’)
Chronic
Renal insufficiency (Refer to Chapter ‘Oliguria and Polyuria’)
Psychogenic
Acute
Anxiety disorders The treatment of anxiety disorders which
includs panic disorders, agoraphobia (fear of crowded
places), simple phobia, obsessive disorder or generalised
anxiety disorders, consists of behavioural therapy
techniques, psychotherapy and pharmacotherapy (Refer to
Chapter ‘Fatigue’).
Hyperventilation syndrome The therapy should be directed
at the underlying causes like brainstem lesions; uraemia;
excess aspirin ingestion or psychogenic disorders (Refer to
Chapter ‘Coma’).
Respiratory alkalosis, if ensues, may be treated by
rebreathing the exhaled air through a paper or rebreathing
bag (in order to supplement carbon dioxide). CNS disorders
with continued hyperventilation may require a carbon
dioxide rebreathing apparatus.
Tetany may be treated with 10 per cent calcium
gluconate IV.
Chronic
Neurocirculatory asthenia (Da costa’s syndrome) (Refer to
Chapter ‘Chest Pain’).
Dyspnoea 153
154 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Epileptic Seizures
10
Epilepsy is derived from the Greek meaning “to seize upon”.
The epileptic seizure is accompanied by abnormal electrical
activity of cerebral cortex and described as “paroxysmal
cerebral dysrhythmia”. It is due to rapid excessive disorderly
electrical discharges of the neurons in a structurally normal
or abnormal cortex or diencephalon. It is characterised by
abrupt spontaneous onset of motor, sensory, autonomic or
psychic disturbances with or without loss of consciousness.
The ictal events are recurrent, stereotyped and transient.
Epileptogenesis is attributed to changes in neuro-
transmitters and abnormal reactions in the neuron cell
membrane levels. The deficiency of the neurotransmitter
gamma amino butyric acid (GABA) and the disturbance in
the extracellular ionic concentration like increased
potassium and decreased calcium play an important role in
the mechanism of a seizure.
A double classification of epilepsies, better adopted, is
based on the
a. Causation
b. Clinical presentation
The causation again has to be viewed in relation to age
at first attack of the seizure. The clinical presentation may
be of
a. Partial type
b. Generalised type (nonconvulsive or convulsive)
c. Status epilepticus
d. Unclassified
These types depend upon the site of abnormal discharges
of the cerebral neurons and the mode of spread. If it occurs
in a localised cortical area, a partial seizure results whose
symptoms reflect the normal functions of the affected
structures. When the ictal propagation to contralateral
hemisphere and other areas occur, a generalised seizure with
loss of consciousness is produced.
The aetiological classification is grouped as
1. Symptomatic (with apparent local or general cause)
2. Idiopathic (with no apparent cause)
3. Psychogenic
AETIOLOGICAL CLASSIFICATION OF
EPILEPTIC SEIZURES
Table 10.1 describes aetiological classification of epileptic
seizures.
Idiopathic
If all the above causes are excluded then only an idiopathic
or cryptogenic origin has to be postulated. Heredity seems
to play an important role in epilepsy and autosomal dominant
mode of inheritance is suggested. Sometimes, generalised
focal seizures can be evoked by external stimulation like
loud noise, music, flashing light, cutaneous stimuli like
touching a particular part of the body or a specific voluntary
movement (reflex epilepsy). An underlying cause cannot
be ascertained usually but occasionally a focal disease may
be associated with reflex epilepsy.
Psychogenic
Psychological factors may precipitate attacks, hysteria is
well documented, with manifestations of somatic symptoms
like convulsions. Certain environments and emotional
feelings, result in over reaction in some situations exhibiting
somatic symptoms like convulsions which are reproduced
without being fully aware of the motives.
Symptomatic
First episode (new onset) seizures in adults or of late onset
(after 20 years) are usually secondary to underlying
pathology as detailed below as against primary seizures
which are usually of early onset.
 156 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 10.1: Aetiological classification of

iii. Hepatic failure
epileptic and seizures
iv. Phenylketonuria
Symptomatic v. Hypoxia
• Local Causes vi. Electrolyte disturbances (Hypo and Hypernatraemia,
a. Infections water retention, hypocalcaemia, alkalosis).
i. Meningitis d. Endocrinal
ii. Encephalitis i. Toxaemia or pregnancy
iii. Cerebral malaria ii. Tetany
iv. Cysticercosis e. Nutritional
v. Tuberculoma i. Rickets@
vi. Leutic ii. Pyridoxine deficiency
iii. Wernicke’s encephalopathy
vii. HIV
f. Anoxaemia
b. Circulation disturbances
i. Asphyxia
i. Cerebral arteriosclerosis
ii. Breath holding fit@
ii. Cerebral thrombosis, haemorrhage and embolism
iii. Subarachnoid haemorrhage Note: The causes marked @ are highly confined to the early onset of
iv. Hypertensive encephalopathy life and especially in infants and children.
v. Heart block (Stokes-Adams)
vi. Long Q-T syndrome
vii. Syncopal epilepsy: During syncope symptoms of epilepsy Local Causes
appear.
c. Space occupying lesions
Infections
i. Angiomatous malformation@ • Meningitis (Refer to Chapter ‘Headache’)
ii. Intracranial tumour • Encephalitis (Refer to Chapter ‘Coma’)
iii. Cerebral abscess • Cerebral malaria (Refer to Chapter ‘Coma’)
iv. Hydrocephalus@ • Neurocysticercosis (Cysticercus cellulose is a systemic
d. Trauma infestation of larval stage of Taenia solium developing
i. Birth injury@
ii. Head injury Haematoma
e. Degenerations Table 10.2: International classification of epileptic seizures
i. Diffuse sclerosis A. Partial (Focal, Local) Seizures
ii. Pick’s disease Simple Partial Seizures
iii. Alzheimer’s disease i. With motor signs
f. Congenital Defects@ ii. With sensory or special sensory symptoms
i. Congenital diplegia iii. With autonomic symptoms
ii. Infantile hemiplegia iv. With psychic symptoms
iii. Porencephaly
Complex Partial Seizures (with Impairment of Consciousness)
iv. Epiloia
i. Simple partial evolving to generalised seizures
General Causes ii. Complex partial evolving to generalised seizures
a. Infections@: Febrile illnesses like pertussis, hyperpyrexia and iii. Simple evolving to complex partial and evolving to
teething (reflex) generalised seizures
b. Intoxications
B. Generalised Seizures (Convulsive and Nonconvulsive)
i. Alcohol
Nonconvulsive
ii. Lead
i. Absence seizures
iii. Arsenic
ii. Atypical absence seizures
iv. Carbon monoxide poisoning
iii. Myoclonic seizures
v. Chemicals like ether, nitrous oxide
iv. Atonic seizures
vi. Drugs like pencillin, lidocaine, cyclosporin, Psychotropic
drugs (lithium, tricyclics, phenothiazines), withdrawal of Convulsive
benzodiazipins i. Tonic seizures
c. Metabolism ii. Clonic seizures
i. Hypoglycaemia iii. Tonic clonic seizures
ii. Uraemia C. Unclassified Epileptic Seizures
 Epileptic Seizures
Fig. 10.1: Life cycle of Taenia solium—Cysticercosis
occasionally in man either by swallowing ova through
contaminated food/hands (even without harbouring adult
worm) or autoinfection through regurgitation of ova from
mature gravid segments of an adult worm, harboured in
the human intestine. In the stomach, the oncospheres
are liberated from the eggs, which penetrate intestinal
mucosa and are carried to numerous sites (muscles,
subcutaneous tissues, eyes, brain, etc.) where they encyst
as cysticerci. (Normally cysticercus cellulosae occurs
in pigs after eating human faeces containing ova. When
improperly cooked measly pork or infected pork
containing cysticercus cellulosae, is consumed by man,
the larva develops into an adult worm) (Fig. 10.1).
The cyst, usually surrounded by a fibrous tissue
capsule, consists of an opalescent bladder containing
larva (single head or scolex) at its bottom with fluid rich
in salt and albuminous material. Neurocysticercosis may
be solitary/multiple or assume racemose (grape like)
form. The larvae live for about 5-20 years in the absence
of inflammatory reaction. If the tissue reaction occurs
in the brain (inflammatory process with associated
vasculitis leading to degeneration of larvae) epileptic
fits, neuropsychiatric manifestations or intracranial
hypertension may result. When the larvae cease to live,
the cysts calcify.
Neurocysticercosis is identified by radiology, CT
scan (measures usually less than 20 mm unlike
tuberculoma which is more than 20 mm) or magnetic
resonance imaging and confirmed by immunodiagnosis,
by ELISA techniques and biopsy of subcutaneous
nodules, if present.
Tuberculoma: It begins as circumscribed patch of tuberculous
leptomeningitis and is cortical or subcortical in cerebral or
cerebellar hemispheres. Tuberculous lesion elsewhere may
or may not be present. CT scan of brain diagnostic.
157
Leutie: (Refer to Chapter ‘Paraplegia’).
HIV: Acute HIV may be associated with transient
meningoencephalitis.
Circulation disturbances
• Cerebral arteriosclerosis: Intimal thickening and
roughening of its lining membrane lead to progressive
obliteration of cerebral artery resulting in ischaemia and
subsequent areas of atrophy. Compensation which occurs
through collaterals may be hindered if the blood pressure
is low or collaterals narrowed. Transient ischaemic
attacks or arterial thrombosis leading to infarction may
result in hemiparesis, dementia (progressive impairment
of higher intellectual functions), emotional disturbances,
epilepsy, or parkinsonism.
• Cerebral thrombosis, haemorrhage and embolism (Refer
to Chapter ‘Coma’)
• Subarachnoid haemorrhage; hypertensive encephalo-
pathy (Refer to Chapter ‘Coma’)
• Heart block (Refer to Chapter ‘Syncope’)
• Long Q-T interval syndrome: Seizures occur secondary
to torsade de pointes tachycardia.
Space occupying lesions
• Angiomatous malformation: Angiomatous malforma-
tions are congenital abnormalities of vascular system.
Arteriovenous malformations (one of the types) consists
of enlarged tortuous vessels encountered in the region
of middle cerebral artery. Bruit may be present over the
scalp due to increased vascularity.
• Intracranial tumour; cerebral abscess; and hydroce-
phalus (Refer to Chapter ‘Headache’)
• Trauma (Refer to Chapter ‘Coma’)
• Degenerations
• Diffuse sclerosis Intellectual deterioration, fits, visual
impairment, gait disturbances in a previously healthy
 158 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
child and spastic weakness of the limbs are the principal
manifestations.
• Alzheimer’s disease and Pick’s disease Progressive
dementia (impairment of memory particularly for recent
events, reasoning and judgement), emotional instability,
insomnia, language deficits, epileptic seizures, constitute
the clinical picture of AD (Memory consists of register
retain, recall and no recall is possible even after providing
clues is highly suggestive of AD as against cerebral
aging). Deterioration of personality, delirium, delusions,
aggression may be encountered as the disease progresses.
Though level of consciousness is normal, confusion may
supervene. The cerebral damage in AD is more global
than focal (as in multi-infarct dementia). This
neurodegenerative disorder occurs in two forms, i.e.
AD-1 in late life and AD-2 in middle life. The evidence
of increased concentration of aluminium in the brain
tissue is being incriminated, apart from a genetic defect
in some cases.
Pick’s disease is a form of primary degenerative disorder
occurring in middle life mostly in women. It is characterised
by progressive dementia, restlessness followed by apathy
and fits later.
Congenital defects
• Congenital diplegia: This type of cerebral palsy in
young children is characterised by mental retardation,
spastic weakness, involuntary movements and ataxia.
The weakness may be more in the lower limbs than the
upper limbs (diplegia) or equal in all (quadriplegia). The
neurological disturbances (motility and coordination and
mental retardation) are variable and nonprogressive.
Traumatic brain damage during delivery, anoxia,
impaired cerebral perfusion and hypoglycaemia are the
incriminating causes.
• Infantile hemiplegia: This type of cerebral palsy
complicates acute infections of childhood. It is mostly
vascular in origin and the onset is sudden with
convulsions. Consciousness may be lost and the limbs
of the affected side are flaccid with extensor response.
The limbs become spastic in the course of few weeks,
in case the hemiplegia does not recover.
• Porencephaly: Porencephaly is a defect in the cerebral
cortex, with a cyst like expansion of the lateral ventricle
extending to pia-arachnoid membrane. It may be
unilateral (secondary to local damage of cerebrum during
late foetal life or early infancy) or bilateral (develop-
mental). Clinical features are amentia and hemiparesis.
Transillumination test may be positive.
• Epiloia (Tuberous sclerosis): This congenital disorder
is characterised by mental retardation associated with
epilepsy, adenoma sebaceum, tumours in other organs
like retinal phakomas. It is due to dysplasia arising in
early embryonic life, and sclerotic masses in the cerebral
cortex.
General Causes
Infections like whooping cough (caused by Bordetella
pertussis) characterised by severe paroxysms of cough and
whoop, may be associated with fits due to cerebral anoxia.
Other infections associated with high fevers may cause
febrile convulsions.
Intoxications (Refer to Chapter ‘Coma’)
Metabolic
• Hypoglycaemia (Refer to Chapter ‘Coma’)
• Uraemia (Refer to Chapters ‘Polyuria’ and ‘Oliguria’)
• Hepatic failure (Refer to Chapter ‘Jaundice’)
• Hyponatraemia (Refer to Chapter ‘Coma’)
• Water retention (Intoxication): The power of the distal
renal tubules of the kidney to produce a dilute urine is
restricted in situations like heart failure, liver failure,
renal disease and postoperative period. Sometimes,
certain tumours like bronchial carcinoma secrete
polypeptide with antidiuretic properties. Some drugs
induce water retention due to release of vasopressin apart
from psychogenic compulsory water drinking. This leads
to water intoxication resulting in dizziness, headache,
confusion, convulsions, raised CSF pressure and even
coma. The plama osmolality is reduced and plsma
sodium is below 130 m Eq/L (Refer to Chapter ‘Coma’).
• Alkalosis
a. Metabolic alkalosis (Refer to Chapters ‘Coma’ and
‘Vomiting’).
b. Respiratory alkalosis Hyperventilation due to
pulmonary pathology, assisted respirations,
meningoencephalitis, hepatic failure, salicylate
poisoning or hysteria cause a reduction in PaCO2
with compensatory decrease in bicarbonate and
increase in pH. Clinical features are tetany, seizures,
cardiac arrhythmias, and impaired consciousness.
• Phenylketonuria: It is an inherited (autosomal recessive)
disorder of aminoacid metabolism. Hyperpheny-
lalaninaemia resulting from impaired conversion of
phenylalanine to tyrosine, consequent to hydroxylase
deficiency, is the basic metabolic abnormality in a new
born.
 Epileptic Seizures
Though no abnormalities are present at birth, the
child fails to achieve the developmental milestones with
impaired cerebral function, leading to mental retardation,
seizures, eczema and behavioural problems.
Diagnosis is confirmed by estimating phenylalanine
levels in serum (> 20 mg%), and by detecting phenyl-
pyruvic acid in the urine which gives a marked green
colour with ferric chloride solution (colour fades in a
few minutes).
Hypernatraemia (Refer to Chapter ‘Coma’).
Hypocalcaemia (Vide infra).
Endocrinal
• Toxaemia of pregnancy (Preeclampsia and eclampsia)
Preeclampsia exists in two forms—mild and severe. It
is characterised by sustained blood pressure of more than
140/90, persistent proteinuria of more than 300 mg/L
after 20th week of gestation. Oedema assumes
significance if the swelling involves hands and face as
well, with a gain in weight of over 2 kg in a week.
It is said to be severe if any one or more of the
following features are present
a. Blood pressure is more than 160/110
b. Proteinuria is more than 3 gm/d
c. Oliguria
d. Persistent visual or cerebral disturbances
e. Pulmonary oedema
Preeclampsia may progress to eclampsia when
seizures develop and coma supervenes in addition to
marked hypertension and proteinuria. It can occur
antepartum, intrapartum or postpartum (first two days).
Serum uric acid and blood urea are raised.
Complications like abruptio placentae (bleeding with
uterine pain during 3rd trimester of pregnancy) and DIC
are to be watched carefully.
The term gestational hypertension is a blood pressure
of 140/90, without proteinuria (or less than 300 mg/L)
after 20 weeks gestation.
• Tetany: Tetany (with paraesthesiae, muscle cramps and
carpopedal spasm) is usually due to alkalosis (vomiting
or hyperventilation) or hypocalcaemia (inadequate
absorption or intake-osteomalacia/rickets) or hypopara-
thyroidism or pseudo hypoparathyroidism or acute
pancreatitis). Severe hypocalcaemic tetany may
occasionally produce seizures. If hypertension,
hypokalaemia and polyuria are associated with tetany
(due to alkalosis), it may indicate primary hyperaldo-
steronism. Sometimes, magnesium deficiency may
account for tetany. The classical signs are:
159
a. Trousseau’s sign (carpal spasm results after applying
a blood pressure cuff and occluding the brachial
artery)
b. Chvostek’ sign (facial contraction on tapping the
facial nerve (over the parotid gland) near the angle
of the jaw)
c. Though laryngismus stridulus, convulsions, carpo-
pedal spasm are common in children, carpopedal
spasm is the usual presenting feature in adults.
d. Serum calcium is low and phosphate is raised with
normal alkaline phosphate in hypoparathyroidism
whereas serum calcium is low and phosphate may
be low or normal with raised alkaline phosphate in
osteomalacia or rickets. X-ray of the skull may show
calcification of the basal ganglia in hypo-
parathyroidism. In alkalotic tetany, the blood pH is
increased with consequent reduction of ionised
calcium, though total serum calcium is normal.
Nutritional
• Rickets: Rickets may be either vitamin-D deficiency
rickets (nutritional) or vitamin-D resistant rickets
(heredofamilial vitamin-D disorders). Seizures may
occur occasionally in the former only.
a. Vitamin-D deficiency rickets: It is a metabolic
disorder of calcium and phosphorus affecting
growing bone (defective mineralisation). It is due to
vitamin-D deficiency (inadequate intake or absorp-
tion) leading to insufficiency of calcium. In intestinal
disease like coeliac disease due to inadequate fat
absorption, vitamin D (fat soluble) is eliminated and
excessive fatty acids in the gut interfere with calcium
absorption, by forming insoluble soaps. It is further
compounded by high phytate intake (wheat flour)
which impairs calcium absorption. Long term
anticonvulsant therapy leads to formation of inactive
metabolites from vitamin-D by hepatic enzyme
induction. The chracteristic striking clinical features
are bony changes (craniotabes, rickety rosary,
Harrison sulcus, pigeon chest, enlarged epiphyses
at the lower ends of the long bones, knock knee or
bow legs), delayed milestone, pot belly, tetany and
sometimes fits.
The radiological examination of the wrist shows
characteristic thickening of the epiphyseal cartilage
and widening of the distal ends (saucer deformity)
and the chemical pathology (vide supra) are
confimatory.
b. Vitamin-D resistant rickets: Vitamin-D must be
hydroxylated to become active, first by the liver
 160 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(calcidiol) and then by the kidney (calcitriol). Vitamin-
D resistant rickets results from impaired
hydroxylation of calcidiol to calcitriol by the
inherited tubular defects like X-linked
hypophosphataemic rickets or in chronic renal
failure. Short statured with florid rickets is the
presenting feature. There is no hypocalcaemic tetany
or muscle weakness. Though therapeutic doses fail
to respond, large doses of vitamin-D are effective.
• Pyridoxine deficiency: The deficiency of pyridoxine
(which plays an important role in the metabolism of
aminoacids) may result in varying clinical features in
adults and children. Convulsions are reported to occur
in infants due to milk diet deficient in pyridoxine besides
irritability of nervous system with a startle response (refer
to Chapter ‘Fatigue’).
• Wernicke’s encephalopathy (Refer to Chapter ‘Coma’)
Anoxaemia
• Asphyxia: Asphyxia occurs antenatally in 50 per cent
of cases, intrapartum 40 per cent and postpartum 10 per
cent. Improved obstetric management has considerably
reduced the incidence of perinatal asphyxia. Cerebral
palsy, i.e. abnormalities of motor function develop
depending on the severity of hypoxaemia like spastic
diaplegia or mental retardation with quadriplegia or
choreoathetotic or ataxic cerebral palsy.
Asphyxia may be induced by pertussis, laryngismus
and breath holding spells. The intensity of asphyxia is
determined by Apgar scoring system. Severe asphyxia
(Apgar 0-2), moderate asphyxia (Apgar 3-4), mild
asphyxia (Apgar 5-7), no asphyxia (Apgar 8-10).
• Breath holding fits: The children below five years, who
are excitable and self-willed, are usually affected. It
consists of a spasm of the respiratory muscle with the
chest fixed in expiration (differing from the spasms of
the laryngismus wherein chest is fixed in inspiration).
The spasms tend to occur whenever there is temper
tantrum (with fear, anger and crying vigorously). When
the breath is held for few seconds, the child becomes
cyanosed, unconscious and limp. If the breath holding
is continued for further few seconds, jerks of the limbs
occur, followed by fits.
CLINICAL PRESENTATION
Partial Seizures
Structural disease of one cerebral hemisphere is account-
able.
Simple Partial Seizures
The abnormal electrical activity is localised to a part of one
hemisphere and consciousness is not impaired. The clinical
manifestations are varied depending upon focal brain
dysfunction.
Motor manifestations Jacksonian epilepsy is one classical
focal seizure. The pattern depends upon where the focus of
excitation exists and its propagation. If the lesion is in the
premotor area, tonic spasm; and if in the motor area clonic
twitches, occur especially over the limbs (fingers or toes),
face (angle of the mouth) and spreads to other muscles on
the same side of the body. The spread of the ictus
corresponds to representation of the movements in the motor
cortex and the march of events depends on involvement of
the lower or upper part of the cortex. The attack subsides in
seconds or minutes usually. Consciousness is retained. Todds
paralysis may occur. If this postictal deficit persists for more
than 48 h an underlying progressive organic lesion may have
to be suspected.
Somato sensory seizure It consists of paraesthesiae like
numbness or tingling or electric shocks confined to one half
of the body. The march is akin to Jacksonian motor seizure
and the lesion is in the sensory cortex (parietal).
Special sensory seizures are
a. Visual hallucinations consist of flashes of light or
coloured lights and the lesion is in the occipital lobe.
b. Auditory hallucinations consist of spoken words or even
songs or buzzing in the ears and the lesion is in the
superior temporal gyrus.
c. Olfactory hallucinations consist of imaginary smells,
unpleasant or pleasant and the lesion is in the inferior
and middle temporal gyri (uncinate seizures).
d. Gustatory hallucinations consist of imaginary tastes
varying from sweetness to bitterness and the lesion is in
the insular cortex.
e. Vertiginous sensation may be the inaugural symptom of
seizure and the lesion will be in the mid temporal lesion.
Autonomic feature It consists of peculiar sensation in
epigastrium, changes in the blood pressure, sweating,
pupillary changes (unilateral or bilateral).
Psychic symptoms like emotional fear, hallucinations, Deja
vu phenomenon and dreamy states.
Complex Partial Seizures
These are usually associated with impairment of conscious-
ness ranging from unawareness of the ictal episode to
 Epileptic Seizures
complete loss of consciousness. They last for few seconds
to few minutes and may be followed by automatism.
The classical example is temporal lobe epilepsy or
psychomotor epilepsy.
This attack consists of
i. Psychic component
ii. Motor component
iii. Automatic component
Psychic component It consists of olfactory or gustatory aura
with hallucinations of unpleasant smell or taste. There may
be visual or auditory aura with distortions of size of objects
or sounds and associated with disturbances of memory.
Deja Vu phenomenon—intense feeling of a familiarity
in unfamiliar surroundings.
Jamais Vu phenomenon—objects appear far away.
Affective symptoms like anger, depression and a dreamy
state or dazed appearance, dystonic posturing of contralateral
upper limb form part of the ictal events.
Motor component Involuntary movements like chewing,
licking or smacking of the lips or blinking or outbursts of
laughing accompany the aura. Clonic movements of the face
and turning of the head and eyes to one side may precede
the altered state of consciousness. The subject becomes
motionless and unresponsive for about 10 to 15 seconds.
Automatic component Here the stereo type automatic motor
activity occurs like buttoning the clothes or removing the
clothes, rearranging objects or throwing articles onto the
floor. In some cases, actions like walking or eating may
continue automatically. Verbal utterances of sentences or
gestural movements like scratching the head or a bizarre or
aggressive behaviour form other aspects or automatism.
Usually the attack lasts for 30 s to 2 min, occasionally it
may be continued for hours.
Partial Seizures Evolving to Secondarily
Generalised Seizures
Both simple and complex partial seizures are potential
enough to evolve into a secondary generalized seizure. A
focal onset may be obvious before it becomes generalised
like a typical grand mal. The focal nature may take the form
of a focal twitching or a visceral sensation or an aura. This
is usually associated with an underlying organic cause,
particularly in the presence of neurological signs in between
the attacks. Electrical evidence of focal discharge during or
after the generalised seizure is contributory.
161
Generalised Seizures
No features referable to one hemisphere only is
appreciated.
Nonconvulsive
Absence seizures (Petit mal) This is usually seen in children
from the 4th year of life up to adolescence. Classical attack
consists of momentary loss of consciousness like stopping
in the middle of a sentence and continuing after a pause
(perseverative automatism). Blank stare, rolling of the eyes,
twitching of eye lids, jerks of the arms and fingers are the
other features. There may be loss of tone, besides these jerks
and blanks. There will be no generalised convulsion, no
warning, it may occur suddenly without postictal phase. The
whole duration may last for less than 10 seconds and such
attacks may be as many as 100 even in the course of the day
(pyknolepsy). These may disappear in adolescence and may
be replaced by grand mal. The subject is usually unaware
of the attack. Invariably it is idiopathic and EEG is highly
characteristic with 3 per s spike and wave discharges.
Atypical absence seizures These seizures occur in children
and last longer than 10 seconds. Mental retardation,
neurological deficits and other types of generalised seizures
are associated features (Lennox-Gastaut syndrome). The
etiology is attributed to organic diffuse brain lesions.
Myoclonic seizures The attack consists of bilateral, sudden
shock like jerks (clonic muscular contractions of the groups
of the voluntary muscles) of the face, limbs and trunk. The
patient may be thrown to the ground suddenly and there is
no disturbance of consciousness usually. It occurs in children
between 5 to 15 years and is familial, being inherited as an
autosomal recessive trait.
Atonic seizures (Drop attacks) This consists of brief attacks
of sudden loss of muscle tone without tonic spasm or clonic
movements or warning. The atonia is confined to the head
and neck resulting in head drop or limbs may be affected
and the patient may fall to the ground often with an injury.
Unawareness of this fall is the only inkling of loss of
consciousness. Usually they are seen in children. The term
akinetic seizures is sometimes used to describe such attacks.
Convulsive
Tonic seizures They consist of muscular rigidity with
opisthotonos and loss of consciousness without clonic
movements. The head and lower limbs are extended. The
 162 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
upper limbs are internally rotated with extended elbows and
flexed interphalangeal joints. This tonic epilepsy may be
associated with organic brain lesions such as mid brain
tumours.
Clonic seizures Occasionally generalised convulsive seizures
may consist of only clonic activity.
Tonic clonic seizures (Grand mal) The convulsions can be
described under there stages
a. Warning stage
b. Convulsive stage
c. Postictal stage
In majority of cases, the warning aura may not be
experienced. It is stereotyped for the individual. Aura may
consist of a motor or sensory component including that of
special senses.
The motor component consists of twitches and turning
of the head and eyes. Sensory component comprises of
numbness over a part of the body. There may be a feeling of
unreality or intense fear, making one to run before the onset
of convulsion.
i. Visual auras (flashes of light)
ii. Auditory auras (imaginary uttered sounds)
iii. Olfactory hallucinations (imaginary smell)
iv. Vertigo
v. Abnormal visceral sensations like funny sensation
in the epigastrium
The convulsions consist of generalised spasm of the
muscles. It begins with a cry due to the spasm of the glottal
muscles and sudden loss of consciouness. If the patient is
in upright position, he falls to the ground and injures himself.
The head and eyes rotate and the mouth is drawn to one
side, the upper limbs get adducted at the shoulder with flexed
elbows and wrists unlike tonic epilepsy. Lower limbs
becomes extended with inverted feet. Respiration is halted
temporarily. This tonic spasm lasts only for about 30 seconds
and is followed by clonic phase in which a series of short
jerks and muscular contractions occur for 1 to 2 min. The
tongue is bitten and there will be foaming at the mouth,
sphincter incontinence occurs. There is profuse sweating
and other features of autonomic over activity.
The postconvulsive stage consists of flaccid limbs and
continued unconsciousness. Pupils are fixed and dilated.
corneal and tendon reflexes are lost. plantar reflexes become
extensor. consciousness may not be fully regained for up to
1 to 2 hours. After regaining consciousness, the patient may
complain of headache and sleep off. Some may remain
confused which may vary from minutes to hours. In some
cases, the attack is followed by postepileptic automatism
consisting of inappopriate actions about which the patient
is unaware. Mental disturbances may be exhibited. In yet
others, transient paralysis of limbs occur lasting for 24 h
(Todds paralysis). The epileptic individual cannot recollect
the attack. The incidence of primary generalised convulsions
is much less than that of secondry generalised seizures
evolved from partial types. Most of these seizures are
indiopathic with or without inherited predisposition. Some
of them may be acquired due to systemic general causes
(vide supra).
Unclassified Epileptic Seizures
These attacks cannot be classified into definite entities due
to insufficient data. This is applicable to neonates and infants
where the cerebral cortex is not fully developed. The
infantile spasms consist of brief attacks ranging from
twitches of the mouth to focal clonic movements without a
fully blown generalised seizure. There may be flexion of
the arms, head, neck and trunk with knees drawn up (Salaam
Seizures). These result from diffuse lesions of the brain like
abnormalities of the pyramidal neurons of the frontal cortex.
The EEG pattern is called hypsarrhythmia. This symptom
complex (West’s Syndrome) usually disappears befor three
years and is sometimes replaced by other types of seizures
when they grow older.
Status Epilepticus
In this condition the fits occur continuously, without
recovery of the consciousness between the attacks or lasting
for more than 1/2 hour. If allowed to continue, deep coma,
hypotension, hypoglycaemia, hyperkalaemia and
hyperpyrexia occur. It is more common in symptomatic
epilepsy than idiopathic. The cause may be a sudden
withdrawal of antiepileptic drugs or a cerebral infarction or
acute meningoencephalitis or metabolic disturbances.
It may be major motor status or minor motor status or
complex partial status.
Generalised (Major Motor Status)
(Convulsive and Nonconvulsive)
This can be a tonic clonic convulsive status or nonconvulsive
absence status. The major motor epilepticus occuring ( with
or without a focal onset) with tonic or clonic movements,
without intervening recovery or consciousness, is a serious
medical emergency.
In the nonconvulsive or absence status, the subject
appears withdrawn with slow volition or may have stupor.
 Epileptic Seizures
Partial (Jacksonian-Minor Motor Status)
Sometimes in localised motor status, the attacks take the
form of persistent clonic movements confined to limited
part of the body which is termed as epilepsia partialis
continua.
Complex Partial Status
Complex patial status is a rare entity which consists of
alternating attacks of total unresposiveness with stereotyped
automatism and partial responsiveness with partial speech.
CLINICAL APPROACH
Diagnosis
The diagnosis of epilepsy involves three stages of evaluation.
The first stage is to decide whether the attack is a seizure
or not by gathering clinical evidence and by differentiating
from such other paroxysmal disturbances.
The second stage is to determine whether the seizure is
generalised or is of focal type. If generalised, is convulsive
or nonconvulsive. If focal, is it simple or partial. This is
feasible by analysing the evolutionary levels of the sensory
motor march of events and dissolution of the abnormal
activity. 85% of the generalised seizues are considered to
be idiopathic and the rest are symptomatic in origin whereas
most of the focal seizures will have an underlying
identifiable cause.
The third stage is to decipher the cause of seizure-
whether symptomatic with systemic insults or idiopathic or
hysterical?
• In Idiopathic epilepsy
i. The age of onset is usually below 20 years.
ii. Family history is forthcoming.
iii. There may be no localising signs in the majority.
iv. Seizure are known to occur for a long time running
to years even.
v. They are confined to cetain times of the day in the
24 hour period.
• In symptomatic epilepsy
i. The onset is late usually above 30 years.
ii. History of an illness or injury prior to the episode.
iii. Neurological signs are elicitable in the interictal or
postictal phases.
iv. A focal or unilateral fit.
v. A possible cause is usually discernible on
examination.
163
• In hysterical epilepsy
i. The convulsions are bizarre in type and not
stereotyped without an introductry aura or postictal
phenomena.
ii. They do not occur solitude and most often occur in
the daytime without injury or urinary incontinence
or biting of tongue. The loss of consciousness is not
complete and hence can be roused by forcible
manoeuvres. Severe contractions of the orbicularis
oculi muscles are encountered while eliciting a
corneal reflex.
The essential requisites for arriving at the desired
decisions are
1. A good painstaking history including the description of
the attack by a reliable eyewitness as well as interrogating
the patient.
2. Physical examination both general and neurological in
particular.
3. Accessory investigations.
History
Since history forms the major basis for diagnosing epilepsy,
an eyewitness account must invariably be sought.
Interrogation of the eyewitness
1. Is there any cry before the individual falls?
2. Is the attack generalised right from the beginning or is
it confined to one part of the body, evolving secondarily
to a generalised type or unilateral?
3. Is there any froth at the angles of the mouth?
4. What is the breathing like; any blueness noticed?
5. How long does the fit last?
6. Is he conscious or not /
7. Is the recovery immediate or delayed followed by
confusion, headache, sleepiness, paralysis, psychic
disturbances or automatism?
8. Is the attack stereotype always?
9. Does the attack occur when alone or surrounded by
people?
10. Any postictal events?
Interrogation of the Patient
1. Is there any warning before the attack?
2. Any injury sustained?
3. Any biting of tongue?
4. Is there any wetting of the clothes due to incontinence
of bladder?
 164 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
5. When did the first attack occur?
a. Is it solitary or frequent?
b. If so, what is the frequency between the attacks?
6. Does the attacks occur during the day time or night time?
7. How is it precipitated?
8. What is the total duration of the seizures?
Drug History and other Chemicals
Insulin, withdrawl of barbiturates or alcohol, insecticide.
Psychosocial History
Psychic traits and social habits like alcohol indulgence.
Family History
If any other member of the family, suffers, it is suggestive
of idiopathic origin.
Past History
Past history of head injury, illnesses, febrile convulsions.
Age of Onset
Infancy: Birth injury, congenital malformations, degene-
ration, acute infections, tetany, breath holding fits
• Childhood and adolescence: Trauma, acute fevers, (upto
20 years) meningoencephalitis, idiopathic
• Young age (adulthood) (up to 40 years): Space occupy-
ing lesions, infections, trauma, endocrinal, metabolism,
alcoholism and drugs
• Middle age (up to 60 years): Vascular lesions, presenile
dementias, metabolic disturbances, neoplasms,
alcoholism and drugs
• Old age (senesence) (beyond 60 years): Vascular lesions,
degenerative lesions, neoplasms
Physical Examination
General Examination
a. Look for evidence of biting of the tongue, personal
injury, incontinence of bladder or rectum.
b. Vascular naevi or sebaceous adenoma (epiloia,
subcutaneous nodules (cysticercosis).
c. Any jaundice or ear discharges.
d. Vital data-pulse rate, respiration, temperature, and blood
pressure, (including postural changes).
Neuropsychiatric Examination
Psychometric examination Memory, intelligence, attitude and
manners, orientation, judgement, mood, and insight may
give a clue to the presence of focal or diffuse brain lesions.
Neurological examination Fundus and visual fields; muscle
tone or paralysis; reflexes and any other focal findings which
enable localisation.
Chest Examination
Cardiovascular examination for any evidence of arthythmias
like heart block; and respiratory system examination for
evidences of any suppurative infections or tuberculosis.
Differential Diagnosis
Nevertheless a seizure has to be differentiated from certain
transient organic neurological conditions or systemic
disturbances or behaviour alterations.
i. Hysterical Seizures (Vide supra)
ii. Syncope: Here the subject often experiences pallor,
sweating, gradual dimming of vision and sinks to the
ground without injury, muscles flaccid, convulsions
usually absent, although occasionally associated with
motor features of tonic-clonic convulsion. Conscious-
ness is regained immediately and completely.
iii. Transient lschaemic Attacks: These attacks last longer
than epileptic seizures and residual signs may persist
for less than 24 h after regaining consciousness. They
may occur many a time during the day and exhibit
consistent symptom complexes since focal cerebral
dysfunction due to ischaemia is confined to the same
area of the brain. Presence of bruit supports the
diagnosis.
iv. Vertebrobasilar insufficiency: The drop attack produces
a sudden fall without warning but the patient gets up
immediately.
Consciousness is retained in contrast to atonic
epilepsy. The attack occurs commonly. Associated
symptoms pertaining to brainstem like diplopia,
dysarthria, dizziness, dysaesthesia, and dysphagia
occur.
v. Migraine: Prodomal symptoms of migraine may
stimulate epilepsy and the headache which is
predominant may be mistaken for postictal event.
Basilarly artery migraine consisting of the vascular
spasm of the vertebo basilar system due to migraine
may result in teichopsia (scintilating figures), diplopia,
 Epileptic Seizures
dysarthria, loss of consciousness and rarely a fit. The
loss of consciousness is gradual and rousable unlike
in epilepsy.
vi. Aural Vertigo: Vertigo may occur as a transient aura in
epilepsy which may be mistaken for an aural vertigo.
The latter is almost always associated with tinnitus,
increasing deafness or abnormal labyrinth and
consciousness is retained.
vii. Narcolepsy: In narcolepsy, the following occur
a. Sleep attacks: There are irresistible attacks of
sleep which can be aroused easily. Convulsive
movements are absent.
b. Cataplexy: There is sudden loss of voluntary
power of movement without disturbance of
consciousness. This is precipitated by emotional
stimuli.
c. Sleep paralysis: It consists of inability to move
hand or foot during the periods of awakening or
falling asleep, although the patient is fully
conscious.
d. Hypnagogic hallucinations in which vivid
terrifying hallucinations occur as patient falls
asleep.
Narcolepsy can be mistaken for epilepsy especially if
one of the four features are manifested and is
differentiated by the circumstances during which the
attacks occur, absence of convulsions and preservation
of consciousness. Such other sleep disturbances also
have to be differentiated from epilepsy.
viii. Tetanus: Lockjaw, muscular rigidity, opisthotonus and
severe intermittent spasms, without loss of
consciousness and history of past injury will clinch
diagnosis, from tonic fits which consist of coma and
decerebrate rigidity. Pyramidal involvement with
conjugate paralysis is elicitable.
ix. Rigors: Usually the consciousness is not lost and
invariably fever appears after the rigor, whether it is
due to infusion rigor or infection rigor.
Determining the Type of Seizure
Primary generalised convulsions usually have onset in
childhood and may be due to inheritance of inborn errors of
brain metabolism. They may be acquired at a later age due
to a variety of systemic disorders. Nevertheless, most of
them are idiopathic. The primary generalised seizures have
to be differentiated from secondary generalised seizures
evolving from partial.
165
Primary Secondary
1. Early onset Late onset
2. Less number of seizures More number of seizures
3. No aura or may be indefinable Aura invariably present
4. Not focal at onset Focal onset
5. No laterised postictal signs Focal signs presents during
postictal phase
6. No mental abnormalities Mental abnormalities present
7. Idiopathic Symptomatic
Partial seizures are more likely to be associated with
local intracranial pathology or general disorders. They occur
usually after 30 years of age. Consciousness may not be
impaired (simple) or impaired (complex) unlike in
generalised seizures where it is invariably impaired. They
are characterised by warning or aura preceding the attacks.
Typical focal, motor or sensory (tingling or visual
hallucinations) or psychic (Deja Vu phenomenon) symptoms
or psychic aura (dreamy state) or recent changes in
personality may be appreciated.
Deciphering the Cause
An attempt should be made to exclude the various local
and general causes of convulsions listed above.
Obvious causes associated with fits do not pose any
problem but certain local causes like intracranial tumours
or cysticercosis or general causes like hypoglycaemia (refer
to Chapter ‘Syncope’) may do so. In intracranial tumours
sometimes convulsions may precede other features like
headache and vomiting. Papilloedema and localising signs
such as local paralysis or sensory loss may manifest sooner
or later.
It is better to consider that every case of epilepsy is
possibly symptomatic and search for the clue for the
diagnosis of the cause. In this endeavour besides the
painstaking history and physical examination of the various
systems, investigations are of immense value.
Investigations
1. Urine and blood examinations: For metabolic disorders
like uraemia, and if necessary for inborn errors of
metabolism (serum creatinine, blood urea, blood sugar
and aminoaciduria). Cysticercosis antigen or
anticysticercosis antibody.
2. Serum electrolytes like calcium, sodium, potassium and
magnesium.
 166 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
3. Liver function tests like serum bilirubin, SGPT and GGT
(if indicated).
4. Serology: VDRL, full blood counts and toxic screens.
5. Radiology:(Neuroimaging-structural and functional)
a. X-ray of the skull for any evidence of increased
intracranial pressure (like silver beaten appearance,
erosion of clinoid processes, separation of sutures
in children); intracranial calcification and any
abnormal vascular markings.
b. CT Scanning: Many space occupying lesions are
identified by the computer tomographic scans. The
diagnostic precision of CT scan is much more
following conray when there will be an enhancement
of the lesion. This is particularly indicated in nascent
(new) seizures or late onset seizures or changing
pattern of seizures.
c. Cerebral arteriography is indicated as in surgical
intervention.
d. Positron emission tomography (PET) scanning,
radionuclide scanning, or magnetic resonance
imaging (MRI) may be occasionally helpful in
obtaining metabolic and morphological information
of the epileptogenous zones. Single photon emission
computed tomography (SPECT) and magnetic
resonance spectroscopy (MRS) allow structure
functional correlation.
6. Lumbar Puncture: Contraindicated if there is increased
intracranial pressure. If done, evidence of pleocytosis
and increased protein content of the CSF is highly
suggestive of underlying symptomatic etiology.
7. Electroencephalography (EEG): This enables to study
the activity for the cortical nerve cells. A normal EEG
shows waves which are regular in amplitude and
frequency without any spike. Rhythmical activity can
be classified as alpha and beta rhythms. Rhythmical
waves of 8 to 12 cycles per second and 0.5 to 1 millivolt
amplitude are observed from the postcentral gyrus areas
especially parieto-occipital region only at rest with the
eyes closed and disappear when the eyes are open (alpha
rhythm). Similarly, a faster rhythm with a frequency of
14 to 22 cycles per second is obtained from the frontal
regions (beta activity). In children, the EEG is different
and shows rhythmical high voltage slow activity 3 to 5
per second called delta waves. This is replaced by theta
waves (4 to 8 per s) as the child grows and finally by
alpha rhythm in adults.
EEG is useful in the diagnosis of epilepsy which
shows the characteristic spike and waves complex.
a. In partial epilepsy like temporal lobe epilepsy,
there may be focal spikes or sharp wave
discharges or paroxysmal rhythmical outburst of
slow delta or theta activity in temporal lobe.
b. In petit mal, it may show generalised spike and
delta wave discharges at a frequency of 3 cycles
per second.
c. In idiopathic epilepsy, it may show a mixed
frequency of paroxysmal widely diffuse multiple
spikes in rapid rhythm or paroxysmal outbursts
of spike and wave activity.
d. In secondary generalised—focal of diffuse
slowing of rhythm and irregular spike and wave
complex at 2.5 seconds or less.
EEG may be modified by certain activating
procedures like drug induced sleep, hyperventilation,
photic stimulation.
EEG normally records only about 30 minutes of
cerebral activity but in telemetry EEG, the EEG is
conveyed from a transmitter attached to an ambulatory
subject, to a recorder used for continuous recording
during 24 h.
The usefulness of EEG is limited since EEG may
be abnormal in about 70 per cent of epileptics only.
The negative findings in the remaining 30 per cent
should not exclude the diagnosis and should be
interpreted in the light of clinical findings and other
investigations.
Though EEG is always abnormal during the
seizure, it may not be practicable. However, an
abnormality may be appreciated if recorded in the
postictal period of 24 h and if it is taken after one week
it may be normal in about 20 per cent of cases.
8. Echoencephalography: Magnetic Encephalography
and vediomonitoring
9. ECG and Holter monitoring, if necessary.
10. Pulse oximetry.
If a confident diagnosis of the nature of the attack is in
abeyance, better wait for observing the seizure or precipitate
it if desirable. The precipitation is done by manoeuvres like
(a) hyperventilation for 3 minutes which may result in petit
mal or other types of seizures, (b) withdrawal from drugs
like barbiturates and alcohol, (c) depriving sleep, and (d)
psychological or certain external stimuli.
After diagnosing the nature of the attack as epilepsy,
investigations are undertaken depending on the age of the
patient, type of seizure, its duration and clinical data from
physical examination.
 Epileptic Seizures
TREATMENT OF EPILEPTIC SEIZURES
The aim of the therapy of seizures is to enable the patient to
lead a normal life as far as possible by (a) long term
pharmacologic control of seizures, (b) advocating relatively
safe occupations, and (c) adequate patient education
regarding factors precipitating seizures and possible dangers
associated with driving, swimming, etc.
Treatment During the Attack
a. Prevent the patient injuring himslf by promptly shifting
him from places of danger or from falling off his bed
during clonic stage.
b. A padded gag (or tightly rolled piece of cloth) or a plastic
airway should be placed between the teeth to prevent
tongue biting.
c. Remove the spectacles and dentures, if any, and loosen
the clothing round the neck.
d. Adopt semiprone position, with head down to avoid
aspiration.
e. Ensure a clear airway by suction and give oxygen to
prevent cerebral hypoxia.
f. Observe for automatism which may develop, after
recovery of consciousness.
Treatment Between the Attacks to Control Seizures
Anticonvulsant Drug Therapy
A single seizure calls for only evaluation rather than long
term drug therapy straightaway. To control recurrent
seizures, an appropriate anticonvulsant drug is given in small
doses and then the dose is increased gradually over a period
of two months start low, go slow. If unresponsive despite
optimal serum levels, add a second drug up to its maximum
dose, and taper the original one in the course of a month.
The combination of drugs is considered only when two
appropriate drugs are tried singley at maximum dose. The
drug therapy is usually maintained for 2 to 4 years and
withdrawal of the effective drug must be gradual over a
period of 4 to 6 wks; only after a seizure-free period of 2
years. (Taper one drug, if free from seizures then only taper
the second) The daily dosage schedules of drugs commonly
used are
i. Phenytoin (150-600 mg)
ii. Carbamazepine (200-1200 mg)
iii. Sodium valproate (400-2000 mg)
iv. Phenobarbitone (60-180 mg)
v. Primidone (250-1000 mg)
167
vi. Ethosuximide (500-1500 mg)
vii. Clonazepam (1-6 mg)
First line drugs are sodium valproate, Carbamazepine,
Phenytoin and Ethosuximide.
Drugs of choice advocated are (a) tonic-clonic seizures
(grand mal primary and secondary)—i, ii, iii, iv and v
(valproate is not beneficial in secondary grand mal seizures);
(b) Partial—ii, i, iv; (c) Absences (petit mal)—vi and iii;
(d) Myoclonic seizures—iii and vii.
New antiepileptic drugs are beneficial in refractory
epilepsies either as monotherapy or as an add on drugs
(Second line drugs).
i. Gabapentin (300-600 mg t.d.s.)
ii. Vigabatrin (0. 75 g to I g t.d.s.)
iii. Oxcarbazepine (100-600 mg t.d.s.)
iv. Fosphenytoin (5-20 mg/kg parenterally)
v. Lamotrigine (100-200 mg b.d.)
vi. Felbamate (I. I. 5 g t.d.s)
vii. Clobazam (5-15 mg/d)
viii. Tiagabine (15-30 mg/d)
ix. Topiramate (200-600 mg/d)
x. Zonisamide (200-600 mg/d)
xi. Levetiracetam (1-3 gm/d)
xii. Pregabalin (150-600 mg b.d)
N.B: Changing to another drug by introducing with its
starting dose and increasing slowly upto average of
therapeutic range and then only withdraw the drug over
about 6 weeks. If the single drug at its maximum dose fails,
then only maintenance with two drugs is considered.
Ketogenic Diet
It may be useful esp, in children.
Surgical Therapy
It is indicated only when the attacks are severe without
adequate control. By and large, only few patients need surgery.
It may include anterior temporal lobectomy for temporal lobe
epilepsy or excision of an organic cerebral lesion or division
of the corpus callosum in intractable epilepsy.
Underlying Cause
It is corrected (by medical or surgical approach) while
anticonvulsants are also administered simultaneously.
Adjunctive Therapy
Glutamic acid is given along with phenytoin and dietary
fats.
 168 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Psychotherapy or Behavioural Therapies
Psychological treatment may be necessary in some cases,
where emotional factors appear to precipitate.
Treatment of Status Epilepticus
(Continuously for > 5 minutes)
Convulsive status is a medical emergency and should not
preferably be allowed to continue for more than 20 minutes.
1. Ensure adequate airway, IV access, and administer high
flow oxygen; if necessary.
2. Give bolus of 50 ml 50% glucose IV
Antiepileptic Drugs
First ½ hour Administer diazepam 10 mg IV over 2 min
slowly wait for 5 minutes, watching for any respiratory
depression (pulse oximetry)
1. If seizures continue, repeat IV diazepam at the rate of
1 mg for 1 minute till seizures cease or upto a total of
10 mg only.
2. (Lorazepam 0. 075 mg/kg IV at 2mg/min) is another
alternative to diazepam).
Second ½ hour If seizures still continue or regardless of
response, administer IV Phenytoin in normal saline (avoid
dextrose since the drug precipitates) 10-15 mg/kg at the rate
of 50 mg per minute upto 250 mg (watching for any
hypotension and continuous ECG monitoring are
imperative). Should not be used in Bradycardia.
(Chlormethiazole is an alternative to phenytoin (5-10 ml of
0.8% infusion over 5 min, then ½ ml/min.) or Fosphenytoin
(preferred to Phenytoin) IV infusion 10-15 mg/kg at the
rate of 100 mg/min. If status persists give phenobarbitone
20 mg/kg IV infusion at the rate of 100 mg/min.
Beyond one hour If seizures still persists, anaesthetic doses
of pentobarbitol 5-12 mg/kg followed by 1-10 mg/kg/hr
infusion or propofol 3-5 mg/kg followed by 1-5 mg/kg/hr
infusion or valproic acid 25 mg/kg IV at the rate of 20-100
mg/min diluted 2:1, upto 1500-2000 mg or Midazolam
0.2 mg/kg followed by 0.1-0.4-mg/kg/hr infusion or general
anaesthesia with halothane and endotracheal intubation may
be necessary.
N.B.: Usually most of the cases respond to Diazepam and
Phenytoin. Be prepared for ventilatory assistance.
• Identify any metabolic or other underlying cause and
treat simultaneously.
• General measures adopted as for the management of
coma, must be followed; if unconsciousness is prolonged
(use suction procedure if necessary)
• Complications if any are to be treated promptly such as-
i. Aspiration pneumonia treated with appropriate
antibiotics.
ii. Cerebral oedema, if occurs, must be promptly treated
with i.v Mannitol (20%), glycerol (10% in 500 ml
of 5% dextrose) and corticosteroids (10 mg of
dexamethasone).
iii. Hyperpyrexia and dehydration, if occurs, treated
appropriately.
• After recovery, a lone term pharmacologic control must
be insisted with oral antiepileptic drugs along with the
management of any discernable cause.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
Symptomatic
Local Causes
Infections
a. Meningitis—(Refer to Chapter ‘Headache’)
b. Encephalitis—(Refer to Chapter ‘Coma’)
c. Cerebral malaria—(Refer to Chapter ‘Coma’)
d. Neurocysticercosis—Apart from anticonvulsant drugs
(vide supra) and measures to control cerebral oedema
with raised intracranial pressure, larvicidal drugs
considerably influence the prognosis i.e.
i. Praziquantel (50 mg/kg/d) givn for 15 days. Oral
prednisolone (if necessary) may be started two days
prior to praziquantel and tapered after 15 days.
Though CT scan shows improvement progressively
even after two years, the actual clinical improvement
is maximum only after three months.
ii. Albendazole (15 mg/kg/d for four weeks) is a good
alternative and economical although comparatively
peak therapeutic responses appear slowly. CT scan
shows partial or complete regression in few cases
after one year.
iii. Metrifonate (7.5 mg/kg/d) appears promising (Figs
10.2A and B).
iv. Surgery is confined to those cases with large cysts
or intraventricular cysts causing obstructive
hydrocephalus.
v. Proper hygiene, health education, pork inspection
are preventable steps.
e. Leutic—(Refer to Chapter ‘Paraplegia’)
Circulation disturbances
a. Cerebral arteriosclerosis without thrombosis—
Arteriosclerosis without thrombosis causing seizures
 Epileptic Seizures
Fig. 10.2A: Cranial CT scan showing decreased attenuating
(low density) lesion, which is enhancing with IV contrast in a
nodular fashion over right frontal area—neurocysticercosis
(before treatment)
Fig. 10.2B: Contrast cranial CT scan after six months showing
complete clearance of the lesion with abendazole therapy
needs only symptomatic therapy with anticonvulsants.
Vasodilators or pentoxyphylline may not be of much
utility. However, antiplatelet drugs may be given. The
associated conditions like hypertension, diabetes
mellitus, hypercholesterolaemia, hyper homocystinaemia
influencing atherosclerosis are better kept under control.
169
b. Cerebral arteriosclerosis with thrombosis, cerebral
embolism, cerebral haemorrhage, subarachnoid
haemorrhage and hypertensive encephalopathy—(Refer
to Chapter ‘Coma’)
c. Heart block (Stokes-Adams syndrome)—(Refer to
Chapter ‘Syncope’)
Space occupying lesions
a. Angiomatous malformation—Consider surgery, if
necessary.
b. Intracranial Tumour, Cerebral Abscess and
Hydrocephalus—(Refer to Chapter ‘Headache’).
c. Tuberculoma.
Anti Koch’s therapy (Refer to Chapter ‘Haemoptysis’)
(Figs 10.3A to C).
Trauma Haematoma (Refer to Chapter ‘Coma’).
Degenerations
a. Diffuse sclerosis: Only symptomatic treatment with
anticonvulsants, as the cause is not known.
b. Pick’s disease and Alzheimer’s disease: The incriminat-
ing cause of dementia and concurrent medical disorder,
if any, may be treated. Co-dergocrine mesylate is
beneficial. Tetra-hydroaminoacridine, an anticholineste-
rase is promising. Apart from anticonvulsants if required,
design suitable social and behavioural therapies.
Neuroleptics (haloperidol or thioridazine) or Beta-
lockers are fairly useful to control abnormal behaviour.
It is better to administer them in low doses initially and
step up gradually.
Congenital defects
a. Congenital diplegia:
i. Drugs are of little value though baclofen and
diazepam may help to reduce spasticity. However,
anticonvulsants are necessary to control seizures.
ii. The child must be facilitated to learn to walk and
use the limbs appropriately. Intensive physiotherapy
is of immense value to prevent contractures and
deformities.
iii. If associated with mental retardation, advocate
special educational programmes to improve the
intelligence quotient.
iv. Surgical procedures are considered to correct
deformities. Postrior rhizotomy is promising.
b. Infantile Hemiplegia: In acute stage, treatment is directed
against the underlying cause, apart from genral measures
being adopted as needed (like unconsciousness). Later
on active and passive movements are encouraged to
prevent contractures. Speech therapy, physiotherapy and
 170 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 10.3A: Two small ring enhancing lesions in the left frontal Fig. 10.3C: Disappearance of lesions after
parasagittal region with surrounding oedema—Left parasagittal anti-Koch’s therapy for further 6 months
tuberculoma
d. Epiloia: Give anticonvulsants to control epilepsy. Mental
retardation may be managed by special learning
programmes and if severe, institutional treatment
considered.

General Causes
Infections Febrile convulsions in children, treated
symptomatically, apart from instituting specific therapy for
the underlying infection.
Intoxications (Refer to Chapter ‘Coma’)
Metabolism
a. Hypoglycaemia: (Refer to Chapter ‘Coma’)
b. Uraemia: (Refer to Chapters ‘Polyuria and Oliguria’)
c. Hepatic failure: (Refer to Chapter ‘Jaundice’)
d. Water retention: Restrict water intake for few days. If
serum sodium is below 130, IV normal saline or
hypertonic saline is given, as needed. Loop diuretics may
Fig. 10.3B: A ring enhancing lesion be employed to prevent possible overexpansion of
after 10 months of therapy extracellular volume.
e. Alkalosis:
behavioural therapy are contemplated as per the needs. i. Metabolic alkalosis—(Refer to Chapter ‘Coma’)
Anticonvulsants are given in appropriate doses for few ii. Respiratory alkalosis—Encourage the patient to
years. If necessary, surgical correction by tenotomy rebreath his own carbon dioxide by breathing into a
considered. paper bag or 5 percent carbon dioxide and oxygen
c. Porencephaly: Treatment is like that of congenital may be administered. Tetany is treated by IV calcium
diplegia. Shunt surgery is recommended if the head is gluconate 10 percent. Specific therapy is directed at
enlarged. the underlying causative disorder.
 Epileptic Seizures
f. Phenylketonuria: The treatment consists of a restricted
phenylalanine diet. The protein is replaced by an artificial
mixture of amino acids low in phenylalanine. This is
supplemented with small quantities of natural foods to
facilitate that amount of phenylalanine necessary for
normal growth. (The blood levels of phenylalanine are
maintained between 3-10 mg%.) This restriction may
be confined to a period of 3-6 years and if required, life-
long.
g. Hypernatraemia (Refer to Chapter ‘Coma’).
h. Hyponatraemia (Refer to Chapter ‘Coma’).
Endocrinal
a. Toxaemia of pregnancy (preeclampsia and eclampsia—
Prompt treatment is necessary and it depends on the
severity of toxaemia. Preeclampsia stage should be so
managed as to prevent eclampsia. In preeclampsia, bed
rest, salt restriction, fluid balance, sedatives and
antihypertensive drugs (only hydralazine, methyldopa,
beta-blockers recommended) are indicated. The delivery
must be timed properly without delaying for more than
two weeks. During this period, any intrauterine growth
retardation is to be ruled out by an ultrasound. (Diuretics
are contraindicated in preeclampsia.)
In eclampsia, if the patient is convulsing, turn her to
one side to prevent aspiration of vomitus or mucus and
caval syndrome, besides other measures of general care.
Oxygen may be administered. Magnesium sulphate (10
ml of 25% IV every 6 h) is indicated for its anticonvulsive
and antihypertensive effects. Continue magnesium
sulphate for 24 h following delivery and then reduce. If
overdosage occurs, calcium gluconate (20 ml of 10%)
is given IV. Diazepam may be considered. In case of
marked hypertension, proteinuria, involvement of central
nervous system demand termination of pregnancy.
However, eclampsia must be controlled before induction
of labour. Foetus must be monitored carefully. Vaginal
delivery or caesarian section attempted as the situation
demands.
b. Tetany
i. Therapy consists of treatment of an acute attack as
well as underlying cause. Acute tetany is treated with
10 ml of 10 per cent calcium gluconate IV slowly
over 3 min., and repeated if necessary.
ii. If tetany is due to primary hypoparathyroidism or
pseudo hypoparathyroidism, or follows surgery,
prolonged replacement with vitamin-D (life long
follow up) is usually effective, i.e. synthetic
analogues of vitamin-D-alfacalcidol or calcitriol
(0.5-5 µg/d) orally.
171
iii. In malabsorption syndrome, parenteral calciferol (7.5
mg monthly) given.
iv. Rickets and osteomalacia; Oral calcium salts and
vitamin-D3 reinforced with dietary supplements
suffice (vide infra).
v. In chronic renal failure, alphacalcidol (5 µg/d) orally
is beneficial.
vi. In alkalotic tetany, due to persistent vomiting IV
saline and acidifying agents like ammonium chloride
in severe cases; and hyperventilation by inhalation
of 5 per cent carbon dioxide in oxygen or rebreathing
his own carbon dioxide by breathing into a paper
bag, are most effective, apart from IV calcium
gluconate.
Nutritional
a. Rickets
i. The chemical form of a vitamin-D exists in 2 forms
(i.e.) D2 (Ergocalciferol) found in fungi and yeasts;
and D3 (cholecalciferol) found in human and animals
(natural). It is converted to 25 OHD in the liver which
in turn forms calcitriol in the kidney. Alpha calcidiol
(a synthetic analogue) is converted into calcitriol in
the liver itself or its derivatives and the dosage
schedule is detrmined by the underlying cause.
ii. Treatment of primary vitamin-D deficiency rickets
includes therapeutic doses of vitamin-D 3 ,
(cholecalciferol or calciferol)—25-50 µg/d) (1 µg =
40 units) together with calcium supplements (0.3-
0.6 g of elemental calcium daily). This schedule is
given till serum alkaline phosphatase returns to
normal and then reduced to prophylactic dose of 10
µg/d. Free access to sunshine and diet rich in calcium
and vitamin-D3 advocated.
iii. Correct underlying malabsorption syndrome, if any.
iv. In vitamin-D resistant rickets, high doses of oral.
(1 mg = 40,000 units) or alphacalcidiol (2-5 µg/d)
or Calcitriol (0.5-3 ug/d) may be considered
calciferol 10000 units/24 h orally, (vit D3) is also
beneficial.
b. Pyridoxine deficiency—The child is usually treated with
pyridoxine (5 mg i.m.) followed by 0.5 mg/d orally for
two weeks. Simultaneously diet containing adequate B6
advocated (refer to Chapter ‘Fatigue’).
c. Wernicke’s encephalopathy—(Refer to Chapter ‘Coma’)
Anoxaemia
a. Asphyxia: Neonatal resuscitation is done as per the Apgar
scoring system, just like for an adult, i.e. airway,
breathing, circulation (ABC). Mild asphyxia requires
only stimulation (spanking and rubbing of the back) and
172 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Epileptic Seizures
oxygen. Moderate asphyxia requires bag and mask
ventilation with 100 per cent oxygen apart from
suctioning of the oropharynx and trachea, especially
when the infant is born through thick meconium. If there
is no response, the infant is treated as that of sevre
asphyxia requiring vigorous resuscitation (endotracheal
intubation with artificial ventilation and oxygenation and
cardiac massage if the heart rate is less than 60).
Umbilical vein catherization may be done for
medication, if required. If the heart rate does not rise
beyond 100/min despite resuscitation, acidosis should
be corrected with sodium bicarbonate (2 mEq/kg) diluted
with 10-25 percent of glucose (1:1). Other drugs used
are adrenaline (0.5 ml 1 in 10,000), alternatively atropine
(0.01 mg/kg); calcium gluconate (10% 2 ml); volume
expanders (20 ml/kg).
If the mother is known to have received any narcotic
drug, naloxone (0.01 mg/kg) is to be given.
b. Breath holding fits: Splashing cold water on the face
helps, the moment the attack sets in. Since it is a
behavioural problem, no active drug or psychotherapy
is indicated. Reassurance, liberal kindness, under-
standing a child and guarding from all excitements are
beneficial. Withhold any aggressive handling or
punishment during the attack. An attempt should be made
to create a congenial environment for the child.
173
Idiopathic Since the cause is not known, the management
of a seizure depends upon general measures and
anticonvulsant therapy during an attack, followed by
appropriate long term drug therapy. If seizures are entirely
controlled for about three years, the dose may be slowly
reduced over one year and finally withdrawn ensuring that
there is no recurrence (vide supra).
Psychogenic Treatment of convulsions due to psychogenic
origin includes
a. Isolation of the patient from the precipitating environ-
ment.
b. Correction of any underlying problem of interrelation-
ship.
c. Social adjustments and modifications to be made as
necessary.
d. Placebotherapy—Parenteral placebotherapy followed by
oral placebo medication sometimes helps, since such
patients are highly vulnerable to suggestions.
e. Special therapeutic procedures like hypnosis, abreactive
therapies, psychotherapy, behavioural therapy, stress
management are beneficial.
f. If there is any associated anxiety or phobia or depression
or conversion reaction, appropriate psychotropic drugs
are considered.
 Chapter
Fatigue
11
Generalised weakness (debility), lassitude and tiredness are the possibility of fatigue due to a physical illness particularly
common subjective complaints. Though these terms are in the earlier stages must be borne in mind and a search
freely used to connote one for the other, they are not should be made for the wide spectrum of trivial to critical
synonymous. The weakness varies in character and extent organic causes rather than simply brushing it aside as due
ranging from malaise to loss of muscular power of neural to stress and strain or a manifestation of psychiatric disorder.
or myopathic origin. It may be persistent or episodic. Debility
often presents per se (asthenia) or may be associated with MECHANISM OF FATIGUE
other symptoms like pallor or weight loss. Lassitude is
Fatigue after physical exertion is predominantly a disorder
disinclination to work or indifference to tasks entrusted and
of muscle metabolism and attributed to
inability to concentrate which may be associated with or
1. Depletion of muscle glycogen and accumulation of lactic
without disease. Normal persons encounter this experience
acid and other metabolites which may lead to poor
which may lead to phobia of disease or it may be merely a
contraction and delayed recovery of muscle
normal physiological response to prolonged stress and strain.
2. Depletion of muscle creatine
Tiredness most often is related to physical effort.
3. Defective formation of phosphagen
Fatigue or excessive tiredness is a complex sensation, With
4. Altered concentration of electrolytes (sodium,
physicochemical and psychological basis which in turn leads
potassium, calcium, magnesium) and disturbance of fluid
to decreased capacity for a physical or mental effort.
balance
Although fatigue follows increased physical activity, it may
5. Inadequate oxygen supply to muscles due to impaired
be experienced without any exertion. It can be physiological,
vascular supply during contraction.
pathological or psychological in origin. The weariness and
feeling ‘below par’ is encountered in normal healthy CAUSES OF FATIGUE
individuals; sometimes influnced by changes in climatic
conditions. It may be precipitated by electrolyte disturbances Causes of fatigue have been listed in Table 11.1
or nutritional deficiencies, or hormonal changes. Unhealthy
life styles, inadequate rest, undue emotional strain and 1. Haematological
overwork may contribute to fatiguability. Exhaustion or
extreme fatigue is a severe form of fatigue which indeed is
Anaemia
a state of altered metabolism. Anaemia connotes reduction in the circulatory haemoglobin
A feeling of general weakness and tiredness may come concentration below 13 gm/dl in men and 12 gm/dl in
on suddenly before the onset or after any acute illness. There nonpregnant women (WHO). The fall in haemoglobin is
remains yet another group of disease in which the weakness usually but not invariably associated with a fall in red cell
is of gradual onset with chronic and indefinite course. A count. Thus in iron deficiency anaemia, the red blood cell
subject who does not feel well, with no other symptoms count may remain normal in spite of significant fall in
suggestive of a disease process, can be readily explained by haemoglobin. Packed cell volume in the haematocrit is
overwork or emotional strain with inadequate rest. However, usually lowered along with haemoglobin levels (38% in men
 Fatigue 175

Table 11.1: Causes of fatigue c. Hormonal deficiency

1. Haematological d. Marrow failure (replacement by fibrous/neoplastic
a. Anaemia tissue or disturbed marrow function due to chronic
b. Polycythaemia infection, uraemia, collagen disease)
c. Methaemoglobinaemia • Increased red cell destruction (usually reticulocytosis)
2. Metabolic and Endocrinal or haemolytic
a. Diabetes mellitus
a. Haemolysis
b. Fluid and electrolyte disturbances
c. Hyper or hypothyroidism b. Haemorrhage
d. Aldosterone deficiency • Blood loss or posthaemorragic
e. Addison’s disease a. Acute posthaemorrhagic anaemia
f. Simmond’s disease b. Chronic posthaemorrhagic anaemia
3. Malnutrition • Refractory anaemia may be due to noncompliance,
4. Infections and Inflammatory Disorders misdiagnosis, chronic infections, chronic blood loss,
a. Occult infections
malabsorption, myelodysplasia.
b. Tuberculosis
c. Connective tissue disorders Morphological Based on the average cell volume (MCV)
5. Neoplasia and haemoglobin concentration (MCHC)
a. Lymphomas • Normocytic anaemia (usually normochronic), e.g.
b. Carcinoma of the bowel, particularly caecum
hormonal (thyroid) deficiency: marrow failure or
c. Carcinoma of the bronchus
d. Any other occult carcinoma replacement; or disturbed function due to prolonged
6. Cardiovascular Disorders disease (chronic infection); haemolysis and haemorrhage
a. Peripheral circulatery failure (rapidly setting) MCV is normal.
b. Central cardiac failure • Microcytic anaemia (usually hypochromic), e.g.
7. Respiratory Disease impaired haemoglobin synthesis (iron deficiency
a. Chronic obstructive pulmonary disease anaemia; noniron deficient anaemia like thalassaemia,
8. Gastrointestinal Disorders
sideroblastic anaemia, occasionally anaemias of chronic
a. chronic dyspepsia
b. Chronic diarrhoea disorders, hookworm infestation). MCV is low.
c. Chronic hepatitis • Macrocytic anaemia (usually normochronic), e.g.
9. Neurological Diseases Impaired DNA synthesis (megaloblastic anaemias due
a. Myasthenia gravis to vitamin B12 pernicious anaemia or folate deficiency);
b. Parkinsonian syndrome (Parkinsonism) myxoedema; aplastic anaemia; chronic liver disease;
c. Insomnia acute haemolysis; acute haemorrhage; drugs like
10. Psychogenic: Anxiety and depressive states; Emotional stress
antifolate phenytoin. MCV is high.
11. Asthenic Syndromes: Tropical neurasthenia, neurocirculatory
asthenia, and chronic fatigue syndrome Clinical essence Fatiguability is highly characteristic of
12. Drugs/Chemicals and Alcohol: Beta-blockers, diuretics, anaemia apart from other symptoms like exertional
alcoholism, tranquillisers, and chronic carbon monoxide
dyspnoea, headache, dizziness, palpitations, dyspepsia,
poisoning.
paraesthesiae, pallor of the skin and mucous membrane/
conjuctivae. Tachycardia, haemic murmur and cardiomegaly
and 35% in women) but not invariably. As a result of with or without heart failure may be encountered.
expansion of plasma volume in pregnancy, relative anaemia Iron deficiency anaemia may be further characterised
occurs, due to altered proportions of red cells and plasma to by glossitis, stomatitis, koilonychia and dysphagia. The
blood volume. (Physiological anaemia). megaloblastic anaemia may be associated with neurological
Classification of the anaemias can be etiological or signs due to the involvement of posterolateral columns and
morphological. peripheral nerves besides glossitis and angular stomatitis
Etiological (Refer to Chapter ‘Paraplegia’). The haemolytic anaemia is
• Decreased red cell production or dyshaemopoietic associated with jaundice without a change in urine colour
(usually reticulocytopenia) (Refer to Chapter ‘Jaundice’).
a. Impaired haemoglobin synthesis Refractory anaemia connotes no response with
b. Impaired DNA synthesis conventional drugs for about 3-6 months. It may be due to
 176 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
noncompliance, malabsorption, misdiagnosis or may be due
to myelodysplasia syndrome, aplastic anaemia, Sideroblastic
anaemia, refractory iron deficiency due to chronic bloos loss
or Helicobacter pylori; paroxysmal nocturnal haemo-
globinaemia or chronic infections.
• Possible Mechanisms of Anaemia
1. Impaired synthesis of haemoglobin or DNA due to
diminished intake; diminished absorption and
increased demands of erythropoietic factors; protein
malnutrition and parasitic (hook worm, tape worm)
infestation.
2. Blood loss
3. Prolonged illness like chronic infections or
inflammations and malignancy
4. Endocrinal diseases
5. Aplasia or hypoplasia of the marrow
6. Haemolysis due to haemoglobinopathies or toxic
factors
Fig. 11.1: Microscopic diagnosis of blood cell disorders
• Diagnosis
Detection of the type and cause of anaemia is possible
by blood examination like
1. Complete blood counts (erythrocytes and
haemoglobin; leucocytes, platelets, ESR)
2. Peripheral blood smear for: (Fig. 11.1)
A. Number and character of RBCs
a. Size (micro, macro or normocytosis;
anisocytosis) and staining of RBC (less
dense suggestive of hypochromic anaemia).
b. Shape (poikylocytosis)
c. Type [Burr cells (RBCs with spiky
projections) suggest malignancy or uraemia;
target cells suggest thalassaemia or
spherocytes in hereditory sphereocytosis or
fragmented RBC (schistocytes) in intra-
vascular haemolysis]
 Fatigue 177

d. Immature red cells like normoblast with Fluid and Electrolyte Disturbances
nucleus present in marrow infiltrations.
a. Salt depletion may be due to either defective intake or
B. Number and character of white blood cells.
excessive loss (through renal or gastrointestinal or
a. Hypersegmented polymorphs suggest B12 or
cutaneous) which may lead to fatiguability and if the
folic acid deficiency
b. Low WBC suggests marrow depression depletion is severe, it will affect the volume of the
c. Eosinophilia suggests parasitic infestation extracellular fluid.
d. Myeloblast or lymphoblast suggests b. Hypokalaemia due to alimentary or renal losses or
leukaemia inadequate intake may result in weakness, fatiguability
C. Number of platelets: Low platelet count and significant depletions may lead to paresis or ileus
suggests marrow depression. or cardiac arrhythmias.
3. RBC indices like MCV, MCHC c. Hypermagnesaemia and hypercalcaemia may affect the
4. Colour Index (CI): muscle metabolism resulting in muscle weakness.
Magnesium is an important activator of the enzymatic
Haemoglobin per cent
0.9 1.09 functions of phosphate transfer reaction and also acts
Red cell count × 20 directly on the myoneural junction. Hypermagnesaemia
Millions/cmm
decreases acetylcholine release and diminishes the
a. If colour index is high, it indicates pernicious excitability of the muscle cell. The effect of calcium on
and other such anaemias. the cell membrane potential and permeability influences
b. If CI is low, it suggests iron-deficiency the neuromuscular function apart from its role in muscle
anaemias. contraction. High calcium concentrations diminish
c. If CI is about unity, it points towards anaemia excitability and lead to flaccidity and weakness.
following haemorrhage. d. Hypophosphataemia: Low levels of inorganic
5. Sickle cell test phosphorus (hypophosphataemia) may be associated
6. Serum iron, transferrin and total iron binding with bone pains and muscular weakness. The former is
capacity, folate, B12 due to osteomalacia resulting from phosphate depletion.
7. Haemoglobin electrophoresis and plasma The latter is due to direct effect of low levels of phosphate
electrophoresis on the nerves and muscles and hyperparathyroidism;
8. Bone marrow examination—hyperplasia in
hypophosphataemia occurs in osteomalacia.
haemolytic anaemia when there is increased RBC
production or sideroblast in the marrow in
sideroblastic anaemia or megaloblast in pernicious Hyper or Hypothyroidism
anaemia (B12 deficiency). Refer to Chapters ‘Goitre’ and ‘Obesity’
9. Further tests depend upon the disorder suspected
(thyroid function tests, liver function tests; Aldosterone Deficiency
antibodies, etc.) Isolated aldosterone deficiency is seen in renal failure
secondary to diabetic nephropathy or hyporeninism or severe
Polycythaemia
postural hypotension. Unexplainable hyperkalaemia is the
Refer to Chapter ‘Cyanosis’. presenting feature which may be aggravated, when sodium
intake is reduced.
Methaemoglobinaemia
Refer to Chapter ‘Cyanosis’ Addison’s Disease
Refer to Chapter ‘Shock’
2. Metabolic and Endocrinal
Diabetes Mellitus Simmond’s Disease

Refer to Chapter ‘Polyuria’ Refer to Chapter ‘Weight loss’

 178 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
3. Malnutrition
The essential modes of malnutrition result from deficiencies
either in
1. Primary phase (availability, storage, processing, socio-
economic factors and customs) or
2. Secondary phase (ingestion and digestion of foods)
a. Defective intake of food due to anorexia or prolonged
vomiting
b. Defective absorption as in steatorrhoea or
3. Tertiary phase (absorption and assimilation)
a. Defective utilisation as in cirrhosis or prolonged
illness
b. Loss of nutrients like proteinuria or glycosuria or
blood loss or
c. Increased nutritional needs as in pregnancy.
The undernutrition may be primarily caloric under-
nutrition (quantitative) or nutrient undernutrition (qualita-
tive). In addition malnutrition may be either an imbalance
in diet or a specific deficiency (quantitative or qualitative
or both). The specific nutritional disorders are protein
malnutrition, vitamin or mineral deficiencies.
Fatigue may be an initial complaint of any nutritional
deficiency.
4. Infections and Inflammatory Disorders
Occult infections
Refer to Chapters ‘Pyrexia of Unknown Origin’ and
‘Haematuria’
Tuberculosis
Pulmonary tuberculosis or tuberculous disease elsewhere
may often present with lassitude apart from low grade fevers
and nocturnal sweats (Refer to Chapters ‘Haemoptysis’ and
‘Chronic Diarrhoea’).
Connective Tissue Disorders
Fatigue is not a striking feature of connective tissue disorders
as compared to the classical arthralgias and other features
(Refer to Chapter ‘Polyarthritis’). Fatigue may be out of
proportion to other presenting symptoms especially in
chronic infections rather than in acute.
5. Neoplasia
Carcinoma of any type, ranging from occult neoplasm to
even with widely disseminated stage may be associated with
fatigue.
Lymphomas
Refer to Chapters ‘Pyrexia of unknown Origin’ and Bleeding
Disorders’
Carcinomas
Carcinoma of the Bowel (Particularly Caecum) Carcinoma of
the caecum and large bowel may present with fatiguability
and weakness apart from vague abdominal discomfort
usually postprandial. Altered bowel habits are characteristic
of left colon neoplasia rather than right colon. Occult blood
or stool mixed with blood and mucus together with blood
clots may account for microcytic hypochromic anaemia.
Carcinoma of the Bronchus Refer to Chapter ‘Haemoptysis’
6. Cardiovascular Disorders
Peripheral Circulatory Failure (Rapidly Setting)
Rapidly setting peripheral circulatory failure as in internal
bleeding may complain of undue fatiguability (Refer to
Chapter ‘Shock’).
Central Cardiac Failure
Acute cardiac failure may result from acute myocardial
infarction or tachyarrhythmias due to marked reduction in
cardiac output.
Heart failure with low cardiac output may result in easy
fatiguability which is related to effort and improves with
rest. It may occur in mitral stenosis and congenital heart
diseases (Refer to Chapters ‘Oedema’ and ‘Chest Pain’).
7. Respiratory Disease
Chronic Obstructive Pulmonary Disease
Wheezing, dyspnoea and cough are much more prominent
features than fatiguability (Refer to Chapter ‘Dyspnoea’).
8. Gastrointestinal Disorders
Chronic Dyspepsia or Diarrhoea
Lassitude is common in chronic diarrhoeas or chronic
dyspepsias due to associated electrolyte disturbances or
anaemia and inadequate ingestion or digestion respectively.
So a careful interrogation should be made about the bowel
habits as well as the digestive capacity of the individual.
Chronic Hepatitis
Refer to Chapter ‘Jaundice’.
 Fatigue
9. Neurological Diseases
Myasthenia Gravis
Refer to Chapter ‘Paraplegia’
Parkinsonian Syndrome
It is characterised by
a. Characteristic mask-like facies and attitude of flexion
b. Poverty of voluntary and emotional movement
c. Muscular rigidity
d. Tremor at rest
e. Shuffling gait
Fatiguability usually precedes neurological signs and is
attributed to akinesia.
Insomnia
Insomnia is the inability to sleep at the normal time for a
normal period (7-8 h). Normally sleep consists of two
distinct states viz. nonrapid eye movement sleep (NREMS)
or slow wave sleep and rapid eye movement sleep (REMS).
These two alternating sleep mechanisms for NREMS and
REMS are monitored in the brainstem and influenced by
serotonin and norepinephrine.
The NREMS consists of four stages and the
sleeplessness complained usually is related to a decrease in
stage-3 and stage-4 sleep. The NREMS and REMS alternate
4-6 times in one night sleep. Insomnia which indicates sleep
deprivation is usually due to a variety of disturbances caused
by disease processes (organic or psychic). The usual organic
disturbances are circulatory disturbances like hypertension
or focal intracranial lesions of the sleep centre or fevers
with physical discomforts. The psychic states causing
insomnia include depression, anxiety or drug related
withdrawal syndrome (alcohol or sedatives).
Sometimes the sleep deprivation may be physiological
due to
a. External disturbing stimuli
b. Disordered conditioned stimuli like change in normal
surroundings
c. Situational problem associated with job pressure and
busy schedule
d. Ageing
The effects of sleeplessness reflect as fatigue and
irritability, lack of concentration, impaired performances and
lack of sense of wellbeing.
179
10. Psychogenic
Fatigue without any organic basic is merely a manifestation
of psychiatric illness like depression or anxiety compounded
by emotional stress.
Affective Psychosis
(Mood and Emotion: Depression)
Abnormal disturbance of mood is a reality in everyday life.
If it is long standing (at least two weeks) and of some
significant magnitude, it indicates a pathological mood
disturbance. Depressive or lowered mood varying from
sadness to sleeplessness is the cardinal feature of depression.
Some may exhibit symptoms of mania in addition to
depression. In general, there are three groups of depressions.
Reactive depression (Neurotic depression, reaction without
psychiatric features) It is a reaction to exogenous adverse
events in life. The symptoms range from mild depression
associated with concomitant symptoms of anxiety, neurosis
and insomnia. The insomnia is usually inability in getting
sleep (early night type). The subjects feel better in a
company.
Endogenous depression (psychotic depression)
i. Unipolar (major manic or depressive episodes): It is
based more on biological factors like life events. The
features of diurnal variation of mood depression (more
in the morning and clearing in the evening),
psychomotor retardation (difficulty in thinking and
withdrawal from activities), pessimistic thoughts, ideas
of unworthiness or guilt, chronic fatigue and somatic
complaints (like anorexia, weight loss, headache,
decreased libido, early morning awakening type, i.e.
waking up at 2 or 3 am at night and unable to sleep
afterwards), are characteristic.
ii. Bipolar: Increased activities which remain unfinished,
elevation of mood, and flights of ideas, constitute
cardinal features of mania which are often interrupted
by episodes of depression, cyclothymic disorder is a
mild form of bipolar disorder.
Secondary depression to Illness, childbirth and drugs Any
chronic illness is likely to be associated with depression.
Drugs like antihypertensives (reserpine, methyldopa and
propranolol), corticosteroids, oral contraceptives and alcohol
dependency are the classic examples of drug induced
depression. Postpartum period may be complicated by
depression.
 180 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Neurosis: Anxiety Neurosis
Anxiety is a common emotional response to external stresses
or may be a result of maladjustment to resolve the internal
conflicts. When it occurs as a symptom, it indicates
disturbance in the internal psychological equilibrium. These
anxiety or neurotic disorders have been classified as
a. Anxiety states or anxiety neurosis (panic disorders,
obsessive compulsive disorders)
b. Phobic disorders
c. Posttraumatic stress disorders (psychic trauma)
The principal components of anxiety are
i. Psychological (fears, tensions, worries, difficulty in
concentration)
ii. Somatic (palpitations, dyspnoea, faint, tremors,
sweating, fatiguability)
Psychiatric parameters like behaviour, sense of reality,
etc. remain unaltered. The affected individuals feel that the
symptoms are really due to an underlying physical illness
and not due to a psychiatric or emotional illness.
Anxiety reaction is of two types
a. Acute: Where the somatic manifestations referable to
autonomic nervous system or any organ, are prominent.
b. Chronic: Where the psychological symptoms are more
marked resulting in physical and mental exhaustion;
sometimes associated with depression.
11. Asthenic Syndromes
Tropical Neurasthenia
Neurasthenia or chronic nervous exhaustion mainly is
characterised by unexplained fatigue and lassitude where
the tiredness is neither relieved by rest nor precipitated by
the usual factors. Insomnia, lack of concentration and mild
degree of anxiety may also be associated. The headache of
a feeling of pressure in the head rather than pain is
complained. Autonomic nervous disturbances and retarded
sexual drive are added features. In tropics this neurasthenia
is precipitated usually by parasitic infestations like chronic
amoebiasis, tropical climatic influences and malnutrition.
Neurocirculatory Asthenia
Da Costa’s syndrome—(Refer to Chapter ‘Chest Pain’)
Chronic Fatigue Syndrome
The cause of this syndrome appears multifactorial. A strong
association between virus infections (like Epstein-Barr virus
(EBV) and Coxsackie B virus) and chronic fatigue syndrome
is identified, which renders many subjects inactive/disabled.
Besides postvirus infections, the other incriminating factors
are immunological disturbances (like functional deficiency
of natural killer cells and impaired interferon production)
and psychosocial morbidity. The corticotrophin releasing
hormone of the hypothalamus is reduced.
Unexplained fatigue appears suddenly which may be
persistent or episodic. The easy fatiguability is not relieved
with bed rest and in fact worsens on trivial exertion with
prolonged recovery time. Severe muscle or joint pains,
headache, feverishness, depression, insomnia are the other
associated features.
12. Drugs/ Chemicals and Alcohol
The long-term use of drugs is a common experience these
days.
a. Beta-blockers cause fatigue, and weakness of leg
muscles in about 30 per cent of patients.
b. Similarly diuretics may produce weakness due to
hypokalaemia; sometimes fatigue or lassitude may result
as a side effect of certain drugs like INH causing
psychiatric depression.
c. Chronic alcoholism and tranquilisers may cause
weariness. (Refer to Chapter ‘Weight Loss’)
d. Chronic carbon monoxide poisoning (inhaled smoke/
exhaust fumes, coal stoves) weakness, headache,
dizziness are the presenting features. Diagnosis is
established by estimating carboxy haemoglobin with
spectrophotometry or Kunkel’s test, i. e. crimson colour
occurs after adding tannic acid to diluted blood (1 in 10).
Pulse oximetry is not helpful, as it cannot differentiale
oxygenated haemoglobin and carboxy haemoglobin.
CLINICAL APPROACH
In evaluating a fatigue patient, the clinician must proceed
in an orderly manner since it is so nonspecific as to have
little significance in the differential diagnosis. However, the
work-up of fatiguability is better facilitated, if it is associated
with other features like anaemia, loss of weight or such
manifestations that offer a clue for the underlying systemic
disorder.
A clear distinction is imperative between fatiguability
of organic basis from that of an affective (functional
disorder). A careful enquiry is necessary whether the
fatiguability is related to effort or overwork or insomnia or
due to underlying possible physical illness. Diurnal variation
of mood, recurrent episodes of depression or anxiety may
lend support for the functional disorder.
 Fatigue 181

History 5. Any moist palms

6. Any arthralgia or arthritis
A standardised work up in the history is likely to yield clues
7. Oedema of the legs
towards the cause of fatiguability: whether organic, psychic
8. Vital data: Pulse rate, respiratory rate, temperature and
or problems of unhealthy lifestyle.
blood pressure.
1. Duration and type of fatiguability: Is it acute, chronic
(persistent) or episodic (recurrent)? Acute fatigue may Systemic Examination
be due to acute infection or electrolyte imbalance or 1. Chest examination for evidence of cardiomegaly,
rapidly setting peripheral circulatory failure whereas the murmurs, sternal tenderness or altered breath sounds
chronic fatigue may be due to psychoneurosis or and/or adventitious sounds.
underlying systemic illness. 2. Abdominal examination for hepatosplenomegaly or any
2. Precipitating factors: Is it related to an effort, lack of other mass.
sleep, overwork, disturbance of mood, emotional stress 3. CNS examination for evidence of wasting of the muscles
or adverse life events. or rigidity or changes in modalities of sensation or altered
3. Family history: May reveal inheritance pattern. reflexes.
4. Other conducive factors
i. Domestic environment, Psychiatric Examination
ii. Working environment, 1. Psychiatric history
iii. Unhealthy life style, a. Type of work and educational record may offer an
iv. Disproportionate work, leisure and sleep (number index of intellectual potential.
of hours of sleep, any difficulty to fall asleep, early b. From the patient’s viewpoint index: Present history
awakening with inability to sleep further). and circumstances, previous (premorbid) personality.
5. Onset: Rapid onset or gradual onset? c. From relatives or friends: Behaviour and family
6. Time of occurrence: Morning (depressive illness) or relationship, family history.
towards evening or any time? 2. Psychiatric examination
7. Appetite: Loss of appetite is suggestive of infections or a. Attitudes and manners
malignancies and increased appetite suggestive of b. Facial expressions
diabetes mellitus. Those who do not eat properly and c. Form of speech and its content
substitute beverages, like coffee appeasing the appetite d. Emotional responsiveness and status (mood)
may complain of fatigue. So dietetic data may be of e. Content of thought, drive and ambition
immense value. f. Cognition (orientation to place, person and time;
short-term and long-term memory; concentration,
8. Associated symptoms like temperature, joint pains,
e.g. month of the year backwards)
weight loss, pallor, dyspnoea, palpitations, cramps,
g. Abstracting abilities, calculations, and judgement
polyuria, and insomnia.
h. Abnormal experiences; and
9. Any history of blood loss.
i. Insight
10. Any previous history of surgery especially 3. Psychological testing
gastrointestinal. a. Objective test
11. Drug history. i. Intelligence test
12. History of emotional stress or episodic anxiety or ii. Multiphasic personality inventory
depression. b. Projective tests
Thematic apperception test (TAT) where 20 pictures
Physical Examination of people in different situations are presented and
General Examination interpretations called for.

1. Appearance: Gloomy or bright Investigations

2. Loss of weight 1. Haematological Examination:
3. Pale conjunctiva and/or tongue or glossitis or chelitis or A. Haemoglobin: males < 14 g/dl; females < 12 g/dl
koilonychia B. Packed cell volume or haematocrit (Hct): males
4. Lymphadenopathy or thyromegaly < 42 per cent; females < 37 per cent
182 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
C. Erythrocytes:
i. Red cell count < 4.5 million per c mm in males
and < 4 million in females
ii. Red cell indices
a. Mean Corpuscular Volume (MCV): 78-94 cµ
(cubic microns)
b. Mean Corpuscular Haemoglobin (MCH):
27-32 µµg (micromicrograms)
c. Reticulocyte count: 0.5 to 2 per cent of RBC
d. Recticulocyte index =
Recticulocyte Actual Hct
count (%) × 2 × Normal Hct
(If reticulocyte index is less than 2%, it
indicates less RBC formation. If more than
2%, it suggests excessive destruction or loss).
e. Red cell distribution width (i.e. RDW = 13.4
+ 1.2% (raised in iron-deficiency anaemia)
f. RBC lifespan (chromium labelling):
decreased survival of RBC in haemolysis.
g. Colour index: (Vide supra)
iii. Blood smear examination for
a. Varying sizes of red cells
b. Varying shapes of RBCs
c. Abnormal red cells (like spherocytes, target
cells, sickle cells, nucleated red cells).
iv. Erythrocyte Sedimentation Rate (ESR)
(Westergren): Males 0-15 mm/h; females 0-25
mm/h
D. Leucocytes: Normal WBC count 4,300-10,000 per
cmm.
E. Thrombocytes: Normal platelet count 1,50,000-
4,00,000 per cmm.
F. Bone mrrow examination to study the bone marrow
reaction whether it is megaloblastic or not. It is
mandatory in aplastic anaemias for hypoplasia or
hyperplasia in haemolytic anaemia.
G. Spectroscopic examination for abnormal
haemoglobin (methaemoglobin up to 1.7 per cent of
total haemoglobin is considered normal).
H. Serum levels:
a. Serum iron levels; ferritin levels: both reduced
in iron deficiency anaemia (normal value of
serum iron: 50-175 µg/dl; normal value of serum
ferritin: Males 30-300 µg/ml; Females 20-120 µg/
ml) (i.e.) 20-120 µg/L. Transferrin saturation is
decreased (NV: 25-40%) and iron binding
capacity is elevated in iron deficiency anaemia
i.e. fraction of transferrin to which iron is bound
expressed as per cent of total transferrin is called
transferring saturation; and transferrin expressed
as amount of iron that it combined is total iron
binding capacity (TIBC) which is 300 mcg/
100 ml.
b. Serum folic acid levels (normal value
2-20 µg/ml).
c. Serum B12 levels and serum B12 absorption test:
(Refer to Chapter ‘Chronic Diarrhoea’)
d. Serum LDH: Raised in megaloblastic anaemias
and haemolytic anaemia or (normal range
55-140 1u/L)
I. Other tests for haemolytic anaemia (Refer Chapter
‘Jaundice’)
Biochemical Tests
A. Glucose tolerance test (GTT)
B. Serum electrolytes (sodium and potassium)
C. Serum bilirubin levels (direct and indirect)
E. T4 and TSH levels
F. Rh factor and LE cell factor (for collagen disease)
G. Assay of circulating acetylcholine receptor antibodies
(for myasthenia gravis)
H. Appropriate tumour markers (for any malignancy)
Stool
Examination for evidence of parasitic infestation.
Urine
For sugar and urobilinogen.
Radiology
i. X-ray of the chest: PA view and lateral view: To
demonstrate any retrosternal goitre, thymoma or any
occult infection or malignancy.
ii. Barium series (Barium meal and/or enema): For any
occult infection or malignancy.
ECG
For evidence of any silent myocardial infarction.
Special Tests
i. Water excretion test: Administer 1500 cc of water to
the fasting subject between 8 am and 8.30 am and
kept in horizontal decubitis. Urine volume is
measured hourly for three hours. Normally diuresis
 Fatigue
is 400 to 500 ml hourly with a total volume of 1200 ml,
i.e. 80 per cent. If the response is impaired, it
suggests organic disease (since it is associated with
a delayed diuresis due to impaired permeability of
the sick cell membrane).
ii. To demonstrate disturbances of neuromuscular
transmission
a. Pharmacological test: Neostigmine 1.5 mg when
given intramuscularly improves the strength of
weak muscles in myasthenia which may last for
about two hours. Similarly edrophonium
(tensilon test) in a dose of 10 mg (2 mg initially
and if well tolerated the remaining 8 mg injected
30 s. later) given intravenously also improves
myasthenic weakness which may last for about
5-10 min.
b. Electrophysiology: Demonstration of a
decremental response (progressive reduction in
the amplitude of muscle action potential) to a
supra maximal stimulus of a motor nerve
repetitively at the rate of about 3 Hz, is valuable
to diagnose myasthenia.
c. EMG: Single fibre electromyography reveals an
increased neuromuscular jitter or variable time
intervals between action potentials related to
same motor unit.
iii. Psychiatric evaluation
a. Interview with relevant history and current
routine life (if necessary with the use of sedatives
like amylobarbitone or thiopentone).
b. Assessment of mental state (vide supra) to clinch
the presence of either neuroses (anxiety state,
phobic state, obsessive compulsive state, hysteria,
hypochondriasis, neurotic depression or neuras-
thenia) or affective psychoses (depression).
c. Psychological testing for measuring psycho-
dynamics by means of objective and projective
tests.
d. Biological markers (the dexamethasone suppres-
sion test and thyrotrophin releasing hormone test
may be useful in assessing depressive illnesses).
TREATMENT OF FATIGUE
A proper perspective of fatigue and elucidation of its causes
are the primary requisites for instituting a rational treatment.
After identifying the different categories of fatigue with
clinical reasoning and objectivity, a group of patients may
emerge wherein differentiation between fatigue secondary
183
to depression and depression secondary to fatigue may
become necessary. Precise therapeutic strategies, including
physical and psychological rehabilitation, are to be adopted
for such cases.
Hence, the therapeutic implications are related to
accountability and duration (whether short or long) of
fatigue.
Symptomatic Treatment
a. Avoid stress and overwork.
b. Rest may improve the exertional fatigue. If unresponsive,
psychological disorder may be operating.
c. Vitamins, minerals and glycerophosphates are of some
value.
d. Electrolyte powders or salted drinks may be beneficial.
e. Maintain adequate calorie diet and correct malnutrition,
if exists.
f. Extra energy may be provided with oral glucose if not
contraindicated.
g. Tranquillisers are helpful in functional fatigue.
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
1. Haematological
Anaemia
Decreased Production of Red Cells
A. Impaired haemoglobin synthesis: Iron deficiency
anaemia It usually results from either blood loss or
dietary inadequacy (low intake or malabsorption) or
hookworm infestation.
Oral iron therapy may suffice, and response is
appreciated within two weeks, though the normal values
are attained in 8-10 weeks. (Haemoglobin usually rises
by one g% per week). However, it is better to continue
iron therapy for 4-6 months even after haemoglobin
returns to normal to replenish iron stores. (Each g of
haemoglobin contains 3.4 mg of iron.)
Addition of vitamin C may enhance its absorption
(About 25% of iron is generally absorbed).
Numerous preparations are available but the following
preparations are in common use.
i. Ferrous sulphate (hydrated): 300 mg (63 mg
elemental iron) tds.
ii. Ferrous sulphate (dried): 200 mg (63 mg elemental
iron) tds.
iii. Ferrous gluconate: 300 mg (36 mg elemental iron)
tds.
 184 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
iv. Ferrous fumarate: 200 mg (65 mg elemental iron)
tds.
v. Ferrous succinate: 150 mg (35 mg elemental iron)
tds.
vi. Ferric ammonium citrate 160 mg (32 mg of elemental
iron) tds.
vii. Iron (III) hydroxide polymerase complex 500 mg (III)
(100 mg of elemental iron) od.
viii. Carbonyl iron (100 mg elemental iron) OD
N.B: Ferrous salts are better absorbed than ferric salts
or time release preparations. Average oral iron may be
100-130 mg/d.
Parenteral iron preparations: (used if intolerance or
refractoriness to oral iron exists)
i. Iron dextran (50 mg elemental iron per one ml) 5 ml
ampoule once daily IM or IV infusion)
ii. Iron-sorbitol-citric acid complex (4 ml ampoule IM
once daily)
The total dosage required is calculated as follows:
250 mg for each gram of haemoglobin percentage below
normal values. Total iron for parenteral use is calculated
as 2. 38 × weight in kg × haemoglobin deficiency in
grams + 1000 mg for iron stores or (15–Patients HB g/
dl) × Body weight in kg × 3 will be the total iron in mg
required to replenish stores as well. Total dosage of iron
should not exceed 2.5 g and the parenteral iron should
not be repeated for at least three months.
The underlying cause is to be identified and treated.
B. Impaired DNA synthesis: Megaloblastic anaemias
i. Vitamin B 12 deficiency: It usually results from
inadequate diet, deficiency of intrinsic factor,
disorders of ileum, blind loops or tapeworm
infestation.
Hydroxycobalamin is given initially 1000 µg
twice weekly IM followed by 1000 µg weekly for
eight weeks. Since there is rapid regeneration of the
blood, the serum iron and potassium levels may drop
which require replacement therapy.
Maintenance doses of hydroxycobalamin
(1000 µg IM every three months) is given. Pernicious
anaemia needs lifelong therapy.
If the megaloblastic anaemia is refractory to
hydroxycobalamin, folic acid may be effective.
However, folic acid or folinic acid must nerver be
given without B12, in B12 deficiency anaemias, lest
neurological damage should occur.
The underlying cause is to be identified and treated.
ii. Folate deficiency (Folates include folic acid and
other related compounds): It usually results from
dietary insufficiency, increased demands as in
pregnancy, diseases of the upper small intestine,
drugs (excessive doses of anti-metabolites, like folate
antagonist methotrexate and antiepileptics like
phenytoin) or alcoholism.
Administer folic acid 5 mg/d orally and maintain
with 5 mg weekly.
Prophylactic therapy with folate supplements
(350 µg/d) in pregnancy or folinic acid (15 mg/d)
during methotrexate therapy is advocated.
The underlying cause is to be identified and
treated.
Blood transfusion is rarely needed in megalo-
blastic anaemias.
C. Marrow failure: Aplastic anaemia: It may be primary
(idiopathic) or secondary to drugs like chloramphenicol,
radiation, infection, marrow replacement by neoplastic
or fibrous tissue.
i. Supportive therapy with blood product transfusions.
ii. Infection may be treated vigorously with appropriate
antibiotics.
iii. Haemopoiesis must be stimulated by androgenic
steroids (oxymetholone 0.2 mg/kg orally for 3-6
months plus prednisolone 60 mg/d for six weeks and
the dose is tapered).
iv. Antithymocyte globulin or antilymphocyte globulin
considered if autoimmune process is incriminated.
v. Bone marrow transplantation carries a good
prognosis especially for younger group (stem cell
transplantation is definitive treatment).
vi. Cyclosporin, glycoprotein haematopoietic growth
factors (colony stimulating factors like granulocyte
colony stimulating factor) or interleukin-3 appear to
hold promise in future.
Secondary aplastic anaemia is treated as above
apart from withdrawing the noxious agent.
D. Hormonal and nutritional deficiencies: Thyroxine
deficiency may lead to anaemia of normocytic or
macrocytic type unless there is an associated iron
deficiency. Adequate doses of thyroid facilitate recovery
in the course of 4-6 months.
Similarly vitamin C deficiency is known to produce
normocytic normochromic anaemia and vitamin-E
deficiency megaloblastic anaemia which are corrected
by appropriate replacement.
 Fatigue
Vitamin B6 or pyrodoxine (plays a significant role
in amino acid metabolism and is required for
haemoglobin formation) deficiency results in microcytic
hypochromic anaemia which is otherwise known as
sideroblastic anaemia since stainable iron (haemosiderin)
is greatly increased in the marrow. Most of them respond
to pyridoxine (100 mg daily).
Since protein is essential for haemoglobin formation
(96% haemoglobin molecules contains aminoacids) its
deficiency can cause anaemia of normocytic type which
responds well to high protein diet (protein globin
containing essential aminoacids, constitutes 96% of
haemoglobin molecule).
Increased Destruction of Red Cells
Haemolytic Anaemias.
Due to Intraerythrocytic Defects
(Refer Chapter ‘Jaundice’)
A. i. Hereditary spherocytosis: Severe haemolytic crises
require blood transfusion. Folic acid is supplemented.
Though spelenectomy is specific it is deferred as far
as possible. Cholecystectomy indicated for
cholelithiasis.
ii. For hereditary elliptocytosis splenectomy may help
but haemolysis is variable.
B. Glucose-6-phosphate dehydrogenase (G6PD)
deficiency: When the precipitating factor causing
oxidant stress (sulphas and antimalarials) is identified
and removed, the recovery is fairly rapid. Blood
transfusion is rarely necessary.
C. Sickle cell anaemia:
i. Folic acid 5 mg daily (since there is accelerated
erythropoietic activity) supplemented.
ii. Sodium bicarbonate given orally to prevent acidosis
(since acidosis predisposes to sickling).
iii. Associated infection treated promptly with appro-
priate antibiotics. Long-term antimalarials
considered, if necessary.
iv. Pain crises treated with analgesics and parenteral
fluids.
v. Sequestration crises: For the sudden fall in
haemoglobin levels blood transfusion, preferably red
cell concentrate is essential to maintain haemoglobin
levels of 10 g per cent, apart from supportive care
with oxygen, parenteral fluids, analgesics and
appropriate antibiotics.
vi. Aplastic crises (Postinfection): Blood transfusion
and antibiotics for infections, till bone marrow
recovers.
185
vii. Other complications (i.e.) decreasing haemoglobin
percentage and PCV without increase in reticulocyte
count. Thrombolic crises may lead to Bone Pains,
Acute chest syndrome, Acute abdomen, stroke, and
priapism.
a. Acute chest syndrome treated with fluids,
antibiotics, analgesics, oxygen, blood
transfusion, if necessary anticoagulants.
b. Haematuria treated with fluids, alkalinisation
of urine and epsilon aminocaproic acid (2-8
g/d).
c. Abdominal colic: May be due to gallstones
or bowel infarct. Treated with fluids,
analgesics and elective surgery. Girdle
syndrome is painful distended abdomen,
which is treated with nasogastric suction, IV.
fluids and blood transfusion.
d. Neurological complications like stroke need
maintenance of haemoglobin levels between
10 and 11 g per cent by chronic transfusion
therapy. Proliferative retinopathy is treated
with laser therapy and photocoagulation.
e. Skeletal: Avasular necrosis of the bones is
managed by avoiding weight bearing or
prosthesis, if necessary and osteomyelitis with
antibiotics.
f. Leg ulcers treated with saline dressing and
silver sulphadiazine applications.
g. Pseudotoxaemia syndrome, which occurs at
the end of pregnancy due to recurrent
infections earlier, may require heparin
therapy.
h. Priapism: Cyproterene acetate or stilbesterol
may abort it. If it is more than 24 hours
cavernosus-spongeosum shunting may be
done to prevent impotence.
viii. Splenectomy is indicated in repeated life-threatening
splenic sequestrations.
ix. Bone marrow transplantation offers an apparent cure.
x. Prevention of crisis, stimulating HbF production by
drugs like hydroxy urea, prevention and early
treatment of infections, avoiding to cold or dehydra-
tion or muscular exertions, folic acid deficiency
should be taken care of.
D. Thalassaemia
i. Periodic blood transfusion to keep the haemoglobin
levels at 10 g per cent is the mainstay of therapy.
Recent trend is to follow a “hypertransfusion”
regimen to maintain haemoglobin level between
10-12 g per cent.
 186 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
ii. Iron overload is treated with iron chelation with
parenteral deferoxamine mesylate (20-40 mg/kg/d
s.c. infusion over 12 h), which is preferably
commenced at the age of five years. Iron therapy
must never be given.
iii. Folic acid (5 mg), vitamin-C (100 mg), and vitamin-
E (200 IU) are supplemented.
iv. Splenectomy indicated when more than 250 ml of
blood/kg/year is needed, preferably as late as
possible. (Prophylactic penicillin given to decrease
the risk of infections after splenectomy.)
v. Bone marrow transplantation: Considered to ablate
the thalassaemic bone marrow stem cells.
vi. Somatic gene therapy is yet another possibility of
cure (introducing normal beta-globin gene into the
thalassaemic bone marrow).
Haemolytic Anaemias due to Extraerythrocytic Causes
A. Autoinmmune haemolytic anaemias
a. Warm type:
i. Prednisolone 60 mg/d for about a month, then
taper the dose. If unresponsive even after six
months, splenectomy is considered. If
splenectomy also fails, immunosuppressants like
azathioprine (100 mg/d) or cyclophosphamide
(100 mg/d) may be tried.
ii. Blood transfusion considered only in life
threatening situations.
iii. Gammaglobulin infusion (0.4-1 g/kg for 1 to 5
days) may be useful.
iv. Danazol (200 mg 6th hourly for two months) may
be effective in some cases.
v. Exchange plasmapheresis.
b. Cold agglutinin disease
i. Immunosuppressive therapy or plasmapheresis
is indicated for primary type.
ii. Secondary type consequent to infections is self-
limiting.
iii. Paroxysmal cold haemoglobinuria is treated with
transfusion of P or Pk blood types, if necessary.
Spontaneous recovery is likely. Avoid exposure
to cold.
c. Drug induced autoimmune haemolytic anaemia
responds to withdrawal of the offending drug.
B. Isoimmune haemolytic anaemias
a. Haemolytic disease of the newborn: Treatment
depends on the intensity. Mild cases may need only
simple transfusion and phototherapy. Severe cases
require exchange transfusion. When the haemoglobin
level < 90 g/L and bilirubin > 100 µmol/L, double
volume exchange transfusion (2 × 80 ml/kg with
maternally compatible blood O group) is necessary,
apart from aggressive basic life support.
Intrauterine foetal therapy (intravascular foetal
transfusion via umbilical vein as guided by
ultrasound) maximizes survival rate, if instituted
before the foetus becomes hypoxaemic.
Of course, antenatal detection of antibodies in the
maternal serum is ideal between 32nd and 36th
weeks, if the mother is Rh negative and father is Rh
positive.
Rh prophylaxis is facilitated by an injection of
gammaglobulin containing anti-D immunoglobulin
(300 µg) at 28 weeks and at delivery time containing
anti-D immunoglobulin (300 µg) as it prevents
sensitisation, in almost all cases.
b. Haemolytic transfusion reaction: Infusion of red cells
of the wrong blood groups or transfusion of Rh
positive blood to a sensitised Rh negative recipient
leads to haemolytic reaction. Treatment includes
cessation of transfusion, IV hydrocortisone (100 mg)
and mannitol to induce diuresis. If shock develops
or anuria persists leading to uraemia, appropriate
treatment is instituted (refer to Chapters ‘Shock’ and
‘Oliguria’).
Anaemias Due to Blood Loss (Posthaemorrhagic)
A. Acute posthaemorrhagic anaemia: Rapid loss of two
litres of blood is fatal, whereas more loss of blood spread
over 1-2 days is not fatal. The treatment is done by
replacing by transfusion of whole blood, packed red cells
or plasma substitutes. Anaemia which develops later may
be corrected, by iron therapy.
B. Chronic posthaemorrhagic anaemia: Haemoglobin may
drop gradually even to 7 g per cent in cases of persistent
or repeated loss of small quantities of blood. The
treatment includes correction of causative factor and iron
therapy.
Refractory anaemia: Symptomatic treatment with RBC
transfusion. If the irondeficiency anaemia is refractory,
H.pylori infection is treated appropriately. (Refer chapter
‘Dyspepsia)’ If there is iron overload iron chealing agents
may be administered. Specific treatment is stem cell
transfusion.
Polycythalaemia: The treatment consists of venesection;
radioactive phosphorous (5 mCi of P32 IV for patients above
50 years which may be repeated one year later).
 Fatigue
Chemotherapy with busulphan (2-4 mg/d) or melphalan
(2-4 mg/d) or hydroxyurea (2 g/d) considered for patients
under 50 years. (Refer Chapter ‘Cyanosis’)
Methaemoglobinaemia (Refer to Chapter ‘Cyanosis’)
2. Metabolic and Endocrinal
Diabetes Mellitus
Refer to Chapter ‘Polyuria’
Fluids and Electrolyte Disturbances
Salt depletion Replace sodium and water with normal saline
depending on depletion status (sodium content of normal
saline is 154 mEq/L). Glucose and water should not be given
since hypotonicity may be aggravated. Circulatory overload
must be avoided. Coexisting deficiencies of potassium/
magnesium or metabolic acidosis also corrected
appropriately. The underlying cause may be treated (Refer
to Chapter ‘Coma’).
Hypokalaemia Replace potassium orally or intravenously
with potassium chloride (1 g of potassium chloride contains
13.4 mEq of K). The diet rich in potassium like fruit juice,
coconut water, milk, and meat may be advised. Usually about
10 mEq of potassium in divided doses is required in
moderate deficiencies. If salt and water depletion is
associated, it should be treated first. Underlying cause of
potassium depletion may be treated (Refer to Chapter
‘Coma’).
Hypermagnesaemia and Hypercalcaemia
a. Hypermagnesaemia: The treatment is directed against
the underlying usual cause of renal disease. As calcium
acts as an antagonist to magnesium, it may be given
parenterally for transient benefit. Dialysis may be done
if necessary.
b. Hypercalcaemia (Refer to Chapter—‘Polyuria’).
Hypophosphataemia
Restore phosphate deficit. Avoid drugs like aluminium
hydroxide. Treat underlying causes like hyperparathy-
roidism, congestive cardiomyopathy, renal tubular defects
and diabetic ketoacidosis.
Hyper or Hypothyroidism
Refer to Chapter—‘Goitre’.
187
Aldosterone Deficiency
Fludrocortisone (0.1 to 0.2 mg/d) corrects electrolyte
imbalance. In hyporeninism, with hypoaldosteronism
frusemide and/or mineralocorticoids help hyperkalaemia and
metabolic acidosis.
Addison’s Disease
Hydrocortisone 20 mg in the morning and 10 mg in the
evening given orally. If vomiting occurs, it is replaced by
hydrocortisone sodium succinate IM. Fludrocortisone (0.05
to 0.2 mg/d) replaces aldosterone. IV fluids administered,
if necessary. Underlying cause like tuberculosis may be
treated. Addisonian (adrenal) crisis is managed with 5 per
cent dextrose saline, hydrocortisone sodium succinate 100
mg parenterally 6th hourly, followed by oral steroids when
the patient’s condition improves.
Simmond’s Disease (Hypopituitarism in Adults)
Treatment includes replacement of demonstrable
deficiencies like
a. ACTH or hydrocortisone 30 mg/d (Cortisone
replacement should preceded thyroxine therapy to avoid
adrenal crisis).
b. Thyroid (thyroxine 0.1 mg/d).
c. Sex Hormones: Depot testosterone esters 250 mg IM
every two weeks in males and ethinyloestradiol 20 µg
with medroxy progesterone 5 mg daily for three weeks,
in females are useful. Gonadotrophin is given for those
requiring fertility, i.e. human chorionic gonadotrophin
(3000 IU weekly IM) and LH/FSH (75 IU IM thrice
weekly) which is continued for 9-12 months with careful
monitoring.
d. Growth hormone deficiency is not treated in adults.
However, in children, growth hormone administered s.c.
(24 units/m2/week—in divided doses daily).
Hypopituitary coma is treated with hydrocortisone
sodium succinate 100 mg IV 6th hourly and then only oral
T3 (10 µg bd).
3. Malnutrition
Protein malnutrition, vitamin or mineral deficiencies
corrected appropriately.
4. Infections and Inflammatory Disorders
• Occult Infections (Refer to Chapters ‘Pyrexia of
Unknwon Origin and Haematuria’).
 188 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

• Tuberculosis (Refer to Chapters ‘Haemoptysis and
Chronic Diarrhoea’)
• Connective Tissue Disorders (Refer to Chapter
‘Polyarthritis’)
5. Neoplasia
• Lymphomas (Refer to Chapter ‘Pyrexia of Unknown
Origin’)
• Carcinoma of the bowel (Refer to Chapter ‘Chronic
Diarrhoea’)
• Carcinoma of the bronchus (Refer to Chapter
‘Haemoptysis’)
6. Cardiovascular Disorders
• Peripheral circulatory failure (Refer to Chapter
‘Shock’)
• Central cardia failure (Refer to Chapter ‘Oedema’).
7. Respiratory Diseases
• Chronic obstructive pulmonary disease (Refer to
Chapter—‘Dyspnoea’).
8. Gastrointestinal Disorders
•
•
Chronic dyspepsia
Chronic diarrhoea } (Refer to respective Chapters)
9. Neurological Diseases
Myasthenia gravis
Refer to Chapter ‘Paraplegia’.
Parkinsonian Syndrome (Parkinsonism)
The treatment includes drug therapy, physiotherapy and
surgery, apart from treating associated symptoms and
underlying cause.
Drug therapy is tailored to the patient’s needs as dictated
by the stages of the disease.
i. Anticholinergic drugs: Trihexyphenidyl (2 mg tds) or
procyclidine (2 mg tds) or benzhexol (2 mg tds) or
orphenadrine (50 mg tds) or benztropine (1 mg tds) or
biperiden (1 mg tds).
These drugs are useful for resting tremor and rigidity
especially in younger people and are to be initiated at
low doses and stepped up gradually.
ii. Beta-blockers like propranolol (40 mg tds) or
metaprolol (50 mg bd) are useful for action tremor.
iii. Antiviral drugs like amantidine (100 mg bd) useful in
early stage of the disease especially in young patients
and can be combined with levodopa. It stimulates
dopamine receptors, apart from anticholinergic effects,
and relieves hypokinesia and rigidity.
iv. Levodopa (dopaminergics): The neurochemical
hallmark of dopamine deficiency is substituted by
administration of levodopa, the dopamine precursor.
The initial dose is 50 mg bd, increasing gradually to
100 mg tid over a period of three weeks. It improves
tremor, rigidity and hypokinesia thereby the functional
capacities by and large. Pyridoxine should not be
administered simultaneously. Drug induced
parkinsonism does not respond to levodopa.
Levodopa can be combined with a peripheral
dopadecarboxylase inhibitor like carbidopa (10-25 mg
tds) or with benserazide (25 mg tds).
v. Bromocriptine (Dopamine receptor agonist) which
stimulates straital postsynaptic dopamine receptors, is
useful when given in combination with frequent small
doses of levodopa rather than alone in early Parkinson’s
disease below 60 years. This drug is also to be started
at low doses with gradual increments over several
weeks (2-20 mg t.d.s.).
vi. Ropinirole (2-24 mg/day in divided doses gradually
increasing) and Piribedil (150-250 mg daily) are non-
ergot derivatives useful as Dopamine agonists.
vii. Selegiline (selective monoamine oxidase (inhibi-
tor)): It is of value in the earliest stage of illness as it
retards the functional impairment and inhibits the
oxidative process (2.5-5 mg/d). Selegiline therapy is
better tolerated in dyskinesias induced by levodopa
(levodopa doses may be reduced) and also in elderly
patients.
viii. Entacapone (catechol-0-Methyl amino transferase
inhibitor) 200 mg recommended along with each dose
of levodopa, when motor fluctuations appear (not used
as initial therapy).
Physiotherapy It helps in amelioration of rigidity and
abnormal posture. Dysarthria and dysphonia may be
improved by speech therapy.
Surgical therapy Stereotactic thalamotomy is considered
only when the response to drugs is not satisfactory. Deep
brain stimulation of thalamic and subthalamic nucleus is a
recent option.
Associated symptoms Associated symptoms like
gastrointestinal, visual, neuropsychiatric problems are to be
 Fatigue
tackled appropriately. Emotional support is necessary to
overcome the stress induced by the disease.
Underlying cause is to be identified and treated accordingly.
Drug induced parkinsonism responds to withdrawal of the
offending drug.
Insomnia
a. General measures (like regular exercises, improving
sleep environment, avoiding stressful situations and
stimulating substances) implemented for improving the
patient’s sleep duration.
b. Reassurance to allay fears of sleeplessness, supportive
psychotherapy are other approaches advocated.
c. Pharmacotherapy: Hypnotics indicated only when
absolutely necessary. Benzodiazapines (flurazepam,
triazolam, nitrazepam) as hypnotics have replaced the
earlier nonbenzodiazapines (barbiturates, methaqualone,
chloral hydrate or triclofos) which are sedative hypnotics.
Antihistamines with sedative effect may be useful
(Therapy must be strictly limited to the actual needs).
Some patients may improve with tricyclic
antidepressants. Psychiatric patients need neuroleptics
with sedative effect. Haloperidol is administered to the
elderly patients with nocturnal agitations and confusional
states (Refer to Chapter ‘Headache’).
10. Psychogenic
Depression
a. The pharmacotherapy is preferred after evaluating the
degree of depression and when the symptoms interfere
with the patient’s normal life. The drug therapy of
depression includes tricyclics (amitriptyline,
nortriptyline, desipramine, doxepin, dothiepin),
monoamine oxidase inhibitors (phenelzine), lithium,
which are grouped as first generation antidepressants.
Selective serotonin re-uptake inhibitors (citalopram,
Escitalopram, Sertraline, Fluvoxamine, fluoxetine,
paroxetine), tetracyclics (Maprotiline, Mianserin) and
others like mirtazapine, ventafaxine, trazodone
trimipramine and adinazolam form the next generation
of antidepressants. The therapeutic strategy is aimed at
correct selection of drug and titration of its dose to
maximise its efficacy and minimise the side effects. The
drug should be continued for about 4-6 months with
ongoing assessment for the need of maintenance
189
treatment further for two years with careful therapeutic
monitoring. Anticonvulsants like carbamazepine or a
calcium channel blocker like verapamil are considered
as alternatives to lithium.
b. Electroconvulsive therapy (ECT) is useful in life
threatening depression or when refractory to
antidepressants. Raised intracranial pressure and/or a
high risk for general anaesthesia, are contraindications.
c. Psychotherapy: Nonpsychotic, nonbipolar forms of
depression of short duration (< one year) especially in
ambulatory patients respond well to psychotherapeutic
strategies like cognitive and behavioural techniques.
Combination with pharmacotherapy may be rewarding.
Anxiety
The comprehensive management includes the assessment
of stressful precipitants and excluding the underlying
medical causes or drug abuse including alcohol. Non-drug
treatment consists of general reassurance, explaining
dimensions of the disorder, counselling, psychotherapy,
behavioural techniques like relaxation, cognitive therapy
and breathing exercises. If unresponsive, pharmacotherapy
with minor tranquillisers may be commenced.
The anxiolytics consist of
i. Benzodiazepines: Long-acting (diazepam,
flurazepam, chlordiazepoxide), and short-acting
(lorazepam, alprazolam, oxazepam, nitrazepam).
They are not given for more than four weeks to
prevent dependence and better tapered slowly to
prevent withdrawal symptoms.
ii. Non-benzodiazepines (meprobamate, buspirone).
The latter takes two weeks to be effective and is
devoid of withdrawal phenomena.
iii. Antidepressants: (tricyclics like imipramine given
initially in small doses and stepped up once in three
days.) It takes four weeks to be effective.
iv. Beta blockers: (propranolol) Help to control somatic
manifestations.
Panic disorders need different drug management which
hinges around tricyclics like imipramine or amitriptyline,
and alprazolam (triazolobenzodiazepine) with increasing
doses till a clinical effect is achieved. Monoamine oxidase
inhibitors like phenelzine considered in refractory cases.
(MAOIs and tricyclics should never be used concomitantly
and a clear interval of at least three weeks is necessary
between the two drugs). Behavioural and cognitive therapies
are supportive.
 190 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
11. Asthenic Syndromes
Tropical Neurasthenia
Underlying tropical conditions like malaria, amoebiasis or
hot surroundings or alcoholism are corrected to improve
fatigue, insomnia and the sense of wellbeing.
Neurocirculatory Asthenia (Da Costa’s Syndrome)
Reassurance as to the absence of organic heart disease is
very essential in winning the patient’s confidence. Specific
treatment for the underlying psychological abnormalities
or elimination of any other precipitant factor, helpful.
Symptomatic therapy, if needed, may be instituted. (Refer
to Chapter ‘Chest Pain’).
Chronic Fatigue Syndrome
The management of chronic fatigue syndrome demands
exclusion of the known causes of fatigue. As the outcome
appears to be related to emotional distress and psychological
morbidity, psychotherapy with or without IV immuno-
globulin therapy in high doses may be beneficial. Antiviral
drugs like acyclovir are often effective in postviral fatigue
of short duration, through not in long-standing chronic
fatigue. Physical rehabilitation with graded exercises
programme and behavioural therapy with psychological
counselling help to reduce the period of disability.
Symptomatic treatment with NSAIDs, antihistamines and
nonsedating antidepressants is useful.
12. Drug and Alcohol
The offending agents incriminated to cause fatigue are to
be withdrawn. The fatigue caused by electrolyte
abnormalities precipitated by certain drugs may be
appropriately corrected.
Chronic Alcoholism
To treat the alcoholic ascertain the intentions of the patient
and explain the therapeutic risk involved. Encourage
decreased consumption of alcohol if not abstinence. It must
never be withdrawn suddenly. Detoxification should be
planned with patient’s consent for strict abstinence.
Tranquillisers may be administered, if necessary, to prevent
withdrawal symptoms. Hypokalaemia associated with
alcohol withdrawl, is appropriately substituted. Similarly,
anticonvulsants may be prescribed. Nutritious diet along
with supplements of vitamins, particularly parenteral
thiamine is necessary.
Disulfiram is the drug of choice for alcohol abuse, during
which period, alcohol should be totally forbidden, to prevent
accumulation of acetaldehyde and the dangerous sensitising
reaction thereof. Initial dose is 500 mg/d as single dose in
the morning for a week, after a minimum of 12 h abstinence
from alcohol (preferably 72 h). The dose may be decreased
later to 250 mg/d, as maintenance dose, for about one year.
The other similar and less toxic drug is calcium
carbimide (50 mg twice daily).
Acamprosate strated immediately after withdrawal
(1.3 to 2.0 gm/d is divided doses) and continue for one year.
Maintain abstinence, after withdrawal with nartrexone (50
mg/day) which may halve the relapse rate. No disulfiram
reaction. Withdrawal symptoms can be controlled with
Benzodiazepines and mild symptoms with beta blocking
drugs.
Conditioned reflex treatment or aversion therapy is
established by giving prenteral apomorphine or emetine and
making the patient drink alcohol, to produce nausea and
vomiting. This behavioral therapy is at times successful as
it creats a strong association between drinking and vomiting.
Psychological assessment may be necessary to ascertain
presence of any underlying psychotic or neurotic problem
which is treated appropriately by psychotherapy and/or
psychotropic drugs like antidepressants.
Social methods of treatment include enrolling the patient
into social agencies like Alcoholics Anonymous (AA) and
counselling by religious heads, may enable conversion to
sobriety.
Chronic carbon monoxide poisoning is treated with
oxygen and prohibit exposure to carbonmonoxide levels
exceeding 35 PPM over 8 hours workday.
Fatigue 191
 Chapter
Goitre
12
Goitre is a front line neck swelling indicating an enlargement
of the thyroid gland (normal weight 15 to 25 grams). It may
or may not imply functional alternations (hyperthyroid,
hypothyroid and euthyroid). The thyroid gland lies in front
and on either side of the trachea and thyroid cartilage. It
consists of an isthmus and two lateral lobes and is placed
just below the cricoid cartilage. The function of the thyroid
gland is to synthesise, store and secrete thyroxine and
triiodothyronine. The thyroid gland predominantly contains
vesicles called follicles or acini whose walls are lined by
cuboidal epithelium and they are filled with colloid. They
are surrounded by capillaries.
THYROID FUNCTION
The basic physiology of thyroid function not only involves
the production and regulation of thyroid hormones but forms
calcitonin, a hormone found in the parafollicular cells ‘C’
cells which are interspaced between the follicles. The latter
lowers serum calcium and phosphorus.
Synthesis and Storage
The iodides are normally consumed in foods (fish,
vegetables and milk) as well as water and absorbed from
the gastrointestinal tract. The thyroid gland traps the
inorganic iodide and oxidises it to organic iodine by a
peroxidase enzyme system. It has remarkable ability to
concentrate iodine up to 40 times the blood level at the rate
of 2 µg per hour. The iodine is incorporated into tyrosine to
form mono and diiodotyrosine. Two iodinated tyrosine
molecules condense to form the tetraiodothyronine
(thyroxine or T4) and triiodothyronine (T3). The hormone
is stored in the clloidal form within follicles of thyroid as
thyroglobulin which is a combination of thyroxine and
thyroid globulin.
Secretion
The thyroid secretes predominantly T4 and a small amount
of T3 (85% of T3 is produced by monodeiodonation of T4 in
other tissues like liver, muscle or kidney and the other 15
per cent of T3 is secreted from the thyroid). They are trans-
ported in the plasma, bound to thyroxine binding globulin
(TBG). Free thyroxine which is less than 0.1 per cent of
total concentration influences the basal metabolic rate and
neurocardiac functions. Though T3 is five times as active as
thyroxine, its rapid action is detrimental to clinical use.
Regulatory Mechanism
The production and release of T4 and T3 is controlled by
thyrotrophin or thyroid stimulating hormone (TSH) from
the anterior pituitary in response to thyrotrophin releasing
hormone (TRH) from hypothalamus. The TSH (thyrotrophin)
binds the TSH receptors of the thyroid plasma membrane
and increases the cyclic AMP production as well as thyroid
cellular function. Thus TSH increases thyroglobulin
synthesis and controls the release of T4 and T3 from the
thyroid gland by proteolysis of thyroglobulin. The secretion
of thyroid hormone is regulated by a rise in the circulating
free T4, which exerts negative feedback for the release of
TSH, so as to maintain a constant level of the circulating
hormones.
CAUSES OF GOITRE
The enlargement of thyroid gland may be of (i) physiological
or (ii) pathological origin. Clinically, enlargement of thyroid
gland may be (a) diffuse (both lobes equally enlarged);
(b) multinodular (both lobes irregularly enlarged);
(c) uninodular (solitary). It may be toxic (hyperthyroidism)
or nontoxic (hypothroidism) or euthyroid.
 Goitre 193

1. Physiological enlargement occurs at puberty or during Nontoxic Goitre (Euthyroid or Hypothyroid)

menstruation or during pregnancy when there is greater
demand for thyroid hormone. It is usually smooth and
diffuse euthyroid goitre, and transient (occasionally
persistent).
2. Pathological enlargement may arise from:
i. Deficiency of iodine (I2)
ii. Goitrogens (natural: brassica; and drugs lithium
carbonate, prolonged administration of iodine
amiodarone)
iii. Hereditary (congenital enzyme defects of thyroid
hormone synthesis-dyshormonogenesis)
iv. Autoimmunity
v. Inflammatory
vi. Neoplasms
Goitrous hypothyroidism may be due to (a) goitrogens
(drugs) (b) iodine deficiency; (c) dyshormonogenesis; and
(d) Hashimoto’s thyroiditis.
Goitrous hyperthyroidism may be due to (a) Grave’s
disease; (b) toxic multinodular goitre; (c) toxic uninodular
goitre; and (d) thyroiditis (rarely).
Euthyroid goitre may be (a) Physiological (b) Simple
goitre (sporadic) or (c) neoplasms.
Simple Goitre
It is defined as thyromegaly, which is not inflammatory or
neoplastic in origin and not associated with hyperthyroidism.
It may be endemic due to absolute iodine deficiency or
sporadic which is multifactorial. The term simple goitre is
usually restricted to sporadic goitre.
Endemic goitre is usually seen in mountainous regions
away from the sea coast with environmental deficiency of
iodine, in water and soil. Goitre is said to be endemic when
it affects about 20 per cent of the preadolescent children. It
presents as a large and painless goitre which is soft, smooth,
symmetrical (diffuse) without any bruit or altered hormonal
state initially. In long standing cases, nodular formation may
occur and the gland may become irregular with altered
consistency. It may cause embarrassment by the disfigure-
ment and possible mechanical obstructive symptoms like
tracheal compression. Occasionally, symptoms suggesting
hypothyroidism may be found. The thyroid gland shows
hyperplasia of the follicular epithelium followed by
epithelial atrophy and increase of colloid. The repeated
episodes of hyperplasia and involution result in nodular
goitre. The nodules of involuted tissue are surrounded by

Causes of Goitre Morphology Functional status

1. Nontoxic Goitre
a. Physiological Smooth and diffuse Euthyroid
b. Simple: Endemic and sporadic Smooth, diffuse or multinodular if Euthyroid or hypothyroid or
c. Goitrogens long standing (MNG) hyperthyroid (HNG)
d. Hereditary
2. Toxic Goitre
a. Primary Smooth and diffuse (Primary) Hyperthyroidism
b. Secondary Uni or Multinodular (Secondary)
3. Thyroiditis
a. Acute Smooth and diffuse (occasionally Hypothyroidism (rarely
b. Subacute (de Quervain’s) uninodular as in Hashimoto’s) hyperthyroidism-de Quervain’s
c. Chronic (Hashimoto’s and Riedel’s) and Hashimoto’s)
4. Thyroid Neoplasia
a. Benign Tumours
Adenomas Uninodular Euthyroid or hyperthyroid if
turns toxic
b. Malignant Goitre
Papillary adenocarcinoma Uninodular Euthyroid or hyperthyroid
Follicular adenocarcinoma (in follicular adenocarcinoma)
Undifferentiated carcinoma (anaplastic)
Medullary carcinoma
Lymphoma
 194 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
hyperplastic tissue and multinodular goitre results. A
localised hyperplasia with encapsulated adenoma is less
common.
Sometimes, the nodule may undergo haemorrhagic or
cystic degeneration and become painful and obstructive
symptoms may get exaggerated. The radioactive iodine
uptake (RAIU) value is increased (50% uptake) and urinary
iodide excretion is very low. (50 µg per 24 h). Serum T3 is
more while T4 is normal and TSH is mildly elevated.
Sporadic goitre is a goitre seen in nonendemic areas
commonly in women in second and third decades. The
pathogenesis seems to be a response to several factors which
ultimately affects adequate hormonogenesis. Consequently,
TSH is hypersecreted which stimulates, leading to excess
thyroid mass. The factors which are manifold may be related
to functional iodine deficiency, genetic predisposition or
thyroid growth immunoglobulin (TGI) without stimulating
adenylate cyclase activity or impaired hormonogenesis due
to depletion of thyroid organic iodine. Like endemic goitre,
the repetitive cycles or hyperplasia and involution may result
in nodule formation. The gland is diffusely enlarged,
symmetrical with soft consistency. Lobulations or nodules
may be felt sometimes. There is no bruit. It is usually
asymptomatic but the clinical features may result from
displacement or compression of trachea or oesophagus in
large goitres. Serum T3 and T4 levels are normal and T3/T4
ratio may be increased. TSH may be slightly elevated or
normal. The radioiodine uptake may be normal or increased.
The term ‘parenchymatous goitre’ connotes degenerative
changes in the epithelial cells and fibrosis whereas the term
‘colloid goitre’ indicates vesicles lined with low cuboidal
epithelium filled with colloid.
Goitrogens
Certain goitrogens cause goitre. They are natural plants
(Brassica), or certain drugs like para-aminosalicylic acid or
phenyl butazone or lithium carbonate and iodides in large
doses or prolonged use. Lithium and iodide inhibit release
of hormone. The thyroid gland is enlarged and the patient
may be euthyroid or hypothyroid. Pressure symptoms are
likely if the enlargement is considerable. Radioactive iodine
Uptake (RAIU) is low as goitrogens interfere with iodide
mechanism of the gland.
Hereditary Biosynthetic Defects (Dyshormonogenesis)
There are six types of enzyme defects associated with inborn
errors of thyroid hormone synthesis. They are autosomal
recessive and the common amongst these rare entities is
associated with nerve deafness (Pendred’s syndrome).
Patients are often children with a history of consanguinity.
Apart from thyroid enlargement, there is cretinism or
hypothyroidism. The thyroid hormone levels are low in
homozygotes while it is normal with raised TSH in
heterozygotes. Diagnosis is confirmed by high radioactive
iodine uptake by the gland displaced by potassium
perchlorate.
Toxic Goitre (Hyperthyroidism)
Toxic goitre is associated with hyperthyroidism. Over
90 per cent of the cases of hyperthyroidism are caused by
(a) primary thyrotoxicosis or diffuse toxic goitre (Grave’s
disease) and (b) secondary thyrotoxicosis with toxic nodular
goitre either multinodular (Plummer’s disease) or uninodular
(single toxic adenoma). The other 10 per cent include
exogenous iodide (Jod-Basedow disease, which results after
iodine administration in endemic and multinodular goitres);
thyroiditis, excess thyroxine intake or TSH secreting
tumours or ectopic TSH like material. The clinical features
of hyperthyroidism include
A. The characteristic symptoms like
1. Features of anxiety state like restlessness,
nervousness, emotional lability, tiredness and
palpitations.
2. Preference to cold or intolerance to hot weather
3. Excessive sweating
4. Weight loss despite increased appetite
5. Pruritus
6. Oligomenorrhoea
B. The characteristic signs like:
1. Goitre: The thyroid enlargement is diffuse and soft
or may be asymmetrical with a smooth or irregular
surface. There may be palpable thrill and a systolic
bruit over the gland.
2. Ocular signs: Exophthalmos (unilateral in the earlier
stages); retracted lids with wide palpebral opening;
with infraorbital puffiness; lagging behind of the
upper eyelids when the patient looks downwards
slowly; infrequent blinking, inability to converge and
ophthalmoplegia—(ophthalmopathy).
3. Hands: Hot moist palms; fine tremors at the
outstretched hands; pulmmers nails (separation of
the finger nail from the nailbed); and finger changes
resembling clubing (thyroid acropachy).
4. Cardiovascular changes: Sinus tachycardia
(persisting during sleep) or atrial fibrillation;
 Goitre
collapsing pulse; systolic hypertensions; cardiac
failure.
C. The atypical manifestations include chronic diarrhoea,
proximal limb girdle myopathy, pretibial myxoedema
(bilateral symmetrical nonpitting swelling over the lateral
malleoli and above) is exclusively a feature of Grave’s
disease (dermopathy).
Thyrotoxic crisis (thyroid storm) is very rare and
presents as severe hyperthyroidism with mania, coma,
fever, diarrhoea, tachycardia and circulatory collapse.
D. Total T3 and T4 are elevated. (The most sensitive test is
T3 which is invariably raised). Free T4 and free T3 are
raised and TSH is decreased; RAIU increased.
Diffuse Toxic Goitre or Primary Thyrotoxicosis
or Grave’s Disease
The triad of diffuse goitre, ophthalmopathy and fine tremors
is highly characteristic of Grave’s disease. Other features
of thyrotoxicosis with dermopathy or acropachy, may be
present. It affects women more commonly in the 3rd or 4th
decade.
The pathogenesis of Grave’s disease, in the recent times,
has undergone elucidation. It is not related to TSH activity
but results from the presence of immunoglobulins which
are antibodies produced by lymphocytes directed against
TSH receptors of thyroid follicular cells. They stimulate
thyroid to hyperfunction via adenyl cyclase-cAMP system.
The long acting thyroid stimulator (LATS) is one such
immunoglobulin found in 50 per cent of patients. Another
immunoglobulin LATS protector (LATS P) is found in LATS
negative patients. A genetic factor is incriminated as there
is a strong familial disposition. HLA typing shows increased
frequency of HLA BW35 and B8 or HLA Dr3. Expression
of HLA D/DR by thyrocytes enables them to present as
autoantigen to autoreactive T cells and propagate
autoimmune pathogenesis. Thereby a heritable abnormality
in immune surveillance is probably responsible for secreting
the immunoglobulins.
The genetic factors may also interact with the
environmental insult (virus or chemical) and the breakdown
of immune surveillance results in loss of recognition of self
antigens (The immune system normally differentiates
between foreign environmental antigens and self antigens
reacting only against the former).
Cell mediated immunity has also been involved in the
pathogenesis. This requires sensitised T lymphocytes to
elaborate stimulatory lymphokines. As the mitogen phyto-
haemagglutinins are found to stimulate the lymphocytes in
195
Grave’s disease to elaborate thyroid stimulating immuno-
globulin against TSH receptor on thyroid follicular cell. It
is suggested that both cell mediated and humoral
autoimmunity are involved in the pathogenesis.
To sum up it is a genetically determined immunological
defect with added environmental insults.
Toxic Nodular Goitre or Secondary Thyrotoxicosis or
Plummer’s Disease
A nodule can be a lobule of a normal tissue, colloid nodule,
goitre cyst, adenoma, focal thyroiditis or carcinoma. The
term toxic nodular goitre encompasses both toxic
multinodular and toxic adenoma (solitary nodular goitre).
It is not an autoimmune disease.
Multinodular goitre usually results from long standing
simple diffuse nontoxic goitre if untreated. When
hyperthyroidism is associated, it is termed as toxic
multinodular goitre. It is usually seen in women over
50 years with a long standing multinodular goitre. The steady
increase in the functional autonomy over long periods
probably causes hyperthyroidism, i.e. adenomatous
hyperfunction within toxic multinodular goitre.
The clinical features differ considerably from Grave’s
disease. It is usually not accompained by increased appetite
and ophthalmopathy. Though the neurological manifest-
ations are less prominent, the cardiovascular manifestations
like tachycardia, atrial fibrillation or cardiac failure tend to
be predominant. Weakness and wasting of muscles are also
common. The thyroid gland enlargement may produce
pressure symptoms like tracheal compression. Retrosternal
extension may be there with possible compression of
mediastinal structures. On palpation of the gland, the
charcteristics are the same as those of nontoxic multinodular
goitre without any bruit. Adenomatous (colloid) nodules
consist of epithelial cells arranged in follicles and filled with
thyroglobulin which is a rich colloid material.
Toxic adenoma is yet another form of hyperthyroidism
produced by autonomous hyperfunction (toxic solitary
nodule). Sometimes two or three adenomas may be present.
The nodule is a follicular adenoma in the thyroid gland which
is otherwise normal. It is a well-encapsulated benign
neoplasm in contrast to localised adenomas areas (vide
supra). It secretes autonomously excess thyroid hormones
without TSH stimulatory effect as such (hot nodule).
The adenoma may grow in size steadly without
symptoms. When it becomes more than 3 cms in diameter,
the features of secondary thyrotoxicosis become overt.
Excess hormones inhibit endogenous TSH secretion
 196 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 12.1: Thyroid scintiscan showing an area of increased I3I1
concentration (hot/overactive) in the isthmic region with
suppression of uptake in the remainder of the gland, suggestive
of nodular goitre
suppressing the remaining thyroid gland with consequent
atrophy. It is usually seen in women over 40 years. A history
of a slowly growing lump in the neck may be forthcoming.
The peripheral manifestations are usually milder with
insidious onset than Grave’s disease. Cardiovascular mani-
festations are prominent. There is no infiltrative ophthalmo-
pathy or myopathy or dermopathy or general anxiety. The
nodule is felt as a well-defined round mass which is firm in
consistency moving freely on deglutition without a bruit
over the gland (It is not palpable when the size is < 1 cm in
diameter). The nodule may undergo necrosis and
haemorrhage with hyperthyroidism being relieved (The
hyperfunctioning “hot” nodule turns to a nonfunctioning
“cold’ nodule). Gross calcification may occur in the
haemorrhagic area, appreciated on X-ray examination. In
50% of subjects, the plasma T 3 alone is raised
(T3 thyrotoxicosis). The other 50% secrete normal hormone
as well as iodinated protein which is measured as PBI, and
the latter is disproportionately elevated. The radioactive
iodine uptake may be increased (Fig. 12.1).
T3 toxicosis may be associated with toxic adenoma
multinodular goitre and Grave’s disease. It is diagnosed
when the clinical manifestations are present along with (a)
elevated T3 levels, (b) low or normal T4 levels in the absence
of thyroxine binding globulin (TBG) deficiency, (c) normal
or low FT4 and (d) normal or increased radioactive iodine
uptake (RAIU) but fails to be suppressed with T3 hormone.
Thyroiditis
Acute Thyroiditis This occurs from bacterial (pyogenic)
infections of the gland. Apart from the consitutional
symptoms like fever and malaise, the gland becomes acutely
enlarged, warm and tender. Cervical gland may be enlarged
and tender. Thyroid function tests show euthyroid status.
Subacute thyroiditis (de Quervain’s or Granulomatous Gaint
Cell Thyroiditis) It is a virus induced inflammation of the
thyroid. It affects usually women aged 20 to 40 years.It is
characterised by painful thyroid enlarged with malaise,
weakness, and low grade pyrexia. Pain may be radiated
towards the angle of the jaw, ears or occiput. The thyroid
gland is very tender and asymmetrical with nodularity.
Hormonal levels may be raised and the hyperthyroid phase
may be followed by asymptomatic hypothyroidism. Each
phase lasts for about 6 weeks and finally the thyroid function
recovers completely in 4 to 6 months.The condition may
simulate mild hyperthyroidism and the course of illness is
self limiting. LOW RAIU and high ESR differentiates from
other causes of hyperthyroidism. Biopsy studies revealing
well-developed follicular lesions (central core of colloid
surrounded by giant cells ) progressing to granulomas are
distinctive.
Chronic Thyroiditis This may be due to (a) Lymphocytic
thyroiditis or autoimmune thyroiditis; or (b) Invasive fibrous
thyroiditis.
• Lymphocytic thyroiditis includes (i) Goitrous
Hashimoto’s thyroiditis; (ii) Primary atrophic thyroiditis
(Nongoitrous hypothyroidism or myxoedema);
(iii) Painless thyroiditis.
i. Hashimoto’s thyroiditis is an autoimmune thyroiditis.
The thyroid follicles are destroyed by an autoimmune
process and antithyroglobulin antibodies and
antimicrosomal antibodies are detected. It may
coexist with other autoimmune disease like diabetes
mellitus. Women between ages of 30-50 are usually
affected. The goitre may involve the entire gland with
firm consistency, smooth surface, and occasional
nodularity and often H shaped. It is usually nontender
but occasionally when the gland enlarges rapidly, it
may be tender. Functionally, the subjects are
euthyroid but hypothyroidism usually supervenes.
Very rarely hyperthyroidism, which is transitory, may
be seen (Hashitoxicosis). Pressure symptoms and
cervical lymphadenopathy are unusual. Initially
RAIU and PBI are increased with normal T4 levels
 Goitre 197

but later all the three are diminished. TSH may be Adenomas are to be differentiated from other benign
normal or elevated. High titres of antibodies to swellings like (i) involutional (colloid) nodules, (ii) cysts,
thyroglobulin (normal up to 1:80) and/or thyroid (iii) localised thyroiditis, and (iv) carcinoma.
microsomes (normal up to 1:400) are present in the
serum of 90 per cent of cases. Biopsy studies reveal Malignant Neoplastic Nodules (Malignant Goitre)
diffuse lymphocytic infiltration with lymphocytes
Malignant neoplasms may be carcinoma or rarely
and plasma cells, obliteration of thyroid follicles and
lymphomas. The former presents as nodule. Malignant
fibrosis.
nodules are derived either from follicular or parafollicular
ii. Primary atrophic thyroiditis (myxoedema) (Refer to
cells (C Cells). They may start de nova in one area and
Chapter ‘Oedema’.)
spread to involve the entire gland or in a goitre of long
iii. Painless (silent) thyroiditis is immunologically
standing. The swelling is usually hard and may grow rapidly.
mediated. It affects women during 4-6 months of
Pressure symptoms like pain on swallowing may be present.
postpartum period. Clinically, it starts as symptomatic
Regional lymph nodes are enlarged and firm. Functionally
hyperthyroidism and is characterised by a painless
these patients are euthyroid. It may metastasise in lung, brain
(silent) swelling of thyroid. It may be short-lived and
or bone. Thyroglobulin levels are high in all carcinomas
exophthalmos is absent. Further low I131 uptake and
except medullary type where calcitonin may be raised.
low antibody titres help to differentiate from Grave’s
disease. Biopsy reveals lymphocytic infiltration of
Carcinoma
thyroid gland. After several recurrent attacks, it may
progress to permanent hypothyroidism after some There are four types of carcinomas, out of which papillary
years. carcinoma is the most common.
• Riedel’s Thyroiditis (Invasive Fibrous Thyroiditis): It is
Papillary Carcinoma: It occurs in the relatively young
a chronic fibrous thyroiditis and a rare form seen in
individuals during 4th decade or even earlier. The neoplasm
middle aged women. Riedel’s etiology is a riddle. There
may present as solitary nodule and remains localised. It
is massive fibrous infiltration of the gland and the
grows slowly and may spread to other parts of the gland
surrounding structures as well. The goitre is
and then to the regional lymph nodes. Sometimes, it may
asymmetrical with remarkably hard consistency and
present as lymph gland enlargement in the side of the neck
adherent to neck structures. Pressure symptoms are out
(lateral aberrant). The diagnosis is confirmed by fine needle
of proportion to its size. Regional lymph nodes are not
aspiration biopsy which shows papillary projections of
enlarged. Hypothyroidism may occur. RAIU is normal
columnar epithelium. Prognosis is relatively good.
or low.
Follicular Carcinoma: This is relatively uncommon, and
Benign Neoplastic Nodules occurs in the 5th decade. It produces early metastases in the
regional lymph nodes, lung or bone. Prognosis is not as
These are termed as adenomas and can be classified as (1)
good as papillary type.
Embryonal adenoma; (2) Foetal adenoma; (3) Follicular
adenoma; (4) Papillary cyst adenoma; (5) Hurthle cell Anaplastic (Undifferentiated): It presents as asymmetrical,
adenoma. They are usually well encapsulated except hard, rapidly enlarging thyroid in the elderly over 60 years.
papillary cyst adenoma. They may arise either in a normal Tumour may be painful and invade the trachea or larynx. It
or a diseased gland and possess a tendency for some principally metastasises in the lungs. Prognosis is poor.
autonomy of growth and function as well. The adenoma
Medullary Carcinoma: It appears as a solid hard nodule in
may be single or occasionally multiple. The follicular
5th decade. The tumour arises from parafollicular cells, and
adenoma is the most common, which consists of nodules
secretes calcitonin. It may be familial as in Multiple
colloid in type. Generally, it appears as a nodule and may
Endocrine Neoplasia (MEN) Type II syndromes. It is more
be palpable. Sometimes it may be seen as a lump in the
malignant than follicular type.
neck. It produces no symptoms except when it turns toxic
(vide supra) or after local haemorrhage with consequent
Lymphoma
sudden painful enlargement. A cyst may develop which is
nonfunctioning after the resolution of haemorrhage. It appears as a firm rapid enlargement of both lobes. It may
Functioning adenomas are not dependant on TSH. be either reticular cell sarcoma or lymphosarcoma.
 198 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Problems of Thyroid Nodules
Clinically, it is to be decided whether
1. Single nodule (usually neoplasm) or multiple nodules
(suggestive of multiple nodular goitre). A discrete nodule
may be felt as single lump in a multinodular goitre.
2. Painful as in thyroiditis or painless as in neoplasms.
3. Regional lymph nodes enlarged or surrounding
structures fixed.
4. Functionally toxic or nontoxic.
Next step is to know the cause of the nodule—whether
it is malignant or nonmalignant. To decipher precisely, the
history of previous irradiation and the physical examination
may be helpful, apart from ultrasonography, fine needle
aspiration biopsy and thyroid scintiscan. The ultra-
sonography differentiates whether the nodule is solid or
cystic. The thyroid scintiscan with radioactive isotopes
uptake and imaging either with I131 or Technetium-99m
pertechnetate, throws light regarding the functional status
of the nodule. If there is less concentration of radioactive
iodine when compared to normal surrounding tissue, it
indicates nonfunctioning or cold nodule whereas increased
I131 concentration is referred as hot or hyperfunctioning
nodule. A cold nodule is usually malignant or sometimes
benign (degenerative adenoma or cyst or functioning colloid
nodule in multinodular goitre). A hot nodule is not malignant
but may be associated with hyperthyroidism. In a multi-
nodular goitre, hypo or hyperfunctioning areas with a patchy
appearance are characteristic. Thallium-201 may get
localised in proportion to the blood flow and differentiates
vascular from avascular solid nodules. So a solitary, solid,
cold, avascular nodule indicates malignancy especially if
the size does not decrease or remains normal despite
suppressive therapy with thyroid for 6 wks.
CLINICAL APPROACH
The approach to a case of goitre (visible and palpable)
entirely rests upon assessing the functional status and
specific aetiopathology of the thyroid swelling. An objective
scoring method to evaluate thyroid status is either by New
Castle Thyrotoxicosis Index or the application of statistical
methods apart from confirming the diagnosis by appropriate
investigations. Morphometric parameters and intrathyroidal
I 131 iodine transit kinetics of the thyroid gland are of
importance for objective evaluation, documentation and
prognostication.
History
a. Age and sex.
b. Time of appearance of swelling and its duration.
c. Any pain or tenderness over thyroid region?
d. Is there any change in the contour?
e. Detailed history about ingestion of drugs.
f. History of radiation in childhood or puberty.
g. Overindulgence of vegetables of Brassica family like
cabbage.
h. Familial history.
i. Asymptomatic or symptomatic—history of weight loss,
in spite of increased appetite, weakness, palpitation,
diarrhoea, etc.
j. Any pressure symptoms like hoarseness, dyspnoea,
dysphagia.
Physical Examination
Local Examination
1. Inspection of the gland from front and sides, for size,
shape, symmetry and mobility.
a. At rest
b. On degulation for mobility: Instruct the patient to
swallow preferably with mouthfuls of water when
any thyroid swelling must rise during deglutition.
The thyroid gland moves up and down with the
larynx on deglutition, since the gland is ensheathed
by the pretracheal fascia fixes it to the laryngeal
cartilages. Sometimes this movement may be absent
especially when fixation occurs as in malignancy.
2. Palpation: Palpate the thyroid of the seated patient (neck
moderately extended) with the fingers of the hand resting
on each side of the gland with the thumb over the back
of the sternomastoid. Position of the cricoid cartilage
should be located, since the superior border of the
isthumus lies just below it. The posterior border of the
left lateral lobe is palpated by relaxing the left
sternomastoid muscle and vice versa. If the enlargement
is slight, the palpation may be facilitated by pushing the
gland and displacing the trachea with opposite fingers.
While palpating, surface (smooth or nodular),
consistency (soft, firm or hard), contour, tenderness,
vascular thrill and fixation are to be observed. The
isthmus of the gland in the midline and pyramidal lobe
which extends upwards from isthmus either to right or
left are appreciated. Diffuse goitre from posterior and
nodular goitre from anterior aspects, are better
appreciated. Sometimes, it is easier to appreciate if the
head is allowed to fall forward and endeavour is made
to palpate the lower border of the gland on deglutition.
Palpation may also be carried out with the patient lying
flat without a pillow. The thumb should compress one
lobe of the thyroid against the trachea, when the
 Goitre
opposite lobe becomes palpable to the thumb of the
other hand.
The enlargement of the thyroid gland can be more
objectively assessed by certain morphometric parameters
like distance from the chin or suprasternal notch to
midisthmus or axial lengths and width of the left as well
as right lobes.
Incidentally look for any enlargement of the regional
lymph nodes.
3. Percussion: Percuss over the manubrium sterni for
dullness due to any retrosternal extension of the thyroid.
4. Auscultation: Auscultate for a systolic or continuous
bruit over the gland and the same should be distinguished
from a transmitted murmur from the heart or a venous
hum (which is obliterated by compressing external
jugular vein while turning the head). Care must be taken
to distinguish transmission from carotid artery by suitable
obliterative manoeuvres.
5. Transillumination test: The pentorch may serve to
distinguish cystic and solid masses of the thyroid gland.
6. Arm raising test (Pemberton’s): Raise both the arms until
they touch the sides of the head, when the thoracic inlet
gets narrowed. Congestion of the face, respiratory
embarrassment or dizziness may appear if the goitre is
large or retrosternal.
7. Look for pressure symptoms if any
a. Brassy cough or dyspnoea due to tracheal
displacement or compression or both (scaberrad
trachea).
b. Dysphagia due to oesophageal compression.
c. Hoarseness or brassy cough due to paralysis of the
recurrent pharyngeal nerve (paralysis of the vocal
cord).
d. Oedema and cyanosis of the head and neck;
distended external jugular veins and dilated
anastomotic veins over the upper anterior chest wall
due to retrosternal goitre obstructing the superior
vena cava.
General Examination
1. Appearance:
a. Face—(i) facial expression of anxiety and fright with
excessive emotional movements; (ii) dull apathetic
and emotionless.
b. Ophthalmological assessment—(i) eye signs (vide
supra); (ii) visual acuity; (iii) visual fields; (iv) Hess
charts; (v) colour vision. If ophthalmopathy is
inapparent clinically, assessment of intraocular
pressure on upward gaze is useful, as an increase of
199
3 mmHg or more over the pressure than the primary
position, favours Grave’s ophthalmopathy, even
without obvious exophthalmos.
c. Any pallor suggestive of anaemia.
d. Lymphadenopathy.
e. Extremities—(i) hands: Hot sweating palms,
Plummers nails (ii) legs: Any swelling over the outer
aspect.
f. Skin: Moist or dry, any increased sweating.
2. Vital signs:
a. Pulse fast or slow; regular or irregular? (If sleeping
pulse rate is also increased it indicates thyroid
hyperfunction.)
b. Temperature: Prolonged pyrexia may be present in
hyperthyroidism.
c. Blood pressure: Systolic hypertension may be present
in hyperthyroidism.
d. Respirations: Stridor may be present in intrathoracic
goitre.
Systemic Examination
a. Cardiovascular system: Any evidence of cardiomegaly;
atrial fibrillation; heart failure.
b. Central nervous system
i. Any ophthalmoplegia
ii. Motor system: Any muscular wasting of the limbs
and trunk; any involuntary movements like tremors;
any hypotonia
iii. Sensory system: Any acroparaethesiae (numbess and
tingling of the fingers due to compression of median
nerve in the carpal tunnel)
iv. Reflexes: Ankle reflex (duration of time 0.36 seconds
with delayed relaxation).
Investigations
Basic Thyroid Function Tests (Secretion and
uptake Studies)
Hormonal Concentration and Binding in the Blood
a. Plasma total T4 and total T3: Total thyroxine is raised in
hyperthyroidism, pregnancy and oestrogen therapy; total
thyroxine is low in hypothyroidism, corticosteroids and
analgesics like NSAIDs and phenylbutazone
administration. Normal range is 5-12 µg per 100 ml
(64-154 n mol/L).
Plasma total T3 is elevated in hyperthyroidism invariably
and may be normal in hypothyroidism. Normal range is
70-190 µg per 100 ml. (1.1-2.9 n mol/L).
 200 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Free thyroxine and tri-iodothyronine measurements
provide reliable means of assessing thyroid status than
total hormonal levels, since they avoid the interfering
effects of TBG (Thyroxine binding globulin) levels.
Free thyroxine—Normal range: 0.8 to 2.4 µg per 100
ml (10.2-30.6 n mol/L).
Free tri-iodothyronine—Normal range: 0.4 to 0.8 ng/L.
c. Protein bound iodine (PBI)—Measures the amount of
circulating organic iodine. Normal range : 3 to 8 µg per
100 ml.
It is raised in hyperthyroidism and decreased in
hypothyroidism.
d. Thyroxine binding globulin (TBG), i.e. protein bound
hormone (normal range : 2 to 4.8 mg per 100 ml).
e. Free thyroxine index (vide infra).
f. TSH raised in hypothyroidism and very low in
hyperthyroidism.
Normal range: 0.4-5 µu/I
g. Reverse tri-iodothyronine (rT3): 10-40 ng/100 ml (0.15-
0.61 n mol/L)
Indices for Metabolic Effects of Thyroid
a. Basal Metabolic Rate: Normal + 20 per cent (Raised in
hyperthyroidism and reduced in hypothyroidism).
b. Serum cholesterol: Normal range 160-200 mg per cent
(Raised in myxoedema and reduced in hyperthyroidism)
c. Urine creatine test
d. Circulation time
e. ECG
f. Measurement of cardiac output
g. Ankle reflex (photomotograph). Relaxation is prolonged
in hypothyroidism. Normal range is 240-380 msc.
Uptake Studies
a. Radioactive iodine uptake of the thyroid gland. A
measured quantity of I131 (usually less than 10 uci) is
administered orally and the thyroid uptake is measured
at 2 h, 4 h, 24 h and 48 h. Normally, the uptake is 20-40%
in 24 h and a high uptake of 65 per cent denotes
hyperthyroid state and a low uptake of about 10 per cent
suggests hypothyroid state. A high 2 h uptake (normal
range is 4 to 10%) is diagnostic of thyrotoxicosis. (Prior
use of iodine containing drugs or contrast media should
be avoided, for at least 2 weeks before the test and
preferably 3 months after myelogram).
b. Technetium uptake: 99 m pertechnetate uptake has
advantage of low radiation, a faster result. This study is
completed within half an hour instead of 24 h. The uptake
at 2 min and 20 min separates the hyperthyroid patients
from euthyroid patients.
c. Radioactive T3 uptake of red cells or resin: It is an
indirect measurement of thyroxine binding protein.
Though T3 uptake parallels the PBI by and large, a
combination of this test and PBI is of greater value to
avoid fallacies. Normal range: red cells 12 to 20 per
cent; resin: 25 to 35 per cent (T3 Resin intake is the
amount of T3 not bound to protein and removed on the
resin that is measured).
d. Free thyroxine index: It is a measurement of product of
T4 values and resin T3 uptake. The index corrects for
abnormalities of thyroxine binding. If free T4 is available
this test is unnecessary (1-4 units).
If both T4 and uptake are raised, it is suggestive of
Grave’s disease. Low T4 levels and uptake study with raised
TSH levels are suggestive of hypothyroidism. A raised T4
level with a low radioiodine uptake is suggestive of
thyroiditis. An increase of TBG and T4 may be encountered
during pregnancy or oral contraceptive pills indulgence in
the absence of hyperthyroid state. T3 resin uptake test may
be useful to rule out hyperthyroidism.
Dynamic Tests for Thyroid/Hypothalaemic
Hypophyseal Function
a. TSH measurement (Thyroid Stimulating Hormone or
Thyrotrophin): Normal value is 0.4 to 5 mU per litre. If
the level is more than 5 mU/L with normal T4, it indicates
thyroid failure as in Hashimotos or iodine deficiency or
drugs like litimum. If it is raised and T4 is low, it indicates
myxoedema. If TSH is not raised, with low T3 and T4
levels, it is suggestive of secondary hypothyroidism due
to pituitary failure. In hyperthyroidism it is very low and
may be undetectable (0.1 mU/L) with increased T4 levels.
b. TSH stimulation test: When the radioiodine uptake is
not increased even after 5 to 10 units of TSH given IV
daily for 3 days, it indicates hypothyroidism due to
thyroid failure.
c. TRH test (Thyrotrophin Releasing Hormone):
Thyrotrophin releasing hormone 200 µg injected IV and
TSH is measured before 20 min and one hour after
injection as well. If the rise in TSH values is less than
2 mU per litre, then it is due to hyperthyroidism and
vice versa. A prolonged and exaggerated rise in TSH is
suggestive of primary thyroid failure. (Normally the
serum TSH rises and even doubles up within 40 min
and then falls rapidly.)
d. Thyroid suppression test: Normally T3 hormone when
given 40 µg 8 hourly for one week, suppresses pituitary
TSH and consequently thyroid radioiodine uptake. If
 Goitre
the pituitary thyroid axis is autonomous (hyper-
thyroidism), T3 does not suppress the uptake by the gland.
Special Tests (For Elucidating Cause)
a. Thyroid imaging or isotope scanning: It is done with
I131 or TC-99 m, Thallium 201, Gallium 67. Normally a
homogenous butterfly profile of 5 × 2 cm in diameter is
observed. It is particularly useful not only for anatomical
characterisation but also for differentiating major causes
of hyperthyroidism (diffuse uptake or solitary nodule or
multinodular), extent of retrosternal goitre, ectopic
thyroid tissue and functioning metastases of thyroid
malignancy (body scan). Gamma scintillation imaging
quantifies and localises the differentially accumulated
isotope iodine where the fluorescent scan localises and
quantifies the content of stored iodine within the gland.
b. Ultrasonography: It differentiates cystic (benign) from
solid cold nodules (malignant).
N.B.: The enlarged area of thyroid uptake of pertech-
netate if increased (hot) and when decreased (cold) or
same uptake as remaining thyroid (neutral). Hot nodules
are never malignant.
c. Immunological test:
i. Thyroid autoantibodies especially thyroid
microsomal and thyroglobulin antibodies are raised
in Hashimoto’s thyroiditis, Grave’s disease and
primary atrophic hypothyroidism.
ii. Thyroid stimulating immunboglobulin (TSI)
antibodies against TSH receptor may be raised in
Grave’s disease.
d. Serum thyroglobulin: Radioimmunoassay of the
thyroglobulin in the serum is raised in metastatic or
recurrent thyroid carcinomas and so serves as a useful
marker for periodical surveillance.
e. Calcitonin assay: It is elevated in medullary carcinoma.
(Normal value is 0-11.5 pg/ml. Normally produced in
‘C’ cells of thyroid.
f. Perchlorate discharge test: I131 is given and after four
hours when the counts are stable, perchlorate is given
orally and uptake measurements are done hourly. 10-15
per cent reduction in counts is normal.
g. Thyroid biopsy:
i. Needle biopsy
ii. Excision biopsy
h. CT scan:
i. Mid orbital
ii. Brain.
201
Other Routine Tests
a. X-ray of the chest may be taken for any evidence of
secondaries or retrosternal goitre or tracheal displace-
ment or cardiomegaly.
b. X-ray of the thyroid for any abnormal calcification (shell
like or punctate).
Diagnostic Strategy at A Glance
1. First step: Measure thyroid hormones like serum T4
concentration, serum free thyroxine and TSH. If the
results are equivocal, measure serum T3.
2. Second step: If diagnosis of hyperthyroidism is still not
confirmed, TRH test may be done.
3. Third step: Radioisotope uptake and combined with
thyroid imaging.
4. Fourth step: Fine needle aspiration biopsy.
TREATMENT OF GOITRE
An enlarged thyroid gland requires a critical evaluation
regarding.
a. Nature of enlargement (diffuse, solitary or multinodular)
b. Analysis of symptoms asymptomatic or symptomatic
(toxic or nontoxic—benign or malignant goitre)
c. Any alteration of function (hypothyroid, hyperthyroid
or euthyroid)
d. Accessory factors like endemecity, age and sex of the
individual, and consistency of the gland play a role in
determining the type of goitre.
This facilitates the choice of the therapeutic modalities
like (i) Antithyroid drugs, (ii) Replacement with thyroxine
and (iii) Suppressive therapy with thyroxine and/or surgery
(iv) Whether any treatment is going to be necessary at all.
Treatment of Nontoxic Goitre
Simple Goitre
(Nonendemic or Sporadic; and Endemic)
In recent cases of sporadic goitre if associated with puberty,
oral potassium iodide 0.1 gm/d is worthy of trial. The risk
of iodides inducing thyrotoxicosis especially in nodular
variety is to be borne in mind. Hence monitoring the gland
for toxicity is imperative in long standing cases of simple
goitres (which may turn into multinodular goitre (even
without iodides).
In simple nodular goitre, thyroxine is given to the point
of tolerance to remove the stimulus of thyroid hyperplasia
(by suppressing the TSH hypersecretion) and lead to
involution of the goitre in most of the cases.
 202 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Thyroxine may also be considered (as replacement
therapy), in case hypothyroidism exists.
In others, partial thyroidectomy is indicated for large
goitres with pressure symptoms or cold nodule or cosmetic
purposes.
In areas of endemic goitre, 1 min of Lugol’s iodine (5%
of iodine dissolved in 10% potassium iodine solution) daily
or iodised salt yields satisfactory results especially if
administered for pregnant women or in childhood.
Goitrogens
Simple withdrawal of pharmacological (lithium, iodine in
large doses for long) or other goitrogens (vegetables of
Brassica family) may be sufficient to control goitrous
hypothyroidism.
Dyshormonogenesis
The goitrous hypothyroidism may be treated with thyroxine.
Treatment of Toxic Goitre (Hyperthyroidism)
Diffuse Toxic Goitre
(Grave’s Disease or Primary Thyrotoxicosis)
A course of antithyroid drugs (carbimazole 15 mg t.d.s. for
3 weeks reducing to 5 mg t.d.s. and maintained with 5-10
mg daily for 18-24 months monitoring neutrophils, T4 and
TSH levels) is given for patients under 40 years.
Propranolol (40 mg t.d.s.) only mitigates the symptoms,
but does not eradicate them.
Destructive therapy with either radioactive iodine (5-10
mCi) orally (preferred only in patients over 40 years) or
subtotal thyroidectomy (carbimazole is stopped 2 weeks
prior to surgery and oral potassium iodide 60 mg t.d.s. is
given) is indicated in relapses. Thyroxine is supplemented
in postoperative cases.
However carbimazole with or without propranolol may
be necessary to control the symptoms in the lag period since
radioactive iodine (I131) is effective only after 4-12 weeks.
Similarly the latent period for antithyroid drugs is about
2 weeks during which period propranonol is useful to control
the symptoms within 12-48 h.
Block and replace regimen with carbimazole till T4 is
reduced and thyroxine is added for one year.
The ophthalmopathy needs special attention to prevent
corneal ulceration. Prednisolone may be useful when
papilloedema or visual defects occur.
Thyroid storm or crisis is treated with sedation
(chlorpromazine), intravenous fluids, carbimzaole,
propranonol, dexamethasone, and iodides (Sodium iodide
is more effective than potassium iodide).
Toxic Nodular Goitre (Secondary Thyrotoxicosis)
Ablative treatment with large doses of radioactive iodine
(15-20 mCi) controls the symptoms rather than the gland
size. Surgery (partial thyroidectomy) is an alternative for
multinodular goitre. Treatment of choice is hemithyroi-
dectomy for single toxic adenoma. (In postoperative cases
thyroxine may be supplemented). Carbimazole is not useful
as relapses occur invariably on withdrawal. Percutaneous
ethanol injection is an alternative.
Associated thyrocardiac disease (atrial fibrillation) is
effectively treated with digoxin and beta-blockers as the
ventricular rate is not controlled with digoxin alone.
Anticoagulants are given preferably till sinus rhythm is
restored by antithyroid drugs or cardioversion.
Other Forms of Hyperthyroidism
• Thyroiditis As hyperthyroidism is transient, antithyroid
drugs are not prescribed. Hyperthyroidism due to painful
thyroiditis (subacute or de quervain’s) may be treated
with aspirin or NSAIDs or prednisolone (10 mg q.d.s.)
for 3 weeks. Propranonol (40 mg q.d.s.) is beneficial.
Painless (postpartum) thyroiditis needs only
propranonol.
• Iodide induced hyperthyroidism It is usually mild and
self-limiting. Carbimazole is given if necessary.
Discontinue administration of iodine or amiodarone.
• Thyroxine induced (Factitious) hyperthyroidism
Clandestine ingestion of thyroxine administration in
unusually emotional persons may result in hyper-
thyroidism. This rare occurrence is diagnosed by very
low serum thyroglobulin levels (which is elevated in
other forms) and iodine uptake. It is treated appropriately.
• TSH secreting tumours Somatostatin analogue is useful.
Surgical excision may be considered.
Thyroiditis
Acute thyroiditis Appropriate antibiotics given. If fluctuation
is elicited, surgical drainage is done.
• Subacute thyroiditis (Vide supra)
• Painless (postpartum) thyroiditis (Vide supra)
 Goitre
Chronic Thyroiditis
• Hashimoto’s thyroiditis (Autoimmune) This goitrous
hypothyroidism requires thyroxine (usually 150 µg)
daily, starting with 50 µg and increase every 3 weeks)
which suppresses TSH. The goitre size may reduce
significantly in the course of few months. Start with
25 µg if IHD is associated.
• Riedel’s thyroiditis Thyroxine corrects hypothyroidism
without any effect on the size of the goitre. Partial
thyroidectomy is indicated if pressure symptoms occur.
Benign Thyroid Nodule
A balanced approach must be sought between suppressive
therapy and surgery. Isotope scan and fine needle aspiration
cytology (FNAC) should be the guiding factors. Patients
with cold nodule without malignancy must be put on
suppressive doses of thyroxine and followed for 6-12 wks.
A fall in TSH level or a decrease in size of the nodule rules
out malignancy. On the other hand, an increase or no change
in the size of the nodule on adequate suppression, calls for
a repeat FNAC and large needle biopsy, if necessary (TSH
should not be lower than 0.5 mu/L).
If TSH is undetectable and autonomously functioning
adenoma is suspected, it is confirmed by scanning, before
treating with I131 or surgery.
Thyroid Cancer
• Differentiated carcinoma:
Papillary or follicular carcinoma is treated by total
203
thyroidectomy followed by large doses of I131 to ablate
any remnant of thyroid. Then thyroxine is supplemented
up to 200 µg/d. If serum thyroglobulin is > 15 µg/L,
tumour metastases or recurrence is suspected, when
further radiotherapy must be considered.
• Undifferentiated anaplastic carcinoma:
It is often inoperable and postoperative therapy includes
a course of external irradiation. Radiotherapy may
relieve pressure symptoms.
• Medullary carcinoma
Total thyroidectomy and ipsilateral neck dissection is
the therapeutic approach. Thyroxine administered
postoperatively. Metastases treated with radioactive
iodine if they could concentrate the tracer doses.
Indomethacin useful for diarrhoea.
• Lymphoma:
It is curable with external irradiation and chemotherapy,
after surgery.
Follow-up
Thyroid cancer patients must be followed postoperatively
every year. Screen for possible recurrence, by neck palpation
and supplement with imaging modalities and/or tumour
markers (thyroglobulin, carcinoembryonic antigen and
calcitonin) as indicated.
Serum T4 and TSH are better assessed by a sensitive
immunoassay to analyse the effects of administration of
thyroid hormone postoperatively.
204 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Goitre 205
 Chapter

Gynaecomastia
13
Gynaecomastia is the enlargement of one or both male CAUSES OF GYNAECOMASTIA
breasts. It is defined as a palpable firm mass in the subareolar
The causes of gynaecomastia can be grouped as
region and measures more than 2 cm in thickness. The
in Table 13.1.
palpable breast is due to proliferation of glandular and
stromal tissue, i.e. ductal elements or interlobular and
Physiological Gynaecomastia
periductal connective tissue with subsequent progressive
fibrosis and hyalanisation. The enlargement varies from a Newborn or Neonatal Gynaecomastia
small subareolar breast button to that of a female breast
It is transient and caused by the placental transfer of maternal
often with feminisation of the nipple.
oestrogens into the newborn. Sometimes fluid can be
expressed which is known as witch’s milk.
PATHOPHYSIOLOGY
The degree of development of the breast depends on the Adolescent Gynaecomastia
ratio of the two sex hormones viz. testosterone and
In puberty, gynaecomastia occurs in about 40 to 50% of the
oestradiol. The oestrogens cause not only the initial
normal boys. In normal puberty without gynaecomastia
enlargement of breast bud but also stimulate the growth of
oestradiol levels are relatively high as compared to
the ductal epithelium as well as growth of the myoepithelial
testosterone towards evening, whereas oestradiol levels in
cells whereas androgens inhibit stimulatory effect of the
pubertal gynaecomastia are often elevated with marked
oestrogens on the breast. The androgens are testosterone
fluctuations in 24 h period. High prolactin in these boys
(testis), dihydrotestosterone (biotransformation of the
may be due to elevated oestradiol (Fig. 13.1).
testosterone in the skin and prostate), and androstenedione
(adernal gland). In the males, oestradiol is formed principally
Climacteric (Senescent) Gynaecomastia
by the conversion of circulating androgens into oestrogens
besides production by testes. Generally, gynaecomastia is It is seen in old age due to conversion of androgens to
caused by increase in the ratio of oestradiol to testosterone, oestrogens in the extraglandular tissue. However, an
i.e. more oestradiol or less testosterone activity due to any underlying hepatic insufficiency or tumours of the testis or
cause can result in gynaecomastia (Testosterone-estradiol adernal gland should not be lost sight of.
ratio is 15-17). In some, decreased testosterone leads to
increased LH which in turn results in an increased production Pathological Gynaecomastia
of oestradiol by testes. Gynaecomastia is usually mild and Decreased Androgen Secretion
occurs in early or mid puberty which resolves spontaneously
in about one year. Gross gynaecomastia occurs generally in Primary Testicular Failure
late puberty. In old age, due to decreased serum testosterone • Congenital anorchia: It is a rare disease in which there
levels, milder forms may be encounterd. Clinical is development of Wolffian system and failure of
significance of gynaecomastia, which is usually painless, is Müllerian duct and gonads.
the high incidence of malignancy of the male breast apart • Klinefelter’s syndrome: The primary defect is the
from disfiguration. presence of two X chromosomes in the male (47 XXY)
 Gynaecomastia 207

Table 13.1: Aetiological classification of gynaecomastia

1. Physiological Gynaecomastia
i. Newborn or neonatal
ii. Adolescent
iii. Climacteric (senescent)
2. Pathological Gynaecomastia
• Decreased Androgen Secretion (Decreased Production)
a. Primary testicular failure
i. Congenital anorchia
ii . Klinefelter’s syndrome
iii. Noonan’s syndrome
b. Secondry testicular failure
i. Infections-Mumps orchitis, Hansen’s disease,
tuberculosis
ii. Castration
iii. Pituitary hypothalamic disorders, e.g. prolactin
secreting tumours
iv. Chronic renal failure Fig. 13.1 Adolescent gynaecomastia
v. Neurological
a. Traumatic paraplegia instead of the normal chromosomal constitution of 44
b. Dystrophia myotonica autosomes with one X and one Y sex-chromosome, i. e.
• Androgen Resistance (Decreased Action) 46 XY. It is characterised by small testes, gynaecomastia,
a. Testicular feminisation sterility, decreased intelligence quotient and a nuclear
b. Reifenstein’s syndrome sex chromatin dot (characteristic of the female)
• Increased Oestrogen Secretion demonstrated in the nucleus of squamous cells of the
a. True hermaphroditism buccal mucous membrane.
b. Neoplasms The length of the testes and the penis is decreased
i. Testicular tumours though the genitalia is apparently normal. The
ii. Adernal carcinoma gynaecomastia is progressive and becomes prominent,
iii. Ectopic hormone (Human Chorionic Gonadotropin- with eunuchoid habitus.
HCG) secreting tumours, e.g. Bronchogenic The gonadotropins are elevated in the plasma and
carcinoma
urine, whereas the testosterone is decreased. The
c. Congenital adernal hyperplasia
mechanism is the diminished testosterone leading to
• Increased Conversion of Androgens to Oestogens
increased luteinising hormone with consequent increased
a. Cirrhosis of the liver
b. Hyperthyroidism
production of testicular oestrogens.
c. Nutritional (refeeding after starvation or malnutrition) It is a genetic disorder of hypergonadotrophic
hypogonadism recognised at puberty with associated
3. Pharmacological: Drugs failure of seminiferous tubules and decreased Leydig
i. Oestrogenic—Oestrogens, digitalis cell function.
ii. Antiandrogenic
• Noonan’s syndrome: It is characterised by short stature,
a. Inhibitors of testosterone synthesis, e.g. Ketoconazole,
webbing of the neck, characteristic facies like inverted
high doses of spironolactone, alkylating drugs
triangular face, low set ears, downward slant of the eyes
b. Inhibitors of testosterone action, e. g. cimetidine, low doses
which are widely spaced (hypertelorism), upturned nose
of spironolactone, cyproterone acetate
iii. Gonadotropins—Human Chorionic Gonadotropin (hCG);
with mental retardation, congenital heart disease and
Human Pituitary Gonadotropin (hPG); Human Menopausal cryptorchidism with diminished penile size in boys and
urinary Gonadotropin (hMG) delayed puberty in girls.
iv. Prolactinogenic—Phenothiazine, methyldopa Secondary Testicular Failure
v. Unknown Mechanism—Busulfan, penicillamine, isoniazid, • Infections—Mumps orchitis and Hansen’s disease:
tricyclic antidepressants These or any other destructive lesion involving the testis
 208 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
may result in Gynaecomastia. Mumps orchitis usually
occurs 7 days after the onset of parotitis and is heralded
by high fever, chills and swollen testis. Sometimes, it
may occur simultaneously or even without parotitis. The
orchitis may be followed by progressive testicular
atrophy.
• Pituitary hypothalamic disorders like pituitary tumours
may frequently secrete large amounts of prolactin, when
associated particularly with secondary hypogonadism.
Testosterone levels are regulated by a biofeedback
mechanism through leutinising hormone (LH). Prolactin
may also indirectly influence testosterone levels by
inhibiting LH. Decreased androgen levels result in
gynaecomastia in hypogonadotrophic hypogonadism
which may be due to an isolated lesion or as a part of
panhypopituitarism.
• Chronic renal failure: In this, increased plasma
gonadotrophins (FSH as well as LH) and reduced
synthesis of androgens is possibly the mechanism of
gynaecomastia (refer to Chapter ‘Coma’).
• Neurological disorders: In disorders like spinal
paraplegia, the testosterone levels may be low and in
some cases the testis may show tubulous sclerosis and
hyalinisation. Since the maintenance of the gonado-
trophic function depends on neural stimuli from the
genital region and in turn the male gonadal function on
FSH and LH secretions, loss of sensation in the genital
area in paraplegias may account for gynaecomastia
(Refer to Chapter ‘Paraplegia’).
In dystrophia myotonia, the testis is small with
damage to seminiferous tubules and Leydig cells, It is a
hereditary disorder characterised not only by dystrophic
disturbances like gonadal atrophy and cataract but also
muscular dystrophy and myotonia.
Androgen Resistance (Decreased Action)
Complete testicular feminisation syndrome This is a
complete variety of male pseudohermaphroditism (one type
of gonad either testis or ovary is present in pseudo-
hermaphroditism). It is an X-linked disorder due to the
deficiency of androgen receptors in target tissues. Though
testis produces high levels of testosterone and oestrogen,
the testosterone receptors in the pituitary are affected. The
external genitalia are that of female type with a shallow
vagina ending blindly in a pouch. The testis is undescen-
ded, menstruation does not occur though the breasts appear
feminine at puberty. Subjects with this syndrome are
46 XY males and phenotypic females.
Reifenstein’s syndrome It is a hereditary type of incomplete
male pseudohermaphroditism. Perineoscrotal hypospadias,
cryptorchidism, (small to normal size) gynaecomastia, and
incomplete virilisation at puberty are the manifestations.
Individuals with this syndrome pass off as men with
incomplete male genitalia development or hypogonadism.
Infertility is invariable. Like testicular feminisation
syndrome it is X-linked disorder of sex differentiation.
Though testosterone, oestrogen, and LH hormones are
elevated, there is partial resistance to androgenic and
metabolic effects of testosterone. Sex chromosome
constitution is XY. Buccal smear is chromatin negative.
Increased Oestrogen Secretion
True hermaphroditism In true hermaphroditism, both gonads
(one testis and one ovary) are present. The external genitalia
may display either normal male external genitalia or normal
female external genitalia or different stages of male to female
spectrum. The external genitalia may not give a correct
indication of the internal reproductive system. It is a rare
genetically determined diorder and is not due to hormonal
imbalance.
Neoplasms
Testicular tumours: Testicular tumours may arise from germ
cells or sertoli cells or interstitial cells of Leydig . Most of
the tumours are malignant occuring between the ages of 18
and 35. The testis may be enlarged, firm and nontender.
Gynaecomastia and raised urinary chorionic gonadotrophins
are the essential features. The former is due to increased
secretion of oestrogens as occurs in Leydig cell tumours or
on stimulation of testis by human chorionic gonadotrophins
produced by choriocarcinoma resulting in more oestrogens.
• Adernal carcinoma: Feminising adernal cortical tumours
may produce oestrogens leading to gynaecomastia. Testis
may become small. with hypoplasia of Leydig cells and
aspermia. Oestrogen levels are raised in the plasma or
urine while gonadotrophins are suppressed.
• Ectopic hormone secreting tumours: Bronchogenic
carcinoma may secrete human chorionic gonadotrophins
which may stimulate the testis leading to increased
oestrogen levels. Gynaecomastia is most often associated
with hypertrophic pulmonary osteoarthropathy.
• Congenital adernal hyperplasia: When 21 hydroxylase
is deficient, increased production of oestrogens occurs
due to the increased production of androstenedione
leading to increased substrate for peripheral aromatase.
This is reflected as feminisation in boys.
 Gynaecomastia
Increased Conversion of Androgens to Oestrogens
Cirrhosis of the liver Damaged liver fails to detoxify circulating
oestrogen and adrenocortical hormones, which in turn may
lead to secondary pituitary depression and decreased
follicular stimulating hormone with consequent testicular
atrophy. So gynaecomastia results from (a) increased
oestrogen levels due to disturbance of normal degradation
of androgens and subsequent increased conversion to
oestrogens; (b) decreased testosterone as a result of (i)
testicular atrophy and (ii) increased sex hormone binding
globulin reducing free testosterone levels; and (c) improved
nutrition with high protein and high calorie diet may resume
gonadotrophin production with refeeding gynaecomastia
(Refer to Chapters ‘Jaundice’ and ‘Oedema’).
Hyperthyroidism Gynaecomastia is seen in a small percent-
age of cases of thyrotoxicosis. The mechanism appears to
be increased conversion of androgens to oestrogens in the
liver. This excess oestrogens and throxine lead to increased
levels of sex hormone binding globulin. So much so more
testosterone is bound to the globulins and free testosterone-
oestradiol ratio is lowered (Refer to Chapter ‘Goitre’).
Nutritional In starvation or malnutrition, the pituitary
gonadotrophins are depressed which in turn lead to
diminished testicular function. In renutrition, they are
increased resulting in increased oestradiol secretion by the
testes, with consequent refeeding gynaecomastia.
Pharmacological (Drugs)
A number of drugs can act by various mechanisms leading
to gynaecomastia.
Oestrogenic
Oestrogen receptors binding, results in oestrogen-like effect
or during oestrogen therapy. Digoxin or griseofulvin are
the classical examples of receptors binding to oestrogen.
Antiandrogenic Drugs
They interfere with the synthesis and binding of androgens
to cytosol receptor protein, e.g. cimetidine. Chronic
alcoholism may be associated with gynaecomastia due to
diminished synthesis of testosterone and decreased
testosterone receptors in the tissues.
Gonadotrophins
Gonadotrophins therapy increases testicular secretion of
oestrogen.
209
Prolactinogenic
Increased prolactin levels, by prolactin stimulators and by
suppression of prolaction inhibiting factor, e.g.
phenothiazine.
Androgenic
Testosterone therapy may sometimes produce gynaeco-
mastia probably due to conversion of testosterone to
oestrogen.
Unknown Mechanism
Drugs like busulfan, tricyclic antidepressants, cause
gynaecomastia which mechanism is ill understood.
CLINICAL APPROACH
The crux of the problem of hypertrophy of the male breast
is to differentiate whether it is due to an increase in the duct
tissue and periductal stroma (glandular tissue), or from fatty
deposits in the mammary region. Collection of this adipose
tissue without glandular elements behind the areola is
otherwise known as lipomastia. In true gynaecomastia, a
smooth firm tissue which is not fixed to the surroundings is
palpable behind the areola, and this glandular tissue usually
measures more than 2 cm in diameter. In cases of doubt
whether the tissue is glandular or adipose in nature,
comparing its consistency to the adipose tissue of anterior
axillary fold may be helpful. Sometimes other causes of the
enlargement of the breast may be carcinoma, neurofibroma
or lipoma.
The next problem in question is whether it is
physiological or pathological. If pathological, is it of
endocrinal origin? If endocrinal, whether gonadal (testicular
failure or sex differentiating disorders); or pituitary or
adernal or thyroid gland at fault. If nonendocrinal, any
underlying systemic disorder to account for the gynaeco-
mastia or any pharmacological etiology or simply familial
origin has to be differentiated.
In the diagnostic evaluation of gynaecomastia, history
usually offers obvious clues.
History
1. Age—Age of presentation may be significant since it is
likely to be physiological in neonates or youngers.
Although, in elderly people, gynaecomastia is
physiological, a careful history should be elicited for
establishing a possible underlying pathological cause.
 210 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
2. Habits—Any alcoholic indulgence or smoking habit?
3. Drug history—Cause becomes obvious if there is history
of intake of above mentioned drugs.
4. Pain—Is gynaecomastia painful or not ? Usually painful
after hCG administration or in paraneoplasms like
bronchogenic carcinoma secreting hCG, or following
refeeding after starvation.
5. Duration—The florid type may regress or progress to
fibrous type or if it is more than one year duration, it is
likely to be fibrous type, which is irreversible.
6. Past History—Past history of any parotitis, or jaundice.
7. Present history of
a. Heat intolerance as in hyperthyroidism
b. Loss of libido
c. Loss of weight
d. Haemodialysis
Physical Examination
An endeavour should be made to see whether the
gynaecomastia is existing per se or associated with any other
pathological state.
General Examination
1. Assess body configuration for feminisation and
distribution of hair or precocious puberty.
2. Examine the breast preferably in supine position. See
whether enlargement is unilateral or bilateral (more
common).
Feel the suspected enlarged breast tissue between
the thumb and index finger, which should be placed on
the inner superior and outer inferior quadrants of the
breast and lift the tissue of the chest wall. If this
subareolar tissue is smooth and firm, not fixed to its
surroundings and measures more than 2 cm in thickness,
it indicates true gynaecomastia. Look also whether any
fluid can be expressed (Witch’s milk in neonates or
nonpuerperal galactorrhoea in adults).
3. Genital examination
a. Testes examination
i. Inspection—Whether present or absent; whether
small and symmetrical (consider chromosome
abnormalities); whether asymmetrical (consider
testicular tumour).
ii. Painful or not (testicular sensation is absent in
testicular atrophy).
iii. Measurement—The normal adult testis (i.e.
beyond 16 years) ranges between 3.5 to 5.5 cm
and average 4.5 cm in length.
b. Any evidence of hypogonadism (small penis, testis
and scrotum—infantile genitalia)
c. Whether external genitalia formation is normal or
abnormal as in hermaphroditism.
4. Nutritional status—Quantitative assessment by objective
measurements (Refer to Chapter ‘Weight Loss’).
5. Body measurements—If span is > 2 inches than height
and feet to symphysis pubis > 2 inches than symphysis
to head, it is suggestive of eunuchoidism.
6. Any lymphadenopathy with or without weight loss.
7. Any thyromegaly.
8. Look for any hypopigmented anaesthetic patches or skin
nodules (Hansens).
Systemic Examination
1. Chest examination—For any evidence of collapse due
to bronchogenic carcinoma.
2. Abdomen examination—For hepatosplenomegaly or
ascites or other evidences of chronic liver disease.
3. Complete neurological examination which includes.
a. Anosmia (associated hypogonadism is known as
Kallmann’s syndrome).
b. Examination of visual fields and fundi for evidence
of pituitary disease or papilloedema.
c. For evidence of neurological problems like traumatic
paraplegias, dystrophia myotonica.
Investigations
If the cause of gynaecomastia is obvious, very little
investigation may be necessary; if there is no obvious cause,
endocrinal evaluation may be imperative.
1. Urine examination—For any evidence of chronic renal
disease. (Refer to Chapter ‘Polyuria’).
2. Complete blood picture and ESR for evidence of any
malignant disease.
3. Radiology
a. X-ray of the skull for any evidence of tumour in
or near the pituitary fossa.
b. X-ray of the chest for evidence of bronchogenic
carcinoma.
c. If necessary, a CT scan of the skull for pituitary
tumours; CT scan or isotope scanning of the
adrenal for any suspected adrenal tumour.
4. Ultrasound examination of the abdomen.
5. Liver function tests for assessment of chronic liver
disease (refer to Chapter ‘Jaundice’), if indicated.
6. Renal function tests for assessment of chronic renal
disease (refer to Chapter ‘Polyuria’), if indicated.
7. Endocrinal evaluation—Measurement of (i) serum
testosterone; (ii) Serum luteinising hormone;
 Gynaecomastia
(iii) estradiol; (iv) hCG level; (v) prolactin level;
(vi) serum androstenidione; (vii) 24 h urinary 17 keto-
steroids, and (viii) thyroid function tests, if indicated.
N.B.: If serum testosterone is decreased and
luteinising hormone increased, it is likely to be
testicular failure. If both are increased, it is suggestive
of androgen resistance or a gonadotrophin secreting
tumour. If both are decreased, it indicates increased
oestrogen production due to sertoli cell tumour of the
testis, adrenal carcinoma, bronchogenic carcinoma,
cirrhosis and hyperthyroidism. Increased hCG levels
point towards gonadotrophin secreting tumours like
chorioepithelioma, seminoma. Raised prolactin levels
confirm the presence of prolactin secreting tumours
like chorioepithelioma, seminoma, extragenital
teratoma. Increased androstenidoine and increased 24 h
ketosteroids are suggestive of adrenal tumour.
7. Chromosomal analysis—To differentiate sex disorders.
A karyotype of 47 XXY confirms the diagnosis of
Klinefelter’s syndrome.
8. Buccal smear examination—For presence of sex
chromatin in the nucleus of the squamous cells which
appear as a dark staining dot. This enables to determine
the nuclear sex of the individuals, as evidenced by
presence of the sex chromatin in female sex chromo-
some constitution and absence of the same in male
chromosome constitution. In Klinefelter’s, this sex
chromatin dot is present.
9. Mammography—May be useful to differentiate
gynaecomastia from lipomastia.
10. Biopsy techniques
a. Biopsy of the Testis to determine the cause of the
testicular tumour.
b. Biopsy of the suspected organ tumours.
c. Biopsy of the breast tissue to differentiate from
neurofibroma or carcinoma and to assess the
histologial changes of gynaecomastia, whether
ductal hyperplasia and lobular formation
predominate or alteration in periductal and
interlobular tissue predominate. These two patterns
usually imply different causal factors, as the former
microscopic picture indicates hormonal etiology
and the latter systemic disorders.
TREATMENT OF GYNAECOMASTIA
The clinician must assess, at the very outset, the significance
of the benign glandular enlargement of male breast whether
211
it is (a) simply physiological or (b) pathological (sometimes
serious even) or (c) pharmacological in origin before
choosing the therapeutic modalities. Consequently, the
management depends on causal factors (vide supra) and/or
how disturbing and embarassing it is to the patient. Further,
the foremost objective is to detect the underlying
pathological condition, which is correctable.
Nevertheless, the latter can be simplifed as
1. Primary testicular failure (a) congenital; (b) acquired
(all conditions other than pituitary lesions)
2. Secondary testicular failure consequent to pituitary
lesions (vide infra)
Symptomatic Treatment
Reassurance
(Since physiological gynaecomastia resolves sponta-
neously).
Medical
a. Tamoxifen (antioestrogen)-Varying degrees of success
rtesult in mild cases by antagonising oestrogen receptors
(dose 10 mg bd).
b. Danazol (100-400 mg bd) is another drug for mild cases
which is a synthetic steroid and acts by suppressing
pituitary gonadotrophin output. (Structurally related to
testosterone, attenuated androgen).
Surgical
Excision through a periareolar incision may be necessary
in severe gynaecomastia (due to organic disease
unresponsive to treatment or prolonged drug therapy) or
for social embarrassment and cosmetic purpose. For the
latter, it is better to wait for about two years for any possible
regression.
Specific Treatment for Specific Causes
Physiological Gynaecomastia
a. Neonatal gynaecomastia is transient.
b. Pubertal gynaecomastia is generally mild and resolves
spontaneously within 12-18 months. Nevertheless gross
gynaecomastia in late puberty requires treatment.
c. Senescent gyneacomastia (secondary to declining
testosterone levels) is better left alone unless, of course,
pathological.
 212 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Pathological Entities
Decreased Androgen Production
Hypogonadism whether hypergonadotrophic (Klinefelter’s
syndrome) or hypogonadotrophic (panhypopituitarism)
results in gynaecomastia.
1. Primary testicular failure:
a. Congenital Anorchia—Androgen replacement
instituted to achieve full desired sexual maturation.
Depo testosterone, i. e. long acting esters (oenanthate
or propionate) of testosterone are preferred (250 mg
IM every fortnight for two years followed by 100
mg every month as maintenance therapy), monitoring
the packed red cell volume every six months and the
symptoms as well.
b. Klinefelter’s syndrome—Correction of androgen
deficiency by testosterone therapy as above, is
beneficial for sexual maturation, although the
infertility and gynaecomastia are not amenable.
However, the latter can be subjected to plastic
surgery, if desired.
c. Noonan’s syndrome—In boys, the replacement is
done with testosterone oenanthate (100 mg at
monthly intervals for 6 months and repeat after 6
months) and hCG (1500 IU) once weekly or pulsatile
GnRH therapy (Gonadotorophin Releasing
Hormone). The bone age must be monitored
periodically to ensure that skeletal maturation is not
disproportionate. Cryptochidism is treated with hCG
course or GnRH intranasally for one month at the
age of 6 years; if unsuccessful, testis is placed in the
scrotum by surgical means. (Oestrogens rise from
conversion from testosterone and may aggrevate
gynaecomastia)
2. Secondary testicular failure:
a. Infections like mumps, Hasen’s disease, tuberculosis
are appropriately and adequately treated so as to
prevent testicular failure especially seminiferous
tubular failure. (Refer to Chapters ‘Haemoptysis’ and
‘Rashes’).
b. Surgical castration resulting in sudden loss of
testosterone, needs replacement therapy.
c. Panhypopituitarism—In the prepubertal male, half
the dose of testosterone is given initially and
increased gradually. If fertility is required injections
of hCG are given, after withdrawing testosterone. In
the postpubertal male, human chorionic
gonadotrophin (hCG) is given (3000 iu weekly IM
for 6 months) to stimulate the testosterone production
followed by a combination of hCG and FSH (as
human menopausal gonadotrophin) 75 iu
intramuscularly thrice weekly for another 9-12
months, if fertility is needed. Pulsatile Gonadotrophic
releasing hot move (GnRH) 1 to 10 µg pulse every
hour through portable infusion pump is necessary if
the cause of hypopituitarism is in the hypothalamus.
d. Prolactin secreting tumours—Bromocriptine (2.5 mg
orally 3 times a day) is beneficial to reduce the
prolactin levels and also for regression of the macro-
adenoma. Tomaxifen may be useful if refractory to
bromocriptine. However, surgical removal may be
necessary in some cases. Radiotherapy may be
required to prevent regrowth, after stopping
bromocritine.
e. Chronic renal failure—(Refer to Chapter ‘Polyuria’.)
f. Neurological causes like traumatic paralpegia and
dystrophia myotonica require only symptomatic
therapy.
Androgen Resistance (decreased action)
i. Testicular feminisation—Surgical intervention may be
undertaken to enlarge the vagina and remove the testis
(because of the potential for malignant change of the
latter). The clitoris may be amputated if hypertrophied.
ii. Reifenstein syndrome—Androgen replacement therapy
is necessitated for Leydig cell deficiency. The
hypospadias and gynaecomastia need surgical
correction.
Increased Oestrogen Secretion
i. True hermaphroditism—Treatment depends on the
presence of sexual inclination/preponderance. If
feminine, appropriate surgical repair of the clitoris as
well as vagina and removal of the testis (to prevent/
diminish the hirsutism) can be done. When masculine,
plastic operations for hypospadias and creating a
scrotum and excision of gynaecomastia can be
undertaken.
ii. Neoplasms—Testicular tumours, are treated by surgical
removal, radiotherapy and/or antitumour chemotherapy
with cisplatin. Triple therapy with chlorambucil,
methotrexate, and actinomycin-D is favoured for
metastastes.
Adernal carcinoma is resected (if possible),
irradiated, followed by o,p, DDD(6-9 gm/day).
Metyrapone (250 mg tds) or aminoglutethimide (250
mg tds) is beneficial for cortisol over production.
hCG secreting tumours like bronchogenic
carcinoma treated accordingly (Refer to Chapter
‘Haemoptysis’).
Gynaecomastia 213
214 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Gynaecomastia
iii. Congenital adernal hyperplasia—Treatment with
optimal dose of cortisone (more in the night and less
in the morning) will suppress abnormal adernal activity
through suppression of ACTH and consequently
production of adrenal hormones (excess cortisone,
however, retards growth).
Increased Conversion of Androgens to Oestogens
i. Cirrhosis of the liver-(Refer to Chapter ‘Oedema’).
ii. Hyperthyroidism-Refer to Chapter ‘Goitre’).
iii. Nutritional-As refeeding gynaecomastia (renutrition
after starvation) results by a mechanism similar to
pubertal gynaecomastia, it is treated accordingly.
215
Gynaecomastia due to malnutrition is managed with
nutritional supplements and symptomatic therapy.
Pharmacological Causes
The list of drugs above (blocking the synthesis of
testosterone or behaving like antiandrogens, etc.) leading
to gynaecomastia, when withdrawn (if feasible), may
facilitate regression of the glandular enlargement. If stil
persists, surgical excision is recommended.
N.B.: If testosterone, Oestradiol, Gonadotrophins (LH,
FSH), hCG, prolactin are normal surgery considered for
cosmetic reasons.
 Chapter
Haematemesis and
14 Melaena
Haematemesis is vomiting of blood and melaena is passing
of black tarry stool. Both symptoms signal gastrointestinal
bleeding. Haematemesis indicates that the source of bleeding
is proximal to the ligament of Treitz and subsequently
melaena may result. However, the bleeding that occurs
below the ligament, usually results in melaena alone since
rarely the blood enters the stomach.
The colour of vomited blood may be bright red or altered
colour (dark red or brownish) depending upon the duration
of contact of blood with hydrochloric acid. If vomiting
occurs immediately after the bleeding, it is a bright red liquid.
On the other hand, if there is any delay in vomiting of blood,
the haemoglobin will be converted into haematin by the
hydrochloric acid, resulting in dark brownish vomitus with
clots (coffee ground).
Melaena indicates relatively slow bleeding in the
gastrointestinal tract. It depends upon the gastrointestinal
transit time. If the transit is rapid, the blood per rectum may
be bright red (haematochezia). Melaena results if the blood
remains in the gut for about 8 h or more. It is due to haematin
which results from contact of blood with hydrochloric acid
and digestive juices.Generally, bright blood per rectum
indicates bleeding from large bowel only. About 50 to 100 cc
of blood is required to produce stickly black usually soft
stool (tarry stool). This may be seen up to three to four days
and occult blood test is positive up to one week. Generally
if 500 cc or more of blood is lost in melaena and 1000 cc or
more in haematemesis, hypovolaemic shock sets in.
Sometimes, if the quantity is less, i. e. 10 to 50 cc, it is only
detected by haem occult test. Black or dark stool may occur
after ingestion of bismuth containing antacids, iron, charcoal
or liquorice. The test has to be done without aspirin or meat
diet, for three days to avoid false positives.
CAUSES OF HAEMATEMESIS AND MELAENA
The causes of Haematemesis and Melaena have been listed
in Table 14.1.
CAUSES OF HAEMATEMESIS
Oesophageal Causes
Portal hypertension In portal hypertension, the portal venous
pressure is more than 10 mm of Hg. This may be due to
obstruction either in the intrahepatic or extrahepatic territory.
Hepatic cirrhosis and noncirrhotic portal fibrosis are the
common causes of intrahepatic portal hypertension, whereas
portal venous thrombosis commonly and hepatic vein obs-
truction rarely, account for extrahepatic portal hypertension.
The aetiology of hepatic cirrhosis is predominantly
alcohol (portal), posthepatitis B (postnecrotic scarring) Refer
to Chapter ‘Jaundice’.
Noncirrohotic portal fibrosis is associated with portal
hypertension and may be due to malaria, schistosomiasis or
polycystic disease of the liver.
The bleeding in portal hypertension is generally from
oesophageal and gastric varices which occurs due to
anastomosis of the left gastric vein of the portal system with
oesophageal, azygos minor veins of the caval system. The
cause of the variceal rupture is due to sudden rise in intra-
abdominal pressure after straining at stool or passage of
large quantities of food down the oesophagus, without
proper mastication. When oesophageal and gastric varices
co-exist, negative pressure in thorax and lax connective
tissue at lower end of oesophagus, account for the more
common oesophageal bleeding, irrespective of portal
pressures.
 Haematemesis and Melaena 217

Table 14.1: Causes of Haematemesis and Melaena

I. Causes of Haematemesis
A. Alimentary
1. Oesophageal
i. Oesophageal varices due to portal hypertension
ii. Reflux oesophagitis
iii. Oesophageal carcinoma
iv. Mallory-Weiss syndrome
2. Gastroduodenal
i. Acute gastric erosions
ii. Gastritis (alcohol, drugs like asprin and uraemia)
iii. Peptic ulcer
iv. Carcinoma of stomach
3. Haemobilia (Bleeding into the biliary tract)
4. Vascular
i. Telangiectasia
ii. Hypertension, cerebrovascular accidents
iii. Aneurysm of aorta (rare)
iv. Hemangioma of stomach
v. Pseudoxanthoma elasticum Fig. 14.1: Endoscopic view of oesophageal
vi. Arteriovenous malformations variceal bleeding
B. Non-Alimentary Causes
i. Blood swallowed from bleeding elsewhere (epistaxis or Distended collateral veins over abdominal wall, ascites
haemoptysis)
and splenomegaly are other diagnostic features of portal
ii. Blood diseases
a. Leukaemia
hypertension. Other stigmata of chronic liver disease like
b. Haemophilia jaundice, liver palms, spider naevi, foetor hepaticus may
c. Anticoagulant therapy also be present.
d. Purpura Barium swallow radiology demonstrates the oesophageal
e. Acute fevers (toxins damage capillary walls) varices or can be visualized by fibreoptic oesophagoscopy
f. Disseminated intravascular coagulation (Fig. 14.1) or ultrasound examination of the abdomen. Portal
II. Causes of Melaena venogram studies will be contributory to diagnose the site
1. Upper Gastrointestinal Lesions and other Causes of Haematemesis of portal venous obstruction.
(Melaena alone results when rate of bleeding is relatively slow) Reflux oesophagitis and oesophageal carcinoma
2. Between the Duodenal Bulb and Caecum
Refer to Chapter ‘Dysphagia’.
i. Inflammations
a. Typhoid Mallory-Weiss syndrome: It is a tear at the oesophagogastric
b. Tuberculosis junction brought on by retching or vomiting, followed by
c. Crohn’s Disease
haematemesis. This is confirmed by endoscopy.
ii. Vascular
a. Mesenteric vascular Insufficiency (ischaemic colitis)
b. Arteriovenous malformations Gastroduodenal Causes
iii. Tumours Acute gastric erosions: Acute ulcers or erosions may be
a. Hemangiomas
associated with ingestion of alcohol or drugs (nonsteroid
b. Polyps
c. Leiomyoma anti inflammatory drugs and steroids and anticoagulants).
d. Lymphoma Dull aching pain in the epigastrium immediately after spicy
iv. Congenital—Meckel’s diverticulum (distal ileum) food or drugs, with vomiting and tenderness is highly
v. Melaena neonatoram due to hypoprothrombinaemia suggestive. Haematemesis and melaena may be the first
3. Lower Gastrointestinal Lesions manifestation. Gastroscopy shows acute inflammation or
i. Colonic lesions erosions and radiological examination may be non-
ii. Anorectal lesions contributory.
 218 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Chronic gastritis The continued use of tobacco, alcohol or
spicy foods may lead to chronic gastritis. Epigastric pain
(aggravated by food) nausea or vomiting, flatulence and foul
breath are the usual symptoms.
Gastroscopy reveals pale atrophic gastric mucosa with
clearly visible vessels in chronic gastritis. Barium meal
shows coarse gastric folds of thickened mucous membrane.
In uraemia bleeding may arise from any part of the
gastrointestinal tract and may present as haematemesis with
melaena, although the common presentation is anorexia or
vomiting.
Peptic ulcer Peptic ulcer includes ulcers occurring in the
mucosal lining of the lower oesophagus, stomach, duodenum
and Meckel’s diverticulum, and anastomotic jejunal ulcers.
Sometimes both gastric and duodenal ulcers coexist. It is
the most common cause of gastrointestinal bleeding.
Duodenal ulcer in its first part accounts for 20 per cent and
half of them rebleed. The diagnosis is essentially based on
symptom complex of dyspepsia and periodic epigastric pain
related to meals. It is usually worse at night and sometimes
radiates to the back, which is aggravated by dietetic errors
and long intervals between meals. It is relieved by food or
after vomiting. The ulcer occurring in the distal part of the
duodenum is usually due to Zollinger-Ellison syndrome. In
gastric ulcers, the pain is also epigastric and may be relieved
by vomiting.
Etiopathogenesis: The etiology of duodenal ulcer is
multifactorial. The main equation in its genesis is acid pepsin
versus mucosal defence. Higher acid output is present in
the majority of cases indicating a sustained increased drive
to the parietal cells. The acid stimulants are common
beverages like tea, coffee, milk, alcohol; drugs like non-
steroid anti-inflammatory drugs, steroids, and theophylline;
and cigarette smoking. Genetic predisposition, associations
with blood group ‘O’, chronic obstructive pulmonary disease
or cirrhosis and increased vagal activity as a reflection of
chronic psychological stress, offer traditional explanation
for hypersecretion.
Whatever the means by which the acid secretion is
stimulated, be it through histamine-H2 receptor, muscurinic
M1 receptor (cholinergic) or gastrin receptor, the final
pathway of liberation of H ions is through H+ - K+ - ATPase
(enzyme serving as a gastric proton pump), in exchange for
K and ultimate coupling of Cl (HCO3 is exchanged for Cl)
to the secretion of H into the gastric lumen. Pepsinogen
secretion usually takes place along with acid secretion by
the parietal cells. This is converted to pepsin by the acid.
When the intragastric pH is maintained at 4 or above, pepsin
output is low and its activity is decreased.
Normally, mucosa maintains permeability barrier. The
mucosal integrity is maintained by mucus, bicarbonate, intact
mucosal blood flow, cell renewal and endogenous
prostaglandins, (which increase the mucus and bicarbonate
secretion and maintains adequate mucosal blood flow).
Spicy diet causes gastric mucosal damage. Recently,
Helicobacter pylori (Campylobacter pylori) infection is
incriminated for the mucosal damage, since ammonia
produced by it, interferes with negative feedback to gastrin
secretion by luminal gastric acid, leading to hyperacidity
and hypergastrinaemia. The antiprostaglandin activity of the
organism also contributes to mucosal damage.
In gastric ulcer, the acid secretion is normal or
diminished. Duodenogastric reflux of bile acids, pancreatic
juice, and lysolecithin, (probably due to defective pyloric
sphincter tone consequent to the failure of hormones like
cholecystokinin) cause mucosal injury. Whatever the means
by which the cytoprotective factors are involved in affecting
the mucosal resistance to acid peptic digestion or
duodenogastric reflux, the disruption of the normal mucosal
barrier facilitates leaking of sodium ion and entry of
hydrogon ion into mucosal tissue resulting in cellular
dysfunction followed by slough and ulceration.
Thus pathogenesis of this ulcer is based on the disturbed
balance between acidpepsin secretion and mucosal
resistance. The ulcers may be acute or chronic and may be
single or multiple. In duodenal ulcer, acid secretion is on
the higher side and in gastric ulcer the mucosal resistance
is defective and acid may not be abnormally high or may
even low. Haematemesis and melaena result from the
ulcerative process, opening up the vessel and the quantity
varies depending on the type of vessel which is eroded. The
diagnosis is confirmed by
1. Radiology with barium contrast techniques or preferably
by double contrast examination. The appearance of ulcer
crater as the barium is collected in the ulcerated area is
characteristic.
2. Endoscopy: Fibreoptic endoscopy facilitates accurate
diagnosis (Fig. 14.2).
3. Fractional test meal (FTM): Gastric secretory function
tests like FTM or alcohol test meal, augmented histamine
test or insulin test may still be of value in assessing the
acid production.
Carcinoma of stomach Epigastric pain or anorexia, loss of
weight and vomiting depending on the site of growth in the
aged are the main features. Left supraclavicular lymph gland
may be enlarged. FTM shows achlorhydria and the barium
meal may reveal the growth (Fig. 14.3). Gastroscopy
facilitates visualisation and biopsy.
 Haematemesis and Melaena
Fig. 14.2: Duodenal ulcer as seen through the gastroscope
Haemobilia
Gallstones ulcerating through gallbladder into the duodenum
or ductal parasitism (Ascaris lumbricoides) or hepatic trauma
may rarely cause haematemesis and melaena. Biliary colic
and obstructive jaundice are the other manifestations.
Duodenoscopic examination demonstrates bleeding from
ampula of Vater.
Vascular Causes
Telangiectasia Telangiectases are multiple dilatation of
capillaries and arterioles usually occurring over the mucosa
Fig. 14.3: Upper GI barium radiograph showing filling defect
in the body of the stomach, diagnostic of gastric carcinoma.
Note coincidental duodenal diverticulum
219
of the nose, mouth or gastrointestinal tract. Bleeding can
occur from one of the sites in the gastrointestinal tract
resulting in haematemesis. A classical example is hereditary
haemorrhagic telangiectasia.
Hypertension, cerebrovascular accidents In some cases of
systemic hypertension as a nature’s outlet, bleeding can
occur from the gastrointestinal tract (with haematemesis)
like haemoptysis. Cerebrovascular accident can lead to
haematemesis presumably due to haemorrhagic gastritis or
duodenitis.
Aneurysm of aorta Abdominal aortic aneurysm rarely
ruptures into the gastrointestinal tract and manifests as
haematemesis and melaena.
Haemangioma of stomach When the development of
circulation is interfered at the stage of undifferentiation of
capillaries, a cavernous haemangioma occurs wherein mixed
arterial venous blood will be present. If the interference is
seen at the stage of differentiation, congenital arteriovenous
fistula results. Any such anomaly in the gastrointestinal tract
may give rise to haematemesis and melaena.
Pseudoxanthoma elasticum It is an inherited disorder with
defect of elastic tissue which weakens vessel wall and may
result in haematemesis. The skin over the neck is of ‘plucked
chicken’ appearance and the retina may have angioid streaks.
Arteriovenous malformations
Vide infra.
Nongastrointestinal Causes
Blood swallowed from bleeding elsewhere Haematemesis
may be due to swallowing of blood from a bleeding lesion
in the nose or nasopharynx or mouth or lungs. A possibility
of swallowed blood from epistaxis or haemoptysis or
bleeding from mouth and throat should be screened.
Blood diseases (Refer to Chapter ‘Bleeding Disorders’)
Causes of Melaena
Upper Gastrointestinal Lesions and Other
Causes of Haematemesis
It usually follows haematemesis or may occur alone with
or without faintness, sweating and collapse.
Between the Duodental Bulb and Caecum
Inflammations
• Typhoid: In Salmonellosis, the organisms get localised
in the lymphoid tissue of the small intestines. The
 220 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
characteristic lesion is inflammation and ulceration of
the Peyer’s patches. Melaena occurs when these ulcers
bleed during second or third week of the enteric fever.
• Tuberculosis: Similarly tubercle bacilli affect the mucosa
and lymphatic tissue causing inflammation and
ulceration in the ileum and caecum. The gastrointestinal
symptoms of colicky pain in the lower abdomen, altered
bowel habits with anorexia, fever, and weight loss are
the presenting features. The abdomen may reveal a
doughy feel and tendermass may be elicited in the right
iliac region. Bleeding may occur from these ulcers. The
barium studies may reveal varying degrees of filling
defects with a shortened ascending colon and a
contracted caecum.
• Crohn’s disease Refer chapter ‘Chronic Diarrhoea’.
Vascular Causes
• Mesenteric vascular insufficiency (Ischaemic colitis):
In acute ischaemia or infarction of the small intestine
abdominal pain may be presenting manifestation or may
appear as ileus and peritonitis. In chronic insufficiency,
intermittent pain may occur in the umbilical region,
following a meal and may last for few hours. The
vasculitis of the arteries of the intestines is associated
with abdominal pain and melaena due to intramural
oedema or ulcerations. This can also occur in
atherosclerosis or atrial fibrillation or congestive heart
failure treated with digitalis. Diagnosis is confirmed by
barium studies which show thumb printing.
Arteriographic studies may be contributory (Refer to
Chapter ‘Acute Abdominal Pain’)
• AV malformation: It is a direct connection between the
arteries and veins without a capillary network. The
afferent and efferent vessels are dilated. They lead to
and form the intertwined malformed channels, which
contain arterial blood. Since the malformation receives
blood at arterial pressure, spontaneous bleeding may
occur.
Tumours
• Haemangioma of jejunum or leiomyoma of small
intestine with ulceration may account for bleeding.
Malignant tumours like (a) adenocarcinoma of the
duodenum may ulcerate and result in haemorrhage. It
may resemble chronic duodenal ulcer radiologically.
Endoscopy and biopsy may confirm (b) lymphomas may
infiltrate the wall of the bowel usually jejunum and ileum
and may be associated with ulceration. Diagnosis is
confirmed by peroral intestinal biopsy and lymph
angiography or by laparotomy.
Congenital Meckel’s Diverticulum Meckel’s diverticulum
situated in the distal ileum is due to persistence of omphalo
mesenteric duct. It may be lined with normal ileal mucosa
in 50 per cent of cases. Heterotropic gastric mucosa is the
most common, secreting acid peptic juice, leading to
ulceration, pancreatic, duodenal or colonic mucosa is seen
in few. This is an important cause of painless gastrointestinal
bleeding specially in children and youngsters. The diverti-
culum is rarely demonstrated by the barium. Technetium
isotope scanning or mesenteric angiography confirms the
diagnosis.
Melaena Neonatorum It is a haemorrhagic disease of a
newborn due to hypoprothrombinaemia as a result of vitamin
K deficiency. The melaena and haematemesis occur in the
first few days of life apart from haemorrhage elsewhere.
Lower Gastrointestinal Lesions
Sometimes conditions causing melaena produce brisk
bleeding when no chemical alteration takes place and bright
red blood passes per rectum instead of a tarry stool. Hence
other causes of lower gastrointestinal bleeding like (a)
colonic lesions (diverticulitis, neoplasms of the colon and
amoebiasis); and (b) anorectal lesions (like haemorrhoids
anal fissures proctitis) which also produce haematochezia,
may have to be differentiated on such occasions.
Upper gastrointestinal bleeding is predominantly
produced by either peptic ulcer group (55%) and gastritis
(20%) or oesophageal varices and tears (20%). The causes
of lower gastrointestinal haemorrhage in order of frequency
are inflammatory bowel disease, haemorrhoids,
diverticulosis of the colon, and neoplasms.
Inflammatory bowel disease Refer to Chapter ‘Chronic
Diarrhoea’.
Diverticulosis This connotes presence of diverticula
(anywhere in the gut) which may be congential or acquired
and clinically significant type is acquired Colonic
diverticula. The severe, painless rectal haemorrhage (big
rectal bleed) may be the inaugural sign of diverticulitis.
Fever, pain or disomfort in left iliac fossa and alteration of
bowel habit are the earlier complaints. A tender thickened
sigmoid may be palpable with or without peritonitis. The
diverticula which are pouchings of the mucosa and serosa
with little muscular support are commonly located in the
sigmoid colon. The weakening of the bowel wall or
increased intracolonic pressure may account for their
formation, most often near the entrance of the blood vessels
from mesentry. Abscess formation or perforation may occur.
 Haematemesis and Melaena
Fistula between colon and bladder or postinfective strictures
are other complications. Barium enema reveals diverticula
appearing as pouchings from the main contour of the colon.
Sigmoidoscopy or colonoscopy are diagnostic (Refer
Chapter Chronic Diarrhoea and Acute Abdominal Pain).
Neoplasms of the colon Colorectal carcinoma may account
for rectal bleeding or frank blood in the stool. Alteration of
bowel habits, discomfort in the rectum and presence of piles
in the elderly must always lead to the suspicion of colorectal
malignancy. Rectal examination or sigmoidoscopy detect
half of the cancers. Barium enema reveals localised
narrowing or a filling defect of 2 to 6 cm long in the barium
outline. Fibreoptic colonoscopy and biopsy are the most
reliable means of diagnosis. Carcinoembryonic antigen may
be elevated in the serum. Adenomatous polyps, though
clinically silent, may present as recurrent episodes of
bleeding and represent a premaligant lesion (usually asso-
ciated with pigmentation of lips Peutz-Jeghers syndrome).
Amoebiasis Though the clinical course of Entamoeba
histolytica infection ranges from chronic mild diarrhoea with
abdominal discomfort to a fulminant dysentery, extensive
destruction of the mucosa and submucosa of the colon may
result in rectal bleeding rarely.
Haemorrhoids Rectal bleeding which is bright red and
unmixed with the stool is most often caused by haemor-
rhoids. They may be internal or external. The former are a
plexus of superior haemorrhoidal veins above the
mucocutaneous junction and the latter are a plexus of inferior
haemorrhoidal veins below the mucocutaneous junction.
Constipation with prolonged straining and congestion from
portal hypertension or heart failure or pelvic tumour are
common causes. Thrombosed external haemorrhoids and
persistent prolapsed internal haemorrhoids (third degree of
piles) can be seen on inspection. Anoscopic examination
may reveal the unprotruded internal haemorrhoids (1st
degree). Second degree piles are those which prolapse on
defaecation.
Proctitis Rectal bleeding can also occur from proctitis.
It may be nonspecific (like ulcerative proctitis which is a
mild form of ulcerative colitis) or specific like gonorrhoeal
origin. Anoscopy may reveal blood and pus in the rectal
ampulla with swollen and friable mucosa.
Hence appearance of blood in the stool, depends not
only on the site of bleeding but on the rapidity of transit.
Thus localisation of the site of bleeding from the colour of
blood in the stool may be misleading, since fresh blood can
occur in very brisk upper gastrointestinal bleeding, besides
classical large bowel bleeding.
221
Clinical Approach
The clinical approach depends essentially on the initial
assessment of vital data (systolic blood-pressure and pulse
rate), haemoglobin content and urine output. If shock is
present, attempts must be made to restore haemodynamic
stability, before exercising the diagnostic work-up for the
actual cause of bleeding. If not shocked, further assessment
can be done by taking the full history and arrive at the proper
diagnosis of site, extent and cause of bleeding.
History
1. Is the blood vomited or coughed? (Refer to Chapter
‘Haemoptysis’ to differentiate between the two.)
2. Is the haematemesis spurious or true (swallowed blood
after haemoptysis or epistaxis being vomited) or true?
3. Any history of bleeding diathesis or hypertension?
4. Any past history of passing bright blood in stool or
melaena or haematemesis or episodes of fainting?
5. Is vomiting painless or associated with pain?
Interpreting Symptoms
1. History of epigastric pain related to food (suggestive of
peptic ulcer), usually pain subsides after bleeding and if
pain persists perforation has to be suspected.
2. History of intake of drugs NSAIDs or Aspirin or Anti-
coagulants (erosive gastritis).
3. Alcohol abuse (bleeding varices) or past history of
jaundice.
4. Any discomfort on swallowing (oesophagitis).
5. Is the retching or vomiting prolonged followed by
haematemesis (Mallory-Weiss syndrome).
6. Any weight loss, loss of appetite and epigastric pain
(cancer of stomach).
7. Is the bleeding simultaneous from other sources like
urinary tract (suggestive of bleeding disorders).
Physical Examination
1. Nonspecific features of blood loss like cold extremities,
sweating, weakness, tachycardia, orthostatic hypotension
(from supine to upright position postural drop in systolic
blood pressure of more than 10 mm of Hg or postural
increase in pulse rate of more that 20/min) indicate 20%
reduction in blood volume. A systolic blood pressure of
< 100 mm of Hg indicates 30 per cent decrease in
circulating blood volume.
2. Specific features like jaundice, lymphadenopathy,
anaemia should be carefully sought.
 222 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
3. Skin examination—Any telangiectasia, perioral
pigmentation of the skin, any purpuric lesions, spider
naevi.
4. Abdomen examination—Distended veins over the
abdomen, any epigastric tenderness, hepatospleno-
megaly or any other masses, or ascites.
5. Chest examination—Any cardiomegaly or evidence of
hypertensive heart disease.
Bedside Manoeuvres
1. Blood examination of the vomitus and detection of pH.
Acidity is common in haematemesis with the exception
of cancer of stomach.
2. Rectal examination—Examine the colour of the stool
and the colour of the blood over the examining finger.
3. Hess Test—For evidence of damage to capillary walls
(vascular purpuras).
4. Pass a nasogastric tube gently to determine the presence
of gastrointestinal bleeding. If blood is present, it is from
either oesophagus or stomach. However, the absence of
blood in the gastric aspirate, in spite of evidence of active
bleeding, indicates pathology below the ligament of
Treitz. (Duodenal-Jejunal flexure). When the aspirate
is clear, it is better to leave the tube in situ till bile stained
fluid appears, since duodenal bleeding can occur with
clear aspirate. If this bile stained aspirate is negative for
occult blood, gastroduodenal bleeding is unlikely.
5. Central venous pressure must be maintained above 80
and below 150 mm H2O (this helps to detect repeat
bleeding).
Investigations
1. Blood examination—Haemodilution usually occurs
about 24 h later (early determination of haemoglobin
may be misleading as normal Hb does not exclude
severe bleeding).
a. Haematocrit (may not accurately reflect degree of
blood loss initially).
b. Haemoglobin, morphology of the red cell and RBC
count.
c. White cell count and differential count.
2. Blood urea—Raised due to loss of blood leading to
prerenal uraemia.
3. Faecal occult blood test—(Guaiac test is positive for
any alimentary tract bleeding. Occult blood test is
negative in a black stool due to iron therapy.)
4. Liver function tests—Especially gamma glutamyl
transferase and blood ammonia.
5. Ascitic fluid analysis—If necessary (for cytology,
proteins and adenosine deaminase for abdominal
tuberculosis).
6. Specific blood tests towards bleeding disorders—
Platelet count, prothrombin time, bleeding and clotting
time, fibrinogen content.
7. Radiological examination
a. Plain X-ray of the abdomen (may not be very useful
unless associated perforation is also suspected).
b. Barium examination has limitations. Gastric erosions
and oesophageal lacerations may not be visualised
and the retained barium may interfere with the
angiography or endoscopy. Barium enema is
considered only when the condition is stable although
it can identify potential source of bleeding. However,
it is better to withhold barium studies for 1 to 2 days
after cessation of active bleeding. It is better not done
if early endoscopy or angiography is contemplated.
8. Endoscopic studies—In massive upper or lower
gastrointestinal haemorrhage endoscopy may not be
that useful since pouring bleeding points interfere with
the visualisation of pathological sites.
a. Oesophagogastroduodenoscopy: This is very useful
to locate the site of bleeding in the oesophagus,
stomach or duodenum accurately. This has to be
done as soon as the haemodynamic stability is
established, since the accuracy rate is more, if
undertaken at the earliest, usually within 24 h.
Endoscopic Stigmata of Recent Haemorrhage
(ESRH) is a risk factor for rebleeding. The presence
of “Visible vessel” in the floor of ulcer may be
associated with continued bleeding or rebleeding.
Biopsy, if necessary can be done.
Helicobacter pylori infection can be diagnosed by:
i. Detecting high urease activity in mucosal biopsy
by rapid urease test (immerse the biopsy piece in
0.5 ml of 10% liquid urea broth with phenol red,
as indicator. Any change in colour of the indicator
due to hydrolysis of urea to ammonia in 3 min is
diagnostic)
ii. Culture
iii. Histopathological identification takes about 4 to
5 days, and
iv. Breath tests (vide infra).
b. Fibreoptic colonoscopy
c. Sigmoidoscopy
9. Ultrasonography
10. Additional investigations
A. If the site of bleeding is not definite still
a. CT scanning
 Haematemesis and Melaena
b. Isotope studies:
i. Breath tests measure the excretion of labelled
CO 2 in the expired air following oral
administration of C-labelled urea. (This is
based on high urease activity of Helicobacter
pylori which detects the products of urea
hydrolysis, thereby indicating its presence).
ii. Radioisotope bleeding scan—Technetium
tagged to red blood cells or albumin can be
used to assess the feasibility of arteriography.
c. GUT angiography: It is effective only in brisk
massive upper gastrointestinal bleeding (rate of
bleeding greater than 0.5 ml per min) at the time
of angiography.
d. String test: May be helpful in the diagnosis of
occult blood from small intestine. (bleeding of
obscure origin is usually from small intestine).
String device such as a weighted umbilical tape
with radio-opaque markers is passed orally down
to the small intestine, while its position is
monitored radiographically. 20 cc of 5 per cent
fluorescence is injected IV and then the tape is
withdrawn. It is examined with guaiac test and
under fluorescent light. The presence of blood
or fluorescence is correlated with the position of
the tape as documented radiologically. This is
diagnostic even though the colonoscopy or
angiography are inconclusive.
B. If the site of bleeding is localised
a. Portal venogram
b. Serum gastrin levels (Secretin stimulation test
may be useful to detect gastrinoma, if the gastrin
levels are equivocal)
TREATMENT OF HAEMATEMESIS AND MELAENA
The aim of initial treatment of haematemesis should be
(a) to allay the anxiety, (b) to restore the blood volume and
(c) to stop haemorrhage and prevent rebleeding.
The source of bleeding (variceal or nonvariceal) must
be identified, besides assessing whether the episode is mild
or life-threatening.
Symptomatic Treatment
1. Put the patient to bed, check the blood pressure and
pulse.
2. If the systolic blood pressure is below 100 mm of Hg,
or the fall of 20-30 mm of Hg in a known hypertensive
223
patient is recorded, or if the systolic blood pressure
falls 10 mm Hg with change in posture (from supine
to upright), or pulse rate is > 100/min consistently, or
Hb% is below 10 g, the blood volume must be restored
by IV haemaccel or dextrose saline before blood
transfusion (minimum 4 pints) is arranged (if facilities
permit central venous pressure is monitored keeping it
at + 3 to + 6 cm of saline, as it guides not only fluid
replacement but warns of a rebleed). The other
measures for shock may be adopted. (Refer to Chapter
‘Shock’)
3. Monitor the amount of blood loss, urine output and
haemoglobin percentage (Hb% poorly reflects the
blood loss initially as the fall may be too slow) besides
recording blood pressure and pulse, at least every 4 h.
Though a fall in haematocrit is not a sensitive indicator
of acute blood loss, it is better maintained between 30-
55%. (Each 500 ml of blood raises the haematocrit by
3-4%).
4. Nasogastric aspiration and lavage—Pass Ryle’s tube
and aspirate the contents of the stomach. Monitor
bleeding with periodic aspirations. Lavage the stomach
with ice cold water or saline (if necessary, adrenaline
or levarterenol may be added) till the returning fluid is
clear, which in turn improves the tone of stomach
musculature and helps control of bleeding.
5. Diazepam may be given parenterally to allay the
anxiety.
6. Diet—Allow only sips of ice water or ice pieces orally.
When once the bleeding stops, milk or bland diet may
be given (avoid gastric irritants).
7. Any offending drug like NSAIDs must be promptly
withheld.
8. H 2 receptor blockers—Rantidine is often given IV
50 mg or pantoprazole (40 mg IV)
9. Haemostatics IV calcium, clauden, adrenochrome
Haemocoagulase (botropase) or ethamsylate can be
given empirically, though of little value.
10. Appropriate laboratory investigations may be done
simultaneously. When once the initial volume deficit
is restored by fluid and blood replacement, all measures
should be adopted to maintain a stable circulatory state
to undertake procedures such as upper GI endoscopy
or colonoscopy (circulatory instability indicates
continuous bleeding or rebleeding). Subsequent
management depends on the response and source or
cause of bleeding. If the source of bleeding is obscure,
laporotomy is considered.
 224 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
SPECIFIC TREATMENT FOR SPECIFIC DISEASES
Haematemesis
Oesophageal Causes
• Oesophageal varices due to portal hypertension
A. Control of acute bleeding episode
a. Confirm that the bleeding is from oesophageal
varices.
b. Pharmacologic agents—to reduce portal venous
pressure.
i. Vasopressin (pitressin) is given (20 units in
100 ml of 5% dextrose over 2 min) and sub-
lingual nitroglycerin may be simultaneously
administered to reduce its side affects. If
required, vasopressin may be repeated at
hourly intervals 3 or 4 times to control the
bleeding by splanchnic arteriolar vasocons-
triction. (Vasopressin is contraindicated in
ischaemic heart disease)
ii. Terlipressin is an alternative (2 mg IV every
6 h till bleeding stops and then 1 mg 6 h for
another 24 h).
iii. Somatostatin—Synthetic polypeptide/
hypothalamic hormone (IV-250 mg bolus
followed by 6 mg/24 h infusion for five days).
iv. Vitamin K 10 mg IM twice daily is beneficial.
c. Local measures
i. Sengstaken balloon tamponade can be kept
inflated for 24-48 h.
ii. Endoscopic sclerotherapy with sodium
morrhuate (preferably after tamponade, if
there is active bleeding at endoscopy).
iii. Oesophageal transection, if the bleeding is not
controlled by the former two measures.
iv. Emergency portacaval shunt may be
considered, if necessary.
d. Hepatic encephalopathy is likely to follow
bleeding episode, when it is treated with lactulose
50 ml orally every 8 h and neomycin 1g orally
every 6 h (Refer to Chapter ‘Jaundice’).
B. Prevention of recurrent bleeding—Recurrent variceal
bleeding (about 60% in one year) is prevented by
a. Sclerotherapy: The sclerosing agents are injected
into the varices once in two weeks till the varices
are obliterated.
b. Surgical measures: Portal systemic shunt or
splenorenal shunt is considered when the liver
function is good, since it prevents rebleeding
effectively, though there is a tendency to hepatic
encephalopathy subsequently. Splenectomy is
indicated for splenic vein thrombosis.
c. Pharmacological agents: Propronolol (80-160
mg/d) may be beneficial since it reduces portal
venous pressure.
• Reflux oesophagitis
A. General measures: Eliminate factors which increase
intra-abdominal pressure; withdraw offending drugs,
alcohol, coffee and tobacco; disallow fatty foods or
any dietary article that aggravates; elevate the head
end of the bed by 15-20 cm.
B. Specific measures
a. Neutralisers like antacids, or coating agents like
sucralfate.
b. H 2 receptor antagonists or proton inhibitors
(Refer to Chapter ‘Dyspepsia’).
c. Reflux suppressants: Alginic acids are useful
since they form a raft which floats on the stomach
contents buoyed by the carbon dioxide released.
In fact the raft provides so to say a mechanical
barrier for the reflux. Antacids when combined
with alginates are superior than alginates alone
since they neutralise the reflux contents like acid,
bile, pepsin and hasten healing of the inflamed
mucosa.
d. Prokinetic agents like metoclopramide,
domperidone, cintapride or bethanechol increase
the contractions of the lower oesophagel sphinc-
ter and hasten oesophageal acid clearance and
gastric emptying.
e. Bile reflux responds better to cholestyramine and
aluminium hydroxide.
f. Iron deficiency due to blood loss may be
corrected by oral iron supplements.
g. Surgery: If symptoms persist despite medical
therapy, surgical treatment may be undertaken
to increase the pressure of the lower oesophageal
sphincter. Associated oesophageal strictures are
treated by dilatation or surgical resection. If
sliding hernia is present, suitable repair and
construction of additional valve mechanism may
be required (Refer to Chapter ‘Dysphagia’).
• Oesophageal carcinoma (Refer to Chapter ‘Dysphagia’)
• Mallory-Weiss syndrome: Conservative treatment
usually suffices. Surgery to control severe bleeding is
rarely needed.
 Haematemesis and Melaena
Gastroduodenal causes
• Acute gastric erosions Antacids to neutralise gastric
contents are beneficial. H2 receptor antagonists (to
inhibit acid secretion) may be effective. When increased
intracranial pressure is the underlying cause, it may be
corrected appropriately (Refer to Chapter ‘Coma’).
• Gastritis (Refer to Chapter ‘Dyspepsia’)
• Peptic ulcer: The measures to control nonvariceal upper
gastrointestinal bleeding are
a. Gastric lavage and supportive therapy (vide supra).
b. Pharmacological agents: Various drugs used to
control bleeding due to peptic ulcer are haemostatics,
antacids, H2 receptor antagonists, and proton pump
inhibitors. Parenterally (Refer to Chapter
‘Dyspepsia’) and Somatostatin (vide supra).
i. Beta blockers—Congestive gastropathy asso-
ciated with long standing portal hypertension
may be present with upper gastrointestinal
bleeding. Propranolol is known to reduce such
frequency of bleeding by reducing portal
venous pressure (vide supra).
ii. Tranexamic acid (500 mg tds) antifibrinolytic,
i.e. inhibits activation of plasminogen to
plasmin; orally is effective since there is an
excessive fibrinolytic activity.
c. Endoscopic techniques: Early endoscopy is prefer-
ably done within 24 h to locate the bleeding vessel
(the stomach must be vigorously lavaged prior to
endoscopy). However, it is not done during active
bleeding. Endoscopic haemostasis is obtained by
thermal methods (electrocoagulation, heater probe,
laser photocoagulation) or nonthermal measures
(Injection of vasoconstrictor or sclerosant materials;
spraying of crystallising collagen; clotting factors or
cyanoacrylate glue; balloon inflation with a 30 ml
2.5 cm maximum radius balloon).
Endoscopic stigmata of a recent bleed that predict
rebleeding is worth noting, i.e. adherent clot or visible
vessel. Rebleeding occurs in two days after the
cessation of earlier episode.
d. Radiological techniques: Though endoscopy
indicates the cause in 94 per cent of cases, barium
contrast studies are helpful in 83 per cent of cases
and they complement each other. If still undetected,
arteriography is considered. Angiographic embolisa-
tion of the bleeding artery is done with autologous
clot, gelfoam which yields dramatic results.
e. Surgery: If there is prolonged bleeding requiring
more than 2.5 litres of blood in 24 h to maintain vital
225
signs, or rebleeding or failure to maintain vital signs
despite adequate fluid replacement, surgery must be
undertaken (excision of bleeding gastric ulcer or
suturing the duodenal ulcer coupled with vagotomy
or partial gastrectomy).
f. Zollinger-Ellison syndrome (gastrinoma): The
treatment of this uncommon disorder, wherein severe
peptic ulceration occurs due to excess of gastrin,
secreted by adenoma of islets of pancreas, consists
of
i. Use of H2 receptor blockers continuously in high
doses with or without anticholinergic agents
ii. Omeprazole; preferably rabeprazole 60 mg/d
orally
iii. Somatostatin
iv. Surgery—Resection of primary tumour and if
possible solitary metastasis
v. When invasive, streptozocin and 5-Fluorouracil
appear beneficial.
• Carcinoma of stomach: While adequate treatment for
hypovolaemic shock is implemented, assessment must
be made regarding stage of the disease and fitness for
surgery. Cytotoxic drugs like 5-Fluorouracil,
Doxorubicin and mytomycin C with or without adjuvant
radiotherapy supported by palliative measures may yield
remission, in a small percentage of cases. However, the
curative treatment is gastrectomy, preceded by effective
preoperative measures enabling surgery.
Haemobilia Some cases of haemobilia resolve, otherwise
surgical ligation of the bleeding vessel or correction of any
underlying precipitating cause may be required.
Vascular
• Telangiectasia Symptomatic treatment is a short-term
measure. Severe gastrointestinal bleeding needs
intestinal resection, though fresh lesions can develop
subsequently. Iron deficiency is to be corrected.
• Hypertension, with cerebrovascular accidents Haemo-
rrhagic gastritis (erosive gastritis) consequent to
cerebrovascular accidents may be treated symptomati-
cally with gastric lavage, parenteral H2 receptor blockers
followed by hourly antacids and oral H 2 receptor
antagonists, apart from the management of cerebro-
vascular accident as such (refer to Chapter ‘Coma’).
• Aneurysm of aorta Ruptured abdominal aortic aneurysm
can be stabilised by using a compression G suit which
exerts counter pressure externally diminishing the rate
of bleeding. The surgical resection of the aneurysm and
insertion of dacron prosthesis or a simple tube graft can
be undertaken later.
 226 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Hemangioma of stomach: It is rare. Surgical excision is
considered, if necessary.
• Pseudoxanthoma elasticum: Treatment is symptomatic.
• Arteriovenous malformations Surgical repair or
excision may be considered but the results are not
satisfactory in most of the congenital cases. Multiple
malformations can be obliterated by embolisation of
Gelfoam pellets set free through a catheter.
Nongastrointestinal disorders Blood swallowed from
bleeding elsewhere To be differentiated and treated
appropriately. (Refer to Chapter ‘Haemoptysis’)
Blood diseases (Leukaemia, etc.) (Refer to Chapter
‘Bleeding Disorders’)
Melaena
Melaena after a bout of haematemesis usually lasts for
3-4 days. General principles of treatment of a sudden attack
of melaena are those enunciated for haematemesis, otherwise
it may not demand emergency measures and the cause can
be worked out, while implementing the supportive measures
(gastric aspirates may clinch the source where the bleeding
is below or above the ligament of Treitz).
Upper Gastrointestinal Lesions and Other Causes of
Haematemesis (Vide Supra)
Between the duodenal bulb and caecum
• Inflammations
a. Typhoid—(Refer to Chapter ‘Pyrexia of Unknown
Origin’)
b. Tuberculosis—(Refer to Chapters ‘Haemoptysis’ and
‘Chronic Diarrhoea’)
c. Crohn’s Disease—(Refer to Chapter ‘Chronic
Diarrhoea’)
• Vascular
a. Mesenteric vascular insufficiency—Ischaemic colitis
is usually nonocclusive and rarely occlusive. Surgical
resection of the gangrenous bowel is required. For
subacute episodes, conservative treatment suffices
as it resolves in 2 to 4 weeks. However, post-
ischaemic stricture resulting in obstruction needs
surgery (refer to Chapter ‘Acute Abdominal Pain’)
b. Arteriovenous malformations (vide supra).
• Tumours
a. Haemangiomas, polyps, leiomyoma—Bleeding from
these benign tumours require emergency operation,
if the haemorrhage is persistent, despite conservative
management and when angiography fails to identify
the source of bleeding.
b. Lymphoma—(Refer to Chapter ‘Pyrexia of
Unknown Origin’)
Congenital Meckel’s diverticulum (Distal ileum) Symptomatic
Meckel’s diverticulum must be removed. Otherwise they
can be left alone, since low percentage of cases are likely to
cause problems during life-time.
Melaena neonatoram due to hypoprothrombinaemia (Haemor-
rhagic disease of the newborn) Vitamin K2 is synthesised
by bacteria in the colon whereas vitamin K1 (phytonadione)
is available in leafy vegetables. Vitamin K1 (1-2 mg) is given
subcutaneously and repeated every 6 h, if necessary. If the
bleeding is not controlled, blood transfusion may be
considered. Synthetic analogues of vitamin K, i.e.
menaphthone or menadione (K3) are better avoided, since
they may produce haemolysis. Haemorrhagic disease of the
new born can be prevented by giving vitamin K to the mother
especially when she is on drugs like aspirin, antibiotics and
anticoagulants.
Lower Gastrointestinal Lesions
• Inflammatory bowel disease (Refer to Chapter ‘Chronic
Diarrhoea’).
• Diverticulosis (Refer to Chapters ‘Acute Abdominal
Pain’ and Chronic Diarrhoea)
• Neoplasms of the colon (Refer to Chapters ‘Weight Loss
and Chronic Diarrhoea’)
• Amoebiasis (Refer to Chapter ‘Chronic Diarrhoea’)
• Haemorrhoids Treatment depends upon the symptoms
and their severity. The early stages of haemorrhoids, i.e.
first and second degree are managed by
a. Medical treatment—Encourage high fibre diet and
plenty of water intake. Avoid the possible strain of
defaecation. Local measures like warm sitz baths and
rectal ointments are beneficial. Apart from bed rest
and local astringent compresses, ruber band ligation
may be considered for prolapsed oedematous
haemorrhoids.
Symptomatic therapy with iron supplements for
anaemia, haemostatics for bleeding, bulk laxatives
for aiding defaecation are beneficial. Diosmin and
calcium dobesilate control acute attacks.
b. Injection treatment for early stages consists of
injecting 1-2 ml of 5 per cent phenol in vegetable oil
above the mucocutaneous junction through
anoscope.
c. Haemorrhoidectomy—Surgical excision is consi-
dered in third and fourth degree prolapse. Other
therapies for haemorrhoids are freezing with a
 Haematemesis and Melaena
cryoprobe using carbon dioxide or nitrous oxide
(cryosurgery) is not generally favoured; anal
dilatation is favoured by some. Electrocautery and
laser therapy do not offer any advantage over surgical
excision.
d. Thrombosed external haemorrhoid needs excision
under local anaesthesia if the pain does not resolve
rapidly.
• Proctitis Treatment may be directed adequately against
specific causes like ulcerative proctitis, i.e. as for
ulcerative colitis or amoebic dysentery (Refer to Chapter
‘Chronic Diarrhoea’) or gonorrhoea (Refer to Chapter
‘Polyarthritis’).
227
If proctitis is associated with constipation it is treated
with increased roughage in the diet, plenty of fluids and
adequate exercise, apart from laxatives (chemical, saline
or hydrophilic agents). Prolonged use of chemical
laxatives may lead to increasing constipation. The local
measures for symptomatic relief may be adopted, if
necessary.
Radiation proctitis is treated with hydrocortisone
(suppositories or rectal instillation). If there is frequent
loose irritating movements, loperamide may be given.
Rectal strictures need no dilatation since they retrogress
spontaneously. Colostomy (if there is severe haemor-
rhage, intractable pain, fistulas) or resection of the
affected portion (if there is obstruction) may be required.
228 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Haematemesis and Melaena 229
 Chapter

Haematuria
15
Haematuria is the appearance of blood in the urine.
Normally, urine contains about 1-2 RBCs per high power
field (with normal activity) which corresponds to one million
RBCs in 24 h urine. The colour of the urine varies with the
amount of blood present. Urine is bright red with appearance
of frank blood in the presence of large amounts, whereas it
is smoky or cloudy with reddish tinge in the presence of
small amounts (due to conversion of part of haemoglobin
into methaemoglobin in acid urine). It may be reddish brown
and the brownish discolouration is attributed to the formation
of acid haematin from haemoglobin. Sometimes, traces of
blood may be present in urine (with appearance of normal
urine colour) which is detectable by the presence of
abnormal number of intact red cells in the centrifuged
deposit of fresh urine. This is described as microscopic
haematuria as against macroscopic (RBCs may be destroyed
or deformed if the specimen is not fresh).
Though the most common cause of red urine is
haematuria, it can also occur due to
1. Presence of blood pigment (haemoglobin) as in
intravascular haemolysis
2. Drugs and chemicals like pyridium and phenolphthalein
or aniline dyes in sweets
3. Food excessive consumption of vegetables and fruits
like beetroot or black berries.
Microscopic demonstration of red cells distinguishes
haematuria from the other rare causes of red urine like
haemoglobinuria.
Haematuria may be due to bleeding anywhere from
glomerulus of the kidney down to the urethral meatus or
prerenal. It may be painful or painless. It may be isolated or
associated with proteinuria and microscopic deposits (cells,
crystals and casts). Passing of blood in the urine may be
encountered (i) at the beginning of micturition followed by
clear urine (urethral or prostatic origin); (ii) at the end of
micturition preceded by clear urine (vesical origin); or (iii)
intimately mixed with urine (renal or ureteric or occasionally
vesical, i.e. from any part of urinary tract other than urethra
or prerenal origin).
PATHOPHYSIOLOGY
The capillary endothelium and basement membrane separate
the blood circulating through the kidney from the urinary
space. Normally, a limited number of red cells may leak
into the urinary space. However, when the capillary
permeability is altered due to any slight injury, more number
of red cells are likely to leak through. The injurious factors
may be (i) hypoxia due to severe exercise or fever, (ii)
increased renal blood flow, (iii) increased filtration pressure,
(iv) toxins (infections and chemicals), (v) immunologic
injury, (vi) neoplastic process, (vii) calculi formation, (viii)
haemostatic abnormalities and (ix) external or iatrogenic
trauma.
CAUSES OF HAEMATURIA
They can best be grouped as due to (i) local urinary tract
diseases and (ii) general (systemic) diseases. The former
can be detailed in relation to the timing of micturition
(Table 15.1).
Local Urinary Tract Diseases
Urethral Causes
Infections (Urethritis)
Haematuria may occur in acute urethritis due to the
congestion of urethral mucous membrane caused by
gonococcal infections or exposure to chemicals. Urethral
discharge, burning sensation and history of exposure offer
the clue for diagnosis.
 Haematuria 231

Table 15.1: Causes of haematuria

B. Ureteric lesions
I. Local urinary tract diseases a. Calculi
1. Beginning of Micturition: Blood in the urine at this stage is b. Tumours
invariably either from urethra or prostate. c. Ureterocele
The urethral causes are d. Trauma
A. Infection—urethritis
B. Caruncle II. General (Systemic) Diseases
C. Calculus a. Haematological
D. Tunours like angioma i. Bleeding disorders
E. Injury ii. Sickle cell disease
The prostatic causes are b. Infections
A. Prostatitis i. Hepatitis B
B. Benign hypertrophy ii. Haemorrhagic fevers
C. Carcinoma iii. Subacute bacterial endocarditis, and hydatid disease
2. End of Micturition: Blood in the urine at this stage is of vesical iv. Parasitic: Malaria, filariasis, schistosomiasis and hydatid
origin. The causes are disease
A. Cystitis c. Malignant hyprtension and Toxaemia of pregnancy
a. Acute cystitis d. Diabetes mellitus
b. Chronic interstitial cystitis e. Collagan disease
c. Radiation cystitis i. Lupus erythematosus
d. Haemorrhagic cystitis ii. Polyarteritis nodosa
B. Calculus f. Scurvy
C. Tumours g. Drugs
a. Papilloma i. Anticoagulants
b. Haemangioma ii. Salphonamides
c. Carcinoma iii. Analgesics
D. Trauma iv. Cyclophosphamide
E. Foreign body h. Neighbouring visceral diseases involving urinary tract
3. Intimately Mixed Throughout: It is probably from any part of i. Carcinoma of the uterus, vagina or colon
urinary tract except urethra (usually renal) or general systemic ii. Inflammatory intestinal ulcerations
disease (prerenal). • Microscopic haematuria per se occurs in:
The causes are 1. Focal glomerulitis (Berger’s disease);
A. Renal lesion 2. Subacute bacterial endocarditis;
a. Acute pyelonephritis 3. Malignant hypertension;
b. Glomerulopathies: Acute glomerulonephritis and other 4. Renal calculi;
glomerular disease 5. Prostatitis;
c. Interstitial nephritis 6. Malignancy and
i. Acute 7. Drugs like anticoagulants.
ii. Chronic In practice most of the cases of haematuria are due to
d. Nephrolithiasis 1. Infections of the parenchyma and pelvis of the kidney
e. Neoplasms 2. Glomerulonephritis;
i. Benign: Angioma, papilloma 3. Renal calculi;
ii. Malignant: Carcinoma (Hypernephroma or Grawitz 4. Tumours of the kidney or bladder; and
tumour), Nephroblastoma 5. Prostatic hyperplasia or malignancy.
f. Renovascular
i. Renal arterial occlusion
ii. Renal artery aneurysm Caruncle Urethral caruncle is granulomatous overgrowth
iii. Renal vein thrombosis of the posterior lip of the external meatus. It is associated
g. Hereditary with painful urination. It is commonly seen after menopause.
i. Polycystic kidney
It is recognised easily on inspection.
ii. Medullary sponge kidney
iii. Alport’s syndrome (Hereditary nephritis) Calculus A calculus may stuck up in the urethra resulting
h. Trauma in sudden cessation of micturition associated with penile
i. Movable kidney (Nephroptosis) pain and due to consequent injury of the urethral mucous
j. Oxaluria
membrane, haematuria may occur. A previous history of
 232 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
renal colic or palpation of the urethra from outside revealing
impacted stone, offers the clue.
Tumours like angioma Angioma of the mucous membrane
of the urethra causes recurrent haematuria. Bleeding may
be spontaneous and unrelated to micturition. There may be
no other presenting features except anaemia. It is rare and
diagnosed only by urethroscopy.
Papilloma of the urethra may cause haematuria or
bleeding may be unrelated to micturition. It is diagnosed by
inspection if it is around external meatus or by urethroscopy.
Injury Membranous urethral injury is usually associated with
fracture of the pelvis. Injury to bulbous urethra occurs due
to a fall. Instruments may injure either the bulbous or
pendulous urethra. The cause of haematuria is self-evident.
Sometimes extravasation of blood and urine may result.
Prostatic Causes
Prostatitis In acute prostatitis, low back pain, perineal or
testicular discomfort, urethral discharge, dysuria and pyrexia
are the presenting symptoms and it is most commonly
encountered in youngsters. It follows ascending urethral
infection or occassionally haematogenous infection. Rectal
examination reveals tense tender enlarged prostate or
fluctuation if there is an abscess formation. Urine
examination shows bacteria and pyuria or haematuria.
In chronic prostatitis symptoms are less striking. The
prostate is enlarged and firm. A crepitus may be elicited if
prostatic calculi are present. Bacteria and pus cells are
present in the urethral discharge or prostatic smear or in the
first sample of urine. Prostatic massage (which is indicated
only in chronic prostatitis but not acute) yields copious
discharge.
Benign hypertrophy (Irritative and obstructive symptoms)
Hyperplasia of the prostatic lobes and thickened anatomic
capsule result in increased outflow resistance and functional
obstruction at vesical neck and intravesicular ureter. The
hypertrophy is possibly related to oestrogen androgen
imbalance. The typical presentation is prostatism (hesistancy,
diminished force of the stream, terminal dribling, frequency)
or acute urinary retention. Gradually, increasing frequency
of micturition and terminal dribbling may be disturbing.
Residual urine (which is appreciated by catheterisation
immediately after voiding) and associated infection may
cause burning micturition and accelerate the obstructive
symptoms. Renal insufficiency may occur if the obstruction
is prolonged. Rectal examination reveals enlarged prostate.
The ultrasound examination confirms the enlargement.
Excretory urogram may show indentation into the inferior
surface of the bladder or hydroureteronephrosis. Cystoscopy
may reveal secondary changes in bladder and bleeding may
be seen from the prostatic surface where the distended veins
may be visible (prostatic varices). Urine examination
clinches the evidence of infection.
Carcinoma Prostatic enlargement due to carcinomatous or
adenomatous type may cause haematuria. Symptoms due
to obstruction at vesical neck or infection or both are
common clinical features. Sometimes symptoms due to
metastases (like low back pain down to one or both legs,
vertebral collapse, pathological fractures or oedema due to
compression of iliac veins by the enlarged lymph glands)
may be the presenting features. Rectal examination reveals
hard nodule in the lateral sulcus of one lobe or the whole
gland may appear stony hard. Serum acid phosphatase and
prostate specific antigen levels are increased. Needle biopsy
establishes the diagnosis.
Vesical Causes
Cystitis
Acute cystitis: Fever with pain and tenderness in the
hypogastrium, dysuria, or burning micturition, frequency,
urgency and haematuria are the cardinal features of acute
cystitis. Urethritis is always associated. The urine may be
cloudy or bloody and microscopic examination may show
numerous pus cells, red cells and bacteria. Infection of
bladder is rarely primary and commonly secondary to
infections of adjacent organs. The causative organisms are
E coil, Pseudomonas, Proteus vulgaris, Mycobacterium
tuberculosis and Schistosoma haematobium. Predisposing
factors are prostatic stone, tumour or use of infected
instruments. Cystoscopy is however contraindicated.
• Chronic cystitis: In chronic cystitis, the symptoms are
usually milder. Cystoscopy may show mucosal irritation
or multiple patches of submucous haemorrhage.
Chronic interstitial cystitis (Hurler’s ulcer) is accom-
panied by painful haematuria and increased frequency
of micturition. The bladder is contracted.
• Radiation cystitis: Multiple telangiectases or necrotic
areas may develop in the vesical mucosa after radiation
for malignant bladder or uterus, even after the original
pathology is controlled.
• Haemorrhagic cystitis: Adenovirus types 11 and 12 are
associated with haemorrhagic cystitis which occur more
commonly in boys unlike bacterial cystitis in girls. Gross
haematuria may persist for 10 to 15 days. Cyclophos-
phamide is yet another cause documented.
 Haematuria
Calculus Vesical calculus may cause few drops of blood in
the terminal urine, frequency of micturition during the day,
history of sudden interruption of the stream associated with
urethral pain and a history of previous renal colic are the
presenting features. Pyuria and nocturnal urination are
additional features, if there is associated infection. The
stones are usually radio-opaque. Excretory urogram reveals
residual urine in the postoviding film. The calculi can be
visualised by cystoscopy.
Tumours
• Papilloma Papilloma may cause profuse gross
haemorrhage and is usually seen in subjects above 25
years.
• Haemangioma Haemangioma may occur as a spider
naevus of the mucous membrane or as a solid tumour.
• Carcinoma Carcinoma of the bladder may cause
haematuria, increased frequency of micturition or penile
pain after micturition or symptoms of cystitis due to
secondary infection. Ureteral orifice occlusion leads to
renal pain. Extravesicular extension may cause
suprapubic pain and involvement of the vesical neck
results in urinary obstruction. Bimanual pelvic
examination may reveal a palpable mass at the base of
the bladder. Cystoscopy and biopsy clinch the diagnosis,
though excretory urograms are usually normal. CT scan
may detect invasion.
Trauma Low abdominal pain with suprapubic tenderness
with or without shock and a history of local trauma are
invariably present. Peritonitis results if the injury is
intraperitoneal and a mass develops in the suprapubic area
if it is extraperitoneal. If the patient can void, haematuria is
detectable. X-ray may reveal fracture of the pelvis. A large
gray area in the vesical region is seen in extraperitoneal
collection of blood and urine. Retrograde cystogram reveals
either intraperitoneal extravasation or extraperitoneal
rupture.
Renal Causes
Renal lesions
Acute pyelonephritis It may herald with fever, chills, pain
in the flanks and loins radiating to the iliac fossae, dysuria,
stranguary, frequency and burning on urination. There may
be tenderness over costovertebral angle. The diagnosis is
confirmed by examining the urine which is of fishy odour
and cloudy in appearance and acidic in reaction. Albumin-
uria and microscopic deposits containing pus cells, red cells,
bacilli with a count of >105 organisms per ml of urine, are
cardinal features. It is usually due to
233
a. Infections (E. coli or tuberculosis, predominantly
associated with diabetes mellitus)
b. Obstruction of the passages (due to calculus or prostate)
c. Congenital malformation.
The risk of infection is increased during pregnancy or
vesicoureteral reflux. In women, it is much more common
because of the anatomical relationship of the short urethra
with the rectum, and much more so in pregnancy due to
atonia of the ureters caused by progesterone and obstruction
by the uterus. The diagnosis is confirmed by identifying the
organisms from culture of the urine, before administration
of antibiotics.
Recurrent urinary tract infections may lead to chronic
pyelonephritis, hypertension and impaired renal function.
Urine examination reveals many pus cells, some RBCs and
epithelial cells. Pyuria with no obvious organisms is
suggestive of tuberculosis or analgesic nephropathy or
urethral syndrome (urethritis and cystitis usually in women).
Urinary tract infections include not only acute pyelonephritis
but cystitis, prostatitis and urethritis.
Glomerulopathies (Acute glomerulonephritis and other
glomerular diseases) It is immunologically induced in
majority of cases by either the antigen—antibody complexes
in the circulation getting trapped in the glomerular capillaries
or formation of antibodies to some fraction of the glomerular
basement membrane and deposition of antibasement
membrane immunoglobulin therein. The granular deposits
of immunoglobulins may be associated with or without
complement deposition. The antigens involved in this
immune complex glomerulonephritis are predominantly
infections, occasionally colonic carcinomas or associated
with multi-systemic diseases like SLE. However, in some
cases, the immune complex glomerulonephritis may be of
unknown etiology. Yet, in some cases of glomerulonephritis,
there may be no evidence of immunological mechanism as
such.
Glomerular diseases are grouped as (1) primary (only
glomerular) and (2) secondary (glomerular and other organ
as well in diseases affecting multiple systems). Either of
this group can evoke a nephritic or nephrotic response. In
nephritis, the clinical picture is associated with oedema,
hypertension, classical microscopic RBC deposits and
< 3 g/24 h Proteinuria; whereas in nephrotic syndrome
insidious swelling > 3 g/24 hr Proteinuria; rarely haematuria;
and hypertension and the clinical features.
• Primary can be classified as
a. Nephritic: Acute GN proliferative GN (diffuse,
cresentic, focal), due to poststreptococcal infections
 234 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
and IgA nephropathy of unknown etiology
respectively.
b. Nephrotic: Proliferative GN (Mesengiocapillary and
mesangial), membranous, minimal change, focal
glomerulosclerosis.
• Secondary can be classified as
a. Nephritic acute GN: Focal proliferative GN, Good
pasture’s syndrome, SLE, vasculitis, Henoch-
Schönlein purpura, and dysproteinaemias.
b. Nephrotic: SLE, diabetes mellitus, other infections
(malaria, hepatitis B), tumours, drugs (gold or
penicillamine) and heredofamilial diseases.
Hence, acute glomerulonephritis syndrome may be (i)
postinfective (with immune mechanism), (ii) idiopathic and
(iii) noninfectious diseases involving multiple systems
(without immune mechanism).
• Primary Nephritic
i. Acute Postinfectious Glomerulonephritis (Diffuse
Proliferative GN): It usually follows one to three
weeks after infections with nephritogenic strains of
group-A haemolytic streptococci. It may also follow
other bacterial, viral and parasitic infections. It is
probably due to circulating immune complexes.
The onset of the disease is recognised by the
appearance of subcutaneous oedema of the eyelids,
legs and back. History of sore throat or impetigo or
fever with chills 1 to 3 weeks earlier may be
forthcoming. Hypertension with or without
encephalopathy and evidence of reduced glomerular
filtration rate (transient) may be present. Urine is
scanty and smoky with high specific gravity
albuminuria and contains blood cells, renal epithelial
cells, RBC casts, and other casts (epithelial and
hyaline casts). Blood chemistry may show azotaemia
and hyperkalaemia. Serum antistreptolysin titres may
be increased and the serum complement especially
C4 is low. Renal biopsy shows diffuse (all glomeruli)
endocapillary proliferative glomerulonephritis. IgG
is deposited.
Most of these subjects (a) may recover unevent-
fully, especially children; or (b) a small number may
develop rapidly progressive glomerulonephritis in the
course of weeks to months with progressive onset
of renal failure, which may be associated with
haematuria, proteinuria, oliguria, hypertension and
characteristic histological appearance of epithelial
cells accumulating into crescents; or may develop
into (c) nephrotic syndrome with heavy proteinuria
(>3.5 G/24 hours) and reduced GFR; or (d) chronic
renal failure in the course of years resulting in
hypertension with small kidneys and end-stage renal
failure.
ii. Cresentic glomerulonephritis and rapidly
progressive GN: It is a form of proliferative GN and
may be idiopathic in origin or associated with
infections or multisystem diseases. It occurs in adults
and presents as acute GN or acute renal failure.
Histology shows large cellular epithelial cresents in
many of the glomeruli.
iii. Focal or segmental glomerulonephritis: This is
characterised by painless haematuria or clinical
picture of acute glomerulonephritis syndrome.
Proliferative and necrotic changes in only some
glomeruli (focal) and in only a segment of the
glomerulus (segmental) is the typical histology
picture. Some of these cases may show immuno-
globulin deposits in the mesangium. Such focal
changes are associated with subacute bacterial
endocarditis or multisystem involvement as in SLE
or periarteritis nodosa (vide infra) or of unknown
origin. Most often prognosis is good.
iv. IgA nephropathy (Berger’s disease): Few symptoms
or asymptomatic, persistent or recurrent haematuria
with or without proteinuria seen. Recurrent episodes
of haematuria may be macroscopic or microscopic.
It is idiopathic in origin and a common cause in
young men. Vague constitutional symptoms may be
complained. Since focal and segmental proliferation
of mesangial cells is seen, this is regarded as one
type of focal proliferative GN. Predominant immuno-
globulin deposited in mesangium is IgA. The
diagnosis is established by (a) increased serum IgA
levels, (b) biopsy of the skin of the forearm (volar
surface showing capillary deposits of IgA in the
dermis, (c) renal biopsy which shows focal or
segmental proliferative glomerulonephritis, and (d)
immunofluorescence microscopy showing diffuse
deposition of IgA in the mesangium. Prognosis is
good.
v. Proliferative mesangiocapillary glomerulonephritis
(Membrano - proliferative GN) vide infra.
• Primary Nephrotic
i. Proliferative mesangiocapillary glomerulonephritis
(membrano prolifeative GN): It occurs in children
of young adults. The clinical presentation is
asymptomatic proteinuria with haematuria or acute
GN or nephrotic syndrome in over 50 per cent of
cases. Hypertension may or may not be present.
 Haematuria
Renal function is impaired in 50 per cent of cases.
Two different types of lesions are described. The
deposition is either in the subendothelial layer of the
capillary wall or the deposition is dense within the
glomerular basement membrane itself. IgG in Type I
and IgM in Type II besides C 3 are deposited.
Persistent low serum C3 is diagnostic marker. If the
GFR is decreased at the onset of the disease or
associated with hypertension, prognosis is poor.
ii. Proliferative mesangial glomerulonephritis:
Clinically, it is difficult to differentiate from minimal
change glomerulonephritis. Pure mesangial
proliferative glomerulonephritis is a primary
glomerular disease, identified by renal biopsy. IgA
deposits or IgM deposits in the mesangium are found
by immunofluorescence microscopy. It may present
as nephrotic syndrome. Heavy proteinuria is
characteristic with haematuria in the majority of
cases. Usually serum C3 levels are normal. Sponta-
neous remissions occur. Prognosis is comparatively
favourable.
iii. Membranous glomerulonephritis: It accounts for
50 per cent of idiopathic nephrotic syndrome in
adults or present as isolated proteinuria. Microscopic
haematuria may be present in some cases. Half of
these cases develop renal failure and 25 per cent
recover spontaneously. Renal biopsy shows thick
leaky glomerular wall, with IgG and complement
deposition along its subepithelial aspect. This
glomerulopathy can also develop secondary to
infections (malaria or Hepatitis B), SLE, malignancy
or drugs (gold or penicillamine) or sickle cell disease.
iv. Minimal change GN: (vide infra)
• Secondary Nephritic
i. Focal proliferative glomerulonephritis: (Vide supra)
ii. Good pasture’s syndrome: It usually affects young
men and consists of pulmonary as well as renal
involvement due to antibasement membrane
antibodies (glomerular and alveolar). Consequently,
haemoptysis and features of cresentic proliferative
glomerulonephritis (haematuria, proteinuria and red
cell casts and acute renal failure) are the presenting
features. Haemoptysis may be recurrent. Chest X-ray
may show infiltrations in the lower zones. Renal
biopsy shows cresentic glomerulonephritis.
Immunofluorescence of the renal biopsy material
reveals linear deposits of the antibody (IgG) along
the glomerular capillary walls. A recent history of
viral infection or inhalation of volatile hydrocarbons
may be forthcoming.
235
iii. SLE: In about 70 per cent of SLE cases, the kidney
is involved. The clinical features of renal
involvement may vary from asymptomatic to massive
proteinuria with microscopic haematuria.
Hypertension and renal failure may be present. Renal
pathology may be diffuse mesangial cell proliferation
(mesangial lupus glomerulonephritis), or focal
cellular proliferation (focal lupus GN), or diffuse
mesangial and endothelial cell proliferation (diffuse
lupus GN), or proteinaceous deposits over the outer
aspect of the glomerular capillary wall (membranous
lupus GN) or obliterative sclerosing lesions of
portions of glomeruli (young stage lupus GN) (Refer
to Chapter ‘Polyarthritis’)
iv. Disseminated vasculitis: Renal involvement in these
cases may include.
a. Inflammatory lesions of small blood vessels
(microscopic polyarteritis) of the kidney and
other viscera (hypersensitivity angitis)
b. Inflammatory lesions of the larger vessels
(polyarteritis nodosa)
c. Granulomatous necrotising vasculitis in the
kidney and other organs (Wegener’s granulo-
matosis and allergic granulomatous arteritis).
The presenting features are haematuria,
proteinuria and renal failure. Hypertension may
be usually associated. The other features are
related to the involvement of different organs.
(Refer to Chapter ‘Polyarthritis’)
v. Henoch-Schönlein purpura (HSP): Glomerulo-
nephritis is another component besides nonthrombo-
cytopenic purpura which presents essentially as
protenuria and haematuria, within four weeks of
onset. Evidence of vasculitis may be present. Renal
failure may occur. Mild diffuse mesangial cell
proliferation (crescents) may be seen depending on
the severity of involvement. Since IgA or IgG
deposits are found in the mesangium and dermal
capillaries, HSP is attributed to circulating IgA
containing immune complexes. Prognosis is good
in the majority of cases. (Refer to Chapter ‘Bleeding
Disorders’).
vi. Dysproteinaemias (Idiopathic mixed cryoimmuno-
globulinaemia): Diffuse proliferative GN may be
seen due to precipitation of cryoimmunoglobulins
in glomerulocapillaries, besides purpura and necro-
tising dermal lesions, arthralgias and hepatospleno-
megaly. It may also cause vasculitis (Refer to Chapter
‘Bleeding Disorders’).
 236 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Secondary Nephrotic
i. SLE: Vide supra
ii. Diabetes mellitus
iii. Infections: Malaria, Hepatitis-B, HIV
iv. Tumours
v. Drugs (Gold, penicillamine); and
vi. Heredofamilial diseases: Vide infra
Glomerulopathies without Immune mechanism
i. Minimal change glomerulonephritis: It usually presents
as overt nephrotic syndrome (marked proteinuria more
than 3 g in 24 hours, hypoalbuminaemia, hyper-
cholesterolaemia with more LDL and oedema)
frequently in children (80%) and uncommonly in adults
(20%). It is the most frequent form of idiopathic
nephrotic syndrome encountered in practice, as
compared to other forms of nephrotic syndrome.
Proteinuria is usually selective (small albumin mole-
cules present and selectivity index is less than 0.2).
Hypertension and microscopic haematuria are rare.
Light microscopic examination is normal. Electron
microscopy shows fusion of foot processes.
Immunocomplexes are not implicated. Tendency to
relapse is its hallmark. Renal function is usually normal.
Acute renal failure may occur but rarely.
ii. Focal and segmental glomerulosclerosis: Clinically,
it is difficult to distinguish between this and minimal
change or mesangial proliferative GN. Patients
principally present as nephrotic syndrome and others
with asymptomatic isolated proteinuria, or accom-
panied by haematuria. Proteinuria is usually
nonselective. Hypertension and progressive decline in
renal function occur later. Sclerosis and hylanisation
of some of the glomeruli (initially juxtamedullary
glomeruli) is the characteristic lesion (focal) and only
a portion of the glomerular tuft is affected (segmental).
Progressive tubulointerstitial damage may be present.
It does not respond to steroids unlike minimal change
GN.
iii. Secondary to heredofamilial diseases (Vide infra):
N.B.
• Diffuse connotes all glomeruli involvement of both
kidneys.
• Focal—Some of the glomeruli
• Segmental—Part of each glomerulus.
Interstitial nephritis The tubules and the interstitium are
predominantly involved than glomeruli and renal
vasculature. Only a small proportion of these lesions result
from infection per se (pyelonephritis vide supra). Exogenous
toxins (drugs and chemicals) and endogenous toxins like
metabolites account for the majority of cases.
i. Acute interstitial nephritis: Usually occurs from drugs
and chemicals or bacterial infections. The drugs include
(a) analgesics (phenacetin, NSAIDs, aspirin); (b) anti-
biotics (methicillin and other penicillins, aminoglyco-
sides, and amphotericin B); and (c) radiographic
contrast media. The clinical manifestations include
acute oliguria and sometimes allergic reactions like
fever, arthralgia and rash, if it is due to drugs. Urine
examination shows microscopic haematuria, pyuria and
eosinophiluria. The renal failure usually responds
readily to withdrawal of the offending drug.
ii. Chronic interstitial nephritis (analgesic nephropathy):
Results from
1. Drugs and chemicals
a. Consumption of analgesics over a long period
b. Cytotoxic drugs (cisplatin and methyl-CCNU)
c. Lithium
d. Heavy metals (lead)
e. Radiation
2. Metabolites (hyperuricaemia, hypercalcaemia,
hypokalaemia)
3. Bacterial infections
4. Neoplasia (myeloma)
Functional abnormalities like diminished GFR may
occur in most of these cases sooner or later due to glomerular
injury and changes in renal microcirculation (Ischaemia)
leading to renal failure. Occasionally, acute papillary
necrosis in nondiabetics with haematuria or even renal colic,
severe anaemia and sterile pyuria are other manifestations
of analgesic nephropathy. Urine shows red cells and pus
cells without any organisms. Appearance of ring shadow in
IVP is characteristic.
Nephrolithiasis Big stones may be asymptomatic and small
stones may result in intermittent pain depending on the
anatomical location of the calculi. The pain may be dull or
excruciating type, or colicky in nature. Pain varies according
to the position of the calculus. Loin pain suggests calculi in
the kidneys; pain radiating from the loin to the groin and
into the genitalia is indicative of ureteral calculi (renal colic);
stranguary or frequency of micturition by day point towards
vesical calculi; and interruption to the urinary flow with
penile pain suggests stone in the urethra. Nausea and
vomiting occur often. The affected subjects present with
haematuria (gross or microscopic), with recurrent urinary
tract infections or features of urinary tract obstruction.
Rarely acute renal failure occurs when associated with
 Haematuria
obstruction to a solitary kidney or bilateral ureters. On
examination tenderness may be elicited in the region of
kidney-ureter-bladder. Numerous RBCs in urinary sediment
with or without evidence of infection is highly suggestive.
Crystals which combine to form stones may also be found
in the urinary sediment. Urine of 24 h may show hyper-
calciuria (> 300 mg), hyperuricaemia (> 750 mg), oxaluria
(> 50 mg) and cystinuria (> 200 mg). The calculi are
identified by radiographic techniques (plain X-ray of the
abdomen or IVP) or by ultrasound examination of KUB
area.
Renal calculi consists of crystals and small quantities of
protein and glycoprotein. Most of the stones are composed
of calcium oxalate (spiky) or phosphate (Big) (75%) which
are radiodense. Others include struvite (MG NH4 PO4), uric
acid and cystine. (Uric acid stones only are radiolucent, i.e.
no radiological shadow). The calcium stones may be due to
hyperparathyroidism or excess of vitamin-D or calcium
intake (nephrocalcinosis). Uric acid stones may be due to
gout or treatment with uricosuric agents. Struvite stones are
due to urinary tract infection with urea splitting organisms
like proteus which possess urease. Struvite is the commonest
cause of staghorn calculi (Triple phosphate big and horny)
which causes obstruction. Cystine calculi are due to
cystinuria consequent to inherited tubular transport defects.
Supersaturation of urine with crystalloids (due to their
excessive excretion or factors which diminish solubility)
leads to precipitation. Infection may predispose, to stone
formation or may result from calculi as an effect. The
necrotic tissue or clots of blood may serve as a nidus for
stone formation. Obtained stones may appear colourless or
coloured (Brown and soft with uric acid or lemon yellow
with cystine stones).
Neoplasms
• Benign papilloma: Angioma or papilloma are
uncommon and may give rise to haematuria which may
be profuse and intermittent. Pyelography shows filling
defect in a papilloma of the renal pelvis.
• Malignant carcinoma—Nephroblastoma (Wilms’
tumour): Papillary carcinoma or squamous cell
carcinoma of the renal pelvis, or adenocarcinoma of the
kidney (hypernephroma) may give rise to haematuria,
flank pain and systemic symptoms. A mass per abdomen
may be detected which can be differentiated from benign
cysts or hydronephrosis by CT and ultrasound. Renal
tumours can be demonstrated by contrast radiography.
Diagnosis is confirmed by percutaneous needle
aspiration for cytology.
237
Embryoma of the kidney (nephroblastoma or Wilm’s
tumour) is usually seen in children. Painful haematuria,
weight loss, abdominal mass (sometimes bilateral) are the
clinical features. An intravenous urogram shows distortion
of calyces and kidney. This tumour contains both epithelial
and sarcomatous cell type including abortive tubules and
glomeruli, muscle, bone and cartilage.
Renovascular
• Renal arterial occlusion: Vascular occlusion of the renal
artery causes haematuria and proteinuria besides flank
or upper abdominal pain, nausea, vomiting, fever and
hypertension. It is due to thromboembolic episodes
consequent to vascular disese, atrial fibrillation, or
endocarditis or mural thrombi. Renal arteriography
confirms the diagnosis. Ultrasound examination is
noncontributory. Renal impairment depends on the
function of contralateral kidney.
• Renal artery aneurysm: It is rare. Haematuria may occur
due to renal congestion or even before the swelling
becomes palpable. It may be associated with hyperten-
sion and a bruit. Plain X-ray of abdomen may show a
ring shadow. Renal arteriography is diagnostic.
• Renal vein thrombosis: The sudden thrombosis of a renal
vein may cause haematuria and lumbar pain with loss
of renal function. If this is gradual, renal function is not
impaired and nephrotic syndrome may result.
Hereditary
• Polycystic kidney: Infantile type is rare than the adult
type. The cysts are filled with fluid (clear or straw
coloured). The inheritance is autosomal recessive in the
infantile and dominant in the adult type. It may be
asymptomatic or present as abdominal lump (unilateral
or bilateral commonly) pain in the renal angles, slowly
developing hypertension or renal insufficiency. Urinary
abnormalities in early stages are polyuria with low
specific gravity and later haematuria with proteinuria.
The nontender palpable polycystic mass differs from
hydronephrosis where fluctuation is rarely present.
Urinary infection is common in the third decade.
Progressive renal failure occurs in the majority. IVP is
characteristic which shows large kidneys with elongated
and bent or distorted calyces reflecting as ring shadows.
Ultrasound and CT examination demonstrate the cysts.
Sometimes polycystic liver and pancreas may also be
associated (Fig. 15.1).
• Medullary sponge kidney: Dilatation of renal collecting
tubules is the essential feature. Medullary sponge kidney
 238 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 15.1: CT scan of abdomen showing adult polycystic
disease of the kidney associated with cysts in the liver and
pancreas
presents as gross or microscopic haematuria, nephro-
lithiasis (calcium stones) or urinary infection. It is
confirmed by IVP which demonstrates the dilated
tubules.
• Alport’s syndrome (Hereditary nephritis): It is charac-
terised by glomerulonephritis (with proteinuria and
haematuria) and extrarenal manifestations like nerve
deafness, ocular disorders like cataract or myopia or
retinitis pigmentosa.
• Trauma It is uncommon and the injury may range from
bruising to laceration. Gross haematuria, flank pain or a
mass in the flank due to extravasation of blood and/or
urine, may be present. Oliguria and shock may be
present. Renal biopsy may also cause haematuria
(transient) in a few cases. History of trauma is diagnostic.
• Movable kidney (nephroptosis) This term is applied
when the kidney can be moved by external manipulation
or when there is excessive respiratory excursion. It may
be asymptomatic or present as dragging pain or Dietl’s
crises (which is due to kinking and partial obstruction
of ureter) presenting as severe pain radiating downwards
and backwards, accompanied by nausea, vomiting,
collapse and haematuria.
• Oxaluria This term refers to presence of calcium-oxalate
crystals in the acid urine. It may account for haematuria
and pain in the loin, apart from frequency of micturition
and nocturnal enuresis. Dietary articles like spinach,
tomatoes, gooseberries and strawberries influence
oxaluria. It may be associated with oxalate calculus (vide
supra).
Ureteric lesions
Ureteric calculus It is associated with painful haematuria
(abrupt ureterorenal colic). They are usually obstructive
(partial or complete) and may pose a threat to renal function
and infection. Cystoscopic examination may reveal
ecchymosis of one ureteric orifice, if it is near the bladder.
Tumours of the ureter They are usually associated with
transitional cell tumours of either the renal pelvis or bladder.
Haematuria is the most common symptom which may be
gross or microscopic. There may be pain if the tumour is
obstructive. A large hydronephrotic kidney may be palpable.
Excretory urograms may show filling defect of the ureter
with proximal dilatation. Urine sediment shows cancer cells.
Ureterocele It connotes ballooning of the submucosal ureter
into the bladder. It may obstruct the vesical neck and result
in hydronephrosis or pyelonephritis. Excretory urogram may
show space occupying lesion on the affected side of the
bladder. A cystogram may reveal reflux usually into the
second ureter and rarely in the ureterocele ureter.
Ureteric trauma Ureteric trauma is usually iatrogenic. If it
goes unrecognised at surgery, there may be a complaint of
pain in the flank and/or lower abdomen on the affected side.
Ileus may be conspicuous. Leakage of urine into the
peritoneal cavity may cause rebound tenderness. Oliguria
or anuria occurs in bilateral ureteral injury. Retrograde
urography reveals the site of injury.
General (Systemic) Diseases
Haematological
Bleeding disorders (Refer to Chapter ‘Bleeding Disorders’)
Sickle cell disease Though the renal injury in sickle cell
disease is predominantly tubulointerstitial, glomeruloneph-
ritis is also documented. Circulating iron bound protein
complexes which appear during sickle cell crisis may be
responsible for the glomerular damage. The normal renal
circulation may be impeded due to increased blood viscosity.
Gross painless haematuria and proteinuria are the
manifestations in sickle cell nephropathy. The source of
bleeding may be from vasocclusive macro or micro infarcts
in the kidney (Refer to Chapter ‘Jaundice’).
Infections
Hepatitis B It is associated with membranous nephropathy
in children and mesengiocapillary GN in adults. Presenting
features may be nephrotic syndrome or non-nephrotic
proteinuria with haematuria. Clinical evidence of associated
 Haematuria
liver disease is more common in adults than in children.
Other features like arthritis, rash, polyneuropathy may also
be present. Humoral immune mechanisms are incriminated.
HBSAg and anti-HBSAg are demonstrable (Refer to
Chapter ‘Jaundice’).
Haemorrhagic fevers Haemorrhagic fevers like arbovirus
infections may present with haemorrhagic manifestations
probably due to coagulation defects (prolonged prothrombin
time and partial thromboplastin time), thrombocytopenia or
disseminated intravascular coagulation or vascular factors
(toxic capillary endothelial damage associated with
increased vascular permeability). The renal damage in the
form of renal interstitial haemorrhages may occur due to
obstruction of the vasa recta from oedema. The toxic
haemorrhagic phase with oliguria may be preceded by a
febrile phase and a hypotensive phase.
Subacute bacterial (Infective) endocarditis Haematuria
accompanied by embolism of renal vessel is not uncommon
in subacute bacterial endocarditis which may manifest as
sudden pain in the loin with microscopic haematuria. This
is to be suspected specially if there is fever in a subject with
a known cardiac disease. Olser’s nodes (red tender nodules
on fingers), changing cardiac murmurs, splenomegaly and
a positive culture for Streptococcus viridans are confir-
matory.
Parasitic
• Malaria: Quartan malarial nephropathy is associated
with Plasmodium malariae and affects children and
young adults. Nephrotic syndrome develops several
weeks after the onset of quartan fever. A small proportion
of patients may develop glomerulopathy. Oedema,
albuminuria and haematuria may appear. Diagnosis is
confirmed by demonstrating the parasitised RBCs (may
appear in “band” form and merozoites arranged in a
rosette) in the peripheral blood smear.
Falciparum malarial glomerulopathy may occur
soon after the onset of fever. Proteinuria, microscopic
haematuria and cylinduria may be seen in about 1/3rd
of cases. This is transient as against quartan which may
lead to progressive renal failure. Diagnosis is established
by demonstrating RBCs containing rings (more than one)
or presence of gametocytes (banana shaped) in the
peripheral smear. (Refer to Chapter ‘Rashes’)
• Filariasis: Filarial glomerulopathy (proliferative GN in
some and nephrotic syndrome relatively common) with
deposits of IgM, IgG and C3 are reported. Urine may
show haematuria and albuminuria (Refer to Chapter
Rashes).
239
• Schistosomiasis: It is caused after contact with water
containing cercariae (infective stage) which penetrate
the skin and migrate to the lungs and mature in the portal
vein S. haematobium affects the genitourinary tract and
causes dysuria and haematuria. S. mansoni though
known to produce dysentery due to ulcers in the lower
gastrointestinal tract and liver fibrosis, may also cause
overt glomerulopathy in a small percentage of cases.
Diagnosis is confirmed by identification of ova in the
stool (S. mansoni) or ova in the urine (S. haematobium)
(Refer to Chapter ‘Pruritus’).
• Echinococcus granulosus (Hydatid disease): Eggs are
swallowed after contact with infected dogs or vegetables.
The larvae migrate through the duodenum and settle in
any of the organs. When the kidney is affected renal
colic with haematuria and hydatid hooklets in the urine
are the presenting features. Renal swelling may be
appreciated before the cyst ruptures. Casoni’s test is
diagnostic.
Malignant Hypertension Refer to Chapter ‘Oliguria’.
Toxaemia of Pregnancy
a. Pre-elampsia: Characterised by hypertension, oedema
and proteinuria (nonconvulsive form).
b. Eclampsia in which hypertension is fairly severe with
convulsions and coma. Usually toxaemia of pregnancy
occurs in the last trimester of pregnancy, or within seven
days after delivery.
The glomeruloendotheliosis and uteroplacental
ischaemia account for the clinical manifestations. Normally,
the blood pressure in pregnancy falls and any pressure
raising upwards should be taken as abnormal. Urine shows
proteinuria, haematuria infrequently and elevated levels of
blood uric acid will be more conclusive than blood urea or
creatinin (Refer to Chapter ‘Vomiting’).
Diabetes mellitus Refer to Chapter ‘Polyuria’.
Renal involvement in diabetes mellitus is a common
complication. The term diabetic nephropathy connotes the
renal lesions occurring in diabetic subjects which include
glomerulosclerosis. Arterionephrosclerosis, chronic
interstitial nephritis, papillary necrosis and peritubular
deposits may also be present. Consequently the clinical
presentations may vary, ranging from asymptomatic
proteinuria, nephrotic syndrome, hypertension to progressive
renal failure. Stages of diabetic nephropathy are increased
kidney size; clinical latency; microalbuminuria: Macro-
albuminuria and renal failure. Though haematuria is not a
 240 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
significant finding per se in diabetic nephropathy, the
ascending pyelonephritis leading to acute medullary necrosis
(acute suppurative pyelonephritis or necrotising papillitis)
or papillary necrosis (characterised by flank or abdominal
pain, haematuria and fever with chills) may account for it.
Collagen Diseases
Systemic Lupus Erythematosus
Polyarteritis Nodosa } (Vide supra)
Scurvy
Scurvy (Avitaminosis C) associated with subcutaneous
ecchymoses, swollen haemorrhagic gums and delayed
healing of wounds may be accompanied by haematuria
which may go unrecognised.
Drugs
The administration of anticoagulants may account for
microscopic haematuria which may be taken as an index of
prolonged prothrombin time particularly with oral
anticoagulants. Sulphonamides are known to produce
haematuria if the urine is not maintained alkaline.
Analgesics (interstitial nephritis) and cyclophosphamide
(haemorrhagic cystitis) (Vide supra) oral contraceptives
cause recurrent haematuria with dull loin pain in young
women due to narrowing of the intra renal vessels.
Neighbouring Visceral Disease Involving Urinary Tract
Diseases of the pelvic organs like (i) carcinoma of the uterus,
vagina, pelvic colon or rectum, and (ii) inflammatory
intestinal ulcerations may cause haematuria due to direct
spread to the bladder wall by the disease process. Carcinoma
of the genitalia, as it progresses may involve the bladder,
which usually results in ulceration and haematuria. Similarly
carcinoma of the colon or any other infective intestinal
ulceration may cause haematuria due to inflamed mucous
membrane, consequent to adherence of the bowel to the
fundus of the bladder. Cystoscopic examination may show
localised congestion at the fundus without any other
pathology.
CLINICAL APPROACH
Haematuria is a definite indicator of the presence of an
abnormality anywhere in the urinary tract or bleeding
diathesis. It may be asymptomatic or symptomatic
(associated with pain, frequency of micturition, etc). When
it is gross it is observed by the patient; when present in
small amounts, microscopic examination enables the
clinician to detect it.
The initial step is to determine whether the gross
haematuria is due to the presence of blood or the red colour
of the urine is due to conditions simulating haematuria (like
haemoglobinuria, myoglobinuria, porphyria, consumption
of certain drugs and large quantities of beetroot which colour
urine red). Pitfalls like menstrual blood getting mixed with
urine during micturition (most often microscopic
haematuria) and other physiological causes like microscopic
haematuria after exercise or lordosis should be eliminated.
If microscopic haematuria is persistent even in small number,
it is all the more significant.
The second step is to confirm the presence of blood by
guaiac test or occult test tablets or more conveniently by
the use of dipstick (orthotolidine). A positive orthotolidine
test may indicate not only presence of blood but also
haemoglobin or myoglobin in the urine. In haematuria the
dipstick is positive along with presence of RBCs in the spun
sediment of urine whereas in haemoglobinuria and
myoglobinuria dipstick is positive with no RBCs in sediment
of urine. However, chemical test is negative when foods or
drugs are implicated to colour urine red.
The third step is to determine the site of bleeding in the
urinary tract.
The fourth step is to identify the cause of bleeding
whether it is due to a disease localised to the urinary tract or
systemic disease or trauma per se.
Such an approach demands for a diligent enquiry into
the history and meticulous physical examination apart from
a thorough detailed physical, chemical, microscopic and
microbiological examination of urine supported by other
relevant investigations.
History
The points to be focussed are as follows:
1. Age and Sex: In children acute nephritis or
haemorrhagic disorders and in young adults, calculus
or tuberculosis generally occur. In the 40 years and
above age group, renal neoplasms or hypertension or
prostatic hypertrophy and in women, urinary tract
infection, cancer of cervix, are usually encountered.
2. Occupation: Common in the workers of dye industry.
3. Any history of trauma preceding haematuria?
4. Any relation to exercise like jogging, since it may
suggest a tumour or calculus, or may be physiological?
5. Any history of intake of drugs like anticoagulants?
 Haematuria
6. Any recent history of fever with chills or lymphangitis
or passing cloudy urine or any chronic illness like
diabetes mellitus?
7. Any previous episode of haematuria (recurrent)?
8. Is it accompanied by other symptoms (like frequency
of micturition, dysuria) or an isolated complaint?
9. Is it painless or painful? If there is pain define its
location, as pain in the loin radiating to the groin
suggests calculus; pain in the perineal region indicates
malignant prostate; and pain during micturition points
towards urethral caruncle or vesical malignancy.
Painless haematuria may be due to renal neoplasms,
polycystic kidney, systemic diseases like hypertension,
sickle cell disease and bleeding disorders.
10. Timing of the appearance of blood during micturition—
Initial, terminal or throughout uniformly mixed (vide
supra).
Physical Examination
General Examination
It includes, looking particularly for
a. Baggy eyelids especially in the morning hours or
puffiness of the face or any oedema of the legs
b. Anaemia
c. Purpura
d. High blood pressure
e. Temperature (UTI, endocarditis or hypernephroma)
Systemic Examination
Abdomen
a. Each kidney should be palpated bimanually to detect
enlargement or tenderness over renal angle or lumbar
quadrants.
i. Placing one hand posteriorly over the angle just
below the last rib and erector spinae and the other
hand anteriorly below the costal margin.
ii. Asking the patient to breathe deeply.
iii. Applying gentle pressure by both hands when an
enlarged kidney may be felt during deep inspiration
as it descends.
b. Palpation over
i. Supra pubic region for evidence of a distended
bladder or tenderness and
ii. For any hepatosplenomegaly.
c. Auscultation for any arterial bruit.
d. Pelvic examination
i. Examination of genitalia for local causes like urethral
caruncle or any nodule or swelling of the epididymis
or genital ulcers.
241
ii. Vaginal examination for any evidence of disease
(neoplasms) in the pelvic organs.
iii. Rectal examination for any enlarged prostate.
Other Systems
Chest examination for any evidence of cardiac lesions and
subacute bacterial endocarditis.
Investigations
Urine Examination
Physical examination
a. Colour
i. Bright red suggests origin from lower urinary tract.
ii. Dark red coloured (reddish brown) suggestive of
large amount of blood present in the urine or due to
retention of blood in the bladder over a time.
iii. “Smoky” suggests the presence of small amount of
blood.
iv. Clear red or brown colour is suggestive of
haemogobinuria.
v. Colour may be normal with small number of RBCs
(microscopic haematuria) or even traces of blood.
vi. Sediment may be red or brown when RBCs settle at
the bottom in the container.
b. Three glass test: When urine is collected in three glasses
at a time, haematuria in the first glass indicates source
either from the urethra or prostate; if present in the
second glass mixed evenly, it suggests the source either
from renal (kidney or ureter) or prerenal, or bladder
sometimes and if present in the third glass usually points
towards the bladder.
c. Examination of urine collected in a tray filled with water.
i. Look for clots and their shape: If triangular shaped
(suggestive of renal pelvis origin), worm shaped
(ureter) and disc-shaped (bladder).
ii. Any other tissue like renal papillary tissue or
neoplastic pieces or mucopus plugs.
d. Specific gravity: Valuable test to assess renal (tubular)
function. If it is 1020 or more, tubular damage is unlikely
(Refer to Chapter ‘Polyuria’).
Chemical examination
a. Reaction: Urinary pH ranges from 4.3 to 8. Normal
urine is usually acidic and may be alkaline if tubular
function is impaired to excrete acid (without taking either
acids or alkalies). Haematuria in acidic urine may be
from kidney or due to beetroot. A pH greater than
8 indicates vesicle pathology or urinary tract infections
 242 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(with organisms likely to form ammonia from urea) or a
phosphatic renal calculi. The red colour of the urine due
to beetroots disappears on alkanisation and reappears
on reacidification.
b. Protein: If proteinuria is associated with haematuria, it
may be due to primary renal disease like glomerulo-
nephritis. The functional severity of the glomerular
damage can be assessed by the amount of protein lost in
the urine.
c. Sugar: For evidence of diabetes mellitus.
d. Chemical test for blood (vide supra).
e. Porphobilinogen (Watson Schwartz test)—It reacts with
Ehrlich’s aldehyde reagent to form a red complex
(confirmed by chromatography).
f. Estimation of 24 hours urine calcium, urate, oxalate,
cysteine helps to determine the cause of stone.
g. Urine protein electrophoresis.
Microscopic examination of centrifuged
urinary sediment (Fig. 15.2)
a. Cells
i. RBCs: Biconcave forms or outlines showing double
b. Tube casts: Fresh urine sample is essential to detect casts
contour in fresh urine; circular with sharp outline in
c. Crystals: Presence of crystals in acid urine points
Fig. 15.2: Urine microscopy showing crystals, cells and casts
dilute urine; crenated deformed and of unequal size
in haematuria of glomerular origin. (Phase contrast
microscopy differentiates glomerular bleeding from
other genitourinary bleeding). More than two RBCs
per high power field (HPF) is abnormal.
ii. Pus cells or leucocytes: The diameter is more than
RBCs and contains granules. When treated with
acetic acid, granules disappear and nuclei are seen.
More than four pus cells per HPF indicates infection.
iii. Epithelial cells: They are larger in size and variable
in shape and their presence in excessive numbers
indicate renal disease. Renal epithelial cells remain
unaltered or appear crowded with fat globules in
glomerulonephritis, depending on its duration.
Epithelial cells derived from the pelvis of the kidney
appear tailed. Prostatic epithelial cells appear
identical. Bladder or vaginal epithelial cells are seen
as collection of squamous cells. Normal urine
contains occasional epithelial cells.
iv. Malignant cells (vide infra): It is not a part of routine
urinalysis.
which are cylindrical in shape with rounded ends or
ragged at one end and formed in the renal tubules by
coagulation of protein. If the cells are impressed on this
matrix, which consists mainly of Tamm-Horsfall
glycoprotein, cellular casts result and if they are not
impressed hyaline casts occur. If the cells impressed
undergo degeneration granular casts result.
i. Red cell casts are seen in acute glomerulonephritis,
malignant hypertension and may appear greenish
(they are demonstrated only in fresh urine or acid
urine; alkaline urine destroys them).
ii. Epithelial casts—Indicate early stage of acute GN.
iii. WBC casts—Indicate acute pyelonephritis.
iv. Hyaline casts—Which are transparent may be found
in glomerulonephritis and occasionally in the normal
urine especially after exercise.
v. Granular casts—Present in any chronic renal disease
or acute tubular necrosis and rapidly progressive GN.
Add a few drops of methylene blue to the urine before
centrifugation; the cells in the casts shows nuclei stain.
More than one cast per 20 HPF is significant.
Certain objects like cotton or prostatic threads and
so called cylindroids, which are of no significance,
resemble tube casts but they are differentiated by their
shape, and sharp outline (Cylindroids are very long,
narrow and tapered).
towards renal calculi. They are chiefly urates, uric acid,
 Haematuria
oxalates and cystine. In alkaline or neutral urine, triple
phosphates are common. They combine to form stones.
d. Bacteria: Cocci or rods may be present in freshly
collected urine, which correlates usually with counts
more than 100,000 organisms per ml of urine (vide infra).
e. Parasites: Ova of Bilharzia haematobium are the only
helminthic ova seen in the urine to cause haematuria.
f. Malignant cells: Cells in the spun sediment are stained
by Papanicolaou method. Transitional cell tumours of
renal pelvis or ureter are better appreciable by Wright’s
stain. Exfoliative cytology enables recognition of
malignant cells.
Microbiological examination Midstream specimen of urine
must be cultured within two hours for identifying the
incriminating organism. Gram’s stain may be helpful.
Blood Tests
Haematological
a. Full blood counts (like red blood cell count, haemo-
globin, white blood cell count, differential count, platelet
count, ESR)
b. Parasites (microfilaria)
c. Sickling
d. Test for integrity of platelet and coagulation components
(if indicated)
e. Anticoagulated blood centrifuged shows reddish brown
plasma in haemoglobinuria whereas in haematuria or
myoglobinuria it is normal.
Biochemical tests
a. Blood urea and serum creatinine
b. Serum protein—A/G ratio
c. Arterial pH; HCO3; and PaCO2
d. Spectrometry—Methaemoglobin gives an absorption
band in the red (if haemoglobin is converted to
methaemoglobin) in addition to the two bands in the
green characteristic of oxyhaemoglobin.
Other biochemical tests (Refer to Chapter ‘Oliguria’)
Special blood tests
a. Complement—Hypocomplementaemia indicates
glomerulonephritis
b. LE cell for collagen disorders
c. Antinuclear factors for collagen disorders especially for
SLE.
d. Blood culture for evidence of subacute bacterial
endocarditis.
Renal function tests
a. Creatinine clearance test
b. Specific gravity test (Refer to Chapter ‘Polyuria’)
243
c. Phenol-Sulphon-Phthalein (PSP) test: For renal
efficiency. After parenteral administration of 6 mg of
the dye, over 60 per cent is excreted in two hours. It
also serves as a clinical measurement of renal blood flow.
d. Acidification test: When oral ammonium chloride 0.1 g
per kg body weight is administered the urine pH falls
below 5.3. In distal renal tubular acidosis, urine pH
cannot be reduced below 5.3 which may be due to failure
of acidification of urine in the distal tubule, i.e. ability
to form acid urine is lost. This test may be useful in
determining the underlying cause of renal calculi since
it is associated with hypercalciuria, hyperphosphaturia
and nephrocalcinosis.
Radiological Investigations
a. Plain X-ray of abdomen for any radiopaque stones.
b. Plain X-ray of chest for evidence of any tuberculosis.
c. Intravenous pyelogram—Useful to determine the level
of obstruction and its probable cause. Radiolucent uric
acid calculi can be outlined. (Refer to Chapters ‘Polyuria’
and ‘Oliguria’)
d. Postvoiding film—For detecting bladder abnormalities.
e. Retrograde pyelography (vide infra).
f. Nephrotomography—45 per cent of sodium diatrizoate
is injected rapidly and a series of tomograms taken. This
test is useful in differentiating renal tumour from a cyst.
A tumour is densely opacified whereas a cyst is
radiolucent with no vessels. This test is replaced by
imaging techniques.
g. Renal arteriography—Valuable to diagnose renal artery
stenosis and to differentiate abnormal vascular supply
from any renal mass (Refer to Chapter ‘Oliguria’).
Imaging techniques
a. Ultrasound examination (sonography)—Useful for
differentiating solid tumours from cysts apart from
assessing the renal size and stones and associated
dilatation of pelvicalyceal system (refer to Chapter
‘Oliguria’).
b. CT scan—Useful to diagnose renal masses and their
extension.
Radionuclide studies
a. Isotope renogram—After IV injection of diethylenetria-
mine pentacetic-acid labelled with technetium
( 99mTcDTPA) provides information about arterial
perfusion of each kidney, and arterial obstruction which
affects any of the three classical phases, i.e. transit time,
peak activity and excretion.
b. Isotope scan—Following injection of Dimercapto-
succinic acid labelled with technetium (99mTcDMSA)
 244 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
images of the kidney can be obtained with a gamma
camera, which can be compared, to assess the function
of each kidney.
Instrumental Investigations (Invasive)
a. Cystoscopy: Ureteric catheterisation permits direct
visualisation of the bladder and ureteric orifices thereby
revealing any bladder lesion or blood dribbling from
one of the ureters especially during the attack. Ureteric
catheters can be inserted during cystoscopy and contrast
medium is injected to outline the ureters and renal pelvis
(retrograde pyelography).
b. Urethroscopy: To detect strictures and stones.
c. Antegrade pyelography: A fine catheter is inserted
percutaneously into the pelvicalyceal system under
ultrasound control and contrast medium is injected,
which procedure sheds light about the details of the pelvi-
calyceal and ureteric pathology.
d. Renal biopsy: This percutaneous technique enables the
clinician to obtain precise information by microscopic
and immunohistological examination of the biopsied
tissue. Though histological diagnosis is forthcoming, the
clinician should weigh the pros and cons of this
procedure, while investigating a case of haematuria.
Nevertheless, it is imperative to appreciate that the
tests providing the data base to establish the diagnosis,
should be suitably tailored as per the relevance of clinical
picture.
TREATMENT OF HAEMATURIA
The therapeutic approach of haematuria depends essentially
on detection of the source of bleeding which may be due to
disease of the urinary tract or disorder of haemostasis. Its
mode of presentation in relation to micturition (initial,
throughout or terminal) and microscopic findings of urinary
sediment (RBCs and RBC casts with proteinuria point
towards glomerulus to urethra wheres RBCs alone towards
renal pelvis to urethra including prostate) are of immense
diagnostic value. If the morphology of RBC is deformed,
the bleeding is from upper urinary tract whereas presence
of RBC of normal morphology indicates lower urinary tract
pathology. Further, haematuria associated with renal colic
offers clue that the bleeding is of renal or ureteric origin.
Symptomatic Relief
1. Anxiety: Reassurance relieves apprehension. Alprazolam
(0.5-1 mg) may be necessary in highly anxious patients.
2. Pain: Bed rest and physical therapy (hot application over
the site of the pain) are the initial measures. High fluid
intake is advised so as to produce a daily urine output of
2-3 litres (provided the renal function is normal).
Antispasmodic-analgesics are administered if the
pain is intolerable. Buprenorphin (0.3 mg IM) or
pethidine (100 mg IM) given. Diclofenac (100 mg IM)
is an alternative. Antispasmodics like atropine sulphate
(1 mg IM) or dicyclomine orally (10 mg) hyoscine butyl
bromide (10 mg QID or 20 mg IM/IV) or drotaverine
(40 mg tds orally or paremerally) may be given. These
drugs may be repeated if necessary. Diclofenac and/or
Drotaverine are preferred.
3. Bleeding: Haemostatics may be given as in haemoptysis.
If the bleeding is severe, blood transfusion may be
necessary.
4. Fever: Appropriate antibiotics are to be considered, if
indicated (vide infra). Antipyretics may be necessary, if
the fever is high.
5. Urinary alkalisers like Disodium hydorgen citrate or
potassium citrate may be considered.
Specific Treatment for Specific Diseases
Initial Haematuria (Urethral and Prostate)
Urethral
• Urethritis: Nonspecific urethritis usually responds to
tetracycline (0.5 g 6—hourly; given for 7 days).
Specific urethritis may be treated accordingly.
Amoxycillin (3 g/d) with probenecid (1 g/d) or procaine
penicillin (2.4 g IM) plus oral probenecid (1 g/d).
Oestrogen cream is beneficial for senile urethritis.
Surgical dilatation and drainage of infected periurethral
ducts done if indicated.
• Caruncle: Treated by local excision.
• Calculus: Small stones can be removed or crushed
transurethrally.
• Tumours: Require resection with or without radio-
therapy. Urethrocystectomy indicated for proximal
tumours.
Prostatic
• Prostatitis: Specific antibiotics according to culture and
sensitivity tests. Cotrimoxazole (two tablets twice daily
for 10 days) or cephalexin (250 mg 6 hourly for seven
days) usually respond.
• Benign hypertrophy: Conservative treatment usually
suffices. Prostatic congestion should be removed.
Voiding urine as the urge develops, protects vesical tone.
 Haematuria
Flavoxate (100-200 mg tds orally) offers symptomatic
relief. Finasteride (5 mg/day/orally) and/or alpha adreno
receptor blockers may be benecificial (Prazosin,
Terazosin and Tamsulosin) for better urinary flow. In
acute retention, an indwelling catheter for 3 or 4 days
restores detrusor tone. If the symptoms are disturbing
or renal impairment is likely, surgery is the alternative.
Transurethral prostatectomy is favoured. Cryosurgery
considered in poor risk patients.
• Carcinoma: Nodular lesions treated by radical
prostatectomy with or without pelvic lymphadenectomy.
Suprapubic implantation of radioactive gold or iodine
appears to be effective in advanced lesions.
Radiation therapy and/or antiandrogen therapy
(orchidectomy with or without oestrogens like stilbestrol
1-3 mg/d or gonadotrophin analogues like buserelin
500 mg 8 hourly SC for one week followed by 100 µg
intranasally 4 hourly or antiandrogenic like cyproterone
100 mg tds) bicalutamide (50 mg) are palliative
measures. Pain from metastatic bone lesions may be
relieved by corticosteroids.
Transurethral resection is a surgical palliative procedure
to relieve obstruction.
Terminal Haematuria (Vesical Lesions)
Cystitis
It is treated with cotrimoxazole or nitrofurantoin or
gentamicin or ciprofloxacin for 10 days depending on the
culture and sensitivity tests. Dicyclomine (10 mg t.d.s.) or
pyridium (200 mg t.d.s.) may be useful for suprapubic pain
and dysuria. Copious fluids are indicated.
Apart from treating recurrent cystitis with appropriate
antibiotics a prophylactic course of nitrofurantoin or co-
trimoxazole or norfloxacin for 6 weeks to 6 months
(depending on the number of recurrences) immediately after
the regular course of treatment, is beneficial.
In chronic cystitis, bladder washes with suitable urinary
antiseptics may be necessary in addition to the therapy
mentiond above.
Factors predisposing to infection like calculi, etc. or
associated infections of genitalia must be corrected, if
present.
Vesical calculi Small calculi require transurethral approach
whereas large calculi require suprapubic transvesical
removal. Installation of hemiacidrin through a cathether
which is clamped for one hour may be beneficial. Analgesics
and antibiotics administered, if indicated (vide infra).
245
Tumours Total cystectomy and prostatectomy indicated for
papilloma and invasive tumours with urinary diversion
measures. Radiation therapy (6000 rads given for 6 weeks
is useful) is supplemented. Chemotherapy is not encourag-
ing. However, 60 mg of thiotepa is dissolved in 60 ml of
normal saline and instilled by catheter weekly.
Immunotherapy with BCG vaccine is being favoured.
Trauma The site of the trauma is drained and a cystostomy
tube is inserted for extraperitoneal ruptures. The rent is
closed transperitoneally and the bladder is drained by
cystostomy in cases of intraperitoneal ruptures.
Total (Throughout) Haematuria (Renal Lesions)
Acute pyelonephritis It is treated with appropriate antimicro-
bial agents initially and may be changed based on culture
reports if necessary. Norfloxacin or ciprofloxacin or other
quinolones are acceptable in most of the cases. Therapy
should last for at least two weeks and better extended up to
4-6 weeks in patients with recurrent infections. Optimum
amounts of fluids (at least 2 L/d) are administered to induce
adequate output. A follow-up of the response to treatment
is mandatory. Prompt evaluation and correction of structural
abnormalities are indicated in relapses and reinfections.
Single dose of the suitable antimicrobials at bed time is
rewarding.
Glomerulopathies
• Acute glomerulonephritis (primary and secondary)
a. Poststreptococcal glomerulonephritis: Conservative
treatment is advised.
• Bed rest
• Salt restriction (1-2 g/d)
• Fluid restriction (maintaining optimum fluid
intake and output chart).
• Diet: Adequate calories from carbohydrates and
fats with less proteins.
• Loop diuretics may be necessitated for oedema
at times.
• Hypertension should be controlled with loop
diuretics or enalapril (in case seizures occur,
parenteral diazepam may be given).
• Penicillin or erythromycin (alternative) may be
helpful, though it does not influence the course
of the disease (Glomerulonephritis associated
with other infections usually resolves with
suitable antibiotics).
b. Rapidly progressive (cresentic) glomerulonephritis:
High dose of steroids considered. Methyl predni-
 246 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
solone 30 mg/kg IV over few hours, every alternate
day for three doses followed by oral prednisolone
60 mg/d tapered over several weeks.
Cyclophosphamide (2 mg/kg daily for three
months) and plasma exchange (2-4 L exchanged
daily for couple of days and then fortnightly till
improvement occurs) are advocated.
Heparin and dipyridamole may be considered.
c. Focal and segmental glomerulonephritis: Treatment
is symptomatic. The underlying systemic disease may
be treated appropriately.
d. IgA nephropathy: There is no specific therapy and
treatment is supportive. Corticosteroids may be of
value in some cases. Antibiotics on long term bsis is
advocated since haematuria is associated with upper
respiratory infections.
e. Good pasture’s syndrome: Methyl prednisolone 1 g
IV on three consecutive days followed by predni-
solone 60 mg/d for six weeks and then taper.
Cyclophosphamide 2 mg/kg/d may be added.
Plasmapheresis and the above immunosuppressive
therapy is effective if the renal function is not
impaired and in pulmonary haemorrhage. If the renal
function is impaired, dialysis and transplantation are
considered.
f. Systemic lupus erythematosus (SLE): Prednisolone
60 mg/d for one month and then tapered over four
week period followed by cyclophosphamide 1-2 mg/
kg/d and/or azathioprine 1-2 mg/kg/d. Plasmaphere-
sis may be considered in very severe caes.
g. Vasculitis: Prednisolone (60 mg/d tapered over 1-3
months) and oral cyclophosphamide (1-3 mg/kg/d
for three months or till the disease becomes
quiescent) are effective. The offending drug leading
to hypersensitivity vasculitis may be withdrawn.
h. Henoch-Schönlein purpura: Treatment is sympto-
matic. Some may have to be treated as for crescentric
glomerulonephritis.
i. Dysproteinaemias: (Refer to Chapter ‘Bleeding
Disorders’)
• Nephrotic syndrome (primary and secondary)
a. Membranoproliferative (mesangiocapillary)
glomerulonephritis: Dipyridamole (75 mg 3 times
daily) and aspirin (325 mg 3 times daily) slow down
the progression to end stage disease. Alternate day
prednisolone regimen is beneficial. Dipyridamole
and warfarin together with cyclophosphamide may
be useful.
b. Mesengial proliferative glomerulonephritis: Treat
with prednisolone (2 mg/kg/d up to 80 mg/d is given
till remission occurs or for 8 weeks). If ineffective
or relapse occurs cyclophosphamide (1-2 mg/kg/d
for 8 weeks) is given.
c. Membranous glomerulonephritis: Spontaneous
remission may occur. Alternate day high dose
prednisolone (120 mg for 8 weeks and tapered), if
given, prior to renal insufficiency, may reduce further
renal impairment. Prednisolone for 4 weeks and
alternating with chlorambucil (0.2 mg/kg for 4
weeks) for a period of six months is an alternative.
Cyclophosphamide (1.5 mg/kg/d given for 1-2 years)
is known to delay the end stage disease. Associated
blood pressure and oedema must be treated.
d. Minimal change disease: Symptomatic treatment is
with bed rest, salt and fluid restriction; high protein
diet; diuretics and IV infusions of albumin. Specific
treatment with prednisolone 60 mg/d for four weeks
or until remission of proteinuria occurs, which should
be tapered over four weeks. If relapses are frequent,
or if no response to prednisolone cyclophosphamide
(2 mg/kg body weight given for six weeks or
continued for two weeks after remission) or
cyclosporin (< 4 mg/kg/d) considered chlorambucil
(0.15 to 0.2 mg/kg/d for six weeks) with prednisolone
effective.
e. Focal/segmental glomerulosclerosis: Prednisolone
(120 mg on alternate days for eight weeks and tapered
over four weeks) is beneficial. If relapses occur,
cyclophosphamide or chlorambucil with predniso-
lone for eight weeks is useful. Hypertension and
oedema are to be corrected. Renal failure should be
appropriately managed, if necessary.
f. SLE: (Vide supra.)
g. Diabetic nephropathy: Tight control of blood
glucose may delay diabetic nephropathy (metformin
should not be given. Sulphonylureas which are
metabolised than excreted like glipizide, must be
chosen; dose of insulin must be adjusted daily)
Effective management of hypertension (with ACE
inhibitors and/or Angiotensin II receptor antagonists
or diuretics like loop diuretics and spironolactone)
and dietary restriction of protein (0.5 gm/kg/d) may
delay progression to renal failure. If renal failure sets
in, treatment for chronic renal failure must be
instituted. Continuous ambulatory peritoneal dialysis
is better than haemodialysis. Renal transplantation
in selected cases may be successful.
 Haematuria
h. Renal vein thrombosis: Established cases need oral
anticoagulant therapy till the symptoms subside.
Risks of pulmonary embolism and impaired renal
function may be treated accordingly, if necessary.
i. Drugs: (Vide infra)
Interstitial Nephritis (Tubular Predominantly)
Withdrawal of drugs like analgesics may stabilise the renal
function. Other causes like bacterial pyelonephritis, multiple
myeloma, Sjögren’s syndrome or metabolic disorders, if
incriminated, may be treated. If acute or chronic renal failure
occurs, treat accordingly.
Nephrolithiasis
• General management Relieve pain with analgesics and
antispasmodic drugs (vide supra). Encourage high fluid
intake 3-5 litres per day. Treat concurrent infection.
Watch for any increasing obstruction (if the obstruction
is longer than four weeks, renal damage may result).
Attempt to sieve urine, for any stones passed for analysis
(calculi < 6 mm) usually pass off within four weeks.
• Specific stone therapy Any known cause of calculi must
be corrected.
a. Uric acid stones: Allopurinol (100 mg tds), xanthine
oxidase inhibitor is beneficial (prophylaxis).
Alkalinise the urine with sodium bicarbonate,
1-2 mEq/kg (1 g = 12 mEq), in divided doses. Reduce
purine diet like meat and beans.
b. Calcium stones: Thiazide (Bendrofluazide-5 mg/d)
decreases calcium excretion. Restrict salt as it
negates hypocalciuric effects of thiazide. Neutral
phosphate (1.5 g tds) or sodium cellulose phosphate
(5 g bd) are the alternatives. Avoid calcium rich diet
like milk and cheese or vitamin D supplements.
c. Oxalate stones: Thiazides, and pyridoxine are
beneficial. Avoid rhubarb, spinach, tomato,
chocolates, tea. Vitamin C is useful for hyperoxaluria.
d. Phosphatic stones: Acidify urine, since alkalini-
sation favours calculi.
e. Cystine stones: Alkalinise the urine. Prescribe low
methionine diet. Penicillamine may be advised (start
0.5 g/d and increase to 1 g/d).
f. Struvite stones: Avoid phosphates and infections with
urea-splitting organisms. Antibiotics beneficial for
triple phosphate staghorn stones. Surgery and
irrigation with hemiacidrin advocated.
• Interventional therapy Percutaneous nephrolithotomy;
Antegrade Nephrostomy Percutaneous chemolysis (with
Trishydroxy Methyl Amine Methane (THAM) dissolves
uric acid and cystine stones; surgical lithotomy
247
(endourologic stone extraction with Dorneir basket or
open surgical removal); lithotripsy (Extracorporeal
Shock Wave Lithotripsy ESWL), (electrohydraulic
lithotripsy or ultrasonic lithotripsy) are indicated when
the stones cannot be dissolved or stones are associated
with obstruction of one month duration. Laser therapy
is an alternative.
• Prophyalxis: Mandelamine may be considered to
prevent infection in nephrolithiasis, since it liberates
formaldehyde and lowers pH of urine, apart from high
fluid intake and appropriate dietary and drug schedule
to prevent nephrolithiasis.
Neoplasms Early surgery offers encouraging results for renal
carcinoma. Radiotherapy and progesterone like hormones
are helpful for metastases.
Wilm’s tumour is radiosensitive and chemotherapy is
effective.
Endoscopic resection and intravesical chemotherapy
with thiotepa or epodyl advised for bladder carcinoma. BCG
vaccine may be effective. Total cystectomy and
transplantation of ureters into ileal channel may become
necessary at times.
Renovascular Surgical revascularisation and angioplasty
yield results in renal artery stenosis.
Hereditary
• Polycystic kidney Treat promptly urinary infection and
associated hypertension. Sodium chloride and sodium
bicarbonate may be supplemented in salt losing states.
If renal function deteriorates, treat as chronic renal
failure. Scanning of family members and genetic
counselling may be undertaken.
Renal trauma Shock and haemorrhage are treated with blood
transfusion. Persistent bleeding requires surgical exploration
and nephrectomy, if necessary.
Movable kidney and Dietl’s crises Abdominal support and
breathing exercises to improve muscle tone may suffice. In
Dietl’s crises, patient is advised to lie on his abdomen or
adopt knee-elbow position. Hot fomentations applied over
the site. Buprenorphine may be administered. Nephrectomy
is indicated in Dietl’s crises or hydronephrosis.
Oxaluria Treatment consists of avoiding diet containing
oxalates and those which facilitate excessive carbohydrate
fermentation in the intestine as well as foods with high purine
content. Administration of magnesia prevents formation of
calcium oxalate crystals. Rendering the urine strongly acidic
reduces calculi of oxalates.
 248 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
In hyperoxaluria, cholestyramine (8-16 g per day) helps
in binding oxalate or calcium lactate (8-14 g per day)
precipitates oxalate in the gut. High fluid intake and
pyridoxine (200 mg/d) are beneficial. Prevention aimed by
giving pyridoxine (up to 10 mg) per day.
Ureteric Lesions
Ureteric calculus Calculi with less than 0.6 cm diameter
may pass off spontaneously. The ureterorenl colic may be
treated symptomatically and antibiotics administered for
control of infection. If progessive hydronephrosis or
recurrent infections occur the calculus is better removed
either by cystoscopic manipulations or surgery or lithotripsy.
Tumours If benign, local excision may be done. Otherwise,
nephroureterectomy and removal of periureteral vesical area
may be considered.
Ureterocele If large, transvesical excision and reimplan-
tation of both ureters into the bladder may be done.
Nephroureterectomy is indicated, if the kidney is damaged.
Trauma Ureteral ligation or end to end anastomosis or
reimplantation of ureter into the bladder or transuretero-
stomy or nephrectomy considered as the case may be.
Treatment of Haematuria due to General (Systemic)
Diseases
Treated symptomatically in addition to specific therapy for
the underlying systemic cause.
1. Haematological (Refer to Chapters ‘Bleeding Disorders’
and ‘Fatigue’)
2. Infections (Refer to Chapters ‘PUO’ and ‘Oedema’)
3. Hypertension (Refer to Chapter ‘Headache’)
4. Diabetic renal lesions (Refer to Chapter ‘Polyuria’)
5. Collagen diseases (Refer to Chapter ‘Polyarthritis’)
6. Drugs (Withdraw the offending drug).
Haematuria 249
 Chapter

Haemoptysis
16
Haemoptysis is the term used to denote coughing out blood CAUSES OF HAEMOPTYSIS
invariably mixed with or without sputum. Coughing is a
Causes of haemoptysis are listed in Table 16.1.
reflex mechanism and can be voluntary also to clear
secretions. The afferent pathway is glossopharyngeal, Table 16.1: Aetiology of haemoptysis
superior laryngeal and vagus nerves. The efferent pathway
1. Respiratory
includes recurrent laryngeal nerve, phrenic nerve and the a. Infections
spinal nerves supplying the respiratory muscles. i. Pulmonary tuberculosis
Coughing consists of three phases: ii. Chronic bronchitis
1. Deep inspiration, followed by forced expiration against iii. Bronchiectasis
closed glottis temporarily. iv. Pneumonia
2. Closure of the glottis and contraction of muscles v. Lung abscess
vi. Pulmonary (Tropical) eosinophilia and parasitic lung
accompanied by relaxation of diaphragm, causes disease
maximum intrathroacic pressure, and vii. Fungal lung disease
3. Sudden opening of the glottis with a sudden fast gush b. Malignancy
of air. i. Bronchogenic carcinoma of the lung
Cough may be acute or chronic, dry or productive. The blood ii. Bronchial adenoma
that is coughed out may be in the form of streaks of blood c. Traumatic
i. Foreign body
or tiny clots or profuse haemorrhage. Sometimes, it may be
ii. Lung contusion
mixed intimately with sputum giving rise to blood stained iii. Lung biopsy (iatrogenic)
secretions. 2. Cardiac
a. Mitral stenosis
PATHOGENESIS OF HAEMOPTYSIS b. Systemic hypertension
c. Pulmonary hypertension
Blood stained sputum may be due to d. Left heart failure
1. Vascular (congestion or rupture or vasculitis or thrombo- 3. Vascular
embolism) a. Pulmonary embolism and infarction
2. Necrotic lesions (bronchial carcinoma; pulmonary b. Arterio-venous malformation
c. Vasculitides
tuberculosis)
i. Polyarteritis nodosa
The underlying mechanisms are: ii. Wegener’s granulomatosis, Microscopic Polyangitis and
a. Pulmonary venous congestion Churg-Strauss syndrome
b. Rupture of small pulmonary or bronchopulmonary d. Good Pasture’s syndrome
anastomotic venules e. Pulmonary haemosiderosis
c. Aneurysmal dilatation of a branch of pulmonary f. Aortic aneurysm rupturing through eroded bronchus.
4. Bleeding Diathesis
artery in a cavity
5. Idiopathic: If followed for one year, some may show evidence of
d. Ulceration of small blood vessels or bronchial walls
pulmonary tuberculosis.
e. Granulation tissue on bronchiectatic walls.
 Haemoptysis
1. Respiratory
Infections
Pulmonary tuberculosis There are two types of tubercular
bacilli, which affect the humans. (a) Mycobacterium
tuberculosis (endemic in man); (b) Mycobacterium bovis
(endemic in cattle). The former is transmitted by inhalation
of the organism in droplets and the latter by ingestion of
infected milk. Haemoptysis for a layman may mean
pulmonary tuberculosis, so is the case to the medical man
also in the majority of cases. It is an early symptom of
pulmonary tuberculosis, usually suspected clinically by a
dull note and crepitations in apices and bronchial breath
sounds. It is confirmed radiologically, which may show early
infiltrations with mottled shadows or consolidation or
cavities (Fig. 16.1). In certain cases, the chest X-ray may
not show anything and clinically also it is silent but, if such
cases are followed up for couple of months, the tuberculosis
may be seen manifesting in the skiagram chest.
Haemoptysis in the early stages occurs due to an erosion
of a small vessel in the caseating lesion and it is small in
quantity. In chronic type of tuberculosis with cavity
formation, severe haemoptysis may occur from rupture of a
dilated artery remaining strangely intact in the wall of the
cavity (aneurysm of Rasmussen’s) or through an eroded
vessel. Similarly, when there is associated fibrosis, secondary
Fig. 16.1: X-ray of the chest showing ill defined opacities with
areas of translucency (cavitation) in both lung fields and
associated fibrosis, diagnostic of bilateral pulmonary
tuberculosis
251
bronchiectasis will be the source of haemoptysis although
tuberculosis infection is very quiet and inactive.
Chronic bronchitis This is usually seen in cigarette smokers
who come with complaints of blood streaked sputum. Acute
infections and occupational exposures to various dusts
account for other cases. It often coexists with emphysema,
probably with a deficiency of Alpha-1, antitrypsin. In fact,
the morning cough of the cigarette smokers is only due to
chronic pharyngo-tracheobronchitis. Wheezing and tightness
in the chest with rhonchi and coarse crepitations are the
physical signs discernible, apart from signs of emphysema in
advanced cases. More often the cause of haemoptysis may
be due to an underlying major factor, rather than simple
chronic bronchitis, which has to be borne in mind.
Bronchiectasis In bronchiectasis, haemoptysis may be in the
form of blood stained sputum or severe haemorrhage which
is due to bleeding from the hyperaemic walls of the cavities
or probably from pulmonary systemic arterial anastomosis.
This is relevant specially, when there is a long history of
cough with purulent expectoration varying with posture.
Clubbing of the fingers and coarse crepitations over the
bases of the lung, one or both sides, is highly characteristic.
Recurrent haemoptysis from granulation tissue of the
cavities may be the only principal symptom without cough
and sputum (dry bronchiectasis). It may result from bronchial
obstruction (foreign body, tuberculous lymph node, cystic
fibrosis) or it may be postinfective (tuberculosis and
measles) or it may be maldevelopment of the bronchi with
dextrocardia (Kartagner’s syndrome), or hypogamma-
globulinaemia. Diagnosis is confirmed by bronchography.
Pneumonia Pneumonia may be due to bacteria, myco-
plasma, virus, fungi, rickettsia or pneumocystis carinii. It
usually presents with acute onset of fever, cough, and chest
pain with a dull note, tubular breath sounds and fine
crepitations. Occasionally, haemoptysis is seen especially
in Klebsiella pnuemonia although rusty sputum is common.
Lung abscess In lung abscess, the sputum is blood stained.
More striking is foetid purulent sputum of short duration
with signs of consolidation or cavitation or atelectasis. It
may result from; (i) aspiration pneumonia (aspiration of
septic material from the nose, mouth and throat); (ii) specific
pneumonias (pneumococcal, Klebsiella and tuberculous
pneumonias); (iii) following bronchial obstruction; (iv)
infected cysts; and (v) metastatic lung abscess (septicaemia).
Diagnosis is confirmed by X-ray of the chest (Fig. 16.2)
and examination of sputum (separates into three layers, if
collected in a conical glass).
 252 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

examination may be unreliable since this mycelium is often

seen even in normal people also.
Cryptococcus neoformans may present as cough, fever,
chest pain. X-ray show patchy consolidation nodules, cavity
or hilar lymphadenopathy. Indian ink study of the sputum
confirms the diagnosis.

Malignancy
Bronchogenic carcinoma of the lung Almost 95 per cent of
the primary lung cancers belong to (i) squamous
(epidermoid), (ii) adenocarcinoma, (iii) large cell, and (iv)
small cell (oat cell). The small cell is usually fast growing
and disseminated whereas, the non-small cell may be
localised. The epidermoid and the oat cell types appear as
central masses while the other two appear as peripheral
masses. Central tumours cause haemoptysis, cough and
dyspnoea. The peripheral types present as chest pain or lung
Fig. 16.2: X-ray chest showing cavity with a fluid level abscess. Recurrent haemoptysis in the form of streaks of
within it characteristic of lung abscess blood in the sputum is an early manifestation. This is to be
suspected in heavy cigarette smokers. Physical signs may
Pulmonary (Tropical) eosinophilia and parasitic lung be that of partial obstruction with localised wheeze. The X-
diseases Haemoptysis sometimes may be a manifestation ray of the chest may show a dense irregular hilar opacity or
of tropical eosinophilia which is due to dead microfilaria a circumscribed peripheral opacity or widening of the
(W Bancrofti) embedded in the lung tissue. Diagnosis is mediastinal shadow (Fig. 16.3). The metastatic manifesta-
confirmed by differential counts showing high eosinophil tions result in dysphagia, hoarseness, tracheal obstruction,
count and micronodular shadows in chest radiograph. Horner’s syndrome and/or superior vena cava syndrome or
Haemoptysis as a symptom is uncommon in pulmonary pleural effusion or spinal cord compression. The nonmeta-
amoebiasis. The hydatid cyst of the lung due to static manifestations may be endocrinal or neurological. The
Echinococcus granulosus is not that common. Haemoptysis
is the only symptom of an unruptured hydatid cyst and
usually precedes before rupture. Diagnosis is confirmed by
X-ray of the chest showing round shadows with lilly
appearance and a positive casoni skin test.
Paragonimiasis (endemic haemoptysis) is due to a lung
fluke Paragonimus westermani which is common in the
far east. Sometimes, in the Indian port cities this may be
encountered. Haemoptysis and chest pain are the presenting
symptoms. X-ray shows small cavities and diagnosis is
confirmed by examination of the ova in sputum or stool.
Eosinophils also increased in (i) allergic disorders
(asthma), (ii) collagen vascular diseases, (iii) skin diseases
(Urticaria, eczema, pemphigus), (iv) Eosinophilic
leukaemia, (v) Loffler’s eosinophilic endocarditis.
Fungal lung disease The fungus Aspergillus fumigatus is
quite common. Recurrent haemoptysis is a characteristic
feature. The diagnosis is confirmed by X-ray of the chest
showing characteristic dense shadow of a ball surmounted Fig. 16.3: X-ray chest showing carcinoma of the bronchus
by a dome of thin air, and also precipitin test. Sputum spreading from hilum into the lung (RT)
 Haemoptysis
endocrinal features occur with small cell tumours (ACTH
and ADH), gynaecomastia in large cell type and hyper-
calcaemia in epidermoid type. The neurological features are
dementia, cerebellar degeneration, polyneuropathy and
myasthenia gravis. Staging of lung cancer involves location
and spread, depending on the involvement of one hemithorax
and regional lymph nodes or beyond (tumour, node and
metastasis—TNM system). The diagnosis is confirmed by
(a) cytology of sputum or pleural fluid, (b) chest X-ray with
tomograms (tumours of less than 6 mm may not be visible),
(c) CT scan, (d) fibreoptic bronchoscopy, and (e) trans-
thoracic needle biopsy.
Bronchial adenoma In bronchial adenoma, haemoptysis is
recurrent with a history of recurrent attacks of pneumonia
of the same lobe. Examination may show localised wheeze
with signs of atelectasis or consolidation. Diagnosis is
confirmed by bronchoscopy.
Traumatic
Foreign body A foreign body in the respiratory tract may
injure the mucosa and cause bleeding immediately. Later
on if it produces obstruction, consequent pathological
changes like collapse, consolidation and suppuration, may
also result in haemoptysis.
Lung contusion A blunt injury may be associated with
haemoptysis even without obvious fractured ribs.
Lung biopsy (Iatrogenic) Rarely needle biopsy or translung
biopsy may result in haemoptysis which will be very
obvious.
2. Cardiac
Mitral Stenosis
The characteristic apical mid-diastolic murmur with
presystolic accentuation and a closing snap (loud first sound)
or opening snap is highly diagnostic. Haemoptysis is
commonly associated with this entity at one stage or other
and is due to:
a. Pulmonary hypertension
b. Left atrial failure
c. Pulmonary embolism/infarction
d. Rupture of broncho-pulmonary anastomotic venules
Systemic Hypertension
In some cases of systemic hypertension, the rapid pressure
in the bronchial circulation may give rise to haemoptysis or
253
may be due to pulmonary venous congestion consequent to
left ventricular failure.
Pulmonary Hypertension
There is increase in the pressure of the pulmonary arterial
circulation due to:
a. Rise of pressure in the left atrium and consquently
pulmonary veins, e.g. mitral stenosis
b. Increased pulmonary blood flow, e.g. atrial septal defect;
c. Diminished circulation in the pulmonary capillary bed
(emphysema). Increased pulmonary vascular resistance
d. Obstruction of pulmonary circulation (recurrent emboli).
Such cases may present themselves with haemoptysis.
e. Idiopathic
Characteristic physical signs of accentuated P2, ejection
systolic murmur in the pulmonary area, right ventricular
hypertrophy and underlying causative condition, help to
diagnose the cause of haemoptysis.
Left Heart Failure
It may be due to left atrial (mitral stenosis) or left ventricular
failure (hypertension). Paroxysmal dyspnoea and orthopnoea
associated with blood stained frothy sputum are highly
suggestive. Signs like crepitations at the bases of the lungs,
cardiomegaly, loud P2 and triple rhythm are confirmatory
of left heart failure which accounts for haemoptysis.
3. Vascular
Pulmonary embolism and infarction (Refer to Chapter
‘Chest Pain’).
Arteriovenous malformation (Refer to Chapter ‘Cyanosis’).
Vasculitides (Uncommon causes)
Polyarteritis nodosa It is suspected, if associated with fever,
joint pains, loss of weight, small nodules along the course
of the Medium size arteries and multiple visceral
involvement like heart (hypertension, myocardial infarction,
pericarditis), lung (pleuritis, asthma), kidney (glomerulo-
sclerosis, renal failure), abdomen (abdominal pain due to
peritonitis, or mesenteric vasculitis or hepatic infarction
associated with underlying chronic liver disease), CNS
(mononeuritis, multiplex, hemiplegia—retinal haemor-
rhages), haematological (eosinophilia and electrophoresis
showing raised gamma globulin). Visceral angiography and
biopsy studies are diagnostic.
 254 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Wegener’s Granulomatosis (small vessel vasculitis) Fever,
cough, sinusitis, glomerulonephritis, and the involvement
of eyes are the presenting features. Hyperglobulinaemia
particularly IgA is characteristic.
ANCA (Anti-Neutrophil Cytoplasmic Antibody) may be
positive others like Microscopic Polyangitis (Glome-
rulonephritis and pulmonary haemorrhages) and Churg-
Stranss syndrome (H/o asthma with fleeting pulmonary
infiltrates and glomeruler lesions belong to small vessel
necrotising vasculitis group).
Good Pasture’s Syndrome
The early clinical features are cough, mild dyspnoea,
haemoptysis and glomerulonephritis which may be
associated with or without renal failure. Immuno-
fluorescence studies reveal antibasement membrane
antibodies in the renal biopsy material and in the serum
which is highly diagnostic.
Pulmonary Haemosiderosis
Recurrent haemoptysis may be accompanied by progressive
breathlessness due to haemosiderin in intra-alveolar macro-
phages and proliferative fibrosis of alveolar walls. The
diagnosis is confirmed by X-ray of the chest showing fine
mottling and the iron laden macrophages in the sputum.
Aetiology is obscure although vascular defects are
incriminated.
Aneurysm of the Ascending Aorta or Arch of Aorta
(Uncommon)
Haemoptysis may result from erosion of the trachea,
bronchus, or pulmonary tissue and ‘weeping’ occurs
Haemoptysis
History
Past history of smoking and/or respiratory disease.
Symptoms
Associated symptoms like cough and expectoration related to
posture and/or the sputum is foetid and three layered.
Tickling sensation in the throat before the episode.
Stool is normal without occult blood.
Blood
Blood mixed with sputum.
Blood is bright red and frothy.
Reaction
Alkaline
throught the eroded portions in aneurysm of ascending aorta
or arch of aorta. Rarely, it may rupture into trachea or
bronchus with dramatic haemoptysis which may be fatal
(Refer to Chapter ‘Chest Pain’).
4. Bleeding Diathesis
Haemoptysis may occur in any one of the bleeding disorders
although epistaxis and bleeding from the gums or into the
skin is much more common (Refer to Chapter ‘Bleeding
Disorders’).
CLINICAL APPROACH
The primary effort on the part of the clinician is to delineate
true haemoptysis from (a) spurious, (b) fictitious
haemoptysis, and (c) haematemesis.
A proper history and physical examination supported
by appropriate investigations is important in this endeavour.
In true haemoptysis, blood comes from lower respiratory
tract below the larynx.
In spurious haemoptysis (a) blood may come from the
nose and gums and pharnyx leading to spitting of thin
reddish fluid, and (b) blood may trickle down the larynx
and be brought out without cough or sometimes with
expectoration.
Hence, it is essential that the oral cavity and naso pharynx
must be invariably examined to avoid this pitfall.
Fictitious haemoptysis is artificially bringing out the
blood deliberately stimulating haemoptysis as seen in
malingers.
In haematemesis, quite often blood from the lungs may
be mistaken for blood from the stomach. Sometimes
expectorated blood may be swallowed and then vomited.
Haematemesis
Past history of alcoholism and/or diseases of the stomach
and duodenum or liver.
Associated symptoms like indigestion and discomfort
in the upper abdomen
Nausea, feeling of faintness and upper abdominal pain.
Stool tarry and occult blood is positive.
Blood mixed with food particles.
Blood is dark coloured—coffee ground and clotted, without froth.
Acidic
 Haemoptysis
The following table may help to differentiate one from
the other.
• Having confirmed that it is true haemoptysis, relevant
points in the history must be elicited like
1. Quantity of haemoptysis—Profuse and large or small
quantities or streaking of blood which is bright red
in colour, (more than one teaspoon is highly
pathognomonic and significant).
2. Recurrence—Is the haemoptysis recurrent or a first
episode? If it is recurrent, it is usually due to adenoma
or dry bronchiectasis.
3. Duration—Long history is usually suggestive of
bronchiectasis.
4. Family history—of tuberculosis or bleeding from
other sites.
5. History of:
a. Injury to the chest
b. Inhalation of foreign matter or use of betel nuts
c. Smoking
d. Use of anticoagulants
e. Prolonged immobilisation
f. Invasive procedures
6. Associated symptoms—like fever, foetid sputum,
dyspnoea, chest pain, anorexia and loss of weight
must be enquired.
Physical Examination
General Examination
a. Decubitus—Bleeding side kept dependant.
b. Oral cavity (mouth and gums) and throat including naso-
pharynx.
c. Any clubbing or hypertrophic pulmonary osteo-
arthropathy.
d. Any tenderness of the calf muscles due to venous
thrombosis or telangiectasia.
Systemic Examination
Cardiac Evidence of pulmonary hypertension as in mitral
stenosis or Eisenmenger’s syndrome (vide chapter cyanosis).
Evidence of left ventricular failure like orthopnoea,
hypertension, cardiomegaly and basal congestion, or aortic
aneurysm.
Respiratory Any localised tenderness of the chest wall or
evidence of friction rub, bronchial breath sounds and coarse
crepitations or localised wheeze or murmur in the lung fields
due to AV malformations.
255
Bleeding diathesis Hess test for the evidence of vascular
purpura and abdominal palpation for any organomegaly.
Fundus Examination for hypertensive changes or
haemorrhages due to bleeding disorders only.
Investigations
1. Chest roetgenogram is all important for the diagnosis
which may show infiltration in the apices suggestive
of tuberculosis or cavity due to lung abscess or ring
shadows and/or tramlines in bronchiectasis or mass
lesion in neoplasm.
Cardiac silhoutte may suggest underlying cardiac
lesions.
2. Tomography—AP and lateral (not undertaken now).
3. Blood—(a) TWC, DC, ESR, (b) bleeding time,
coagulation time, prothrombin time, fibrinogen, (c) LE
cell and (d) LDH (raised in pulmonary embolism).
4. Sputum examination
a. Macroscopic
b. Microscopic—For organisms, parasites and
cytology (inflammatory or malignant cells).
Eosinophils in asthma and neutrophils in chronic
bronchitis (COPD)
c. Culture
5. ECG—for any chamber hypertrophy or pulmonary
embolism.
6. Fiberoptic bronchoscopy—Bronchoscopic biopsy and
cytological study or bronchial secretions for culture.
7. Bronchography
8. Scanning
a. CT (Fig. 16.4) or HRCT
Fig. 16.4: CT scan of thorax showing a large irregular mass in
the region of anterior basal segment of the left lower lobe
suggestive of bronchogenic carcinoma
 256 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Isotope (in pulmonary embolism underperfusion
in normally ventilated lung seen although X-ray
is normal).
9. Angiography—(a) Pulmonary and (b) Bronchial
10. Needle biopsy of the lung (not done usually)
11. Specific pulmonary function tests.
It is better to avoid unnecessary diagnostic procedures,
unless and otherwise, other investigations are inconclusive.
TREATMENT OF HAEMOPTYSIS
The patient is usually alarmed by the expectoration of blood,
which may be scanty, moderate or massive. Scanty
haemoptysis requires no active treatment other than
assurance and exploring the underlying cause. Moderate or
massive (> 600 ml) haemoptysis should be treated, more so
the latter one with intensive monitoring, inclusive of
endotracheal intubation facilities, as it is life, threatening at
times. The treatment can be as follows:
1. Bed rest and reassurance.
2. Tranquiliser: Diazepam (5-10 mg parenterally) to allay
the anxiety.
3. Posture: Recumbent position and encourage to lie on
the affected side of the chest, to immobilise the bleeding
area and minimise aspiration as well as spread into the
healthy areas.
4. Fluids or blood transfusion: Start crystalloids or colloids
IV infusion. Keep the blood ready, to be transfused if
the bleeding is profuse.
5. Haemostatics: (i) Adrenochrome or ethamsylate
(ii) calcium gluconate and (iii) vitamin-K (iv) haemo-
coagulase (botropase) may be given parenterally to
promote clotting, though none may be that effective.
6. Antibiotics: (i) A routine five-day course of antibiotics
is useful in preventing secondary infection of the blood
remaining in the bronchopulmonary area; (ii) If the
underlying cause is bronchiectasis, oral ampicillin or
cephalosporins 250 mg 6 hourly is given initially and
alternative antibiotics administered for 7-10 days as per
the culture and sensitivity of the sputum examination,
apart from postural drainage; (iii) If tuberculosis is
incriminated antituberculous treatment given (vide infra)
7. Antitussive: Linctus codeine or dextromethorphan or
noscapine may be used to suppress the cough, if
troublesome (suppressing the cough may endanger
aspiration pneumonia).
8. Bronchoscopy: Aspiration of blood from the bronchial
tree may be occasionally needed to prevent atelectasis.
9. Endobronchial tamponade: On rare occasions, by means
of flexible bronchoscope, a Fogarty catheter with balloon
is passed into the site of bleeding and the balloon is
inflated to undertake further surgical measures and
selective bronchial artery embolisation.
Respiratory
Infections
Pulmonary tuberculosis
a. General treatment: Rest, good nutritious diet,
isolation of the open cases.
b. Specific treatment
i. Chemotherapy and
ii. Rarely surgery.
i. Chemotherapy: The duration of course of primary
chemotherapy may be either six months (Rifampicin
(450 ml) + isoniazid (300 mg) + pyrazinamide (1500
mg) + etnambutol (800 mg) (Pyrazinamide is given for
first-two months only); or streptomycin (1 gm) daily)
given for two months followed by rifampicin + isoniazid
for four months); or nine months (rifampicin + isoniazid
+ ethambutol or streptomycin given for two months
followed by rifampicin + isoniazid for seven months.
Pyridoxine (10 mg) may be given to prevent possible
peripheral neuropathy due to isoniazid. Corticosteroid
drugs may be considered in acute cases for about six
weeks and if necessary continued for twelve weeks
specially in fulminating cases.
Drug resistant infections need additional drugs
(second line) like PAS (5 g.b.d. orally), ethionamide (0.5
g.b.d. orally), prothionamide (0.5 g.b.d. orally),
cycloserine (0.25-1 g.b.d. orally), oflaxacin (400 mg bd)
or ciprofloxacin (750 mgbd) orally, kanamycin
(0.75-1 g i.m. once daily). Amikacin (0.75-1g IMld)
Viomycin (0.5-1 g i.m. twice daily) and capreomycin
(0.75-1 g i.m. once daily). If possible the pattern of drug
resistnce may be detected on the basis of culture and
sensitivity studies and then the drug combination is to
be decided, using at least two second line drugs along
with two primary drugs, for 18 to 24 months, like
kanamycin and isoniazide along with PAS and
ethionamide for 6 months and later ethionamide, PAS
and isoniazid for 12 months. Three new drugs (not used
before) should be started. Cross resistant drugs avoided
4 to 6 drugs. (Primary or secondary drugs) advocated
parenteral drugs used only for 3-6 months.
Nevertheless, relapsed cases or poor compliance
causes with therapeutic failure wherein drug sensitivity
shows full susceptibility of organisms to primary group
of drugs, are treated for 8-10 months with the following
regimen.
 Haemoptysis
Five drug regimen—Rifampicin, isoniazid,
pyrazinamide, ethambutol and streptomycin, for 2
months, and
Four drug regimen—Rifampicin, isoniazid,
pyrazinamide and ethambutol, for 1 or 2 months, and
Three drug regimen—Rifampicin, isoniazid and
ethambutol, for 5 or 6 months.
Retreatment programme with second line drugs must
be considered, if therapeutic response is poor and when
culture and sensitivity studies are not possible.
Antituberculosis drug induced hepatotoxicity, i.e.
more than 3 times upper normal limits of transaminases,
calls for nonhepatotoxic drugs like streptomycin,
Ethambutol and quinolones temporarily. Once liver
function test normalises, i.e. less than two times the upper
normal limits of transaminases, the first line drugs re-
introduced slowly under close supervision.
ii. Surgical treatment—Pulmonary resection is rarely
required.
Chronic bronchitis
a. Avoid bronchial irritation by stopping smoking and
avoiding dusty atmosphere.
b. Control cough and facilitate expectoration with suitable
cough mixtures including mucolytics.
c. Treat respiratory infection promptly with appropriate
antibiotics.
d. Inhalation of salbutamol is beneficial, for the airway
obstruction.
e. Occasionally low concentration oxygen therapy for
about 16 hours in the course of a day may be beneficial
in hypoxaemic patients.
f. Mechanical ventilation is rarely required.
Bronchiectasis
a. Check underlying cause, including sinusitis.
b. Expectorants and mucolytic agents are beneficial.
c. Institute appropriate antibiotic therapy to keep infections
under check.
d. Clear the bronchial secretions by physiotherapy—
postural drainage for at least 5-10 minutes twice daily,
adopting a position wherein the lobe aimed to be drained
is uppermost, to facilitate the maximum drainage by
gravitation, and/or postural percussion.
e. Surgical treatment—resection for the affected pulmonary
segments.
Pneumonia Refer to Chapter ‘Chest Pain’.
Lung abscess Prolonged treatment with antibiotics as per
the results of culture and sensitivity examinations of the
257
sputum for 4-6 weeks is necessary. If the sputum is of
foetid odour, anaerobic abscess is to be suspected and treated
with metronidazole orally or parenterally. Postural coughing
may be beneficial. If the abscess becomes chronic, surgical
resection may be required.
Tropical eosinophilia Diethylcarbamazine (100 mg tds) for
10 days is given. If necessary a short course of prednisolone
for one week may be considered.
Parasitic lung diseases Paragonimiasis Praziquantal 25
mg/kg b.d. is given for 2 days orally. Bithional 15 mg/kg on
alternative days in divided doses for 3-4 weeks orally is
also reported to be effective. For localised lesions, surgical
treatment may be necessary.
Fungal lung disease Aspergillosis Amphotericin 0.25-2
mg/kg daily IV slowly alone with flucytosine 150-200 mg/
kg daily orally in divided doses is effective for invasive
cases. Aspergilloma needs surgical removal as antifungal
therapy is not of value.
Malignancy
Bronchogenic carcinoma of the lung Treatment is directed
as per the type of bronchial carcinoma. Treatment for
(1) non-small-cell lung cancer is essentially surgery and/or
radiotherapy. Inoperable cases are treated with 3000 rads
followed by combination chemotherapy. Cyclophosphamide
(400 mg/m2) IV, adriamycin (40 mg/m2) IV, methotrexate
(40 mg/m2) IV, lomustine or CCNU (30 mg/m2) given orally
and repeated every 3 weeks are beneficial recently.
Gemcitabine and Carboplatin or Paclitaxel + Carboplatin
achieved response rate as high as 50%. Biologic therapy:
Gefitinib (250 mg/d) improves well-being though response
rate is 10-18%.
Treatment for (2) small-cell (oat) lung cancer is
essentially chemotherapy with or without radiotherapy. The
commonly used combination therapy is as follows: vindesine
(3 mg/m2) IV, on day 1 and VP-16 or etoposide (120 mg/
m2) IV on day 2 and 3 (6 pulses of this treatment at 3 weeks
intervals). Etoposide with either cisplatin or carboplatin is
also recommended.
Yet another effective regimen for more agressive therapy
is cyclophosphamide (400 mg/m2) IV, adriamycin (40 mg/
m2) IV, and vincristine (2 mg/m2) IV, every 3 weeks.
Though different combinations are in vogue, doxoru-
bicin (adriamycin), cyclophosphamide and etoposide
combination preferably with vincristine is said to be
effective.
Laser therapy through bronchoscope is palliative, if
bronchial obstruction is present.
 258 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Bronchial Adenoma
Surgical resection of the bronchus containing the tumour
along with the pulmonary segment, if necessary is indicated.
Traumatic
Foreign Body
An inhaled foreign body, which usually gets lodged in the
right main bronchus, is extracted by bronchoscopy or
bronchotomy. If suppurative pneumonia in the collapsed lobe
exists, appropriate antibiotic therapy is instituted.
Lung Contusion
Since the elasticity of the lungs is decreased and the
resistance to air flow is increased in lung injury, mechanical
ventilation support is needed to facilitate adequate alveolar
ventilation and reduce the work of breathing. Blood gases
should be monitored to maintain optimum arterial saturation.
Supportive hydration or blood transfusion with central
venous pressure control is necessary. Supranormal delivery
of oxygen to tissues, prevents multiple organ failure.
Circulatory support with inotropes and control of sepsis are
mandatory.
Lung biopsy (Iatrogenic) Symptomatic treatment and if
necessary, blood transfusion are indicated.
Cardiac
Mitral Stenosis
Though surgery (balloon valvuloplasty or mitral valvotomy
or valve replacement) is the ultimate treatment, medical
management may be feasible if symptoms are not disabling.
This consists of treatment of congestive heart failure (Refer
to Chapter ‘Oedema’), atrial fibrillation (Refer to Chapter
‘Palpitations’), anticoagulants to prevent systemic embolism
and antibiotics to prevent infective endocarditis. Diuretics
may be necessary for episodic pulmonary congestion.
Physical exertion and excess sodium intake are avoided.
Systemic Hypertension
Refer to Chapter ‘Headache’.
Pulmonary Hypertension
a. Eliminate causative factors. Surgical correction of
underlying cause may be undertaken.
b. Reduce resistance to pulmonary blood flow with
pulmonary vasodilators (nitroglycerine; nifedipine; ACE
inhibitor, hydralazine, or phentolamine) and oxygen.
c. Administer anticoagulants, if recurrent pulmonary
embolism is associated with pulmonary hypertension.
d. Improve the disturbed cardiovascular status due to right
ventricular pressure overload with diuretics and inotropic
agents like digoxin.
e. Sildenafil may be beneficial.
Left heart Failure
Refer to Chapter ‘Dyspnoea’.
Vascular
Pulmonary embolism and infarction: (Refer to Chapter
‘Chest Pain’)
Arteriovenous malformation: (Refer to Chapter ‘Cyanosis’)
Vasculitides
Polyarteritis nodosa: (Refer to Chapter ‘Polyarthritis’)
Wegener’s granulomatosis: Corticosteroids (1 mg/kg) may
be administered in tapering doses for 6 months along with
cyclophosphamide (2 mg/kg orally daily) for one year after
complete remission. Azathioprine (2 mg/kg orally daily) is
an alternative to cyclophosphamide.
Good pasture’s syndrome: (Refer to Chapter ‘Haematuria’)
Haemosiderosis: Corticosteroids may be considered.
Anaemia, if present requires iron therapy.
Aortic Aneurysm: Rupturing through eroded Bronchus.
Apart from symptomatic treatment, resection of the
aneurysm and grafting of the aortic defect may be considered
if technically feasible.
Bleeding Diathesis
Refer to Chapter ‘Bleeding Disorders’.
Idiopathic
Symptomatic treatment is indicated. On follow-up, if
pulmonary tuberculosis develops, it may be treated
accordingly.
Haemoptysis 259
260 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Headache
17
The term headache or cephalalgia includes unpleasant pain
sensations in any region of the cranial vault. Though this
does not carry much of clinical significance in majority of
cases, at times, it may be first symptom of a serious disorder.
Hence, one should approach this common clinical problem
with utmost care and alertness.
1. Acute single episode, e.g. Meningitis
2. Acute recurrent attacks, e.g. Migraine
3. Chronic and continuous, e.g. Tension headache
MECHANISM OF HEADACHE
The cranium and brain are insensitive. But structures
surrounding the cranium like skin, muscles, arteries, nerves,
periosteum of the skull, and nasal cavities are pain sensitive.
Similarly, within the cranium the venous sinuses and theri
tributaries, dural and cerebral arteries, dura (anterior and
posterior fossa only), cranial nerves like trigeminal,
glossopharyngeal, vagus and upper three cervical nerves
have receptors for pain. Stimulation of these structures
provokes the pain and the sensation is carried to the thalamus
through trigeminal nerve for supratenotorial structures and
9th, 10th and upper three cervical nerves for infratentorial
structures. The visceral diseases are associated with pain
referred to the superficial tissues of the scalp. This referred
pain is explained on the basis, that the trigeminal nerve is
the somatic sensory nerve corresponding to the vagus.
Main Factors Responsible for the Headache
1. Tension in the muscles usually psychological
2. Inflammation of the bones of the cranium
3. Dilatation of the vessels
4. Compression or traction of the nerves
5. Altered CSF flow, e.g. meningeal irritation, lowered
intracranial pressure, and tumours
6. Referred pain
CAUSES OF HEADACHE
Causes of headache are listed in Table 17.1.
Vascular Headache
Migraine (Sick Headache) The term is derived from ‘Megrim’
which means hemicrania. It is characterised by acute
paroxysmal headaches which are usually unilateral,
associated with photophobia, phonophobia and vomiting.
There clinical syndromes are identified:
1. Classic or neurological migraine
2. Common or atypical migraine
3. Symptomatic migraine
The classic or neurological migraine consists of three phases
i. Transitory neurological aura (visual, sensory or motor)
due to initial vasoconstriction
ii. Headache which is due to vasodilation, associated with
photophobia and/or phonophobia
iii. Gastrointestinal disturbances like vomiting, which may
relieve headache.
Visual aura consists of (a) a bright spot in the centre
expanding towards the periphery with scintillating figures
at the spreading edge (teichopsia), which may be coloured
(fortification spectra); (b) scotoma; and (c) hemianopia.
Apart from these varying flashes of light, rarely paraesthesia
and numbness of both the hands and circumoral area or
weakness of one-half of the body may be experienced with
or without mood disturbance. These neurological
disturbances last for about half an hour and followed by
unilateral (right or left) rarely bilateral, headache with
throbing or jabbing or boring quality. The presentation is
stereotyped. Gastrointestinal disturbances and vasomotor
changes like pallor, sweating, cold extremities may be
conspicuous and this attack lasts usually for two hours to
two days. It may be complicated by residual neurological
 262 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 17.1: Causes of headache

1. Vascular Headache
i. Migraine
ii. Cluster headache
iii. Hypertension
iv. Toxic-infective—uraemia, alcohol, industrial toxaemia,
typhoid, nitrites, vitamin A excess, heat exhaustion
v. Giant cell arteritis
vi. Carcinoid syndrome
vii. Hyperviscosity syndrome
2. Musculoskeletal
i. Tension headache
ii. Cervical fibrositis
iii. Cervical spondylosis
iv. Osteitis of the cranial bones
3. Neuritides
i. Neuritis
ii. Neuralgia
4. Meningeal Fig. 17.1: Magnetic resonance angiography showing
i. Meningitis microaneurysm of the left internal carotid artery
ii. Subarachnoid haemorrhage
5. Space Occupying Lesion
i. Intracranial tumour (Fig. 17.1) or anti-phospholipid syndrome. The headache is
ii. Cerebral abscess invariably unilateral and may be associated with focal
iii. Subdural haematoma neurological signs.
6. Altered CSF Flow
i. Hydrocephalus The variants of migraine are:
ii. Postlumbar puncture
Basilar artery migraine It is due to ischaemia of hindbrain
iii. Pseudotumour cerebri or benign intracranial hypertension
7. Trauma—Head Injury circulation and is usually associated with vertigo, staggering,
8. Referred Pain diplopia and drowsiness.
i. Ocular
Ophthalmoplegic migraine Recurrent attacks of unilateral
ii. Dental
iii. ENT—sinusitis headache with paralysis of extraocular muscles.
iv. Temporomandibular joint dysfunction Retinal migraine Recurrent attacks of retinal ischaemia may
9. Anoxaemia and hypercapnia
lead to bilateral optic atrophy.
i. Anaemia
ii. Emphysema Facioplegic migraine Recurrent hemifacial paralysis is an
iii. Poisons uncommon variant.
10. Psychogenic
i. Anxiety Abdominal migraine In children, abdominal pain and
ii. Depression vomiting may accompany migraine.
iii. Fatigue
iv. Insomnia Childhood paroxysmal vertigo It may manifest as simple
v. Sick headache evasion syndrome vertigo with or without headache.
The aetiology of migraine is complex. It may be
hereditary and starts in early adulthood continuing up to
deficit due to irreversible ischaemic damage (hemiplegic late middle life, more often in women. It is triggered by
migraine). refractive errors, dietitic factors like cheese, chocolates
Common migraine consists of unilateral headache, with containing tyramine, psychological stress or menstruation.
sides alternating, and nausea. Vomiting and visual It appears there is disruption of blood brain barrier, rendering
complaints are rare. The aura are absent. the alteration in the cerebral circulation by the vasoactive
Symptomatic migraine is caused by an intracranial substances like amines (serotonin) or plasma kinins. An
vascular anomaly like intracranial aneurysm or angioma initial vasoconstriction followed by vasodilatation of
 Headache
cerebral and extracranial blood flow, accounts for the aura
and headache. The patient with migraine is often
conscientious type of personality endeavouring to be a
perfectionist.
Cluster Headache
(Migrainous Neuralgia or Horton’s Syndrome)
The name is derived from the nature of the attacks which
consists of repeated bouts of headache daily usually lasting
for 6 to 12 weeks, rarely spreading over a year with freedom
from attacks for one year, before another cluster of
headaches begin. It is unilateral confined always to the orbit
or temple with nonthrobbing character (same orbit affected
in each attack). The eye becomes red and watery with
swelling of the lid and miosis. The face also may turn red
and ipsilateral nasal congestion and rhinorrhoea. It can occur
at anytime of the day more during the night times after about
two hours of sleep or sometimes during day and night. The
attack lasts for 20 to 60 minutes. There are two varieties:
(a) upper syndrome and (b) lower syndrome. The upper
syndrome consists of pain around the eye spreading to the
vertex or occiput. The lower syndrome consists of pain in
the cheek and jaw with partial Horner’s syndrome and
ipsilateral hyperhidrosis. It is usually seen in middle aged
men and may be triggered by alcohol, emotional stress or
nitroglycerine or histamine.
Hypertension
The headache in hypertension is not related to the height of
pressure but due to vasodilatation with consequent stretching
of the surrounding sensitive structures and increased
intracranial venous pressure. The headache is mostly in the
morning hours and felt in the temporal region and all over
the head. It is reduced by rest and increased by mental and
physical strain.
In ischaemic strokes, headache is usually mild due to
vasodilatation of the surrounding vessels, whereas in
haemorrhage, the headache is severe on the side of lesion
(Refer to Chapter ‘Palpitations’).
Toxic-Infective
Changes in the permeability and their calibre are likely to
cause headache accompanying the toxi-infective states. It
is like histamine headache relieved by pressure over the
carotid artery on one side or jugular compression on both
sides. Toxaemia due to enteric fever or uraemia, poisons
like lead or drugs like nitrites, excess of vitamin A, and
263
alcohol bouts may account for headache. Hence, the
importance of taking history in this direction. Acute episodic
headaches are common in heat exhaustion and heat stroke,
the pathogenesis of which may not only be associated with
salt and water deficiency but failure of cardiovascular
response to external high temperature.
Giant Cell Arteritis
This is an infrequent cause of headache usually in the elderly
people. This is uni or bitemporal, throbbing headache. Onset
may be sudden accompanied by fever, combing or touching
the scalp may be unpleasant. The arteries are thickened,
tender and pulseless. ESR is raised.
Carcinoid Syndrome
Flushing, blotchy skin, and red hands may be associated
with severe headache in this syndrome. (Refer to Chapter
‘Diarrhoea’)
Musculoskeletal
Tension Headache
It is usually bilateral or occipital extending often to the top
of the head or temporal or frontal region. There may be a
feeling of pressure or dull pain, nonthrobbing in character.
It tends to occur late in the day and worsens as the day
advances, persisting continuously for hours or days or even
weeks.
Tenderness or nodular areas may be present over the
scalp or posterior neck muscles or over the occipital and
supraorbital ridges. Neck muscles may be stiff. The
mechanism of this headache seems to be muscle contraction
associated with psychological stress (anxiety or depression
or situational stress). The onset is in adolescence or
adulthood with no familial background.
Cervical Fibrositis
Cervicogenic headache may be produced by the fibrositis
of the neck muscles. The aches may be localised to the back
of the head and may extend to other regions. The movements
of the neck may elicit pain and restrict the movements.
Cervical Spondylosis
Spondylosis of the cervical vertebrae may cause occipital
or sometimes frontal headache. Secondary muscle spasm
may contribute to prolonged pain or it may be caused by
irritation of the cervical nerve roots. Sometimes the pain
 264 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
may radiate to the arms. The movements of the neck may
be painful and limited. Diagnosis is confirmed by the
degenerative changes seen in the skiagram of the cervical
spine and by reproducing or aggravating the pain on full
range of neck movements (Refer to Chapter Pain in the
Extremities).
Osteitis of the Cranial Bones
Headache due to osteitis is burning or borning in character
with tenderness of the scalp. Radiography demonstrates
characteristic changes like mottling of the thickened bone
with islands of osteoporosis in the bones. Osteitis deformans
(Paget’s disease), may cause headache.
Neuritides
Neuritis and Neuralgia
Headache may be due to neuritis and neuralgia of the
supraorbital, auriculotemporal, great occipital or trigeminal
nerves. The pain tends to follow the nerve distribution, e.g.
one of the divisions of the trigeminal nerve or sensory
divisions of C1 to C3 roots. Tenderness of the nerves and
hyperalgesia of the affected region may be present.
The characteristic features of trigeminal neuralgia is short
paroxysms of severe lancinating unilateral pain lasting few
seconds and confined to trigeminal distribution. The agonising
pain may provoke a facial twitch. The paroxysms may
continue to occur for days or weeks followed by remission.
Objective sensory loss is absent. It is usually seen in people
over 50 years and the pain is precipitated by exposure to cold
air or washing the face or chewing. After an attack of herpes
zoster of the 5th nerve, persistent neuralgic pain with
hyperalgesia occurs after the vesicles disappear.
Meningeal
This meningeal irritation may be due to infections like
meningitis or subarachnoid haemorrhage.
Meningitis
In meningitis the headache is increasingly severe, constant
and bursting in character and radiates down to the neck and
back, lasting for days to a week. Signs of meningeal irritation
(meningism) like nuchal rigidity, and positive Kernig’s sign
and Brudzinski’s sign, photophobia and fever are associated.
The common causes are pyogenic (pneumococcus or H
influenzae or E. coli) or tuberculous or viral infections of
the pia mater and arachnoid. The diagnosis is confirmed by
CSF analysis, i.e. appearance, cells, protein, glucose and
organisms.
Subarachnoid Haemorrhage
In subarachnoid haemorrhage, a normal person complains
of headache which is severe and sudden radiating down the
neck and spine. There may be associated signs of meningeal
irritation, cranial nerve palsies, drowsiness with or without
hemiplegia and coma may become prolonged. The common
causes are ruptured aneurysms or arteriovenous
malformations or a bleeding tendency. The diagnosis is
confirmed by lumbar puncture. If the CSF is bloody, it is
due to haemorrhage. Sometimes traumatic lumbar puncture
may result in a bloody CSF. This is differentiated by
centrifuging the fluid, when the supernatant fluid is
xanthochromic in haemorrhage as against colourless nature
in traumatic puncture. Fundus examination may show
subhyaloid haemorrhage (below the lens). CT or MRI,
angiographic studies diagnostic.
Space Occupying Lesions
Intracranial Tumour
The general symptoms like headache, papilloedema, and
vomiting often indicate space occupying lesion. It is
unilateral in the early stages and throbbing or bursting in
character; often occurs in the early morning, sometimes
nocturnal, lasting for few minutes to one hour and passes
off as the day advances. The duration of headache may get
prolonged as the disese progresses until it becomes
continuous and diffuse. It is aggravated by coughing or lying
or stooping and is relieved by sitting.
The headache is due to traction on the cerebral blood
vessels with consequent abnormal states of tension, and
raised intracranial pressure. (Intracranial hypertension
results from cerebral oedema due to obstruction of venous
drainage and interference with CSF circulation.) The other
features of raised intracranial pressure like vomiting which
is not preceded by nausea (projectile), papilloedema and
visual failure develop. Localising signs with or without fits
depend upon local irritation cum damage at the site of the
tumour or shifting of intracranial contents by the increased
pressure. The diagnosis is confirmed by accessory investi-
gations of radiography, angiography, encephalography or
CT scanning or MRI.
The intracranial tumours may be (i) encapsulated,
noninfiltrating (meningioma or acoustic neuroma);
(b) infiltrating malignant like gliomas; (c) pituitary
adenomas; (d) blood vessel tumours (angioma); (e) infective
(tuberculoma); and (f) cysts (colloid).
 Headache
Cerebral Abscess
Intracerebral abscess may occur after head injury or otitis
media, presenting as headache, drowsiness and vomiting
associated with fever or focal signs. A chronic abscess may
behave very much like a cerebral tumour. The common
modes of infection may be local spread from an infected
focus or a metastatic spread from cardiopulmonary
infections.
Subdural Haematoma
Blood slowly accumulates in the subdural space resulting
in a subdural haematoma due to trauma or infections or
malignancies of dura or bleeding disorders. The symptoms
may follow immediately after an injury or most often after
a latent interval of several months. Headache, localising
signs, personality changes, fluctuating character of the
drowsiness or confusion with a dilated fixed pupil are highly
suggestive of a subdural haematoma (Refer to Chapter
‘Coma’).
Altered CSF Flow
Hydrocephalus
The CSF pressure is increased in conditions associated with
increased intracranial pressure like meningeal reaction and
space occupying lesions. An increase in the volume of the
CSF within the skull with or without increased pressure
(normal 50 to 180 mm of water) is the essential feature of
hydrocephalus. Headache which is paroxysmal in the early
stages becomes constant and radiates down the neck.
Vomiting, papilloedema and other features distinctive of
increased intracranial pressure may follow (Refer to
Chapters ‘Paraplegia’ and ‘Coma’).
Post-lumbar Puncture
The intracranial pressure may be lowered as occurs after a
lumbar puncture. The headache which is throbbing is
intensified by sitting and relieved by lying unlike in
increased intracranial pressure.
Pseudotumour Cerebri
The intracranial pressure may be raised without a space
occupying lesion in pseudotumour cerebri or benign
intracranial hypertension. Several conditions like intracranial
venous thrombosis or head injury or excess of steroids or
vitamin A, severe anaemia and chronic obstructive
pulmonary disease are some of the recognisable causes. At
265
times, the cause may not be obvious, although this is
common in obese young women. Headache, vomiting,
papilloedema and visual disturbances may be present
without focal neurological signs. Secondary optic atrophy
and permanent visual loss may ensure if untreated. The
lumbar puncture reveals presence of increased CSF pressure
with normal CSF. Further investigations like CT scan or
MRI even do not show any abnormality.
Trauma (Head Injury)
Post-traumatic headache like a postcontusional syndrome
may be associated with localised headache, giddiness,
inability to concentrate after a minor closed head injury.
The headache appears within a day or so, worsens for few
weeks and then subsides. It is a constant or intermittent dull
ache intensified by exertion or noise or alterations in posture.
Neck injuries involving carotid sheath may result in severe
paroxysmal throbbing unilateral headache with ipsilateral
dilated pupil and facial sweating due to sympathetic
dysfunction (post-traumatic dysautonomic cephalalgia).
Referred Pain (Reflex Headache)
Headache may be due to:
a. Ocular diseases (glaucoma or refractive errors or
iridocyclitis) cause supraorbital or retro-orbital headache
b. Inflammation of sinuses (sinusitis) cause pain in the
frontal region or ear infections.
c. Dental infections or irritations (apical abscess, caries or
impacted teeth)
d. Dysfunction of temporomandibular joints (temporo-
mandibular arthritis due to over closure of the jaws
leading to forward sliding of the mandibular condyle or
inflammatory synovitis).
These conditions cause headache reflexly through
trigeminal nerve and upper cervical nerves as the latter join
the descending tract of the fifth cranial nerve.
Anoxaemia and Hypercapnia
Anoxaemia
Anaemia is a classical example for causing headache due
to anoxaemia. Since, the brain cannot store energy nor
function by anaerobic metabolism, it is highly susceptible
to disorders of cerebral circulation. Probably this explains
the rhythmical beatings or throbbing within the head.
In emphysema, not only hypoxaemia but chronic cough
may account for severe head pain.
 266 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Similarly poisons like carbon monoxide, carbon dioxide,
etc. may account for headache due to anoxaemia. In the
former if carboxy-haemoglobin is >50%. Seizures, coma
may results apart from headache, vomiting, tachypnoea.
Hypercapnia (Rise in arterial PaCO2 )
It indicates that alveolar ventilation is inadequate for
metabolic needs. When hypercapnia is chronic, early
morning headaches result.
Psychogenic Headache
Headache may be complained of in emotional upsets and
fatigue states. The ache may be a feeling of pressure or tight
band over the vertex persisting constantly without
responding to analgesics. Assessment of psychic status may
unfold the underlying anxiety reaction, with a sense of fear
and insecurity or depression or hypochondriasis or
conversion hysteria. The pain may be constant, spreading
over months or evey years. A depressed patient, usually a
middle aged female, may complain of pain which is usually
continuous starting in one cheek spreading to the neck or
behind the ear or opposite side of the face. There will be no
organic causes to account for headache in these cases. Lack
of sleep or withholding the drugs may be forthcoming.
Headache may be used as an excuse for avoiding certain
situations. And this is particularly encountered in migraine
subjects, which is termed as sick headache evasion
syndrome.
CLINICAL APPROACH
Certain queries have to be made in precision to arrive at the
diagnosis of the cause of headache; whether it is due to (a)
intracranial, (b) cranial (c) extracranial or (d) systemic causes
(hypertension, anaemia, constipation, premenstrual time).
Although diagnosis can be made on the history alone in
most of the cases, particular attention must be bestowed to
distinguish a presumed trivial headache from that of a
potential underlying serious condition.
History
Document in detail the following aspects.
Location and Direction of Spread
This may be in the frontal (frontal sinusitis or eye strain);
temporal (temporal arteritis); occipital (cervical spondylosis
or subarachnoid haemorrhage); over vertex regions
(psychoneurosis); or unilateral (migraine) or bilateral
(tension headache) or diffuse (head injury). Unilateral
headache when becomes bifrontal or bitemporal, it indicates
increased intracranial pressure.
Character
The quality of pain may be dull aching with feeling of
tightness or pressure (musculoskeletal) or superficial
stinging or darting or burning (neuralgia) or throbbing
(hypertension) or bursting (intracranial tumour).
Intensity
Is it a mild, moderate and severe pain or variable?
Duration and Frequency
a. Is it chronic being persistent or continuous for days
together, with slight variations (tension headache)?
b. Is it paroxysmal and recurring lasting for hours
(migraine)?
c. Is it momentary lasting for seconds (neuralgia)?
d. Is it acute first single episode (subarachnoid
haemorrhage)?
e. Total duration of the headache including the duration of
each paroxysmal attack.
Periodicity
a. Does it occur in the early morning hours (intracranial
tumour)? The pain is severe in the morning and less as
the day passes off.
b. Does the pain occur in the evenings (eye strain, mental
strain) or night time disturbing the sleep (cluster
headache)?
Age and Sex
a. Is the onset of headache since childhood, or early
adulthood or more common in women as in migraine?
b. Is the onset after the age of 50 years as in temporal
arteritis or subdural haematoma (more in men).
Aggravating and Relieving Factors
Stuffy rooms, excessive smoking, alcoholic indulgence, lack
of sleep, mental or eye strains. Sometimes constipation are
some of the aggravating factors. Headache aggravating by
stooping or recumbency is specific in intracranial tumours.
It may be relieved by rest in the horizontal position
(functional and post-lumbar puncture) or applying pressure
with palms over the scalp (tension headache). The pain is
relieved in the upright position (sinusitis). Does cough
trigger headache? Overuse of analgesics and stopping the
same may result in rebound headache.
 Headache 267

Associated Symptoms Examination of Oral Cavity

Any visual disturbances, nausea and vomiting (migraine) a. Is there any caries tooth?
or vomiting without nausea, vertigo and fits (intracranial b. Is the tongue pale?
tumour), nasal obstruction or discharge (sinusitis), acute c. Is the throat congested?
fevers of any cause; or any anxiety, depression
(psychogenic). Examination of the Neck
History of Trauma or Hypertension or Bleeding or any
a. Range of cervical movements
Refraction Problem or Episodes of Nasal Discharge, etc.
b. Is there any tenderness over the nape of the neck?
c. Is the pain provoked on movements of the neck?
Family History
d. Compress the jugular vein and see whether the headache
Common in migraine and hypertension. is increased.
e. Compress over the carotid arteries to see whether the
Scheme of Examination headache is relieved.
The point of prime importance is to decide whether headache
Examination of the Chest
is with physical signs or without abnormal signs. Incidentally
the personality of the patient must also be assessed. Look for:
a. Cardiomegaly
General Examination b. Accentuation of the second sound in aortic area
c. Murmurs
a. Evidence of anaemia
d. Any evidence of emphysema or COPD with diminished
b. Vital signs
vesicular breath sounds.
i. Blood pressure to be recorded.
ii. Pulse—whether tachycardia or bradycardia? (Falling
CNS Examination
pulse and rising blood pressure suggest space
occupying lesion). A systematic examination in the conventional order
iii. Respirations—slow or fast or normal? including
iv. Temperature—elevated or normal? a. Meningeal irritation
c. Sensorium—altered or not? b. Acuity of vision, fundi for papilloedema and pupillary
changes
Systemic Examination c. Signs of focal neurological damage.
Examination of the Head
Psychic Status
a. Look for tenderness of the scalp or hyperaesthesia.
Anxiety, depression or hypochondriasis.
b. Look for any depressed fractures or burr holes.
c. Any tender thickend pulseless arteries over the temporal
Investigations
region.
d. Auscultate the cranium for any intracranial bruit. 1. Urine examination for evidence of disorder of renal
system
Examination of the Face 2. Blood—RBC, haemoglobin TC, DC, ESR, VDRL,
a. Tenderness over the sinuses area (frontal and maxillary) Alkaline Phosphatase (Raised markedly in pagets
b. Any nasal stuffiness or any discharge from the nose and disease)
ears 3. Refraction test and fundus exam
c. Redness and watering of the eyes 4. Lumbar puncture and CSF analysis if indicated
d. Pallor of the conjunctiva 5. Radiology
e. Increased ocular tension—gentle palpation of the closed i. X-ray of (a) sinuses, (b) chest, (c) cervical spine and
eye; recording of intraocular pressure (d) skull; (e) pan oral views of the jaws
f. Any temporomandibular joint involvement ii. Angiography and digital subtraction angiography if
g. Hyperaesthesia over the trigeminal areas indicated
h. Depressed facies. iii. CT Scan (Fig. 17.2)
 268 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 17.2: Cranial CT scan showing well defined high density
mass over the left parietal parasagittal region adjacent to falx
with inferior extension up to corona radiata of left parietal
region—Meningioma
Fig. 17.3: Carnial MRI showing butterfly tumour
(glioma) of the corpus callosum
iv. Radioactive isotope brain scan
v. Magnetic Resonance Image (MRI) (Fig. 17.3).
6. EEG
7. Biopsy of the temporal artery
8. Psychiatric assessment—(a) Psychologic testing with
objective and projective tests (thematic apperception
test); (b) Abreaction test with pentothal or methidrine.
The list of the investigations mentioned above may not
be necessary in each case of headache. They have to be
judiciously used as the occasion demands.
TREATMENT OF HEADACHE
The clinician must recognise the pattern of pain, occurring
anywhere from the orbit back to the suboccipital area and
decipher its aetiopathogenesis, before planning the thera-
peutic protocol. Obvious precipitating factors and other
symptoms accompanying headache, invariably offer the
diagnostic clues. Most often it is of extracranial origin
(tension headache, cervical spondylosis, or referred from
adjacent structures) rather than cranial (osteitis) or intra-
cranial causes (meningeal, vascular and space-occupying
lesions). Recurrent or continuous headache over a period
of time, without neurological features or characteristic
presentations, may point towards a psychogenic basis.
However, prior elimination of possible organic cause of
headache is mandatory, before psychogenic headache is
entertained. Comprehensive investigations may be necessary
in some cases.
Symptomatic Treatment
(Before Establishing Clinical Diagnosis)
1. Remove any trigger factor.
2. Readjust lifestyle.
3. Non-narcotic analgesics (paracetamol, aspirin and
NSAIDs) are given according to the intensity of pain
(Refer to Chapter ‘Low Backache’).
4. Mild narcotics like codeine or propoxyphene can be
resorted to.
5. Avoid major narcotics.
6. Other treatment modalities are.
a. Relaxation therapy
b. Psychotherapy
c. Behavioural modification
d. Biofeedback therapy.
Specific Treatment of Specific Diseases
Vascular Headache
Migraine
The therapy consists of treatment of an acute attack with
5HT agonists (ergotamine and sumatriptan) (25-100 mg)
with or without analgesics and prophylaxis.
i. During acute attack—Ergotamine tartrate 1 to 2 mg
given at the onset of headache 12 mg/week. Dihydro-
ergotamine 1 mg given intramuscularly in severe
 Headache
headache and repeated (0.5 mg to 1 mg) every 8 hours
up to a maximum of 3 mg/d if necessary. Also it can be
given sublingual 2 mg up to 6 mg maximum. Relief
from the attack is due to constriction of extracerebral
arteries. Frequent use may lead to peripheral
vasoconstriction and gangrene. Sumatriptan (50-100
mg) is recommended soon after attack. (should not
exceed 300 mg in 24 hrs). Rizatriptan (10 mg) is
another antimigraine drug. In established phase,
promethazine hydrochloride 25 to 75 mg or
metoclopramide 10 mg or prochlorperazine (10-15 mg)
may be considered for further amelioration. Simple
analgesics like aspirin or paracetamol (with or without
metoclopropamide) or NSAIDs are useful adjuncts.
ii. Prophylaxis—This constitutes two aspects, i.e.
avoiding precipitating factors and drugs. The daily
maximum doses are flunarizine (5-10 mg), propranolol
(80-160 mg), amitryptyline (10-150 mg), and
cyproheptadine (12-20 mg) are usually advocated.
Other drugs suggested are ergonovine maleate (0.6-2
mg), methysergide 2-8 mg (should not be given for
more than 4 months); clonidine (0.1-0.2 mg), verapamil
or diltiazem (120-240 mg), phenelzine (15-75 mg)
Pizotifen (1.5-3 mg). Antiepileptic drugs like sodium
valproate (extended releaseform) and topiramate are
effective (Preventive medication is given for 6 months
or longer even and withdrawn gradually after frequency
of attacks subsides).
iii. Status migrainosus—Dihydroergotamine and
metoclopramide or prochlorperazine are useful most
often. Amitriptyline and parenteral NSAIDs may be
supplemented. Some advocate prednisolone (100 mg/
d) and taper rapidly over 4-7 days.
iv. Migraine variants—Other transient symptoms
associated with headache are effectively treated with
calcium channel blockers (verapamil and diltiazem).
Nifedipine is not favoured as it causes cerebral
vasodilatation. Drug prophylaxis may be necessary.
v. Premenstrual migraine responds to depo estrogensor
diuretics.
Cluster headache Sublingual ergotamine (given at bed time)
is effective. Indomethacin is beneficial. A short course of
prednisolone suppresses the attack. Preventive therapy
includes calcium channel blockers (verapamil) amitripty-
line, or methysergide. Lithium carbonate (600-900 mg/d)
worth of trial in chronic cluster headache.
Hypertension The treatment includes pharmacological and
nonpharmacological therapy. Curable forms of hypertension
269
(5%) if present, are to be corrected by surgery wherever
necessary.
Nonpharmacological therapy includes sodium restriction
(no added salt), weight reduction, pruning alcohol, prohibit-
ing smoking, modifying lifestyle and relaxation.
The pharmacological approach is directed towards a
stepped up care therapy in addition to nonpharmacological
methods. It is undertaken only after ascertaining the high
pressure readings at least thrice at intervals of four to seven
days. In small percentage of cases, surgical treatment may
be necessary for secondary hypertension.
The antihypertensive drugs currently used and their daily
dosages are:
i. Diuretics—(Refer to Chapter ‘Oedema’)
ii. Sympathetic inhibitors (sympatholytics)
a. Central—Clonidine (0.1–0.2 mg), methyldopa
(250-2000 mg)
b. Ganglion blocking agent—Trimethaphan (0.8–
6 mg/min)
c. Peripheral (postganglionic sympathetic nerve
endings—Reserpine (0.1–0.2 mg), guanethidine
(10-120 mg) not in vogue now.
iii. Adreno receptor blockers
a. Beta blockers—Propranolol (40-320 mg),
Metoprolol (50-200 mg),
atenolol (25-100 mg), acebutolol (200-1200 mg),
pindolol (10-60 mg), sotalol (120-480 mg),
Timolol (20-80 mg),
Bisoprolol (5-10 mg); celiprolol (200-500 mg/d)
b. Alpha blockers—Prazosin (0.5-10 mg),
phentolamine (2.5-5 mg IV), phenoxybenzamine
(20-40 mg orally or 1 mg/kg IV) Doxazosin
(1-4 mg/d) Terazosin (2-10 mg/d); Tramsulosin
(0. 2-0. 4 mg/d).
c. Alpha and beta blockers- Labetalol (200-1200
mg); Carvediol (6.25-50 mg/d)
iv. Calcium channel blockers- Dihydro pyridine calcium
channel blockers (DCCB) like Nifedipine (30-180
mg) Felodipine (5-10 mg), nitrendipine (5-40 mg),
Amlodipine (2-10 mg), Benidipine 4 to 8 mg/d)
Lacidipine (2-4 mg/d); clinidipine 5-10 mg/d.
Nondihydro pyridine calcium channel blockers
(Non-DCCB) like verapamil (120-180 mg),
diltiazem (60-360 mg)
v. ACE inhibitors—Captopril (25-100 mg), enalapril
(2.5-40 mg), lisinopril (5-40 mg), Penindopril (4-8
mg), ramipril (1.25-10 mg).
vi. Angiotensin II receptor antagonists-Losartan
(25-100 mg/d); Valsartan (80-30 mg/d); Irbesartan
 270 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(150-300 mg/d) Candesartan (4-16 mg/d)
Telmisartan (20-80 mg/d).
vii. Vasodilators—Hydralazine (25-100 mg), minoxidil
(2.5-50 mg), diazoxide (15-30 mg/min IV drip),
Sodium nitroprusside (0.5-10 mg µg/kg/min IV drip).
Initial therapy (monotherapy) consists of a diuretic or
beta blockers or calcium antagonists or ACE inhibitor.
Second step (dual or combination therapy) is increase
the dose of the first drug or substitute another drug of a
different group.
Sequential monotherapy: If the addition of a second drug
yields great reduction in the pressure, then the first drug is
discontinued retaining the second one.
The next step (triple therapy) is either substituting the
second drug or adding a third drug of a different group.
The most favoured combinations are beta-blocker and
DCCB (dual therapy) or ACE inhibitor, diuretic and DCCB
(Triple therapy).
In malignant hypertension, blood pressure should not
be lowered too rapidly lest stroke should occur.
Hypertension is said to be known as resistant if BP is
> 140/90 mm Hg despite > 3 drugs in full doses including
diuretic.
In hypertensive emergencies with high diastolic blood
pressure (150 mm of Hg), rapidly acting IV agents like
diazoxide or nitroprusside or trimethaphan are administered.
The other parenteral drugs are Labetalol or Diltiazem or
Verapamil Subsequently replaced with oral drugs as the
condition improves. Nowadays, oral nifedipine (5-10 mg
sublingually) results in graded reduction which may be
repeated after half an hour or oral clonidine (0.1-0.2 mg)
every hour as needed. Frusemide (20-40 mg IV) is beneficial
to maintain a smooth urine flow and safe diastolic level.
Refractory or resistent hypertension needs evaluation such
as renal artery stenosis or phaeochromocytoma.
In elderly people with systolic hypertension Amlodipine,
Diuretics, Alpha-blockers are used.
Toxi-infective Treat the underlying cause, besides
symptomatic therapy.
Giant cell arteritis Refer to Chapter ‘Polyarthritis’.
Carcinoid syndrome Refer to Chapter ‘Chronic Diarrhoea’
Musculoskeletal
Tension Headache NSAID or a nonhabit forming analgesic
usually help. Muscle relaxant drug may be supplemented.
The underlying anxiety or a depressive factor is to be
identified and treated. Benzodiazepines are to be avoided
strictly because of habit forming hazard. Amitriptyline in
doses of 5-75 mg/d or chlordiazepoxide (10-20 mg/d) is
beneficial. Biofeedback therapy, physical therapy (massage)
and relaxation techniques may be considered.
Cervical fibrositis NSAIDs, physical therapy and neck
exercises are advocated.
Cervical spondylosis (Refer to Chapter ‘Pain in the
Extremities’)
Osteitis of the cranial bones NASIDs prescribed for one
week followed by maintenance dose for about a month.
Prednisolone may be of value but not recommended usually.
Treat specific cause if any. Alendronate (40 mg/d) for six
months effective in Pagets disease. Salcatonin 50 i.v. thrice
weekly to 100 i.v. daily s.c. relieves pain.
Neuritides (Neuritis and Neuralgia)
• Drugs to reduce inflammation (NSAIDs) or interfere
with transmission of pain(analgesics) or inhibit re-uptake
of transmitter (tricyclic antidepressants) are considered.
Vitamins B1 and B12 may be of value. Prednisolone (40-
60 mg/d) and acyclovir (1-2 g/d) in divided doses are
advocated in some cases of cranial neuritis.
• Trigeminal neuralgia is treated with carbamazepine
(increasing doses gradually up to 1 g a day) and/or
phenytoin (100 mg t.d.s.). Clonazepam (1 mg t.d.s) may
be effective. Surgical treatment includes injection of
trigeminal ganglion with alcohol or intracranial section
of the sensory root of trigeminal nerve or suboccipital
craniectomy for decompression of trigeminal nerve.
• Postherpetic neuralgia may respond to tricyclic
antidepressants, anticonvulsants and topical anaesthetics.
Interferon and vidarabine are found to be beneficial.
Transcutaneous nerve stimulation may help.
Meningeal
Meningitis
• Pyogenic meningitis: Immediate therapy must be
instituted for a better outcome. The antibiotics chosen
are based on the specific causative organism and should
be given parenterally. Bactericidal drugs are preferred
than bacteriostatics. Ampicillin (100-200 mg/dk/d) and
gentamicin (2.5-5 mg/kg/d) form the mainstays of
therapy, which should last for 10-14 days. Benzyl
penicillin 10000 units is given intrathecally.
Chloramphenicol (50-100 mg/kg/d) and a third
generation cephalosporin like cefuroxine (100-200 mg/
kg/d) are better considered if the organism is yet to be
 Headache
identified. Meropenem 1 gm two or three times given
IV. Dexamethasone is a good adjunct. Supportive therapy
with fluids and general care of an unconscious patient
as well s symptomatic therapy for hypotension, seizures,
etc. should be instituted. For meningococcal infections,
rifampicin 600 mg. b.d. for two days is advocated
symptomatic therapy for any fits or shock instituted.
• Tuberculous meningitis: Chemotherapy with rifampicin
(600 mg), and isoniazid (600 mg), pyrazinamide (1.5 g)
and streptomycin (1 g) must be given at the earliest for
three months followed by rifampicin and isoniazid for
one year pyridoxine (50 mg) may be supplemented. Oral
prednisolone (20-40 mg/d) is beneficial. Intrathecal
hydrocortisone (25-50 mg) twice a week is considered
whenever necessary. Supportive therapy is essential as
above. Ventricular drainage is necessitated in case
obstructive hydrocephalus occurs.
• Viral meningitis: Treated symptomatically. It is a self-
limiting disease in which the patient invariably recovers
completely.
Subarachnoid haemorrhage Refer to Chapter ‘Coma’.
Space Occupying Lesions
Intracranial tumour Treatment is usually surgical excision.
When it is surgically inaccessible, cerebral decompression
(subtemporal for supratentorial tumours and suboccipital
for infratentorial tumours) is done. When surgery is not
possible raised intracranial pressure must be lowered by
dexamethasone (4 mg. q.d.s. orally or parenterally) or 200
ml of 20 per cent mannitol. Associated symptoms like
vomiting and seizures are controlled symptomatically.
Headache responds well to steroids.
Malignant gliomas require surgical resection followed
by radiation therapy and chemotherapy with nitrosoureas
(BCNU 200 mg/m2 every 6 weeks or oral CCNW 110 mg/
m2 every 6 weeks).
Prolactin or growth harmone secreting tumours respond
to bromocriptine.
Cerebral abscess Acute abscess is treated with penicillin
or betalactam antibiotics. Surgery is withheld for about a
month. However burrhole aspiration may be done during
this period. Surgery is indicated in deepening coma in acute
phase or in chronic abscess. Associated seizures are treated
with anticonvulsants.
Subdural haematoma Surgical evacuation of the haematoma
is done.
271
Altered CSF Flow
Hydrocephalus The treatment depends on the underlying
cause. In obstructive hydrocephalus, ventricular drainage
is done. In communcating hydrocephalus, repeated lumbar
punctures may be necessary. If the visual acuity fails,
suboccipital decompression is done.
Post-lumbar puncture Patient is kept in the bed with the
foot of the bed raised so as to relieve the intensity.
Administration of intravenous fluids may be necessary to
compensate the lowered intracranial pressure, apart from
symptomatic therapy.
Pseudotumour cerebri or benign intracranial hypertension
The drugs precipitating the raised intracranial pressure
without a space occupying lesion as such must be withdrawn.
Repeated lumbar punctures may facilitate reduction of CSF
volume. Frusemide or corticosteroid for short period is
beneficial. If vision is threatened, lumboperitoneal shunt
and surgical decompression may be necessary Lamotrigine
may be beneficial.
Trauma (Head Injury)
Refer to Subdural Haematoma—Vide supra and Chapter
‘Coma’.
Referred Pain
The treatment of most of the causes of referred pain belong
to ophthalmologist or Dentist of ENT surgeon.
Ocular Ocular causes of headache are appropriately treated,
e.g. correction of refractive errors glaucoma with timolol
eye drops.
Dental Treatment belongs to the dentist. However, dental
infections are treated with appropriate antibiotics and good
oral hygiene. In periodontitis, mouth washes and application
of counter irritants are helpful.
Sinusitis The treatment includes antibiotics like oral
cephalexin or ciprofloxacin or clarithromycin for 10-14 days,
analgesics and tincture benzoin inhalations are helpful.
Decongestants or expectorant mixtures are supplemented.
In recurrent and chronic cases of maxillary sinusitis,
puncture and lavage may be considered. In refractory cases,
operation to establish drainage may be needed. Nasal
endoscopic manoeuvres preferred by and large.
Temporomandibular joints Temporomandibular arthritis or
inflammatory synovitis is treated with NSAIDs and if
necessary with antibiotics.
 272 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Anoxaemia and Hypercapnia
• Anaemia (Refer to Chapter ‘Fatigue’)
• Hypercapnia (Refer to Chapter ‘Cyanosis’)
• Emphysema (Refer to Chapter ‘Dyspnoea’)
• Poisons
Most of the poisons cause alarming symptoms barring
few which cause headache like alcohol (refer to Chapter
‘Coma’), carbon dioxide (Refer to Chapter ‘Dyspnoea’) and
carbon monoxide. If the saturation of blood is below 40 per
cent, headache is a prominent symptom, which can be
relieved by removing the person from the vitiated
atmosphere and exposing to fresh air. 100 per cent oxygen
is administered to lower the carboxyhaemoglobin level to
less than 5 per cent. IV mannitol given if cerebral oedema
occurs (Refer to Chapter ‘Coma’).
Psychogenic
Anxiety Benzodiazepines are effective to control the
symptom. (alprazolam or clonazepam started with 0.5 mg
three times a day and gradually increase the dose up to 4
mg a day for a period of six months and then taper slowly).
Buspirone (5 mg b.d.); or clobazam; (5-10 mg/d) or
Dothiepin 15 mg/d. The tricyclic antidepressants may be
effective though depression is absent. Behavioural therapy
helps to overcome the phobias. Psychosocial stresses must
be eliminated. The patient should be explained about the
minor nature of his illness.
Depression Antidepressant drugs are beneficial. (amitripty-
line—75-150 mg daily or fluoxetine—20 mg daily or
citalopram (20-40 mg/d) or mirtazapine (15-30 mg/d) are
given for about six weeks and continued for another six
months or more at reduced doses.) Cognitive therapy may
be combined to overcome the negative pattern of thinking
responsible for the depression.
Fatigue (Refer to Chapter ‘Fatigue’).
Insomnia Avoid unnecessary thinking and tensions. Adopt
optimum exercise. A full meal, habit of reading before going
to bed, and setting up a good environment conducive for
sleep facilitate to overcome the sleeplessness. Drugs are
avoided as far as possible. Drugs, if at all chosen, should be
not habit forming. A hypnotic drug should be prescribed
only as an adjunct. Benzodiazepines like diazepam or
alprazolam are avoided as they encourage dependence.
Nitrazepam (5-10 mg) is beneficial. It is better given every
3rd night and preferably for not more than 3 weeks at a
time. Non benzodiazepines like zopiclone, zaleplong or
zolpidem are prescribed for upto a few weeks. The
nonhypnotic drugs like antidepressants citalopram (20-40
mg/d) or mirtazapine (15-30 mg/d) in endogenous
depression, or for those waking up in early hours; phenytoin
for nightmares; analgesics for sleeplessness due to pain;
dextroamphetamine for hyperkinetic individuals or
Parkinson’s patients; neuroleptics (phenothiazines or
haloperidol) in psychiatric patients, are usually prescribed.
Sedative hypnotics must be discouraged (Refer to Chapter
‘Fatigue’).
Headache 273
274 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Impotence
18
Impotence may be defined as the inability to attain an
adequate erection for vaginal penetration and maintain the
erection through the normal sexual intercourse up to
ejaculation. The male dysfunction is to be differentiated from
infertility or sterility which is an inability to procreate. So a
potent man may be sterile and an impotent man may be
fertile. Infertility is defined as failure to bring forth an
offspring even one year after a normal marital relationship
without contraceptives.
The normal male sexual function consists of five phases:
i. Libido (Sexual desire)
ii. Erection (Enlarged and stiffened)
iii. Ejaculation (Seminal expulsion)
iv. Orgasm (Climax of sexual activity)
v. Detumescence (Flaccid state)
The sexual power is variable depending upon the
physicomental make up, environment and time. It may be
reduced in certain situations like stress, fatiguability,
apprehensions and transient worries. The impotence is said
to be relative when a person cannot have coital erections
with one woman but may have effective coitus with his wife
and vice versa. Some individuals may fail to have sexual
intercourse under conventional situations and are able to
perform the normal intercourse under special circumstances
and certain stimuli.
Impotence occurs principally in two forms (1) Erectile
failure and (2) Ejaculation disturbances.
1. Erectile failure in which erection cannot be attained or
maintained, may be of four types.
i. Total in which erection cannot be obtained or
maintained,
ii. Partial with inadequate erections,
iii. Erections may occur but sexual intercourse is not
achieved (occurrence of premature ejaculation, i.e.
ejaculation before or immediately after penetration),
and
iv. Gradual onset of erectile incompetence following
normal potency.
2. Ejaculation is a reflex reaction to the collection of semen
in the bulbous urethra ultimately resulting in its
expulsion. Ejaculation disturbances may be of four types:
i. Premature ejaculation
ii. Indefinitely delayed ejaculation
iii. Absence of ejaculation and failure to complete the
sexual act
iv. Retrograde ejaculation (Normally prevented by
partial bladder neck closure and occurs if the
sphincters fail).
Apart from sexual dysfunctions like erectile failure and
premature ejaculation, another dysfunction is sexual
withdrawal, i.e. decreased frequency of sexual activity in
the absence of any sexual disorder like impotence.
ANATOMICAL AND PHYSIOLOGICAL BASIS OF
MALE SEXUAL DYSFUNCTION
The body of the male organ is composed of three elongated
masses of erectile tissue (two corpora cavernosa and corpus
spongiosum) which are surrounded by a dense fibrous
sheath. The vascular supply is derived from the internal
pudendal arteries. The blood from the cavernous spaces is
returned by dorsal veins. The innervation is derived from
second, third and fourth sacral nerves through the pudendal
nerve and pelvic plexuses. The parasympathetic nerves arise
from ventral root segments of S2 and S3 and the sympathetic
component is derived from L1 and L2 cord segments.
Libido is influenced by psychic factors and androgens.
The penile erection is a reflex event accomplished by
increased inflow of blood into cavernous spaces via internal
 276 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

pudendal arteries (8 ml of blood of the flaccid state is Table 18.1: Causes of erectile dysfunction
increased to about 62 ml in the erectile state). This vascular 1. Physiological: Ageing
phenomenon is independent of muscular compression 2. Pharmacological
exerted by the ischiocavernous and bulbocavernous muscles. a. Antihypertensive drugs
The filling of blood under pressure results in ballooning of b. Antipsychotic drugs (major tranquillisers and antidepressants)
the erectile tissue to such an extent that it makes it elongated c. Anticholinergic drugs
and hard. This adequate erection is a neurovascular event d. Antihistamines
and the neuronal component is controlled through e. Other drugs
i. Cimetidine
reflexogenic and psychogenic stimuli. The former is
ii. Levodopa
mediated by parasympathetic efferents to the vessels of
iii. Ethionamide
corpora cavernosa and ischiocavernous and bulbocavernous iv. Spironolactone
muscles as well as sympathetic fibres reaching the genitalia v. Estrogens
through hypogastric plexus. The parasympathetic fibres vi. Drug addiction (heroin, barbiturates, amphetamine)
dilate the arteries and constrict the veins besides secretion vii. Alcohol
of mucus by the Littre and bulbo urethral glands for viii. Chlorotrianisene
lubrication. This inherent reflex mechanism starts from the ix. Cyproterene
glans which contain highly organised sensory end organ x. Statins
system and this sexual stimulation spreads to sacral portion xi. Clonazepam
xii. Cytotoxic drugs.
of the cord through pudendal nerve along with impulses
3. Pathological
from the adjacent areas and reaches the cerebrum. The actual A. Primary (no organic cause but due to psychological influences)
sexual stimulation is of course initiated by psychogenic and a. Anxiety
other various sensory stimuli. b. Depression
When sexual stimulus becomes intense, sympathetic c. Phobias
impulses reach genitalia and initiate emission which is the d. Situations like stress or marital disturbance.
forerunner of ejaculation. The seminal emission results from B. Secondary (organic)
contraction of vas deferens, contraction of muscular coat of a. Endocrinal
prostate and contraction of seminal vesicles. The seminal i. Testicular failure (primary and secondary
hypogonadism)
filling of internal urethra transmit signals to sacral cord and
ii. Hyperprolactinaemia
in turn cause contraction of the muscles of the pelvic floor
iii. Hyperthyroidism
including ischiocavernous and bulbocavernous muscles, iv. Diabetes mellitus
which compress the base of the erectile tissue. The pressure b. Penile
thus exerted in genitalia and urethra results in ejaculation. i. Peyronie’s disease
The orgasm is due to rhythmic contraction of the ii. Priapism (failure of detumescence)
bulbocavernous and ischiocavernous muscles and is a climax iii. Phimosis
of the sexual excitement due to pleasurable perception which c. Vascular
is a cortical sensory phenomenon influenced by psychic i. Atherosclerosis of large pelvic vessels
ii. Arteriosclerosis of small penile vessels
factors. It includes the entire period of emission and
iii. Leriche’s syndrome
ejaculation.
d. Neurological
The detumescence (flaccid state) occurs after the i. Temporal lobe lesions
excitement disappears and is a consequence of vasoconstric- ii. Stroke
tion of the arterioles of the erectile tissue and venous iii. Spinal cord lesions
drainage thereof, emptying the sinuses. iv. Peripheral neuropathy and autonomic neuropathy
v. Pelvic surgery involving nervi erigentes, pelvic
CAUSES OF ERECTILE DYSFUNCTION (ED) trauma, prostatectomy
e. Systemic disease
Causes of erectile dysfunction can be physiological, i. Congestive heart failure
pharmacological or pathological (Table 18.1). ii. Renal failure
Common causes may be due to drugs, diabetes mellitus iii. Cirrhosis of liver
and depression. Most of the cases are due to psychological iv. Malignancy
 Impotence
factors although organic causes like diseases or drugs may
account for the rest of the cases.
The loss of libido may be due to androgen deficiency. If
it is due to nonendocrinal factors (psychic factors) the semen
volume is normal and emission is present. Emission may be
absent due to androgen deficiency, retrograde ejaculation
and sympathetic denervation. Premature ejaculation is
usually functional in origin. Similarly, absence of orgasm is
also functional provided libido and erection are normal.
Detumescence may fail due to priapism.
Physiological
The inability to perform a completely normal sexual act may
occur in the advancing years due to ageing processes.
Increasing time to attain full erectile state and decreasing
frequency with less amounts of ejaculate are characteristic.
Retention of potency as age advances is variable and
probably related to psychosocial and genetic factors.
Pharmacological
Antihypertensive Drugs
Antihypertensive drugs like guanethidine may cause
premature ejaculation; clonidine may cause decreased libido;
methyldopa and reserpine may cause impotence due to
increased prolactin secretions. Spironolactone acts as an
antiandrogen (competing with androgens for binding to
androgen receptor).
Antipsychotic Drugs
Antipsychotic drugs like phenothiazine may produce
impotence due to increased levels of prolactin. Peripheral
parasympathetic action by imipramine may account for
impotence.
Anticholinergic Drugs
Anticholinergic drugs like trihexyphenidyl, benztropine, and
atropine may be responsible for impotence through
neurological blockade, increased prolaction secretion or
decreased testosterone levels.
Antihistamines
Antihistamines like diphenhydramine, hydroxyzine are
known to decrease libido and cause impotence by atropine
like action.
277
Other Drugs
Cimetidine produces impotence on the same anology of
spironolactone. Oestrogens cause impotence as they are
incapable of supporting sexual libido when Leydig cell
function is directly inhibited (independent of systemic
suppression of LH). Alcohol and the other drugs capable of
causing addiction possibly induce impotence due to direct
toxic effect on the testis, inhibition of hypothalamic pituitary
system and nutritional deficiencies. Cyproterone and drugs
used in cancer chemotherapy cause impotence due to
testicular failure consequent to toxicity on the spermatogenic
tubules and diminished testosterone levels. The sexual
dysfunction can be attributed to a drug only, if potency is
restored after discontinuing the drug.
Pathological
Primary (Functional)
Sexual dysfunction is usually an expression of anxiety,
depression, phobias or obsessional disorders. The
psychological factors may be recent (stress and frustration)
or remote (during formative years) in origin. Anxiety leads
to sympathetic excitation and consequent inhibitory and
motor influences on the sexual act. The anxiety may be a
symptom of physical inferiority, guilt over earlier
masturbatory practices or sexual exposures. Impotence is a
common complaint in depressive illness as a part of change
in mood and decreased vitality. In some intercourse is
possible only with fetishistic behaviour like insisting of
unusual dress or make up. Earlier sexual exposures or fears
or threat in a sexual situation or current marital disturbance
may also be accountable.
Secondary (Organic)
Endocrinal
Testicular failure It may be primary due to abnormalities of
testicular functions (i.e. primary hypogonadism) or
secondary to hypothalamic pituitary defects (secondary
hypogonadism).
Normally, the testicular functions are hormonal and
reproductive.
i. Hormonal: Involves androgen production by the
interstitial cells of Leydig which lie between the
tubules and depends on LH levels.
ii. Reproductive: Involves spermatogenesis, by
seminiferous tubules whose function depends on
androgen levels and FSH.
 278 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Both aspects are under the control of pituitary gonado-
trophic hormones which are stimulated by hypothalamus
through its pulsatile releasing hormone (GnRH). The
gonadotrophins are.
Leutinising Hormone (LH) stimulates Leydig cells which
secrete testosterone and Follicle Stimulating Hormone
(FSH) acts directly on the spermatogenic tubules by binding
the surface of sertoli cells in the tubules, to secrete androgen
binding protein and inhibin.
The testosterone secretion is regulated by LH and
spermatogenesis depends upon FSH as well as testosterone
(since LH influences spermatogenesis by accelerating the
testosterone synthesis and FSH influences the sensitivity of
the testis to LH). The spermatogenic tubules which produce
inhibin regulate FSH secretion and testosterone itself
regulates the LH levels.
The primary testicular failure (primary hypogonadism)
may be due to Klinefelter’s syndrome, cryptorchidism,
infections (viral or bacterial), drugs (spironolactone, heroin
or cancer drugs), radiation exposure or surgical castration.
The secondary hypogonadism may be due to Kallmann’s
syndrome, Prader-Willi syndrome or pituitary tumours. In
primary hypogonadism, azo-ospermia, plasma testosterone
levels are low and gonadotrophin levels as well as oestradiol
are raised (Hypergonadotropic). (If both spermatogenesis
and Leydig cells are defective plasma testosterone levels
are low (< 10 nmol/ Lt) with azo-ospermia.) If tubules alone
are impaired sperm count is low (< 20 million/ml). In
secondary hypogonadism the gonadotrophins and testo-
sterone levels are low and do not respond to clomiphene
(Hypogonadotropic).
The testicular failure depends upon time of onset of
disease. It may be Prepuberal hypogonadism. This cannot
be usually diagnosed in boys under the age of 16 or 17 since
it is difficult to differentiate from physiological delayed
puberty. Sexual maturation does not occur resulting in
external genitalia and the secondary sex characteristics,
failing to develop in adult life. Disproportionately long
extremities occur due to the failure of closure of epiphyses
of the long bones so that the arm span is more than 5 cm
greater than height and lower body segment is more than
5 cm longer than upper body segment. Eunaquism (complete
failure of genital development) or Eunuchoidism (partial)
leads to excessive height (unless otherwise associated with
complete pituitary defect) with no sexual hair (hairless face
chest and pubic region), small genitalia with lack of libido
and potency. Some may develop gynaecomastia. This
prepuberal hypogonadism may be due to primary testicular
(prepuberal destruction or malformation of testis) or
pituitary-hypothalamic defects like:
a. Pituitary infantilism (fails to grow physically and mature
sexually although mentally alert)
b. Hypogonadotrophic hypogonadism with anosmia
(Kallmann’s syndrome)
c. Obesity with hypogonadism may be present in addition
to dwarfism, and diabetes insipidus (Frohlich’s
syndrome)
Certain genetic disorders may be associated with obesity
and hypogonadism in addition to
i. Diabetes mellitus of maturity onset type, mental
retardation and hypotonia (Prader-Willi syndrome)
ii. Polydactyly, mental retardation with retinitis
pigmentosa (Lawrence-Moon-Biedl syndrome)
iii. Nerve deafness, diabetes mellitus and retinitis
pigmentosa besides primary hypogonadism like picture
(small testes, low testosterone, high gonadotrophin
levels and normal secondary sexual characteristics)—
Alstrom’s syndrome
iv. Diabetes mellitus, secondary hypogonadism,
polydactyly with iris coloboma (Biemond’s syndrome)
v. Mental retardation, acrocephalosyndactyly and
characteristic facies (Carpenter’s syndrome)
vi. Nerve deafness, mental retardation (Weiss syndrome)
Puberal hypogonadism
a. Klinefelter ’s syndrome (seminiferous tubular
dysgenesis)—Subjects usually complain of small testis
at puberty and infertility and/or gynaecomastia after
puberty (Refer to Chapter ‘Gynaecomastia’).
b. Refenstein variant normal male with infertility (Refer
to Chapter ‘Gynaecomastia’).
Postpuberal hypogonadism If the onset of disease is post-
puberal, the growth is not affected, i.e. body proportions
are normal. There is regression of secondary sex charac-
teristics and the external genitalia may undergo partial
atrophy or hypoplasia. Loss of libido and potency with
vasomotor symptoms like flushings and dizziness or mild
chills may be present. This may be due to any pituitary lesion
or testicular damage secondary to infections (like mumps,
tuberculosis or gonococcal), trauma, surgical castration or
radiation damage. Obesity with small genitalia and sparse
sexual hair with normal testosterone and normal sperm count
and urinary FSH are due to end organ resistance or isolated
LH deficiency.
Sometimes minor forms of hypogonadism may occur
due to malnutrition (particularly zinc deficiency) or
hypothyroidism.
Hyperprolactinaemia Prolactin secreting pituitary tumours
may present as space occupying lesions with symptoms like
 Impotence
headache and visual defects along with hypogonadism due
to prolactin excess. 90 per cent of men with increased
prolactin concentrations complain of impotence and
decreased secondary sexual hair, with mild gynaecomastia
or galactorrhoea. If the prolactin levels are above
2,000 mU/L (the upper limit of normal levels is
approximately 360 mU/L), it is highly suggestive of a tumour
in the absence of pregnancy, renal failure or phenothiazine
therapy. The plasma gonadotrophins and testosterone values
may be decreased. There is normal pituitary response to the
leutinising hormone releasing hormone (LHRH). However,
there is diminished response to provocative tests such as
TRH (Thyrotropin releasing hormone) or metoclopramide.
Hyperthyroidism Sympathetic overactivity may be inhibitory
for erectile response, accounting for impotence in
hyperthyroidism. (Refer to Chapter ‘Weight Loss and
Goitre’).
Diabetes mellitus There appears to be a premature develop-
ment and accelerated atherosclerosis in diabetics, depending
upon the duration of the disease. These atherosclerotic
lesions result in plethora of symptoms depending on which
artery is affected. If there is atherosclerosis of the large pelvic
vessels and arteriolar sclerosis in the small penile vessels,
organic impotence may result. Besides this vascular basis,
autonomic neuropathy may account for impotence by
interfering with, sacral parasympathetics controlling blood
flow to the erectile tissue. The atherosclerosis is related to
decreased high density lipoproteins (HDL) whereas
neuropathy is related to decreased myoinositol content of
the affected nerves and ischaemia of the peripheral nerves
(due to atherosclerosis of the nutrient vessels of the nerves).
Norepinephrine content of corpora cavernosa is also
decreased. 50 per cent of diabetics may develop impotence
within six years of the onset of the disease. (Refer to Chapter
‘Polyuria’).
Penile
Peyronie’s disease It is an idiopathic inflammatory disorder
with fibrosis of tunica albuginea. Pain associated with
erection or obstructive effect on the normal tissues may cause
impotence. It may present with hard plaques along the shaft
and glans or with lateral deviation of the penis.
Priapism Priapism is painful, prolonged erection due to
thrombosis of the penile vessels. Ultimately this leads to
fibrosis of the vascular network with consquent erectile
impotence. It may be seen in chronic myeloid leukaemia or
sickle cell anaemia, or may be idiopathic.
279
Phimosis Phimosis may affect male sexual function through
pain in the glans.
Vascular
Atherosclerosis of large pelvic vessels and arteriosclerosis
of small penile vessels Atherosclerosis of large pelvic vessels
and arteriosclerosis of small penile vessels such as pudendal
and profunda arteries may lead to inadequate perfusion of
the penis with erectile dysfunction. Obliteration of smaller
vessels of the cavernous tissue is associated with ageing or
diabetes. The gradual diminishing of erectile function may
be due to these progressive changes. Measurement of penile
blood pressure or phalloarteriography aids the diagnosis of
vascular insufficiency.
Leriche’s syndrome (Aortic bifurcation obstruction
syndrome)
Since continuous increased blood flow into the vascular
spaces is needed for effective erection, in Leriche’s
syndrome there is obstruction to the distal aorta with
consequent impaired blood supply leading to impotence.
Neurological
Temporal lobe lesions The temporal lobe is concerned with
hearing (superior temporal gyrus); smell and taste (uncinate
and hippocampal regions); visual perceptions (posterior
lobe); speech (dominant hemisphere towards the insula-
spoken speech; posterior portion receptive speech); and
memory and emotional state (posterior part and amygdaloid
nucleus) of any individual. Anterior lobes are related to
sexual capacity and lesions therein may result in impotence.
Stroke Major sexual dysfunction may happen after
unilateral stroke. If the right hemisphere is dominant for
the activation of normal sexual function, there is higher
incidence of impaired sexual function after affection of right
hemisphere rather than left.
Spinal cord lesions Since the integrity of the reflex arc is
related to reflex erections, any injury to these pathways like
cauda equina lesions, tabes dorsalis, and cord transections
can result in impotence.
Peripheral neuropathy and autonomic neuropathy Some of
the peripheral neuropathies, and autonomic insufficiencies
(like dysautonamia) may lead to absence of reflexogenic
erections, although psychogenic erections can occur, as
compared to upper motor neurone lesions, where the
contrary occurs.
Pelvic surgery involving nervi erigentes Sometimes damage
to nervi erigentes (nerve supply to penis) during total
 280 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
prostatectomy or pelvic surgery can cause impotence as the
nerve runs through lateral portion of the prostate and
adjacent to rectum.
Systemic Diseases
Congestive heart failure In congestive heart failure, there is
decreased cardiac output with impaired penile blood supply
and physical disability like breathlessness may account
further for impotence.
Renal failure In chronic renal failure, diminished
testosterone and raised oestradiol levels may play a role
besides neuropathy, which may be responsible in the
haemodialysed patients.
Cirrhosis Endocrinal factors may account for 70 per cent
of cirrhotic patients developing decreased libido and potency
due to decreased testosterone and increased oestradiol
associated with testicular atrophy. (Testis is less than lower
normal limits 4½ cm, 2½ cm and 2½ cm.)
Malignancy In malignancy, debility and depressed mood per
se may account for erectile dysfunction although cancer
chemotherapy can also result in dysfunction due to toxic
testicular failure.
CLINICAL APPROACH
It was generally believed in the past that impotence was
predominantly of psychological origin, but in recent times
improved diagnostic techniques uncovered that physical
defectes are responsible for up to 50% of cases of sexual
impotence. Hence a thorough search must be made for an
underlying organic cause although there may be an interplay
between functional and organic problems since subjects with
organic disease may have coexisting psychological
influences.
History
While evaluating the male sexual dysfunction the first step
should be to distinguish between psychogenic erectile
impotence and decipher whether the former is causative or
coincidental. The following features differentiate one from
the other.
a. Onset: It is sudden in psychological and gradual with
progressive deterioration in organic.
b. Pattern: Dysfunction is episodic in psychological and
persistent during all sexual situations in organic
disorders, with a previous history of normal sexual
functions.
c. Nocturnal erections: Present in sleep as well as on
awakening in the morning in psychological; absent or
diminished in organic.
d. Response: Tends to be selective of partner and situations
or responds to masturbation in psychological origin
whereas there is no response in organic erectile
dysfunction.
e. Noctural penile tumescence (NTP): In psychogenic, the
duration of erectile episode and rigidity are normal
whereas in organic the erectile episodes are decreased
in number and duration with decreased rigidity or even
absent (vide infra).
The second step is to obtain the description of
a. Sexual interest (androgen deficiency or hyperpro-
lactinaemia may lead to loss of sexual interest).
b. Erection (painful or deformed as in Peyronie’s disease)
c. Ejaculation (premature or absent as in anxiety or
retrograde ejaculation due to autonomic neuropathy).
Premature ejaculation may be mistaken for erectile
failure as loss of erection follows ejaculation rapidly.
The third step is to obtain a careful history regarding
a. Drug treatment or alcohol abuse; or heavy cigarette
smoking (erectile and/or ejaculatory failure is common
with drugs)
b. Previous pelvic surgery, or spinal cord surgery
c. Psychological stresses, phobias, depressions and anxiety
d. Any underlying systemic disease like diabetes mellitus
or debilitating illness like disseminated malignancy
e. Puberal status
Physical Examination
Special attention must be paid to neurovascular abnor-
malities and endocrinal function.
General Examination
1. Facies: (a) anxious, (b) depressed, (c) uneasy and
irrational apprehension, and (d) alcoholic facies
2. Appearance: Obesity or generalised wasting or pallor
(anaemic)
3. Neck: Any thyromegaly
4. Measurements: (a) Body height (b) span
5. Examination of the genitalia
A. Evidence of androgen deficiency: Varies with time
of onset
i. Foetal (pseudohermaphroditism)
ii. Prepuberal (eunuchoidism)
iii. Postpuberal (impotence/infertility) adult testis
size varies from 15-30 cm.
 Impotence
a. Hair distribution over the face and body
b. Gynaecomastia
c. Genital
iv. Testis is small ( If the length of testis is less than
4 cm, it indicates hypogonadism as well as
spermatogenic function of the testis since
seminiferous tubules form 75% of the testis.
Prepuberal testis measures about 2 cm).
v. Small penis
vi. Small scrotum
B. Look for presence of testicular sensation (it is absent
in small atrophied testis) and varicocele
C. Penile examination
a. Any evidence of Peyronie’s disease or phimosis
b. Feel the penile pulse
c. Measure penile circumference
6. Peripheral pulses; For evidence of any atherosclerotic
changes
7. Blood pressure and any postural fall.
Systemic Examination
1. Neurological examination:
i. Emotional state
ii. Sense of smell, sense of taste, acuity of hearing, fields
of vision and fundus examination
iii. Weakness or wasting of the muscles
iv. Sensory system: Any impairment of superficial
sensations as well as proprioceptive sensations and
sensation over the perineum (S2 to S5)
v. Reflexes: Superficial reflexes like bulbo cavernous
reflex (indicates S 2 to S3 integrity); anal reflex
(indicates S4 to S5 integrity); deep reflexes (lost in
peripheral neuropathy)
vi. Visceral reflexes for evidence of cauda equina lesions
vii. Autonomic neuropathy (testing autonomic nerves by
cardiovascular reflexes): (Refer to Chapter
‘Syncope’)
2. Chest examination: For evidence of cardiovascular
disorders and heart failure
3. Abdomen examination: For evidence of ascites and
organomegalies or any abdominal or groin bruits
Investigations
1. Urine
a. Fixed specific gravity and albuminuria and granular
casts, for evidence of chronic renal failure.
b. Evidence of glycosuria, to exclude diabetes mellitus.
281
c. 24 h urinary excertion of 17 ketosteroids: Low in
secondry hypogonadism.
d. 24 h excertion of LH and FSH: Low in secondry and
high in primary hypogonadism.
e. Postcoital urine examination for evidence of sperms
which indicates restrograde ejaculation.
2. Blood
a. Blood sugar, urea and serum creatinine: To exclude
diabetes mellitus and renal disease.
b. GGT and AG ratio: For the evidence of chronic
hepatic disease.
c. Cholesterol fractions and triglycerides: For evidence
of atherosclerosis.
d. Hormonal profile
i. Testosterone secretion is in Leydig cells depends
on LH.
ii. Gonadotrophins (FSH and LH), stimulation test
can be done with GnRH or clomophene or hCG
if values are on border line. If FSH alone is
elevated and LH as well as testosterone are
normal, it is suggestive of Sertoli cell syndrome
only. If gonadotrophins are elevated and
testosterone is low, it is due to hyalanisation of
seminiferous tubules. If all the three hormones
are low, it is due to gonadotrophin deficiency. If
all are normal, it is suggestive of ductal
obstruction or maturation failure.
iii. Prolactin
iv. Thyroxine and TSH level
e. VDRL for leutic infection
3. Buccal smear and karyotype
Buccal smear examination for barr bodies and
karyotyping of lymphocytes to determine sex
chromosomal disorders like 47 XXY. It is indicated when
gonadotrophins are elevated.
4. Semen analysis
(Normal sperm count excludes hypogonadotrophism
and also aids in identifying associated infertility)
a. Total volume : 2 to 6 ml
b. Sperm count: 50 to 100 million/c cm
c. Motility: > 60 percent are motile and not more than
20% of abnormal
d. Chemical analysis: Look for the presence of fructose
in azoospermic patients. If this is present obstruction
of the ejaculatory duct is excluded.
e. Morphology: > 50 percent are of normal forms. (If
the sperm concentration is less than 20 million and
motility is less than 40 percent, it is usually
suggestive of infertility).
 282 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Special Investigations
A i. Measurement of penile blood pressure by doppler
techniques. Penile systolic blood pressure is
determined with a doppler stethoscope. (Blood
pressure cuff of 3 cm size is placed around the base
of the male organ and inflated little over brachial
systolic blood pressure. The stethoscope is placed
over one of the corpora in the dorsolateral region
and the sound heard during deflation is penile systolic
blood pressure). A normal pressure indicates normal
blood flow.
ii. Penile index: If the penile systolic blood pressure is
equal or below 20 mmHg of brachial systolic blood
pressure (i.e. penile index > 0.9), it is suggestive of
psychogenic impotence, whereas if it is > 30 mm
Hg below brachial systolic blood pressure (i.e. Penile
index <0.6), it indicates organic impotence.
B. Measurement of Nocturnal Penile Tumescence (NPT):
Measurement of sleep erections is also useful in
differentiating psychogenic and organic impotence but
the procedure requires a specialised sleep laboratory and
it is time consuming and expensive. It is done with a
mercury strain gauge attached to a recorder. Continuous
measurements of penile size and sleep stage are recorded
for three consecutive nights.Correlation of a normal
erection with REM sleep, represents a normal response
and indicates psychogenic impotence.
C. Measurement of penile rigidity is also made by a
tonometer using transducer methods, apart from NPT
studies.
D. Angiography: Selective angiography of internal iliac or
pudendal arteries or cavernosography are of academic
interest. Doppler shows blood flow status.
E. Cystometrogram: It is useful in establishing the cause
of erectile dysfunction in diabetic patients. If a
neurogenic bladder is noted, it is likely that the problem
of erectile dysfunction is secondry to autonomic
neuropathy rather than a vascular or psychic causative
factor.
F. Bulbocavernous reflex latency: In psychogenic
impotence it is normal (i.e. 35 ms) whereas it is
prolonged in organic importence (i.e. 40 ms).
G. Radiology (if indicated: Skull X-ray and CT scan or MRI
for intracranial pathology accounting for impotence).
H. Testicular biopsy is particularly useful to differentiate
primary testicular failure from obstructive azoospermia.
Normal prepuberal testicular histology of undifferen-
tiated Leydig cell and immature germinal epithelium may
be seen in hypogonadotrophic hypogonadism.
Currently newer tests are forthcoming such as
1. Induction of artificial erection by intracavernosal
injection of smooth muscle relaxants like papaverine.
2. Alprostadil (PG E1) transurethrally as MUSE (medicated
urethral system for erection) or intracavernosal self
injection. If it does not induce erection, it may be due to
vascular cause.
3. Psychophysiological testing in response to visual erotic
stimuli and xenon washout. Nevertheless the value of
such tests is undergoing evaluation for adoption as
additional investigative procedures.
TREATMENT OF IMPOTENCE
As the erectile dysfunction/premature ejaculation is an
embarrassing predicament, the physician must exercise
extraordinary tact and patience to gain the confidence of
the subject, while analysing the sexual history. The primary
objective is to find out whether the dysfunction is from the
very beginning or a subsequent event. The next step is to
identify the cause of neurovascular and muscular
inadequacy, whether it is organic (Disease or drug induced)
or psychological or both. Before implementing the
therapeutic option, the sex partner is better subjected to
gynaecological examination for any obstructive pathology
or vaginismus.
Symptomatic Treatment
1. Reassurrance after systemic examination including the
emotional aspects and perceptions of both partners.
2. Counselling
a. to reduce sex anxiety by clearing misconceptions,
through proper sex education.
b. to lessen the stress and strain of day-to-day life.
c. to improve empathy and cooperation of the partner.
3. Correction of any psychological and/or behavioural
factors.
4. Non-pharmacological therapy
a. Ensure tranquil and relaxed environment.
b. Stimulation technique: Squeeze on the either side of
the coronal ridge on the glans penis and shaft
respectively while also applying steady pressure
squeezing the glans at frenulum, for couple of
seconds, which may be repeated couple of times
before orgasm occurs. Treatment by this method for
a few weeks may obviate premature ejaculation.
c. Condition the response to visual erotic stimuli.
d. Mechanical treatment
 Impotence 283

i. Implantation of a penile prosthesis. It is made incriminating factors should be identified to prevent or

from silicon rubber and is of two types—Non- reduce the duration and severity of the dysfunction.
inflatable and inflatable. The earlier devices have Supportive psychotherapy for marital relationship is one
been superseded by a self-contained inflatable facet of sex therapy. Further behavioural treatment and
prosthesis with a pump and reservoir placed appropriate psychotropic drug therapy for anxiety and
inside a pair of penile silastic cylinders which depression may enhance the individual’s performance up
are relatively easier for implantation and to his expectations.
manipulation.
ii. Vacuum erection devices (motorized and manual) Organic Causes
or constrictive ring.
Endocrinal
e. The other techniques include corporal dilation and
A. Testicular failure (Fig. 18.1):
electrostimulation therapies.
i. Primary testicular failure: As the conditions causing
5. Pharmacotherapy
androgen deficiency are irreversible, treatment is
a. Intracavernous injection of smooth muscle relaxants
androgen replacement therapy only. It consists of oral
like papaverine or vasodilating agents like
preparations (testosterone undecanoate 80 to 120 mg
phentolamine and prostaglandin E1 combined or
bd; or intramuscular injections of long acting esters
single or moxisylate (Useful in vascular E.D.).
(Refer to Chapter ‘Gynaecomastia’) or subcutaneous
b. MUSE (Medicated Urethral System for Erection)
implants (600-1000 mg in the form of 3-5 fused
PGE1 (Alprostadil) 250 microgram by intraurethral
pellets into the subcutaneous tissue of anterior
administration useful especially in vasculogenic
abdominal wall which is time consuming though the
erectile dysfunction.
duration of testosterone levels are maintained even
c. Androgen therapy which is often prescribed is of
up to 6 months).
little help unless hormone related erectile dysfunction
In the pubertal male, small doses of testosterone
exists.
are given initially and increased gradually to achieve
d. Sildenafil citrate orally 25-100 mg one hour before
masculinisation (development of secondary sexual
sexual activity (usually 50 mg). Useful in psycho-
characters, increased muscle mass and restoration
genic ED and neuropathnic ED. Minimal use in
vasculogenic ED and no use in fibrous replacement
of cavernous tissue. Verdenafil and Eadenafil are
other drugs (Relaxes blood vessels in penis and
lungs).
e. Centrally acting drugs
i. Trazodone
ii. Fluoxetine
iii. Naltrexone
f. Ephedrine (50 mg) or Imi Pramine (75 mg) beneficial
in retrograde ejaculation (i.e.) bladder sphincter fails
to close during ejaculation.
6. Surgical treatment
a. Surgical implantation (vide supra)
b. Repair of penile anomalies
c. Revascularisation surgery may be beneficial in
selected cases.

Specific Treatment
Psychogenic or Situational Factors
The intrapsychic dynamics of each partner and their marital
relationship and interaction must be assessed. Also the
Fig. 18.1: Hypogonadotrophic hypogonadism in a 28-year old
male. (A) Underdeveloped genitalia and absent pubic hair
before treatment (B) Appearance of pubic hair and developed
genitalia after treatment with alternating cycles of
gonadotrophins (hCG, LH, FSH) and testosterone
 284 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
of libido and potency). In the postpubertal male,
adequate hormonal replacement restores normalcy.
hCG 3000 IU/WK for six months and hCG (As
Above) + FSH > 75 IU thrice a week for one year
restores fertility.
ii. Secondary testicular failure: The causes of secondary
hypogonadism like tumours of the pituitary or
hypothalamus should be excluded. Hormonal
replacement therapy is instituted subsequently for
the prepuberal or postpuberal males as the case may
be (Refer to Chapter ‘Gynaecomastia’).
For delayed puberty, the treatment includes
intermittent testosterone (50-100 mg IM monthly)
for six months to be repeated if necessary after six
months; Human Chorionic Gonadotropin (HCG)
(1500 units IM weekly thrice for six months) after
withdrawing testosterone; FSH 75 IU thrice weekly
(or) both FSH and LH 75 IU each thrice weekly with
alternating cycles of gonadotrophins and testosterone
or pulsatile GnRH therapy. (Gonadotrophin releasing
hormone). Refer to Chapter ‘Gynaecomastia’.
B. Hyperprolactinaemia (Refer to Chapter ‘Gynaeco-
mastia’)
C. Hyperthyroidism (Refer to Chapter ‘Goitre’)
D. Diabetes mellitus (Refer to Chapter ‘Polyuria’)
Penile
A. Peyronie’s disease: Appropriate surgery is done, if
necessary.
B. Priapism: Nonsurgical treatment consists of irrigation
of the penis with diluted heparin solution (2000 units of
heparin in 200 ml saline) 2-4 ml for 5 min through scalp
vein needle, followed by massage and light pressure,
every time. Another procedure is multiple puncture
techniques to let out blood under tension. Treating any
obvious underlying cause is beneficial. Surgical
treatment by sapheno-cavernous bypass relieves spasm.
C. Phimosis: Treated by surgery.
Vascular
Revascular surgery or endarterectomy may be helpful. For
impotence due to aortic obstruction, reconstruction above
the origin of external iliac arteries prevents possible damage
to autonomic nerves resulting in worsening of potency.
Neurological and systemic diseases: Symptomatic therapy
for dysfunction instituted, while treating the underlying
cause accordingly.
Drug induced (Pharmacological) dysfunction: It is corrected
by prompt withdrawal of the same.
Physiological dysfunction: It may be treated with hormones
if deficiency exists, or by spacing conveniently.
Impotence 285
286 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter

Jaundice
19
Jaundice is yellow discolouration of the sclera, mucosa or Uptake and Transport Phase
skin due to raised serum bilirubin (conjugated or
The unconjugated (indirect) bilirubin that is liberated
unconjugated) levels. This is mostly formed by the
normally into the blood stream is transported to the liver.
haemoglobin breakdown in the reticuloendothelial system;
This water insoluble pigment is bound to plasma albumin
and also from myoglobin as well as cytochrome-C.
and does not pass through the kidney into urine.
Haemoglobin which is released from effete red cells is
Consequently it is present in the body fluids proportionate
broken down to iron and globin, besides bilirubin. Iron is
to the albumin content therein. (Alcohol disassociates it from
stored in the liver, globin is made available for the synthesis
albumin which forms the basis of indirect Van der Bergh
of haemoglobin once again in the red bone marrow and the
reaction) In the liver cell, the albumin gets dissociated and
bilirubin is excreted into the bile. About 1 to 1.5 g haemo-
the bilirubin is bound to ligandins (cytoplasmic anionic
globin, out of total 750 g of haemoglobin in the body, is
binding proteins) and this hepatic uptake of bilirubin is
catabolised daily. Normally serum bilirubin is about 1 mg
followed by transportation to the endoplasmic reticulum in
percent and exists in two forms (i) Conjugated (direct) and
the liver cell which is the site of the enzyme glucuronyl
(ii) Unconjugated (Indirect). Only when it is raised to 2 mg
transferase.
percent or more jaundice is recognised clinically by the
discolouration of the sclera, since the elastic tissue therein,
Conjugation Phase
possesses affinity for bilirubin.
In the microsomes of liver cells, unconjugated bilirubin gets
METABOLISM OF BILIRUBIN conjugated with the glucuronic acid by the activity of
glucoronyl transferse and converted to bilirubin glucuronide.
An insight into metabolism of bilirubin is imperative to
This is what is known as conjugated bilirubin (direct) which
understand jaundice (Fig. 19.1).
is water soluble and readily passes through the kidney. This
direct bilirubin pigment reacts directly with Ehrlich’s
Formation of Bilirubin (Breakdown of Haemoglobin)
aldehyde reagent, without the addition of alcohol (direct
Haemoglobin contains non-iron residue (protoporphyrin) Van den Bergh reaction).
besides iron and globin. The oxidation of protoporphyrin
(isomeric type III) results in the formation of biliverdin Excretory Phase
initially which is rapidly reduced to bilirubin. About 85
Alimentary phase The conjugated bilirubin is excreted
percent of the bilirubin is derived by this mechanism and
through bile canaliculi and enters the intestine.This is not
the remaining 15 percent is derived from the destruction of
absorbed as such and 50% of it gets converted into urobilino-
matured erythroid cells in the bone marrow and also from
gen by the action of intestinal bacterial flora. Some of the
certain nonerythroid factors like muscle pigment
urobilinogen is absorbed from the intestine back into the
(myoglobin) and respiratory enzyme (cytochrome-C).
liver through portal blood and most of it is re-excreted into
Iron + Protoporphyrin + Globin U Haemoglobin the bile (entero-hepatic circulation). Urobilinogen that is
Haemoglobin U Iron + Bilirubin + Globin not absorbed is known as stercobilinogen and is responsible
 288 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 19.1: Normal bile pigment metabolism

for the brown colour of the faeces. The daily faceal
stercobilinogen is about 300 mg.
Renal phase The small remaining portion of urobilinogen
(5%) which is not re-excreted by the liver into the gut, enters
the blood stream and gets excreted in the urine as
urobilinogen, as such. The daily urinary urobilinogen is 2-4
mg. Both urobilinogen and stercobilinogen are oxidised to
urobilin and stercobilin respectively, after exposure to air.
Pathophysiological Mechanisms
Thus an increase in the breakdown of red blood cells leads
to increased serum levels of unconjugated bilirubin, (which
is not found in urine) and the consequent increased bilirubin
excretion by liver results in excess of stercobilinogen in
stool leading to dark urine and stool, i.e. haemolytic
jaundice.
On the other hand, if the liver cells are damaged, all
bilirubin cannot be excreted and so diffuses into blood
through hepatic sinusoids; which bilirubin appears in the
urine. Further, the damaged liver cells excrete less bilirubin
than normal into the bile and so stercobilinogen in the faeces
is decreased with consequent pale stool. That pigment which
reached the intestine is transported back to the damaged
liver (enterohepatic circulation) which is incompetent to re-
excrete into the gut with consequent increased urinary
urobilinogen. Sometimes intrahepatic obstruction occurs in
the course of some cases of parenchymatous jaundice, when
bilirubin does not reach the intestine causing colourless
stool. Consequently, there is no enterohepatic circulation
and so urobilinogen is absent in the urine and reappears
when the cholestasis subsides as occurs in hepatocellular
jaundice.
 Jaundice
If direct bilirubin does not enter the gut at all due to
complete obstruction of the biliary channels, bilirubin
regurgitates into blood stream and appears in the
urine.Consequently no urobilinogen appears in the urine
since no bile is passing into the gut and no stercobilinogen
is formed with resultant colourless acholic stool, i.e.
obstructive jaundice.
Hence Jaundice can occur either due to increased
bilirubin production or decreased bilirubin clearance.
CLASSIFICATION AND CAUSES OF JAUNDICE
Classification and causes of jaundice are an enlisted in Table
19.1.
Anyone of the three clinical types of jaundice described
Table 19.1 can occur, due to either infections or drugs (lytic
effects, hepatotoxicity, hypersensitivity or cholestasis) or
malignancy or during postoperative period (blood trans-
fusion, septicaemic shock or bile duct injury).
1. Haemolytic Jaundice (Pre-hepatic)
The presenting symptoms may be due to the underlying
cause, rate of haemolysis and anaemia, rather than jaundice
which is mild. Evidence of increased haemoglobin
breakdown, is reflected by unconjugated hyperbilirubi-
naemia and jaundice, reticulocytosis, decreased plasma
haptoglobins and increased urobilinogen or haemoglo-
binuria. Haemolysis with anaemia and jaundice occur
usually due to either intracorpuscular or extracorpuscular
defects.
It may occur either in the circulation (Intravascular) or
in Reticuloendothelial system (Extravascular).
Intracorpuscular Defects (Congenital and Acquired)
Congenital (Membrane, haemoglobin and enzyme defects)
• Hereditary Spherocytosis (Acholuric Jaundice) or
Congenital Haemolytic Anaemia (Membrane defect)
It is characterised by splenomegaly, mild jaundice,
anaemia, spherocytosis, reticulocytosis and increased
osmotic fragility (laking begins at 0.5 to 0.75% of saline
and completes at 0.4% as against the normal value of
0.45 and 0.3 respectively). In the peripheral smear, the
erythrocytes are unduly thick and spherical unlike normal
biconcave appearance and the spherocytes are microcytic
and stain deeply without any pallor in the centre. Gall
stones may occur in about 50 percent of cases. It is due
to autosomal dominant inheritance. (The unduly fragile
blood cells with congenital abnormalities of the red cell
membrane, are easily destroyed)
289
• Hereditary eliptocytosis
The morphology of red blood corpuscle is oval or
elliptical. The clinical features are identical as above
though it is usually asymptomatic.
• Hereditary haemoglobinopathies (Haemoglobin
defects) The RBC contains 200-300 million molecules
of haemoglobin. Each molecule contains four heme
groups and one globin unit. Each globin unit consists of
two dissimilar pairs of polypeptide chains, which are
designated as alpha and beta. Each chain is made up of
141-146 amino acids. Normally there are three different
types of haemoglobins present in adults (HbA 97% and
other two haemoglobins HbA2 and HbF 3%). Haemo-
globinopathies constitute abnormalities in haemoglobin
chains. Though the differences between normal and
abnormal haemoglobins are minute, the clinical effects
are far-reaching.
a. Sickle cell anaemia The sickle(s) haemoglobin
differs from normal haemoglobin by substitution of
amino acid in the beta chains of the haemoglobin
molecule, i.e. valine instead of glutamic acid. It is
due to homozygous inheritance of a gene from both
the parents. The heterozygous inheritance has sickle
cell trait. Anaemia (Hb 6-8 gm% with reticulocytes
10-20%) jaundice and hepatosplenomegaly may be
present. Pulmonary infections or infarctions,
meningeal infections or cerebral thrombosis with fits
or hemiplegia, haematuria due to renal infarcts and
hand-foot syndrome (painful swellings of hands and
feet) are additional presentations. There is impaired
physical development with increased tendency for
pulmonary infections and vasoocclusions. The crises
may be from vasoocclusion, haemolysis, aplasia of
marrow or sequestration. Painful haemolytic crisis
occurs due to microinfarcts.
The crisis consists of attacks of abdominal pain
or bone and joint pains, fever and vaso occlusive
episodes (involvement of the central nervous system-
hemiplegia; pulmonary vasculature-pulmonary
infarction; kidneys-haematuria). Such recurrent
episodes ultimately produce damage of any organ
like lung, kidney, liver and skeletal system (aseptic
necrosis of the femoral head). Sequestration crisis
(liver and spleen become engorged with blood and
enlarge rapidly from trapped RBCs with a sharp fall
of Hb% and PCV) is a dangerous complication.
Septicaemia or renal failure are common terminal
events. Diagnosis is confirmed by (i) demonstration
of the sickling phenomenon with sodium metabisul-
phite and (ii) demonstration of haemoglobin-S on
electrophoresis.
 290 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 19.1: Aetiological classification of jaundice d. Hypothyroidism

e. Breast milk jaundice
Haemolytic Jaundice (Prehepatic)—Increased Bilirubin Production
B. Cell Damage and Impaired Excretion
A. Intracorpuscular Defects
a. Acute hepatitis (infections)
1. Congenital
i. Viral infections
a. Hereditary spherocytosis or Acholuric Jaundice and
ii. Septicaemia
Hereditary eliptocytosis (Cell membrane defect).
iii. Leptospirosis
b. Hereditary haemoglobinopathies (globin defects)
iv. Amoebiasis
i. Sickle cell anaemia
b. Acute hepatitis (Chemicals and Drugs)—Alcohol,
ii. Thalassaemia
tetracycline, rifampin, paracetamol, methotrexate,
c. Hereditary enzymopathies (enzyme defects)
chlorpromazine, halothane, methyldopa
i. Glucose-6 phosphate dehydrogenase deficiency
c. Chronic hepatitis
ii. Pyruvate kinase deficiency
d. Cirrhosis
2. Acquired
e. Hepatoma
a. Paroxysmal nocturnal haemoglobinuria (complement
f. Congestive heart failure
sensitivity due to structural or biochemical defect of
membrane) Obstructive Jaundice (Post-hepatic)
b. Spur cell anaemia (membrane defect) A. Intrahepatic Cholestasis (Impaired Excretion)
B. Extracorpaucular Defects-(Acquired) 1. Congenital
1. Immune a. Benign familial recurrent cholestasis
a. Autoimmune b. Recurrent intrahepatic cholestasis of pregnancy
i. Acquired haemolytic anaemia due to agglutinins c. Alpha-I antitrypsin deficiency
(acute or chronic) d. Dubin-Johnson syndrome
ii. Haemoglobinurias e. Rotor’s syndrome
b. Isoimmune 2. Acquired
i. Incompatible blood transfusion a. Infections
ii. Rh incompatibility i. Viral hepatitis
c. Drug induced-Methyl dopa; L-dopa; Mefanimic acid. ii. Septicaemia
2. Nonimmune iii. Hydatid cyst
a. Infections: b. Chemicals and drugs—Alcohol, chlorpromazine, oral
i. Malaria contraceptives, testosterone, anabolic steroids,
ii. Septicaemia nitrofurantoin, chlorpropamide
b. Chemicals c. Cirrhosis: Primary biliary cirrhosis
i. Industrial poisons d. Cholangitis: Ascending and sclerosing
ii. Drugs: Chlorpromazine, sulphonamides e. Carcinoma of the intrahepatic bile ducts (cholangio
c. Animal and vegetable poisons—snake venom, favism carcinoma)
d. Physical agents: Burns B. Extrahepatic Cholestasis—(Biliary Obstruction) Posthepatic or
e. Hypersplenism Surgical
f. Intravascular trauma due to 1. In the wall of the duct (luminal)
i. Prosthetic valves (Cardiac haemolysis) a. Obliteration of bile ducts
ii. Thrombotic thrombocytopenic purpura (Micro- b. Choledochal cyst
angiopathic haemolytic anaemia) c. Biliary stricture: injury
iii. Haemolytic uraemia syndrome d. Cholangitis
iv. Disseminated intravascular coagulation e. Carcinoma of the bile duct
v. March haemoglobinuria f. Pancreatitis and pancreatic malignancy
2. Outside the lumen (extra luminal)
Hepatocellular Jaundice (Hepatic) a. Tumours and Metastases
A. Impaired Hepatic Uptake and Transport or Conjugation i. Carcinoma of the gallbladder
1. Congenital ii. Carcinoma of ampulla of vater
a. Physiological jaundice iii. Carcinoma of the head of the pancreas
b. Gilbert’s disease iv. Metastasis in the lymph glands of porta hepatis
c. Crigler-Nazzar syndrome b. Hydatid cyst
d. Lucey-Driscoll syndrome c. Duodenal diverticulum
2. Acquired 3. Inside the lumen (intraluminal)
a. Drugs—Chloramphenicol, rifampin, vitamin K a. Gallstones in the common bile duct (choledocholithiasis)
b. Hepatitis
b. Parasites
c. Cirrhosis
 Jaundice
b. Thalassaemia: There are two groups of thalassae-
mias—one affecting the alpha chain and the other
affecting the beta chain of haemoglobin. Alpha
thalassaemia is rare. The classical thalassaemia major
is beta thalassaemia or Cooleys anaemia (infantile).
It represents the homozygous state as against beta
thalassaemia minor which is a heterozygous state
(adult form). It is inherited as a recessive character
and encountered in the Mediterranean, south Pacific,
parts of Asia including India and Central Africa
regions. The essential diagnostic features are severe
anaemia of iron deficiency type, right from infancy
with massive hepatosplenomegaly. Jaundice is mild,
if present. The face is characteristic with broad base
of the nose and prominent maxillae (Mongol type).
Skull is enlarged due to marrow hyperplasia (bossed
skull). Growth is retarded resulting in short stature.
Thalassaemia minor is asymptomatic with mild
persistent anaemia and usually diagnosed in adult
life when any other member of the family is affected
or when chronic anaemia is being evaluated. Blood
film shows increased number of target cells,
basophilic stippling, nucleated red cells and
microcytes. MCHC is markedly reduced. HbA2 is
increased in thalassaemia minor (5% instead of
normal 2.5%) whereas it is normal in thalassaemia
major cases. Foetal haemoglobin is increased to 90
percent in major and up to 6 percent in minor.
However HbA is absent or grossly reduced in
thalassaemia major. The skeletal lesions are striking
usually in major cases which consist of thinning of
the cortex (hair-on-end appearance). Cholelithiasis
and leg ulcers may develop in thalassaemia major,
as in sickle cell anaemia. Few patients reach
adulthood.
• Hereditary Enzymopathies (Enzyme defects)
a. Glucose-6 phosphate dehydrogenase deficiency
(G6PD): This X-linked enzyme within the
erythrocytes is deficient and the deficiency reflects
the susceptibility to haemolysis especially on
exposure to infections (like viral or malarial), drugs
(like pamaquine, sulphonamides, nitrofurantoin and
sometimes Vitamin K) or fava beans (favism). About
100 variants of G6PD are described. Hemizygotes
(affected males) inherit abnormal gene from their
mothers who are carriers (heterozygotes.) The
clinical features resemble that of acute haemolytic
anaemia with rise in unconjugated bilirubin and
reduction in plasma haptoglobins. Heinz bodies in
291
red cells (haemoglobin precipitates) are
demonstrated by supravital staining. Some may have
chronic haemolytic anaemia. Diagnosis is confirmed
by a history of acute haemolytic episodes relating to
exposure to oxidant drugs, a dye reduction test using
cresyl blue, methaemoglobin reduction test,
glutathione stability test, and fluorescent spot test.
For accurate inference, better wait for two weeks
after reticulocytosis (following acute haemolysis)
since high reticulocyte counts may give rise to false
positive reading.
b. Pyruvate kinase deficiency: The clinical features are
suggestive of congenital haemolytic anaemia
(nonspherocytic) with jaundice and hepato-
splenomegaly. It is inherited as autosomal recessive
character and usually presents in childhood.
Acquired
• Paroxysmal Nocturnal Haemoglobinuria (vide infra)
• Spur cell anaemia: Severe hepatocellular disease like
cirrhosis may result in altered RBC morphology (such
as irregularly shaped red cells with spicules and bizarre-
shaped fragmented red cells associated with
acanthocytes) with haemolytic anaemia. The membrane
of the spur cells contains excess cholesterol which
reduces the fluidity of the cell membrane with
consequent deformity.
Extracorpuscular Defects
Immune
• Autoimmune: Acquired haemolytic anaemia is
invariably due to acquired extracorpuscular defect, and
usually seen in adults. The haemolysis occurs by the
action of autoantibodies (globulins act as antibodies)
on the patient’s own red cells. These autoimmune
antibodies may be warm antibodies or cold antibodies;
the former reacting at body temperature and the latter
reacting in cold. The haemolysis due to warm antibodies
may be due to lymphoma, chronic lymphatic leukaemia,
lupus erythematosus, drugs (methyldopa) or idiopathic.
The cold antibody mediated haemolysis may be either
due to cold agglutinin disease (which may be acute
occurring two weeks after mycoplasma infections or
chronic as in lymphoma) or idiopathic or paroxysmal
cold haemoglobinuria (vide infra).
a. Acquired autoimmune haemolytic anaemia: It may
be acute or chronic. Acute type is commonly seen in
children (Lederer’s anaemia). It is associated with
constitutional symptoms, rapidly progressing
292 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
anaemia, jaundice, and splenomegaly. The haemo-
lysis may occur after mycoplasma or viral infections.
Chronic acquired haemolytic anaemia is seen in
adults persisting for months and years. It is associated
with lymphatic leukaemia, lymphoma, lupus
erythematosus or drugs (methyldopa). The clinical
features are those of (i) anaemia, (ii) haemolysis
(jaundice, hepatosplenomegaly with or without
fever) and (iii) the underlying disease.
Antibodies are demonstrated on the red cells and
in the serum. A positive direct Coomb’s test and
presence of warm antibodies on immunoelectro-
fluoresence, are contributory.
b. Haemoglobinurias: Normally haemoglobin breaks
down in the cells of the reticuloendothelial system.
In certain conditions, the haemolysis is intravascular
resulting in haemoglobinaemia. When the level of
plasma haemoglobin exceeds the renal threshold, it
result in haemglobinuria. The urine appears red
which has to be differentiated from haematuria. (The
microscopic examination of the centrifuged
specimen shows red cells in haematuria). The colour
of plasma is pink or red in haemoglobinuria whereas
in haematuria the colour of the plasma is normal.
Haemoglobinurias may be acute or chronic.
Acute haemoglobinurias are due to isoimmune and
non-immune causes. Chronic haemoglobinurias are
paroxysmal and result from exercise, exposure to
cold, leutic infections or due to acquired intra-
corpuscular defect with excessive sensitivity to
complement as in paroxysmal nocturnal haemo-
globinuria (vide infra).
i. Paroxysmal cold haemoglobinuria: The IgG
antibody formed is directed against the antigen
of the red cell surface and Donnath Landsteiner
test is positive. (Plasma of refrigerated whole
blood becomes red on rewarming with haemoglo-
binaemia). It is associated with fever and chills,
pain in the abdomen or back, acholuric jaundice
and haemoglobinuria. It occurs after viral or
leutic infections.
ii. Paroxysmal nocturnal haemoglobinuria
(PNH): It is a rare haemolytic disorder with an
acquired intracorpuscular abnormality related to
defect of the membrane and sensitivity to
complement. The red cells fix more C1 than
normal red cell per unit of the antibody present
but the antibody may not be necessary for the
lysis of the red blood cells. The acquired defect
of the red cell membrane makes the red cells
unduly sensitive to lysis when the pH of the blood
becomes more acidic during sleep. The
granulocytes and platelets appear to share the
membrane defect of the PNH red cells. It usually
affects young adults. Weakness, yellow discolora-
tion of the skin, evidence of chronic haemolysis,
intermittent haemoglobinuria accompanied by
abdominal pain and fever anaemia, mild
hepatosplenomegaly are the clinical manifesta-
tions. Pancytopenia, venous thrombosis,
susceptibility to infections are the accompani-
ments. The diagnosis is confirmed by
demonstrating haemolysis with incubation of the
patient’s red cells in the acidifide normal serum.
This test is useful specially when haemoglobin-
uria is not obvious. Red cells transfusion and
steroids useful.
Isoimmune
a. Incompatible blood transfusion: Incompatible blood
transfusions result in the haemolysis of the transfused
red cells. Fever with chills and backache followed by
jaundice are the usual symptoms which occur after the
transfusions of few millilitres of incompatible blood. In
severe cases, haemoglobinaemia and haemoglobinuria
occur leading to anuria and acute tubular necrosis.
b. Rh incompatibility: In the majority of people red cells
contain Rh antigen-D and they are known as Rh
positives. The children of Rh positive father and Rh
negative mother may be Rh positive. The Rh negative
mother gets sensitised by the Rh positive factor present
in the foetal red cells. The anti-Rh antibodies thus
produced, penetrate the placenta and produce haemolysis
of the foetal red cells. Usually the first child escapes the
disease unless the Rh negative mother is made sensitised
by an earlier Rh positive blood transfusion. Similarly
haemolytic disease may occur due to incompatibility of
the ABO groups, i.e. if the mother belongs to group O
and foetus is A or B, the anti-A or anti-B antibodies may
result in haemolysis of the foetal cells. This occurs even
in the first pregnancy. The three clinical forms vary in
severity. The severest form consists of oedema and
hepatosplenomegaly resulting in fatality in few hours
(erythroblastosis fetalis). The severe form consists of
deep jaundice, within 24h of birth with splenomegaly
and cutaneous haemorrhages with kernicterus (icterus
gravis neonatorum). The third and mild form is
characterised by congenital anaemia of the new born
with mild jaundice and splenomegaly.
 Jaundice
Non-immune
• Infections: Infections like malaria, septicaemia may
result in haemolytic anaemia, sometimes the
haemolglobin falling to 3 g in one or two days.
• Chemicals: Industrial poisons like lead, copper salts,
naphthalene (moth balls), drugs like phenyl hydrazine
and pamaquine, cause haemolytic anaemia especially
when it is associated with glucose-6 phosphate
dehydrogenase deficiency.
• Animal and vegetable poisons: Animal poisons like
snake venom or exposure to fava beans (Vicia fava) may
produce haemolysis by direct toxic effects specially those
with G6PD deficiency.
• Physical agents (burns): In severe burns, when the red
cells pass through the burnt areas intravascular
haemolysis occurs resulting in haemoglobinuria, since
the red cell membrane is unstabe at high temperature
(above 49°C).
• Hypersplenism (Refer to Chapter ‘Bleeding Disorders’)
Intravascular Trauma
a. Prosthetic valves Haemolytic anaemia can occur in
whom replacement with prosthetic valves is done in
open heart surgery. The haemoglobin levels may fall
up to 5 g even, with fragmented red cells,
reticulocytosis and haemoglobinuria and other
evidence of haemolysis. The haemolysis is of
mechanical origin due to trauma to the red blood
cells.
b. Thrombotic thrombocytopenic purpura (Refer to
c. Disseminated intravascular
coagulation
d. Haemolytic uraemia syndrome
}
Chapter
‘Bleeding
disorders’)
e. March haemoglobinuria Haemoglobinaemia and
haemoglobinuria are observed after a prolonged
march or any such exercise. Rhabdomyolysis and
myoglobinuria may also occur.
Hepatocellular Jaundice (Hepatic)
Impaired Hepatic Uptake and Transport or
Conjugation of Bilirubin
Congenital
• Physiological jaundice: This neonatal jaundice is due
to primary defect in the transport or conjugation of
bilirubin in the liver, without any organic disease. It
occurs after 24h between 2 to 15 days of life espicially
in premature infants due to immature hepatic enzyme
system with decreased activity of glucuronyl transferase.
293
Generally, the activity of glucuronyl transferase increases
within two weeks after birth and jaundice may disappear.
Jaundice may be prolonged if it is associated with
hypothyroidism. When the unconjugated bilirubin is 20
mg per 100 ml or more, it may lead to kernicterus and
prove fatal.
• Gilbert’s disease: It is a chronic unconjugated non-
haemolytic hyperbilirubinaemia due to the glucuronyl
transferase deficiency. Jaundice is mild and usually
appears in the second decade. It is detected only on
routine examination as there is paucity of systemic
symptoms. Liver function tests and liver histology are
normal. The serum bilirubin is increased 2 to 3 fold,
after prolonged fasting or low calorie diet (400 calories)
due to decrease in glucuronyl transferase activity,
whereas it is decreased with phenobarbitone, due to
increased activity of the enzyme.
• Crigler-Najjar syndrome: This may be due to complete
or partial deficiency of the enzyme. Complete deficiency
is seen in infants, and the level of unconjugated bilirubin
is very high (more than 20 mg per 100 ml).Kernicterus
is a fatal complication. Phenobarbitone has no effect. In
partial deficiency, jaundice is less severe and may appear
in adolescence. Bile contains more unconjugated
bilirubin and less conjugated bilirubin unlike in the
complete deficiency where there is no conjugated
bilirubin at all. Phenobarbitone is effective in partial
deficiency.
• Ducey-Driscoll syndrome: Bilirubin conjugation is
inhibited by hormones during pregnancy with
consequent unconjugated hyperbilirubinaemia.
Acquired
Apart from hereditary deficiency of the enzyme, certain
drugs (like chloramphenicol, vitamin K)or liver cell damage
(as in hapatitis or cirrhosis) or hypothyroidism (where
normal maturation of the enzyme is delayed in cretins) or
breast fed infants (developing jaundice due to pregnanediol
in breast milk) may account for the acquired deficiency of
the glucuronyl transferase with consequent impairment of
bilirubin conjugation.
Cell Damage and impaired excretion (Acquired)
Hepatocellular Disease (infective and toxic): The hepato-
cellular damage leads to impairment of metabolism of
bilirubin (uptake by hepatocytes, transport of bilirubin to
microsomes for conjugation and excretion of conjugated
bilirubin through the microvilli into biliary canaliculi) and
facilitates diffusion of conjugatd bilirubin into hepatic
 294 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
sinusoids and blood stream. Further an intrahepatic
obstructive element is added by the swollen hepatocytes and
infiltration of inflammatory cells, resulting in regurgitation
of bilirubin from canaliculi into blood. The degree of damage
to hepatocytes and consequent impaired excretion is
reflected by raised plasma transaminases and conjugated
bilirubin.
This hepatocellular jaundice may result from
a. Infections like viral (hepatitis viruses, Epstein-Barr,
Yellow fever, Cytomegalo), septicaemia, leptospirosis,
amoebiasis, malaria.
b. Chemicals and drugs-alcohol, drugs like rifampin,
methotrexate, methyldopa, anaesthetics like halothane.
c. Pregnancy-HELLP. (Haemolysis, Elevated Liver
Enzymes, Low Platelet count).
Acute hepatitis (infective)
a. Viral hepatitis: Apart from the common hepatitis-A
(HAV) and hepatitis-B viruses(HAB), Non-A non-B
hepatitis viruses have been recently documented, i.e.
hepatitis-C (HCV) and hepatitis-E (HEV) and HGV in
addition. Delta virus (HDV) is also incriminated.
Hepatitis-A and B virus infections predominantly
appear identical in their clinical presentation although
the incubation period is 1 to 6 months or more in
hepatitis-B (Serum hepatitis) as against 2 to 6 weeks in
hepatitis-A (infectious hepatitis). The mode of entry of
hepatitis-B virus is through blood, i.e. needles or
haemodialysis, nonpercutaneous (sexual contacts,
perinatal transmission) whereas that of hepatitis-A virus
is faeco-oral, which is endemic in our country.
Non-A, non-B viruses, i.e. hepatitis-C is usually
transmitted parenterally (post transfusion) and its
incubation period is 1 to 5 months. It produces acute
liver disease leading to chronic hepatits with cirrhosis
like hepatitis-B. Hepatitis-E is spread enterically and its
incubation period is 2 to 9 weeks. It is responsible for
many epidemics of jaundice (water-borne epidemics)
like HAV and causes acute hepatitis only without
progressing to chronicity but may prove fatal in the 3rd
trimester of pregnancy. Delta virus (hepatitis D) infects
patients as co-infection with hepatitis-B virus or
superinfection in hepatitis-B carriers. It causes severe
acute viral hepatitis or decompensated chronic liver
disease. The mode of infection is similar to HBV and
the delta antigen is frequently detected in the serum of
B carriers. Hepatitis G is transmitted like hepatitis-B.
Acute hepatitis is diagnosed by detecting HGenv
antibodies. It can cause fulminant liver failure.
Clinical features of acute viral hepatitis (HAV)
classically are constitutional symptoms like fever,
anorexia, nausea, mild abdominal pain followed by
jaundice usually after 1 to 2 weeks. In the majority of
cases, there is tender hepatomegaly, in a few
splenomegaly and cervical lymphadenopathy. The urine
is highly coloured with bilirubin and urobilinogen in
the urine. Sometimes, cholestatic presentation may be
there due to compression of the intrahepatic biliary ducts,
by altered cellular pattern. In this phase, urobilinogen
disappears in the urine and when the recovery sets in, it
reappears. The colour of the stool is pale during the
cholestasis due to absence of stercobilinogen. The serum
transminases (SGPT, SGOT) are increased. The alkaline
phosphatase is mildly elevated during the intrahepatic
obstructive phase. The serum bilirubin and the
prothrombin time are increased proportional to the
severity of the disease. Anti-HAV of IgM class (for 2
months) and IgG (which rises slowly and persists for
life) may be detected in hepatitis-A infection.
The cholestatic phase may be prolonged unusually
in some cases with biochemical evidence of cholestasis
such as elevated alkaline phosphatase and cholesterol.
Sometimes it may become fulminant with rapid onset
of hepatocellular failure. Usually the course of viral
hepatitis (HAV) is uneventful with complete recovery
or rarely, if ever, develops fulminant hepatitis. Carrier
state or chronicity is unknown.
The clinical features of hepatitis-B virus infection
and, hepatitis-A infection are similar although the onset
in the former is insidious with a prolonged prodromal
phase. Urticaria, pleuritis, arthralgia or arthritis are the
prodromal manifestations before the onset of jaundice
and hepatosplenomegaly. About 10 percent of infective
individuals become asymptomatic carriers as against
rarity of carrier state in hepatitis-A. Further, it is
characterised by potential sequelae like chronic
persistent hepatitis, chronic active hepatitis, cirrhosis and
hepatocellular carcinoma. There are 3 antigens and 3
antibodies related to HBV infection.
i. The surface antigen (HBsAg) is the earliest marker,
occurring after 4 weeks of exposure even before
biochemical evidence of hepatitis and present upto 1-6
months. It indicates active present infection or a carrier
state if it persists for >6 months. Specific antibody
(Anti-HBs) occurs in most individuals after the
disappearance of HBsAg which indicates past infection
and immunity to HBV in the majority, although a few
cases are reported to be infective in the presence of
 Jaundice
anti-HBs (probably due to mutants of HBV). Anti HBs
appears after five and half months and last for more
than five years. If present alone it is due to vaccination
only.
ii. HBeAg (Pre core antigen) is found only in patients
who are positive for HBsAg. It reflects viral activity
and high infectivity. It is present for 6-12 wks after
acute illness and then absent with a tendency for more
liver damage and chronicity. Anti-HBe indicates past
infection and persists.
iii. Core antigen (HBcAg) is found only in the liver cells
in the absence of HBsAg. It indicates viral replication
and recovery from HBV is said to be complete only
when the core particles are no longer found in the liver.
Anti-HBc IgG is present in moderate amounts in all
the cases of acute HBV infection and indicates acute
and past infection although the HBsAg is negative. This
antibody appears after three months and lasts for more
than five years. Circulating form of HBcAg is HBe Ag
as former is not found in blood. Anti HBc IgM is
present (high amount) in acute infection and absent in
past infection unlike Anti HBc IgG. Which is present
in Past infection and in acute infection.
DNA polymerase (present in the core) activity can be a
sensitive index of viral replication (i.e.) present in acute
infection and may persist for years in chronic carriers
reflecting continued infectivity.
In those who are positive for HBsAg, detection of IgM
anti-HBc is essential for differentiating carrier state from
acute HBV infection. So serological tests for HBV are
(1) HBsAg (2) Anti HBs (3) HBeAg (4) Anti HBe (5) DNA
polymerase (6) Anti HBc IgG
IgM
Hepatitis-C virus is responsible for 90 percent of post
transfusion hepatitis since the incidence of post transfusion
type B hepatitis has appreciably reduced after routine
screening for HBsAg. The prodromal phase may be
prolonged as in HBV and cirrhosis or hepatoma chronic
hepatitis or chronic carrier state may be a sequel. It is often
subclinical. Antibody tests +ve at < 4 months.
Hepatitis E virus which behaves like hepatitis-A does
not lead to chronic liver disease. Fulminant hepatitis is less
common. Anti HEV detection is diagnostic.
Other viruses
• Epstein-Barr, Cytomegaloviruses (Refer to Chapter ‘PUO’)
a. Yellow fever caused by arbovirus spread by Aedes
mosquitoes presents with fever, jaundice, bleeding
and oliguria.
295
b. Septicaemias (Refer to Chapter ‘Shock’)
c. Leptospirosis (Refer to Chapter ‘Pyrexia of
Unknown Origin’)
d. Rickettsial fever (Refer to Chapter ‘Pyrexia of
Unknown Origin’)
e. Amoebiasis The protozoa are carried from caecum
and ascending colon to the liver via portal venous
system and cause cytolytic action resulting in focal
necrosis. This amoebic hepatitis may be a precursor
of suppurative amoebic hepatitis (liver abscess),
when jaundice may occur (Fig. 19.2).
Fig. 19.2: Ultrasound scan of the abdomen showing cystic
space occupying lesion in the left lobe of the liver (both sagittal
and transverse scans)—Amoebic abscess of the liver.
Acute hepatitis (Toxic)
• Chemicals, Drugs and Toxins
a. Alcohol Acute alcoholic hepatitis may occur in a
known alcoholic without symptoms of previous liver
disease. It can result in acute or chronic inflammation
of the liver parenchyma. The longer the duration of
drinking and larger the quantities consumed, the
greater the chances of developing alcoholic hepatitis
and cirrhosis. It is usually seen after a recent bout of
heavy drinking. The clinical picture may vary from
hepatomegaly without symptoms to a state of critical
illness. Not all drinkers develop liver disease. Factors
like alpha-1 antitrypsin deficiency may predispose.
The onset may be vomiting, jaundice, tender
hepatomegaly and even ascites with or without fever.
The liver may show fatty degeneration which is
reversible. The ratio of SGOT and SGPT is more
than 2. Obstructive type of jaundice may be present.
 296 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Drugs Several drugs can cause jaundice like (a) direct
hepatotoxic drugs like tetracycline, paracetamol,
mercaptopurine, valproic acid; (b) drugs causing
hepatitis like syndrome due to host idiosyncracy, e.g.
halothane, methyldopa, rifampin, pyrazinamide,
ethionamide isoniazide; (c) drugs causing chronic
active hepatitis like paracetamol, chlorpromazine,
oxyphenisatin (laxative), methyldopa, halothane; or
(d) drugs like methotrexate causing cirhosis. The
clinician must be aware of such drug induced liver
disease with hepatocellular jaundice. Withdrawal
(suffices)
c. Toxins Food toxins like mycotoxins, Amanita
mushrooms, senesiosis and paraquat, are also
incriminated in toxin induced hepatitis.
Chronic hepatitis It is a chronic inflammatory reaction of
more than six months duration, which is recognised by
continued abnormal liver tests. This may be either chronic
persistent hepatitis or Chronic active hepatitis (CAH), which
is differentiated positively only by liver biopsy. It is either
viral or toxic or antoimmune origin.
In chronic persistent hepatitis, there is minimal fibrosis,
infiltration of mononuclear cells in the portal area without
any alteration in the lobular architecture and characteristic
absence of cirrhosis. Hepatitis-B, Hepatisis-C viruses,
alcohol, drugs like INH, methyldopa and cytotoxics are the
causative agents. Fatigue, anorexia and hepatomegaly may
be present. Prognosis is excellent, although rarely progresses
to CAH.
In chronic active hepatitis, piecemeal necrosis (necrosis
of the liver cells at the limiting plate between parenchyma
and connective tissue) or bridging necrosis (between central
vein and portal tract) and fibrosis are invariably present with
distortion of lobular architecture which can lead to cirrhosis.
CAH may follow hepatitis-B or HCV or oxyphenisatin and
other drugs like Methyl dopa, nitrofurantoin amiodarone,
penicillamine; or may result from cellular immune reaction.
So much so it occurs in association with autoimmune disease
especially in young women or may be drug induced when
IgG is markedly high and LE cells are present (Lupoid CAH)
or may follow Hepatitis B (B type CAH).
Autoimmune Chronic Active Hepatitis
There are 3 types and auto antibodies vary in each type. In
type I the antibody is antinuclear antibody (ANA) or
antismooth muscle antibody (ASA) in type II antibody is
antimitochondrial antibody (AMA) and in type III antibodies
to soluble liver antigen. Type I may be associated with other
autoimmune disease apart from signs of liver disease.
Recurrent acute episodes are documented. Clinical features
are highly variable ranging from asymptomatic to fatal
hepatic failure. Jaundice is persistent or recurrent with
hepatosplenomegaly and spider naevi or extra hepatic
manifestations like arthropathy, skin eruptions,
pleuropericardial involvement, colitis and glomerulo-
nephritis. The sequelae especially secondary to hepatitis-B
or HCV include cirrhosis or hepatocellular carcinoma. About
50 percent may be fatal within five years of the onset of
symptoms.
Cirrhosis Jaundice in cirrhosis is a late manifestation and
rarely severe. It is usually diagnosed by the presence of
ascites with distended veins over the abdominal wall and
splenomegaly due to portal hypertension, followed by signs
of hepatic insufficiency like palmar erythema, spider naevi,
testicular atrophy, oedema and jaundice and neuropsychiatric
changes. The architecture of the liver is irreversibly altered
with regenerating nodules. (Refer to Chapters Oedema and
Coma). There are many varieties of cirrhosis documented
1. Cryptogenic (portal or micronodular)
2. Alcoholic and/or nutritional deficiencies (portal or
micronodular)
3. Posthepatitis/chronic active hepatitis (postnecrotic or
macronodular)
4. Primary-biliary and secondary biliary (micro and later
macronodular) (Vide infra.)
5. Inherited metabolic abnormalities (Wilson’s disease,
Haemochromatosis, alpha-I antitrypsin deficiency)
(micro and later macronodular)
6. Cardiac (portal or micronodular)
7. Other forms of cirrhosis
i. Chronic inflammatory bowel disease
ii. Fibrocystic disease of the pancreas
iii. Intestinal bypass for obesity
iv. Budd-Chiari syndrome
v. Chemicals (arsenic)
vi. Drugs (methotrexate)
vii. Parasitic: Schistosomiasis (Refer Chapter—’Weight
Loss’
Hepatoma—Refer “pyrexia of unknown origin.”
Congestive heart failure Hepatocellular anoxia and
consequent liver cell damage in heart failure may result in
jaundice. Increased pigment overload of hepatocytes from
excessive destruction of blood in the lungs (infarcted area
or extravasated blood into the pulmonary alveoli) sometimes
contribute.
 Jaundice
Obstructive Jaundice (Post-hepatic)
This can be intrahepatic or extrahepatic. Usually intrahepatic
obstructive jaundice is acute, i.e. lasting less than three
months and invariably due to medical disorders. Intrahepatic
obstructive jaundice can also be chronic like in primary
biliary cirrhosis. The extrahepatic obstructive jaundice is
generally chronic, lasting for more than three months and
usually due to surgical conditions.
In acute obstructive variety, jaundice is deep, pruritus,
pain in the right hypochondrium and intermittent fever and
xanthopsia, are the usual symptoms. Nontender
hepatomegaly is invariably present. Gallbladder and spleen
may be palpable. The stool is pale and urine shows no
urobilinogen.
In chronic variety, progressive jaundice, Protracted
Pruritus, xanthoma, steatorrhoea due to bile salt deficiency
with consequent fat soluble vitamin and calcium
deficiencies, portal hypertension with hepatosplenomegaly
are common. The biochemical changes like raised serum
bilirubin, alkaline phosphatase and cholesterol are
diagnostic. If the obstruction is not relieved eventually
secondary biliary cirrhosis develops. Ascending cholangitis
may be an early complication. Hepatobiliary imaging
procedures aid evaluation.
Intrahepatic Obstructive Jaundice or Intrahepatic
Cholestasis (Impaired Excretion)
Congenital
• Benign familial recurrent cholestasis: It is a rare entity
with recurrent atacks of pruritus and jaundice. During
the attack, serum alkaline phosphatase and bile acids
are raised. Liver biopsy shows cholestasis and during
remissions it is normal. The familial incidence and
proneness for the younger age group are highly
suggestive.
• Recurrent intrahepatic cholestasis of pregnancy: In
some women, intrahepatic cholestasis occurs during
pregnancy in the third trimester probably due to
increased sensitivity to the hepatitic excretory functions
of oestrogens. The clinical features are jaundice and
pruritus. Serum bilirubin, alkaline phosphatase and
cholesterol are raised. These abnormalities readily
subside after delivery and revert to normal in 1 to 2
weeks. It may recur in subsequent pregnancies.
• Alpha 1 Anti-trypsin (AT) deficiency: It is alpha-1
globulin produced by the liver and is a serine proteinase
inhibitor, the most potent of which is the enzyme
297
neutrophil elastase. Homozygous deficiency of serum
AT is associated with liver disease which includes
cholestatic jaundice in neonates (neonatal hepatitis) and
progressive cirrhosis in later life as well as emphysema.
The release of proteinases during the inflammatory
processes causes excessive tissue damage due, to low
protective AT levels (normal value is more than 180
mg%) and failure to secrete AT from hepatocytes may
further lead to cellular damage. AT inclusions are readily
visible in the hepatocytes.
• Dubin-Johnson syndrome: It is a familial disorder with
defect in excretion of conjugated bilirubin. So it is
predominantly conjugated hyperbilirubinaemia.
Jaundice may commence at any age and may be
intermittent with pain in the right hypochondrium.
Constitutional or gastrointestinal symptoms may or may
not be present. There may be mild hepatomegaly. Liver
histology shows black or brown pigment in hepatocytes.
Oral contraceptives may precipitate the changes for the
first time.
• Rotor’s syndrome: It is akin to Dubin-Johnson syndrome
without pigment in the liver cells. There is impairment
of hepatic storage capacity. It is inherited as autosomal
dominance with impaired penetrance.
Acquired
Intrahepatic cholestasis occurs (with or without mechanical
obstruction) due to obstruction in the pathway between site
of conjugation of bilirubin pigment in the liver and its
excretion into the biliary canaliculi. The classical
illustrations are
• Infections: Viral hepatitis (Vide supra)
• Chemicals and drugs: Drug induced cholestasis may
be due to steroids (oral contraceptives, methyl
testosterone, anabolic steroids, phenothiazine
(chlorpromazine), nitrofurantin and chlorpropamide,
apart from alcohol.
• Primary biliary cirrhosis: It is an autoimmune disease,
affecting the liver with progressive nonsuppurative,
destructive cholangio-hepatitis, with an impairment of
bile excretion, resulting in chronic intrahepatic
obstructive jaundice. The onset is insidious with pruritus
as initial presention in middle aged women. Jaundice is
painless and occurs within two years of the onset of
pruritus. Hepatosplenomegaly, melanotic pigmentation
of the skin, xanthomatous lesions (xanthoma,
xanthelasma), steatorrhoea, dark urine without
urobilinogen are the other features. Bone changes, portal
 298 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

hypertension and hepatocellular failure supervene.

Presence of antimitochondrial antibodies, raised IgG and
IgM levels and alkaline phosphatase along with patent
extrahepatic bile ducts are diagnostic.
• Cholangitis: Ascending cholangitis occurs due to
ascending infection of the bile ducts above the
obstruction resulting in intermittent high fever with
rigors consequent to suppuration (Charcot’s fever).
Sclerosing cholangitis may be primary fibrosis of
the bile ducts (intrahepatic and extrahepatic) due to
idiopathic chronic inflammation or secondary to calculi
or malignancy. There is intermittent jaundice or chronic
pain in the right side of the abdomen which eventually
leads to secondary biliary cirrhosis and liver failure.
• Cholangiocarcinoma: Jaundice is invariably present
in cholangiocarcinoma as compared to hepatocellular Fig. 19.3: CT abdomen showing hepatomegaly with mixed
carcinoma. Tender hepatomegaly with anaemia and density lesion in the middle of the liver. Mild intrahepatic biliary
haemoperitoneum may be present. Serum alpha dialation and satellite nodules seen and portal vein is effaced
fetoprotein (Fetal Alpha-I globulin) is raised in majority by the lesion—Cholangiocarcinoma
of cases (Fig. 19.3).

Extrahepatic Obstructive Jaundice

Extrahepatic Obstructive Jaundice or Extrahepatic
Cholestasis (Biliary Obstruction) (Fig. 19.4)
In the wall of the duct (Luminal)
• Obliteration of bile ducts: It is due to failure of
development of biliary passages resulting in obstructive
jaundice soon after birth, within the first week. Persistent
absence of bile in faeces is highly diagnostic. It may be
fatal if the obstruction is not relieved since liver failure
sets in within six months.
• Choledochal cyst: The enlargement of the common bile
duct due to congenital weakness of the duct results in
intermittent jaundice, colicky pain in the right half of
the upper abdomen and abdominal cystic mass, in girls
Fig. 19.4: Biliary tract in relation to duodenum
under 10 years (Fig. 19.5(b)). and pancreas
• Biliary stricture: An acquired stricture may result due
to injury during operation in 95 percent of cases and the
remainder results from external truma or erosion of the • Carcinoma of common bile duct: Most of the malignant
duct by gallstone. Episodic pain, fever with chills and biliary tumours are adenocarcinomas, like gallbladder.
mild jaundice suggestive of cholangitis, are Persistent pain or deep discomfort early and progressive
characteristic. There may be tenderness in the right upper jaundice, anorexia, loss of weight are the presenting
quadrant. Transhepatic cholangiogram, raised features. Gallbladder is palpable. If the obstruction is
conjugated bilirubin and alkaline phosphatase are unrelieved, biliary cirrhosis sets in. Barium meal series
diagnostic. show extrinsic pressure on the duodenum and ultrasound
• Cholangitis: Ascending and sclerosing cholangitis (Vide examination shows dilated bile duct. Transhepatic
supra) cholangiogram is diagnostic.
 Jaundice
Figs 19.5A and B: (A) Endoscopic retrograde cholangio-
pancreato-graphy (ERCP). Normal ERCP showing gallbladder
and biliary tract, pancreatic duct, endoscope with catheter from
above downwards; (B) Endoscopic retrograde cholangio-
pancreato-graphy (ERCP) Showing spherical enlargement of
common bile duct—Choledochal cyst
Pancreatitis and Pancreatic malignancy
a. Acute pancreatitis: Oedema of the head of the pancreas
compresses the intrapancreatic bile duct (refer to Chapter
Chest Pain).
b. Chronic pancreatitis affects the wall of the duct by
cicatrical contraction (refer to Chapter Dyspepsia).
In pancreatic malignancies, most of the subjects are
elderly and jaundice is progressive, pain in the epigastrium
or right upper quadrant may be present, which may radiate
to the back and is relieved in prone posture. Sometimes it
may be painless. Hepatomegaly and distended gallbladder
may eventually develop. General emaciation and dyspeptic
symptoms are common. Diagnosis is usually made on
ultrasound examination, radiology or endoscopic retrograde
cholangiopancreatography (ERCP) (Fig. 19.5(a)).
Outside the lumen (Extraluminal) Pressure on ducts from
without may result in jaundice, due to
• Carcinoma of the gallbladder or common bile duct or
ampulla of Vater or head of the pancreas (Fig. 19.6) and
metastases in the lymph glands of the porta hepatitis.
• Hydatid cyst (Vide infra)
• Duodenal diverticulum: It may obstruct common bile
duct and is diagnosed by barium meal.
Inside the Lumen (Intra-luminal)
• Gallstones (Choledocholithiasis): Bile contains
cholesterd, bile pigments, phospholipids. Different kinds
of stones form depending on concentration of contents.
Gallstones are of three types: (1) cholesterol type, (2)
pigment type (calcium bilirubinate) and (3) mixed type.
This is usually seen in obese women around forty
years. They may be single or multiple. If the gallstones
299
remain in the gallbladder as such, symptoms are absent
(silent gallstones). Some of them, associated with
chronic cholecystitis, may complain of epigastric
discomfort after a full meal. If the stone is lodged in the
cystic or common bile duct, biliary colic occurs. The
depth of jaundice is proportionate to the degree of
obstruction. Associated fever and chills indicate
cholangitis. Recurrent attacks of right upper abdominal
pain (hypochondric and epigastric) with radiation into
the interscapular area is highly characteristic.
Hepatomegaly may be present in calculous biliary
obstruction. If the stones are in the ampulla of Vater,
acute or chronic pancreatitis results. Occasionally, the
inflamed gallbladder containing gallstones may become
adherent and rupture usually into the duodenum resulting
in biliary fistula and duodenal ileus. Diagnosis is
confirmed by radiology or ultrasonography.
Percutaneous transhepatic cholangiography offers
information regarding exact location and extent of
obstruction.
• Parasites Ascarides: Ascaris lumbricoides which
inhabits in the upper small intestine may wander and
occasionally enter the biliary passage from the duodenum
and block the bile duct.
Distomas Clonorchis sinensis infestation, which
results from eating infected fish, directly invades the
bile duct and may account for recurrent attacks of
jaundice. Diagnosis is confirmed by the presence of eggs
in the faeces.
Echinococcus granulosus: Apart from hydatid cyst in
liver or gastrohepatic omentum pressing on bile duct, it
may rupture into a duct and membrane piece or daughter
cyst may block the duct.
• Secondary biliary cirrhosis: occurs secondary to chronic
obstruction to bile flow usually in the extrahepatic sites
(like gallbladder disease or cholangitis). Clinical features
of the underlying cause are striking. Biochemical
evidence of cholestasis, absence of mitochondrial
antibody and imaging procedures help the diagnosis.
CLINICAL APPROACH
Though jaundice is clinically obvious, determining the cause
of jaundice demands a painstaking history, methodical
examination and battery of investigations (vide table).
Jaundice is confirmed chemically by the presence of raised
bilirubin in the blood (between 1 and 2 mg% indicates latent
jaundice and the symptom becomes overt only beyond 2
mg%). Normal value is 0.3 to 1 mg%.
 300 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
History
1. Age and sex: In the new born, jaundice is transient as in
physiological jaundice or may be obstructive due to
congenital obliteration of the bile ducts or may be
haemolytic due to Rh incompatibility. In childhood or
adults, viral hepatitis is common. In the elderly, hepatic
or pancreatic malignancies are probable. In women,
gallstones constitute a common cause.
2. Drug exposure, any injections or transfusions or contact
with a jaundice patient; or extramarital sexual contacts.
3. Alcoholism
4. Occupation, e. g. Weil’s disease in sewer workers.
5. Familial history : Other members of the family may be
affected in congenital hyperbilirubinaemia, haemolytic
jaundice or gallstones.
6. Previous history of chronic dyspepsia or jaundice
(recurrent jaundice may be due to a stone in common
bile duct or benign recurrent intrahepatic cholestasis).
7. Any prior surgery
8. Onset: Insidious with constitutional symptoms (viral
hepatitis); acute onset (biliary calculi); fluctuating
(carcinoma of ampulla of vater or haemolytic episodes).
If fever persists after jaundice’ suspect malaria, liver
abscess or, cholangitis.
9. Pain: Painless and progressive (viral hepatitis or chronic
pancreatitis); painful jaundice (may be constant as in a
growth) or intermittent (gallstones).
10. Symptoms of anaemia.
11. Pruritus as in cholestasis.
12. Digestive upsets: Anorexia, nausea, abdominal
discomfort in pericteric stage of viral hepatitis or long
history of dyspepsia as in chronic calculous cholecystitis.
13. Colour of urine and stool: If the urine is dark and a
normal or pale stool (hepatocellular jaundice;) if the
urine is dark with colourless stool, (obstructive jaundice);
and if the urine colour is normal and deepens on standing
with dark stool, (haemolytic jaundice). The stool may
be alternately acholic and cholic with corresponding
alteration in colour of the urine (choledocholithiasis).
14. Course: (varying) Short duration or intermittent
(gallstones); if it lasts for weeks (viral hepatitis); and if
it is progressive or lasting for months (it may be due to
malignancies of the hepatobiliary system or occasionally
intrahepatic cholestasis).
Physical Examination
General Survey
1. Eyes: Scleral icterus pale palpebral conjunctiva (yellow
discoloration of the eyes is seen due to drugs like
mepacrin or carotinaemia). Excess of subconjunctival
fat may simulate jaundice but its unequal distribution
differentiates from jaundice.
2. Skin
a. Colour: pale yellow colour in haemolytic jaundice;
bright yellow colour in hapetocellular jaundice;
greenish yellow in obstructive jaundice.
b. Scratch marks: obstructive jaundice
c. Xanthoma
d. Bruising (prothrombin time prolonged)
e. Vascular spiders
f. Rashes
3. Diminished hair: axillary or pubic regions.
4. Any parotid enlargement (alcoholic cirrhosis)
5. Lymphadenopathy: malignancies
6. Oral cavity
a. Yellow discoloration of the oral mucosa and underneath
the tongue
b. Pallor of the tongue for evidence of anaemia
7. Hands: Clubbing, white nails (hypoproteinaemia),
Dupuytren’s contractures (alcoholic), palmar erythema
(mottled redness of the thenar and hypothenar
eminences), koilonychia (anaemia)
8. Cachexia of the limbs (cancer or cirrhosis)
9. Any gynaecomastia or testicular atrophy (small and
nontender)
10. Peripheral oedema
Systemic Examination (Abdominal)
a. Hepatomegaly
i. Size mild enlargement (hepatitis) moderate
enlargement, (obstructive jaundice)
ii. Tenderness: amoebic or alcoholic hepatitis,
congestive heart failure, hepatoma occasionally
iii. Surface: smooth surface (cholestasis) nodular surface
(malignancy)
iv. Consistency: firm in hepatitis; hard in malignancies
b. Gallbladder enlargement: If palpable it indicates
obstruction of the common bile duct (enlarged in 90%
of noncalculous obstruction and 10% of cases in
calculous obstruction), i.e. Courvoisier’s law connotes
that is unlikely to be due to gallstones because of fibrotic
changes.
c. Enlarged spleen: suggestive of portal hypertension or
haemolytic anaemia.
d. Ascites with enlarged veins (caput medusae is number
of collateral veins running from umbilicus) suggest
portal hypertension.
e. Auscultation of the abdomen: for any venous hum
(intrahepatic portal hypertension) or bruit over the liver
(regenerating nodules), or friction rub (malignancies).
 Jaundice
Investigations
Urine Examination (Urine containing bilirubin is brownish
yellow or dark brown)
a. Bilirubin: It is tested by
i. Foam test (shake the urine in a container and look
for the yellow froth on the top; normally the froth is
colourless).
ii. Methylene blue test—When few drops of methylene
blue are slided down the test tube containing one ml
of urine, the colour changes to green in the presence
of bilirubin. (It is not a specific test, since the yellow
coloured urine and blue dye may produce a green
mixture).
iii. Harrison spot test (with Fouchet’s reagent)—Add 5
ml of 10 percent barium chloride to 10 ml of urine
and the mixture is filtered. Then add two drops of
the Fouchet’s reagent on to the dried filter paper. A
blue green colour indicates the presence of bilirubin.
iv. Ictotest—Place five drops of urine on a square of
the test mat. Then place the ictotest tablet in the centre
of the moistened area. Add two drops of water on
the tablet. A bluish-purple colour appears around the
tablet, if bilirubin is present.
[Pitfalls: Urine may be abnormally coloured due to drugs
or other endogenous pigments, e.g. yellow urine due to drugs
like riboflavin, brown due to furazolidin, red urine due to
haemoglobinuria or pyridium, red orange due to rifampicin,
brownish black due to alkaptonuria, port wine colour due
to porphyria.]
Bilirubin is absent in haemolytic jaundice (acholuric
jaundice) and present in both hepatocellular and obstructive
jaundice.
b. Bile salts: Hay’s test—Sprinkle sulphur particles on the
surface of the urine placed in a wide mouth bottle instead
of test tube. If bile salts are present, sulphur sinks (since
surface tension of bile salts containing liquid is lowered),
instead of sulphur floating as in normal urine.
N.B. Both bile pigments and bile salts are present in the
early stages of jaundice but later on only bile pigments are
present in many cases, probably due to liver ceasing to
produce bile salts.
c. Urobilinogen is examined by Ehrlich’s aldehyde reagent.
Add 1 ml of the reagent to 10 ml of urine. After 3 to 5
minutes, normal urine shows a faint reddish colour which
intensifies on heating. If urobilinogen is present in
excess, a distinct red colour appears in cold urine. If no
red colour appears even on heating, it indicates absence
of urobilinogen.
301
It is absent in obstructive jaundice, whereas it is in
excess in hepatocellular and haemolytic jaundice (sometimes
in nonjaundiced states).
d. Haemoglobinuria
e. Haemosiderin: (Stains with prussian blue)
Stool
Pale coloured stool (absence of stercobilinogen) is
suggestive of obstructive jaundice. Excess of neutral fat
together with striated meat fibres or starch is suggestive of
obstruction of pancreatic duct. Absence of stercobilin and
presence of starch as well as meat fibres suggests obstruction
to the ampulla of Vater. Continued absence of
stercobilinogen in the stool and urobilinogen in the urine
indicate complete biliary obstruction.
Blood
Apart from blood counts (Refer to Chapter ‘Fatigue’)
• Liver Function Tests
a. Estimation of serum bilirubin (both direct and
indirect): (Normal values: Direct 0.1 to 0.3 mg% and
indirect 0.2 to 0.7 mg%). Direct (conjugated)
bilirubin is more in obstructive jaundice and indirect
bilirubin (unconjugated) is more in haemolytic
jaundice or whenever conjugation is decreased as in
Gilbert’s disease; whereas both types of bilirubin are
in excess in hepatocellular jaundice. Dermal
icterometer compressed gently on the infant’s nose
indicates approximate bilirubin concentration or
bilirubinometer using blood sample from heel prick
measures bilirubin concentration in neonates.
b. Van der Bergh reaction: Direct (obstructive
jaundice), indirect (haemolytic), biphasic (hepato-
cellular).
c. Serum enzymes
i. Transaminases SGPT (ALT), SGOT (AST) are raised
in liver cell damage.
ii. Alkaline phosphatase (ALK-P) raised in obstructive
jaundice.
iii. 5-Nucleotidase (NT) raised in cholestasis.
iv. Gamma Glutamyl Transpeptidase (GGT) elevated
in liver cell damage especially alcoholics.
v. Alpha-1 antitrypsin deficiency seen in cirrhosis.
d. Serum proteins
i. Albumin globulin ratio may be reversed (decreased
albumin reflects extent of liver dysfunction; globulin
is raised in autoimmune chronic active hepatitis).
 302 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Serum albumin-Ascitic fluid albumin is >1.1 in portal
hypertension.
ii. Prothrombin time: Deficiency results from liver cell
damage and prothrombin time is prolonged.
iii. Flocculation tests: Zinc sulphate turbidity, thymol
turbidity and thymol flocculation.
iv. Plasma protein electrophoresis.
v. Haptoglobins reduced in haemolysis.
e. Serum lipids: Serum total cholesterol and cholesterol
esters estimations (usually show decreased total
values and esters fraction in diffuse liver disease and
raised in cholestasis).
Viral load and phenotyping for hepatitis C.
Immunological Tests
a. Hepatitis-B surface antigen (HBsAg) or HBeAg or anti
HBcIgM or DNA polymerase is a serological marker
for acute hepatitis-B infection. Serological tests for past
infection of Hepatitis-B infection include Anti HBS, Anti
HBe, Anti HBc IgG. Markers like HBc Ag and HBV
DNA polymerase are found in liver. However DNA
polymerase is found in serum also unlike HBc Ag.
Presence of HBs Ag for more than six months. HBe Ag
and HBV-DNA polymerase <105 copies (negative)
define carrier status.
Presence of HBs Ag for more than six months; HBe Ag
and HBV DNA polymerase >105 copies (i.e.) positive
(done only if HBe Ag is negative) imply chronic hepatitis
presence of Anti HBs alone implies previous vaccination.
Anti HAV IgM; Anti HCV; anti HDV IgM and anti HEV
IgM are other markers.
b. Alpha fetoprotein is a market for hepatoma.
c. Coombs’ test positive in acquired haemolytic anaemia
and negative in intracarpuscular defects.
Immunoglobulins
a. IgA and IgG raised in portal cirrhosis.
b. High titres of antinuclear factors, smooth muscle
antibodies (reflected in high levels of IgG in
immunoglobulin electrophoresis); in autoimmune
chronic active hepatitis.
c. High titres of antimitochondrial antibodies (reflected in
raised levels of IgM in immunoglobulin in
electrophoresis) in primary biliary cirrhosis.
Bromsulphalein Excretion
Useful in preicteric phase of viral hepatitis or cirrhosis but
not useful in the presence of jaundice as such.
Other Tests
Serum
a. Ferritin
b. Ceruloplasmin: Low in (Wilson’s disease) WD
c. Copper (Total): Low in (Wilson’s disease) WD
d. Free copper is high
e. Ammonia (arterial blood)
f. Haemoglobin electrophoresis
Radiology
a. Plain X-ray abdomen for gallstones and calcification of
the pancreas
b. Cholecystogram
c. Barium meal series
i. Carcinoma of the head of the pancreas shows
classical inverted-3 shape
ii. Internal fistula due to peptic ulcer may show barium
filled biliary passages.
d. Contrast radiology (if indicated)
i. Percutaneous transhepatic cholangiography (PTC)
especially for biliary ductal calculi
ii. Endoscopic retrograde cholangio pancreatography
(ERCP)
iii. Transplenic portal venography and portal pressures
iv. Angiography: arteriography of hepatic artery
v. Hypotonic duodenography (for visualising duodenal
loop and ampulla of Vater)
Imaging Procedures
Ultrasonography This is very useful noninvasive
investigation of abdominal structures, specially in
extrahepatic obstruction. It is particularly valuable in
detecting dilatation of the bile ducts or gallstones or
neoplasms, or in guiding percutaneous needle biopsy. It is
unrewarding in common bile duct stricture. If the bile ducts
are found to be dilated, PTC and ERCP are useful.
CT scanning For detecting abdominal masses. In some
cases, anatomical level of obstruction may be provided (Fig.
19.6).
Magnetic resonance imaging (MRI) Particularly useful for
assessing hepatic and portal vein patency; detecting hepatic
masses and differentiating haemangiomas from other
tumours.
Radionuclide scanning Useful in assessing biliary patency
and excretion, parenchymal changes, and neoplasms.
Liver Biopsy
(Preferably guided by ultrasonography) Prior to biopsy, it
is advisable to give vitamin K for three days and blood
 Jaundice 303

transfusion facilities to be made ready. Extrahepatic

obstruction should be ruled out, before this invasive
procedure.

Endoscopy
Laparoscopy
Further evaluation of haemolysis (unconjugated
hyperbilirubinaemia)
1. Blood film for morphology: spherocytes, target cells,
fragmented red cells
2. Reticulocytosis
3. Decreased serum haptoglobins
4. Osmotic fragility test—The red cells are unduly fragile
and fragility is increased
5. Sickle cell test
6. Coombs’ test negative in congenital haemolytic jaundice
and positive in acquired autoimmune causes [Red cell
Fig. 19.6: CT can showing an ill defined mass in the region of
the head of the pancreas and a filling defect present over the
antibody for direct Coombs and circulating anti body
body of the stomach adjacent to distal part of the pancreas. for indirect Coombs test latter merely indicates excess
Matted bowel loops and obliteration of the peripancreatic fat of antibody]
planes seen—carcinoma of the pancreas 7. Cold agglutinins

Table 19.1: Differential diagnosis of types of jaundice

S.No Clinical features Hepatocellular Obstructive Haemolytic

and investigations

1. Onset Insidious with constitutional Acute and associated Chronic and fluctuating
symptoms with pain
2. Depth of jaundice Variable (mild to moderate Progress steadily or Mild
or severe) intermittent
3. Pruritus Mild and transient Severe Absent
4. Anaemia Rare May or may not be present Severe
5. Colour of skin Bright yellow Greenish yellow Pale yellow
6. Liver enlargement Mild Moderate Normal or mild to
moderate
7. Spleen enlargement May be palpable Rarely palpable Often palpable
8. Gallbladder Not palpable May be palpable Not palpable
9. Urine
Bilirubin Present Present Absent
Urobilinogen Present (disappears only Absent Present
to reappear again)
10. Colour of stool Normal or pale Pale or acholic Normal or dark
11. Serum:
bilirubin Both direct and indirect Predominantly direct Predominantly indirect
Bilirubin present Bilirubin present bilirubin present
Transaminases Very much increased Slight increase Normal
Alkaline phosphatase Slight increase Very much increased Normal or slight increase
Flocculation tests Positive Negative Variable
A:G ratio Reversed or normal Normal Normal
Prothrombin time Increased Normal till late in disease Usually normal
12. Radiology Of no value Of immense value May be of value
 304 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
8. Glucose-6 phosphatase deficiency test
9. Haemoglobin electrophoresis
10. X-rays of the skull, hands and long bones
Intravascular haemolysis features are haemoglobinuria
haemosiderinuria, methaemalbunaemia and low haptoglobin
whereas extravascular (RES) leads to splenomegaly
(moderate).
If evidence of haemolysis is absent and still there is
increased unconjugated bilirubin, i.e. nonhaemolytic
unconjugated bilirubin, it is likely to be Gilbert’s disease
(in which signs of chronic liver disease are absent) or heart
failure.
Clinical evaluation supported by simple tests of urine,
stool and blood, undoubtedly enables the detection of the
type of jaundice accurately in the majority of cases but it
lacks specificity. Hence the need for invasive and/or
noninvasive sophisticated investigations, which may
ultimately establish the precise site and nature of lesions,
accounting for the icterus.
TREATMENT OF JAUNDICE
The management of jaundice, for a successful outcome,
imposes considerable strain on the physician, because of its
prolonged or persistent nature, although it is apparently
spotted out most often by a layman. An endeavour to identify
the type and cause of jaundice, whether it is due to
overproduction (haemolytic), defective uptake or
conjugation (hepatocellular); Impaired excretion
(obstructive) of bilirubin, is mandatory for a comprehensive
therapeutic approach. In clinical practice medical jaundice,
by and large, is more common than surgical while the
acquired causes are frequently encountered than inherited.
Prevention is, however, more visionary than seeking for a
cure.
Supportive/Symptomatic Treatment
1. Withdraw incriminating drugs.
2. Bed rest is essential for helping regeneration. If not
feasible, “up and around” limited movements avoiding
exhaustion may be permitted.
3. Diet: An adequately high calorie diet, consisting of more
carbohydrates (including glucose), optimum proteins and
as far as possible fat-less diet is advocated. Intravenous
glucose and other replacement fluids may be necessary
if vomiting hinders adequate food intake.
4. Vitamins
i. Vitamin B complex is beneficial.
ii. Parenteral vitamin K prevents hypoprothro-
mbinaemia.
iii. Other fat soluble vitamins are given in deep jaundice
due to cholestasis.
5. Cholagogues: Low doses of oral magnesium sulphate.
6. Antiemetics: Metoclopramide, domperidone, ondan-
setron are recommended.
7. Antacids and digestives help associated Dyspepsia.
8. Anti-pruritic measures
a. Oral
i. Antihistamines like Loratidine 10 mg/d or
Clemastine 1 mg b.d
ii. Hormones—sublingual methyltestosterone (25
mg per day) for men and norethandrone (10 mg
t.d.s.) for women, may be effective although
jaundice is likely to worsen.
iii. Cholestyramine (4-6 g per day) reduces the
amount of bile acids by binding them in the colon
and excretion therafter.
iv. UDCA (Ursodeoxy Cholic Acid) 10 mg/kg/d has
variable effect.
b. Local—soothing calamine lotion or warm alkaline
baths are helpful.
Treatment of Specific Types of Jaundice
Haemolytic Jaundice
(Refer to Chapter Fatigue)
Hepatocellular Jaundice
Physiological jaundice (Neonatal) No treatment is required
generally. However, barbiturates (phenobarbitone) may be
given for maturation of the new born liver. In case, it is
prolonged (> 2 weeks) and intense (serum bilirubin 20 mg%)
with or without superimposed erythroblastosis, phototherapy
(exposure to intense illumination of blue or white light)
facilitates isomerisation of bilirubin to esily excretable water
soluble isomers (shielding of eyes, monitoring temperature,
replacement of extra fluids are essential). Exchange
transfusion may be considered with a 20 ml syringe and a
3-way stop-cock alternating withdrawal and transfusion of
about 500 ml of properly matched blood.
Acute hepatitis
a. Viral infections—(Hepatitis viruses and other viruses
like Epstein-Barr). For acute viral hepatitis-supportive/
symptomatic treatment is beneficial (vide supra). Anti-
 Jaundice
viral therapy ribavirin (100 mg bd) may be considered
for HAV infection. No alcohol is allowed up to one year.
Role of cortisone and liver extract is empirical.
Lipotropic factors are not recommended. Barrier nursing
and extra caution while dealing with the blood are
obligatory in HBV infection. Silymarin 70-140 mg bd
stimulates liver regenerative ability. UDCA 150-300 mg
bd useful especially in cholestasis. Indigenous
compounds, whose pharmacology is unknown, do not
actually aid the healing process although bilirubin levels
may fall. Lamivudine is preferred for HBV and given
for 6-12 months after resolutions of hepatitis. If HCV is
not resolved within 3 months treatment started (Vide
infra).
Epstein Barr and cytomegaloviruses (Refer to Chapter
‘PUO’)
Yellow fever treatment is symptomatic. Immunization
with single dose gives immunity for 10 years.
b. Non-viral infections
i. Leptospirosis is treated with doxycycline (100 mg
b.d. for 7 days) or benzyl penicillin (600-1200 mg,
i.e. 1-2 million units every six hours for one week),
and appropriate therapy instituted, if any organ
failure, like renal failure, occurs. Doxycyline 200
mg/wkly once during risk of exposure is an effective
prophylaxis
ii. Q fever (Refer to Chapter ‘Pyrexia of Unknown
Origin’)
iii. Hepatic amoebiasis is treated with tinidiazole (2.1
g/d for 2 days and 1.2 g/d for 8 days) and
oxytetracycline (1 g/d for 10 days) supplemented
with chloroquin (0.5 g b.d. for 2 days and 0.25 g
b.d. for 18 days) (Cipro floxacin and metronidazole
IV and chloroquin beneficial in liver abscess)
iv. Septicaemia is treated with appropriately antibiotics
(Refer to Chapter ‘Shock’)
v. Malaria hepatitis is treated with Quinine or Artesunate-
(Refer Chapter ‘Rashes’).
c. Alcoholic hepatitis—No alcohol is allowed. High calorie
diet, supplemented with vitamins is provided.
Prednisolone (30 mg/d in divided doses for one month
and then tapered) is beneficial. Hypoglycaemia,
hypokalaemia, magnesium deficiency and/or anaemia
treated appropriately. Silymarin, phospholipids are
useful.
Fulminant hepatitis: (Acute hepatocellular failure i. e acute
hepatic encephalopathy due to any acute parenchymal liver
damage like viral hepatitis). In less than 4 wks and/or
305
Subacute hepatocellular failure i. e occuring between 4th
to 24 weeks with progressive ascites and Encephalopathy.
(Refer chapter ‘coma’). Treatment is aimed to support and
accelerate hepatic regeneration.
i. General measures
a. Nutrition is maintained with adequate dietary
calories through 300 g of glucose orally (Ryles
tube) or parenterally. (More glucose provides the
maximum protein sparing effect and enables to
utilise fat stores),
b. Proteins must be withdrawn initially and given
later up to 25 g/d.
c. Appropriate fluid and electrolyte replacement is
to be done.
d. General care as for any unconscious patient
should be undertaken (Elevate head of bed to
reduce ICP).
e. Strict intake and output chart is maintained.
f. Protect airway with endotracheal tube.
ii. Conservative management
a. Avoid precipitating factors (alcohol, diuretics,
sedative drugs, etc.).
b. Minimise toxin production and reduce its
absorption, by bowel cleansing or colonic lavage;
lactulose orally 50-100 ml/d (acidic medium
created and prevents absorption of ammonia) and
oral neomycin 1 g six-hourly (reduces urease
producing bacteria and other bacteria).
c. Reduce cerebral oedema with Mannitol 20%
(1 g/kg body weight) so as to keep intracranial
pressure below 25 mmHg or maintain cerebral
perfusion above 50 mmHg, and below 65 mm
Hg . The other drugs used are frusemide (20-40
mg IV; Dexamethasone (12-20 mg/d) or Glycerol
(30 ml tds). If these measures fail induction of
phenobarbitone coma may be tried, i.e 5 mg/kg
followed by 1-3 mg/kg/hr.
d. Reduce acid secretion with H 2 receptor
antagonists.
e. Administration of L-ornithine L-asparate reduces
ammonia and prevent cerebral odema.
f. Ondansetron (4-8 mg orally twice daily or 8 mg
IV slowly) is an useful antiemetic. Granisetron
(1-2 mg daily orally or 1 mg diluted to 5 ml IV
slowly over 30 secs) is an alternative.
g. Phenytoin may be given as prophylaxis in stage 3 and 4,
i.e. stupor and coma respectively.
 306 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
h. Hepatotropic agents like insulin and glucagon or N-acetyl
cystein may be beneficial.
iii. Treat appropriately possible complications like
a. Metabolic disturbances- Hypoglycaemia,
Metabolic acidosis, electrolyte imbalance like
Hypokalaemia
b. Sepsis (Infection associated with Hypoxaemia)
— Vancomycin and 3rd generation cephalo-
sporins useful
c. GI Bleeding and associated anaemia
d. Clotting abnormalities
e. Renal failure
f. Respiratory failure
g. Cardiovascular collapse
h. Acute pancreatitis
iv. Specific therapy for causes like poisoning with
acetaminophen, amanithphalloides, copper sulphate
may to considered (i.e.) N–acetylcystein; Penicillin
with silibinin, and D-penicillamine respectively.
v. Empirical measures
a. Corticosteriods—Hydrocortisone hemisuccinate
IV 100 mg 4th hourly.
b. Levodopa or bromocriptine (to aid neurotrans-
mission).
c. Ketoanalogs of essential amino acids.
vi. Heroic measures (artificial hepatic support systems
and others)
a. Exchange transfusion
b. Plasmapheresis
c. Continuous cross circulation, with baboons or
human volunteers.
d. Extracorporeal haemoperfusion (charcoal, pig
liver).
e. Hyperbaric oxygen therapy.
f. Liver cell transplant.
g. Bioartificial liver support with molecular
adsorbent recirculated system (MARS)
h. Gene therapy
Chronic hepatitis
a. Chronic active hepatitis-B
i. Avoid strictly hepatotoxic agents.
ii. If the disease is active (as assessed by biochemical
parameters), antiviral agents (alpha interferon 5-10
mega units/m2/d for 3-6 months; adenine arabinoside
10 mg/kg body weight for 3 days and half the dose
for 3 weeks) are given to inhibit HBV replication.
Lamivudine 100 mg/d for about 1 year and above or
adefovir 10 mg for about one year are beneficial.
Response appears to be better if interferon therapy
is preceded by a short course of prednisolone, for
six weeks. Recently Entecavir (1 mg) is introduced
which is promising.
The carriers also should be followed periodically.
The contacts should be immunised, if anti-HBs Ag is
negative.
b. Hepatitis-C infection may be treated with alpha
interferon (3 million units s c alternate day) along with
Ribavirin (500 mg b d) for 6 months is beneficial.
Pegylated interferon alpha-2a (180 mcg/wk for 48 weeks
s c) is a better alternative along with Ribavirin.
c. Autoimmune chronic active hepatitis: Corticosteroids
are life saving (Prednisolone 30 mg/d) given and tapered
gradually to 10 mg/d and maintained for two years.
Monitor the response by monthly liver function tests and/
or biopsy half yearly. Azathioprine (50 mg/d) may be
added to facilitate reduction of cortisone doses. The
maintenance therapy may be withdrawn following
remmision for one year. If relapse occurs, restart
treatment (75% are known to relapse).
• Wilson’s disease: Penicillamine (1.5 g/d) with cortisone
preferably produces cupriuresis (Free Serum copper kept
<10 ug/dl). Pyridoxine supplement is necessary. If
remission occurs, i. e serum ceruloplasmin >20 mg/dl,
the dose is reduced and continued life long. If toxic
effects occur, trientine dihydrochloride (1. 2-2. 4 g/d)
may be given. Zinc 150 mg/d may be added for life long.
Tetrathiomolybdate is a potent anticopper agent.
• Hepatic Cirrhosis (portal cirrhosis) (Refer to Chapters
‘Oedema’ and Haematemesis): Chronic hepatic
encephalopathy or portalsystemic encephalopathy is not
only associated with chronic liver disease but with portal
systemic bypass presenting as disordered mentation with
raised ammonia levels, which is treated as follows:
i. Treat precipitating factors like GI bleeding or
metabolic disturbances or infections or drugs/toxins.
ii. Ammonia production is lowered or removed by
a. Lactulose 30 to 60 g/d (osmotic pingative)
b. Nonabsorbable aminoglycosides like neomycin
influence ammonia producing flora (1 gm/6h
oral for not more than 4 weeks) or metronidazole
(7. 5 mg/kg/qid. for not more than 2 weeks)
 Jaundice
c. L-ornithine L-aspatate lowers ammonia through
stimulation of urea cycle and urea formation as
well as synthesis of glutamine.
d. Moderate protein restriction (vegetable protein
increases nitrogen balance)
iii. Water soluble vitamins and minerals like zinc are
beneficial.
iv. Colonic bypass or surgical excision may be
considered. (No shunt operation is to be done during
encephalopathy).
v. Liver transplant is the final choice.
Obstructive Jaundice
The treatment depends on the underlying cause which
includes medical (treating malabsorption, pruritus,
cholangitis); mechanical (lithotripsy ) and surgical.
Intrahepatic
a. Viral hepatitis (vide supra): Intrahepatic (a) Viral
hepatitis (Vide supra)
b. Primary biliary cirrhosis: Treatment is mainly
symptomatic.
i. Correct malabsorption by replacement with vitamins
(vit. A: 1,00,000 U/i.m. monthly or 25,000-50,000
units orally; Vit. D: calciferol 0.25 mg to 1 mg/day
orally or Alfacalcidol 1µg/day orally (Vit D = 10
mcg = 400 IU) Vit. E: 10 mg/d; Vit K: 10 mg I.M.
monthly) and minerals (calcium 1 g/d; zinc 220 mg/
d). Dietary fat is substituted with mediam chain
triglycerides limiting to 40 g/d.
ii Treat pruritus as above.
iii Treat cholangitis with appropriate antibiotics
adequately.
iv. Drugs like penicillamine (250 mg/d initially and
gradually increased to 1.5 g/d is likely to benefit after
18 months (the drug is better avoided in the
asymptomatic and first and second stages). Other
drugs like colchicine, chlorambucil, azathioprine are
used without much effect.
v. Recently lone term treatment with UDCA (12-15 mg/
kg/d) is advocated to improve survival rate without
liver transplantation
vi. Biopsies done yearly may help to assess the outcome.
vii. If deterioration leads to hepatic failure, liver
transplantation is considered.
c. Primary Sclerosing Cholangitis-UDCA improves
symptoms and liver function, tests only, without much
307
effect on prognosis. Extrahepatic structures excised or
stented at ERCP. Liver transplantation may be needed.
d. Cholangio Carcinoma- Palliative surgical bypass or
doxorubicin may be useful.
Extrahepatic
a. Cholangitis (ascending and sclerosing)—Appropriate
antibiotics are necessary (cefotaxime 1 g 8th hourly and
metronidazole—0.5 g 8th hourly). Biliary drainage may
be attempted if necessary (either extrabiliary with a T-
tube or intrabiliary with silicone stent in the common
bile duct).
b. Tumours of the gallbladder and bile duct and pancreas
the treatment includes surgical excision or palliative
tubal drainage or local intrabiliary irradiation. Pancreati-
coduodenectomy or segmental resection is undertaken
for carcinoma of the ampulla of Vater.
Most often palliative measures are undertaken for
pancreatic cancers (cholecystojejunostomy or endoscopic
insertion of a stent in the bile duct or gastroenterostomy to
prevent duodenal obstruction) since curative surgical
resection (Whipple operation) is rarely feasible.
c. Pancreatitis (Refer to Chapters ‘Chest Pain’ and
‘Dyspepsia’)
d. Gallstones: Asymptomatic gallstones do not require
treatment usually. Treatment of symptomatic gallstones
includes surgical (cholecystectomy) and nonsurgical.
The latter consists of mechanical (lithotripsy),
endoscopic approach (sphincterectomy) and medical
dissolution of radiolucent stones with chenodeoxycholic
acid and ursodeoxycholic acid (7.5 mg/kg each per day).
It is advisable to give oral bile salt treatment, before and
after extracorporeal shock wave lithotripsy. In recent
times, laparoscopic technique is being preferred to
conventional surgery.
e. Parasites
Ascaris lumbricoides: is treated with piperazine salts
(100 mg/kg), Pryantel pamoate (10 mg/kg), levamisole (2.5-
5 mg/kg). Mebendazole 100 mg bd for 3 days or
Albendazole 400 mg once are other alternatives. Surgery
may be undertaken, if necessary. (Refer to Chapter ‘vomiting’)
Clonorchis sinensis: Praziquantel 25 mg/kg tds for two
days; chloroquine is beneficial when given as for hepatic
amoebiasis. Biliary drainage may be undertaken be facilitate
the exit of eggs.
Echinococcus granulosus Albendazole (400 mg bd for 1 to
3 months) may be given. The hydatid cyst is excised, if
possible, avoding spillage.
 308 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Secondary biliary cirrhosis may be prevented by relieving
the obstruction to bile flow. If liver failure occurs, treatment
as for hepatic encephalopathy (Vide supra) is instituted.
Prevention
1. Haemolytic jaundice: Refer to Chapter ‘Fatigue’
2. Hepatocellular jaundice
a. Personal hygiene is all important since viral
infections occur invariably through contaminated
water and food, (faecal-oral route) or contaminated
syringes and blood, or sexual transmission or
mosquito bites (transmitting yellow fever).
b. Immunoprophylaxis: Passive immunisation within
2-7 days of exposure to infection is beneficial when
given immunoglobulin is in doses of 600 units twice
at 30 days interval.
Active immunisation against HBV infection is done by
plasma derived or recombinant or chemically synthesised
vaccines at 0, 1, 6 months intervals. If possible, antibody
titre may be done to assess the efficacy of the vaccine.
Vaccine against HAV infection is also available (Two doses
at 2-4 wks apart I.M. and immunity lasts for 10 years if
booster given at 6 months otherwise lasts only for one year).
Yellow Fever vaccine is compulsory for entry into Africa or
South America.
3. Obstructive jaundice: Early treatment of biliary
infections prevents diseases of the pancreas and
gallbladder. Moderate intake of neutral fat and restriction
of cholesterol containing foods; avoiding sedentary
habits and obesity, help to prevent biliary stasis and
cholelithiasis.
Jaundice 309
310 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter

Low Backache
20
Pain along the spinal column especially the lower part of Hence the causes of backache can arise from
the back from first lumbar vertebra to lumbosacral junction 1. within the lumbar canal (spinal cord and roots),
is a very common presentation in clinical practice. The pain 2. in the wall of the lumbar canal (Vertebral column—
may be due to disorders of the bony spine and associated vertebral bodies and intervertebral discs) and
soft tissues (ligaments and muscles) or the spinal cord and 3. outside the lumbar canal (soft tissues and joints).
its roots or referred pain due to disease of any abdominal or
pelvic viscera. It may be mild or severe, with slow or sudden CAUSES OF BACKACHE
onset, persistent or recurrent and of short or long duration. Aetiology of backache is enlisted in Table 20.1.
To understand the symptom complex, an insight of the Table 20.1: Aetiology of backache
structure of the spine or vertebral column is necessary.
The 33 vertebral bodies are articulated by intervertebral discs 1. Spinal cord and Roots
a. Spinal tumour
and the anterior and posterior ligaments hold them together.
b. Cauda equina lesions
The pedicles and laminae placed posteriorly are fused and 2. Lesions of the Vertebral Column
form a posterior canal which encases the spinal cord. The a. Degenerations
muscles which support this vertebral column are attached i. Disc prolapse (sciatica)
to the transverse processes laterally and spinous processes ii. Lumbar spondylosis
posteriorly. The vertebral column gives the erect posture b. Infections
and movements of vertebrae provide mobility to the body i. Tuberculosis
ii. Typhoid
facilitating other various postures. The four curves present iii. Osteomyelitis
in this column and at different junctions of the various groups iv. Pagets disease
of vertebrae (cervical, thoracic, lumbar, sacral) are important c. Metabolic
biomechanically, to centre the head on to pelvis and disburse i. Osteoporosis
the stresses at both ends. The spinal nerves innervate the ii. Hyperparathyroidism
vertebral and paravertebral structures. d. Nutritional
i. Osteomalacia
The intervertebral disc consists of hyaline cartilage plates ii. Fluorosis
placed on the top and bottom of the nucleus pulposus, which e. Autoimmune diseases
merges with the cancellous bone of the vertebra on one i. Rheumatoid spondylitis
side and with the annulus fibrosus on the other side. Nucleus ii. Ankylosing spondylitis
f. Neoplastic
pulposus, central in position, is jelly like and elastic fibro
i. Multiple myeloma
cartilage, forming 15 percent of the disc. This is surrounded ii. Secondary deposits
by annulus fibrosus, which is a strong elastic membrane g. Congenital
forming a dense capsule for the nucleus. The fibres of the i. Lumbar stenosis
annulus mix with the fibres of anterior and posterior ii. Sacralisation
ligaments and bind the vertebral bodies. The discs are like iii. Spina bifida occulta
coiled-up springs and act as shock absorbers. Contd...
 312 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Contd... Cauda Equina Lesions

iv. Spondylolysis Pain in the low back (L2 to S5) is the earliest symptom
v. Spondylolisthesis which is intensified by movements and coughing. It may
h. Traumatic radiate to either of the legs, which is followed by numbness
i. Compression fracture of the lumbar vertebrae and difficulty in walking. Atrophic flaccid paralysis of glutei,
ii. Fracture of transverse processes and spinous processes
i. Osteochondritis
hamstrings and muscles below the knee occur, depending
i. Calve’s disease of the spine (vertebra plana) on the root that is compressed. The sensory loss again
ii. Scheuermann’s disease (adolescent kyphosis) depends on which posterior roots are affected. If the sensory
3. Soft Tissues and Joints loss is over the foot and posterior and outer side of the leg,
a. Soft tissues usually, it is L5 and S1. If the lower sacral roots are involved,
i. Fibrositis the saddle shaped anaesthesia extending over the buttocks
ii. Fibromyositis and upper thighs result. If S1 root is affected, ankle jerk is
iii. Rupture of the ligaments (sprung back)
lost whereas knee jerk is present. If L3 root is affected,
iv. Lumbo-sacral strain
v. Postural strain knee jerk is lost and ankle jerk is present, plantar reflex
b. Joints unelicitable. In the advanced cases, where 2 and 3 sacral
i. Sacroiliac joint tuberculosis roots are compressed, bladder and bowel functions are
ii. Sacroiliac strain disturbed leading to the retention of urine and faeces and
4. Referred Pain impotence. If the lower sacral roots are compressed, anal
A. Physiological—Huge gravid uterus and bulbocavernosus reflexes are lost. Lower limbs may be
B. Intraabdominal diseases
cold and cyanosed with dependent oedema. Trophic changes
i. Chronic peptic ulcer
ii. Cholecystitis
may occur. These lesions include neoplasms or chronic
iii. Pancreatitis arachnoiditis, disc proplapse, a constricting fibrous band,
iv. Neoplasms of the colon and congenital lesions like spondylolisthesis, spina bifida
v. Retroperitoneal lesions occulta, lumbar stenosis.
a. Kidney affections
b. Lymphomas Lesions of the Vertebral Column
c. Tumours of pancreas or stomach with retroperitoneal
involvement Degenerations
vi. Aneurysms
a. Aneurysm of the abdominal aorta Disc Prolapse (Sciatica) Sciatica is pain along sciatic nerve
b. Aortic dissecting aneurysm distribution which is formed by fusion of anterior primary
C. Pelvic division of L4-S3. Disc prolapse is often precipitated by
i. Sigmoid colon pathology lifting heavy objects with the spine in flexed position resulting
– Ulcerative colitis in immobilising pain and a feeling of something giving way
– Diverticulitis
in the back. The intervertebral disc protrusion may be
– Neoplasms
ii. Gynaecological conditions nuclear or annular. The sites of nuclear protrusions are dorso
– Menstrual disorders medial or dorso lateral into the canal or more laterally into
– Retroverted uterus the foramina. The annular fibrosus bulges in all directions
– Salpingitis when there is collapse of the intervertebral disc. These
– Malignancy of the ovary herniations occur commonly between L4 and L5 or L5 and
iii. Prostatic pathology S1 vertebral bodies (Figs 20.1A and B).
– Prostatitis
This protrusion compresses the spinal nerve passing to
– Neoplasms
the foramen one segment below, i.e. L4 disc compresses
5. Psychogenic
the L5 nerve and L5 disc affects the S1 nerve. The onset of
low back pain is sudden or sub-acute and radiates down
Spinal Cord and Roots the back of the affected lower limb after couple of days. It
Spinal Tumours is aggravated by coughing or sneezing, stooping or sitting
or walking and relieved by lying on the normal side with the
Refer to Chapter ‘Paraplegia’ affected limb flexed.
 Low Backache 313

Figs 20.1A and B: (A) Compression of fourth lumbar root due to posterior herniation of the disc between third and fourth
lumbar vertebrae (B) Site of protrusion (nuclear or annular) in intervertebral disc

The biomechanics of the lumbar spine may be altered
leading to spasm of the sacrospinalis muscles, which causes
flattening of the lumbar curve and scoliosis. The lumbar
spine is flexed usually to the affected side at the level of the
prolapsed disc with a lateral tilt, i.e. scoliosis (convexity of
curve) is to opposite side of sciatic pain. Tenderness may
be present over the vertebral process at the level of the
affected disc.
The neurological signs vary from the root involved (Fig.
20.2). If L5 root is affected, the pain may radiate towards
outer aspect of the leg with weakness of the peronei and
dorsiflexors of the toes and a foot drop occurs sometimes.
Sensory loss is present on the dorsum of the foot and lateral
aspect of the leg. Ankle jerk is normal. The plantar reflex is
flexor. If the S1 root is affected, weakness of eversion and
plantar flexion of the foot with slight wasting of the affected
muscles, as well as sensory loss over the outer half of the
foot result. Ankle jerk is lost. Lasegue’s sign (straight leg
raising test) is a valuable indicator of the root pressure.
Limp gait will be obvious on the affected side. CSF shows
raised protein content up to 100 mg with a normal cell count.
X-ray examination reveals narrowing of the intervertebral
space and sclerosis of the adjacent vertebral bodies with
osteophyte formation (due to calcification of the elevated
periosteum of the vertebral bodies) at the margins of affected
joints or normal findings. The myelogram may demonstrate
the prolapse as a filling defect. Discography to visualise the
disc by injecting radiopaque directly into the disc is not a
common procedure. A spinal CT scan or MRI is more
helpful (Fig. 20.3). Spinal tumour, vertebral collapse,
sacroilitis, neoplasm in pelvis, are other causes of sciatica.
Lumbar spondylosis or osteoarthritis of the spine It is
commonly seen in older age groups with males having a
higher incidence. Pain and rigidity of the back are common
complaints. In some cases the pain may radiate down the
sciatic nerve and the root compression may give rise to
radiculopathy. There is no obvious deformity of the spine
except obliteration of the normal lumbar lordosis. These
degenerative changes may result in lumbar spinal stenosis.
X-ray of the lumbosacral spine shows extensive oestophyte
formation in the vertebral bodies, marginal exostosis and
intervertebral bridging due to shrinking of vertebral margins
and narrowing of the intervertebral spaces (Fig. 20.4).
314 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 20.2: The lumbosacral plexus

 Low Backache
Fig. 20.3: MRI of the lumbosacral spine showing degenerated
L 4 –L5 and L5 –S 1 discs with minimal postero-central disc
prolapse at both levels as well as thecal sac indentations
Fig. 20.4: Osteoarthritis of the spine X-ray of the lumbar spine
showing osteophytic outgrowths (spurs) at the margins of the
vertebral bodies with narrowing of the intervertebral spaces
Infections
Tuberculosis It is the common infection of the vertebral
column. (Pott’s syndrome) The back pain is subacute and
chronic aggravated by movement and not relieved by rest.
There is tenderness over the spine of the affected region.
Anvil test is positive, i.e. a tap over the vertex of the head
315
may produce pain at the affected area of the spine. Similarly
pain is experienced when the patient is asked to walk on the
heels. As the disease advances, referred pain also occurs
due to irritation of nerve roots. In some cases, the patient
may present himself with paraplegia and gibbus or cold
abscess appearing below the inguinal ligament as psoas
abscess or internal to the anterior superior iliac spine or
para spinal abscess or may surface into the petits triangle.
X-ray shows narrowing of the disc space with erosions of
the affected vertebral body, destruction and collapse of the
vertebral bodies. A paravertebral abscess shadow with soft
tissue mass may be seen.
Osteomyelitis It affects the appendages as well as the
vertebral body. The disease may start with severe pain and
fever. Limitation of joint movement may be marked. X-ray
examination may show diffuse areas of radiolucency due
to bone destruction or sequestrum or involucrum and new
bone formation, although it does not show any abnormality
in acute stage.
Spinal epidural abscess due to vertebral osteomyelitis or a
blood-borne infection invading the epidural space may also
present itself as pain in the back with spinal tenderness and
fever in the early stages. If not adequately treated, it may
result in paraplegia due to cord compression.
Typhoid fever It may affect the bones and typhoid spine
appears after some weeks of typhoid fever. There is pain
and tenderness of the back as well as stiffness, due to
inflammatory affections of the ligaments, discs and vertebral
periosteum. This manifestation is very uncommon now.
Paget’s disease It is very rare. Pains in the bones of skull
and limbs are common rather than back pain. There may be
deformity of the spine and lower limbs (like kyphosis and
bowing of long bones). Features of compression of the
cord than roots are more often due to spinal deformity
associated with vertebral collapse. X-ray of the spine shows
dense, irregular, wavy trabeculations. X-ray of the skull
shows thickening of the two tables with areas of porosis
and sclerosis (mottled and woolly). The aetiology is
unknown but the presence of intranuclear inclusions in the
osteoclasts of bones of the pegetic subjects only, leads to
the concept of slow virus infection.
Metabolic Causes
Osteoporosis (Atrophy of bone)
Pain is usually in the low back and radiates round the trunk
(girdle type), into the buttocks, and down the limbs. The
pain is aggravated by movements and coughing. A trivial
injury may result in vertebral collapse, when the pain may
 316 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
be more severe. There may be kyphosis due to wedging of
the vetebral bodies and diffuse tenderness over the spine.
Osteoporosis is due to defective formation of bone matrix
(osteoid), leading to reduction of bone substance and
consequent fractures. This may be nutritional, endocrinal,
prolonged costisone therapy and postmenopausal in origin
and also due to prolonged immobilisation and senescence,
Blood chemistry (calcium, phosphorus, alkaline phosphatase
and proteins) is normal. X-ray shows anterior wedging,
biconcave appearance of vertebral bodies, and compression
fractures of the vertebrae in some cases.
Hyperparathyroidism
Bone involvement is recognised in about half the cases in
this disorder, where in backache is a complaint. Associated
symptoms like abdominal pain, weakness, anorexia, polyuria
and polydipsia, due to hypercalcaemia and renal calculi may
also be present. Serum calcium and alkaline phosphatase
are raised and serum-phosphorous is reduced. The skiagrams
show demineralisation and occasionally bone cysts and
pathological fractures. It may be primary (adenoma) or
secondary (ch-renal failure) or Tertiary
Nutritional Causes
Osteomalacia (Softening of the bone) This is a deficiency
disease of adults due to lack of vitamin D and consequent
impaired calcium and phosphorus absorption. There is
normal amount of bony substance with reduced contents
of calcium and other minerals. The progressive
decalcification leads to the replacement of bone substance
with uncalcified soft osteoid tissue. So the ratio of calcium
phosphate matrix is diminished unlike normal ratio in
osteoporosis. The pain in the back is more diffuse and may
be dull or severe due to strain of the tender, soft bones of
the spine. It is aggravated by activity and relieved by rest.
Tenderness on pressure is elicited. There may be deformities
like kyphosis, scoliosis or coxa vara. There may be
carpopedal spasm and proximal myopathy with waddling
gait. Spontaneous fractures may occur. Serum calcium and
phosphorus are low and alkaline phosphatase is raised. X-
ray of the bones may show generalised rarefaction. There
may also be spontaneous fractures. In addition, there may
be pseudofractures (Looser’s zones) in the areas where the
arteries cross the bones like lateral border of the scapula,
inferior femoral or medial femoral shaft (Milkman’s
syndrome).
Fluorosis If the fluorine content of the water is more than 3
to 5 parts per million, skeletal fluorosis and dental fluorosis
can occur. The former consists of sclerosis of the bones of
the spine, calcification of the ligaments and also ossification
of the tendinous insertions of the muscles. The latter consists
of mottling and corroding of the teeth. Enamel is rough,
with bands of brown pigmentation separating the chalky
white patches. The earliest symptom may be pain in the
back and limitation of movements and may progressively
develop compression myelitis.
Autoimmune Diseases
Rheumatoid spondylitis (Rheumatoid arthritis of spine) The
spine is affected in some cases as a late manifestation.
Though the sacroiliac or the cervical spine may be affected
initially, other parts of the spine may be involved slowly,
that too during excacerbations. There may be kyphosis and
tenderness of the spine. The primary involvement of the
small joints of the extremities and atrophy of the subchondral
bones offer the clue. X-ray shows decalcification of a
number of vertebrae and narrowing of the intervertebral
spaces anteriorly (refer to Chapter ‘Polyarthritis’).
Ankylosing spondylitis This is a disease of the spine in early
adulthood. There is inflammation not only of the spine but
also sacroiliac joints and large joints of the limbs. The pain
is confined to the back in the early stages with stiffness and
pains at sacroiliac joints particularly in the mornings. This
pain may subside with activity as the day progresses and
recurs with prolonged sitting posture. Radiation to the back
of the thighs with progressive limitation of movement may
be associated. Pain becomes worse progressively and the
disease spreads to other parts of the spine. The muscles of
the paraspinal region and the large joints undergo painful
spasm which results in forward flexion of the spine, flexion
abduction deformities of the hip and flexion of the knees.
Enthesopathy (pain along tendon insertion sites) is
characterstic small joints rarely involved. There is limitation
of the chest expansion and movements of shoulder.
Ultimately the sacroiliac joints will be fused and the spine is
ankylosed with immobile forward flexion.
X-ray of lumbosacral spine and sacroiliac joints shows
a. Sacroiliac joints
i. Early stage—Ill-defined joint margins and
osteoporosis.
ii. Later stage—Subchondral sclerosis and obliteration
of the joints.
b. Lumbar spine
i. Early stage—Squaring of the anterior portions of
the lumbar vertebral bodies with straightening.
ii. Later stage—Bamboo spine. Calcification and
ossification of intervertebral discs and vertebral
ligaments. The bony bridge occurring between
 Low Backache
adjacent vertebrae, i.e. syndesmophyte, is vertically
disposed, as against osteophyte of osteoarthritis
which is a horizontal or oblique bony outgrowth.
Neoplastic Lesions
Multiple myeloma Pain in the bones usually in the back is the
salient feature due to plasma cells invading the bone cortex
of the vertebrae or other flat bones. Sometimes the
presenting symptom may be pathological fractures or
multiple circumscribed swellings. Other features are
anaemia, renal failure, signs of hyperviscosity like headache
with visual disturbances, coma, bleeding. X-ray shows
multiple punched out osteolytic areas (Fig. 20.5). Urine may
show Bence-Jones protein and diagnosis is confirmed by
demonstrating plasma cells in the bone marrow and M-
band (Mono clonal) on serum electrophoresis.
Fig. 20.5: Diagnostic of multiple myeloma—lateral radiograph
of skull showing punched out areas of rarefaction (osteolytic
defects)
Secondary deposits Though haemangioma of the vertebrae
is also a common primary tumour, metastatic tumours of
the vertebrae (origin from thyroid, lung, breast and prostate)
involve the spine more often. Pain in these cases is dull and
constant, not relieved by rest. Root compression or cord
compression may occasionally result. X-ray shows irregular
destructive lesions with extension into the medullary cavity
and reactive new bone formation.
317
Congenital
Lumbar stenosis The spinal canal is narrowed due to
developmental defects and/or acquired causes like
spondylosis and fluorosis. Lumbar stenosis presents with
the features of pain in the back or along the sciatic nerve
without spinal stiffness and a positive Lasegue’s sign. Also
there may be interference with the blood supply to the cauda
equina leading to pain in the posterior aspect of the thighs
and calves. It is aggravated by exercise or walking, without
muscle cramps and gradually relieved by rest. This
claudication type of pain (pseudo claudication) (i.e.)
neurogenic (cauda equina) claudication is relieved by sitting
and not by standing still; the walking distance is variable
and the peripheral pulses present, as against fixed walking
distance and feeble or absent pulses in vascular intermittent
claudication. The pain may be followed by weakness and
numbnss of the legs. The spinal stenosis may give rise to
cauda equina compression. Antero posterior X-rays of the
spine shows diminished interpedicular distance; and lateral
X-rays shows diminished anterio posterior diameter in the
spinal canal, i.e. from the middle of posterior margins of
the vertebral bodies to the base of the spinous processes.
Sacralisation of the 5th lumbar vertebra This is a develop-
mental anomaly, when either one or both transverse
processes are so large as to fuse with the base of sacrum
or ilium. This results in a foramen like opening instead of a
broad cleft. Constant back pain over the area of sacroiliac
joint, usually after 20 years (since final ossification of the
vertebral column occurs), is complained of on the affected
side. The subject may find it difficult to sit on the side
involved. There may be acute exacerbations radiating down
the back of the leg. The lumbar curve is flattened and lumbar
scoliosis with convexity to the affected side may be
appreciated. Tenderness of the sacroiliac joint is elicited.
The pain is attributed to the impact of transverse process
on the ilium and the strain of the ligament of the sacroiliac
joint on the spinal movements. X-rays reveal sacralisation.
Spina bifida occulta Failure of fusion of the two halves of
the vertebral arch posteriorly causes this defect (fusion
normally occurs in the first year of life). The spinal cord
and the meninges are normally formed. However, the dura
is attached to the skin by a fibrous band. As the child grows,
around the age of 10 years this band or membrane exerts
traction on the cord resulting in symptoms of those of
chronic cauda equina lesions. The early complaint is the
peculiar gait with equinovarus deformities of the feet. Some
may have chronic low back pain in adulthood. Examination
may reveal a thick overlying skin sometimes covered by a
 318 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
dimple or naevus or fibrolipomatous mass or tuft of hair.
Palpation over the lumbo sacral region may reveal the defect
as a depression, which is the most common site of spina
bifida. X-rays of the lumbo-sacral region show absence of
neural arches of the vertebrae in the lumbo-sacral region,
widening of interpedicular spaces without erosions of
pedicles.
Spondylolysis and spondylolisthesis Spondylolisthesis is
forward displacement of L5 vertebra over S1, or L4 vertebra
over L5, and is associated with defect in neural arch at pars
interarticularis on either side. Spondylolysis or
prespondylolisthesis is the presence of neural arch defects
without forward slipping of the vertebra. Spondylolisthesis
is usually seen in children and adolescents. This can also
occur due to a trauma of the normal spine which may cause
fracture of the articular processes or pedicles and the
vertebra may be displaced forward.
Dull low back pain is usually complained which is
aggravated by activity and relieved by recumbency.
Tenderness is elicited at the site of displacement. The pain
is attributed to impinging of mobile lamina of affected
vertebra, on the fibrocartilaginous tissue occupying the
pseudarthrosis defect with the consequent compression of
the nerve root. There may be limitation of flexion movement
associated with girdle pains, radiating to the toes or
coccygeal region which may be increased by hyperextension
of the back. On examination, a prominence of the spinous
process of affected vertebra with a depression above is
present. A transverse groove may be seen extending across
the back at the level of depression over the waits. The space
between the ribs and iliac crest is diminished and the bi-iliac
distance is increased. Lumbar lordosis is exaggerated. The
neurological deficit due to radiculopathy may be present
especially when there is coexisting prolapse of the disc.
Skiagram of the lumbosacral spine shows
a. Lateral view reveals the slipping of the vertebra.
b. AP view demonstrates the ‘arc’ sign, i.e. the lower
border of the slipped vertebra joining the line of both
transverse processes forming the arc. (X-rays of the
affected vertebra taken from above reveal the arc.)
c. Oblique views show the bony defects in pars
interarticularis as an outline of terrier (a type of puppy
dog) at the superior articular processes with the neck
of the dog corresponding to pars interarticularis.
Traumatic
Vertebral fractures usually result due to a fall from a height
or a vehicle accident. In the former, the fractures of the
vertebral bodies usually consist of compression of anterior
part of the vertebra resulting in wedge fracture without
cord injury. In the latter, it may be an asymmetrical fracture
involving the body as well as the pedicles and laminae with
fracture dislocation and cord injury. Old fractures of the
lumbar vertebra are significant as in kummel’s diseases when
pain is complained, after a lapse of time of injury. X-ray
shows wedging of the vertebra with normal intervertebral
spaces.
The fractures of transverse processes are usually due
to muscular violence. There is extensive tearing of the
paravertebral muscles. Severe pain in the back with
paravertebral tenderness and painful movements of the
flexion are present. Spinous processes may be involved due
to direct injury or hyperflexion of the spine resulting in
avulsion of the spinous processes. A swelling with crepitus
or irregular spinous process may be elicited apart from pain
and tenderness.
Osteochondritis
Calve’s disease of the spine (Vertebra plana) This is localised
osteochondritis of vertebral body seen usually in children.
Back pain, muscle spasms, local tenderness, prominence
of the affected spinous process are the presenting features.
Deformity of kyphosis or scoliosis develops gradually.
Collapse and flattening of the vertebra occurs. X-ray show
a dense flattened vertebra with normal discs.
Scheuermann’s disease (Adolescent kyphosis) This is another
cause accounting for dull back pain usually in adolescence
due to irregular ossification of vertebral epiphyses and plates
of the dorso lumbar region of the spine. The shoulders may
be rounded. Chest is flat with kyphosis. Skiagram shows
anterior wedging of the vertebrae with mottling of upper
and lower epyphyses and diminished intervertebral spaces.
Soft Tissues and Joints
Soft Tissues
Fibrositis (Myofascitis) and fibromyositis The lumbar
musculature and their fascial coverings may be the seat of
back pain. The pain will be of sudden onset related to
stooping which may be increased by movements of the
muscles and relieved by warmth. In severe attacks marked
spasm of the lumbar muscles, makes the subject take to
bed. On examination, tender nodule may be palpable due to
local muscular spasm or herniation of the fatty lobules
through thin fascial covering of the paravertebral muscles.
Fibrositis of the lumbar region is generally called lumbago.
This may be traumatic or rheumatic or infective in origin.
 Low Backache
Sprung back Overflexion of the lower lumbar spine tears
the posterior supportive ligaments of the lumbosacral region,
specially supraspinous ligaments and interspinous ligaments.
Usually low back pain is complained of, which is worsened
during flexion of the spine and relieved by rest and relaxation.
Marked tenderness is elicited between spinous processes
of L4 to L5 or L5 to S1. Lumbar lordosis is prominent. There
is no involvement of any nerve root. Usually, there is history
of a fall or lifting a heavy object or slipping over a kerb. X-
ray shows normal findings.
Lumbosacral strain Forceful hyperextension of the spine may
tear the ligaments and sometimes the facets may subluxate
on each other (Facet’s syndrome). Lumbosacral region is
unstable since it is a junction of a mobile and an immobile
part of the vertebral column with variations in the lumbo-
sacral angle which is normally 120°. Lumbo-sacral strain
can be acute or chronic. Acute form presents as sudden
low back pain accentuated by movements, which stretch
the ligaments. Marked spasm of the back muscles and
limitation of movements, increased lumbar lordosis are
present. Usually the patient assumes a flexion attitude which
relieves the strain of the ligaments. The sacrospinalis and
gluteus maximus muscles are affected. Sometimes the nerve
root irritation may cause sciatica and associated neurological
findings are elicitable. This occurs due to a sudden body
movement. In the chronic form, symptoms vary from
attacks of acute pain with intervening painless periods or
there may be constant pain with or without sciatica.
Postural strain Normal posture is a forward pelvic inclination
of about 30° as measured from the posterior superior iliac
spine to the upper border of symphysis pubis. Postural errors
may be due to a habit, occupation, protruberant abdomen
or structural changes due to disease or injury. An individual
with long slender back or obesity is more prone to postural
strain due to poor muscle tone. The postural strain may be
precipitated by unaccustomed work or exercise or induced
by particular posture like sitting or stooping for a long time
or sleeping in soft sponge cushions. Postural scoliosis or
structural scoliosis is a common deformity. The diffuse
low back pain associated with these postural errors is
essentially a functional defect. It is attributed to poor
musculature with easy fatiguability and severe strain on the
lumbosacral region, leading to increased tension of the
supportive ligaments. Functional scoliosis disappears on
bending forward unlike structural scoliosis.
Joints
Sacroiliac strain Pain and tenderness present over the joints
either on palpation or when ilium is pressed inwards.
319
Lasegue’s sign is positive. The pain may radiate down the
leg and worsens on standing on one leg. It is caused by a
sudden jerk while stepping from a kerb or during last trimester
of pregnancy or after delivery or lifting a heavy object.
Tuberculosis of sacroiliac joints Pain is chronic over the
affected joints and usually unilateral. It is increased by
movements like turning over in the bed or sitting in the
affected side for a long time or forward bending on climbing
the staircase. Tenderness is elicited over the joint by
compressing the iliac bones. The patient walks with short
steps. It may remain asymptomatic and presents as an
abscess over posterior region of the joint.
Referred Pain
It may arise from intra-abdominal and pelvic conditions
(physiological or pathological). This may be referred to the
lumbar or sacral region. Inflammatory diseases of the kidney
like pyelonephritis or colon or pancreas may produce
backache in the lumbar region. Examination of the urine for
proteinuria and pus cells; barium enema examination for
any colonic pathology and biochemical examination for raised
serum amylase levels respectively, aid the diagnosis.
Aneurysm of abdominal aorta may account for pain in the
low back. Examination of the abdomen reveals a pulsating
mass.
The referred pain in the sacral region is mostly due to
pelvic diseases like (a) gynaecological, (b) urological and
(c) sigmoid colon problems.
Gynaecological
Salpingitis, endometritis and other pelvic inflammtory
diseases or tumours of the ovary or malposition of uterus
or uterine malignancy or endometriosis may account for
backache.
The pain in endometriosis begins during the premenstrual
periods and worsens in the menstrual period. Pelvic
examination may be imperative in these conditions. Tender
indurated nodules in the cul-de-sac is diagnostic.
In tumours like carcinoma, the pain may be due to
involvement of the nerve plexus Abnormal uterine bleeding
or vaginal discharge are the presenting features in the majority
of cases.
Urological
Backache may be associated with inflammatory or neoplastic
disease of prostate. It may be radiating into one leg if seminal
vesicle is involved. Burning and urinary frequency are
 320 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
associated features. Rectal examination and scanning aid
the diagnosis. Acid phosphatase and prostate specific antigen
(PSA) raised in malignant prostate.
Sigmoid Colon Pathology
i. Ulcerative colitis—(Refer to Chapter ‘Chronic
Diarrhoea’.)
ii. Diverticulitis—(Refer to Chapter ‘Haematemesis and
Melaena’).
iii. Neoplasms—(Refer to Chapter ‘Haematemesis and
Melaena’).
Psychogenic
Back pain may be functional in origin with a background of
anxiety or depression. There will be no organic disease of
the spine or the surrounding structures and examination is
essentially negative. In hysterical persons, the spine may be
held at right angles excessively bent. Any attempt to move
the spine will be greatly resistant, although the spine gets
straightened up readily in the lying posture on the bed. Some
of the movements which were apparently painful at one
time or other are executed with comfort. Frank malingerers
may also present with such features but these will be less
dramatic and not that over reactive.
CLINICAL APPROACH
Diagnostic evaluation of low backache demands a
comprehensive analysis of the underlying pain. In this
endeavour, a detailed history and systemic examination of
the complex structure of the back along with the limbs and
appropriate investigations supporting the clinical suspicion,
are highly essential in the diagnosis and amelioration thereof.
History
Analysis of Pain
a. Site
i. Is it central (lumbar) or sacral region?
ii. Is it lateral (sacro iliac region)?
If so, is it unilateral or bilateral?
b. Mode of onset
i. Is it sudden and acute following the lifting of heavy
object as in disc prolapse or trauma or after arising
in the morning or unusual exercise?
ii. Is it slow or subacute like in tuberculosis or tumours
of cauda equina?
c. Duration
i. Is it of short or long duration?
ii. Is it periodic (chronic intermittent) as in disc
prolapse?
d. Character
i. Is it dull or excruciating or claudication type of pain?
ii. Is it localised or diffuse?
e. Intensity
i. Is it mild or severe?
f. Radiation
i. Does it radiate to buttocks, thighs, legs and toes?
g. Aggravating and relieving factors
i. Is it aggravated by movements like forward bending;
or coughing and sneezing which disturb the root by
raising the intraspinal pressure as in spinal tumour
and prolapse; or resting as in spondyloarthropathies;
or during menstruation; or standing or walking?
ii. Is it relieved on resting; or by lying flat with flexed
knees, or on manipulating the positions?
h. Associated Symptoms
i. Paresthesiae, twitchings of the muscles
ii. Swelling of the feet
iii. Temperature
iv. Urinary symptoms and
v. Gynaecological complaints
Additional Factors
i. The age
ii. Sex of the patient
iii. Past history of any systemic illness
iv. Predisposing factors causing strain or sprain or injury
Certain special features may help the clinician to locate
the source of pain.
1. If the pain is of muscular origin, it is diffuse and the
pain increases on stretching the muscles.
2. If the pain is from ligamentotus affections, it is deep
seated and localised and elicited by spinal movements
and finger pressure. If the interspinous ligaments are
involved, the pain will be diffuse and segmentally
distributed.
3. If the pain is due to involvement of the nerve, motor
and sensory features are obvious.
4. If the pain is of osseous origin, it is dull over the bones.
5. If the pain is of discogenic origin, it will be increased on
coughing or sneezing; comfortable on lying and
uncomfortable on sitting.
 Low Backache
Examination
Physical Examination
It includes (a) examination of the back and general
examination for (i) spinal signs, (ii) tension signs and
(iii) neurological signs.
A careful survery of the back is done in standing, sitting
and lying positions, alongwith the lower limbs.
Inspection
a. Any abnormal curvature of the spine
b. Distorted posture like pelvic tilt or flexion of the hip and
knee
c. Asymmetry of the paravertebral structures, gluteal and
lower extremities
d. Gibbus
e. Deep furrow above the iliac crest or any other deformity
f. The way the decubitus is changed.
Palpation
a. Tenderness over the spinous or transverse process of
lumbar vertebra or sacroiliac region or between iliac
crest and 12th rib
b. Tender nodules over the painful areas
c. Paraspinal muscular spasm
d. Compression of iliac crests
e. Mobility of the spine—forward flexion, lateral flexion
or extension of lumbar spine movements are executed
and any limitation is noted. (Flexion range varies
considerably in standing and sitting positions in functional
cases).
f. i. Measurement of range of spinous movement by
spondylometer or measuring distance between the
tips of the fingers and floor in spinal flexion.
ii. Measurement of the stretching of skin during spinal
flexion over lumbar or sacral region.
g. Tension signs
i. Straight leg raising (SLR) test (Lasegue’s sign)—In
supine position, the leg is rised straight, flexing at
hip with knee extended; when there is pain and
limitation of flexion of thigh, before the leg is lifted
to normal extent of 65° to 90°, due to spasm of
hamstrings and absence of pain on repeating the
manoeuvre with flexed hip and knees as well
(Lasegue’s sign is positive). Dorsiflexion of the foot
increases the pain due to the stretch of the sciatic
nerve (L4 to S3). SLR is represented as an angle at
which the pain is appreciated. Ex: SLR + 45°.
ii. Crossed SLR test: When the normal leg is raised the
pain increases on the affected leg due to root
compression in the spinal canal.
321
iii. Femoral nerve stretch test: In prone position, the
knee is flexed so as to make the heel come nearer
the buttock, when pain and limitation of movement
indicates 3rd lumbar (L3) root lesion.
Neurologic Examination
Motor system, sensory system, reflexes including sphincters,
gait including heel to toe walk should be meticulously done
to localise the root lesion.
General Examination
All pulses in the lower limbs must be palpated in addition to
examination of the abdomen, including rectal and pelvic
examinations, to account for any pathology of the intra-
abdominal viscera, producing referred pain in the low back.
Occasionally the psychological aspects or malingering
problems of low back pain may have to be delineated.
Investigations
The clinician after careful evaluation must discriminate the
investigations to be done on a priority basis which supports
the clinical suspicion.
1. Radiological
a. X-ray of the lumbosacral spine
i. Anteroposterior view focussing both sacroiliac
joints
ii. Lateral view
iii. Oblique view, if necessary for viewing pars
interarticularis
iv. Axial view to visualise narrowing of the
intervertebral spaces specially between L5 and
S 1 with marginal sclerosis (prolapse disc);
osteophytic changes (spondylosis); vertebral
destruction due to infections or tumours;
congenital anomalies (sacralisation, spondylo-
listhesis); and haziness, sclerosis and fusion of
the sacroiliac joints with calcification of the
ligaments (ankylosing spondylitis).
b. Plain abdominal X-ray for calcification of the
pancreas or renal calculi
c. Special radiological investigations
i. Myelography is done in disc prolapse or
intraspinal tumours or any block in the spinal
canal.
ii. Intravenous pyelography if renal diseases are
suspected for referred pain.
iii. Barium enema pictures or colonoscopy if colonic
pathology is suspected.
 322 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

d. Ultrasonography if intra-abdominal lesions causing Preventive Steps

referred pain is suspected.
e. Bone densitometry Avoid precipitating factors like the following:
If T score is –1 to –2.5 (Osteopenia) and –2.5 a. unusual spinal movements
(Osteoporosis) b. lifting heavy objects above hip level or in stooping
f. CT scan to detect diseases of the spinal cord and position with knees extended
nerve roots and erosions of the vertebral bodies or c. use of soft cushions for long periods
abdominal aortic aneurysm. d. long travels in sitting position and
g. MRI e. unusual postures.
2. Haematological
a. Blood counts Symptomatic Relief
b. ESR—raised in caries spine and ankylosing 1. Adequate rest given to the affected parts helps early
spondylitis. resolution (absolute bed rest in supine position on a firm
3. Biochemical mattress or hard surface for 3-4 weeks followed by
a. Serum—calcium, phosphorus, alkaline phosphatase. nonweight bearing period of one week and gradual
Acid phosphatase PSA may be rised in prostatic mobilisation as in prolapsed disc).
neoplasms. 2. Physiotherapy—Encourage spinal exercises after careful
Rheumatoid factor positive in rheumatoid spondylitis. assessment. Graded exercises regularly with the help of
b. Electrophoresis if indicated for paraproteins. a physiotherapist for two weeks, strengthen the back
c. Lumbar puncture and CSF analysis. muscles and stabilise the spine during unseen strains.
4. Urine analysis specially for Bence-Jones proteins 3. Physical therapy—(a) Local hot fomentation;
(Paraproteins) (b) Kneading massage after application of heat; (c) Infra-
5. Other tests—not routinely done red rays for 20 min daily over the affected area for one
a. Radiological week; (d) Short wave diathermy—an area of electrical
i. Discography field is so produced as to improve the blood circulation
ii. Epidurography in the muscles; (e) Other therapies like cryotherapy (in
iii. Epidural venography the form of alternate heat and cold); ultrasonic therapy
iv. Spinal angiography and microwave therapy may be beneficial for deeper
b. Electrodiagnosis pain.
i. Electromyography 4. Spinal support—(a) Lumbosacral belt or spinal brace
ii. Nerve conduction velocity restrict undesirable spinal movements; (b) Pelvic traction
iii. Somatosensory evoked potentials with 30 to 40 kg weight may be beneficial in spondylosis,
c. Radionuclide bone scan disc prolapse and sacralisation.
d. Vertebral biopsy. 5. Pain relievers—(a) Somatic non-narcotic analgesics—
Aspirin (750 mg 6 h), acetaminophen (600 mg 6 h),
TREATMENT OF LOW BACKACHE dextropropoxyphene (65 mg tds); ketorolac
The clinician must incisively pinpoint whether the different tromethamine (10 mg 6 h); NSAIDs (refer to Chapter
presentations of lumbago (pain in the lower part of the ‘Polyarthritis’); or narcotic analgesics—codeine (30 mg
back) and sciatica (pain in the distribution of the sciatic 6 h), pentazocine (30 mg IM 6h), pethidine (50 mg IM
nerve) present as (a) lumbago (local or referred from 6 h). Local anti-inflammatory ointments, oils and sprays;
viscera), (b) lumbago and sciatica together, or (c) sciatica occasionally local infiltration of hydrocortisone and
per se, with seat of pathology in the lower back, yet without xylocaine mixture in areas of pain. (b) Neuropathic:
lumbago as such. The underlying cause of pain in the back Anticonvulsants—Carbamazepine (200 mg 6 h),
(acute or chronic), is then explored and managed phenytoin (100 mg tds), clonazepam (1 mg 6 h)
accordingly. Various methods of therapy are available gabapentin (300 mg t.d.s) and/or antidepressants—
(sometimes even longstanding and uninterrupted) which doxepin (50 mg tds), amitriptyline (25 mg tds), (c)
consist of both preventive and curative aspects. They can Muscle relaxants—Chlorzoxazone (500 mg 6 h);
be grouped as symptomatic (physical and physiotherapies, carisoprodol (175 mg 6 h); Methocarbamol (100 mg
spinal support, pain relievers) and specific surgical and parenterally or 500 mg orally 6 hourly), diazepam (5-10
psychological. mg orally or parenterally 6 h).
 Low Backache
Specific Therapy for Specific Diseases
Spinal Cord and Roots
Spinal tumours (Refer to Chapter ‘Paraplegia’ (Weak
Legs).)
Cauda equina lesions (Refer to Chapter ‘Paraplegia’ (Weak
legs).)
Lesions of the Vertebral Column
Lumbar spondylosis (Refer to Chapter ‘Pain in the
Extremities’.)
Lumbar disc herniation If there is no response after an
optimum period of conservative treatment for symptomatic
relief (rest, physical, spinal support, analgesics,
chemonucleolysis, i.e. injection of chymopapain into disc
space; epidural injection with 20 ml of 0.75% lignocaine
and 100 mg of hydrocortisone or 80 mg of methyl
prednisolone) or progressive neurological deficits occur,
surgical decompression (laminectomy) must be undertaken.
Occasionally facet rhizotomy or fusion of the spine may be
necessary. Disc replacements in selected case advocated.
Infections
• Pott’s disease (Refer to Chapter ‘Pain in the
Extremities’).
• Osteomyelitis (Refer to Chapter ‘Pain in the
Extremities’).
• Paget’s Disease: If NSAIDs fail, salmon calcitonin (100
units three times weekly for six months); diphosphonate
or disodium etidronate 5 mg/kg/d orally and mithramycin
may be beneficial. Hip arthroplasty, if necessary,
considered.
Metabolic
• Osteoporosis
a. Increased elemental calcium supplements (1.5 g daily)
vit D3 (calciferol) (10,000 units/d) or Alfa calcidol
(1 µg daily upto 5µg) or calcitriol (0.25 µg daily upto
1 µg)
b. Hormone replacement (progestogens with conjugated
equina oestrogen 0.625 mg)/24 hrs if postmenopausal
Raloxifene (60 mg daily)
c. Intranasal calcitonin or salmoncalcitonin (100 IU/d SC)
if necessary
d. Bone stimulating drugs like anabolic steroids and/or
sodium fluoride are beneficial
e. Bone regulators (Bisphosphonates) etidronate; 90 day
cycle (400 mg daily for 14 days followed by calcium
(500 mg) and vit D3 (440 1.U)/day for 76 days. 90 day
323
cycle can be repeated (recommended for vertebral
osteoporosis). Alendronate (10 mg/d) is indicated for
osteoporosis at any site including post-menopausal
osteoporosis.
f. Strontium ranelate
g. Recombinant human parathyroid hormone (Teripara-
tide).
h. Natural Vit. K2-7 (f, g, h are new options)
•. The risk factors like nicotine and alcohol abuse, sedentary
habits, etc. should be corrected. Calcium rich diet
recommended.
• Hyperparathyroidism
The treatment for primary type is usually surgical removal
of the adenoma. In elderly people, hypercalcaemia is
treated with IV saline and if necessary magnesium and
potassium, should be supplemented. Salmon calcitonin
(200-400 units tds subcutaneously) is other alternative
in reducing serum calcium. Mithramycin (25 µg per kg
IV) or neutral phosphate IV (500 ml 0.1M) are also
effective (usually given once only).
Nutritional
• Osteomalacia: 2,000-4,000 units per day of vitamin D3
(Cholecalciferol) given for three months followed by
200-400 units per day. In case of malabsorption, vitamin
D in large doses (10,000 units) and calcium carbonate
(4 g per day) may be necessary. Vitamin D is
supplemented during anticonvulsant therapy. In renal
osteomalacia, dihydrotachysterol (0.2-1 mg per day) or
calcitrol (0.25 µg per day) or alfacalcidol (up to 5 µg per
day) are effective. (Refer to Chapter ‘Epileptic Scizure’).
• Fluorosis: There is no effective treatment for fluorosis
and prevention is all important. However, the effects of
fluorine poisoning sans backache (due to fluoride leak
during manufacture of superphosphate or smelting
aluminium) should be treated with IV calcium (since
calcium is converted to calcium fluoride).
Autoimmune Diseases
Rheumatoid spondylitis (Refer to Chapter ‘Polyarthritis’.)
Ankylosing spondylitis (Refer to Chapter ‘Polyarthritis’.)
Neoplastic
Multiple myeloma (Refer to Chapter ‘Bleeding Disorders’)
a. High fluid intake (3 litres) provided there is no renal
impairment.
b. Chemotherapy—Cyclophosphamide IV (300 mg/m 2
weekly), or melphalan (7 mg/m2 daily for four days
every 4-weeks) with or without prednisolone (40 mg/
 324 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
m2 for four days) is given for 1 or 2 years till the
paraprotein, haemoglobin and beta microglobulin levels
are stable with clinical improvement for at least three
months. Doxorubicin and BCNU combined with
cyclophosphamide and melphalan or Doxorubicin and
BCNU combined with vincristine and prednisolone or
vincristine. Doxorubicin and Dexamethasone are
chemotherapeutic regimens other options are high dose
pulse dexamethasone with or without thalidomide or
Bortezomib alone or in combination with Dexametha-
sone. Allopurinol (300 mg/d) may be required to prevent
hyperuricaemia. Bone marrow or stem cell transplan-
tation is a final option.
c. Radiotherapy is useful for localised problems.
d. Appropriate supportive therapy if renal failure,
hypercalcaemia, intercurrent infections occur.
Secondary deposits If vertebral destruction leads to
instability, immobilisation is beneficial. Radiotherapy (4000-
5000 rads) given within a period of one week, is the mainstay
for spinal metastases. Decompression surgery is indicated
if the neurological deficit is progressive.
Congenital
Lumbar canal stenosis Lumbar laminectomy (extensive) yields
relief, from exercise induced symptoms of cauda equina
claudication.
Sacralisation Spinal support and symptomatic therapy
suffice. If L5 root is involved laminectomy may be required.
Spina bifida occulta If symptomatic, passive movements and
exercises of lower limbs may improve power. Bladder
disturbance like enuresis is treated with oxybutynin or
desmopressin. If disabling symptoms develop, surgical
intervention is indicated, i.e. tenotomy to correct the feet
deformities or dissection of the constricting band or
occasionally laminectomy, as the case demands.
Spondylolysis and spondylolisthesis Conservative treatment
like bracing, local heat, bed rest, traction and corticosteriod
infiltration may suffice. Stabilising operations indicated when
neurological deficit develops or symptoms are unremitting.
• Traumatic
Conservative treatment initially (methyl prednisolone
injection reduces cord oedema) and care is bestowed as
for paraplegia if present. Surgical management may be
instituted to relieve compression. Manipulative reduction
of vertebral deformity is undertaken, if necessary.
• Osteochondritis
Calve’s disease Recumbency position may retard the
compression. Radiation therapy may be necessary if
eosinophilic granuloma is incriminated.
Scheuermann’s disease Absolute bed rest in hyperextension
position is insisted in active stage followed by a back support.
A body cast or a brace is required as a corrective device.
Promote exercises which strengthen the back muscles.
Surgery is indicated for severe disabling back pain or
deformity and signs of cord compression.
Soft Tissues and Joints
• Fibrositis and Fibromyositis (Refer to Chapter ‘Pain in
the Extremities’.)
• Sprung Back
For mild cases, conservative treatment is advised as for
disc prolapse (local anaesthetics if necessary). Intractable
cases require stabilisation by spinal fusion.
• Lumbosacral Strain
Bed rest in flexed position helps. The knee rest and back
rest are elevated. Local heat and analgesics are useful.
Pelvic traction with 60 kg weight is applied with the
foot of the bed raised. Exercises are initiated, when pain
subsides. Abdominal and gluteus maximus muscles
should be strengthened while hip flexors are kept
inactive. Avoid postures like rising from sitting position,
bending forward or sleeping in prone position.
• Postural Strain
Avoid incorrect postures. Appropriate postural exercises
may be designed to improve the muscle tone or
strengthen the musculature. Symptomatic relief with
analgesics and/or muscle relaxants may be necessary.
Proper pelvic inclination is secured by suitable measures.
• SacroIliac Strain
Bed rest, spinal support, physical therapy, analgesics,
injections of steroid and local anaesthetic facilitate
recovery. Avoid excessive bending and lifting.
Subluxation, if present, requires manipulation.
• Tuberculosis of the Sacroiliac Joint
Prolonged immobilisation in a cast and specific
antikoch’s treatment with supportive therapy yield
desired results. (Refer Chapter ‘Haemoptysis’).
Occasionally intra or extra-articular arthrodesis may be
required.
Referred Pain
Referred pain from intra-abdominal diseases is treated
according to the seat of pathology.
 Low Backache
Cholecystitis (Refer to Chapters ‘Acute Abdominal Pain and
Dyspepsia’.)
Chronic peptic ulcer (Refer to Chapter ‘Dyspepsia’.)
Pancreatitis (Refer to Chapter ‘Chronic Diarrhoea’.)
Kidney affections (Refer to Chapter ‘Haematuria’.)
Lymphoma (Refer to Chapter ‘Bleeding Disorders’.)
Neoplasms of the colon (Refer to Chapter ‘Chronic
Diarrhoea’.)
Pelvic inflammations and gynaecological causes (Refer to
Chapter ‘Acute Abdominal Pain’).
325
Prostatic pathology (Refer to Chapter ‘Haematuria’.)
Aneurysm of abdominal aorta (Usually conservative
treatment is given. Surgical repair may be necessitated at
times with graft replacement or with a stent graft.
Psychogenic Pain
Psychotropic drugs, psychotherapy, hypnotherapy, TENS
(transcutaneous electrical nerve stimulation)—(Refer to
Chapters ‘Vomiting’ and ‘Vertigo’.)
326 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Low Backache 327
 Chapter
Obesity
21
Obesity is the term derived from the Latin word “OB-
EDERE” which means overeat. It is defined as excessive
accumulation of body fat with an increase in weight of
20 per cent or more above the ideal weight. The body fat is
more than 23 per cent of body weight in men and more
than 26 per cent of body weight in women. Ideal weight is
the standard range of weight where the life expectancy is
greatest. It is calculated by comparing with standard tables
for height and weight in relation to age and sex.
CHEMICAL COMPOSITION OF BODY COMPARTMENTS
The body mass consists of four compartments—extracellular
compartment, intracellular compartment, bone and adipose
tissue. The Lean Body Mass (LBM) is formed by the first
three compartments (30% of which is made up of skeletal
muscles and 20% comprises viseral compartment). LBM is
calculated in kilograms by the equation [21 + 21.5 × 24 h
excretion of creatinine in grams]
Total Body water (L)
LBM
0.73
and the difference between the body weight and the lean
body mass indicates the amount of body fat. Approximately
the intracellular compartment (protoplasm) forms 50 per
cent; the extracellular 24 per cent, adipose tissue 19 percent
and bone 7 per cent of the body weight. Electrolytes are
distributed in the various compartments as given below.
Potassium and phosphorus in the intracellular
compartment; sodium and chloride in the extracellular fluid
(plasma, interstitial fluid, connective tissue, bone and
transcellular fluid); calcium and phosphorus in the bone;
and insignificant amounts of electrolytes in adipose tissue.
The total body water forms about 60 per cent of body
weight (intracellular fluid 36%; and extracellular fluid 24%).
Hence, any gain in the weight can be due to retention of
fluid, which is a pitfall in the diagnosis of obesity. So the
body weight must be taken into consideration in
nonoedematous patients for assessing the degree of obesity,
although fluid retention is supposed to facilitate fat
metabolism and storage. Sometimes lean body mass itself
may contribute to overweight as in atheletes with good body
build and musculature.
PATHOPHYSIOLOGY
The food consumed as carbohydrates and fats is stored in
the fat cells for the body for energy purposes. Proteins
contribute less since a part of it is spent for metabolic action
(i.e. specific dynamic action). Glucose is the major fuel for
the body metabolism and it is maintained by glycogenolysis
or synthesis from amino acids. Glycogen stores and the
amino acid pool are short-term energy storage systems.
Excess intake of food leads to excess production of glucose
and amino acids leading to formation of fat (as triglycerides)
which is a long term energy store. When the short-term
energy system is unable to cope with the energy demands
the fat is oxidised to carbon dioxide and water, a reaction
which is irreversible.
The regulation of eating depends upon interaction
between hunger and satiety centres. In fact the appetite is
controlled by the ventrolateral feeding centre (stimulatory)
and ventromedial satiety centre (inhibitory) of the
hypothalamus through cerebral cortex.
In the majority, obesity is related to overating behaviour,
i.e. excess of intake of calories. Heat is normally generated
following absorption of food, i.e. dietary thermogenesis or
specific dynamic action. But a metabolic defect with a
genetic background such as absence of special ability to
burn off excess calories, seems to exist in obesity, thereby
facilitating more calories for storage as fat, i.e. production
 Obesity
of heat is less and energy is not wasted as heat. Besides this
physical inactivity, i.e. decreased calorie expenditure
contributes. The pathophysiology of obesity is further
attributed to increases in number as well as size of fat cells
and this excess adiposity not only increases the body weight
but also influences the hypothalamic activity.
In addition obesity may be associated with either endocrinal
or genetic disorders, or drug display (secondary obesity).
Methods to Estimate Body Fat
Direct Methods
Densitometry measurement of total body water and
potassium; and estimation of fat cell mass by uptake of fat
soluble inert gases are highly technical and not applicable in
clinical practice.
Indirect Methods (Anthropometric Measurements)
a. Skinfold measurements: Skinfold thickness is measured
by calibrated skin calipers over triceps (men 12.5 and
women 16.5 mm) and subscapular areas (> 25 mm), which
indicate thickness of both skin and subcutaneous fat.
b. Midarm circumference is measured with a tape measure
(men 29.3 and women 28.5 cm)
c. Abdominal (waist-midpoint between lowest part of costal
margin and superior border of iliac bone-i.e. below the
ribs and above the umbilicus) circumference measured.
(Men: >102 cm and women: > 88 cm)
d. Gluteal (hips) circumference is measured at the point of
maximum protruberance of the buttocks.
e. Abdominal Gluteal Ratio (AGR)—Above 0.85 for women
and 0.9 for men carries greater risk.(waist-hip ratio)
f. Height weight ratios:
i. Body mass index or Quettlet’s index, i.e. W/h2 is
weight in kilograms and H is height in metres).
The normal index is 18.5 to 24.9. If the index is between
25 and 29.9 (mild overweight: low risk)
Obesity is > 30. May be mild moderate and serve class I
30-34.9 (mild risk); class II 35-39.9 (moderate risk) and
class III > 40 (high risk)
ii. Ponderal Index (cuberoot of weight in kilograms
divided by height in meters)
Generally ideal body weight can be determined by:
1. Broca’s index = Height (cm) minus 100.
2. Adding or substracting 5 pounds to 100 pounds for
women and 110 for men for every inch of the height of
329
the subject above or below 5 feet and 10 per cent to 20
per cent added for average or large frame respectively.
Height in inches chest in expansion in inches
3.
17
= weight in pounds (+10 or –10)
Types of Obesity
1. Clinical Types
Android Type (Central / Visceral) The distribution of body
fat is confined to the upper half of body (predominantly
abdominal) seen in men. The subscapular skin fold thickness
measured by calipers is more than 25 mm or the waist to
hip girth ratio is more than 0.85.
Gynoid Type The fat distribution is confined to the lower
half of body (predominantly gluteal and femoral) seen in
women. The subscapular skin fold thickness is less than 25
mm and the waist to hip girth ratio is less than 0.85.
Overall Obesity or Total Body Obesity (Generalised)
It is distributed both in the upper and lower halves of the
body. This generalised obesity (both trunk and arms) tends
to be present throughout life.
2. Morphological Types
Hypertrophic It is adult onset with normal number of fat
cells but increased in size and the weight gain is due to fat
deposition. Obesity is central and confined to the trunk,
sparing the extremities.
Hyperplastic Hypertrophic The number of fat cells and size
increase during childhood. Obesity is generalised and tends
to be lifelong.
Degree of Obesity
It is determined by body mass index and anthropometric
measurements. Mild obesity may not be significant but severe
or morbid obesity leads to pathological sequelae.
Risks Related to Obesity
Obesity is a considerable risk factor for metabolic, vascular
disorders and mechanical disabilities (vide infra). The life
expectancy is said to be reduced roughly by 1 per cent for
everyone pound of excess weight, (i.e.) if a person
presumed to live up to 80 years, has 10 pounds of excess
weight, his life may be shortened by 8 years.
 330 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

CAUSES OF OBESITY customs may also influence. The overweight appears to

start from early childhood, where there is increased number
Table 21.1 enlists aetiological components of obesity.
and size of fat cells.
Table 21.1: Causes of obesity Genetic factors like obesity gene is identified whose
1. Simple obesity protein product is leptin, which decreases food intake and
a. Constitutional increase energy expenditure. When leptin deficiency or leptin
b. Alimentary obesity: Overeating or compulsory overeating resistance exists obesity may result.
with less physical activity
2. Endocrinal obesity
a. Hypothalamic pituitary disorders
Alimentary Obesity
i. Fröhlich’s syndrome Eating behaviour like continuous nibbling facilitates excess
ii. Pituitary tumours
of food intake. Compulsive overeating specially of sweets
iii. Empty sella syndrome
iv. Internal hydrocephalus with third ventricle involvement and chocolates is similar to addiction of alcohol. This is
v. Encephalitis undoubtedly due to emotional or psychological factors. An
b. Thyroid: Hypothyroidism intake of excess of say 100 calories per day will add about
c. Parathyroid: Pseudohypoparathyroidism 1lb of body weight in the course of one month. Excessive
d. Adernal cortex: Cushing’s syndrome consumption of carbohydrates may lead to increase in
e. Pancreas: Insulinoma
thermogenesis (body’s tendency to produce heat) by
f. Gonads
i. Menopause
increasing the concentrations of T3 levels as against T4.
ii Pregnancy Obesity results when such a response fails to occur.
iii. Polycystic ovaries (Stein- Leventhal syndrome) Physical activity maintains the caloric balance. If a person
3. Congenital Disorders (Syndromes) weighing 60 kgs walks 3 miles per hr, expends at the rate of
a. Prader-Willi
5.2 calories per minute. Similarly, if he runs, he spends 19.4
b. Lawrence-Moon-Biedl
c. Alstrom calories per minute, i.e. if one walks for one hour daily, the
d. Biemond’s caloric expenditure amounts to about 300 calories. Hence,
e. Carpenter too much food or too little exercise or both may lead to obesity.
f. Weiss In some cases mere hypometabolism without thyroid
4. Disorders of Adipose Tissue
a. Multiple lipomatosis
deficiency as such, may account for obesity.
b. Dercum’s disease
c. Partial lipodystrophy Endocrinal Obesity (Secondary)
5. Drugs
a. Steroids:glucocorticoids and oestrogens Hypothalamic Pituitary Disorders
b. Insulin
Fröhlich’s syndrome or dystrophia Adiposogentalis It is
c. Tricyclic antidepressants
d. Sodium valproate due to anterior pituitary hypothalamic dysfunction by a
tumour like craniopharyngioma. The resulting hyposecretion
N.B. Generally causes of gain in weight may be due to pregnancy or
leads to marked genital hypoplasia and obesity from early
muscular hypertrophy as in athletes apart from too much adipose tissue
or oedema.
age, conspicuously round the face, trunk, shoulders and
hips with slender limbs. There may be associated sleep
Simple Obesity (Primary) disturbances like somnolence and polyuria.
Pituitary tumours Pituitary tumours like (a) chromophobe
Certain aetiological factors like genetic susceptibility (thrifty
adenoma may have moderate obesity and the depression of
metabolic trait), physical inactivity, addiction for sweets,
sexual function or (b) basophil adenoma may result in painful
added fats, excess refined carbohydrate or carbohydrate
adiposity with cutaneous striae and amenorrhoea. The
drinks, overeating for emotional reasons, are incriminated.
symptoms may be absent or appear later. Sometimes,
tumours may develop between the floor of the third ventrical
Constitutional Obesity
and pituitary like craniopharyngioma and result in consequent
Obesity is seen in certain families very often. Though genetic hypothalamic disturbances like obesity, genital hypoplasia,
factors are responsible, social, economic status and family disturbances of sleep, temperature regulation, and cranial
 Obesity
diabetes insipidus. Endocrine evaluation includes tests for
hyposecretion of the anterior pituitary hormones like FSH
and LH and/or 24 h urine for measuring gonadotrophins or
steroids.
Empty sella syndrome It is an largement of sella turcica
with cerebrospinal fluid rather than a tumour. Pituitary gets
compressed and results in obesity and hypertension. Visual
field defects are not common. It is usually seen in multiparous
women. It is diagnosed by X-rays of the sella or tomography
which may show characteristic ballon appearance of the
sella, without erosions of its floor.
Internal hydrocephalus with third ventricle involvement
Distension of the floor of the third ventricle may compress
the sella and pituitary and result in obesity and genital
hypoplasia due to obstruction in the aqueduct of sylvius by
any intracranial tumour.
Encephalitis Obesity with genital atrophy may result due
to the involvement of the hypothalamus as a post encephalitic
sequel. Polyuria, polydipsia may also be associated. (Refer
to Chapter ‘Coma’.)
Thyroid (Hypothyroidism)
Obesity is associated with hypothyroidism because of the
decreased basal metabolic rate and caloric needs. The weight
gained associated with poor appetite, dry skin, puffy eyelids
with thick lips and nonpitting oedema are all highly
characteristic. (Refer to Chapter ‘Oedema’.)
Parathyroid (Pseudohypoparathyroidism)
It is characterised by obesity, hypertension, short stature,
short metacarpals and metatarsals, with absence of knuckles
or the 4th and 5th fingers while making a fist. The
parathyroids are often hyperplastic but the renal tubules do
not respond to parathyroid hormone due to a genetic defect.
Low serum calcium, raised phosphorous and increased
immunoreactive parathyroid hormone levels are the
biochemical parameters.
Adernal Cortex (Cushing’s Syndrome)
Hyperfunctioning of the adernal cortex results in Cushing’s
syndrome wherein the body fat is distributed
characteristically in the face, neck and trunk (buffalo
obesity). Associated weakness, amenorrhoea, purple
abdominal striae, hypertension, osteoporosis and impaired
carbohydrate tolerance are highly suggestive. Cortisol levels
331
in the urine or plasma are elevated. Failure of suppression
of urinary cortisol to less than 30 µg per day (normal urinary
cortisol 20-100 µg/24 µh) or plasma cortisol to less than 5
µg % (normal plasma cortisol is 9-24 µg% and normal
cortisol secretory rate /24 hours is 5-25 µg) after 1/2 mg of
dexamethasone every 6 h for 48 hrs is highly diagnostic.
Plasma ACTH level is low in adernal tumours and increased
in ACTH producing tumour (pituitary or ectopic pathology).
(Normal value of ACTH = < 80 pg/ml).
Pancreas (lslet Cell Adenoma)
Insulinomas or beta cell islet tumours leads to
hyperinsulinism. The clinical featurs are those of
hypoglycaemia with sudden attacks of hunger, weakness,
sweating and paraesthesia. The fasting blood sugar of 50
mg% during the attack and immediate recovery after
administration of glucose are characteristic. This recurrent
hypoglycaemia may lead to increased caloric intake and may
lead to obesity in some cases. The plasma insulin, proinsulin
and C-peptide are all increased in insulinomas and particularly
increased plasma proinsulin is diagnostic (20% more than
insulin). Normally I.V. insulin suppresses C-peptide and this
suppression does not occur in insulinomas.
Gonads
Menopause It results from the cessation of ovarian function
at about 50 years of age. This leads to activity of the pituitary
leading to increased gonadotrophic hormone production.
There is considerable increase in weight in some women
along with vasomotor instability (Hot flushes),
emotionalism, hirsutism and osteoporosis. In some women,
amenorrhoea may be the only indication, between ages 45
and 55.
Pregnancy Normally a women may gain about 12 kg during
pregnancy. About one third, i. e. 4 kg may be attributed to
an increase in adipose tissue, about 2 kgs for water retention
and the remaining for foetus, placenta and uterus. Some
women may gain more than this schedule weight and this
extra weight remains even after cessation of lactation.
Further pregnancies perpetuate obesity.
Polycystic Ovaries (Stein-Leventhal syndrome)–PCOS.
Polycystic ovaries are associated with obesity, hirsutism,
irregular menstrual periods with either prolonged
amenorrhoea or abnormal bleeding, infertility and enlarged
polycystic ovaries. Increased LH and testosterone with low
or normal FSH are the typical biochemical observations.
 332 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Congenital Disorders Other Drugs

• Prader-Willi Syndrome Which include cyproheptadine, tricyclic antidepressants,
•
•
•
•
•
Lawrence-Moon-Biedl Syndrome
Alstrom’s Syndrome
Biemond’s Syndrome
Carpenter’s Syndrome
Weiss’s Syndrome
}
Disorders of Adipose Tissue (Lipodystrophies)
(Refer Chapter
‘Impotence’).
occasionally streptomycin and valproate.

Multiple Lipomata
Systemic lypomatosis is characterised by the formation of
fat deposits (lipomas) over the neck or supraclavicular
regions on lower half of the body or lipomas of varying
sizes may be scattered. Hypertriglyceridaemia,
hyperinsulinaemia and hyperuricaemia may be present. Fat
cells in the lipoma are small probably due to the formation
of new adipocytes.
Dercum’s Disease (Adiposis Dolorosa)
In Dercum’s disease, the obesity is generalised. Painful
subcutaneous fatty deposits of varying sizes up to 5 cm are
present in the extremities. Women are usually affected and
belong to postmenopausal group. It may be familial, and
failure to synthesise 18 carbon fatty acids is the biochemical
abnormality.
Partial Lipodystrophy
The obese appearance of the lower half of the body with
lipoatrophy in the upper half of the body is characteristic of
acquired partial lipodystrophy. Women are usually affected,
proteinuria with or without renal disease and hyperglycaemia
are common. Complement system is abnormal and C3 levels
may be low.
DRUGS
Steroids
Corticosteroids given for longer duration cause weight gain
and in some cases may lead to Cushing’s syndrome.
Similarly, 17-β oestradiol, oral contraceptives and anabolic
steroids can result in weight gain due to increase in adipose
sites.
Hypoglycaemic Agents
Insulin and sulphonylureas can also lead to increase in weight.
COMPLICATIONS OF OBESITY
The increased deposits of adipose tissue in the visceral and
intramuscular space may ultimately result in metabolic and/
or vascular sequelae. The android variety is more susceptible
to obesity related disorders particularly diabetes mellitus,
hypertension, hypertriglyceridaemia and low HDL.
Hypertension is three times common. Diabetes mellitus and
hyperlipidaemia are two times common than nonobese
individuals. The fatality is primarily through vascular
complications like coronary artery disease or cerebrovascular
disease. The other complications due to mechanical and
physical stresses are cholelithiasis, locomotor disabilities,
hypoventilation (Pickwickian’s syndrome – obstructive sleep
apnoea syndrome) and syndrome X.
Syndrome X (Reaven’s Syndrome / Insulin Resistance
Syndrome / Metabolic Syndrome)
Insulin resistance is a state of decreased insulin sensitivity
with less than normal response and it is reflected by increased
insulin requirements (> 200 units/d).
Obesity (particularly android or overall types) is
associated with cluster of risk factors like hypertension,
diabetes mellitus (Type 2), and Dyslipidaemia. Insulin
resistance with metabolic abnormalities like
hyperinsulinaemia, and hyperuricaemia is identified as
syndrome X or metabolic syndrome.
Pathogenesis
The hyperinsulinaemia (i.e fasting insulin > 89.4 Pmol/L)
and impaired glycaemic responce to insulin, reflects insulin
resistance (decreased insulin sensitivity). Decreased number
of insulin receptors and intracellular defect in glucose
metabolism beyond the receptor, account for insulin
resistance (apart from insulin receptor antibodies and
postreceptor defects in the action of insulin). Consequently
hyperinsulinaemia occurs secondary to increased insulin
secretion (in order to maintain euglycaemia) and further
addition of insulin, (due to decrease in its hepatic extraction).
Such hyperinsulinaemia and insulin resistance lead to lipid
changes, hypertension and diabetes mellitus.
Lipolysis of increased abdominal fat leads to release of
free fatty acids. This results in hypertriglyceridaemia which
 Obesity
is usually accompanied by increased VLDL and decreased
HDL cholesterol.
Hyperinsulinaemia leads to hypertension due to renal
sodium retention or sympathetic nervous activation or
hypertrophic effects of vascular smooth muscle or increased
intracellular calcium.
Diabetes mellitus is one of the common complications
of obesity. The ingested carbohydrate is diverted into fat
depots. The glucose in the adipose tissue is utilised for fatty
acid synthesis and esterified to triglycerides for which
process, insulin is required. A stage may occur when the
fat depots accept no more fat derived from glucose as they
are already overstuffed, thereby facilitating glucose
accummulation in the blood. The overwork and ultimate
exhaustion of islets of Langerhan’s contribute to further
the development of diabetes mellitus in obese individuals.
All these three factors, i.e. hypertension, impaired glucose
tolerance and lipid changes, may predispose to (premature)
atheresclerosis, with consequent coronary heart or
cerebrovascular disease other features are Microalbuminuria
raised CRP; and hypercoagulability due to increased
plasminogen activator in hibitor-1 and fibrinogen levels. Apart
from obsity; genetic basis is incriminated.
CLINICAL APPROACH
The diagnostic evaluation is based on the initial assessment
of the degree of obesity in relation to the patient’s weight
compared with that of ideal body weight. The next step is
to determine whether obesity is primary or secondary. The
third step is assessment of the risk associated with body fat
and its distribution.
History
1. Age: Childhood, pregnancy, middle age or climacteric.
2. Sex: Both sexes are equally affected in childhood but
incidence in women is higher after puberty.
3. Familial incidence: Usually, it runs in higher
socioeconomic families. Any other member of the family
having similar complaint?
4. Onset of obesity: Is it static, progressive or abruptly
appeared? (Abruptly appeared in hypothalamic lesions:
progressive overeating or pregnancy and static
endocrinal.)
5. Eating habits
i. Appetite: Whether it is increased.
ii. The type and amount of food taken should be
enquired in detail to assess the caloric intake.
333
6. Physical activity: Type of work, type of exercise
undertaken during the day to assess the caloric
expenditure.
7. Any history of preceding infections: Any associated
symptoms like visual impairment, headache, vomiting,
polyuria, amenorrhoea, Whether pain is present in the
fat deposits? Any disturbances of sleep and temperature?
8. Drug history: Any intake of drugs which can cause
obesity?
9. Psychological factors: Psychological factors like
unhappiness or boredom, conflicts and other emotional
reasons, if any, have to be considered. Psychiatric history
from the patient to be correlated with that of the relative.
Physical Examination
General Survey
1. Appearance
a. Body stature: Is it short stature or normal stature?
b. Distribution of fat: Android or gynoid type?
c. Face: Moon or rounded face? Baggy eyelids?
d. Neck: For any thyromegaly.
e. Hands and feet: Syndactly or polydactyly? Short
metacarpals and metatarsals?
f. Skin: Is the skin dry and coarse or fine and silky or
any purple striae.
g. Hirsutism.
2. Oedema: Pitting oedema if present, it may be due to
associated water retention.
3. Genitalia and secondary sexual characters: Is genitalia
normal or ill developed?
4. Measurements: record
(a) Height, (b) Weight, (c) Chest measurements
(insipiration, and expiration), (d) Abdominal (waist)
circumference, (e) Gluteal (hips) circumference,
(f) Triceps skin fold thickness, (g) Subscapular skin
fold thickness and (h) Midarm circumference.
5. Blood pressure: To be recorded with a large cuff which
encircles 75% of the arm.
Systemic Examination
1. Cardiovascular examination for evidence of
cardiomegaly due to hypertension or atherosclerosis.
2. Respiratory system for evidence of hypoventilation, cor
pulmonale or chronic bronchitis.
3. Abdomen: The distension has to be judged whether it is
due to subcutaneous fat or fluid. Any abdominal herniae.
 334 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
4. Examination of the genitalia (Refer to Chapter
‘Impotence’).
5. Pelvic examination for any palpable enlarged ovaries.
6. CNS examination
a. Visual fields
b. Papilloedema
c. Retinal pigmentation
d. Cranial nerve plasy
e. Prolonged relaxation of the ankle reflex (foot comes
slowly to the starting position)
Investigations
1. Urine examination
a. 6 litres of urine per day with a specific gravity below
1006 is suggestive of diabetes insipidus, and if the
specific gravity is above 1015 after restriction of
fluids, diabetes insipidus can be eliminated.
b. 17 ketosteroids: In Cushing’s syndrome due to
adenoma, the values are low or normal; due to
hyperplasia high or normal; due to carcinoma very
high (normal values are men: 7-25 mg/day; women:
4-15 mg/day).
c. Urinary 24 h free cortisol is raised in Cushing’s
syndrome.
2. Biochemical tests to be performed depending upon clinical
suspicion.
A. Hormones
a. Thyroxine and thyrotrophin (TSH) levels
b. Testosterone and oestradiol
c. (i) Cortisol levels and
(ii) Overnight Dexamethasone suppression test;
(Plasma cortisolis less than 5 µg % at 8 AM
in normal subjects after 1 mg of
dexamethasone given orally at 11 PM previous
night). Non-suppression suggests Cushing’s
syndrome.
d. ACTH.
e. FSH, LH, Prolactin
B. Blood glucose levels (fasting and postprandial)
C. Radioimmunoassay of insulin; Proinsulin and C-
peptide
D. Serum lipids cholestrol and its fractions; triglycerides
E. Serum uric acid
F. Serum leptin
3. Cyclic AMP response: Exogenous parathyroid hormone
when given as IV infusion, the cyclic AMP response is
impaired in pseudohypoparathyroidism, whereas the
response is normal in hypoparathyroidism.
4. Basal Metabolic Rate (BMR)
5. Radiological examination
a. X-ray of skull, (AP and lateral views) to visualise
pituitary fossa)
b. X-ray of chest PA view (to assess the cardiac
silhouette)
c. Abdominal X-ray for calcified adernal tumour
d. CT scan—If indicated
6. Ultrasonography for polycystic ovaries.
TREATMENT OF OBESITY
Whatever be the cause of obesity, treatment is directed
towards the energy imbalance, and weight reduction is
possible only by decreasing the energy intake or increasing
the energy output or both. The former has a greater potential
for achieving the goal than the latter. In this regard, patient’s
motivation and education for a change in lifestyle is all the
more important.
To reduce the caloric intake, structured low calorie diets,
appetite suppressants and gastric surgery, if necessary, are
rewarding. To achieve caloric loss, appropriate exercises,
thermogenic drugs, and bypass surgery are to be adopted.
Symptomatic Treatment
Therapeutic Lifestyle Changes
Diet It should be structured as to keep the caloric needs
lower than the actual caloric expenditure. In this endeavour,
the energy needs or energy output can be initially estimated
and the calories are so restricted as to obtain a weekly weight
loss of 0.5 to 1 kg. For instance, a caloric deficit of 3,500
kcall per week is presumed to result in a loss of about 0.45
kg per week. Generally a low calorie diet is constructed to
give about 800-1000 kcal per day, containg 150 g of
carbohydrates with dietary fibre, 50 g of protein and 25 g
of fat along with vitamins and minerals.
Very-low-calorie diets (400 kcal per day) may be
necessary in severe obesity and to ameliorate the related
metabolic complications.
Therapeutic starvation (< 20 kcal per day) For a period of
two weeks (with only water, minimal caloric drinks with
allowances of protein supplements, vitamins and mineral)
only in a hospital, may result in a initial weight loss of 1 to
1.5 kg per day, which may slow down gradually. Of course
the long-term results are not that satisfactory.
 Obesity
Exercise and increased activity Regular physical exercise
is complementary in the weight reduction programme.
Physical exercise which is a complex physiologic act is of
two types. The first type known as dynamic or aerobic or
endurance involves the stretching of major muscle groups
in a rhythmic pattern and the entire body is in motion.
Examples are walking, jogging, running cycling, swimming,
etc. which expend varying amounts of calories ranging from
5 to 10 calories per minute. In the second type known as
static or isometric, the muscles contract against fixed objects
and the body is static. The former is advisible for obese
subjects.
The exercise period ideally should be for about 45
minutes to one hour without break and preferably so as to
raise the heart rate to maximum of (200-age in years). It is
better stepped up gradually within the limits of tolerance of
the patient. Regular daily exercise is insisted rather than
episodic increased activity. (The energy expenditure during
light activity is 1.1 to 3, moderate activity 3.5 to 7, heavy
activity 7 to 10 and sleep 0.6 to 0.8 kcal/min).
Behavioural Treatment
Identify and modify maladaptive eating, activity and thinking
habits.
Drug Therapy
a. Noradrenergic agents: - Diethylpropion (75 mg as
single dose daily). Phentermine (30 mg per day before
breakfast), Mazindol (2 mg per day).
b. Serotonergic agents: Fenfluramine (20 mg twice daily
before meals, gradually increased to 120 mg). and
Dexfenfluramine. These are withdrawn due to
occurrence of cardiac valve lesions and pulmonary
hypertension or psychosis. These anorexigenic drugs
may be given for 6-12 months and tapered slowly
which results in weight loss of an average of 0. 25
kg per week. Some patients may regain some weight
when treatment is discontinued. Intermittent courses
of anorexigenic drug therapy may prove beneficial.
c. Noradrenergic and serotonergic agents: - Sibutramine
(10-15 mg daily for 3 months). If responsive, may
be continued further.
d. Pancreatic lipase inhibitor- Orlistat (120 mg –360
mg per day for 12 weeks). If 5% reduction in weight
occurs, it may be continued for 1-2 years.
e. Bulk preparations: Methyl cellulose (1. 5 gm with
300 ml of warm liquid half an before food) or Guar
gum dissolved in water may be given 15 min. before
335
meals which gives a feeling of satiety with less
calories.
f. Diuretics better used judiciously, if necessary, along
with sodium restriction.
g. Metformin as adjunctive therapy in persons at risk
to diabetes sodium restrictions.
h. Thyroxine: It role is not beneficial at all in obesity,
since the low BMR is attributed to increased body
surface with relatively poor oxygen consumption by
fatty tissues (BMR measures oxygen consumption
in terms of surface area of the body). However, it
may be beneficial if hypothyroidism coexists.
i. Leptin: Recombinant human leptin induce weight
loss, if there is leptin deficiency.
j. Rimonabant (20 mg/d).
N. B. Two antiobesity drugs cannot be combined, if
weight loss is < 5% of initial body weight or regains weight
(> 3 kgs) after previous weight loss, the drug should be
discontinued.
Psychotherapy
Overeating arises as a habit most often out of bordeom and
psychological background. In this regard, psychotherapy
or antidepressants like fluoxetine are sometimes advocated
along with nutritional education to change the behavioural
pattern of eating.
Physical Therapy
Body massage with appropriate oils may help not only in
weight reduction but retain the integrity of the skin, without
the appearance of folds.
Bariatric Surgery
Obese patients with a body mass index of > 40 or 100%
above the ideal body weight may not respond satisfactorily
to the above therapeutic measures. In such cases bypass
operations like gastric bypass or jejuno ileal bypass may be
undertaken. Follow-up of cases and study of short and long-
term complications favour gastroplasty (to delay gastric
emptying) than small intestinal bypass (to inhibit absorption).
Sleeve gastrectomy decreases hormone grelene which
decreases hunger.
Treatment of Insulin Resistance Syndrome (IRS)
• Diabetes mellitus treated with insulin and insulin
sensitizers—glitazones, Metformin and Vit. E. which also
delays LDL oxidation.
 336 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Obesity (Vide supra);
• Dyslipidaemia—statins and omega-3
• Hypertension—ACE inhibitors (ACEI and statins help
endothelial function). Aspirin and Antibiotic useful.
Specific Treatment for Specific Underlying Cause
Simple obesity Symptomatic Treatment (Vide supra).
Endocrinal Obesity
Hypothalamic-Pituitary Disorders
a. Fröhlich’s Syndrome: The treatment consists of the
surgical removal of the hypophyseal stalk tumour. It
appears reasonable to prescribe gonadotrophin
hormones. Other hormonal deficiencies are replaced,
as required.
b. Pituitary tumours: The treatment of pituitary tumours
(adenomas) depends on the nature of the tumour. If it is
a basophil adenoma causing endocrinal symptoms
(Cushing’s disease) trans-sphenoidal surgery is done
followed by external radiotherapy with a linear
accelerator. Implantation of yttrium or proton beam
therapy are alternative forms of irradiation. Following
adenomectomy, dexamethasone (0.5 mg) is given till
plasma cortisol level is > 180 nmol/L. If no tumour is
detected in the pituitary dependent Cushing’s disease,
hypophysectomy is indicated. If the diagnosis is not
clear, bilateral adrenalectomy with pituitary irradiation
is considered to prevent Nelson’s syndrome, i.e.
pigmentation of skin and enlargement of the adenoma
following bilateral adrenalectomy alone for Cushing’s
disease of pituitary origin. Steroid synthesis inhibitors
(metyrapone, aminoglutethimide) may be given.
Ectopic ACTH secretion syndrome needs somatostatin
analogues besides above mentioned measures.
If it is a chromophobe adenoma, hypopituitarism
develops (i.e. depressed sexual function, moderate
obesity and hypoglycaemia) and pressure symptoms
appear subsequently. All the hormonal deficiencies must
be replaced appropriately like sex hormones. Cortisol
replacement will always precede thyroxine therapy, since
the latter facilitates degradation of cortisol, leading to a
possible adernal crises.
If pressure symptoms develop, surgery must be
undertaken.
c. Empty sella syndrome: Treatment is ressurance and
symptomatic. Hypertension, if present, may be treated
accordingly. CSF rhinorrhoea may require surgical
correction. Radiation or pituitary surgery is
contraindicated.
d. Internal (obstructive) Hydrocephalus: (with 3rd ventricle
involvement): When the obstructive tumour cannot be
treated effectively by radiotherapy or surgery, shunting
operation (Insertion of a valve into one lateral ventricle
with drainge into the atrium via juglur vein) may be
beneficial.
e. Encephalitis: The hypothalamic involvement in epidemic
encephalitis lethargic a (Type A) resulting in obesity and
genital atrophy is rare and treatment symptomatic.
Thyroid (Hypothyroidism) (Refer to Chapter ‘Goitre’).
Parathyroid (Pseudohypoparathyroidism) The treatment
of pseudohypoparathyroidism is similar to hypopara-
thyroidism. In the acute stage IV calcium is necessary.
Replacement therapy in the long run is provided by 1-α
hydroxy cholecalciferol (alfa calcidol) 0.5-5 mcg/d or 1,
25 dihydroxy cholecalciferol (calcitriol) whose dosage is 1
to 3 mcg/d. Calcium levels must be monitored.
Adrenal cortex (Cushing’s syndrome) Adenomas of the
adernal cortex must be surgically removed and subsequently
0.5 mg dexamethasone given. Carcinomas are also to be
removed surgically besides irradiation and administering
adernocortical inhibitor mitotane (op DDD). an isomer of DDT
(6-10 g/d). Excess of cortisol can be reduced by metyrapone
(250 mg t ds) or aminoglutethimide (250 mg tds).
Pancreas (Insulinoma) The treatment consists of surgical
removal of insulinoma. If the tumour cannot be located,
subtotal (85%) pancreatectomy is indicated or else medical
treatment may be instituted. Diazoxide (0.3 g to 1.2 g/d) is
given intravenously or orally. However, serious
hypoglycaemia requires intravenous glucose (25 to 50 g)
as a bolus. Thiazides may be considered.
Gonads
a. Menopause: Vasomotor symptoms may respond to
clonidine (50 mcg bd) or synthetic steroid – Tibolone
(2.5 mg/d) conventional hormonal replacement therapy
may be necessary in some cases, i.e. cyclical ethiny1
oestradiol (0.01 to 0.02 mg/d) for 21 days in the month
with medroxy-progesterone acetate (5 mg/d) for the
remaining 10 days. Nevertheless, close clinical
monitoring is done for any endometrial cancer or venous
thromboembolism or hypertension.
b. Pregnancy: The treatment is purely symptomatic,
Restriction of excessice salt intake may be beneficial
for the gain in weight due to sodium and water retention
consequent to ovarian, placental and adrenal steroid
hormones. Avoid recurrent pregnancies which can
perpetuate obesity.
 Obesity
c. Polycystic ovaries (Stein-Leventhal syndrome): Therapy
must be individualised depending on the presenting
complaint. Reduction of weight by diet and exercise is
advised as this itself may restore the cycle or make the
treatment effective, for obesity. Clomiphene citrate (50
mg daily orally) when given for 5 days every month
may induce ovulation, correct menstrual abnormality
and facilitate pregnancy. Alternatively antiandrogen
(cyproterone acetate - 50 mg bd on days 1 to 10) when
given along with ethinyl oestradiol (30 mcg daily during
the first 3 weeks of the month) may improve hirsutism
and restore regular menstruation in about 75% of cases.
If these methods fail ovarian androgen secretion can be
decreased by wedge resection of 1/3-1/2 of each ovary
or laparoscopic ovarian diathermy.
If the woman does not desire pregnancy and is hirsute,
oestrogen cum progestogen oral contraceptives are given
to suppress the ovarian and possible adrenal androgen
production.
Epilation may be done if needed. When LH secretion is
more, tamoxifen (20 mg a day on day 2 to 6 of the cycle)
is preferred to clomiphene, since the oestrogenic factor
of the latter may further increase the release of LH
production.
337
Congenital Disorders
The genetic diseases associated with obesity namely
Alstrom’s syndrome, Biemond’s syndrome, Carpenter’s
syndrome, Weiss syndrome, Laurence-Moon-Biedl’s
syndrome and Prader-Willi syndrome are clinically evident
and the treatment is symptomatic.
Disorders of Adipose Tissue
Multiple lipomata: The only treatment is surgical removal
of the lipomas for cosmetic or other reasons.
Dercum’s disease: The treatment is symptomatic.
Partial lipodystrophy: The treatment is symptomatic.
Drugs
Prompt withdrawal of the drugs or replacement is
considered.
Although overall treatment may result in weight
reduction, maintaining the reduced weight poses a major
problem. A strict vigil and watch, on a long-term basis is
imperative, (regarding the disciplined dietary regimen,
increased physical activity, behavioural pattern) and
impressing the hazards of obesity, may contribute to the
successful maintenance of reduced weight.
338 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Oedema
22
Oedema is defined as an increase in the interstitial fluid of
the extracellular compartment presenting as either collection
of fluid into the skin and subcutaneous tissue of the legs
symmetrically (peripheral oedema) or throughout the body
symmetrically with or without collection of fluid into the
serious cavities (dropsy or anasarca), or at times strikingly
confined to the face especially periorbital or just lower
eyelids. Six litres of fluid should be accummulated in
interstitial space before finger pressure leaves behind pitting
impressions as against nonpitting varieties of oedema.
Swelling of the legs may also be due to hydrophilic
mucoprotein ground substance in the dermis (mucinous
oedema) or subcutaneous fat or lymph oedema with
secondary fibrosis of the skin and subcutaneous tissues.
PATHOGENESIS
Normally water constitutes about 60% of the total body
weight and it is distributed mainly into two major
compartments—intracellular. For example, a person
weighing about 65 kilograms may contain 40 litres of water.
The intracellular fluid forms 70% of the 40 litres (28 litres)
whose volume is not readily altered and the majority of it is
contained in the muscles. The extracellular fluid representing
30% of the total body water (12litres) is further subdivided
into interstitial fluid (including lymph) (9-10 litres) and blood
plasma (2-3 litres).
It is the interstitial fluid that is adjustable and it is
determined by the intake of water and elctrolytes (like
sodium) as well as the loss through the lungs, kidneys and
skin. The antidiuretic hormone of the pituitary, the
aldosterone of the adernal gland, natriuretic hormone
(peptides from cardiac atria) and glomerular filtration rate
act as regulators. There is a free interchange of fluid between
three compartments continuously—intracellular, interstitial
(intercellular) and intravascular; and 75% of the water of
the blood passes through capillary walls, every minute.
The distribution of water between the interstitial and
intravascular compartments at the capillary levels, depends
upon certain factors like (Fig. 22.1)
1. Hydrostatic pressure of the capillaries
2. Hydrostatic pressure of the interstitial fluid
3. Colloid osmotic pressure of the plasma
4. Colloid osmotic pressure of the interstitial fluid
5. Permeability of the capillary wall
6. Effective lymphatic drainge
7. Free venous circulation
The hydrostatic pressure at the arterial end of the
capillary ( which is more than the hydrostatic pressure within
the interstitial fluid tissue pressure, i. e. -2 to -3 mm hg)
tends to cause transudation of fluid out of capillaries while
the colloid osmotic pressure of the plasma tends to draw
the fluid back into the capillaries.
a. Thus (a) low colloid osmotic pressure (hypoproteinaemic
states) or (b) high hydrostatic pressure at the venous
end of the capillary (increased venous pressure
congestive heart failure) results in increase in the
interstitial fluid presenting as oedema. (c) The
permeability of the capillary vessels depends upon the
integrity of the capillary endothelium. Oedema may result
due to loss of vascular integrity and consequent increased
permeability of the small vessels like in allergy or cellulitis.
(d) Any block in the lymph vessels, which generally
have a large collateral circulation, must be extensive for
the oedema to occur.Reduced lymph flow leads to
increase in tissue pressure and interstitial protein
concentration as in filarial lymphangitis or secondary
deposits in the lymph nodes (e) Venous obstruction as
in deep venous thrombosis may result in oedema due to
impediment of venous circulation and increase in the
hydrostatic pressure at the venous end of the capillaries.
Oedema usually manifests when the extra cellular (interstitial)
fluid is increased by 10% or more.
 340 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 22.1: Diagram of pathophysiology of oedema

CAUSES OF OEDEMA Contd...

Oedema can classified as generalised and localised. It may B. Localised oedema may be due to
be pathological or physiological (Table 22.1). 1. Increased venous pressure
i. Venous thrombosis or pressure from outside
Table 22.1: Aetiological classification of oedema ii Obstruction to inferior vena cava
iii. Varicose veins
I. Pathological oedema 2. Increased capillary permeability
A. Generalised i. Infections
1. Cardiac: Congestive heart failure ii Allergy
2. Renal ii. Injury
i. Nephrotic syndrome iv. Exposure to extremes of temperature (heat or cold)
ii Acute glomerulonephritis v. Orthostatic sodium retention
3. Hepatic: Cirrhosis 3. Restricted lymphatic flow
4. Nutritional a. Obstruction
i. Hypoproteinaemic states i. Filariasis
a. Protein malnutrition ii. Malignany
b. Protein losing gastroenteropathy b. Inherited lymphatic deficiency: Milroys oedema
ii. Beriberi 4. CNS disorders (Neuropathic oedma)
iii Epidemic dropsy
5. Severe anaemia (chronic) II. Physiological Oedema
6. Endocrinal and metabolic
1. Posture (immobility in the sitting position with interference in the
i. Myxoedema
venous circulation)
ii. Pretibial Myxoedema
2. Pregnancy
iii. Premenstrual tension
3. Hot climate
iv. Gross (severe) obesity
v. Water excess
7. Drugs: Nifedipine, Amlodipine Steroids, insulin, NSAIDs,
Thiazolidinediones
Pathological Oedema
8. Immunological Generalised
i. Angioneurotic oedema
ii. Dermatomyositis Cardiac oedema
9. Idiopathic cyclic oedema Cardiac congestive heart failure This is usually diagnosed
when there is tachycardia, prominent jugulars, tender
Contd... hepatomegaly, besides oedema, i.e. congestion in the
 Oedema
peripheral circulation and congestion confining to the lungs
simultaneously. The usual causes are hypertension,
ischaemic heart disease, valvular disease (aortic or mitral),
congenial heart disease and emphysema (refer to
Chapter’Dyspnoea’).
• Pathogenesis of cardiac oedema
– Increased central venous pressure The central venous
pressure is increased to 25 cm of water from normal
pressure of 4 to 8 cm with a corresponding rise in
the hydrostatic pressure in the capillaries, exceeding
that of colloid osmotic pressure of the blood. As a
result, there is transudation of fluid into the tissue
spaces with consequent increase in the interstitial
volume and oedema formation.
– Retention of salt and water The cardiac output is
decreased as a result of which the renal blood flow
is reduced. Renin angiotensin system and
symphathetic nervous system are activated in turn
(i.e. interaction of renin angiotensinogen produces
intrarenal formation of angiotensin II in the former
and catecholamines in the latter) resulting in
vasoconstriction. The altered intrarenal
haemodynamics along with this vasoconstriction
increases the tubular reabsorption of the glomerular
filterate leading to retention of salt and water. The
angiotensin II also stimulates the aldosterone
production which in turn contributes to accumulation
of fluid apart from vasoconstriction. In other words,
the oedema is essentially due to two factors (i)
increased venous pressure and (ii) decreased cardiac
output with decreased effective blood volume, which
activates the renin-angiotensin-aldosterone system
as well as sympathetic nervous system; increases
the secretion of antidiuretic hormone, and reduces,
the secretion of natriuretic hormone, leading to the
retention of sodium and water.
Renal Oedema (Nephrotic syndrome and acute
glomerulonephritis) Acute glomerulonephritis or nephrotic
syndrome presents as universal symmetrical oedema. It is
marked in the legs in ambulatory subjects and in the
lumbosacral region when the patient is recumbent, with a
characteristic puffy face. The diagnosis entirely depends
upon careful chemical and microscopic examination of the
urine which shows marked albuminuria and deposits like
RBCs and cellular casts in the former, and hyaline casts in
the latter.
The cause of the acute glomerulonephritis usually
follows three weeks after the infection with group A
341
haemolytic streptococci of type 12 due to antigen and
antibody reaction.
The causes of nephrotic syndrome are multiple like
a. Membranous glomerulonephritis
b. Diabetes mellitus
c. Lupus erythematosis
d. Renal venous thrombosus
e. Amyloidosis
f. Chemical toxicity
The mechanism of oedema is predominantly due to
decreased colloid osmotic pressure which results from
massive albuminuria. Normally the hydrostatic pressure
makes the fluid escape from the capillary which is prevented
by the colloid pressure of the plasma proteins which draws
fluids from the intercellular tissue into the capillaries. The
reduction of colloid osmotic pressure facilitates the counter
balanced hydrostatic capillary pressure to make the fluid
escape from the capillaries into the tissues. This deficit in
effective plasma volume leads to the retention of sodium
and water (vide supra). Generally speaking, the renal
oedema may be nephrotic or nephritic. The pathogenesis of
the nephrotic oedema is essentially due to reduction in the
osmotic pressure as well as effective blood volume whereas
in the nephritic oedema it is due to increased capillary
permeability in addition to the above discussed factors.
Hepatic edema
Hepatic: Cirrhosis of the liver presents itself with features
of portal hypertension due to altered hepatic Vasculature
(abdominal wall veins distension, ascites, splenomegaly) and
inadequate hepatic cellular function (neurocirculatory
changes and jaundice).
There are several varieties of cirrhosis of which portal
cirrhosis is the most common, caused by viral hepatitis,
alcoholism and/or nutritional deficiency. The others being
biliary cirrhosis or cardiac cirrhosis. The mechanism of
oedema in these causes is essentially due to
i. decreased albumin synthesis by liver with consequent
low plasma osmotic pressure; and
ii. increased portal venous pressure due to obstruction
of intrahepatic circulation and lymphatic drainage.
This tends to deplete the effective body fluids with
consequent diminished renal blood flow and formation of
aldosterone and antidiuretic hormones leading to retention
of sodium and water (vide supra). Also increased capillary
permeability due to anoxaemia may contribute. The fluid
retention may be confined to the peritoneal cavity (behind
the congested portal venous system and obstructed
lymphatics) as well as the legs.
 342 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Nutritional edema
• Hypoproteinaemic states The nutritional deficiencies
due to inadequate diet for long periods or
malabsorptions and protein losing enteropathy or
hypoalbuminaemia in cirrhosis or nephrotic
syndrome may result in hypoproteinaemic states and
consequent oedema. When the serum albumin falls
below 2.5% g, colloid osmotic pressure also falls
correspondingly, with expansion of intercellular fluid
space due to transudation of salt and water out of
capillaries with clinically evident oedema.
• Beriberi: Beriberi of the wet variety is associated
with swollen legs due to vitamin B1 deficiency. This
vitamin B1 acts as a coenzyme in carbohydrate
metabolism of the heart muscle as well as nerve cell
and facilitates the oxidation breakdown of the pyruvic
acid and lactic acids. In the absence of B1 this lactic
acid accumulates due to defective oxidation, leading
to intracellular oedema and water retention (hydropic
degeneration of Wenckebach) with consequent loss
of full contractility of the heart muscle. In other
words, the oedema is due to indirect involvement of
the heart muscle with or without associated protein
malnutrition (Hence, the term cardiac beriberi was
in vogue) Raised pyruvic and lactic acid levels in the
blood are absolutely confirmatory. Nevertheless, this
entity is becoming uncommon in recent times.
• Epidemic dropsy Epidemic dropsy is argemone oil
poisoning, which is a contaminant of mustard oil
used for dietary purpose, since argemone mexican
seeds are found to be mixed up with the stocks of
mustard seeds. The toxic principle of argemone oil
is sanguinerine which causes capillary dilatation. This
is diagnosed by the presence of swollen legs with
aching of muscles at bones and joints. Fever may be
present and skin may show patchy pigmentation and
nodular eruptions and cardiomegaly may occur later.
It is diagnosed from the careful history of
consumption of mustard oil.
Severe Anaemia (Chronic) Anaemia per se usually does
not present as swollen legs although it does occur due to
increased venous pressure coupled with tissue anoxia and
capillary permeability in severe chronic anaemia.
Nevertheless if the hypoproteinaemia is associated as
usually happens, this may be contributory (vide Chapter
‘Fatigue’).
Endocrinal and Metabolic
• Myxoedema: The word myxoedema means mucus
and swelling since material accumulated in the skin
is a mucopolysaccharide staining like mucus and
gives an impression of oedema. This swelling of the
legs usually does not pit on pressure although it
occurs in some cases. The diagnosis is obvious
clinically by the chracteristic facies like puffy eyelids,
thick lips, dry and coarse skin,hoarse voice, thining
of the eyebrows at the ends, unexplained weakness
and increase in weight. It is confirmed by biochemical
investigations like low thyroxine values (low T4) and
high TSH values and less concentration of radioactive
iodine. The common spontaneous primary atrophic
hypothyroidism may be due to destruction of thyroid
tissue by autoimmune mechanism or iatrogenetic or
genetic inhibition of thyroid hormone biosynthesis
(autosomal recessive due to peroxidase deficiency
usually). (Refer to Chapter ‘Goitre’)
• Pretibial myxoedema: Oedematous swelling above
lateral malleoli or legs and/or feet in past or present
thyrotoxicosis.The skin is raised, thickend and
pigmented. This dermopathy can be diagnosed by
increased T4 levels and the increased activity of the
gland as seen with increased radioactive iodine uptake.
Premenstrual tension There may be recurrent
periodic weight gain due to fluid retention before the
onset of menstruation in the 3rd and 4th decades of
life. There may be mastalgia, anxiety or feeling of
inadequacies, besides oedema which may be due to
increased antidiuretic hormone.
• Water excess/intoxication: The volume of the body
water particularly in the extracellular compartment,
if in excess, caused by more intake than the capacity
for excretion or increased sodium intake or
reabsorption of sodium due to heart failure or liver
disease results in expansion of the volume of the
body fluid and decreased concentration (dilution) of
plasma electrolytes like sodium. (Normally ADH
secretion is inhibited so as to enable the kidneys to
excrete the excess water). Overt odema is apparent
only if 3-4 litres of fluid accumulates. If water excess
develops acutely or severe, water intoxication results
characterised by headache, nausea, vomiting,
weakness, abdominal cramps, coma and
convulsions.
Gross obesity Refer to Chapter ‘Obesity’.
Severe Drugs Apart from drugs causing angioneurotic
oedema, they may produce swollen legs as with nifedipine
or amlodipine due to peripheral vasodilatation or with steroids
due to fluid retention clonazepam produces facial oedema
sometimes.
 Oedema
Immunological
Angioneurotic oedema It is an immediate type of
hypersensitivity and characterised by oedema of the dermis
as well as the subcutaneous tissues. It is usually I gE
dependent and associated with seasonal respiratory allergy,
secondary to inhalation of pollens or animal dander or
ingestion of shellfish or vegetables or drugs or sometimes it
may be due to hereditary deficiency of complement
associated with absence of C1 inhibitor (C1INH).
The diagnosis is based on the occurrence of angioedema
suddenly with self-limited tendency. It is confirmed by
testing specific allergens for a wheal or a flare and passive
transfer of this reaction with the serum of the affected person
to a normal individual. The mechanism of oedema is due to
increased capillary permeability
Dermatomyositis: Periorbital and perioral oedema may be
the presenting feature of this entity strikingly although the
painless weakness of the proximal muscles of the limbs or
neck muscles and skin changes like erythema or dermatitis
may also be contributory, The diagnosis can be confirmed
only by muscle biopsy or raised creatinine phosphokinase
(CPK) and aldolase of the serum (Fig. 22.2).
Fig. 22.2: Periorbital oedema due to dermatomyositis.
Idiopathic cyclic oedema This periodic oedema is usually
seen in women who experience appreciable diurnal weight
changes more towards the evenings. It may be related to
menstrual cycles and appears to be due to increase in the
capillary permeability. Emotional background, autonomic
343
dysfunction and high concentrations of cyclic adenosine
monophosphate in the plasma are contributory. It is often
accompained by obesity, diabetes mellitus, diuretic abuse
(a puzling feature of development of oedema while on
diuretics or soon after stopping them, probably due to
exaggerated stimulation of renal mechanisms for conserving
sodium and water.)
Localised Oedema
Increased Venous Pressure
– Venous thrombosis: In localised oedema one or other
extremity will be swollen primarily due to venous or
lymphatic obstruction or both. In venous obstruction,
the venous pressure is raised with corresponding
increase in the hydrostatic pressure of the capillaries
and consequently more fluid escapes from the
vascular to the interstitial compartment. localised
cyanosis may be present due to stagnation of blood
flow, in addition to localised oedema in venous
obstruction.
In venous thrombosis, there may be mild fever with
pain in the calf region. The leg may be swollen and on
examination distended veins and warmth present. Apart from
simple clotting that may occur in phlebothrombosis, the
veins may be occluded by pressure from outside due to
neoplasms or secondary deposits in the lymph nodes,
Pregnancy or recumbency. (Refer to Chapter ‘Pyrexiua of
Unknown Origin and Pain in the Extremities’)
Obstruction to inferior vena cava is diagnosed by the
presence of not only oedema of both legs but also prominent
dilated tortuous abdominal wall veins with direction of blood
flow from below upwards throughout, i.e. below the
umbilicus and above the umbilicus as well. Thrombophlebitis
of the femoral vein during puerperium leads to painful white
leg (Phlegmasia albadolens).
Varicose veins Normally blood flows from superficial veins
of the leg into the deep veins through perforating veins.
The valvular competence prevents blood flowing from deep
veins to superficial veins. The sequential incompetence of
the valves causes dilation of superficial veins (varicosities)
Though the term ‘varicose’ means dilated, the varicose veins
are not only dilated but also tortuous and elongated. Besides
these dilated superficial veins in the lower extremities, dull-
aching discomfort and swelling may be present.
Varicose veins may be primary with normal deep veins
or secondary due to the deep venous insufficiency. Pitting
oedema of the lower leg with pigmentation and ulceration is
suggestive of secondary varicose veins. The Trendelenburg’s
test can be performed to determine the competence of the
 344 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
valves at the saphenofemoral junction (elevate the leg till
the blood is completely emptied from superficial veins; place
2 fingers over the saphenofemoral junction 5 cm below and
medial to the femoral pulse; make the patient to stand from
the supine position keeping the fingers intact; if the veins
begin to fill, it is suggestive of incompetence of the deep or
communicating valves; then release the fingers; if the
varicosities fill quickly, it is suggestive of incompetence of
the saphenofemoral valve).
Predisposing factors of varicosities can be appreciated
by history of prolonged standing or consumption of oral
contraceptives or past history of deep venous thrombosis
occlusion by foetus or tumours.
Increased capillary permeability The capillary permeability
may be increased due to infections or allergies or injuries.
The local tenderness and raised temporary redness is
suggestive of inflammation. Swelling may be not only due
to inflammatory oedema but also at times due to lymphatic
oedema as often happens in cellulitis. More albumin escapes
in the tissue spaces increasing the osmotic pressure of tissue
fluid. (Normally little albumin escapes and reenters via
lymphatics). The oedematous fluid contains high protein
content of 3 to 4 g percent.
After an injury pseudoatrophy may result wherein oedema
of the limb may be associated with atrophy of the skin and
underlying bone changes. (Sudek’s atrophy).
Some patients may complain of oedema in summer
months due to increased capillary permeability. Heat oedema
may occur after initial exposure to hot climate in a few, as
a physiological adaptation with aldosterone mediated salt
and water retention, which may disappear on continued
heat exposure.
Exposure to cold may result in bright pink or bluish
swollen nonpitting areas of the skin associated with itching
(chilblains). This is due to local areas of vasoconstriction
and vasodilatation beyond, with consequent static dilatation
of the venules (secondary to anoxaemia caused by arteriolar
vascular spasm) leading to oedema. In orthostatic sodium
retention, there seems to be an abnormal capillary leak of
protein which is marked in upright position. So oedema is
present in the evening and absent in the morning hours.
Restricted lymphatic flow (Non-Pitting oedema) Since the
lymphatics facilitate proper drainage, any lymphatic
obstruction will only result in excess of interstitial fluid in
the limb. Repeated lymphatic obstruction leads to thickening
of the skin and pitting factor disappears as in filariasis or
malignancy. The lymph oedema fluid may contain high
protein content of 4 g percent.
Rarely a hereditary disease known as Milroy’s disease
may present as oedema of one or both legs, usually in
women, due to congenital anomalies of the draining
lymphatics. This may be seen at birth or at puberty or later
in life. Other members of the family may also be affected.
the striking feature of lymph oedema is painless swelling of
the affected limb usually starting over the dorsum of the
foot and ankle, progressing upwards. Initially the texture of
the skin is normal with tendency for pitting less readily,
which later disappears as the skin becomes thickened.
However, the characteristic feature of Milroy’s disease is
distinct demarcation between the swollen and nonswollen
portions, at the level of a particular joint (ankle or knee).
CNS disorders Oedema may be seen in paralysed limbs due
to decreasd lymphatic and venous drainage on the affected
side. In some neurological disorders, oedema may be present
due to the involvement of vasomotor fibres. Cauda equina
lesion may produce cold cyanosed lower limbs with
dependent oedema. Neuropathic oedema occurs in DM.
Physiological Oedema
Prolonged dependency of the lower extremities, as happens
while travelling sitting upright for longer distances, may
cause swollen legsa due to increased pressure and gravitation.
Oedema of the legs occurs in 25% of noncardiac pregnant
women due to compression of the iliac veins by the growing
foetus and increased secretions of aldosterone with
consequent retention of sodium and water. This physiological
basis of oedema in pregnancy has to be carefully delineated
from possible underlying pathological mechanisms like
toxaemia of pregnancy.
CLINICAL APPROACH
Certain data is important in arriving at the exact cause of
oedema, which has to be processed by interrogation and
investigations.
History
a. Age and sex—Renal causes of oedema are more
common in children whereas oedema in females may
be due to pregnancy or puerperium or premenstrual
tension or varicose veins.
b. Family history—If other members of the family are
affected, it may be nutritional in origin or hereditary.
C. Posture—Is it related to posture?
i. Long distance travelling in upright position
 Oedema
ii After prolonged recumbency (resuming upright
position for the first time after prolonged
recumbency, may present as oedema for the first
few days)
d. Dietary history
e. History of alcoholism and drugs
f. History of bleeding of long duration
g. Any history of recurrent sore throats or history of fevers
with rigors
h. History of chronic diarrhoea
i. Any oliguria, or smoky urine, or pruritus
j. Any dyspnoea on exertion or orthopnoea or cough
k. Any anorexia and haematemesis
l. Any exposure to extremes of climate
m. Onset
i. Is it sudden onset, e.g. acute nephritis?
ii Is it intermittent (angioneurotic oedema related to
certain types of foods; or idiopathic cyclic oedema
related to menstruation)?
iii. Is it after prolonged standing (chronic venous
insufficiency)?
Physical Examination
General Examination
Appearance
a. Nature of oedema
i. Is the oedema generalised or localised?
ii Is the oedema symmetrical or asymmetrical?
iii Is it asymmetrical to begin with and later assumes
symmetrical presentation?
iv. Is the oedema pitting or nonpitting?
v. Any warmth over the oedematous areas?
b. Distribution of oedema-The striking features are?
i. Swollen legs in cardiac oedema?
ii Puffiness of face and then swollen legs in renal
disorders
iii Swollen legs following distension of abdomen in
hepatic oedema
In bedridden patients, the oedema is elicited by swelling
in the secral region whith pits readily.
c. Pallor
d. Facies-Sunken eyes and cheeks with prominent malar
bones; or a sallow and bloated face with congested
watering eyes and trembling lips are (some of the
characteristic features of cirrhosis)
e. Presence of wheals or urticaria
Oral cavity: Sore tongue, cracked lips or other evidence
of malnutrition
345
Neck: For any thyroid enlargement or lymphadenopathy
Skin:
a. Is the skin coarse and thick?
i. Generalised—Myxoedema
ii Localised—Filariasis
b. Is the skin atrophied with oedema—Sudek’s atrophy?
c. Any urticaria or other evidence of allergy
Veins:
a. Any varicose veins in the legs
b. Any tenderness of the calf muscles and positive Homan’s
sign-venous thrombosis
Joints: Any swollen tender joints with limited movements
Look for any jaundice, vascular spiders, gynaecomastia,
testicular atrophy
Systemic Examination
• Cardiovascular examination: For evidence of distended
neck veins, cardiomegaly with valvular heart disease
hypertensive heart disease leading to congestive heart
failure or pericardial involvement.
• Respiratory system: For evidence of chronic bronchitis
and emphysema leading to chronic cor pulmonale or
fluid in the pleural cavity.
• Abdominal examination: Any evidence of distended
abdominal veins and free fluid or splenomegaly offers a
clue to the presence of cirrhosis. Determine the direction
of flow of blood in the distended veins of the abdominal
wall to indicate the site of obstruction-whether away
from the umbilicus (portal), below upwards throughout
(inferior vena cava), above downwards throughout i.e.
above and below the umbilicus (superior vena cava). If
only free fluid is there with tender enlarged liver and
hepatojugular reflux, it is of cardiac origin. If there is
only free fluid, it may be renal or hypoproteinaemia.
Rectal examination for prostate enlargement and pelvic
examination.
• CNS examination: Any evidence of paralysis of the limbs
or other neurological disorders.
Investigations
1. Routine urine examination for physical, chemical
(albumin), microscopic (cells and casts) and also 24 h
proteinuria.
2. Blood
a. RBC haemoglobin, TC, DC, ESR
b. MCV, MCHC
3. Biochemical
a. Blood urea
 346 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Serum creatinine—Raised in renal disorders
c. Albumin globulin ratio—Altered in cirrhosis of liver
d. Gamma Glutamyl Transferase—raised in alcoholic liver
e. T4 levels decreased and TSH levels increased in
myxoedema
f. Protein estimation of the pleural/peritoneal fluid. Low
in a transudate and high in an exudate.
g. Serum albumin—Ascites albumin gradient is >
1.1 gm/dl in cirrhosis of liver as against tuberculous
peritonitis in which it is < 1.1 gm/dl.
4. Radiology
a. X-ray of chest—PA view for cardiac silhoutte and
evidence of pleural effusions
b. Barium swallow studies—For oesophageal varices
c. Intravenous pyelogram—To asses the kidney outlines
and urinary tract
d. X-ray of the underlying bone, if there is localised
infection
5. Ultrasound examination of the abdomen
6. ECG
7. Circulation time if indicated
8. Echocardiography (useful for confirming diagnosis or
cause of CHF)
9. Special investigations (if necessary)
a. LE cell
b. Serum enzymes
i. Serum creatine phosphokinase
ii Serum aldolase
iii LDH
c. Serum electrolytes
d. Protein estimation of the subcutaneous fluid
e. Serum complement
f. Oesophagoscopy
g. Biopsy of the liver, kidney or muscle
h. Venogram
i. Lymphangiogram
TREATMENT OF OEDEMA
The accumulation of excess fluid in the interstitial space
caused by various mechanisms (vide supra) needs
therapeutic designs to mobilise the interstitial fluid, so as to
maintain a constant extracellular fluid vulume. The
therapeutic approach varies according to whether oedema
is generalised due to transudation of salt and water or
localised due to increased permeability of small blood vessels
or venous/lymphatic obstruction. This can be accomplished
by both symptomatic and specific modes of treatment for
the underlying systemic disease.
Symptomatic Relief
1. Restriction of dietary sodium (200 mg or less i.e. 0.5 g
of salt or less) to facilitate reduction of water content
and draw the interstitial fluid intravascularly.
2. Various diuretics facilitate urinary excretion of sodium
and water (consequent to diminished reabsorption of
salt and water from the renal tubules). The choice of
diuretics depends upon severity of oedema. High
potency diuretics (loop diuretics) may be required in
severe cases.
The commonly used diuretics are
a. Loop diuretics (acting at the loop and ascending limb of
Henle)
i. Frusemide (40-80 mg)
ii Bumetanide (0.5-4 mg)
iii Ethacrynic acid (50-100 mg)
iv Torasemide (2-20 mg)
v Metolazone (2.5-5 mg)
b. Distal potassium losing diuretics (thiazides acting at distal
convoluted tubule)
i. Benzthiazide (25-100 mg)
ii Chlorothiazide (500-1000 mg)
iii Hydrochlorothiazide (50-100 mg)
iv Chlorthalidone (50 mg)
c. Distal potassium sparing diuretics (acting at distal
convoluted tubule and collecting duct system)
i Spironolactone (50-100 mg)
ii Triamterene (50-100 mg)
iii Amiloride (5-10 mg)
d. Osmotic diuretics like mannitol (acting at the
glomerulus) and carbonic anhydrase inhibitor (acting at
the proximal tubule) are not used in peripheral oedema.
Complications of electrolyte depletion, especially
potassium, may follow diuretic therapy, giving rise to
increased sensitivity to digoxin or hepatic encephalopathy.
3. Elevation of the unilateral oedematous limb and/or
application of elastic crepe bandage from distal end of
metatarsals up to the knee may be helpful in venous/
lymphatic oedema, as it facilitates the absorption of
interstitial fluid by gravity and constant pressure.
Specific Treatment for Specific Diseases
Generalised Oedema
• Cardiac Congestive Heart Failure
1. General measures: Insist on bed rest, small frequent
meals with less salt, satisfactory daily bowel movement,
and movements of the lower limbs.
 Oedema
2. Pharmacotherapy:
a. Digoxin 0.25 mg twice or thrice a day is given after
a loading dose of 1 mg orally, if necessary. (The
loading dose is indicated only in the absence of
previous digitalisation). The dosage is regulated by
the pulse/heart rate. The maintenance dose of 0.125–
0.25 mg is preferably given for five days in a week.
since digitalis toxicity may be precipitated by
hypokalaemia, appropriate doses of potassium salts
are supplemented simultaneously. Recent trends are
to reserve digoxin administration for treatment of
severe heart failure with sinus rhythm only, when there
is no responce to diuretic cum ACE inhibitor therapy.
b. Diuretics—Frusemide is given orally and if necessary
parenterally. In severe heart failure, combination of
diuretics may be considered (vide supra).
c. Vasodilators—Venous dilators like nitrates, which
reduce preload (pulmonary congestion), arterial
dilators like hydralazine which reduce after load and
mixed (venous and arterial) dilators like captopril,
enalapril or lisinopril are particulary useful in the
treatment of moderate and severe heart failure (start
at lowest dosage to avoid possible hypotension).
d. Consider carvedilol in conjunction with a,b, and c.
e. Sympathomimetic amines—Inotropic agents like
dobutamine or dopamine can be used to augment
cardiac output. Amrinone is useful in severe
congestive heart failure refractory to conventional
treatment.
f. Anticoagulants are given to treat or prevent
thromboembolism.
g. Other drugs—Sedatives, antibiotics, antiarrhythmic
drugs are indicated as necessary.
3. Oxygen is administrated, if required.
4. Eliminate precipitating factors and possible underlying
remediable causes, rendering it refractory to treatment.
5. Treat the cause
6. Avoid NSAIDs
7. In refractory cases final option is heart transplantation.
Renal
• Nephrotic syndrome: In nephrotic syndrome,
corticosteroids relieve oedema. Albumin infusion is
indicated in severe cases. When oedema is mild or
moderate diuretics like frusemide with or without
spironolactone induce effective diuresis. Treat the
underlying cause of nephrotic syndrome like idiopathic,
systemic or offending drugs. (Refer Chapter Haematuria)
• Acute glomerulonephritis (Refer to Chapter ‘Haematuria’)
347
Hepatic Cirrhosis
1. General Measures: Nutritious diet with high calorie,
proteins and trace nutrients. Avoid hepatotoxic agents
like alcohol, chemicals and other medications.
(Methotrexate)
2 Symptomatic measures:
a. Sodium and water restriction.
b Spironolactone (100 to 200 mg a day) is the ideal
diuretic with or without frusemide. Prolonged
excessive administration of diuretics may give rise
to salt depletion. Features of sodium depletion appear
(though still oedematous), which in turn may lead to
uraemia (hepatorenal syndrome). Diuretics are
stopped if Na is < 128 mol/L and serum creatinine >
160 µ mol/L.
c. IV infusion of albumin and paracentesis (up to 3 L)
are beneficial if sodium restriction and diuretic
therapy fail.
d Le Veen shunt—Useful in patients who are not
terminally ill with ascites resistant to treatment.
e. Transjugular intrahepatic portosystemic shunt for
refractory ascites.
3. Complications
a. Variceal bleeding (Refer to Chapter ‘Haematemesis’)
b. Hepatic encephalopathy—Stop diuretics and restrict
proteins if precoma develops. (Refer to Chapter
‘Coma’)
c. Spontaneous bacterial peritonitis—Prophylaxis with
appropriate antibiotics advocated.
Treat Underlying Cause
a. Alcoholic liver disease (Refer to Chapter ‘Jaundice’)
b. Chronic hepatitis (Refer to Chapter ‘Jaundice’)
c. Primary biliary cirrhosis (Refer to Chapter ‘Jaundice’)
d. Wilson,s disease (Refer to Chapter ‘Jaundice’)
e. Haemochromatosis—(Repeated phlebotomies of 500 ml
each (250 mg iron) twice weekly or twice monthly till
the serum iron and ferrtin are normal.
Chelating agents like desferrioxamine given as s.c.
infusion over a period of 12-16 h (removes 10-20 mg
of iron per day) oral ascorbic acid given along with the
chelater enhances iron excretion.
Low iron diet, drinking tea and milk with meals
(inhibit iron absorption) and large doses of phosphate in
the diet (enhance faecal excretion of iron) are beneficial.
f. Schistosomiasis (Refer to Chapter ‘Weight Loss’)
g. Budd-Chiari syndrome (Refer to Chapter ‘Acute
abdominal pain’)
 348 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Nutritional
• Hypoproteinaemic States
a Protein malnutrition-It is treated with high calorie
and high protein diet (proteins up to 1.5/kg). The
diet is made up of protein rich foods (animal sources
or plant sources). Children with kwashiorkor may
be handfed with dried skimmed milk mixed with
sugar or flour and oil given 4 to 5 times a day.
Additional sources may be further supplemented by
groundnut cake and micronutrients. the cause of
hypoproteinaemia due to either defective intake/
absorption /assimilation may be identified and treated.
The albumin fraction of serum proteins should be >
3.5 g% (3.5 g% indicates mild malnutrition and 3
g% indicates severe malnutrition).
b. Protein losing enteropathy-Institution of appropriate
therapy for the underlying disorder may restore the
normal protein metabolism. (Refer to Chapter
‘Chronic Diarrhoea’)
• Beriberi The treatment is given early lest heart failure
should occur. Thiamine (50-100 mg) is given I.M. for
first few days followed by oral thiamine (10 mg tds).
The clinical response is invariably dramatic. Vitamin B
complex in generous doses may be simultaneously given.
Dietary sources of thiamine should be listed and
instituted.
• Epidemic dropsy Mustard oil contaminated with seeds
of poppy weed (argemone oil) must be identified and
avoided. (Argemone oil is identified when brown to
orange red colour develops on adding nitric acid to the
suspected sample). Capillary damage may be restored
by vitamins C, E and P.
• Nutritional deficiencies must be corrected. Supportive
therapy for cardiac failure, watery dirrhoea, glaucoma
and possible bleeding from haemangioma may be
instituted.
Severe Anaemia (Refer to Chapter ‘Fatigue’)
Endocrinal and Metabolic Myxoedema (Refer to Chapter
‘Goitre’) Adjust thyroxine, given as single dose, to keep
TSH <5mu/l and treatment is life long. Associated anaemia
or IHD treated appropriately.
• Pretibial myxoedema: (Refer to Chapter ‘Goitre’)
• Premenstrual tension: Oedema in premenstrual tension,
if necessary, is treated with diuretics or small doses of
progestin dominant oral contraceptives or vitamin B6.
• Gross obesity: In Lipoedema, diffusion of fluid from the
small vessels containing excessive fatty deposits occurs
into the surrounding tissue, which is amenable to weight
reduction measures. (Refer to Chapter ‘Obesity’)
• Water excess—Basic treatment is to restrict water intake
to ½ to 1 litre. Frusemide may be considered. Saline
solution administered if a real sodium deficitency exists.
In water intoxication, hypertonic saline is employed.
Drugs
Withdraw the offenting drug.
Immunological
• Angioneurotic oedema: When once angio-oedema
develops, antistamines may not be that effective.
However, prolonged administration of antihistamines is
beneficial if the attacks are recurrent.
Stanozolol (2.5 to 5 mg daily) or danazol (200-800
mg) daily may reverse the biochemical deficiency of
the inhibitor of the activated first component of the
complement system, in hereditary angio-oedema.
Possible airway obstruction is treated with adrenaline
(0.5 ml 1 in 1000 IM) and chlorpheniramine (10 mg)
and hydrocortisone (100 mg IM). Serum containing C1
inhibitor (IV) may be required for laryngeal oedema
associated with hereditary angio-oedema (refer to
Chapter ‘Pruritis’).
• Dermatomyositis (Refer to Chapter ‘Paraplegia’)
Idiopathic Cyclic Oedema
• Salt less diet, prolonged rest in the supine position, elastic
stockings, adjusting emotional situations are the useful
simple measures. Diuretics are effective only initially.
ACE inhibitors, bromocriptine, progesterone may be
considered.
Localised Oedema
Increased Venous Pressure/Venous Insufficiency
• Venous thrombosis: The aim of treatment is to prevent
damage to the valves of the veins, dissemination of
thrombus and pulmonary embolism (Refer to Chapter
‘Pain in the Extremities’).
• Inferior Vena Cava obstruction: Symptomatic treatment
with diuretics may be beneficial. The underlying causes
of a possible malignancy invading inferior vena cava
should be probed and appropriate chemotherapy and
radiotherapy may be insituted. In the absence of any
neoplasm, causes like polycythaemia and other
hypercoagulable states may be investigated and treated
accordingly.
Varicose Veins
a. Nonsurgical measures: When oedema is associated with
varicose veins, elastic support (with properly fitting
stockings or elastic crepe bandage, applied carefully from
metatarsals up to just below the knee), frequent periods
 Oedema
of elevation of the legs, encouraging walking and
avoiding prolonged standing are helpful to reduce the
hydrostatic pressure.
Varicose ulcers generally heal with topical
antibiotics, compression bandages and elevation of the
extremity. Some ulcers require skin grafting.
b. Compression sclerotherapy: Injection of 0.5 ml of
sclerosing solution (3% sodium tetradecyl sulphate) into
each varix followed by continuous pressure to that venous
segment with elastic bandages for 6 weeks facilitates
fibrosis between the two valves of the collapsed vein.
c. Surgical measures: surgical treatment consists of removal
of the varicose veins and incompetent perforating veins.
Trendelenburg’s test is done to determine whether the
valve at the saphenofemoral junction is competent. If the
varicosities fill (due to blood being forced through
incompetent deep venous valves) stripping the vein should
be done since ligation will not cure.
Illuminated powered phlebectomies is one of new
techniques for removal of varicose veins avoiding stripping
of the long saphenous vein. Laser therapy is yet another
option.
Increased Capillary permeability: A diffuse spreading
infection of the skin of the leg or deeper tissues due to
coccal infection is treated with appropriate antibiotics.
Allergic oedema associated with wheals and itching is
relieved by removal of offending agent and appropriate
antistamines and corticosteroids if necessary.
349
Post-traumatic vasomotor dystrophy requires vigorous
physical therapy. occasionally sympathectomy is considered
to overcome vasomotor symptoms.
Avoid extremes of temperature (heat or cold) so as to
maintain permeability.
Elastic support may be beneficial in orthostatic sodium
retention.
Restricted Lymphatic Flow
• Obstruction
a. Filariasis: In unilateral oedema due to chronic
lymphatic obstruction, elastic crepe bandage for
couple of months and diethyl carbamazine with or
without diuretics may be helpful. Ivermectin is a
recent option. Long acting penicillin given parenterally
(1.2 to 2.4 million units once in 2 or 3 weeks)
prevents recurrence of affection of lymphatic vessels
and consequent solid oedema (Refer to Chapter
‘Rashes’).
b. Malignancy: (Refer to Chapter ‘Weight Loss’)
Inherited lymphatic deficiency-Milroy’s oedema
Treatment is symptomatic. Surgical excision of
sheets of double fascia may be considered at times.
CNS Disorders Treatment is symptomatic. (elevation,
massage and compression bandage). Ephedrine (30-60 mg)
tds advocated for neuropathic oedema due to diabetes
mellitus.
350 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Oedema 351
 Chapter
Oliguria
23
Oliguria generally connotes less than 400 ml of urine output
in 24 h (Formation of normal urine is about 1 ml per min,
i.e. 1.5 litres in 24 h). With normal diet 500 ml is the minimum
amount of urine necessary to excrete the solutes like urea
and electrolytes to preserve the “milieu interieur”. If the
solutes to be excreted are increased (normal 600 mOsmol)
and the renal concentrating power is reduced (as occurs in
catabolic states or severe infections) a daily output of more
than 800 ml of urine is required to excrete the urinary
constituents. On the other hand, if the solutes to be excreted
are decreased as in a diet rich in carbohydrates and fats and
low in proteins and salt, even 250 ml of urine is enough for
the purpose. So oliguria, indeed, is inadequate urine
production (200-800 ml to facilitate excretion of adequate
amounts of solutes in order to maintain ‘milieu interieur’).
Anuria is suppression of urine formation with urine
output of less than 100 ml in 24 h. Oliguria, if continued,
leads to acute renal failure with an accumulation of nitrogen
wastes (urea and creatinine, and potassium).
RENAL FUNCTIONS
In health, the kidneys perform two functions predominantly.
• Excretory function
a. Excretion of nitrogenous and other waste materials
like urea, creatinine, uric acid, drugs and retention
of vital substances.
b. Water and electrolytes with maintenance of hydrogen
ion equilibrium.
• Secretory function
a. Renin-angiotensin system—Renin is an enzyme,
produced in the juxtaglomerular cells and control of
its release exists in the maculodensa. In the presence
of sodium depletion or a fall in the glomerular
filtration rate, excess amounts of renin are released.
Renin acts on a globulin precursor in the plasma
(hypertensionogen) to produce eventually angiotensin II,
which is an active vasoconstrictor agent and plays a role in
the homeostasis by increasing the aldosterone secretion.
b. Erythropoietin hormone which stimulates
erythropoiesis.
c. Prostaglandins of the renal medulla may play a part
in the regulation of blood pressure as they have some
hypotensive properties.
Urinary flow indeed is regulated by (1) rate of glomerular
filtration, (2) rate of tubular absorption or (3) both.
PATHOPHYSIOLOGY
Cortex forms 70% of the total renal mass, and medulla
30% (outer medulla 20% and inner medulla 10%). The
performance by the kidneys depends upon adequate renal
circulation. Normally, the kidney’s share is about 20 to 25%
of the cardiac output. 93% of this total renal blood flow
perfuses the cortex, 6% outer medulla and 1% inner medulla.
The hydrostatic pressure within the glomerular capillaries
facilitates the filtration of fluid into the Bowman’s capsule
from the plasma. If the cardiac output is reduced as in
hypotension of cardiac failure, correspondingly the renal
blood flow is also reduced with consequent reduction of
the glomerular filtration rate and oliguria sets in, i.e. oliguria
develops when renal blood flow and/ or glomerular filtration
rate (GFR) is reduced.
ACUTE RENAL FAILURE (ARF)
Subdivision
It is divided into prerenal, renal and postrenal. It occurs
when the kidneys are unable to
a. Excrete waste products
b. Maintain water and electrolyte homeostasis
It is invariably associated with either oliguria or anuria
in the initial stages which usually lasts for about 1 to
3 weeks, and may be of obstructive or nonobstructive origin.
 Oliguria 353

The latter may be associated with prerenal or renal failure
and the former with postrenal failure. Sometimes there may
be acute-on-chronic renal failure (Table 23.1).
Prerenal Failure
It is functional failure without structural damage and occurs
in clinical settings associated with hypotension, leading to
decreased renal blood flow. When the blood pressure is
normal, the outer cortex gets maximum renal flow and a
portion of it perfuses the inner or juxtamedullary part of the
cortex. When the blood pressure is decreased, the
circulation in outer cortex is markedly reduced. GFR is
decreased by selective cortical vasoconstriction (due to
interstitial oedema and swelling of the endothelial cells of
glomerulus and peritubular capillaries) and greedy tubular
reabsorption of sodium and water occurs, resulting in small
amounts of concentrated urine with low sodium.
Under such circumstances renin is released locally and
angiotensin II is formed with consequent intrarenal
vasoconstriction. The resulting renal ischaemia further
contributes to oliguria and this stage is immediately reversible
with appropriate management. Further angiotension II
induces the adrenal cortex to release aldosterone which
promotes reabsorption of sodium.
Renal (Intrarenal) Failure
This gets established due to structural damage. If the oliguria
is severe and prolonged, focal necrosis occurs in the tubule
due to diminished glomerular perfusion; glomerular
coagulation with microthrombi; obstruction of tubular lumina
by cellular debris; and back diffusion of the glomerular filtrate
into interstitium across the walls of damaged tubules and
this is termed as acute tubular necrosis. Sometimes,
circulatory disturbances are absent and necrosis occurs due
to direct toxic damage to the tubules. Occasionally, necrosis
may involve both glomeruli and tubules which is known as
“renal cortical necrosis”. The onset of acute tubular necrosis
is indicated when oliguria persists even after the blood
pressure is restored to normal. It may be further confirmed
by estimating the urinary sodium concentration which is
invariably increased.
Similarly, urinary urea is decreased in tubular necrosis
since the nitrogenous wastes are not excreted by impaired
kidney function and the specific gravity of urine is fixed at
1010 or less (vide infra). Apart from untreated prerenal
failure or ingestion of nephrotoxins, any severe
parenchymatous lesion like acute glomerulonephritis,
pyelonephritis (interstitial nephritis), vasculitis, interfere with
renal blood flow and cause intrarenal failure.
Postrenal Failure
It denotes acute obstruction to urine flow into the bladder
or distal to the bladder. This acute obstructive uropathy
may present in different ways. In the initial periods of partial
mechanical obstruction medullary function may be impaired
resulting in polyuria. However, in acute total obstruction,
absolute anuria occurs, i.e. zero urinary volume. Such acute
postrenal failure can only occur when there is one single
functioning kidney or bilateral simultaneous ureteric
obstruction or any obstruction at bladder neck or urethra.
Obstruction, if not relieved, leads to hydronephrosis or
bladder hypertrophy (if distal) or infections and renal atrophy.
CAUSES OF OLIGURIA
Oliguria can be classified as in the Table 23.1.
Table 23.1: Causes of Oliguria or acute renal failure
I. Prerenal Failure
1. Hypovolaemia or inadequate circulating blood volume (shock
kidney)
a. Loss of fluids
i. From the gut—Diarrhoea and vomiting
ii In the urine—Diabetic coma
iii From the skin—Excessive sweating (effect of heat)
b. Loss of blood
i. Gastrointestinal haemorrhage
ii Postoperative
iii Obstetrical accidents—Uterine haemorrhage
c. Loss of plasma
i. Burns
ii Road accidents
2. Diminished cardiac output (inadequate pumping of the heart)
a. Myocardial infarction
b. Congestive heart failure
c. Pulmonary embolism
d. Pancreatitis (acute)
3. Vasodilatation
a. Anaphylaxis—Penicillin, bee stings, snake venoms
b. Septicaemia
i. Severe infections
ii Septic abortions
II. Renal Failure (intrinsic) (refer to Chapter ‘Haematuria’)
1. Tubular: Acute tubular necrosis (reversible)
A. With circulatory disturbance (anoxic or postischaemic due to
causes listed under prerenal failure)
B. Without circulatory disturbances (toxic)
a. Pigment induced
i. Acute haemolysis as in G6PD deficiency
ii Haemolytic—uraemia syndrome
iii Incompatible blood transfusion
iv Rhabdomyolysis
Contd...
 354 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Contd... tubular necrosis must be entertained. Glomerulopathies and

b. Chemical induced other entities with consistent structural renal damage, leading
i Nephrotoxic drugs (sulphonamides, tetracyclines, to intrinsic renal failure must be differentiated from acute
aminoglycosides, phenacetin, NSAIDs, penicillamine, tubular necrosis. The essential point to be decided is whether
cytotoxic drugs) there is hypovolaemia or obstruction or sepsis.
ii Metals (copper sulphate) Though initially, the patient may feel normal, the clinical
iii contrast media features of uraemia appear after some days. Prerenal failure
c. Hepatorenal syndrome
signs are those of dehydration and circulatory collapse with
2. Glomerular: Acute glomerulonephritis and other glomerulopathies
impaired excretory function of the kidney. Renal failure signs
3. Glomerulo—Tubular
a. Renal cortical necrosis appear with frank uraemia.
b. Multiple myeloma Life-threatening biochemical abnormalities like
4. Interstitial: Acute interstitial nephritis (Acute severe pyelo- hyperkalaemia (cardiac arrhythmias or neuromuscular
nephritis or drug affect the Interstitium and pelvicalyceal system) depression) and metabolic acidosis (Kussmaul’s breathing)
5. Vascular result apart from raised plasma urea and creatinine. If urea
a. Disseminated intravascular coagulation is raised more out of proportion to creatinine dehydration
b. Vasculitis (Polyarteritis Nodosa and systemic Lupus or hypercatabolic state (fever) considered. Assessment of
Erythematsus) hydration may show volume overload with pulmonary
c. Eclampsia
congestion or oedema. Hyponatraemia may result (<120
d. Malignant hypertension.
e. Papillary necrosis mmol/L) leading to fits. The anticipated features of uraemia
f. P-Falciparum malaria in oliguric patients are (i) gastrointestinal disturbances
(Impedence of microcirculation.) like parrot tongue, anorexia, nausea and vomiting;
g. Acute bilateral renal arterial occlusions (ii) neurological abnormalities muscular twitchings, fits
h. Acute renal venous occlusions drowsiness and coma; (iii) cardiovascular abnormalities like
III. Postrenal Failure arrhythmias and pericarditis; and (iv) Haematological
(Obstruction to urinary tract) (Refer to Chapter ‘Haematuria’). abnormalities like normocytic normochromic anaemia, due
1. Ureters (Intraureteral and extraureteral) to impaired erythropoietin production; thrombocytopenia
a. Ureter of single functioning kidney
and coagulation disturbances with bleeding tendencies.
b. Bilateral ureters—Stones, necrotic papillae, pus, uric acid
crystals, extrinsic compression—tumours, retroperitoneal Postrenal failure are those of renal failure coupled with signs
(periureteral) fibrosis. of obstruction. Intercurrent infections may complicate the
2. Bladder picture.
a. Bladder tumours involving both ureteric orifices After a few days to four weeks of oliguria, the diuretic
b. Stones phase begins, if the patient does not succumb. Urine volume
c. Pelvic carcinoma and retroperitoneal tumours increases rapidly which heralds the healing of nephron. As
d. Prostatic enlargement the nephron function is still impaired, uncontrolled loss of
3. Urethra water and electrolytes continues. Despite diuresis,
a. Strictures
glomerular filtration rate remains low. Consequently, the
b. Valves
biochemical changes may show upward trend for several
c. Tumours
days, then cease to rise and fall gradually later.
Complete recovery occurs in the course of six months
Acute-on-Chronic Renal failure with normal biochemical findings. though tubular dysfunction
Acute renal failure may develop if infection or fluid loss (diminished concentrating ability), often persists. It does
occurs in a subject with chronic renal failure. not cause any clinical problem and it is compatible with
normal health. In the differentiation between prerenal failure
Clinical Essence or azotaemia (azo means containing nitrogen) and established
renal failure (ATN), the following are the useful criteria
The clinical features and the course of acute renal failure 1. Character of urine
predominantly centre round the causal condition besides 2. Ability to excrete creatinine and urea as well as to
oliguria. The cardinal features last for about 1 to 3 weeks. conserve sodium
Acute tubular necrosis sets in as a complication of prerenal 3. Response to diuretics (Vide infra)
azotaemia, if it is not corrected in time. Nevertheless, if the Nevertheless, in obstructive uropathies (postrenal
oliguria persists longer than four weeks, diagnosis of acute azotaemia) the serum sodium is usually normal and urinary
 Oliguria 355

sodium is less than 20 mmol/L and the other values, though Pigment induced (Refer to Chapter ‘Jaundice’)
variable, resemble prerenal parameters. the measurement Hepatorenal syndrome it denotes renal failure affecting
of serum osmolality is not useful in the differentiation since patients with severe liver disease (ascites, jaundice and
it remains normal. hepatic insufficiency) who are adequately hydrated. The
syndrome is usually precipitated by factors like diuretic
Clinical Discussion therapy, paracentesis, infection or haemorrhage and/or
Prerenal Failure circulatory changes. The low urinary sodium concentration
with a high urine/plasma creatinine ratio are striking indices.
Refer to Chapter ‘Shock’ The pathogenesis of the progressive renal failure is probably
due to intrarenal vasoconstriction.
Renal Failure
Glomerular Acute Glomerulonephritis and other
Tubular: Acute Tubular Necrosis (Vide supra). Glomerulopathies (Refer to Chapter ‘Haematuria’).

Diagnostic Renal Indices—urine and blood profiles

Prerenal Azotaemia Established Renal Failure (ATN)

I. Urinalysis
1. Specific gravity >1020 Fixed 1010 or <1010
2. Proteinuria Mild Moderate
3. Microscopic deposits Insignificant Significant cellular sediment and muddy brown casts
II. Chemical constituents of urine and blood
1. Urine osmolality (mosm/kg) >500 <350
2. Urinary sodium (mmol/L) <20 <40
3. Urinary urea (mmol/L) Increased Decreased
>250 mmol/L <160 mmol/L
4. Ratio of BUN/Serum creatinine >20 (i.e. 30) <20 (i.e. 10)
(Normal upper limit is 20)
5. Serum sodium High Low
(135-144 mmol/L)
6. Urine: Plasma (Osmolal ratio) >1.3:1 <1.1:1
7. Urine/ Plasma urea >10 <10
8. Urine/Plasma creatinine >40 <20
U/P Na
9. FENa = × 100 <1 >1
U/P Cr
(Fractional excertion of Na which relates to Na clearance to creatinine clearance)
(FENa=Excreted fractuin of filtered sodium)
10. Renal failure index = <1 >1
Urine Na
Urine/Plasma creatinine
III. Diuretic response
i. Normal saline (1000 ml/1 h) Improves urine output No response
(carefully monitered)
ii. Mannitol (2oo ml of 20 % iv Urine output restored No response
in 20 minutes)
iii. Frusemide Urine output restored No response
(100 mg bolus IV at the rate of 10 mg per min)
 356 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Glomerulotubular
• Renal cortical necrosis: Cortical necrosis follows usually
obstetrical haemorrhage. If complete, it presents as
anuria and if incomplete, as oligoanuria (unlike ATN
presenting as oliguria) with little or no recovery in the
former and unpredictable recovery in the later.
• Multiple myeloma: It is a malignant proliferation of
plasma cells in bone marrow in particular and may be
associated with renal hypoperfusion and ARF due to
either hyperviscosity or toxic effects from deposited
immunoglobulin light chains in glomeruli and/or tubules
(light chain nephropathy) or associated hypercalcaemia.
Interstitial
Acute severe pyelonephritis (Refer to Chapter
Acute interstitial nephritis } ‘Haematuria’)
Vascular
• Disseminated intravascular
coagulation
• Vasculitis (Polyarteritis nodosa
and other vasculitides)
• Eclampsia
} (Refer to Chapter
Haematuria)
• P Falciparum malaria (Refer to Chapter
} ‘Coma’)
• Malignant hypertension: The renal changes are
secondary to vascular lesions espicially the small
arteries and arterioles, which are described as
malignant nephrosclerosis. Hypertension is severe with
diastolic blood pressure over 130 mm of Hg. There is
no past history of either acute nephritis or renal
oedema. Papilloedema is an important diagnostic sign
which occurs early unlike in primary renal disease
where the renal failure is very much advanced even
by the time the papilloedema develops. The transient
cerebral attacks, seizures, haemoptysis or haemate-
mesis, congestive heart failure are the additional
features. The urine shows albuminuria and haematuria
and specific gravity is usually fixed at 1010. Serum
creatinine and blood urea are elevated.
• Papillary necrosis The renal papilla is highly susceptible
to bacterial infections. It may also be caused by
diabetes mellitus, gout and phenacetin containing
analgesics. Papillary damage eventually leads to renal
lesions of chronic interstitial nephritis without
glomerular changes. Haematuria, pyuria and mild
proteinuria are common. Oliguria with acute renal
failure may occur especially in a diabetic or in a patient
with chronic obstruction. Pyelogram shows a ring
shadow.
• Acute renal arterial occlusion Acute oliguric renal
failure occurs in acute occlusion of the renal artery,
in a solitary kidney. In the presence of normal
functioning of both imdneys, sudden occlusion of one
renal artery may result only in hypertrophy of the
contralateral kidney, with normal biochemical
parameters, whereas acute bilateral renal arterial
occlusions result in oliguria. The resulting infarct may
produce sudden pain in the flank or upper abdominal
region with haematuria and pyrexia. Acute occlusion
may occur in mitral stenosis, atrial fibrillation,
myocardial infarction, bacterial endocarditis or
abdominal trauma.
• Renal vein occlusion The sudden thrombosis of the
renal vein in a solitary kidney or renal veins in both
kidneys without adequate collateral circulation result
in oliguric renal failure. Haematuria, severe lumbar
pain are the associated features. Oliguria does not take
place if the occlusion is gradual with adequate collateral
circulation. Instead nephrotic syndrome results, with
massive proteinuria with or without few RBCs. Renal
vein thrombosis is usually associated with
membranous glomerulonephritis or hypernephroma,
dehydration or trauma.
Postrenal Failure
Ureters
• Stones (Refer to Chapter ‘Haematuria’)
• Necrotic papillae and pus (Vide supra)
• Uric acid crystals: Ureteric obstruction from uric acid
crystals occurs when uric acid precipitates in the renal
tubules at levels of 1.19 mmol/L or 20 mg/dl.
Hyperuricaemia occurs in primary gout or
hyperlipidaemia or after cytotoxic drugs or diuretics or
aspirin. Uric acid stones may form with low urine pH
and high purine diet.
• Bladder (Refer to Chapter ‘Haematuria’)
Urethra
• Urethral stricture: Dysuria, bifurcation of the urinary
stream or weak stream, urinary retention with infection
are presenting symptoms. The stricture may be
congenital or acquired due to gonorrhoea or trauma or
as a complication of malignancy.
• Urethral valves: Posterior urethral valves which are
folds of mucosa are present only in the males. Difficult
urination, weak stream, distended bladder, urinary
incontinence with infection are the manifestations. Both
stricture and valves are diagnosed by urethrogram.
• Urethral tumours: Refer to Chapter ‘Haematuria’
 Oliguria 357

Acute-on-Chronic Renal Failure d. Dysuria

e. Prostatism (hesitancy, slow stream normally
Due to adaptive mechanisms, multisystem manifestations
maximum flow rate of urine is 18-30 mL/sec and
of uraemia (urine and blood) do not appear until GFR is
frequency)
decreased to 25 percent of normal. Hypertension may
f. Any recent surgery including gynaecological or
develop early. Specific causes like diabetes mellitus,
urological surgery
glomerulonephritis, polycystic kidney may be present.
D. Acute-on-Chronic Renal Failure
Urinary infection or anticholenergic drugs may precipitate
Check for symptoms of chronic renal failure like nocturia,
acute-on-chronic renal failure in subjects with urinary
anorexia, vomiting, bone pain or fits and symptoms of
obstruction or analgesic nephropathy.
the precipitating event, to ascertain whether CRF
CLINICAL APPROACH underlies an apparent ARF.

The etiological diagnosis of oliguria or anuria is based on Physical Examination

the clinical setting and an endeavour to elicit history, physical
examination and urinalysis, and decide which of the four A. Prerenal Failure
groups of acute renal failure is present. Fundamentally, the Examination for
history of a reduction in the quantity of urine may be either a. Volume status
due to retention of urine with intact functioning kidneys or i. Dehydration (poor skin turgor, no sweat, dry
suppression of urine due to acute renal failure. So one has mucous membrane, tachycardia, flat neck
to make sure that there is no retention of urine before pro- veins with CVP < 5 cm of water, and
ceeding to evaluate oliguria, whether it is due to established hypotension)
renal failure (acute tubular necrosis or glomerular diseases) ii. Overload—(Vide infra)
or impairment of kidney function (extrarenal factors). b. Any evidence of septicaemia due to severe infections
c. Any altered sensorium
History d. Chest examination for evidence of either pulmonary
embolism or cardiac infarction
A. Prerenal Failure e. Any other systemic disease.
a. History of fluid loss (diarrhoea or vomiting or both), B. Renal Failure
bleeding episodes
Look for
b. Past history of diabetes mellitus
a. Overload—Oedema of the eyelids or pulmonary
c. Drug history (including radio contrast agents)
oedema, i.e. >3 kg of water and CVP > 5 cm of
d. Any history of acute episodes of pain in the chest
water.
e. Acute severe infections
b. Jaundice due to incompatible blood transfusion, or
f. History of reduced intake of fluids due to various
hepatorenal syndrome
causes
g. Any history of recent surgery or trauma or burns c. Skin—Butterfly rash
h. Any obstetric episode. d. Anaemia (usually present in acute-on-chronic renal
B. Renal Failure failure. It takes two weeks time for anaemia to set
History of in, in acute renal failure.)
a. Recurrent attacks of tonsillitis e. Arthralgia
b. Urinary tract infection f. High fever due to urinary tract infection
c. Arthralgia or hypertension g. Evidence of hypertension (not present in acute tubular
d. Haemoptysis or haematuria necrosis)
e. Untreated prerenal failure (Since any of the causes h. Palpation of the abdomen for evidence of enlarged
of prerenal failure, if not corrected in time, may lead kidneys
to acute tubular necrosis) i. Examination of the heart
C. Postrenal Failure i. For evidence of any bacterial endocarditis
History of (leads to acute anuric renal failure due to
a. Colicky pain embolic occlusion of the renal arteries)
b. Haematuria ii. Friction rub—Pericarditis in severe uraemia
c. Anuria iii. S3 gallop
 358 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
j. Examination of the respiratory system
i. Type of respiration—Kussmaul, tachypnoea
ii. Crepitations
C. Postrenal failure
a. Look for any swelling over suprapubic region
(distended bladder in bladder neck obstruction).
b. Any tenderness in the loin or over the kidney
anteriorly.
c. Palpate for any mass per abdomen (palpable kidney).
Hydronephrosis may be present since most of the
tumours of the bladder develop in the posterior half
and occlude urethral orifice.
d. Rectal examination for any evidence of prostate
enlargement.
e. Vaginal examination for pelvic tumours.
f. A bladder catheter may reveal postvoid residual urine
of > 50 ml which may be due to bladder neck
obstruction.
D. Acute-on-chronic renal failure
Examine with special reference to signs of chronic renal
failure like anaemia, muscle twitchings, ecchymoses,
pigmentation, hypertension and pericarditis.
Investigations
Urinalysis
(Bladder catheterisation to be done for urine examination if
necessary). Simple urine tests are very valuable in
differentiating prerenal azotaemia (shock kidney) from
established renal failure (toxic kidney both endogenous and
exogenous toxins).
Naked eye appearance: If urine is dark, it is either due to
a. Diminished secretion of urine or haemoglobinuria.
Smoky urine is due to small quantities of blood. Foamy
urine is seen in nephrotic syndrome
b. Specific gravity (vide supra table)
c. Bence Jones protein
d. Sediment
i. Excess WBCs suggestive of pyelonephritis or
papillary necrosis; and WBC casts indicate acute
interstitial nephritis.
ii. RBCs with casts are suggestive of glomerular disease
whereas RBC alone may be suggestive of calculi.
iii. Eosinophila suggest allergic interstitial nephritis.
iv. Crystals—if uric acid crystals present, it is uric acid
nephropathy.
v. Casts—Brownish pigmented cellular casts are seen
in acute tubular necrosis and Brownish pigmented
granular casts may be seen in haemoglobinuria or
myoglobinuria.
e. Ocult blood test (if positive without haematuria, it is
suggestive of myoglobinuria or haemoglobinuria.)
f. Urine culture
g. Urine osmolality
Blood Tests
a. Full blood count (TC, DC absolute eosinophil count,
RBC, Hb% and ESR); peripheral smear for burr cells in
haemolytic-uraemic syndrome.
b. High haematocrit value indicates dehydration.
c. Serum colour—If pink, it is suggestive of haemolysis
with haemoglobinuria, and normal colour in rhabdomyo-
lysis with myoglobinuria. (Serum Myoglobin > 80 µg/L)
d. Blood urea
e. Serum creatinine (High blood urea and normal or small
elevated creatinine is suggestive of prerenal failure
whereas if both values are high, it is suggestive of acute
tubular necrosis.)
f. Electrolytes
i. Serum sodium decreased
ii. Serum potassium increased
iii. Serum bicarobonate decreased
g. Other chemical constituents
i. Serum calcium reduced
ii. Serum phosphate increased
iii. Serum alkaline phosphatase increased
iv. Serum uric acid increased (disproportionately high
in interstitial nephritis)
v. Serum bilirubin (both direct and indirect)
vi. Blood sugar.
vii. Plasma lactate (increased if ARF is due to sepsis)
h. Clotting screen like fibrinogen and platelet count (both
decreased)
i. Blood culture in septicaemia or SBE.
Dye Reduction Spot Test or Dye Reduction Test
Using cresyl blue determine glucose-6 phosphate
dehydrogenase deficiency (RBC enzyme defect).
Radiology
a. Plain X-ray of the abdomen is done for calculi or
retroperitoneal disease.
b. IVP is to determine papillary necrosis or renal calculi.
(May precipitate ARF in myeloma)
c. Retrograde pyelogram is to detect patency of ureters.
d. Rapid sequence IVP to detect renovascular hypertension,
where X-ray films are taken at 1/2, 1, 2, 3, 4, minutes
after injecting the contrast in 30 seconds. The usual
IVP is followed later.
 Oliguria
e. Radiology of bones is for changes like osteomalacia,
osteitis fibrosa or osteosclerosis.
Ultrasonography To detect stones or size of the kidneys
which is markedly enlarged in accute obstructive uropathies
or small in acute on chronic renal failure. (Small kidney is <
10 cms and large kidney is > 14 cms).
Small kidney: Bilateral in CRF and unilateral in Renal artery
stenosis.
Large kidney: Bilateral in polycystic kidney and unilateral in
hydronephrosis or renal vein thrombosis.
Cystoscopy
If necessary.
ECG
For changes due to hyperkalaemia or hypocalcaemia.
Renal Biopsy
Indicated only if (a) diagnosis is not clear and in cases
described as ‘out of blue’; (b) renal function does not return
in three weeks and when the kidneys are of normal size; or
(c) there is intrinsic renal failure. Possible bleeding tendencies
are to be borne in mind.
Further Investigations
Blood
a. Antinuclear factors (to confirm SLE)
b. Antistreptolysin titres (to confirm streptococcal
glomerulonephritis)
c. Serum complement C-3, C-4, (reduced in immune
complex nephritis)
d. Acid phosphatase (raised in prostatic carcinoma)
e. Prostate specific antigen (raised in prostatic carcinoma)
f. Renin estimation (elevated in ARF)
g. Immunoglobulin electrophoresis (to exclude multiple
myeloma) Paraproteins show the ‘M’ band (i.e.)
monoclonal and not IgM.
Imaging Techniques
a. CT scanning for diagnosing any renal pathology.
b. Radioisotope renogram—The radionuclide studies are
helpful in assessing the renal blood flow, cortical function
and functional status of obstructive uropathy.
i. Isotope renography—131 hippuran injected
intravenously and both renal angles are monitored
with gamma counters and the curve obtained for
each kidney. The curve has vascular secretory,
excretory component and unilateral differences
359
detected. It is useful to screen hypertension patients
with unilaterla renal vascular disease.
ii. Gallium Citrate (67Ga) may be helpful in different-
iating drug induced interstitial nephritis from acute
tubular necrosis since there will be no uptake of 67Ga
in acute tubular necrosis.
iii. Renal scan or scintigraphy: Kidney structure and
function examined by using gamma camera, instead
of a counter and different isotopes.
c. Renal angiography—The arteriogram study is a last
choice because of its hazards. Embolic occlusions in
the arterial system can be demonstrated by retrograde
femoral aortography or selective renal angiography.
d. Renal venography—useful to detect renal vein thrombosis
or for determining tumour extension.
e. Micturating cystourethrogram—The urinary bladder is
filled with contrast media through urethra. Series of
X-rays are taken during micturition to diagnose
vesicoureteric reflux, i.e. retrograde flow of urine from
bladder up the ureters.
TREATMENT OF OLIGURIA
The mechanism of the decreased urine output or suppression
of the urine formation (cardinal feature of acute renal failure)
is most often apparent from the clinical settings, offering
initial clues. The management of oliguria remains the same
irrespective of the cause, unless a disease requiring specific
treatment is detected. Prompt early treatment restores renal
function smmothly. It is imperative to rule out prerenal
(mannitol yields diuresis) and postrenal (ultrasound
examination especially if anuria alternates with polyuria)
factors, before establishing presence of intrinsic renal failure.
In essence, therapeutic modalities encompass both
conservative and dialytic measures depending on the clinical
status.
The crux of the problem is to ascertain whether it is
prerenal or acute tubular necrosis. If urine output cannot
be established with fluid challenge, frusemide or mannitol,
a regimen of dopamine (1 to 3 ug/kg/minute) and frusemide
(100-200 mg 6-hourly) is worth considering. If still there is
no response, then it can be presumed that acute tubular
necrosis has set in.
Prerenal Failure
Replace circulating volume with appropriate optimum
amount of fluids as rapidly as possible. (It is better to
monitor the central venous pressure to assess the rate of
fluid administration to avoid possible overload). Inotropic
 360 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
agents may be judiciously used. Treat the casual condition
by appropriate measures (Refer to Chapter ‘Shock’). If
oliguria persists, despite restoration of normal blood
pressure, suspect the onset of acute tubular necrosis,
which is to be established (vide supra) and treated
accordingly (vide infra).
Intrinsic Renal Failure
Tubular (Acute tubular necrosis)
A. The underlying cause must be immediately treated.
B. Oliguric phase (includes conservative and dialytic
therapy)
1. Conservative therapy
a. General measures:
i. Maintain fluid chart by measuring daily intake
and output.
ii. Record body weight daily (should be reduced
or at least unchanged).
iii. Withdraw any nephrotoxic drugs or adjust
the dosage of drugs used.
iv. Prevent infection with prophylactic
antibiotics and GI bleeding with H2 receptor
antagonists.
b. Fluid balance:
i. Restrict fluid intake to compensate the
previous day’s losses, i.e. through skin and
lungs (500-700 ml) and the urine output, as
well as an additional 400 ml/d, so as to
maintain normal volume status.
ii. If overloaded, induce diuretics with IV
frusemide.
c. Diet:
i. Restrict proteins to 20-40 g a day. Endo-
genous protein breakdown is minimised by
giving more carbohydrates (100-300 g
glucose orally or IV) and fats (which also
make up the necessary calories). Nandrolone
also prevents endogenous protein metabolism.
ii. Oral sodium chloride < 2 g/d is allowed (no IV
saline to be given).
iii. Potassium is forbidden unless low (avoid
foods rich in potassium).
iv. Total parenteral nutrition if necessary—
hypertonic glucose solution and L-essential
amino acids (renal failure fluid).
d. Diuretics: High dose frusemide (200-400 mg IV)
and mannitol (12.5-25 gm IV) are beneficial (as
oligurie phase is converted into nonoliguric renal
failure).
e. Correction of biochemical abnormalities
i. Hyperkalemia—IV glucose with or without
insulin (1 unit of insulin for 2.5 to 5 grams of
glucose). Correct sodium and water deficit
to restore circulation. Exchange resins
(calcium resonium 50 g orally or per rectum);
calcium polystyrene sulphonate 15 g orally
6-hourly or 30 g as retention enema for 9 h.
Calcium gluconate 10-30 ml of 10% IV
slowly. Correction of acidosis will also reduce
serum potassium.
ii. Hyperphosphataemia—Aluminium hydroxide
gel 2 g tds.
iii. Acidosis-50 ml of 8.4% (5o mEq) bicarbo-
nate IV or 0.5 g tds orally or 1/6 molar lactate.
f. Symptomatic treatment
i. Infection—Appropriate antibiotics.
ii. Convulsions—Diazepam parenterally.
iii. Anaemia—Packed cells transfusion,
erythropoietin.
iv. Hypertension—If present, ACE inhibitors.
v. Congestive heart failure or pulmonary
oedema-Treat accordingly (Refer to Chapter
‘Dyspnoea’).
vi. G.I. Bleeding—Desmopressin 0.3 ug/kg IV
over 20 min or intranasally; conjugated
oestrogene 0.6 mg/kg/d (Refer to Chapter
‘Haematemesis’).
2. Dialytic therapy: Indications for dialysis are
i. Biochemical changes-Blood urea 100 mg %;
serum creatinine 10 mg; serum bicarbonate <10
meq; pH < 7.2; serum potassium > 6 mEq/L.
ii. Volume overload (pulmonary oedema, congestive
heart failure) pericarditis, GI bleeding.
iii. Hypercatabolic ARF, i.e. daily rise of blood urea
20 mg, creatinine 1 mg, potassium 1 mEq and
fall of bicarbonate < 2 mEq/L.
iv. Haemodialysis is effective even in severe cases
but cardiovascular stability and adequate blood
pressure are the pre-requisities. The peritoneal
dialysis is useful even with cardiovascular
inadequacies but only in less severe cases.
Continuous arteriovenous haemofiltration (CAVH)
or venovenus haemofiltration is particularly
beneficial for those who are not suitable for
haemodialysis or peritoneal dialysis.
C. Diuretic phase: Since glomerular filtration rate is lowered
and urine output is increased, sufficient fluids, salt,
potassium are provided and sodium bicarbonate, if
needed. Dietary protein must be restricted.
 Oliguria
D. Recovery phase: When urine volume returns to normal,
as the renal failure improves, normal diet is started.
E. Unresponsive phase: If recovery does not occur after
6 weeks, renal biopsy may be done. Maintenance dialysis
or renal transplantation considered.
Pigment induced (Refer to Chapters ‘fatigue’ and ‘Bleeding
Disorders’)
Hepatorenal syndrome Volume expansion may be done
judiciously, monitoring cardiovascular system and
extracellular fluid volume. If renal failure gets established,
treat as above.
Glomerular
Glomerulopathies (Refer to Chapter ‘Haematuria’)
Glomerulotubular
Multiple myeloma (Refer to Chapter ‘Bleeding Disorders’)
Renal Cortical necrosis: Necrosis of the glomeruli and
tubules as occurs in retroplacental haemorrhage (compli-
cation of pregnancy) leads to anuria or oligoanuria. Daily
haemodialysis for some weeks is worth trial though the
recovery is unpredictable.
Interstitial
Acute pyelonephritis (Refer to Chapter ‘Haematuria’)
Acute Interstitial nephritis (Refer to Chapter ‘Haematuria’)
Vascular
Disseminated intravascular coagulation (Refer to Chapter
‘Bleeding Disorders’)
Vasculitis (Refer to Chapter ‘Polyarthritis’)
Eclampsia (Refer to Chapter ‘Epileptic Seizures’)
Malignant hypertension: Malignant hypertension or
accelerated phase is a medical emergency. Antihypertensive
drugs used intravenously are frusemide (20–80 mg IV) or
sodium nitroprusside (0.3-1.0 mg/kg/min. IV) or diazoxide
(150-300 mg. IV) or trimethophan (1-10 mg/ min IV) or
labetolo(20 mg/h to 200 mg/h) Alternatively sublingual
nifedipine (5-10 mg) is safe and effective.
Aggressive treatment to lower the blood pressure too
rapidly must be avoided lest stroke or myocardial infarction
should occur. Control reduction over several hours to 24 h
is desirable. Bed rest and sedation are beneficial. When once
the patient becomes asymptomatic, and the blood pressure
improves, antihypertensive drugs instituted orally.
When acute renal failure develops, control of blood
pressure may involve risk. However, diuresis if occurs indi-
cates successive therapy. Dialysis is required if serum pota-
ssium or creatinine increases or pulmonary oedema occurs.
Papillary necrosis: Severe acute pyelonephritis may lead to
acute necrosis of the papilla when fragments of renal tissue
361
appear in urine. Suitable antibiotics must be administered
and any underlying cause like diabetes mellitus is treated.
P Falciparum Malaria (Refer to Chapter ‘Coma’).
Acute renal artery occlusions: When occlusions of large
arteries occur, endarterectomy may restore renal function.
Anticoagulation is indicated in occlusion of small arteries.
Acute renal vein occlusions: Surgical removal of clot may
be helpful. Anticoagulants are prescribed. Recanalisation of
renal vein may be attempted when nephrotic syndrome
develops. If there is infected renal vein thrombi, nephrec-
tomy is done.
Postrenal Failure
Obstruction to the urine flow at any level in the urinary
tract must be cleared without any delay to prevent infection
and progressive renal dysfunction. If obstruction is relieved,
massive diuresis occurs due to impaired tubular dysfunction
in some cases, when fluids and electrolytes (sodium
potassium, magnesium) should be replaced suitably,
preferably monitoring urine volume and electolytes (both
serum and urine). When biochemical changes return to
normal, the underlying cause may be managed further.
This depends on the nature of obstruction (remediable
or not) which calls for urethral catheterisation or
percutaneous nephrostomy (if ureters are dilated) or
anastomoses of ureters to a loop of ileum opening into the
abdominal wall or leaving stents in the ureters (in
irremediable cases). Infection must be treated aggressively
with appropriate antibiotics. Dialysis may be indicated before
surgical intervention. Nephrectomy may be necessary in a
single kidney damage. If both kidney are damaged
irreversibly, treat as for chronic renal failure.
Ureters
• Stones: Stones in the ureters may be dealt surgically, if
necessary (Refer to Chapter ‘Haematuria’)
• Papillary necrosis: (Vide supra)
• Uric acid crystals: Hyperuricaemic patients may develop
oliguria due to deposition of uric acid crystals. Therapy
of such uric acid obstructive nephropathy includes
allopurinol and acetazolamide (for diuresis and
alkalinisation of urine) or haemodialysis.
• Multiple myeloma (Refer to Chapter ‘Bleeding
Disorders’)
• Retroperitoneal fibrosis or congenital pelviureteric
junction due to neuromuscular defect Since the flow of
urine is prevented causing hydroureter and subsequently
 362 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
hydronephrosis, lysis of ureters and implantation into
peritoneal cavity for the former and surgical repair of
the stenotic area or nephrectomy (if the damage is
severe) for the latter may be done.
Bladder
• Tumours (Refer to Chapter ‘Haematuria’)
• Stones (Refer to Chapter ‘Haematuria’)
• Prostatic enlargement: Compression of the prostatic
urethra by the enlarged prostate with consequent effects
on the bladder and renal function, is treated by
transurethral resection of the prostatic tissue, which
relieves the outflow obstruction.
Urethra
• Urethral stricture: Repeated dilatation, internal urethro-
tomy or urethroplasty indicated as the case may be.
• Urethral valves: Destruction by overstretching with
dilators or bilateral ureterovesicoplasty may be needed.
• Urethral tumours: For proximal tumours,
urethrocystectomy and for distal tumours resection
considered.
Oliguria 363
 Chapter
Pain in the Extremities
24
Pain in the limbs, either in the arm or leg, may be superficial,
deep or referred from either somatic structures or viscera.
It occurs predominantly as either a musculoskeletal or a
neurovascular problem. The superficial as well as the referred
pain are well localised, as compared to the deep pain which
is often poorly localised. The onset of pain may be sudden
or gradual or episodic, especially related to alterations in
posture. The painful experience of conscious awareness of
the pain stimulus (sensation) and awareness of the intensity
and localisation of the sensation (perception) are appreciated
only after the pain impulses reach the thalamus and perietal
cortex respectively. It is difficult to assess the patient’s
quality, or quantity of pain as there are varying degrees of
emotional overlay, influencing the dimensions of pain,
irrespective of the extent of pathology.
CAUSES OF PAIN
Pain in the Upper Extremities
Somatic origin of pain (particularly adhesions around the
shoulder joint or subacromial bursitis or fibromyositis) is
common than neuropathic pain (pain in the distribution of a
single peripheral nerve—neuralgia or root pains due to
trauma, sudden lifting strain or degenerative conditions of
the cervical vertebrae compressing more often C6 and C7
roots) (Fig. 24.1). Though paraesthesia is invariably of
neurological origin, sometimes vascular or vasomotor
causes may account for it in certain cases. Acroparaesthesia
connotes subjective tingling sensation in the palmar surfaces
Table 24.1: Causes of pain in the extremities
Causes Upper limb
1. Cutaneous Cellulitis
2. Locomotor
a. Muscles i. Myofibrositis
ii. Myositis
iii. Cramps—rare
of the finger tips, with or without signs of organic nervous
lesions.
Pain in the Lower Extremities
Some of the causes of backache described in Chapter Low
Backache are associated with pain in the lower limbs
distributed along the buttock, back of the thigh and posterior
or lateral aspect of the calf and foot termed sciatica. Pain in
front of the thigh due to hip disease or L2 and L3 vertebral
pathology or pain in the inner portion of the thigh (obturator)
or pain in the lateral aspect of the thigh (meralgia
paraesthetica) or pain in the feet due to polyneuritis or root
pains or for that matter any local pathological processes,
are to be discriminated according to the location of pain,
which may be somatic or neuropathic in origin.
Mechanism of Pain
A gross or microscopic tissue injury is usually followed by
release of arachidonic acid and the biosynthetic cascade
comprising prostaglandins, thromboxane, mono hydroxy
fatty acids and leukotrienes. Inflammation, which is the
tissue reaction to injury, is especially due to leukotrienes.
Pain is due to inflammation by and large. The first sequence
of pain is hyperalgesia. The second reaction is release of
neuropeptides like bradykinin and histamine, combining to
produce pain. The third stage is reflex contraction or spasm
of the muscle due to release of calcium which combines
with adenosine triphosphate with consequent energy deficit.
Lower limb
Cellulitis
i. Myofibrositis
ii. Myositis
iii. Cramps—more common
Contd...
 Pain in the Extremities 365

Fig. 24.1: The cervico-brachial plexus in the posterior triangle of the neck and upper part of axilla

b. Tendon sheaths and bursae i. Tendonitis i. Tendonitis

ii. Tenosynovitis ii. Tenosynovitis
iii. Bursitis iii. Bursitis
c. Bones i. Osteomyelitis i. Osteomyelitis
ii. Pott’s disease ii. Pott’s disease
iii. Neoplasms iii. Neoplasms
iv. Congenital fusion of vetebrae iv. Sacralisation of the fifth lumbar
vertebra
v. Trauma v. Trauma
d. Joints i. Periarthritis of the shoulder joints i. Sacroiliac or hip or knee joints
(osteoarthritis)
ii. Cervical disc herniation ii. Lumbar spondylosis and
and cervical spondylosis lumbo-sacral disc herniation
iii. Rheumatoid arthritis iii. Baker’s cyst
3. Lymphovascular i. Lymphangitis i. Lymphangitis
ii. Thrombophlebitis and ii. Thrombophlebitis and
deep venous thrombosis deep venous thrombosis
iii. Acute or chronic arterial occlusion iii. Acute or chronic arterial occlusion
iv. Raynaud’s disease—more common iv. Raynaud’s disease—less common
v. Erythromelalgia
4. Neurological
a. Peripheral nerves i. Brachial neuritis i. Sciaticaneuritis
ii. Causalgia ii. Causalgia
iii. Sympathetic dystrophy iii. Sympathetic dystrophy
iv. Entrapment neuropathy iv. Meralgia paraesthetica
v. Polyneuritis v. Polyneuritis
b. Plexus, spinal nerves roots
i. Radiculitis i. Radiculitis
ii. Tumours ii. Tumours (cauda equina)
iii. Rib pressure syndrome

Contd...
 366 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Contd...

c. Meninges i. Pachy meningitis i. Pachy meningitis

ii. Tumours of the meninges ii. Tumours of the meninges
d. Cord i. Spinal neoplasms i. Spinal neoplasms
ii. Meningomyelitis ii. Meningomyelitis
iii. Syringomyelia iii. Syringomyelia—less common
5. Referred pain (from viscera) Angina pectoris Malignant disease in the pelvis
6. Psychogenic i. Anxiety i. Anxiety
ii. Hysteria ii. Hysteria

Cutaneous Tendon Sheaths and Bursae

Cellulitis
It may show swelling, hyperaemia and tenderness with
constitutional response like high fever. These visible signs
of inflammation are confined to the dermal and subcutaneous
tissue. It indicates absence of gross suppuration, although
it may be seen at the portal of entry, e.g. punctured wound.
The common causative organism is streptococci.
Locomotor
Muscles
Myofibrositis It consists of pain and stiffness in the muscles
like trapezius, supraspinatus origins, buttocks and low
lumbar regions. Tender points may be found along the upper
border of the trapezius or outer border of the gluteus besides
acute tenderness on deep pressure. The pain and stiffness
are marked on movements and relieved by rest. This entity
is also termed as fibromyalgia which is a relatively common
form of nonarticular rheumatism and exists per se or
associated with hypothyroidism or rheumatoid arthritis.
Myositis (Refer to Chapter ‘Paraplegia’)
• Cramps Muscle cramps are sudden painful contractions
of one of the muscles of the foot or leg. They are
nocturnal and last for few minutes leaving behind a
sensation of soreness for days even. They may occur
in occlusive arterial disease, in tetany due to alkalosis or
calcium deficiency, primary dysmenorrhoea pregnancy
or exposure to severe heat. Unusual physical activity
during day time, cold feet or persons engaged in certain
Tendonitis Calcareous or noncalcareous tendonitis is fairly
common in the bicipital and supraspinatus tendons.
Calcareous tendonitis of the shoulder joint consists of
inflammation of the capsulotendinous cuff especially the
supraspinatus portion with deposits of calcium salts. Pain
and tenderness over the deposits and restricted shoulder
movements are characteristic.
Epicondylitis (tennis elbow) results from chronic strain
of the forearm muscles with consequent tears and chronic
inflammations of the tendons at their respective origins from
the epicondyles. Pain is predominantly on either medial or
lateral aspects of the elbow and radiates upwards or
downwards. It is aggravated by grasping or volar flexion
of the wrist.
Tenosynovitis It is inflammation of synovial sheath of the
tendons and may be due to infection or trauma or rheumatoid
arthritis. The flexor tendons in the palm and trigger finger
or extensor sheaths of the dorsum of the wrist or tendons
of the thumb are usually involved. Pain and tenderness are
prominent over the affected regions and pain is aggravated
by stretching of the affected tendons.
Bursitis The inflammation of synovial bursae may occur as
a result of rheumatoid arthritis, bacterial infections, trauma
or gout (crystal induced bursitis). It is characterised by
severe loal pain and tenderness with limited mobility. Calcific
deposits in the bursae are identified on X-rays.
Bones
a. Osteomyelitis

}
occupations like dress making, musicians, and mining,
b. Pott’s disease
may be predisposed to nocturnal cramps. Writer cramps
c. Neoplasms (Refer to Chapter ‘Low Backache’)
consists of spasm and cramp like pain of the affected
d. Congenital
muscles of the hand, while writing (especially those who
e. Trauma
write with the intrinsic muscles). The writing becomes
bizarre and does not confine to a steady line. The
Joints
specificity of cramps occurring on writing, with normal
movements of the hand for other purposes, is highly Periarthritis of the shoulder joint It is an inflammation of the
diagnostic. articular synovia, tendons, tendon sheaths and paratendinous
 Pain in the Extremities 367

bursae and ligamentous capsular bands. It may be associated

with or without an underlying organic lesion like rheumatoid
arthritis or diabetes mellitus involving joints. Deposits of
aggregates of calcium containing crystals, comprised of
hydroxyapatite and calcium pyrophosphate dihydrate, around
the joint is known as calcific periarthritis. The common
presentation is painful shoulder, sometimes painful upper
extremity, aggravated by shoulder movements. Tenderness
is obvious at the tendinous insertions. It may progress and
result in marked restriction of the shoulder joint movements
leading to frozen shoulder.
Cervical disc herniation and cervical spondylosis Degeneration
of the cervical discs and herniation thereof is one of the
common causes of pain in the upper extremity. Herniation
may be dorsolateral or dorsomedial and occurs usually
between 5th and 6th cervical vertebrae and/or C6, C 7
vertebrae. The acute herniation is usually dorsolateral causing
compression of the root. The chronic cervical disc
degeneration is associated with dorsomedial herniation and
secondary osteoarthritic changes (cervical spondylosis),
which may cause cord compression.
In acute disc Prolapse the onset is sudden with pain
spreading from the back of the neck to the back of the
shoulder down the arm and wrist to the index and middle
fingers. Pain is aggravated by movements. If the 6th cervical
root is affected, paraesthesiae of the thumb and index finger
with diminished supinator jerk and if the 7th root is affected
paraesthesiae of the index and middle fingers with loss of
biceps reflex are the presenting features.
If C8 and T1 roots are involved, the pain may resemble
coronary artery disease. Weakness of the concerned muscles
and sensory changes are uncommon. X-ray may show
narrowing of the disc spaces (Fig. 24.2) and contrast
myelography demonstrates occlusion.
In cervical spondylosis, the onset is insidious. Pain and
stiffness of the neck is present, which usually recurs. In
the dorsomedial herniation, the cervical cord and anterior
spinal artery may be compressed giving rise to (a) upper
motor neurone weakness of the lower extremities and lower
motor neurone weakness of the upper limbs,
(b) paraesthesiae in the arms and legs, and (c) sensory loss
of a dermatome pattern in the upper limbs and disturbance
of pain and temperature and in some cases joint sense in the
lower limbs due to involvement of long tracts. The reflexes
will be diminished or lost at the level of compression and
increased beyond (spondylytic myelopathy). The
movements of the neck may not cause pain unless it causes
pressure on the nerve root. X-ray may show narrowing of
the disc spaces and osteophyte formation in the straight
Fig. 24.2: X-ray of the neck showing oesteophytes at C6 and
C7 with narrowing of the intervertebral disc space diagnostic
of cervical spondylosis
X-ray. Osteophytes encroaching on the intervertebral
foramen is appreciated only in oblique views. Contrast
myelogram may show occlusions and compression of the
cord. Proteins may be raised in the CSF. MRI is the choicest
investigation to localise the cord and root compression in
recent times.
Rheumatoid arthritis (Refer to Chapter ‘Polyarthritis’).
Sacroiliac or Hip or Knee Joints (Osteoarthritis) (Refer to
Chapter ‘Low Backache’)
A degenerative disorder is characterised by the degeneration
of cartilage and hypertrophy of the bone at the articular
margins with minimal articular inflammation and without
any systemic manifestations. The pain in the joints is
worsened by activity and relieved by rest. The swollen
joint is due to bone enlargement rather than soft tissue
swelling and coarse crepitus may be felt in the joint.
Osteoarthritis of the hip is most disabling with limitation
of internal rotation and extension of the hip initially. X-ray
may show narrowing of the joint space, Osteophyte
formation and lipping of the marginal bone with thickened
subchondral bone.
Lumbar spondylosis and lumbosacral disc herniation
(Refer to Chapter ‘Low Backahe’).
Baker’s cyst It is a synovial cyst in the popliteal fossa causing
pain in the popliteal space and a stiff joint. If it ruptures,
there may be marked inflammation of the leg with a painful
swollen limb.
 368 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Lymphovascular
Lymphangitis, Thrombophlebitis and Deep Venous
Thrombosis
(Refer to Chapter ‘Oedema’)
Acute or Chronic Arterial Occlusion
Arterial occlusion may be sudden in onset with pain, reduced
skin temperature, numbness with an inability to use the leg,
pallor and colour differences between the limbs. In chronic
insufficiency, the pain occurs on exercise or walking
(intermittent claudication). Examination of the peripheral
pulses may show absent or feeble pulsations and postural
changes (if the limb with obliterative vascular disease is
raised 45° above the horizontal plane, it blanches quickly
than normal; if it is placed in the dependent position later,
there will be delay in venous filling and flushing). Pain at
rest indicates critical ischaemia. The occlusive disease is
invariably due to atherosclerosis and acute ischaemia due
to thromboembolism or trauma. Diagnosis is confirmed by
Doppler test or arteriography. Calcification may be revealed
on radiography. Low (< 0.9) ankle brachial index (ABI) and
high (> 0.9) toe systotic pressure index (TSPI) diagnostic.
Raynaud’s Disease
(Refer to Chapter ‘Cyanosis’)
Erythromelalgia
It is a vasomotor disorder where the blood vessels are
dilated unlike Raynaud’s. Redness of the feet, burning or
pain are the presenting features. It is usually precipitated by
exercise, heat or dependent position of the limb.
Neurologial
Peripheral Nerves
Brachial neuritis (Neurologic amyotrophy) Severe pain over
the shoulder girdle radiating down the arm or the neck
followed by paralysis of the painful muscles. Wasting of
the muscles, loss of jerks and loss of sensations may be
present. Usually C5, C6 and C7 nerves are affected. It may
be due to an infection or injection of vaccines or injury
(postoperative or post-partum).
Sciatica (Refer to Chapter ‘Low Backache’)
Causalgia (Post-traumatic sympathetic dystrophy) Causalgia
is continuous burning pain in the distribution of the affected
peripheral nerve following trauma. Touch may be felt as
painful sensation and accompanied by sympathetic nervous
dysfunction. The skin becomes glossy and atrophic. The
bones become osteoporotic. Joints become stiff and
extremities may become cold.
Reflex sympathetic dystrophy (Shoulder-hand syndrome)
Reflex sympathetic dystrophy is due to overactivity of the
local sympathetic nervous system. The symptoms include
burning pain increased by the movement of the distal joints,
swelling and sweating. Synovitis is evident in the affected
joints. Atrophic changes in the skin, nails, bones, stiff joints
and contractures may develop later. Both extremities may
be involved although shoulder-hand syndrome is a common
form. An internal disorder like myocardial infarction or
diabetes mellitus initiates reflex sympathetic dystrophy.
Sometimes an external injury may also be incriminated
resulting in atrophy of the cutaneous and subcutaneous
structures (Sudeck’s atrophy). The shoulder-hand syndrome
is a combination of scapulohumeral periarthritis with
restricted shoulder mobility and sudeck’s atrophy of the
hand and wrist. X-ray show patchy osteoporosis of the
underlying bones.
Entrapment neuropathy (Carpal tunnel syndrome) Burning pain
and numbness in the first-three fingers, wrist, occasionally
forearm is especially experienced during nights. There may
be tenderness over the carpal ligaments. When the wrist is
tapped, tingling is experienced in the fingers (Tinel’s sign)
or after sustained flexion of the wrist (Phalen’s sign). There
may be wasting of the thenar eminence with weakness of
the abduction of the thumb and sensory loss over the radial
3½ fingers. It is caused by pressure of the median nerve
while it passes through the space between the wrist bones
and carpal ligament, which occurs in systemic diseases like
rheumatoid arthritis, oedema and myxoedema. Similarly less
common types of nerve entrapment may involve the ulnar
or radial nerves.
Meralgia paraesthetica This term was coined by Roth in 1895.
The lateral femoral cutaneous nerve (L2–L3 roots) may be
compressed in pregnancy or obesity resulting in pain and
paraesthesia over the outer aspect of the thigh. It is usually
affected by the posterior fascicle of the inguinal ligament
during pregnancy or obesity, or systemic diseases (like
diabetes mellitus or malignancy), trauma, and constant use
of belts.
Polyneuritis (Refer to Chapter ‘Paraplegia’).
Plexus, Spinal Nerves Roots
Radicultis (Vide supra—Disc herniation and also Chapter
‘Paraplegia’)
 Pain in the Extremities 369

Tumours A spinal tumour may present as pain, radiating in

the distribution of one or more spinal roots, (frequently
encountered when it is extramedullary). The pain is
aggravated by the movements of the spine or coughing and
temporarily relieved by changes in posture. The associated
motor symptoms, objective sensory changes, reflexes and
other effects of compression on the cord help the diagnosis.
(Refer to Chapter ‘Paraplegia’).
Rib pressure syndrome (Cervical rib, scalenous anticus;
costoclavicular, thoracic outlet syndrome) The compression
or stretch of the lower trunk of the brachial plexus and
subclavian artery between the clavicle and first rib is the
essential feature of this syndrome (Fig. 24.3). The
rudimentary rib derived from the 7th cervical vertebra
(cervical rib) or enlarged 7th cervical transverse process
may compress resulting in pain down the inner aspect of
the arm, usually worse during nights, with paraesthesiae
and sensory loss over C8 and T1 roots, besides wasting of Fig. 24.3: Thoracic outlet and site of compression
the muscles of the hand. The vascular symptoms due to
compression of the subclavian artery, (like attacks of
blanching, coldness or cyanosis of the fingers with unequal Cord
radial pulses) may also be encountered. The diagnostic
features are (a) paraesthesiae and numbness on abducting
the arm to 90° and rotating externally, which disappear on
•
•
•
Spinal Neoplasms
Meningomyelitis
Syringomyelia
} (Refer to Chapter ‘Paraplegia’)
bringing the arm back to normal position; (b) diminished
radial pulse when the arm is abducted with the head rotated Referred Pain (From Viscera)
to the opposite side (Adson’s test) and (c) presence of a
bruit in the supraclavicular fossa. Angina Pectoris
The cervical rib can be made out on palpation as a bone
(Refer to Chapter ‘Chest Pain’)
swelling of the neck or radiographically. Sometimes, the
same symptoms can be seen due to a fibrous band without Malignant Disease in the Pelvis
the accessory rib or due to descent of the shoulder occurring
in middle life. EMG, nerve conduction and somato sensory (Refer to Chapter ‘Low Backache’)
evoked potential studies confirm the diagnosis. Apart from
X-ray of the neck (AP View). Psychogenic
Pain may be a manifestation of either anxiety or hysteria
Meninges i. Anxiety (Refer to Chapters ‘Chest Pain and Fatigue)
Pachy meningitis It is leutic in origin which causes pain ii. Hysteria (Refer to Chapters ‘Coma and Paraplegia)
down the arm or over the shoulder due to strangulation of
the posterior roots. The pain may be followed by atrophy CLINICAL APPROACH
of the muscles corresponding to the anterior roots involved. In the investigation of pain in the extremities, it should be
Signs of pyramidal compression in lower limbs with made mandatory, that each of the structures that is likely to
objective sensory hanges below the level of lesion are be the underlying cause (muscles, bursae, bones, joints,
elicitable. blood vessels on one hand and neurological, both peripheral
Primary and metastatic tumours of the meninges (Refer to and central nervous system) should be examined
Chapter ‘Paraplegia’) systematically with a careful look at the painful region.
 370 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
The second manoeuvre is to determine the origin of
pain by analysing its (a) mode of onset; (b) location;
(c) distribution; (d) intensity; (e) character; (f) duration;
and (g) accompaniments.
History
History revolves round the analysis of pain an associated
features.
Analysis of Pain
i. Mode of onbset Is the pain sudden or gradual or episodic?
Arterial occlusions, nocturnal muscle cramps, ruptured
synovial cyst, disc prolapse are sudden in onset. Bursitis,
tendonitis, arthritis, neuritis, chronic arterial occlusions
are gradual in onset. Rib pressure syndrome or Raynaud’s
disease are episodic in onset.
ii. Location
a. Distal portions or proximal portions (inner aspect of
the thigh – obturator pain)
b. Unilateral or bilateral
c. Joints or muscles
iii. Distribution
a. Pain due to peripheral nerve disease follows cuta-
neous distribution of the particular nerve involved.
b. Root pains follow cutaneous distribution of the
corresponding spinal segment (dermatome pattern).
c. Central pain, like in the spinal cord, and spontaneous
deep root pain is due to irritation of the spinothalamic
tract.
d. Referred pain is felt in the cutaneous root areas in
relation to segmental supply of the affected viscus.
e. Psychic pain has no fixed anatomical correlation.
iv. Intensity Mild, moderate or severe
v. Character
a. Is it superficial (localised) or deep (poorly localised
and dull) or referred (well localised and follow
sclerotome or embryological rather than dermatome
distribution)?
b. Is it throbbing, burning, stabbing, lightning or
cramplike?
vi. Duration: Momentary, short duration or constant.
vii. Accompaniments
a. Root pains are aggravated by coughing or sneezing
and relieved by change of posture.
b. Muscular (somatic) pains may be aggravated on
movement and relieved at rest.
c. Neuropathic pains are accompanied by sensory
symptoms whereas referred pain is not accompanied
by paraesthesiae or objective sensory changes.
Associated Features
Associated features are (a) Loss of weight; and (b) systemic
diseases like diabetes mellitus, mitral valvular disease or
collagen diseases.
Past history includes (a) any history of lifting heavy objects,
(b) trauma, (c) exposure to cold, and (d) herpes zoster.
Personal history includes (a) smoking, (b) alcohol, (c) drugs,
and (d) occupational details.
Physical Examination
The aim is focussed to decipher whether the pain is
neurological or non-neurologial (skeletal or vscular)? The
presence of paraesthesiae may be neurological or vascular
or vasomotor and never skeletal or referred origin.
General Examination
a. General stance for any scoliosis, kyphosis or any rib
contour asymmetry or other deformity.
b. Any appreciable loss of weight or anaemia to account
for underlying systemic disease.
c. Fever for evidence of any infection.
d. Blood pressure differences in the limbs.
Local Examination
Inspection
i. of the extremities for: (a) swelling; (b) pallor; (c)
erythema, hyperaemia or red streak; (d) varicose veins
or prominent superficial veins; (e) muscles-any atrophy;
and (f) joints for any swelling.
ii. The lumbar region (a) Is lumbar lordosis lost and
flattened? (b) Any scoliosis or kyphosis?
Palpation
a. Temperature differences like coldness
b. Muscle tenderness or any fibrositic nodules and
circumference mesurements
c. Bones—for any cervical rib
d. Nerves—for any tenderness or thickening
e. Blood vessels—any difference in the pulses, or Homan’s
sign
f. Glands—any glandular enlargement (pressure on the
brachial plexus causes pain in the arm)
g. Joints
i. Range and rhythm of the spinal movements (both
cervical and lumbar)—forward flexion, hyper-
extension, lateral rotation.
ii. Joint mobility, e.g. sacroiliac joint where subluxation
(due to pregnancy or injury) or arthritis (due to
 Pain in the Extremities 371

tuberculosis or ankylosing spondylitis) may induce c. Positive blood cultures

pain by forced abduction and external rotation of d. Night blood for MF
the flexed thigh; extension of the thigh, or e. VDRL
compression of the anterior iliac spine. f. Rheumatoid factor
h. Crepitus—Crepitus over the osteoarthritic knee joint or g. Blood sugar
any crepitus over the area of cellulitis due to gas
producing organisms like clostridia. CSF
If necessary for any raised protein and pleocytosis.
Systemic Examination
CNS examination Radiology
a. Motor system—Evaluate the power in sequence of big
a. X-ray of the cervical spine—AP, lateral and oblique
joints both the upper or lower limbs depending upon the
views for evidence of (i) cervical spondylosis; (ii)
limb affected.
Vertebral status; (iii) Disc herniation; (iv) cervical rib;
b. Sensory system—Any objective sensory changes.
(v) Neurofibroma shows enlarged intervertebral
c. Reflexes
foramen of the affected root and AP view reveals eroded
i. Deep reflexes diminished or exaggerated or
pedicles.
normal.
b. X-ray of the lumbar spine for evidence of spondylosis
ii. Superficial reflexes-Plantar-extensor or flexor.
such as narrowing, lipping, irregular facets or osteophyte
iii. Visceral reflexes-any incontinence or retention of
formation.
urine.
c. X-ray of the joints for any presence of calcium in cases
d. Any evidence of cervical sympathetic paralysis.
of bursitis, osteophytes or narrow joint space.
e. Stretch Test
d. X-ray of the chest for any Pancoast’s tumour.
i. Straight leg raising test—(Refer to Chapter ‘Low
e. Contrast Myelography.
Backache’)
ii. Popliteal compression—Radiating pain aggravated ECG
by pressure over the tibial nerve through popliteal
fossa, If indicated.
iii. Passive stretching of the hip joint to elicit pain and
Special Tests
assess range.
iv. Flexion of neck causes paraesthesiae down the trunk If indicated.
and limbs (Lhermitte’s sign.) a. CT Scan
f. Independent heel and toe walking b. MRI
i. Heel walking excludes weakness of the dorsi flexors c. Doppler test
(L5). d. Nerve conduction Velocity studies-delayed in neuritis.
ii. Toe walking can exclude weakness of the gastroe- (Normal is 42-74 m/s)
soleus (S1). e. Ankle systolic pressure index (< 0.5 suggestive of severe
Abdominal examination chronic arterial occlusion)
a. Palpate for any mass per abdomen. f. Phlebogram
b. Vaginal or rectal exam for any pelvic mass which may g. Arteriography
be pressing on sacral plexus. h. Arthrogram
Cardiovascular examination Auscultate for any (a) murmurs;
(b) arrhythmias; and (c) bruit. TREATMENT OF PAIN IN THE EXTREMITIES
Pain either in the upper or lower extremity is of multifactorial
Investigations origin, depending on which of the anatomical structure (skin,
Blood muscle, bone, joint, vessel or nerve) is the seat of pathology.
The clinician must endeavour to delineate the cause by a
a. Total TWC - Leucocytosis diligent approach to design an appropriate therapeutic
b. ESR elevation strategy.
 372 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Symptomatic treatment:
i. Somatic Pain: Analgesics (Refer to Chapter ‘Polyarthritis’)
ii. Neuropathic Pain: Gabapentin 300 mg tds with or
without Methyl cobalamin (500-1500 mcg)
Specific treatment for specific diseases.
Cutaneous
Cellulitis
Appropriate antibiotics and nonsteroid anti-inflammatory
drugs (NSAIDs) are to be displayed.
Locomotor
Myalgias (Muscle Pains)
Fibrositis and myofibrositis
a. Drugs-NSAIDs, analgesics and muscle relaxants (Refer
to Chapter ‘Low Backache’).
b. Local measures—Hot water fomentations, massaging
with ointments containing rubifacients, mephenesin, or
topical analgesics, if necessary xylocaine injection into
the specific tender sites, may be given.
Myositis (Refer to Chapter ‘Paraplegia’)
Cramps
a. Raise the foot of the bed.
b. Stretch the affected muscles and massages.
c. Drugs (for symptomatic relief)—Diphenhydramine
(50 mg before bed time) or vitamin E (400 mg before
bed time) or quinine sulphate (300 mg tds).
d. Correct underlying cause—Unusual physical activity
or strenuous work; any offending drug; electrolyte
disturbances (hypocalcaemia, hypomagnesaemia,
hyponatraemia); neuromuscular disorder or circulatory
disturbances.
Carnitor (Levo Carnitine) 500 mg twice daily.
Tendons and Bursae (Vide infra)
Bone Pains
Osteomyelitis Rest, appropriate antibiotics for 4-6 weeks,
remove infected prosthesis. If necessary surgical
debridement and external stabilisation may be done.
Pott’s disease
a. Rest with hyperextension of the spine
b. Immobilisation by orthopaedic methods
c. Antituburculous drug treatment (Refer to Chpaters
Chronic ‘Diarrhoea’ and Haemoptysis).
d. Surgery if necessary (costotransversectomy and spinal
fusion).
Joint Pains
Periarticular pain
a. Tendonitis—NSAIDs local steroid injections (if necessary)
and physical therapy. Surgical repair if rupture occurs.
b. Bursitis—Rest, NSAIDs and if necessary local steroid
injection.
c. Adhesive capsulitis (Periarthritis or frozen shoulder)-
NSAIDs, physical therapy and shoulder exercises, if
necessary local steroid injections, failing which surgical
manipulation.
Articular pain
a. Arthritis (Refer to Chapter ‘Polyarthritis’)
b. Cervical spondylosis and cervical disc prolapse—Cervical
radiculopathy requires conservative treatment (rest for
2-4 weeks, immobilisation with a cervical collar,
intermittent neck traction with 2-4 kg weight, and
analgesics or decompression surgery (foraminotomy,
excision of disc or laminectomy and anterior discectomy
depending on the stage of the disease).
c. Lumbar spondylosis and lumbar disc prolapse—
Conservative treatment (rest for 2-4 weeks on a firm
mattress or a hard surface, immobilise with corset or
body cast, pelvic traction, analgesics and muscle
relaxants, local injections of steroids or local
anaesthetics, physical therapy and graded exercises) or
surgery (laminectomy and spinal fusion; if there is no
herniation, degenerative material is removed from inter
space after making a window in the ligamentous
annulus).
Lymphovascular Causes
Lymphangiitis
Rest to the limb and elevation of the affected part, glycerin
mag sulph bandage, NSAIDs and appropriate antibiotics,
supplemented with diethylcarbamazine.
Thrombophlebitis
Bed rest for a few days, analgesics, elastic compression
bandage and if necessary appropriate antibiotics.
Deep Venous Thrombosis
Bed rest for one week with affected limb elevated 15° above
heart level, elastic bandage for three months, analgesics,
 Pain in the Extremities
anticoagulants (initially low molecular weight heparin
followed by warfarin for three months). If necessary
thrombolysis with streptokinase or venous thrombectomy
in selected cases. Preventive measures (physical exercise
and anticoagulants) are mandatory in the high risk groups
(abnormal venous walls, venous stasis and hyper-
coagulability of blood).
Acute Arterial Occlusion
Anticoagulation with IV heparin immediately and analgesics
are indicated. If the colour of the skin improves or neural
function restores within three hours of occlusion, surgery
is not warranted. If ischaemia persists, embolectomy should
be done within 12 hours.
Chronic Arterial Occlusion
Upper limb is tolerated than the lower limb. Abstinence from
smoking, optimum foot care avoiding trauma or infection,
withdrawal of beta-blockers are advised. Vasodilators,
analgesics, large dose of vitamin ‘E’ may not be all that
helpful. Surgical measures like angioplasty or bypass grafting,
and/ or lumbar sympathectomy or amputation (if gangrene
sets in) are undertaken. Though pentoxyfylline is useful
cilostazol, clopidogrel are effective.
Raynaud’s Phenomenon
Treat as per the underlying cause like Raynaud’s disease
(Refer to Chapter ‘Cyanosis’); vasculitis (corticosteroids
or other immunosuppressants). Cold exposure, vibrating
tools and beta-blockers should be avoided.
Erythromelalgia
Raising the legs usually helps. Occasionally sympathectomy
may be necessary.
Neurological Causes (Neuralgias)
Peripheral Nerves
Acute brachial neuritis (Neuralgic amyotrophy) Treatment is
symptomatic with analgesics, as pain subsides usually within
a fortnight and complete recovery is possible in 3 to 6 months.
Corticosteroids may be helpful in some cases.
Sciatica (Refer to Chapter ‘Low Backache’)
Causalgia Sympathectomy offers complete relief.
373
Reflex sympathetic dystrophy External application of heat or
cold to the affected areas; exercises; control of pain with
analgesics, NSAIDs sympathetic nerve block and short-
term prednisolone, constitute the therapeutic approach.
Entrapment neuropathies (Nerves involved are median, ulnar,
peroneal, posterior tibial) Avoid repetitive movements of the
affected joint and pressure over the elbow, knee or ankle.
Splinting of the joints may be beneficial. Underlying causes
like diabetes mellitus or hypothyroidism and rheumatoid
arthritis must be treated simultaneously. In some cases,
decompression surgery or transposition of the nerve may
be necessary. Corticosteroid infection into the affected region
is beneficial.
Meralgia paraesthetica If obesity is associated reduce the
calorie intake, local infiltration of a mixture of 2 ml of
hydrocortisone and 3 ml of 2% lignocaine just medial to
anterior superior iliac spine may be beneficial; incision of
fascia lata from the neural opening up to inguinal ligament
may be necessitated occasionally.
Peripheral neuritis (Refer to Chapter ‘Paraplegia’)
Plexus, Spinal Nerves Roots
Radiculitis (Vide supra-disc prolapse) Rib pressure syndrome
Avoid carrying heavy articles on the shoulder. Shoulder girdle
muscles must be strengthened by graded exercises,
symptomatic relief with analgesics and rest in a sling may
be helpful. In some cases, the anatomical abnormality of
the thoracic outlet needs surgical correction (Fig. 24.4).
Fig. 24.4 X-ray showing supernumerary rib extending outward
from the 7th cervical from the 7th cervical transverse process
and overlying the proximal portion of the first thoracic rib on both
sides (cervical rib-bilateral). X-ray showing removal of the
cervical rib on the left side, the aggravating factor of brachialgia
 374 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Meninges
Tumours Tumours of the respective anatomical structures
need surgical intervention.
Pachy meningitis and meningomyelitis Treatment depends on
the nature of infection of the dura mater or other structures.
Leutic infection of the meninges is treated with procaine
penicillin 0.6 to 1.2 grams daily for three weeks. In case of
penicillin allergy, oxytetracycline (500 mg four times daily)
or doxycycline (100 mg t.d.s.) or erythromycin stearate
(500 mg four times daily) can be given for four weeks. If
pyogenic organisms are incriminated, appropriate antibiotics
are chosen and if subdural abscess forms, surgical
intervention is warranted after 3 or 4 weeks. Symptomatic
treatment may be initiated as indicated for paraplegia (vide
Chapter ‘Paraplegia’).
Cord
Syringomyelia Surgical decompression of the foramen
magnum or syrinx may relieve the symptoms.
Reffered Pain
Apart from somatic pain (shoulder joint and supra spinatus
tendon) and neuropatic pain (nerve root or peripheral nerve),
pain may be referred from viscera as in angina (arm) or
pelvic malignancy (lower limb).
Treatment of angina (Refer to Chapter ‘Chest’ Pain)
Treatment for malignancy (Refer to Chapter ‘Weight Loss’)
Psychogenic
Anxiety (Refer to Chapters ‘Pain and Fatigue’)
Hysteria (Refer to Chapter ‘Coma’)
Pain in the Extremities 375
 Chapter

Palpitations
25
Palpitation is an unpleasant awareness of the heart beat. Table 25.1: Causes of Palpitations
This conscious appreciation of the heart’s action is Physiological
usually due to a change in the heart rate or rhythm or (a) Physical stress
increased force of cardiac contraction with consequent (b) Emotional turmoil
unusual movement of the heart being felt in the thorax Pathological (Cardiac and Noncardiac)
Cardiac
(Fig. 25.1). 1. Cardiac arrhythmias
The palpitations may be rapid or slow, regular or irregular, A. Disturbances in impulse formation
light or heavy and the latter usually follows increased stroke (a) Sinus rhythm—Sinus tachycardia, sinus bradycardia
volume. Some patients get upset easily with an occasional (b) Ectopic rhythms:
i. Escape rhythm
extrasystole, while others may not even bother with serious ii. Extrasystoles
and chaotic arrhythmias. This widely experienced symptom iii. Supraventricular tachyarrhythmias:
may be physiological or pathological (i.e. cardiac or • Atrial tachyarrhythmias: Atrial fibrillation, atrial
noncardiac origin). flutter, Atrial tachycardia.
• Junctional tachycardias: Nodal tachycardia; AVNRT
• Accessory pathways mediated tachycardias (pre-
CAUSES OF PALPITATIONS excited tachycardias) (i.e.) AVRT; WPW syndrome.
NB: Paroxysmal supraventricular tachycardias include both
Causes of palpitations are pointed in Table 25.1. AVNRT and AVRT.
iv. Ventricular tachyarrhythmias
B. Disturbances in impulse conduction: (SA block;AV block)
C. Disturbances in both impulse formation and conduction: Sick
sinus syndrome
2. Hypertension
3. Acquired valvular diseases
A. Mitral valve disease
B. Aortic valve disease
4. Congenital heart disease—VSD, ASD, PDA
5. Acute myocardial infarction
6. Cardiomyopathy
Noncardiac
1. Haematological—Anaemia.
2. Metabolic—Hypoglycaemia
3. Endocrinal—Thyrotoxicosis, menopausal syndrome, carcinoid
syndrome
4. Abdominal—Dyspepsia, hiatus hernia, gastric distension,
flatulence
5. Infections—Febrile states
6. Drugs/Chemicals—Tobacco, alcohol, ephedrine, thyroxine, digoxin,
salbutamol, nicotine, alcohol.
7. Psychic—Anxiety states, neurocirculatory asthenia
Fig. 25.1: Origin and conduction of cardiac impulse Thus palpitations arise from stress or diseases or drugs.
 Palpitations
PATHOLOGICAL
Cardiac
Cardiac Arrhythmias
A. Disturbances in Impulse Formation
Sinus rhythm:
Sinus tachycardia The heart rate is faster than 100 beats
per min rarely exceeding 160 with a gradual onset and
cessation. It is uninfluenced by rest, exercise or posture. It
is commonly associated with exercise, emotion, fever,
cardiac failure or thyrotoxicosis. Pressure over the cartoid
sinus may have no effect or may reduce the rate gradually
followed by rapid return to the original rate.
ECG is characterised by shortening of the PP intervals
below 0.6s with normal P waves followed by normal QRS
complexes.
Sinus bradycardia Rate is 60 per min. It is seen commonly
in athletes or occurs pathologically in jaundice, myxoedema,
raised intracranial pressure and with drugs like digoxin or
β-blockers.
The ECG shows prolongation of the PP interval to one
second or more and the P waves occur regularly, followed
by normal QRS complexes. Usually no treatment is
necessary except after myocardial infarction when atropine
(0.3-1.2 mg IV slowly) is often effective.
Ectopic rhythms
Escape Rhythm—(Nodal Rhythm) These rhythms are those
initiated by lower centres, when the normal sinoatrial node
fails to initiate the impulses. When the AV node becomes
pacemaker continuously nodal rhythm appears. If may
Fig. 25.2 (a): Atrial extrasystole—Normal QRST complex with abnormal P occurring early in the cardiac cycle
Fig. 25.2 (b): Nodal extrasystole—P wave coincides with QRS complex of normal configuration occurring prematurely
377
occur apparently in normal individuals or may be associated
with underlying heart disease like hypertension or coronary
artery disease. choking sensation may be complained of
besides palpitations. ECG shows P waves with varying
position (before QRS or lost in QRS or after QRS) and
configuration (inverted) depending on where the cardiac
impulse arises in the AV node (head, body or tail). QRS
complexes are normal at the rate of 40-50 per minute.
Extrasystoles They arise from an abnormal focus either in
the atria or ventricles or occasionally AV node. They occur
earlier than expected in the cardiac cycle followed by a
pause and a strong ventricular contraction thereafter. The
sensation of emptiness in the chest or a missed beat or a
sudden thud are often complained of. They are often found
in healthy people and caused by over indulgence of tobacco,
alcohol and coffee, dyspepsia or anxiety. They may be found
also in association with chronic heart disease like ischaemic
heart disease. It is of significance if they are found 5 or 6
per min or occurring near the T wave (R on T) as they
herald the onset of ventricular tachycardia.
The diagnosis of extrasystoles clinically may be made
when the irregularity disappears on exercise, pulse deficit
is less than 20 and by the presence of ‘a’ waves, premature
beat before the pause and a loud first sound after the pause.
ECG in atrial variety shows an abnormal P wave and a
normal QRST in the extrasystole. The compensatory pause
is incomplete (Fig. 25.2 (a)).
In a nodal variety, P wave may or may not be seen
before the premature beat or follow normal QRS
(Fig. 25.2 (b)). In the ventricular variety, the normal
complexes are followed by large abnormal complex wherein
 378 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 25.2 (c): Ventricular extrasystole—QRS complex of ventricular extrasystole widened with T wave and ST segment
displaced in opposite direction to the abnormal QRS complex. P waves submerged in the abnormal ventricular complex

Fig. 25.3: Atrial fibrillation—Absence of P waves with varying RR intervals

the QRS is high and wide and T wave is in the opposite
direction to QRS. The P wave is obscured partially or
completely by the ventricular complex. The compensatory
pause is complete unlike in atrial or nodal extrasystoles
(compensatory pause means that interval between two R
waves before and after extrasystole is twice that of normal
R-R intervals).
The right ventricular extrasystoles are characterised by
the wide QRS complex with the main deflection upward in
lead-1 and downward in lead-3 and vice versa in
extrasystoles arising from left ventricle.
Similarly, the basal extrasystoles are characterised by
abnormal QRS complexes deflected upwards in al the 3
leads as against the apical extrasystole where the deflection
is downwards.
In the interpolated variety of extrasystole, the premature
beat is interpolated between 2 normal beats (i.e.), 3 beats
occurring during the time that is normally occupied by
2 beats.
It is significant if they are found more than 10 per minute
or >30 per hour as against <10 per hour when it is not
significant. If occurs near the T wave (R on T) i.e. no gap
before T wave they herald the onset of ventricular
tachycardia. (Salvo is two successive ventricular
extrasystoles at the rate of 100 per minute).
Supraventricular Tachyarrhythmias (Atrial and Junctional)
Atrial tachyarrhythmias
1. Atrial fibrillation—It is a common irregular tachycardia.
The pulse is irregularly irregular in both rhythm and
volume. There will be a pulse deficit of more than 20;
‘a’ waves are absent. The first sound varies in intensity
after the pause. There is no premature beat before the
pause. The heart rate usually exceeds 130 per min.
Exercise has no influence or may increase the irregularity.
It is paroxysmal or persistent (chronic).
The ECG shows absence of P waves and rapid irregular
“f” waves and irregular RR intervals (Fig. 25.3). It is usually
due to organic heart diseases (valvular or non vavular) or
noncardiac causes like thyrotoxicosis or acute infections.
Occsionally it may be a lone fibrillation.
2. Atrial flutter It is usually a regular tachycardia and far
less common. It may be irregular when associated with
varying block. The pulse rate is 160 and above, which
is uninfluenced by posture or exercise. There is usually
a fixed relationship between atrial flutter waves and
ventricular response. The pressure over the carotid sinus
causes abrupt slowing of the ventricular rate and when
the pressure is released, it quickens abruptly. Sometimes,
the degree of block may suddenly change spontaneously.
ECG shows flutter waves with a regular saw-teeth like
appearance without clear isoelectric intervals and interrupted
by ventricular complexes with a fixed or varying AV ratio
(Fig. 25.4). The etiology is similar to that of atrial fibrillation.
3. Atrial tachycardia (unifocal and multifocal)
This regular ectopic tachycardia is due to increased
automaticity of single atrial focus. It may be paroxysmal
or continued type or with AV Block. It may be due to
digitalis or may be with or without structural heart
 Palpitations 379

Fig. 25.4: Atrial flutter—Atrial rate is high and regular whereas the ventricular rate is low depending on the AV ratio. The
upstroke and downstroke of the waves without isoelectric intervals, resembling saw-teeth, is characteristic.

Fig. 25.5A: Nodal (junctional) tachycardia—Rapid, regular QRS complexes of relatively normal
configuration with no apparent P waves

disease. Tobacco, Alcohol, Stress, Gastric Disturbances
may trigger. ECG shows abnormal P configuration and
P wave axis occurring before QRS complex which is
narrow and with a rate of 100-250. No retrograde
P wave seen (i.e) positive P wave in AVR and negative
P wave in L2. Carotid sinus massage does not terminate
the attack. It is not influenced by exercise or change of
posture. The term multifocal atrial tachycardia (MAT)
indicates multifocal origin. The rhythm is irregularly
irregular resembling atrial fibrillation. It is seen is COPD
cases. ECG shows presence of P waves having 3 or
more different morphologies preceeding QRS with
varying PP intervals.
Junctional tachycardias
i. Nodal (Junctional) tachycardia: This occurs due to
automaticity of Junctional tissue. The incriminating
causes are drugs like Digitalis or Theophylline or
Catecholamines or ischaemia. Regular cannon waves
seen in Jugular veins. ECG shows regular narrow ORS
complexes of relatively normal configuration with a rate
of 120-130 per minute with no apparent P wave.
(Fig. 25.5A)
ii. Atrioventricular nodal re-entrant tachycardia(AVNRT):
This is the commonest variety of paroxysmal
supraventricular tachycardia with or without underlying
heart disease. Digitalis may be incriminated. It begins
and ends abruptly. The mechanism involved is reentry
and the entire tachycardia circuit is confined to dual
pathways (slow and fast) within AV node. The heart
rate varies from 140-250 per minute. Carotid sinus
massage terminates abruptly or the rate may slow down.
The P waves may be hidden in QRS or retrograde P
waves seen after QRS. The R-P interval is <100 ms.
Accessory pathways mediated tachycardias
i. Atrioventricular Re-entrant tachycardia (AVRT): This
is another variety of paroxysmal supraventricular
tachycardia but less common. After normal conduction,
reentry from ventricle to atrium by the accessory
pathway occurs either retrogradely (and comes down
the AV node completing the circuit which is not apparent
on the surface ECG, i.e (concealed) or may be bi-
directional (antegradely and retrogradely), i.e. capable
of antegrade conduction also resulting in pre-excitation
of the ventricle which is seen on the surface ECG
(manifest) as in WPW syndrome.
AVRT is of two types—orthodromic and antidromic.
When the reentry circuit passes antegradely through AV
node and retrogradely through accessory pathway, it is
known as Orthodromic Tachycardia (Narrow complex
Supraventricular tachycardia). If it is in the reverse
direction, i.e antegradely through accessory pathway
and retrogradely through AV node, it is termed as
 380 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fig. 25.5B: PSVT-Rapid, regular ventricular complexes of normal configuration and slightly modified
T waves due to fusion of P with preceding T (before treatment)
antidromic tachycardia (Broad complex tachycardia).
ECG shows P waves after QRS. (P may be flat, negative,
positive or retrograde). The R-P interval is >100 ms
(Fig. 25.5B).
ii. Wolff-Parkinson-White Syndrome: In this syndrome, a
congenital accessory pathway is present which conducts
in both antegrade and retrograde directions. The impulse
from atrium passes down the accessory pathway rapidly
bypassing the AV node (short P-R interval) and excites
the ventricle (preexitation) before it reaches via AV node
(slurred upstroke of the R wave known as Delta wave).
This asynchronism of the impulses in the ventricle results
in wide QRS interval. This syndrome is purely an ECG
diagnosis seen in normal sinus rhythm. It may be
associated with heart diseases like hypertension or
Ebsteins’ anamoly or without any heart disease as such.
The clinical significance of this entity is that it may
predispose to AVRT when the characteristic ECG
changes (i.e. short PR interval, delta wave and wide
QRS) disappear or may predispose to atrial fibrillation
which may degenerate into ventricular fibrillation. So
every case of supraventricular tachycardia must be
screened for WPW syndrome after the tachycardia
episode.
N.B: Narrow complex tachycardia (< 120 ms) include
both supraventricular (ectopic rhythm) and sinus
tachycardias.
Ventricular Tachyarrhythmias
a. Ventricular tachycardia (VT): This is less common than
SVT. Most of the patients with this arrhythmia have
underlying structural cardiac disease, usually ischaemic.
Occasionally, no structural heart disease may be evident
when the prognosis is good. It may be haemodynamically
stable, i.e. no clinical evidence of shock, regular
tachycardia with > 120 per minute at rest and uniform
(monomorphic) QRS configuration of >120 ms in
duration, i.e. broad complex tachycardia or haemo-
dynamically unstable when ventricular tachycardia is
sustained. Clinically, jugular pulsations are less compared
to heart rate and carotid sinus pressure is ineffective. It
may progress to ventricular fibrillation. The ECG shows
QRS complexes of abnormal and uniform configuration
with slight irregularity of RR cycles. P wave may be
less frequent than QRS complexes Monomorphic
(Ref. Fig. 33.3a).
Ventricular tachycardia with varying QRS
morphology, is termed as polymorphic VT which is
usually irregular in rate, haemodynamically unstable and
rapidly degenerates into ventricular fibrillation. A special
form of polymorphic VT with prolonged QT interval
with varying axis (some waves upright and others
inverted) is described as Torsade de pointes tachycardia.
Apparently, it may look like ventricular fibrillation in ECG
but it is actually a VT with varying axis.
b. Ventricular fibrillation: It is characterised by rapid,
irregular, ineffective ventricular twitches without
effective cardiac output resulting in periods of asystole.
It is usually a terminal event or occasionally these
paroxysms may be exhibited as attacks of Stokes-Adams
Syndrome with syncope and convulsions. ECG shows
rapid, regular or irregular oscillations varying in amplitude
and width representing QRS complexes without apparent
isoelectric interval (Ref. Fig. 33.3b).
c. Ventricular Extrasystoles: Vide Supra.
N.B: Broad complex tachycardias (> 120 ms) include both
ventricular tachyarrhythmias and supraventricular
tachycardia with conduction block.
B. Disturbances in Impulse Conduction
Sinoatrial block:
Though sinoatrial node initiates the impulse, it is not
propagated to the atrium. This is reflected clinically as
dropped beats both at the wrist and apex. If prolonged,
atrial standstill results when dizziness is experienced. Atirial
‘a’ wave in the cervical veins are absent. This may be due
 Palpitations
to digitalis or hyperkalaemia or sensitive carotid sinus or
atrial ischaemia. ECG shows a pause during which the P
and QRST complex are lost. The pause is approximately
equal to two normal P-P intervals in a long strip.
Atrioventricular block It is defective conduction of the impulse
from atrium to ventricle either in the form of delay in
transmission (through AV node or bundle) or complete
interruption. Thus it is classified as (1) First degree heart
block (prolonged atrioventricular conduction time) (2)
Second degree heart block (Partial heart block) (3) Third
degree heart block (Complete heart block).
a. First Degree Heart Block—This is an electro-cardiographic
diagnosis in which P-R interval is prolonged and constant
i.e. > 0. 2 second, as compared to sinus bradycardia in
which the P-R interval is constant and < 0. 2 second.
b. Second Degree Heart Block—This is suspected when
the rhythm is regular and slow with intermittent pauses.
On auscultation, it is appreciated from the absence of a
ventricular beat with simultaneous observation of atrial
‘a’ waves in the jugular veins and dropped beats at the
wrist. The dropped or missed heart beat due to a weak
premature contraction in extrasystoles is differentiated
from partial block by simultaneous auscultation, when
the long pause invariably follows the precocious
premature beat. The ECG in partial block shows
ventricular response only to every second or third sinus
impulse depending on the ratio (2: 1 or 3: 1 block) and
the PR interval remains constant. (Mobitz Type II). When
progressive prolongation of the PR interval occurs until
finally the ventricular complex is dropped, it is known
as wenckebach phenomenon. (Mobitz Type I).
c. Third Degree Heart Block—The cardiac rate is slow
(40 beats per minute) and regular. There are more atrial
waves in the jugular veins than the apical beats. The
intensity of the first heart sound changes irregularly and
sometimes accentuates sharply (cannon sounds) in
complete heart block. Caroid sinus pressure may further
slow the heart if the block is partial and may be
ineffective if the block is complete. The slow regular
rhythm does not alter with exercise in complete heart
block as against a slight increase in the heart rate or
abrupt slowing due to further impairment of
atrioventricular conduction in partial heart block. Attacks
of syncope with or without convulsive seizures may
occur due to prolonged asystole (Stokes-Adams
Syndrome). ECG in complete heart block shows more
P waves than QRS complexes, the later bearing no
constant relationship to the P waves, i.e. there is complete
dissociation between the atrial and ventricular complexes
381
with varying PR interval. None of the atrial impulses
will reach the ventricles and the ventricle beats
independently in response to a pacemaker in the AV bundle
or ventricle musculature (Ref. Fig. 33.1 and 33.2).
If the block is high in the conducting system, the QRS
complex is normal and if is low, the QRS complex widens.
The heart block is usually due to coronary artery disease,
drugs like β-blockers, verapamil or digoxin, and acute
infections.
C. Disturbances in both Impulse Formation
and Conduction
Sick Sinus Syndrome (Sino atrial disease): This sinus
node dysfunction, which usually results from atherosclerosis
fibrosis or hypertension in the elderly includes (1). Sinus
Bradycardia, (marked with or without asystole),
(2) Supraventricular tachycardia alternating with
bradycardia (Brady teachycardia Syndrome) and (3) sinus
pause (Sino Atrial standstill) due to disturbances in impulse
formation with or without sinus arrhythmia (nonphasic)
(4) Sino atrial block due to disturbances in impulse
conduction. It may be associated with palpitations and
dizziness or syncope due to pauses/ asystole. (1), (2) and
(4) (Vide supra). (3) Sinus pause—There is momentary
failure of the sinus node to initiate an impulse, resulting in
failure of atrial contraction. It is detected clinically by the
dropped beat both at the wrist and cardiac apex. If the
pause is prolonged, dizziness or syncope may result.
ECG shows a pause without atrial or ventricular
contraction whatsoever between two normal PQRST
complexes. The pauses are not exact multiples of normal
P-P interval. It may occur after gagging or encountered in
hypersensitive carotid sinus cases. Sinoatrial standstill is
secondary to either sinus pause or sinoatrial block
(Refer Fig. 33.4).
Hypertension
Established hypertension is said to be present when the blood
pressure readings exceed 140/90 mm of Hg. Hypertension
may be primary (essential) 90 percent or 10% secondary to
renal diseases (renal artery stenosis, glomerulonephritis,
chronic pyelonephritis, polycystic disease); endocrinal
disorders (phaeochromocytoma, Conn’s syndrome,
Cushing’s syndrome polycystic ovaries (PCOS), empty sella
syndrome); toxaemia of pregnancy); coarctation of aorta;
and drugs (steroids) or drug abuse (cocaine).
It may be persistent, transient (acute nephritis or toxaemia
of pregnancy), or paroxysmal (phaeochromocytoma).
 382 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Accelerated or malignant hypertension (cotton wool spots
and/or papilloedema) may develop in any type of
hypertension (except in coarctation of aorta), provided the
diastolic blood pressure is severe (>130 mm of Hg) and
more so when it rises rapidly.
Sometimes, instead of both systolic and diastolic
pressure elevations, systolic pressure alone may be high
⎛ >140 ⎞
(systolic hypertension). ⎜ ⎟ When blood pressure is
⎝ < 90 ⎠
raised at times and normal at others it is called border
line or labile hypertension. However, World Health
Organisation has classified the patient with borderline
hypertension as one having resting systolic blood pressure
of 140-160 mm of Hg and resting diastolic blood pressure
of 90-95 mm of Hg, both measurements present on several
occasions. Recent classification is Prehypertension. >
135/85 mm Hg
Hypertension stage 1 → 140-159/90-99
Stage 2 → 160-179/100-109
Stage 3 → 180/ >110
‘Pseudohypertension’ (erroneously elevated cuff
pressure as high as 50 mm of Hg when compared with
intra-arterial pressure due to exessive sclerosis of large
arteries) is differentiated from true hypertension by Osler’s
manoeuvre, which is done by inflating a blood pressure
cuff above the systolic pressure and palpating carefully the
radial and brachial arteries. If one of these arteries is palpable
despite being pulseless the patient is said to be Osler’s
positive. On the other hand, if the artery collapses and cannot
be palpated, it is said to be Osler negative. In the former,
cuff pressure readings exceed true intra-arterial readings
by 10-54 mm of Hg.
The pathogenesis of hypertension is generally attributed
to increased peripheral resistance especially in the renal
vessels. Renin secreted by the juxtaglomerular apparatus in
the kidneys acts on the globulin precursor of the plasma
(angiotensinogen) from liver and produces angiotensin-I.
The angiotensin-converting enzyme facilitates further
conversion of angiotensin-I to angiotensin-II, which is a
powerful vasoconstrictor. The angiotensin-II leads to
reabsorption of sodium and water from distal tubule of the
kidney and also increased secretion of aldosterone by direct
stimulation of adrenal cortex, with consequent retention of
salt. Thus two major determinants concerning the blood
pressure are identified i.e. extracellular fluid volume and
Renin- angiotension- aldosterone system (RASS). Besides,
the circulatory RASS, a tissue RASS exists which is activated
by the non-ACE pathway. The vascular sensitivity or
reactivity thereof determines the development of
hypertension.
The patients are usually symptom free and the
hypertension is often detected on routine examination. But
sometimes symptoms like palpitations, insomnia, irritability,
headache, and dizziness may be complained. The
palpitations are attributed to increased stroke volume or
due to increased catecholamine release as occurs in
phaeochromocytoma. The associated physical signs may
be attributed to the underlying cause or complications of
hypertension reflected in cardiac, cerebral, retinal and renal
manifestations.
Acquired Valvular Diseases (Refer to Chapter ‘Dyspnoea’)
Congenital Heart Disease
Congenital heart diseases like Atrial Septal Defect (ASD),
Ventricular Septal Defect (VSD), and Patent Ductus
Arteriosus (PDA) are associated with palpitations due to
increased left to right shunts.
An ejection systolic murmur with a fixed wide split of
the P2 in the pulmonary area is suggestive of ASD.
The pansystolic murmur in the 4th intercostal space
and a thrill in the 4th intercostal space with a loud P2 sound
is highly suggestive of VSD.
A continuous machinery murmur, maximal in the
second left intercostal space near the sternum is a clue for
PDA.
Acute Myocardial Infarction (Refer to Chapter Chest Pain)
Cardiomyopathy (CMP)
This predominant dysfunction of myocardium (excluding
the conventional ischaemic, hypertensive, valvular and cor
pulmonale lesions) is classified as congestive cardio-
myopathy, restrictive cardiomyopathy and hypertrophic car-
diomyopathy.
Congestive (dilated) cardiomyopathy is characterised by
cardiac dilatation with congestive heart failure (failure of
both left and right sided chambers and is manifested by
palpitations, dyspnoea and oedema). Examination may show
gallop sounds, murmurs of mitral and tricuspid
regurgitations and arrhythmias. Diastolic murmurs are absent
usually. Alcohol abuse incriminated. Viral infections usually
result in myocarditis (toxic myoarditis) which may be
associated with palpitations due to changes of rhythm and
may progress to congestive dilated CMP.
Restrictive cardiomyopathy is rigidity of myocardium
restricting ventricular filling and simulates constrictive
pericarditis. Fibroelastosis is one of the causes.
 Palpitations
Hypertrophic cardiomyopathy is marked hypertrophy
of the left ventricle especially in the interventricular septum
usually leading to obstruction of the ventricular outflow
tracts. The characteristic systolic ejection murmur is heard
along the left sternal border sometimes even at the apex
(Refer to Chapters ‘Chest Pain’ and ‘Syncope’). Cause is
unknown.
Noncardiac
In hyper kinetic circulatory states like anaemia and
thyrotoxicosis, palpitation is a common feature, which may
be due to high resting cardiac output (normal 2.5 to 4.4 L
per square metre of body surface area per minute) and
increase in the force of contraction and tachycardia. The
rate of blood flow is increased resulting in the full bounding
pulse and warm hands. Systolic pressure is often raised
with a wide pulse pressure. Palpitations are experienced on
exertion in mild anaemia and present at rest in severe types.
Of course, anaemia can be recognised by other glaring
features like pale conjunctiva or tongue and thyrotoxicosis
by the obvious enlargement of thyroid with tremors and
loss of weight.
In menopausal syndrome, the palpitations may be
associated with flushes and sweats.
If palpitations are associated with episodes of flushing,
diarrhoea or asthma, carcinoid syndrome may be the
underlying cause.
Hypoglycaemia may occur after over dosage of
hypoglycalmic agents or spontaneously. Features like
sweating, tremors, palpitations, feeling of apprehension,
occur due to catecholamine release, which disappear on
the administration of glucose.
Palpitations may be provoked by gastric distension or
dyspeptic symptoms or hiatus hernia. The latter is diagnosed
by the associated pain in the supine as well as bending
forward positions and relieved by sitting upright.
Palpitations, a feature of febrile states, are not prominent
in acute infections but fairly common in chronic infections
like pulmonary tuberculosis.
Drugs can produce palpitations by causing extrasystoles
or tachycardia.
Anxiety and phobic symptoms also cause palpitations.
The mechanism involved in this is increase in the force of
cardiac contraction, sinus tachycardia mediated via release
of catecholamines. Generally the heart rate increases on
exercise, but undue increase or failure to decrease on stopping
the exercise, is a feature of anxiety or cardiac neurosis
(neurocirculatory asthenia) (Refer to Chapter ‘Chest Pain’).
383
CLINICAL APPROACH
In the evaluation of palpitation, the first thing is to call for
clarification from the patient what he exactly means by
palpitation.
History
Further analysis of the palpitation revolves around the
following questionnaire.
1. Description of palpitation
i. Is it a missed heartbeat followed by a throb
(extrasystoles) or run of premature and strong beats?
ii. Is it a heavy heartbeat isolated (aortic regurgitation
or hypertension)?
iii. Is it a racing heart (paroxysmal tachycardia or sinus
tachycardia), i.e. rapid and regular?
iv. Is the racing heart irregular and chaotic (atrial
fibrillation)?
2. Since how long?
3. Periodicity?
4. How frequently it occurs?
5. Is the onset sudden or insidious?
6. Duration of palpitations: If it lasts for a moment, it is
likely to be extrasystoles.
7. Is the onset spontaneous or gradual?
8. Relieving factors: Is it relieved by any manoeuvres like
holding the breath or stooping or drinking ice water or
massaging neck in the carotid sinus region?
9. Provoking factors (effort, anxiety or any stressful
situation or gastric distension)
10. Associated features like tremors and loss of weight;
fatigue or dyspnoea as in anaemia or cardiac failure;
sweating, headache as in phaeochromocytoma; angina
or syncope or severe bradycardia
11. Any past history of rheumatic fever or ischaemic heart
disease?
12. Drug history—Salbutamol and antihypertensive drugs
(when postural hypotension may lead to palpitations due
to reflex tachycardia); and any excessive consumption
of tobacco or coffee.
Physical Examination
General Examination
It may not be useful always especially in the absence of the
symptom during the examination.
1. However, examination of the pulse is the most important
aspect.
a. Pulse Rate—If the pulse rate is between 100 to 140
beats, it is usually sinus tachycardia. If it exceeds, it
 384 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
is suggestive of ectopic tachycardia. If the rate is
slow with regular rhythm, it is either sinus
bradycardia or nodal rhythm or complete heart block.
b. Rhythm
i. If the rhythm is irregular and fast, it is suggestive
of atrial fibrillation or atrial flutter with varying
block or multiple premature beats.
ii. If the rhythm is irregular and at a normal rate, it
may be a treated case of atrial fibrillation or
premature beats.
iii. If the rhythm is irregular and slow, it may be
sinus bradycardia with ectopic beats or partial
heart block.
iv. If rhythm is regular and fast it is either sinus
tachycardia or paroxysmal supraventricular
tachycardia or atrial flutter or ventricular
tachycardia.
2. Blood Pressure should be checked to record any
unexpected rise or fall. Better record blood pressure in
the supine position as well as after standing for three
minutes; and also in both upper and lower extremities.
3. Temperature
4. Examination of the conjunctiva for evidence of anaemia
5. Evidence of thyroid enlargement
6. Examinations of hands—Particulary for evidence of
sweating and tremors.
Systemic Examination
Cardiovascular system
a. Pulse—(Vide supra)
b. Simultaneous palpation of the pulse and auscultation of
the heart and assess the regularity. If it is irregular, pulse
deficit may offer the clue. If it is more than 20, it is
suggestive of atrial fibrillation.
c. Examination of the cervical veins
i. If the normal ‘a’ ‘v’ waves are seen separately (‘c’
is rarely seen), it is suggestive of sinus tachycardia.
ii. If it is not distinctive, it is atrial tachycardia.
iii. Cannon waves—if cannon waves occur irregularly,
it is suggestive of complete heart block or multiple
ectopic beats or junctional tachycardia or ventricular
tachycardia. They occur regularly in nodal rhythm,
nodal ectopics and paroxysmal nodal tachycardia.
iv. If the ‘a’ waves are more frequent than the heart rate,
it may be atrial flutter with 2:1 ratio of atrioventricular
block. If the heart rate is more than the ‘a’ waves, it
is suggestive of ventricular tachycardia.
d. Position of the apical impulse and assessment of
cardiomegaly
e. Auscultation
i. Heart sounds—Auscultate the heart sounds
particularly for intensity and its variations, and other
abnormalities. The analysis of first heart sound is
particularly important in elucidating palpitations. The
first heart sound may be loud as in hyperkinetic
circulatory disorders or mitral stenosis or
tachycardias. It may be decreased in intensity if there
is a long delay between atrial and ventricular
excitations, i.e. prolonged P-R interval, or mitral
regurgitation. Its intensity may vary in complete heart
block, in atrial fibrillation, ectopic beats and
ventricular tachycardia. Sometimes, the first heart
sound may accentuate sharply from time to time in
complete heart block (Cannon sounds).
Wide splitting of the first and second sounds is
appreciable in ventricular tachycardia, whereas if the
sounds are single in a case of regular tachycardia, it
is suggestive of supraventricular tachycardia.
Aortic component of the second heart sound may
be accentuated in systemic hypertension and
pulmonary component in pulmonary hypertension
due to acquired valve disease or congenital heart
disease. It may be decreased in intensity due to aortic
stenosis or pulmonary stenosis.
ii. Any diastolic extra sounds: An abnormal third
(ventricular) or fourth (atrial) heart sound may be
heard in hypertension or cardiomyopathy (third heart
sound may be physiological and usually audible in
normal children and adults below 40 years).
Superimposition of atrial and ventricular added
sounds may give rise to summation gallop in
tachycardias which can be discerned as four sounds
by slowing the heart rate with carotid sinus
stimulation.
iii. Murmurs—For the evidence of congenital or
acquired heart diseases.
f. Bedside manoeuvres
i. Posture and excercise: Changes of posture and
exercise may result in heart rate, varying from minute
to minute and the increase in rate is gradually
progressive in sinus tachycardia, whereas in
paroxysmal tachycardia the rate is uninfluenced. In
atrial flutter, the ventricular rate may be fixed or the
rate may be increased in mathematical ratios
depending upon the variations in the block.
On exercise, multiple premature beats disappear;
whereas in atrial fibrillation, the rhythm becomes more
irregular.
 Palpitations 385

In sinus bradycardia, the rate gradually increases Motion Examination

with exercise whereas there is slight acceleration
For evidence of intestinal parasites like amoeba or giardia
or no change in the nodal rhythm. In sinoatrial block, the
or Hookworm.
rate doubles abruptly on exercise, whereas in partial heart
block there is abrupt slowing or a slight increase in
the heart rate. In complete heart block, there is no change Radiological Tests
at all. a. X-ray chest—For abnormal cardiac silhouette or any
ii. Carotid sinus pressure (one side only at a time)—In associated lung pathology.
sinus tachycardia, there is gradual slowing followed b. Barium meal X-ray—To account for dyspepsia.
by rapid return to the previous rate on release of
pressure. In paroxysmal supraventricular Surface ECG
tachycardia, the attack abruptly reverts to normal
It is the most deciding investigation in majority of cases.
sinus rhythm or no change.The response in nodal
Since the palpitations may be evanescent enough, it may
tachycardias is variable—slows the junctional
not be possible, although preferable, to record the ECG
discharge rate or terminates abruptly or no change.
during the attack of palpitations. It may reveal the
In paroxysmal ventricular tachycardia, there is
arrhythmias (ectopic tachycardias, sick sinus syndrome or
no effect at all. In atrial flutter, there is abrupt
AV. Block), ischaemic changes or ventricular hypertrophy.
slowing of the rate (without sinus rhythm being
It is always better to compare with the old ECGs if possible.
restored) and on release of the pressure, there is
Exercise ECG may be sometimes useful when the resting
abrupt reversion to the original rhythm. In atrial
ECG is not informative regarding rhythm disturbances or
fibrillation, slowing occurs although gross
ischaemic changes.
irregularity remains.
Prolonged ECG Recording This noninvasive investigation is
In sinus bradycardia or sinoatrial block or partial heart
useful in correlating the arrythmias with the symptomatology
block, the carotid sinus pressure results in further slowing.
and documenting the arrhythmias as well as the ischaemic
In nodal rhythm, the ventricular response may be slight
changes, if any. including silent ischaemia.
slowing or no change. This manoeuvre has no affect in
The ambulatory electrocardiographic monitoring (Holter
complete heart block. However, in cases of paroxysmal
recordings and dynamic electrocardiography) facilitates the
complete heart block, who present with sinus rhythm, the
evaluation, by studying larger number of cardiac cycles
carotid sinus pressure may produce Stokes-Adams attack
exceeding 1 lakh in 24 h. Analysis depends on identification
or result in paroxysmal heart block itself.
of QRS complexes by their shape and timing.
Abdominal examination Presence of tender hepatomegaly with The diagnosis of arrhythmia is based on the coincidence
associated increased jugular venous pressure and abnormal of symptoms with recorded rhythm disturbances.
physical signs over the precordium indicate heart failure. A symptomatic recording is seldom helpful. The finding of
a normal ECG during the symptoms may suggest that
Psychiatric examination Assess the psychiatric symptom-
arrhythmias is not the basis of the palpitations. The 24 h
atology particularly disorders of affect or the expressions
tape monitoring is valuable and brief arrhythmias are
of emotions such as anxiety or emotional lability (emotional
common findings on tape in asymptomatic patients. Hence,
incontinence).
it is essential to match the timing of the symptoms with the
relevant portion of the ECG. Event recorders (running solid
Investigations
state units which freeze a sample of the ECG on pressing a
These may be tailored depending on the index of suspicion. button by the patient) are an alternative to the prolonged
tape recordings.
Blood Tests
Exercise Test (Treadmill Stress Test)
a. Haemogram—to assess anaemia.
b. Blood sugar—for hypoglycaemia or diabetes mellitus. Ventricular ectopic ativity may be precipitated by exercise,
c. Serum thyroxine levels—T3 and T4 levels to assess the which may not be detected in the Holter’s monitoring
thyroid status. specially when they are infrequent.
 386 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Oesophageal Electrocardiography
This noninvasive technique is useful to diagnose
arrhythmias.
His Bundle Electrocardiograms
They are useful in evaluating the nature of the AV junctional
diseases or conduction delay in the His bundle or branches
or premature beats.
Echocardiogram
This can be carried out if necessary, to evaluate the cardiac
performance.
Electrophysiological Testing
This invasive procedure (involving introduction of multi-
polar catheter electrodes into the vascular system and
positioning the electrodes at various sites inside the heart
and recording electrical activity) may be necessary in very
exceptional cases, when a patient complains of angina or
dyspnoea or syncope during palpitations due to rhythm
disturbances and when noninvasive studies fail to reveal
the same.
TREATMENT OF PALPITATIONS
The crux of the problem in the treatment of palpitations is
to decide whether it is organic (cardiac or noncardiac) or
psychogenic. Palpitations, indeed cause fear out of
proportion to the gravity of the clinical setting. they are
usually innocent or rarely life threatening. Anxiety which
may be the cause or effect of palpitations is treated with
reassurance and tranquilisers. Clinical evaluation with the
aid of ECG, may establish the diagnosis.
Cardiac Origin
Physical manoeuvres, pharmacological agents and
cardioversion (electical) are usual modes of treatment.
Catheter ablation and surgical treatment of arrhythmias are
indicated in extraordinary circumstances.
Cardiac Arrhythmias
A. Disturbances in impulse formation
i. Sinus tachycardia: Precipitating cause is eliminated and
beta blockers given,
ii. Sinus bradycardia: No treatment is necessary. If
synocopal attacks occur, it may be treated as for Stokes-
Adams syndrome or sick sinus syndrome. (Refer to
Chapter ‘Syncope’).
iii. Escape rhythm: No treatment is necessary. Exercise or
atropine eliminates. Any underlying cause like
hypertension or coronary artery disease may be
simultaneously treated.
iv. Extrasystoles:
a. Atrial premature beaks—Same as for sinus
tachycardia.
b. Nodal premature beats—Ensure reassurance. Avoid
Tobacco, Alcohol, Caffeine and adopt general
measures, such as adequate sleep and free from
stress.
c. Ventricular premature beats—These may not require
treatment in majority of cases. However, if
troublesome in a healthy patient, betablockers, or
mexilitine or amiodarone are beneficial. Lidocaine is
indicated in ‘R on T’ types in postmyocardial
infarction patients. Treatment is directed by and large
at the underlying cause, if any.
v. Supraventricular Tachyarrhythmias:
a. Atrial fibrillation: Treatment revolves round (i)
control of ventricular rate (ii) restoration of sinus
rhythm (iii) maintenance of rhythm (iv) prevention
of embolic complications; while assessing to correct
any reversible cause and haemodynamic status.
If haemodynamically unstable (hypotension and angina),
and not responding to resuscitation, electrical cardioversion
(50-360 j) is adopted with prior heparin.
If haemodynamically stable, elective electrical or medical
conversion is programmed after oral anticoagulation for 3
weeks (Electrical cardioversion is not indicated in Chronic
Rheumatic Heart Disease).
i. Control of ventricular rate is done with digoxin or
betablockers (Propranolol or sotolol) or non-
dihydropyridine calcium channel blockers (verapamil).
ii. Restoration of sinus rhythm, in acute cases, is achieved
with drugs like amiodarone or Flecainide besides Digoxin
(Propafenone indicated when standard therapy has failed
or contraindicated). If paroxysmal-amiodarone or sotolol
or Flecaimide considered. If chronic–digoxin with or
without amiodarone advocated if resistant and recurrent–
amiodarone and flecainide recommended is achieved
with drugs like amiodarone or Flecainide besides Digoxin,
(Propafenone when standard therapy failed or
contraindicated) if paroxysmal-amiodarone or sotolol or
Flecainide considered; if chronic digoxin with or without
amiodarone; and if resistant and recurrent amiodarone
and Flecainide recommended. When it cannot be
 Palpitations
restored, chronic anticoagulation therapy is advocated
to avoid embolic complications.
iii. Maintenance of rhythm: If left ventricular hypertrophy
or valvular disease present, amiodarone is effective. (When d.
atrial diameter is <60 mm). In congestive heart failure,
amiodarone and dofitalide recommended. In coronary
artery disease, betablockers like sotalol, and in hypertension
flecainide and propafenone and in WPW syndrome ibutilide e.
or procainamide are the drugs of choice.
iv. Embolic complications are prevented by anticoagulation
for 3 weeks before medical cardioversion and for 4 weeks
after cardioversion to achieve target INR of 2.5 or
prothrombin time 2.5 times of controls. (If left atrial
thrombi are seen by transoesophageal echocardiography,
cardioversion is better delayed). Left atrial appendage
resection may be undertaken, if anticoagulation is
ineffective or contraindicated.
Interventional options (I) AV Nodal ablation or
modification for rate control (2) Radiofrequency catheter f.
ablation of surgical maze procedure; pulmonary vein isolation
or correction of valvular lesions are the options for the
maintenance of sinus rhythm, apart from contemplating atrial
pacing or implanatable atrial defibrillator.
b. Atrial flutter: Digoxin, betablockers or verapamil
are used to control the ventricular rate. Other useful
drugs are amiodarone, disopyramide, quinidine or
flecainide. Synchronised direct current cardioversion
at low energies is usually effective. Atrial overdrive
pacing is the alternative manoeuvre.
c. Atrial tachycardia: Amiodarone is the preferred drug.
Other Antiarrhythmic drugs like Flecainide,
proparfenone or sotalol are the alternatives. Nodal g.
blocking or slowing drugs like betablockers (esmolol)
or calcium channel blockers (Verapamil or diltiazem)
may be required in recurrence, if not Beta Blocked,
or if WPW syndrome is not present) or adenosine
are considered. Digoxin does not terminate though
slows down the rate catheter ablation in selected
cases is indicated. Electrical cardioversion is
ineffective. The underlying cause, if any, is to be
Fig. 25.5C: PSVT—After treatment with verapamil (5 mg IV over 3 minutes) normal sinus rhythm restored.
Note distinct P and T waves
387
eliminated. Physical measures or adenosine may be
used to demonstrate AV Block with persistence of
the atrial arrhythmia.
Nodal Tachycardia: Withdraw any offending drug
like digoxin, otherwise IV amiodarone or betablockers
or calcium channel blockers may be useful
cardioversion is not indicated.
Atrioventricular nodal reentrant tachycardia:
(AVNRT). If physical measures like valsalva’s or
increasing vagal tone by carotid sinus massage (one
side at a time) fail, adenosine IV (I2 mg) aborts the
attack (adenosine may exacerbate bronchospasm in
astumaties). Other useful drugs are betablockers,
amiodarone, flecainide, digoxin. Failure of the above
treatment may call for cardioversion. Electrical pacing
may be helpful. Radiofrequency ablation is useful in
long-term cases. Prophylaxis with amiodarone or
sotalol beneficial.
Atrioventricular re-entrant Tachycardia (AVRT):use
of vagal manoeuvres and IV adenosine should be
used to terminate the episode veerapamil 5 mg IV
over 3 minutes is an alternative (Fig. 25.5C). This
shold not be given if β-blocker is given vecently.
(Ability to block AV node by adenosine in useful for
terminating re-entry SV arrhythmias as the node
forms part of circuit). The treatment options are
same as above. When AV nodal agents are
unsuccessful, electrical cardioversion is indicated.
Radiofrequency ablation may be considered in
selected cases.
Wolff-Parkinson-White (WPW) Syndrome:
Prophylaxis with amiodarone flecainide,
propafenone, disopyramide are favoured though no
treatment is required in presence of normal sinus
rhythm only. Drugs like digoxin, verapamil,
betablockers, lignocaine are to be avoided. Radio-
frequency ablation is the choicest option. In selected
cases, surgical ablation of accessory pathway
contemplated.
 388 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
In patients with pre-exicited atrial fibrillation, electrical
cardioversion is to be done as an emergency. If not feasible,
amiodarone or flecainide used. No digoxin, betablockers or
calcium channel blockers should be given. Amidarone is
recommended for prophylasis. In pre-excited AVRT, treatment
is initiated with adenosine or amiodarone or flecainide apart
from vagotonic measures (Carotid sinus massage).
vi. Ventricular tachyarrhythmias:
a. Ventricular tachycardia—Intravenous lignocaine
given as a bolus 1.5 mg/kg followed by an infusion
of 2-4 mg/min in 2-4 h. If recurrs, Procaineamide
or Amiodarone (medical cardioversion) can be given
followed by DC. In resistant cases, Bretylium tosylate
IV may be given (medical defibrillator). Flecainide
or sotalol are alternatives. In haemodynamic
compromise, synchronised DC cardioversion with
100-400 J can be done followed by lignocaine or
amiodarone intravenously. Oral prophylaxis with
amiodarone or sotalol can be continued. If not
adequately controlled, automatic intracardiac
cardioverter defibrillator may be implanted, or
catheter ablation or surgery of isolated site
entertained.
In Torsades de pointes IV magnesium or lignocaine given
while medications known to prolong QT interval are
withdrawn, besides correcting any electrolyte imbalance.
b. Ventricular fibrillation—Immediate treatment with
defibrillator (300-400 J) along with adrenaline 1 mg
IV (10 ml of 1 in 10000) followed by 20 ml of saline
flush. Repeat defibrillation and adrenaline every three
minutes for three cycles, while continuing
cardiopulmonary resuscitation. (CPR should not be
stopped for > 10 sec except for defibrillation). When
there is response, Lignocaine 100 mg IV to be
repeated followed by 2-mg/min infusion or
amiodarone (5 mg/kg) intravenously. Correct
reversible causes like hypoxia, with oxygen,
hypokalaemia with potassium supplements and
Acidosis with 50 ml of 8.4% sodium bicarbonate
IV. Asystole due to complete heart block or sick sinus
syndrome must be distinguished from that of
venticular fibrillation as treatment of former differs
(Refer to Chapter ‘Syncope’) Long-term prophylaxis
with antiarrhythmic drugs like lignocaine,
Procaineamide or Bretylium can be considered.
Automatic implantable cardioverter defibrillator is
recommended if the ejection fraction is <40 per cent.
If such measures are not immediately feasible,
cardiopulmonary resuscitation (basic life support, i. e. clear
air way, mouth-to-mouth breathing, and external cardiac
massage) is instituted within 2-4 min while seeking for
advanced cardiac life support. (Refer to Chapter ‘Syncope’).
The complete loss of cardiac function suddenly, can
result not only from ventricular fibrillation or asystole but
also from electromechanical dissociation, i. e. ECG is normal
without pulse, when 10 ml of 10% calcium gluconate IV is
given and 1 mg of adrenaline IV is indicated every 5 min.
Prognosis is poor in myocardial than correctable
extramyocardial causes of electro-mechanical
dissociation.
c. Ventricular extrasystoles- (Vide supra)
B. Disturbances in impulse conduction:
i. Sinoatrial Block: Treatment is rarely necessary.
Withdraw any offending drug. If syncopal attacks
occur, atropine may be given 0.6-1mg sc or
epinephrine 0. 3 to I cc of 1 in 1000 solution may be
administered.
ii. AV Block—Refer to Chapter ‘Syncope’
C. Disturbances in impulse formation and conduction:
1. Sick Sinus Syndrome (Refer to Chapter ‘Syncope’).
i. Sinus Bradycardia—Vide Supra.
ii. Superventricular Tachycardia alternating with
bradycardia—Vide supra.
iii. Sinus pause
If the pause is sufficiently long, syncopal attacks may
occur. If troublesum despite drugs like atropine, Permanent
pacemaker implantation is beneficial.
iv. Sinoatrial Block-Vide supra.
2. Hypertension-Refer to Chapter ‘Headache’.
3. Valvular lesions
Aortic regurgitation and mitral regurgitation can be
stabilised with vasodilators. Other Valvular lesions as well
as congenital heart lesions may also be treated medically
and surgical intervention is undertaken if warranted.
4. Acute Myocardial Infarction Refer to Chapter ‘Chest
Pain’.
5. Cardiomyopathy (CMP)
Congestive CMP
Treatment is as for congestive heart failure (Refer to Chapter
‘oedema’) oral anticoagulation and appropriate anti-
arrhythmic drugs are instituted before considering cardiac
transplantation. Immunosuppressive drugs may be tried.
Hypertrophic obstructive CMP (Refer to Chapter ‘Syncope’)
Restrictive CMP
Restrict salt. Display diuretics and oral anticoagulants. Treat
the specific cause like sarcoidosis; amyloidosis;
haemochromatosis endomyocarditis or fibroelastosis.
 Palpitations
Noncardiac Origin
1. Anaemia—(Refer to Chapter ‘Fatigue’).
2. Thyrotoxicosis—(Refer to Chapter ‘Goitre’).
Menopausal syndrome—(Refer to Chapter ‘Obesity’).
Carcinoid syndrome—(Refer to Chapter ‘Chronic
Diarrhoea’ and ‘Pruritus’)
3. Hypoglycaemia—(Refer to Chapter ‘Coma’)
389
4. Flatulence—(Refer to Chapter ‘Dyspepsia’)
5. Febrile States—(Refer to Chapter ‘Pyrexia of Unknown
Origin’)
6. Tobacco, alcohol, caffeine and drugs inducing
palpitations are prohibited.
7. Anxiety States—(Refer to Chapter ‘Fatigue’).
Neurocirculatory asthenia—(Refer to Chapter ‘Chest
Pain’)
390 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Paraplegia
26
The presentation of this symptom is very complex since
there are many modalities in operation. Nevertheless, a careful
interrogation and analysis will usually throw light regarding
the nature of the condition whether it is organic or functional.
If organic, whether it is neurological or not. If it is non-
neurological simple weakness of the legs as a component
of general weakness or rheumatoid arthritis which may
produce some difficulty in using the lower limbs indirectly.
The neurological causes of the weak limbs are usually due
to disease of the spinal cord (Fig. 26.1) and roots or spinal
and peripheral nerves, occasionally due to disorders of the
muscles or intracanial lesions. Two cardinal points are of
primary importance in approaching these cases.
1. Whether it is of sudden or gradual onset.
2. Whether the tone is spastic or flaccid.
Fig. 26.1 Ascending and descending tracts in the cross-section of spinal cord depicting their functions
Sometimes, spastic paraplegias may have flaccidity to
begin with for about three weeks due to spinal shock.
Similarly paraplegia in extension with extensor hypertonia,
(due to incomplete involvement of the spinal cord affecting
the pyramidal tracts only) may develop into paraplegia
in flexion (due to coplete involvement of the cord
including reticulo spinal tract). So the tone has to be
interpreted carefully in relation to other features, whether it
is spinal shock or paraplegia in flexion as occurs in
trauma without the intermediary stage of paraplegia in
extension.
CAUSES OF PARAPLEGIA
Causes of paraplegia are pointed out in Table 26.1.
 392 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Table 26.1: Causes of paraplegias

Contd...
I. Spastic Paraplegias B. Gradual onset
A. Acute onset a. Hereditary
a. Spinal i. Myelodysplasia
i. Acute myelitis ii. Peroneal muscular atrophy
ii. Spinal cord injuries b. Motor neurone disease
iii. Cord compression c. Cauda equina lesions
1. Pott’s disease d. Peripheral neuropathy
2. Secondaries (vertebra) e. Myasthenia gravis
3. Haemorrhage into a syringomyelic cavity f. Myopathies
4. Metastatic epidural abscess
iv. Cord infarctions
v. Caisson disease Spastic Paraplegias of Acute Onset
b. Cerebral
i. Thrombosis of the unpaired anterior cerebral artery Spinal
ii. Thrombosis of superior sagittal sinus Acute myelitis: It may be due to infections or demyelination.
c. Functional: Hysteria.
a. Infections
B. Gradual onset
a. Spinal i. Pyogenic;
i. Cord compression ii. Tuberculosis;
ii. Infections (Erb’s paraplegia) iii. Leutic; and
iii. Degenerative (Motor neurone disease) iv. Herpes zoster
iv. Demyelinating (Multiple sclerosis) b. Demyelinating disease
v. Deficiency disorders (nutritional neuropathies) i. Disseminated encephalomyelitis;
1. Subacute combined degeneration of the cord (vitamin
ii. Disseminated myelitis with optic neuritis; and
B12 neuropathy)
2. Pellagra
iii. Disseminated sclerosis
3. Spastic paraplegia-lathyrism Initially there is sudden onset of flaccid paralysis of the
vi. Developmental lower limbs, with pain in the back at the level of the lesion.
1. Syringomyelia There is sensory loss with a horizontal segmental level and
2. Hereditary spastic paraplegia impairment of sphincter control with retention of urine. The
3. Friedreich’s ataxia tendon reflexes are diminished and plantar reflex is extensor.
b. Cerebral
Later it becomes spastic with exaggerated reflexes.
1. Cerebral diplegia
2. Hydrocephalus
Sometimes, it may be less sudden due to paraplegia in
3. Parasagittal meningioma extension with slight sensory loss. Myelitis is confined to
II. Flaccid paraplegias few segments longitudinally (transverse) or extending
A. Acute onset upwards (ascending).
a. Spinal The CSF shows excess of protein and excess of cells
i. Stage of spinal shock: (polymorphs) in pyogenic myelitis and mononuclears in
1. Acute myelitis
others. If there is pyogenic infection elsewhere in the body,
2. Acute cord trauma
3. Acute cord infarction the myelitis may be attributed to pyogenic infection.
ii. Acute poliomyelitis Tuberculous myelitis may result from tuberculous
iii. Spinal anaesthesia (caries) of the spine. The paraplegia may also be due to
iv. Polyneuritis (Guillain-Barre syndrome) compression, from tuberculous pachy meningitis or
v. Acute cauda equina lesions extradural tubercular abscess or interference with the
vi. Muscles
vascular supply of adjacent segments either by endarteritis
1. Polymyositis
2. Metabolic myopathies or compression of the radicular arteries.
i. Periodic paralysis syndrome Leutic infections may result in meningomyelitis due to
ii. Myoglobinuria meningovascular lesions. A history of exposure with positive
b. Brain stem stroke (Pons) (Refer Chapter ‘Coma’) VDRL is usually forthcoming. The CSF shows excess of
c. Hysteria cells-mononuclear and raised protein (increased globulin is
Contd... invariable) with a positive serology. This is uncommon now.
 Paraplegia
Herpes zoster infection extends rarely to the spinal cord
causing necrosis of the cord and myelitis. Paraparesis with
myoclonus or hiccups may occur. The vesicular eruption
in segmental distribution is diagnostic and in case of doubt
zoster antigen may be demonstrated in the cells of CSF.
When myelitis is due to demyelinating disease like acute
disseminated encephalomyelitis, features of cerebral lesions
may be present. Flaccid paralysis of the limbs with a loss
of deep reflexes and presence of extensor plantar response
may develop. Bladder disturbances like retention or
incontinence and a variable sensory loss are often associated.
CSF may show excess of mononuclear cells and raised
protein or may be normal. Fundus examination shows no
abnormality. History of specific fevers or vaccination may
be forthcoming.
In disseminated myelitis with optic neuritis, the occular
lesions of pain in the eyes and bilateral central scotoma or
loss of vision may occur simultaneously or separately. The
spinal cord lesion is of transverse myelitis type. Fundus
examination shows a swelling of the disc disproportionate
to the loss of vision.
In disseminated sclerosis, acute form is uncommon.
The paraplegia, sensory loss, exaggerated tendon reflexes,
extensor plantars and sphincter disturbances may be seen
along with or without cerebral manifestations like
convulsions, cranial nerve palsies, nystagmus and vertigo.
Spinal cord injuries If the spinal injury is severe as to result
in complete interruption of the spinal cord, it leads to flaccid
paraplegia due to spinal shock with loss of all modalities of
sensation and reflexes below the lesion and paralysis of the
bladder and rectum.
When the shock passes off in about three weeks time,
the reflex activity is restored and paraplegia in flexion
appears.
In less severe injuries, where the complete interruption
is not there as in spinal concussion, the disturbances may
be sudden or gradual and features vary from paralysis with
sensory loss or mere paralysis without sensory loss or a
Brown-Sequard syndrome. Spinal concussion results in
temporary paraplegia with sensory loss of posterior column
type predominantly.
Cord compression Spinal cord compression may come
suddenly or gradually. If it is sudden, there is flaccid
paraplegia due to spinal shock with a horizontal level of
sesory loss and absent reflexes with sphincter disturbances-
the picture is that of acute myelitis. In vertebral diseases
considerable pain in the spine with an angular deformity
and obvious radiological evidence of destruction of vertebra
is common. In haematomyelia, dissociated sensory loss is
393
characteristic apart from acute paraplegia.
The usual causes are:
1. Pott’s disease
2. Neoplasma (metastatic deposits)
3. Multiple myeloma
4. Fracture dislocation
5. Epidural abscess
6. Haematomyelia
7. Haemorrhage from angioma
Cord infarctions When the anterior spinal artery is affected,
there is weakness of the muscles innervated with loss of
pain and temperature on the opposite side. Similarly, if one
posterior spinal artery is involved, all modalities of sensation
are effected at the level of the lesion and spastic paralysis
with loss of joint and vibration sense, below the lesion on
the same side.
The vascular lesions of the spinal cord result in softening
of the ischaemic portion of the cord which is terned
myelomalacia.
Caisson disease In Caisson disease or compressed air
sickness, the tissues of those working at high pressures in
the underground tunnels or submarine works, absorb the
gases of the air, if the workers are transferred to normal
atmospheric pressure suddenly. These gases, specially
nitrogen in solution, in the tissues are released as bubbles of
gas in the nervous system causing disruption of the nerve
tissue and interference of the blood supply. Symptoms occur
in half an hour to a few hours after decompression and
depend on the localisation of the bubbles of nitrogen. Root
pains are common at onset followed by acute paraplegia
with anaesthesia and sphincter paralysis.
Cerebral
• Thrombosis of the unpaired anterior cerebral artery It
may result in paraplegia with or without cortical type of
sensory loss.
• Thrombosis of superior sagittal sinus It may lead to
bilateral pyramidal lesions with the involvement of the
lower limbs as well as headache, vomitting, and
convulsions. The veins of the skull may be congested
and papilloedema sometimes may be present.
Functional
Hysteria Hysterical paralysis is usually of sudden onset. It
may be associated with flaccidity or hypertonia. Flaccid
paralysis is very common. Since the weakness of limbs is
related to the ideas of the affected person, the distribution
is often paradoxical, i.e. gross weakness of the limbs may
 394 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
be present in lying position but not while standing or the
weakness is related to one joint. The contraction of the
antagonistic muscles as well as prime movers occur when
a voluntary movement is attempted. The rigidity may increase
in proportion to the passive movement of the rigid part.
The tendon reflexes, abdominal reflexes and plantars are
not affected. The sensory loss does not correspond to that
of a sensory tract or a spinal segment or a peripheral nerve
lesion. The gait is bizarre with variable stiffness and feet
appearing glued to the ground and remarkable spinal
curvatures. The other associated features of the hysterical
personality may be forthcoming and intense emotional
reaction may be precipitated when attempts are made to
break the symptom complex.
N.B: The flaccidity of accute paraplegias may become
chronic spastic paraplegia when the neuronal shock passess
off, whereas chronic paraplegias will have spasticity present
right from the beginning.
Spastic Paraplegias of Gradual Onset
Spinal
Cord compression Compression of the spinal cord may be
divided into
1. Extramedullary
a. Exradural (Vertebral)
b. Intradural (Meninges and nerve roots)
2. Intramedullary
Extramedullary Extradural Lesions
i. Disc prolapse: Though sudden paraplegia due to acute
central lumbar disc prolapse at L1-L2 is rare, it is usually
a slow progressive degenerative process of the disk with
intervertebral disc protrusions, resulting in cord
compression leading to spondlytic myelopathy. Most
often, disc protrusion compresses the spinal nerve one
segment below, (e.g. 5th lumbar disc protrusion
compressing the first sacral nerve) resulting in weakness
of one leg, often preceded by backache and sciatica.
ii. Extradural tumours: Vertebral neoplasm may be a
sarcoma or a cavernous haemangioma or myeloma or
osteoma, or more often vertebral metastasis. In
extradural compression, root pains occur early and the
spinal compression features are usually symmetrical and
bilateral. The sequence of development is motor
symptoms, sphincter disturbances and sensory changes.
A gibbus (angular deformity of the spine) and radiological
evidence of vertebral destruction are usually obvious.
The onset of the symptoms is rarely gradual (Vide supra).
The protein content of CSF is slightly increased.
Extramedullary Intradural Lesions
The sequence of symptoms are usually sensory, motor and
sphincter disturbances. The first symptom is usually sensory
with pain radiating along the affected root. It may be
unilateral or bilateral, intensified by coughing or sneezing or
movements of the spine. Paraesthesia may result by
compression of the ascending sensory tracts. The motor
symptoms develop later and they are confined to lower limbs
usually, if the lesion is over the lower half of the dorsal
region and lumbar segments. It is asymmetrical in the early
stages, i. e. one limb being involved before the other. The
onset of symptoms is usually gradual.
When the anterior roots are involved, lower motor neuron
signs at that level and upper motor neuron signs with sensory
loss below the level of the lesion, and sphincter disturbances
may present themselves.
The clinical features of spinal compression at different
levels vary as follows.
a. If the lesion is in the thoracic cord, spastic paraplegia
with corresponding objective sensory changes is present.
b. If the lesion is in the lumbar segments (L3 - L4), there is
lower motor neuron lesions of the thigh muscles and
spastic paralysis of the remaining muscles with loss of
knee jerk and exaggerated ankle with corresponding
sensory loss.
c. If the lesions are in the sainal segments, (S1 - S2) the
calf muscles are atrophied and hamstrings are weak with
loss of ankle jerk and preservation of knee jerk with
appropriate sesory loss.
Vertebral tenderness on pressure or percussion may be
elicited although the vertebral are normal. The protein
content of the CSF is greatly increased which is yellow
in colour (xanthochromia), With a normal cell count
below block, i.e. Froin’s syndrome.
The causes of extramedullary intradural lesions are
a. Meningeal
i. Pachy meningitis
ii. arachnoiditis
iii. meningioma
iv. infiltration due to hodgkin’s disease and leukaemia
and
v. rarely hydatid cyst
b. Nerve roots-Neurofibroma
Intramedullary Lesions
Distinction from extramedullary lesion may sometimes, not
be possible. However, in cases of intramedullary sources
of compression (ependymomas, gliomas and angiomas),
 Paraplegia
the root pains are not common. Motor symptoms are usually
bilateral with dissociated sensory loss below the level of the
lesion. Bladder and rectal disturbances may occur early.
Local tenderness of the spine is unusual and auscultation
may show bruit over the site of angioma, Block in the
subarachnoid space occurs later.CSF may show usually
low protein content than the extramedullary compression.
Imaging procedures like CT or MRI are diagnostic
(Fig. 26.2).
Fig. 26.2: MRI of spinal cord showing
intramedullary ependymoma
Segmental localisation in relation to vertebra: Since the
spinal cord terminates at L-1 vertebra, the spinal segments
do not correspond with the vertebrae numerically. To
localise the exact vertebral level corresponding to the
compression in terms of spinal segments, for cervical
vertebrae add one; for upper dorsal (1 to 6) add two; and
for lower dorsal (7 to 9) add three. The 10th dorsal arch
overlies L-1 and L-2 segments. The 11th dorsal arch overlies
L-3 and L-4. The 12th dorsal arch overlies L-5. The sacral
and coccygeal segments lie opposite to L-1 vertebra.
Infection (Erb’s paraplegia) In Erb’s paralysis there is a gradual
progressive paraplegia with an early involvement of the
bladder and minimal sensory changes due to spinal
meningovascular lesions of leutic origin.
Degenerative (Motor neurone disease) In amyotrophic lateral
sclerosis, there may be stiffness and dragging of the muscles
especially when tired or painful cramps may be the inaugural
presentation. The upper motor neurone signs develop in the
395
lower limbs and the presentation is entirely motor without
any sensory changes. The disease becomes overt when
anterior horn cells are involved leading to fasciculation and
atrophy in upper limbs, i.e. lower motor neurone signs.
Features of bulbar palsy may be encountered.
Demyelinating [Disseminated sclerosis (Multiple sclerosis)]
It may present as motor weakness of the lower limbs and
later spastic paraplegia and ataxia with posterior column
involvement and sphincter disturbances like precipitancy.
Other features like that of cerebellar like intention tremor,
scanning speech, nystagmus or brainstem features like
transient diplopia with spells of vertigo and vomiting may
also encountered. However, ocular symptoms like blurring
vision with central scotoma and papillitis followed by
temporal pallor of the optic disc is highly characteristic.
Remissions and relapses are well-documented.
CSF may show increased mononuclear cells and
moderately raised protein with raised gamma globulin (1gG)
and reduced C9 complement. Evoked potentials may be
useful and CT scan may demonstrate focal areas of
demyelination seen as reduced density and contrast
enchancement.
Deficiency disorders Nutritional deficiencies may result in
neurological disorders affecting the peripheral nervous
system (vide infra) and central nervous system like cord,
e.g. B12 deficiency and nicotinic acid deficiency.
• Subacute combined degeneration of the cord: It is usually
accompained by symmetrical paraesthesia, stocking and
glove type of sensory loss due to peripheral nerve
involvement and weakness of the muscles and upper
motor neurone signs due to pyramidal tract involvement
and ataxia with loss of joint and vibration sense due to
posterior column degeneration. The tendon reflexes
depend upon the extent of peripheral neuropathy. So
ankle jerks or later knee jerks may be lost. Glossitis,
macrocytic anaemia and histamine fast achlorhydra are
other features of this type of degeneration due to
deficiency of vitamin B12.
• Pellagra: In chronic nicotinic acid deficiency cases there
may be degeneration of posterio-lateral columns of the
spinal cord with spasticity and exagrated tendon reflexes
with loss of vibration and position sense resulting in
ataxia. In addition there will be dermatitis, diarrhoea and
dementia.
• Lathyrism: Spastic paraplegia of nutritional origin may
be due to directly dietary deficiency as above or may be
due to a toxic dietary factor as in consumption of
Lathyrus sativus pulses (kesari dal) contaminated with
 396 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
seeds of Vicia sativa (akta). It is said that consumption
of diets with over 30% of kesari dal containing the
neurotoxic principle (i.e.b-oxalyl amino alanine) for a
period of six months results in larythism. The onset is
with stiffness of legs followed by slow progressive
spastic paralysis of the lower limbs. Objective sensory
changes clinically are absent though sclerosis of the
posterior columns may be seen. The various clinical
stages are described as (a) latent stage; (b) no-stick; (c)
one-stick; (d) two-stick stage; and (e) crawler stage.
Developmental
• Syringomyella: The compression of pyramidal tracts
results in the weakness of the lower limbs with upper
motor neurone signs; associated with wasting of the
small muscles of the hands due to involvement of the
anterior horn cells with insidious onset. There is
dissociated sensory loss over the areas innervated from
the affected segments of the cord.
In haematomyelia (haemorrhage into a syringomyelic
cavity), similar signs may develop suddenly.
• Hereditary spastic paraplegia: Usually affects several
siblings in childhood between 3 to 15 years wherein
progressive weakness of lower limbs occurs. Spasticity
with exaggerated reflexes and extensor plantar reflexes
are elicited.
• Friedreich’s ataxia: It is a heredofamilial disorder with
degeneration of cerebellar or spinocerebellar neurones
and posterior lateral colmuns usually seen in adolescence
with early complaints of weakness and unsteadiness of
stance. The tendon reflexes are lost with extensor plantar
and loss of joint and vibration sense. In addition, pes
cavus and scoliosis are present. Nystagmus and
dysarthria or optic atrophy may be seen.
Cerebral
Cerebral diplegia The weakness and spasticity are present
since birth due to defective development of the pyramidal
tracts. But the prenatal or natal cases (symptoms at birth)
are likely to improve whereas the postnatal cases (symptoms
in the first three years of life) are likely to progress. The
extensor plantar response present in infancy continues and
the spasticity is predominant with plantar flexion of the ankle,
extension at the knee and adduction at the hip resulting in
scissor attitude of the legs and gait.
Hydrocephalus (increased volume of CSF within the skull
with or without increased pressure). In hydrocephalus, the
lower limbs may show weakness and spasticity with
exaggeration of tendon reflexes with extensor plantar due
to ventricular distention causing thinning of the cerebral
hemispheres, associated with atrophy of the cortical ganglion
cells.
It may be congenital or acquired. There is conspicuous
enlargement of the head in the congenital variety whereas
in acquired obstructive hydrocephalus symptoms of
increased intracranial pressure are conspicuous.
The volume of CSF is increased with normal pressure
(compensatory) or with increased pressure (hypertensive).
The latter can be obstructive or communicating. If the
pressure within the lateral ventricles differs from pressure
in the subarachnoid space, it is obstructive, whereas the
pressure is same in both ventricles and spinal spaces, in
communicating type.
Parasagittal meningioma (Meningioma of the falx cerebri)
Meningioma arises from the cells of the arachnoid villi and
projects into the dural venous sinuses. A tumour of the falx
in paracentral region produces weakness of the lower limbs
usually beginning in the feet. Postural sensibility is impaired
and retention of urine may occur. Jacksonian convulsions
occur due to excitation of corticospinal fibres.
X-ray of the skull may show local erosion of the bone
superficial to meningioma and new bone formation, in the
form of spicules, around the eroded area with a network of
vascular channels of the bone surrounding the spicules.
FLACCID PARAPLEGIAS
Acute Onset
Spinal
Stage of spinal shock (Acute Myelitis, Acute Cord Trauma,
Acute Cord Infarction) (Vide Supra)
Acute poliomyelitis Muscular weakness and/or paralysis of
the lower limbs is more common than the upper limbs due
to poliovirus infections. Paralysis is flaccid in type with
lower motor neurone signs without sensory loss (due to
the involvement of anterior horns cells of the grey matter
of the spinal cord) and asymmetrical in distribution since
only some muscles are affected leaving others behind. It is
always preceded by fever and headache with pain in the
limbs associated with tenderness. In this ascending type, it
spreads upwards and respiratory paralysis may result which
can be recognised if the subject fails to count beyond 12
with one deep breath. Improvement sets in towards the end
of first week with subsequent wasting of muscles and
contractures.
In adult poliomyelitis, the clinical picture is that of acute
transverse myelitis without sensory loss.
 Paraplegia
The diagnosis is confirmed by CSF analysis wherein
there is rapid increase of cells up to 250 per c.mm.
(lymphocyte being preponderant cell) and raised protein.
Spinal anaesthesia Acute necrotising myelitis following spinal
anaesthesia consists of paraplegia of sudden onset associated
with wasting of muscles, impaired sensations and loss of
sphincter control.
Guillain-Barre Polyneuritis: It is an acute postinfective
demyelinating ascending neuropathy, mostly motor, affecting
proximal muscles. It may advance to affect all limbs and
cranial nerves; with possible respiratory involvement.
Albumino cytological dissociation of CSF is characterstic
(Vide infra).
Acute cauda equina lesions (Vide infra).
Muscles
i. Polymyositis (Vide infra)
ii. Metabolic myopathies
• Periodic paralysis syndrome: Periodic paralysis may have
familial tendency with or without changes in serum
potassium levels. Hypokalaemia may give rise to flaccid
paralysis of voluntary muscles suddenly, lasting for
several hours. Determination of serum potassium levels
may not be contributory. Evaluation of urinary potassium
may be helpful in accounting for the deficit. (Urinary
excretion is less than 20 mEq. per litre in gastro intestinal
causes whereas in conditions like excess diuretics,
mineralocorticoid activity; and renal tubular disease, the
urinary concentration will exceed 20.) Recurrent flaccid
paralysis due to potassium deficiency can occur in
Conn’s syndrome (primary aldosteronism) or hyper-
thyroidism and familial periodic paralysis also. The latter
is fairly uncommon with periodical attacks of paralysis
lasting for few hours to several days precipitated by a
high carbohydrate meal or after excessive exercise.
The ECG may shows low flat T-waves and
prominent U-waves. Prolonged P-R interval.
Occasionally, in hyperkalaemia muscular weakness
can occur as in adynamia episodica hereditaria (periodic)
or renal failure (single attack) where the serum potassium
content is high and the ECG shows tall T waves. The
urinary potassium does not increase. Drugs like
Losartan; Addison’s disease; Metabolic acidosis; Any
delay in analysis or haemolysis in the sample are some
causes of hyperkalaemia.
• Myoglobinuria: Myoglobinuria can occur in acute forms
of polymyositis, in crush injuries of muscle or necrosis,
acute alcoholic indulgence or idiopathic. It is chracterised
by muscle pain and tenderness with weakness of the
limbs which usually clears up in a couple of days time,
accompained by myoglobinuria.
397
Functional
Hysteria Flaccid paralysis may suddenly occur in hysteria
where tendon reflexes are normal with paradoxical posture
of the affected limbs. The sensory changes may be glove
and stocking type but the anaesthetic area is demarcated
from the normal area of sensibility by a sharp border unlike
polyneuritis where the transition is always gradual.
Faccid Paraplegia of Gradual Onset
Hereditary
Myelodysplasia Myelodysplasia is a heredo familial cause of
flaccid paraplegia. In children, there is weakness of the
legs with dissociated sensory loss, absent reflexes, impaired
sphincter control and examination of the spine shows
meningocele or a sacral dimple. Spina bifida is usually
associated which may be seen radiologically.
Peroneal muscular atrophy The early symptoms are muscular
weakness and wasting beginning symmetrically in the
peroneal or small muscles of the feet and later those of the
hands; confining to the peripheral parts of the limbs only.
The wasting tends to spread proximally up to the junction
of the middle and lower thirds of the thigh, leading to so
called ‘inverted champagne bottle’ appearance. There may
be slight superficial sensory lose over the periphery of the
limbs. The tendon reflexes and the planter reflexes are
usually lost.The sphincters remain normal. It is a hereditary
disorder usually occurring in adolescence, characterised by
the degeneration of peripheral nerves with secondary
changes in the anteior horn cells of the spinal cord.
Motor Neurone Disease
The degeneration of anterior horn cells of the spinal cord
leading to weakness and wasting of the affected muscles
invariably occur in the upper limbs one after another
(progressive muscular atrophy). Occasionally, the atrophic
weakness may occur in the anterior tibial muscle and
peroneal, resulting in uni or bilateral foot drop.
Cauda Equina Lesions
Refer to Chapter ‘Low Backache’.
Peripheral Neuropathies
They may be categorised as
1. Polyneuropathy (symmetrical)
2. Mononeuritis multiplex (asymmetrical)
3. Mononeuropathy
 398 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
The pathology may be axonal degeneration with normal
or slightly reduced conduction velocity or segmental
demyelination with either completely blocked or slowed
conduction. The presentation may be predominantly motor
sensory or mixed. Polyneuropathy is generalised
derangement of function of several peripheral nerves
(including cranial nerves) simultaneously, with symmetrical
and peripheral distribution of muscular weakness and
wasting associated with pain (constant burning), tenderness
pressure and sensory disturbances like numbness, with glove
and stocking type of anaesthesia, usually affecting the distal
segments more than proximal.
Mononeuritis multiplex is a disorder involving more than
one peripheral nerve simultaneously, resulting in the motor
and sensory disturbances, asymmetrically, e.g. vasculopathy
due to diabetes mellitus or polyarteritis nodosa.
In mononeuropathy only an individual nerve is involved
with precise neurological deficit, e.g. trauma, compressive
or entrapment neuropathy.
Polyneuritis (polyneuropathy) is due to various causes
like:
1. Infections-Diphtheria, leprosy. HIV.
2. Inflammatory—Acute demyelinating neuropathy
(Guillain-Barre Syndrome); Sarcoidosis; chronic
inflammatory demyelinating polyneuropathy (CIDP).
3. Deficiencies-Chronic alcoholism, vitamins B1 and B12.
deficiency.
4. Metabolic-Diabetes mellitus, porphyria (uncommon)
5. Toxins-Lead, arsenic
6. Drugs-INH, phenytoin metronidazole, excess of B6
(100 mg/d)
7. Trauma
8. Malignancies-Carcinoma of the bronchus, Myeloma
9. Vasculitides-Periarteritis nodosa, SLE
10. Hereditary-Peroneal muscular atrophy
The more important and common causes seen in clinical
practice are diabetes mellitus, deficiency disorders, drugs
and infectious neuropathy. Different presentations are
encountered with different causes. Apart from sensory
impairment, motor weakness usually affects the periphery
of the limbs, producing sometimes foot drop. Nevertheless,
in G-B polyneuritis and carcinomatous neuropathy, proximal
segments are involved more than distal. Though clinical
features generally are the same, yet the differential diagnosis
of the cause of polyneuritis depends upon the specific
features in the history and examination. Pain and tenderness
of the muscles with ataxia due to loss of postural sensibility
are striking in alcoholic and diabetic neuropathies. Sensory
involvement is predominant in neuropathies due to diabetes
mellitus and drugs. Motor involvement are is predominant
in G-B polyneuritis. Both motor and sensory involvement
are notable in dietary deficiencies, alcoholism and leprosy.
In neuropathies associated with carcinoma, it can be either
motor or sensory presentation. The features of neuritis must
be differentiated from those of vascular occlusions by
examining carefully the arterial pulses of the limbs. Automatic
neuropathy may be part of polyneuropathy.
Myasthenia Gravis
Myasthenia is chracterised by undue fatigability of certain
groups of muscles with associated weakness increasing
towards evening due to the impairment of conduction at
myoneural junction of striated muscles. It is more common
in females.
The basic concept is that acetylcholine is necessary for
the conduction of the impulse and cholinesterase enzyme
splits and inactivates this substance. In myasthenia, there is
marked reduction of functioning acetylcholine receptors and
90% of the patients reveal autoantibodies binding to
acetylcholine receptors. (Antiacetylcholine receptor
autoantibodies). The symptoms are attributed to the blocking
of neuromuscular transmission. This autoimmunity is
humoral (antibody mediated autoimmune disease) and
thyoma or thymic hyperplasia or thyrotoxicosis may be
associated.
The proximal or girdle muscles may be affected (pelvic
is less common than shoulder). The muscles that are
affected frequently are ocular muscles with ptosis and
diplopia, bulbar muscles with dysphagia, facial muscles with
chracteristic snarling appearance on smiling, jaw muscles
with difficulty in chewing, weakness of neck muscles
causing the head to fall forward, and weakness of respiratory
muscles resulting in dyspnoea besides weakness of the
limbs. Slow progression may lead to permanent weakness
of muscles espicially those affected earlier.
Clinical diagnostic test with anticholinesterase substance
like neostigmine is striking in the course of 5 to 15 min.
So in the case with edrophomium chloride IV, or IM which
test has to be done carefully when facility for immediate
respiratory assistance is made available. Test is positive if
muscle power improves.
Muscle biopsy, electrophysiologic responses and elevated
circulating antibodies against acetycholine receptors confirm
diagnosis.
Myasthenia is known for remission and relapses and
this episodic or recurrent typr of paralysis can be seen in
other conditions like hypokalaemia, primary aldosteronism,
 Paraplegia
multiple sclerosis, and myasthenic syndrome (Eaton-
Lambert) which is often associated with carcinoma of the
bronchus or other sites.
Myopathies
These may be heredofamilial or acquired myopathies.
The heredofamilial (inherited) group can be:
a. Pseudohypertrophic muscular dystrophy
b. Limb girdle type
c. Facioscapulohumeral type
d. Distal muscular dystrophy
The acquired myopathies are due to
a. Polymyositis
b. Polymyalgia rheumatica
c. Endocrine and metabolic myopathies
d. Alcohol myopathy
e. Carcinomatous myopahty
Pseudohypertrophic muscular dystrophy Though these
affections of the muscles do not produce a picture of
paraplegia as such, in primary muscular dystropgies, the
early symptoms of weakness in the legs and a positive family
history should make one to suspect it. When fully developd,
the calf muscles, quadriceps and glutei muscles, supraspinati
and deltoids, though exhibit hypertrophy, are really weak.
This results in a waddling gait and the characteristic mode
of rising from the squatting position by clasping the legs
with hands and climbing up to assume the upright position.
It is due to an X-linked recessive inheritance. Serum creatine
phosphokinase is elevated and electromyography may
indicate weakness as myopathic than neurogenic.
It may be a severe type (Duchenne) or benign type
(Becker). The age of onset is 1 to 5 years with a short life
span in the former as against 5 to 25 years with almost
normal life span in the later.
Limb girdle type (ERB’S) The onset of symptoms appears
between the age of 15 and 35 starting either with the shoulder
or pelvic girdle. Weakness and wasting usually begins in
the shoulder-girdle spreading to the pelvic girdle later or
vice versa. It is an autosomal recessive muscular dystrophy.
EMG and muscle biopsy confirm the diagnosis.
Facioscapulo-humeral type Fascial involvement occurs early
and usually associated with weakness of the shoulder-girdle
muscles. Bilateral winging of the scapulae and inability to
raise the arms above the head, and pouting appearance of
the lips with a characteristic transverse smile are highly
diagnostic. It is inherited by an autosomal dominant
mechanism.
399
Distal muscular dystrophy The onset of the weakness and
wasting of the muscles occurs distally in extremities either
anterior tibial muscles and calves or small muscles of the
hands. It spreads proximally later. It is also inherited by an
autosomal dominant mechanism with age of onset between
40 to 60 years.
Polymyositis In polymyositis, there may be symmetrical
weakness of the proximal muscles more than the distal
muscles of the lower limbs. It may be painless or painful
and tender. The other muscles which are affected are neck
muscles, shoulder muscles and pharyngeal muslces.This
weakness may result in difficulty to walk or climb stairscases
or difficulty to swallow or hold the neck. The tendon
reflexes may be diminished. Periorbital oedema, arthralgia,
scaly patches over interpharyngeal joints, erythematus rash
over the face and upper chest, myoglobinuria are the other
features which are present. When skin manifestations are
present, it is called dermatomyositis. Other collagen disease
or malginant disease may also be associated with it.
Polymyositis is a lymphocyte mediated autoimmune process
triggered by factors like viral infections. Diagnosis is
confirmed by the presence of increased serum levels of
creatinine phosphokinase and aldolase which may mirror
the disease activity. Muscle biopsy is confirmatory. EMG
shows polyphasic potentials, fibrillations, and abnormally
brief action potentials.
Polymyalgia rheumatica It occurs in patients over 60 years
and more in women. Muscular pain with local tenderness
in the shoulder girdle and neck or pelvic region is the principle
complaint. Muscle weakness is not at all significant. Joint
pains or swelling may occur.Temporal arteritis may be
associated.Though ESR is very high,serum enzymes, EMG
and muscle biopsy are normal.
Endocrine and metabolic myopathies Myopathies are not
uncommon due to endocrinal disorders (like thyrotoxicosis,
hypothyroidism, Cushing’s syndrome and corticosteroid
therapy for long periods specially triamcinolone) wherein
progressive weakness of proximal limb and girdle muscles
occur with difficulty in walking or sitting or combing.
Thyrotoxic myopathy is chracterised by progressive
weakness and wasting of the muscles usually confined to
the muscles of pelvic girdle with symmetrical distribution
(Basedow’s paraplegia) or shoulder-girdle muscles.
Fibrillations may be seen and tendon reflexes are variable.
Creatinuria is usually present though the serum enzymes
are not elevated. Symptomatic myasthenia is also seen in
hypothyroidism with increased volume of the calf muscles
(Hoffmann’s syndrome).
 400 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Alcoholic myopathy Progressive proximal muscle weakness
and wasting is common in chronic alcoholics. Sometimes
severe drinking spree may lead to rapid development of
widespread muscle pain, cramps and oedema with
myogloinuria. Cardiomyopathy with decompensation may
accompany. Serum enzymes may be raised.
Carcinomatous myopathy Weakness and wasting of the
proximal muscles of the limbs may be seen in carcinomatous
myopathy, and sometimes bulbar and ocular involvement.
Fatigubility of myasthenic type is sometimes seen without
satisfactory response to neostigmine. Bronchogenic, (Eaton-
lambert) renal, gastric carcinomas and leukaemia may be
associated. The typical electrical reaction is striking reduction
in amplitude of the action potential with normal strength of
the voluntary contraction.
CLINICAL APPROACH
Weakness of the legs ranges from (a) minor causes such as
general weakness after an illness or (b) as a major symptom
either due to consequences of a systemic disease with
profound tissue wasting or disorders of muscles and nervous
system.
Often weakness result from interference with motor
pathways anywhere from precentral cortex down to the
muscle, either upper or lower motor neurones. Sometimes
disturbances from disease of the basal ganglia or cerebellum
or posterior columns may be described as weakness.
Further difficulty in walking may be expressed as weakness,
in disease primarily affecting the joints with or without
wasting of the concerned muscles. So one should analyse
the weak legs with utmost care for labelling a proper
diagnosis.
History
a. Age of onset-Muscular dystrophy occurs in early age
group.
b. Family history-Peroneal muscular atrophy.
c. Mode of onset-Is the onset gradual or sudden?
d. Is weakness symmetrical or asymmetrical?
e. Is it progressive or intermittent?
f. What activities interfere with weakness?
g. What circumstances make the weakness more obvious?
h. Any exposure to heavy metals or industrial solvents.
i. Drug history
j. Dietary history and alcohol indulgence
k. Any recent history of viral infections or associated
systemic diseases like diabetes mellitus or malignancy.
l. Any history of trauma.
m. Any history of paraesthesiae or burning discomfort.
Physical Examination
General Examination
General survey inclusive of (a) skin, (b) pes cavus
(suggestive of a heredofamilial neurological disorder) (c)
scoliosis or any such abnormalities, (d) joints, (e) postural
hypotension, and (f) sweating disturbances.
Systemic Examination
After examining the main systems of cardiovascular,
respiratory and alimentary systems, concentrate on the
detailed examination of the central nervous system
methodically with special emphasis on points like.
a. Distribution of weakness or wasting (Proximal, distal
generalised or diffuse) In spinal cord lesions, the
weakness and wasting may be predominantly distal,
whereas the myopathic weakness is proximal. In root
lesions, it is confined to the root distribution only whereas
in peripheral nerve lesion it is confined to the region of
the affected nerve, e.g. foot drop.
b. Type of sensory loss and its distribution
i. In spinal cord lesions, there is sensory level, (total
loss of all modalities of sensation) or posterior
column sensory loss or dissociated anaesthesia or a
Brown-Sequard type of sensory distribution.
ii. In root lesions, there is appropriate dermatome
sensory loss.
iii. a. In peripheral nerve lesions, all forms of sensations
lost appropriate to the nerve distribution; there is
no abrupt line of demarcation since neighbouring
nerves may overlap into the affected territory.
b. If there is selective damage of the fibres, the
involvement of the more susceptible long fibres
may result in sensory disturbances at the tips of
the toes or fingers irrespective of the nerve supply,
and spreads proximally as the shorter fibres are
also involved which results in the characterstic
glove and stocking distribution of sensory loss.
iv. If there is no sensory loss at all, it is suggestive of a
motor neurone disease or a pure lateral column
involvement or poliomyelitis.
v. Hysterical sensory loss does not correspond with
the distribution of the loss of a sensory tract or a
peripheral nerve and the anaesthetic area is sharply
demarcated.
c. Reflexes Extensor plantar response suggests spinal cord
disease. (Pyramidal tract)
Exaggerated deep reflexes with extensor plantar response
suggest a spinal cord compression.
 Paraplegia 401

Absent deep reflexes with extensor plantars may be seen Investigations

in Friendreich’s ataxia or subacute combined degeneration 1. Blood Examination
of the cord. a. ESR
b. Blood counts
Methodical Examination of CNS c. VDRL
Motor System d. Blood sugar
e. Serum potassium
a. Power f. Serum enzyme studies like aldolase and CPK
b. Tone (spastic or flaccid) g. Serum vitamin B12 (lower limit of normal level is
c. Involuntry movements like fasciculations, associated
140 micrograms)
with muscular wasting are highly characteristic of motor
2. Lumbar Puncture (CSF)
neurone disease
a. Dynamics
d. Nutrition • Wasting or hypertrophy
e. Coordination b. Cytology
c. Chemical examination for proteins, sugar and
Sensory System chlorides
d. Adenosine deaminase.
a. Superficial sensations—Light touch, pain (pin-prick) and 3. Radiology
temperature a. X-ray examination-detect lesions in
b. Deep sensations—Joint sense, vibration sense pressure (i) lumbar spine (ii) sacroiliac or hip joints
over the muscles (tenderness is characteristic of b. X-ray of the skull for any parasagittal meningioma
polyneuritis, or polymyositis) c. Chest X-ray for any infection or neoplasm.
d. Contrast radiography (myelography)- To localise the
Reflexes
level of the disc lesions or spinal block
a. Superficial reflexes—Plantar and abdomianl e. CT Scan or MRI of spinal cord
b. Tendon or deep (stretch) reflexes—Knee jerks, ankle 4. Electromyography For electrical analysis of nervous and
jerks and presence of clonus muscular activity.
c. Organic reflexes—Examine the state of sphincters 5. Nerve conduction velocity studies for diagnosis of
(retention or incontinence) axonopathies with or without demyelination.
Spine Deformities or tenderness over the vertebra and 6. Biopsy
mobility of the spine. a. Muscle
Trophic disturbances of the skin (Bed sores) or b. Sural nerve
perforating ulcers or Anomolies of sweating. 7. Any other appropriate tests like thyroid function tests
or LE cell or porphyrin metabolic or heavy metals in the
Special Signs urine or potassium in urine.
a. Straight leg raising test
b. Kernig’s sign TREATMENT OF PARAPLEGIA
c. Palpation of the nerves for tenderness and thickening The different levels of the upper or lower motor neurone,
at which the disordered function, leads to weakness of legs
Gait suddenly or gradually, must be primarily identified, before
a. Observe whether patient can stand without support with initiating appropriate treatment, be it medical or surgical.
the feet drawn together—with eyes closed and eyes It may be relevant in this endeavour to answer three
opened. questions.
b. Ask him to walk (if necessary with support), and observe What is thie lesion? (Clinical diagnosis)
the type of abnormal gait-whether high steppage or
Where is the lesion? (Anatomical diagnosis)
waddling or spastic.
c. Ask him to stnd on one foot, then on the other. How is the lesion caused? (Pathological diagnosis)
d. Ask him to walk along the line, with the toe touching The nature of the disease is such, that the patient is
the heel. highly susceptible to complications, which may delay the
 402 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
recovery or result in a disability or prove fatal. Hence, the
general care of a paraplegic subject is all the more important.
General Measures
1. Bed—A sponge-rubber bed on fracture boards or ripple
bed is ideal.
2. Posture—Change the position of the patient frequently
by rolling gently to either side. Keep the lower limbs
extended, supporting the calves with small pillows
underneath, and the projecting feet dorsiflexed.
3. Nutrition—High protein and high calorie diet with
supplements of vitamins and minerals prescribed.
4. Care of the skin—The skin should be kept absolutely
clean (by soap cleaning and keeping it dry with the use
of spirit/dusting power) and wrinkles of the bedsheet
must be avoided lest bed sores should occur. Protect
the bony prominences or pressure points with pads. An
alternating pressure mattress is beneficial.
In case bed sores develop, they should be promptly
treated by irrigating with hydrogen peroxide and antibiotic
dressing. The necrotic tissue may be removed and
subsequently saline dressing may be used. If necessary,
cultures should be made from the sores and appropriate
antibiotics given.
5. Care of the bladder—As retention of urine leads to
cystitis and ascending pyelonephritis, drainge of bladder
must be done by an absolute aseptic procedure with a
selt-retained catheter. Parasympathomimetic drugs
(carbachol 1 ml SC) were used erstwhile suprapublic
cystostomy may be considered later, if the bladder
function does not recover. In case urinary infection
occurs, it must be treated promptly. An automatic bladder
evacuating sterile urine, is to be aimed. In case of urgency
or frequency, oxybutynin (2.5-5 mg bd) and for retention
bethanechol (10-20 mg tds) may be useful.
6. Care of the bowels—Constipation is treated with
laxatives at bed time. Leakage after an enema is to be
taken care of.
7. Flexor spasms—exciting factors like moving of the
lower limbs over the bed clothes should be avoided.
Hyoscine Hydrobromide (1/100 gm) sublingually is
helpful. Muscle relaxants are sometimes of value.
Tizanidine (1-2 mg tds) is beneficial. Intrathecal alcohol
or section of the ventral roots are beneficial.
8. Physiotherapy—Massage, passive movements of the
joints of the paralysed limbs, and encouraging voluntary
movements, help to develop residual muscle power and
prevent flexor contractures. Train the patient to walk
between parallel bars or crutches as early as possible.
9. Rehabilitation—Early rehabilitation, recreational facilities,
helping the patient to cope with the disability, and
providing sedentary occupation will raise the morale.
Specific Treatment for Specific Disease
1. Spastic Paraplegias of Acute Onset
Acute myelitis Apart from the general measures, treat the
specific cause of myelitis.
a. Tuberculous myelitis with antituberculous treatment
(refer to Chapter ‘Chronic Diarrhoea’ and haemoptysis).
b. Leutic myelitis with procaine penicillin (2.4 millions units
IM), and probenecid (500 mg for 10 days) and later
benzathine penicillin (2.4 million units weekly for 3
weeks-watch for jaricsh-herxheimer reaction 2 to 8 hours
after therapy). if allergic to penicillin, oral tetracycline
(2 gm/d for one month) indicated.
Herpes simplex myelitis treated with oral acyclovir (200
mg five times a day for 2 weeks or IV 5 mg/kg tds for five
days). Famciclovir, valaciclovir are other alternatives.
Disseminated myelitis with optic neuritis (neuromyelitis
optica). Corticosteroids or ACTH helpful.
Spinal cord injury Immobolisation on a flat bed and if
necessary traction is advocated. Surgery is to be done to
relieve the pressure or compression and facilitate recovery,
only when the cord is not divided completely.
Spinal cord compression
a. Tuberculous spinal osteitis is treated by immobilisation,
good diet and antituberculous treatment. Costotran-
sversectomy and spinal fusion or rarely laminectomy
indicated.
b. Neoplasms: Surgical removal of the tumours indicated.
For mertastases, local irradiation with or without
chemotherapy preceded by steroids in high doses (to
reduce oedema) is considered.
For multiple myeloma (Refer to Chapter ‘Low
Backache’).
c. Acute disc protusion and facture dislocation may require
surgical intervention.
d. Epidural abscess and pachymeningitis require early
decompression by laminectomy supported by appropriate
antibiotic course. (Recovery of paralysis is unlikely if
treatment is delayed for epidural abscess).
e. Epidural haemorrhage: Emergency evacuation of the
blood clot is done. Hematomyelia needs conservative
treatment.
 Paraplegia
Cord infarction Treatment is symptomatic.
Caisson disease Recompression is done immediately by
placing the patient in an air lock and normal pressure is
restored very slowly. Slow decompression of people exposed
to high pressure is a preventive measure.
Thrombosis of the unpaired anterior cerebral artery (Refer to
Ischaemic Stroke, Chapter ‘Coma’).
Thrombosis of superior sagittal sinus: Treatment is
symptomatic. Appropriate antibiotics given( if infective in
origin). Dexamethasone may be beneficial for reducing
cerebral oedema.
Hysteria (Refer to Chapter ‘Coma’).
2. Flaccid Paraplegias of Acute Onset
Spinal shock: Treatment is symptomatic.
Poliomyelitis
i. In acute stage complete bed rest is essential. Analgesics
or diazepam may be useful.
ii. Limbs are so placed as to facilitate relaxation of the
paralysed muscles. Gentle passive movements advised
from the beginning, to counteract spasm.
iii. If respiratory paralysis develops (breathlessness or
vital capacity <1L), assisted ventilation is to be carried
out (intermittent positive pressure respiration applied
through an endotracheal tube or a cuffed intratracheal
tube via tracheostomy especially if bulbar paralysis
coexists. A Bird type respirator is considerd if the
respiratory problem is slight).
iv. If bulbar paralysis occurs alone, patient should be
nursed in the semi-prone position with the foot of the
bed raised by 45 cm. Prevent fluids and secretions
entering the lungs by suction. Tracheostomy may be
done, if necessary.
v. In convalescent stage, active exercises are encouraged
preferably after 2-3 weeks of onset of paralysis.
Suitable splints help to prevent contractures.
vi. In later stage, residual disbilities (contractures and
deformities) are corrected by orthopaedic measures.
vii. In chronic stage (cold paralysed limbs), lumbar
sympathectomy may be considered to improve
circulation.
Spinal anaesthesia Treatment is symptomatic.
Acute infective demyelinating polyradicular neuropathy
(immunologically mediated) Besides symptomatic treatment
ACTH or cortisone helpful. If bulbar and respiratory
paralysis occur, treat as for poliomyelitis intravenous
403
immunoglobulin 0.4 gms/kg/d for 5 days, highly beneficial.
Methyl Prednisolone (1 gm IV) for 3 days is beneficial.
Acute cauda equina lesions The injuries of cauda equina due
to fracture or dislocation of the spine below 1st lumbar
vertebra need immediate immobilisation on the flat bed with
or without traction. Consider operative measures to relieve
the pressure.
Treatment of infarction of cauda equina symptomatic.
Muscles
a. Polymyositis: Prednisolone (60 mg daily) is given for
about three weeks; taper the dose daily to reach an
optimum maintenance dose, which is to be continued
for couple of years.
If the disease is severe and response to steroids is
inadequate, azathioprine (2 mg/kg/d) is given with or
without low doses of steroids. Some prefer cyclo-
phosphamide or methotrexate or even chlorambucil.
Immune globulin 2 gm/kg once in a month is promising.
Physiotherapy and rehabilitation are important after the
acute stage.
b. Periodic paralysis: Hypokalaemic periodic paralysis is
treated with potassium chloride (6 gm = 80 mEq of
elemental potassium) daily during the attack. (Thirty ml
of KCl contains 3 gm = 40 mEq/mmol of elemental
potassium). Spironolactone (25 mg four times daily)
may reduce the frequency. Acetazolamide (250 mg four
times daily) is an affective prophylactic (If magnesium
is low, it is better to correct it).
Hyperkalaemic periodic paralysis is treated with IV
calcium gluconate to provide cardioprotection and insulin
plus glucose (1 unit + 2½ gm of glucose).
Normokalaemic periodic paralysis responds to sodium
chloride, whereas potassium worsens it.
c. Myoglobinuria: Treatment is symptomatic. If it is due
to acute polymyositis, treat accordingly.
3. Spastic Paraplegias of Gradual Onset
Cord compression (Vide supra).
Erb’s paraplegia Vide supra–Acute myelitis (Leutic Myelitis).
Motor neurone disease Treatment is symtomatic. Baclofen
(5-15 mg tds) may be helpful for spasticity. Neostigmine
(15 mg tds) may be beneficial for bulbar weakness.
Antibiotics may be given for secondary infection.
Antigutamate (Riluzole) useful (50 mg bd).
Multiple sclerosis
1. Acute relapse is treated with
i. ACTH (80 units/d for a week and tapering it over
three weeks) or
 404 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
ii. Methyl prednisolone (1 gm/d for five days) to retard
the disease process.
iii. Plasma exchange, i.e. 7 exchanges of one plasma
volume on alternate days is also recommended.
2. Relapsing and remitting cases are managed with
(i) Interferon-beta (1b) 8 million IU (0.25 mg) subcu-
taneously every other day, (ii) Interferon-beta (1a) 30
ug intramuscularly once weekly, (iii) Glatiramer 20 ug
SC daily, (iv) Immunoglobulins 0.15-0.2 gm/kg IV
monthly for two years.
3. Primary progressive cases may be treated with (i) methyl
prednisilone 1 gm/d for five days monthly
(ii) Methotrexate 7.5 –20 mg/week orally with or without
monthly corticosteroids. (iii) Cladribin.
4. Secondary Progressive cases are managed with
(i) Interferon-Beta (1 b) 8 million IU SC every other
day (ii) Mitoxantrone 12 mg/m2 of body-surface area
IV every 3 months not exceeding 140 mg/m2.
Established immunosuppression with predniosolone,
azathioprine, cyclopsporine, cyclophosphamide for long term
may be beneficial to reduce relapses in some cases. Recently
Mycophenolate mofetil with or without allopurinol is yet
another immunosuppressive agent being employed.
Symptomatic management of spasticity with Baclofen,
Tizanidine or Dantrolene or Diazepam are beneficial.
Botulinum toxin IM is beneficial. Intrathecal baclofen pump
gives dramatic relief.
Urgency of micturition may be restrained with
Oxybutylin (5 mg bd), Bethanechol (20 mg three times daily)
may be effective for retention.
Clonazepam (1-4 mg/d) is helpful for intention tremor.
Neuritic pains may respond to carbamazepine (200 mg
tds) or Gabapentin (300 mg tds). Mechanical aids may be
employed, if necessary.
Immunoglobulin IV given for Immune related
neurological disorders.
Nutritional neuropathies
• Subacute combined degeneration of the cord
Vitamin B12 1000 mcg given IM on alternate days for
10 days followed by reduced doses weekly for six
months, then 100 mcg monthly lifelong. Vitamin B
complex may be supplemented.
• Pellagra Nicotinamide 100 mg parenterally, then 200 mg
tds orally is administered. Vitamin B complex may be
supplemented.
• Lathyrism: Treatment is symptomatic. Lathyrus seed is
detoxified by soaking it in hot water or boiling partially.
Developmental
• Syringomyelia: Treatment is symptomatic. Analgesics
may be necessary. Occasionally decompression of the
spinal cord and aspiration of the central cavity may be
necessary.
• Hereditary spastic paraplegia: Treatment is symptomatic.
• Friendreich’s ataxia: Treatment is symptomatic.
Acetylcholine precursors like choline (6-12 gm/d) with
or without lithium (increases choline levels in the blood)
may be helpful.
Cerebral
• Cerebral diplegia Treatment is symptomatic.
Physiotherapy is considerable value. Baclofen reduces
spasticity. Correct the deformity by surgical procedures.
Posterior rhizotomy in selected cases is of considerable
benefit.
• Hydrocephalus (Refer to Chapter ‘Haedache’).
• Parasagittal meningioma Early surgical removal is done.
It is prone to recur.
4. Flaccid Paraplegias of Gradual Onset
Hereditary
• Myelodysplasia: Treatment is symptomatic so long as
the lesion is nonprogressive. If necessary consider
laminectomy and removal of lipoma or fibrous band like
factors exerting pressure on the spinal cord.
• Peroneal muscular atrophy: Physiotherapy and
appropriate appliances are advocated.
• Motor neurone disease (Vide supra.)
• Cauda equina lesions: The underlying cause of
compression of cauda equina, like disc prolapse, chronic
lumbar canal stenosis, spondylolisthesis, neoplasms,
chronic arachnoiditis should be identified and treated
appropriately. Early decompression by laminectomy or
releasing the cord from adhesions under antibiotic cover
or removal of neoplasm is advocated.
• Peripheral neuropathies: The essential step is to identify
the underlying cause of polyneuritis and treat it
appropriately.
Physical measures (daily massage and passive move-
ments) promote motor recovery and prevent contractures.
The feet are better supported by means of sand bags placed
under the soles or splints may be used to prevent foot drop.
Analgesics may be required if the pain is severe. When
recovery begins, active mevements are encouraged with
the help of a physiotherapist.
 Paraplegia
Since sensory loss may predispose to trauma, careful
attention should be paid to the feet. If foot ulcers occur,
healing should be promoted appropriately by rest (avoiding
weight bearing) and suitable dressings.
Hansen’s neuropathy is treated with dapsone (100 mg)
with clofazimine (50 mg) daily plus rifampin (600 mg) with
clofazimine (300 mg) once a month, given for two years.
Analgesics and appropriate splints are of value. In selected
cases nerve grafting and hand surgery may be considered.
Guillain-Barre Syndrome-(Vide supra) Nutritional
deficiencies associated with peripheral neuropathies
(thiamine, vitamin B 12’ pyridoxine) are appropriately
corrected and supplemented with vitamin B complex.
Alcoholic neuropathy is treated with thiamine parenterally
followed by oral therapy. Other vitamins may be
supplemented. Deaddiction may be instituted.
Treatment of toxic neuropathy is to eliminate the source
of the exposure and administer chelating agents.
Diabetic (peripheral) neuropathy is treated with
carbamazepine, amitriptyline with or without fluphenazine.
Other useful drugs are gabapentin, methyl cobalamine,
Benfotiamine, Alpha-lipoic acid, Gamma Linolenic acid.
Topical capsaicin cream is effective for painful focal
neuropathies.
Diabetic autonomic neuropathy leading to postural
hypotension is treated with fludrocortisone or indomethacin,
liberal salt diet and elevated head position during sleep.
Delayed gastric emptying treated with metaclopramide or
domperidone or Itopride or cintapride. Ephedrine may reduce
the neuropathic oedema.
Vitamin E in large doses may prevent the onset of
hereditary neuropathy. Corticosteroid therapy may be
beneficial.
Neuropathies associated with other systemic disease are
appropriately treated.
Myasthenia gravis Anticholinesterase therapy is the standard
treatment for myasthenia gravis. Anticholinesterases like
neostigmine (prostigmine) constitute one of the types of
parasympathomimetic agents. The usual dose of
neostigmine is to begin with 15 mg orally every 4 hours or
1 mg IM 2-4 hours. The dosage can be steadily increased
till maximum effects are appreciated. Since the action of
neostigmine is of short duration, long acting
anticholinesterases are entertained, i.e. pyridostigmine (60
mg orally every 4 h or 2 mg IM 2-4 hourly) and ambenonium
chloride (10 mg orally six hourly). The muscarinic side
effects are neutralised by giving atropine 0.6 mg IM or
propantheline 15 mg. Overdosage may lead to cholinergic
405
crisis (sweating, pallor, excessive salivation, fasciculations
and small pupils) is treated with IV atropine (1 mg) maximum
of 8 mg; oropharyngeal airway and mechanical ventilation,
if necessary, apart from withholding the anticholinesterase
drugs. Steroids may be beneficial in refractory cases.
Edrophonium chloride-Tensilon (2 mg IV and if
necessary may be repeated 4 mg IV after five min) is useful
only for diagnostic purposes and not for ongoing treatment,
as it improves symptoms dramatically but briefly. This
anticholinesterase is also of value in differentiating
myasthenic crisis from that of cholinergic crisis (i.e.)
muscle weakness improves dramitically in myasthenic crisis,
when anticholinesterase dose is to be increased whereas
muscle weakness worsens in cholinergic crises, when the
anticholinesterase dose is to be reduced.
Myasthenic crisis is treated by initiating respiratory
support and withholding anticholinesterase drugs for 3-7
days. They are given a trial when cholinergic drug
responsiveness develops and substituted as improvement
occurs.
The other line of treatment is immunosuppression with
drugs (prednisolone, azathioprine, cyclophosphamide and
methotrexate) or plasmapheresis Immunoglobulin is useful
(if IgA levels are low, anaphylactic shock may occur).
Myopathies
a. Heredofamilial (inherited) myopathies—treatment is
symptomatic (passive stretching of muscles,
physiotherapy and mechnical devices). Gene therapy is
promising.
b. Acquired myopathies
i. Polymyositis (Inflammatory myopathy)—(Vide
supra.)
ii. Endocrinal myopathies
a. Thyrotoxic myopathy is reversible.
b. Myopathy associated with hypothyroidism
improves with thyroxine.
c. Steroid myopathy resolves on withdrawal of the
steroids.
iii. Metabolic myopathies
a. Periodic paralysis (Vide supra)
b. Alcoholic myopathy—Withdrawal of alcohol may
facilitate gradual recovery.
iv. Carcinomatous myopathy—Supportive therapy
besides appropriate management of the underlying
malignancy. Fatiguability and weakness of
myasthenic type may be associated but the response
to neostigmine is not properly sustained and
disappears quickly.
406 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Paraplegia 407
 Chapter

Polyarthritis
27
Joint symptoms like pain and swelling are pressing mediator for vasodilatation and recruitment of inflammatory
complaints in clinical practice. The pain may be of articular cells. Free oxygen radical mediated synovial damage may
(arthritis) or periarticular (periarthritis) origin. The affections facilitate persistence of inflammation. The neural pathway
of the joints may be one facet of a systemic disease responsible for arthralgia, may be that noxious stimuli
(involving multiple systems) with articular as well as extra- stimulating the pain receptors and transmitting pain signals
articular manifestations or confined to joints only with to dorsal horn via afferent nerves (myelinated A delta fibres
features of articular involvement. Joint disorders may not and unmyelinated C fibres). Pain impulses then ascend in
only be associated with pain and swelling, tenderness, either spinothalamic tracts to lateral thalamus or
warmth and erythema but also stiffness (with limited spinoreticular tracts through connection with limbic system,
movement) or synovial effusion or crepitus. so as to mediate sensory as well as affective aspects of
The pattern of joints affected may be monoarthritis or pain respectively. Increased intra-articular pressure (normal
polyarthritis; peripheral joints (small or large or sacroiliac minus 8 cm to minus 12 cm of H2O) and stress over the
and spine;) symmetrical or asymmetrical; transient and periarticular tissues also contribute.
migratory or progressive; acute or insidious with relapses,
only to become chronic. The joint manifestations may be
self-limiting without residual changes or may be progressive
with irreversible changes, leading to deformities, or
hypermobility.
The structures involved in the articular lesions may be
either cartilage and ligaments or synovium. In periarthritis,
usually one of the larger joints is involved and manifestations
are due to tendinitis, tenosynovitis, bursitis, capsulitis,
fibrositis, myositis, bone-tendon junction syndromes
(enthesopathies), or muscle-tendon junction syndromes
(tennis elbow) depending on the structures affected in the
periarticular (tendons and bursae) or extra-articular (fascia,
muscle and bone) regions (Fig. 27.1).

MECHANISM OF ARTHRITIC PAIN

Neuropeptides like substance ‘P’ which are released from
the sensory nerve terminals may play a role in activating
nociceptors (pain receptors) besides acting as a chemical Fig. 27.1: Knee joint (sagittal view)
 Polyarthritis 409

PATHOGENESIS OF SWOLLEN JOINTS Contd...

The swelling of the joints may be due to: d. Progressive Systemic Sclerosis (PSS)
a. Synovial proliferation, as in rheumatoid arthritis. e. Mixed connective tissue disease.
b. Joint fluid undergoing changes like (i) increased D. Seronegative arthropathies (Spondyloarthritides)
a. Ankylosing spondylitis (Marie-Strümpell disease)
quantities and bloodstained as in trauma or haemophilia;
b. Reiter’s syndrome (reactive arthritis)
(ii) inflammatory and purulent changes as in infections; c. Psoriatic arthritis
and (iii) crystals deposition as in gout. d. Enteropathic arthritis
c. Overgrowth of the bone as in osteoarthritis. e. Juvenile rheumatoid arthritis
d. New periosteal bone formation as in hypertrophic f. Behçet’s syndrome
E. Idiopathic
pulmonary osteoarthropathy.
a. Sarcoidosis
e. Involvement of bursae or synovial tendon sheaths b. Relapsing polychondritis
alongside the joints. c. Palindromic rheumatism
f. Complete disorganisation of joint without pain as in d. Intermittent hydrarthrosis
Charcot’s joint. II. Degenerative (Mechanical)
a. Oesteoarthritis
b. Neuropathis joints (charcot)
CAUSES OF OLIGO AND POLYARTHRITIS i. Tabes dorsails
ii. Syringomyelia
They can be grouped predominantly as (i) Inflammatory:
III. Metabolic
microbial or immunological (ii) Noninflammatory: a. Gout (microcrystalline)
mechanical or metabolic (Table 27.1). b. Pseudogout (microcrystalline) (crystal deposition
diseases)
Table 27.1: Causes of oligo and polyarthritis c. Ochronosis (alkaptonuria)
d. Hyperlipidaemia
I. Inflammatory (Infectious or Immunological) e. Amyloidosis
A. Infectious arthritis (microbial) f. Haemochromatosis
a. Bacterial [Streptococcus, Staphylococcus, Gonococcus g. Wilson’s disease
(septic), Brucellosis, Tuberculosis, rarely Less Common Arthritides
Erysipelothrix rhusiopathiae] 1. Hereditary (Congenital Arthropathies)
b. Viral (hepatitis-B, arboviruses, parvoviruses, rubella, a. Connective tissue disorders: Ehlers-Danlos syndrome
Epstein-Barr virus) b. Gargoilism (Hurler’s syndrome)
c. Clamydia (Lymphogranuloma venereum, C. c. Arthrogryposis multiplex congenita
Trachomatis) 2. Endocrinal
d. Mycoplasma a. Acromegaly
e. Spirochaetal (leutic and lyme diseases) b. Hypothyroidism
f. Mycotic (sporotrichosis, histoplasmosis, coccidioido- c. Hyperparathyroidism (primary and secondary).
mycosis) 3. Haematological
g. Parasitic (filariasis). a. Sickle cell anaemia
B. Reactive/Postinfectious arthritis (during or soon after b. Haemophilia
infection without pathogens not entering the joint) c. Henoch-Schönlein purpura
a. Rheumatic fever d. von Willebrand’s disease.
b. Jaccoud’s arthritis
4. Neoplastic
c. Reiter’s disease (sexually transmitted and post-
a. Carcinoma of the bronchus (Hypertrophic pulmonary
enteric)
osteoarthropathy)
d. Other postinfectious entities
b. Lymphomas
i. Brucellosis
c. Occult neoplasm
ii. M. tuberculosis
5. Traumatic Arthritis
iii. Leutic secondary stage
a. Direct trauma
iv. Erythema Nodosum Leprosum (ENL)
b. Indirect trauma
C. Immunological (connective tissue disorders)
6. Iatrogenic
a. Rheumatoid arthritis and its variants
a. Drugs like hydralazine
b. Systemic lupus erythematosus (SLE)
b. Serum sickness
c. Vasculitis (Polyarteritis nodosa)
c. Breast or thoracic surgery
Contd...
 410 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Thus the categories of polyarthritis are (1) inflammatory
(microbial and immunological or idiopathic), (2) degenerative
(mechanical) and (3) metabolic. Sometimes the situation
varies depending upon whether the arthritis is acute,
intermittent or chronic and the pattern of joint involvement
may be mono or oligo (Pauci) or polyarthritis (Table 27.2).
Table 27.2: Causes of monoarthritis
1. Inflammatory
a. Pyogenic (septic)
b. Tuberculous
c. Rheumatoid arthritis (acute onset)
d. Intermittent hydrarthrosis
e. Ankylosing spondylitis (spondyloarthropathy)
2. Degenerative
a. Osteoarthritis
b. Neuropathis joints
3. Metabolic (crystal deposition)
a. Gout
b. Pseudogout
4. Haematological: Haemophilia (Haemarthrosis)
5. Neoplastic
a. Haemangioma
b. Synovial chondromatosis
c. Lipoma (in subsynovial fat)
d. Synovial xanthoma (pigmented villonodular synovitis)
6. Traumatic Arthritis (Haemarthrosis)
a. Direct trauma
b. Indirect trauma, secondary to postural strain
c. Osteochondritis dessicans
N.B. Monoarticular presentation of polyarticular disease should be
borne in mind.
I. Inflammatory Arthritis (Infectious or Immunological)
A. Infectious arthritis (Microbial)
Infection associated arthritis can be:
1. Infectious arthritis (directly related to local microbes
which can be demonstrated in the joint).
2. Parainfectious arthritis wherein microbes are
demonstable in the blood or extra-articular foci but
not in the joint.
3. Postinfectious arthritis (secondary to inflammation
influenced by microbes, not directly growing in the
synovium), and
Reactive arthritis (during or soon after infection
somewhere in the body at a remote site without
microbes entering the joint) i.e. synovitis induced
by deposition of antibodies and antigens (Host
reaction).
Bacterial arthritis
• Pyogenic (septic) arthritis Acute pyogenic arthritis is
caused by Staphylococcus, streptococcus, or
Gonococcus, which is a part of widespread infection by
haematogenous spread or by infections extending from
adjacent tissues. Large joints are involved especially the
knee and it is usually monoarticular. The affected joints
exhibit all signs of acute inflammation, i.e. pain, swelling,
warmth and erythema; associated with fever and chills.
The onset is abrupt. Diagnosis is confirmed by
examination of the synovial fluid (which may be cloudy
or purulent) and determination of causative organisms
by culture. X-ray of the joint may slow:
1. Distended joint capsule.
2. Narrowing of joint space.
3. Bony erosions.
4. Osteoporosis of the articular surfaces.
• Gonococcal arthritis: It is invariably secondary to
genitourinary or oro-rectal transmission of Neisseria
gonorrhoeae via bloodstream. Though it is an acute
polyarthritis of asymmetrical involvement with fever at
the onset, it subsides after few days and may persist as
monoarticular arthritis. Initially there is synovitis followed
by purulent effusion, and untreated destruction ends in
ankylosis. History of exposure and purulent urethral
discharge, two to three weeks prior to joint symptoms,
is usually elicited, in gonorrhoea. Urethritis or cervicitis
is common.
The other features of dermatitis (papular, pustular,
haemorrhagic or necrotic) on the distal extremities;
tenosynovitis of several joints, myocarditis and toxic
hepatitis may be encountered in disseminated infections.
This infection is uncommon since the introduction of
antibiotics.
Diagnosis is confirmed by demonstrating (a) the
organism from the urethra, prostate or cervix and
sometimes in synovial fluid (25% only) and (b) positive
gonococcal complement fixation test.
• Brucellosis (Undulant fever): It is usually caused by
Brucella abortus through milk or milk products. The
onset is insidious with fever and generalised pain
especially over the vertebrae and sciatic nerve
distribution. Arthralgia or swollen painful joints without
local warmth especially knee joints and orchitis are
characteristics. Fever lasts for two to three weeks
alternating with periods of remission.
The diagnosis is confirmed by isolating the organism
from the blood or positive cultures of bone marrow and
with agglutination titres greater than 1 in 160.
 Polyarthritis
• Tuberculosis: The exciting factor is Mycobacterium
tuberculosis. It is usally monoarticular affecting knee or
hip joint or spine. The joint is swollen and doughy due
to synovial inflammation. Though erythema is
inconspicuous, it is tender with restricted movements.
Fluctuation or pateller tap can be elicited if there is
effusion. Constitutional symptoms may be present.
Skeletal and articular involvement occur. The two clinical
types are (1) granular (osseous and synovial-
nondestructive) and (2) exduative or caseous (osseous
and synovial-destructive). Muscle atrophy of the affected
area may be present. Synovitis is followed by destruction
of articular cartilage and fibrous ankylosis. The organism
can be cultured from synovial exudate and biospy of
the synovial tissue reveals typical tubercle. Radiological
appearance of the peripheral joints are similar to that of
pyogenic arthritis with subchondral bone destruction or
vertebral destruction and collapse or paravertebral
shadow in the thoracic area and widening of the psoas
shadow in lumbar area.
Viral
• Hepatitis-B Arthritis may be associated with or without
jaundice. The joints may be monoarticular or polyarticular
involving both small and large joints without residual
damage. It is symmetrical and transient or may persist
for several months. Rash, fever, and lymphadenopathy
are other features.The liver function tests are abnormal.
The hepatitis-B antigen may be present in the serum as
well as in the synovial fluid. The complement levels of
serum and synovial fluid are low (Refer to Chapter
Jaundice).
• Arbo viruses Acute polyarthritis due to chickungunya
virus is similar to the Australian epidemic polyarthritis
(Ross river virus). The only difference is locomotor
symptoms occur acutely early in the disease and last
for a week. The arthritis is self-limiting without any
sequelae.
• Parvovirus, rubella and Epstein-Barr viruses: Human
parvovirus induces arthritis with symmetrical
involvement of small as well as large joints. Though
rashes are known to occur in children, it is absent in
adults. The arthritis improves within two weeks but
occasionally it may be relapsing.
• Rubella virus may manifest as polyarthritis involving
peripheral small joints especially in young women. It
may coincide with or occur shortly after exanthem.
Arthritis lasts for about two weeks without any residual
damage.
411
• Epstein-Barr virus (EBV) is implicated in the
pathogenesis of rheumatoid arthritis. The infection does
not manifest as arthritis, but causes the typical features
of infectious mononucleosis. An immune response to
this virus, is postulated suggesting that this could be the
cause of rheumatoid factor production by B cells in
rheumatoid arthritis, since the virus is a polyclonal
stimulator of B cells.
Chlamydia
• Lymphogranuloma venereum: It is a sexually transmitted
disease caused by C. trachomatis serotypes L1, L2, or
L3. It is characterised by painless ulcer in the genitalia
with painful inguinal lymphadenopathy (buboes). Fever
and arthralgia may be present. Complications like arthritis
with sterile effusions or meningoencephalitis or fistula-
in-ano may occur. Diagnosis is confirmed by history of
exposure preceding three weeks and isolation of LGV
strain of Chlamydia. Apositive complement fixation test
and Frei Skin test are contributory.
• Chamydia trachomatis: Genital infection is associated
with urethritis, epididymitis, pelvic inflammatory disease
and develop complications like arthritis. It is diagnosed
by isolating the organism in tissue culture, or by
documenting leucocytic urethral exudate and excluding
gonococcal infection, or by ELISA. It is found
concomitantly in 25% of men with gonococcal urethritis.
Mycoplasma
• M. pneumoniae is like a bacterium without cell wall
(Eaton’s agent) and spreads through pulmonary
secretions. Apart from the features of fever, pharyngitis
and pneumonia, monoarticular arthritis may occur as a
complication besides polyneuritis, encephalitis,
myocarditis, hepatitis or Stevens-Johnson syndrome. It
is diagnosed by fourfold rise in complement fixation
and development of cold agglutinis.
Spirochaetal
Leutic: In leutic infections, transient polyarthritis may
occur in the secondary stage. There may be neuropathic
arthropathy due to loss of proprioceptive sensation with
progressive damage resulting in disorganisation of joints.
There may be increased mobility and instability of the
joints with crepitus (Charcot’s joints). At present leutic
arthritis is uncommon. In congenital varieties, the knees
are usually affected which present as swollen, tender
joints with minimal pain (Clutton joints). It is seen in
puberty period.
 412 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Lyme disease: This disorder is predominantly present in
the United States and European countries. Once thought
to be viral it is now found to be due to treponema like
spirochaetal which is transmitted by tick. It is an acute
monoarticular arthritis usually affecting knee; sometimes
other joints may be affected including temporo-
mandibular. The joint is swollen with warmth. It may
be recurrent or persisting. Skin lesions (erythema
chronicum migrans) may precede the arthritis and febrile
episodes may accompany the cutaneous as well as the
arthritis lesions. No significant residual damage is known
to occur. Tetracycline given 250 mg / 6 h for 10-20
days.
Mycotic
• Sporotrichosis: It produces synovial infection of the
joints usually proximal to the site of inoculation which
is indicated by the presence of a painless red papule. It
extends along lymphatic channels and involves one or
many large joints. Diagnosis is confirmed by culture of
the joint fluid.
Other systemic mycotic infections may involve
joints in the disseminated forms and the polyarthritis is
usually transient.
Parasitic (Filariasis) Filariasis is caused by Wuchereria
banerofti and Brugia malayi which inhabit in human
lymphatics. The gravid females discharge microfilariae
(embryos) which eventually reach bloodstream. They are
taken up by female mosquitoes (Culex fatigans) during their
blood meal, where they develop into infective forms in 10-
20 days. During the mosquito feeds the infective larvae are
inoculated into the humans where they reach maturity in 5-
18 months. This creamy white thread like nematode causes
acute synovitis of knee or hip joint at times. Though urticaria
occurs early in some cases, certain inflammatory episodes
are common, i.e. fever, lymphangitis, epididymo-orchitis
and lymphadenitis. Later, obstructive features like varicose
groin glands, lymph scrotum, chyluria and elephantiasis may
develop. The parasitic aetiology is established by peripheral
blood examination for microfilaria in the night blood or half
to one hour after administering 100 mg of diethy-
lcarbamazine orally or by QBC test (Refer to Chapter
Rashes).
B. Postinfectious Arthritis
Rheumatic fever Rheumatic fever is a recurrent acute
inflammatory disease with group-A haemolytic streptococcal
infection of the pharynx after a latent period of 10 days to
few weeks. It is commonly seen in the young age group
between 5 and 15 years. It is presumed to be an
immunological phenomenon since the streptococcal proteins
and sugars which are antigenic, produce antibodies reacting
with human connective tissue resulting in various clinical
manifestations. It is characterised by major manifestations
like:
1. Polyarthritis: It is fleeting in nature and involves usually
large joints. The pain and swelling last for few days,
only to appear in some other joints. The swelling is
reversible with no residual damage. Temporo-
mandibular, sternoclavicular joints and spine are not
involved.
2. Carditis: It includes (a) pericarditis with or without
effusion (rub), (b) myocarditis (cardiomegaly, soft
first sound, Carey Coomb’s, mid diastolic murmur or
congestive heart failure), (c) endocarditis (regurgitation
due to inflammation of mitral and aortic valves with a
pansystolic murmur and early diastolic murmur
respectively).
3. Non-tender subcutaneous nodules attached to
superficial surface of the joint capsules or other fascia
on the elbows, knees or back of the head (usually 3 to
6 weeks after fever).
4. Cutaneous lesions like erythema marginatum (usually
not seen in Indian population).
5. Chorea occurs three months after fever.(Sydenham’s).
The minor clinical features are (i) fever; (ii) arthralgia;
(iii) history of previous rheumatic fever or rheumatic heart
disease; and (iv) laboratory findings like leucocytosis,
elevated ESR (>20 mm/h), elevated C-reactive protein (7-
820 µg/dl), elevated antistreptolysin titre (>200T odd units),
a prolonged PR interval (> 0.2 s), a throat swab culture
positive for group-A Streptococcus.
Either two major or one major with two minor
manifestations are necessary for the diagnosis of acute
rheumatic fever according to revised Jones criteria.
Jaccoud’s arthritis Due to recurrent attacks of rheumatic
fever, chronic mild deformity of small joints occurs. It results
from the fibrosis of periarticular structures (capsular
fibrosis) rather than synovitis since the affected joints cause
little or no symptoms and can be corrected by passive
movements. Diagnosis is obvious as it occurs in the context
of established rheumatic fever.
Reiter’s disease (Postsexual or postdysenteric) It is an acute
reactive arthritis in the young males and follows either enteric
infections (Shigella, Salmonella, Yersinia) or exposure to
Chlamydia trachomatis genitial infection. The order of
symptoms is a bacterial urethitis, conjunctivitis, mono or
polyarthritis and mucocutaneous lesions. The joints involved
 Polyarthritis
are those of lower limbs (midtarsal, ankles, knees), sacroiliac
and spine (hips involvement rare) usually with asymmetrical
distribution. The affected joints are painful, swollen, tender
and erythematous and may contain fluid. It persists at least
for four weeks and the average duration is three months. It
may have spontaneous remmision or take a course of
recurrent attacks and produce deformities. This is one type
of sero-negative spondylo-arthropathy with a high incidence
of HLA B-27 antigen, iritis, enthesopathy, painless ulcers
round the meatus or glans penis in circumcised cases and
painless ulcers of oral mucosa may be present and
hyperkeratotic papules in the palms and soles in sexually
acquired Reiter’s disease. The full blown Reiter’s syndrome
may not be always present. Reactive arthritis is a new name
for the old name Reiter’s syndrome. Diagnosis is confirmed
by (1) family history and presence of HLA B-27.
Histocompatibility antigens, (2) raised ESR (3) Urine
collected (in the first of two glasses) shows debris in
urethritis as against in Prostatitis where it is more in the last
sample (4) lipo-polysaccharide (LPS) based enzyme
immunoassay (5) Immunoblotting for detecting antibody
response 1gM, 1gG, 1gA (6) synovial fluid showing
numerous polymorphs and also large mononuclear cells with
ingested polymorphs (Reiter’s cells) and Macrophages
Containing neutrophils (Peking cells) and (7) X-ray of the
joints—Showing subchondral osteoporosis, erosions of joint
margins and narrow joint spaces, periosteal new bone
formation over the shaft of the affected joint, sclerosis and
fusion at the sacroiliac joint, and syndesmophytes forming
as nonmarginal bony bridge over the lumbar spine.
Other postinfective types Brucellosis, tuberculosis (Poncet’s
disease), leutic infections (Vide supra)
Erythema nodosum leprosum (ENL) Hansen’s case
undergoing treatment may suddenly develop fever,
erythema nodosum and polyarthritis. Thickened
peripheral nerves and other characteristic features offer
the clue for diagnosis.
C. Immunological (Connective Tissue Disorders)
Rheumatoid arthritis It is a chronic inflammatory systemic
disease characterised by relapsing symmetrical arthritis of
the small as well as big joints. Rarely the onset may be
acute and febrile. The joints involved usually are
metacarpophalangeal (proximal interphalangeal) and
metatarsophalangeal joints, knees, elbows and wrists. (Distal
interphalangeal joints are spared) Temporomandibular and
upper cervical spine may also be affected. Monoarthritis
and lumbar involvement are very uncommon. Morning
stiffness or tenderness and swelling of the joint, palpable
413
synovium around the joint margin with or without effusion
can be elicited. The swelling is due to inflammation of the
soft tissues surrounding the inflamed joints. In severe
involvement, there is wasting of the muscles related to the
joints. The characteristic features are painful limitation of
movements and destruction of articular cartilage and bones
(erosive) leading to deformities like
i. “Boutonniere” deformity (flexed proximal interphalan-
geal joints).
ii. Swan neck deformity (hyperextension of proximal
interphalangeal joints and flexion of distal
interphalangeal joints).
iii. Ulnar deviation of the fingers
iv. Atlanto-axial dislocation
The extra-articular manifestations are:
i. Subcutaneous nodules over the neighbouring bones
and tendons (the common site being extensor surface
of the elbows).
ii. Ocular manifestations like episcleretis, scleritis.
iii. Respiratory: Pleurisy, pulmonary fibrosis, rheumatoid
nodules in the lung (Caplan’s syndrome).
iv. Cardiac: Pericarditis and aortic regurgitation.
v. Vascular: Raynaud’s phenomena, and peripheral
cutaneous ulcers.
vi. Peripheral neuropathy or entrapment neuropathy.
vii. Lymphadenopathy.
viii. Anaemia.
Disease severity is not only assessed by clinical
parameters and ESR but also DAS (Disease activity score)
whose range is 0-9.4.
The aetiopathogenesis is multifactorial.
i. Genetic factors (HLA DR 4 linked).
ii. Psychosomatic factors.
iii. Infections like EBV.
iv. Allergic factors.
v. Nutritional factors.
Anyone or all of the above factors may trigger the
immunological events and inflammatory response in synovial
tissues. An exogenous antigen encounters the circulating
lymphocyte which transforms into a large plasma cell
producing antibodies. The antigen antibodies and complement
form the immune complex. The phagocytic cells containing
lysosomes (enzyme producing sacs) destroy this complex.
During this process some of the lysosomes escape from
the phagocytes and their proteases invade the cartilage and
synovium. The inflamed synovium forms a pannus which
produces collagenase capable of destroying the cartilage.
Recently heat shock proteins have been incriminated. The
exogenous heat shock proteins of the invading organisms
 414 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

produce antibodies, and T cells directed against them may

react with endogenous human heat shock protein resulting
in autoimmune reaction.
Diagnosis is confirmed by:
1. Clinical criteria like symmetrical swelling of one or more
joints esp. hands continuously for not less than six weeks.
(symmetrical)
2. Radiology: X-ray of the joints shows initially soft tissue
swelling, joint effusions and osteoporosis; later
destruction of articular cartilage and narrowing of joint
space, and finally bony trabeculations obliterate the joint
space, destruction of bone, ankylosis and deformities
occur (Fig. 27.2).
3. Serological tests
i. Agglutination reactions: Sheep cell agglutination test
or latex fixation test (agglutination occurs when
the serum contains rheumatoid factor which is an
immunologlobulin (i.e. an autoantibody to patient’s
own antigenic determinants of fragments of IgG).
Most laboratories detect IgM rheumatoid factor
only and the non IgM factors are not detected.
Rheumatoid factor is positive in 85% of cases.
(Repeat rheumatoid factor test after 4-6 months in
the first 2 years since it may take (6-24 months to
become positive). The latex test is sensitive and
positive in majority of cases.
(A titre of 1:40 or more is significant)
ii. Inhibition test: This more sensitive test uses rheum-
atoid serum, unknown euglobulin and a standard
gammaglobulin latex suspension. The euglobulin
of the normal serum neutralises the rheumatoid
factor and inhibits agglutination whereas euglobulin
of rheumatoid serum facilitates agglutination since
it has no effect on the rheumatoid factor.
4. Haematological: High erythrocyte sedimentation rate
(ESR), hypochromic normocytic anaemia.
5. Other blood tests: Raised C-reactive protein, reversal of
A:G ratio, LE cell (positive in 20 % of cases), antinuclear
antibodies (positive in 30% of cases).
6. Synovial fluid analysis
i. High neutrophil count
ii. High fibrinogen content (clots spontaneously)
iii. Poor mucin clot (by adding 1 % of acetic acid,
mucin precipitated in a cloudy solution which breaks
up on agitation, whereas normally a ropy clump
forms in a clear solution which does not break up
on agitation).
iv. Low levels of complement and glucose, compared
to serum levels drawn simultaneously.
v. The total protein of more than 8 g/dl with high
globulin and low albumin (< 50%)
Fig. 27.2: X-ray of hand showing periarticular osteoporosis,
narrowing of the joint spaces and soft tissue swelling around
the affected joints besides radio-ulnar and radio-carpal
dislocation with subluxation of Ist metacarpophalangeal joint
suggestive of rheumatoid arthritis.
7. Immune complex: Presence of large amounts of immune
complex indicates a positive test for mixed cryoglobulins.
8. Biopsy
i. Histological changes of synovial membrane are (a)
hyperplastic synovial membrance, (b) pannus
(Villous folds) of inflammatory granulation tissue
superimposed by fibrinoid necrosis on proliferative
synovitis, and (c) involvement of articular cartilage
(replacement by fibrous connective tissue at the
periphery and destruction from within the bone).
ii. Histology of blood vessels: Shows focal vascular
changes with inflammatory cell infiltration of the
wall, narrowing of the lumen and perivascular
haemorrhages.
iii. Histology of rheumatoid nodules shows areas of
fibrinoid necrosis at the centre surrounded by
monocytes and lymphocytes, vasculitis of small
vessels may predispose to nodule formation.
Juvenile rheumatoid arthritis (Still’s disease) This chronic
arthritis occurs before 16 years of age. The onset may be:
i. Polyarticular with the involvement of five or more
joints without extra-articular manifestations.
ii. Polyarticular with the involvement of four or fewer
joints with sacroilitis in boys and iridocyclitis in
girls.
iii. With systemic manifestations like high intermittent
fever, macular or maculopapular rash, lympha-
 Polyarthritis
denopathy, hepatosplenomegaly, pericarditis and
subsequent arthritis. Subcutaneous nodules are
rare. 70% of JRA may have spontaneous or
permanent remission in their adulthood. Permanent
blindness, crippling deformities of the joints may
occur.
The diagnosis is confirmed by
a. Polyarthritis of more than six weeks duration
associated with any of the other classical features.
b. Increased acute phase reactants like ESR and C-
reactive protein.
c. Rheumatoid factor (IgM) is negative by standard
methods although special tests for IgG and IgA may
be positive in some cases.
d. X-rays: Soft tissue swelling, juxta-articular
osteoporosis, juxta-articular periosteal new bone
formation, narrowing of the joint spaces due to
cartilage destruction, ragged erosions and cupping
of the ossification centres due to destruction of the
bone, bony ankylosis.
N.B. Juvenile Idiopathic Arthritis (JIA) includes all forms
of arthritis where cause is not known. Since, all children do
not present with features resembling adult rheumatoid
arthritis the name is changed from juvenile Rheumatoid
Arthritis to JIA.
• Felty’s syndrome Rheumatoid arthritis, splenomegaly
and leucopenia with high titre of rheumatoid factors and
HLA DR4 are characteristics. A positive antinuclear
antibody test, high titre of immunocomplexes and
complement levels are useful in diagnosis.
• Sjögren’s syndrome (Sicca syndrome) Dry eyes, dry
mouth and recurrent salivary gland swellings are the
characteristic features, with or without association of
rheumatoid arthritis or other connective tissue disease.
Pulmonary infections and fibrosis, dysphagia and
atrophic gastritis and dyspareunia are other features.
There is a strong association with HLA B8, HLA DR3
and DR4. Incidence of lymphoma is not uncommon.
The diagnosis is confirmed by (i) crude
measurement of ocular secretions (a filter paper strip is
placed in the palpebral fissure and if there is less than 10
mm of wetting in 5 min it is abnormal); (ii) positive
rheumatoid factor; (iii) positive antinuclear antibody; (iv)
hypergammaglobulinaemia; and (v) histological changes
of lymphocyte infiltration in the biopsied salivary gland.
Systemic lupus erythematous (SLE) SLE exhibits remarkable
diversity. The clinical features include fever, rash (malar
butterfly rash, i.e. hyperkeratotic, follicular plugging over
nasal bridge extending cheeks: discoid rash, i.e. erythema;
pigmented hyperkeratotic oedematous papules leading to
415
atrophic depressed lesions); nonerosive arthritis, myositis,
serositis (Pleuritic and pericarditis), endocarditis, vasculitis
with Raynaud’s phenomenon, renal involvement, (nephritis-
albuminuria more than half a gram per day, RBCs and casts),
hepatosplenomegaly (lupoid hepatitis and jaundice),
lymphadenopathy, CNS involvement (peripheral neuropathy,
fits, psychosis). The course of disease is heralded with
exacerbations and remission. (Refer to Chapters
‘Haematuria’ and ‘Pyrexia of Unknown Origin”). Some
patients may have features of antiphospholipid syndrome
(Thrombosis; thrombocytopenia recurrent miscarriages);
myelitis; demented.
The aetiology is unknown but factors like female sex
hormones (since women are more susceptible) facilitate
immune responses in individuals with genetic susceptibity
(HLA DR2 and HLA DR3).
Interplay between genetic mechanisms and host of
environmental factors initiates the disease and immunological
processes precipitate it. The cells in the tissues are damaged
by deposition of autoantibodies and immune complexes.
(The autoantibodies have specificity for nuclear antigenic
determinants.) Certain drugs like hydralazine and isoniazid
are known to produce lupus syndrome.
The diagnosis is established by (1) LE cell test positive
in 80% of cases (polymorphs contain denatured nuclei)
(Fig. 27.3); (2) antinuclear antibody test positive in 95% of
cases, (i) antibodies to Smith (SM) antigen and (ii) double
strandard DNA antibody titres are highly specific;
Figs 27.3A and B: LE cell phenomenon (Normal neutrophil
phagocytose freely lying denatured nucleus of a damaged
leucocyte) LE cell rosette
 416 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(3) circulating anticoagulants as indicated by prolonged
thromboplastin time; (4) low C3 and C4 levels; (5) positive
lupus band test detected from the skin of the forearms; (6)
immune complexes: circulating immune complexes in the
serum demonstrated by Rajii cell assay (not specific); and
(7) haematological: leucopenia and lymphopenia, thrombo-
cytopenia, normocytic or normochromic anaemia or
haemolytic anaemia. (8) Rheumatoid factor positive in 40%
(9) Anti phospholipid antibodies raised predisposing to
thrombosis (10) Antibodies to Ro (SS-A) and La (SS-B)
positive. (Refer to Chapter ‘Pyrexia of Unknown Origin’)
Vasculitis Many entities of vasculitis are described affecting
large, small medium and small arteries or arterioles or venules
or capillaries. They may be primary or secondary to
infections or connective tissue disorders. Immune
mechanism especially deposition of immune complexes in
the vessel wall leads to inflammation and damage to the
vessels resulting in ischaemia. (Antibody mediated or allergic
angitis). They include:
i. Giant cell arteritis: Temporal arteritis and Takayasu’s
arteritis (Large Vessels) (Refer to Chapter ‘Headache’)
ii. Systemic necrotising vasculitis: Polyarteritis nodosa,
Churg-Strauss syndrome and allergic granulomatosis
(Medium size) (Refer to Chapter ‘P.U.O’).
iii. Small Vessels.
a. Wegener’s granulomatosis (Refer to Chapter
Haemoptysis); Microscopic polyangyitis
b. Hypersensitivity vasculitis (Drug reactions)
All the vasculitis syndromes may present with arthralgia
or warm and painful joints with or without effusion without
any bony erosions and synovial hypertrophy. Other features
include fever, urticaria and multisystem involvement
(pericarditis and myocarditis, pleural effusion, glomeru-
lonephritis, peripheral neuropathy or altered sensorium, and
abdominal pain). History of previous respiratory infection
or display of drugs like penicillin, phenylbutazone may be
forthcoming.
The diagnosis is confirmed by the biopsy of the skin
which shows characteristic accumulation of neutrophils
with fragmentation in the vessel walls. Detection of
antineutrophil cytoplasmic antibodies (ANCA) may be of
value as it is positive in 90% of Wegener’s disease and 75%
in microscopic polyangitis. Renal or mesenteric angiography
is contemplated if necessary.
Progressive systemic sclerosis PSS (Three forms are
described i.e. Scleroderma, Generalised Progressive
Systemic Sclerosis and CREST syndrome).
Scleroderma is characterised by fibrosis in the skin as
well as internal organs with joint manifestations and
obliterative arterial lesions. The skin manifestations occur
in three stages (i) non-painful pitting oedema stage;
(ii) indurative stage and (iii) atrophic stage. They involve
face, neck and hands. An abnormal nail fold capillary pattern
(decreased number of capillary loops and dilatation of the
existing loops) as seen in nasthermascope is a good indicator
of scleroderma.
In Generalised Progressive Systemic Sclerosis, internal
organs like lungs, gastrointestinal tract, heart, and kidney
may undergo fibrotic changes with manifestations like
dyspnoea, cough, dysphagia or malabsorption,
cardiomyopathy with congestive heart failure or Proteinuria,
hypertension and myopathy. Usually small joints of the hands
and feet, ankles, wrists elbows and knees may be involved
with limited range of movement and subsequent
contractures. The vasospastic symptoms like Raynaud’s
phenomena may occur prior to the onset of other
manifestations CREST syndrome which is a subset of
progressive systemic sclerosis comprises calcinosis,
Raynaud’s phenomenon, oesophageal hypomotility,
Sclerodactyly and Telangiectasia. (CREST). The diagnosis
is established by (1) radiology: Chest X-ray and barium
swellow; (2) immunological: presence of antinuclear
antibodies (antibodies to nucleolar antigens and centromere)
and (3) skin biopsy.
Mixed connective tissue disease (MCTD) Connective tissue
diseases overlap with each other. MCTD combines features
of SLE, PSS and Polymyositis. Anti-Ribonuclear Protein
(Anti-RNP) antibody present.
D. Seronegative Arthropathies
(Seronegative RA excluded)
Ankylosing spondylitis Polyarthritis is rather unusual in
ankylosing spondylitis. When occurs, it involves large joints,
knees and feet (especially heel pain) in adolescence, and
may lead to ankylosis and deformity over a period of 3 to 5
years. Peripheral joint involvement is usually asymmetrical.
There may be associated iritis and aortitis. Genetic factor
influences the development of the disease and HLA antigen
with B27 specificity which is inherited is found in 95% of
patients. The possible environmental factors like infections
of the bowel (Klebsiella, Yersinia and Shigella) are linked
with the ankylosing spondylitis and immune response to
these bacteria produce antibodies which initiate the disease
process (Refer to Chapter ‘Low Backache’).
Reiter’s syndrome: (Vide supra).
Psoriatic arthritis Psoriasis may be associated with arthritis
involving small joints or the hands symmetrically simulating
 Polyarthritis
rheumatoid arthritis without rheumatoid factors. Sometimes
the distal interphalangeal joints only may be involved, with
some degree of asymmetry or monoarticular arthritis or
spondylitis may be encountered. Unique associations with
HLA-C (CW6) and in spondyloarthropathic presentation with
HLA B27 antigen are found. In psoriasis per se HLA B27 is
absent. The examination of the hand shows pitting and
discolouration of the nails or subungual keratosis. It is often
destructive with osteolysis and deformity. The diagnosis is
suggested by the typical skin or nail lesion of psoriasis which
precede arthritis by months to years. The presence of HLA
antigen rules out rheumatoid arthritis. X-rays show erosive
changes and narrowing of the joint spaces; dissolution of
terminal phalangeal tufts; whittling of all metatarsals and
metacarpals and cupping of the proximal ends of the
phalynges.
Enteropathic arthropathy Enteropathic arthropathy (ulcerative
colitis, Whipple’s and Crohn’s disease) may be associated
with the involvement of large joints. This arthritis of
inflammatory bowel disease lasts for few weeks and the
activity of the underlying disease determines the recurrence.
Sacroilitis and spondylitis may resemble ankylosing
spondylitis. The HLA B27 antigen is usually absent in
peripheral arthritis and present in those who ultimately
develop ankylosing spinal disease.
Whipple’s disease is rare and arthritis may precede the
intestinal symptoms. Enteropathic arthropathy is not known
to produce any residual damage (Refer to Chapter ‘Chronic
Diarrhoea’).
Behçet’s syndrome It is characterised by painful orogenital
ulcers, severe ocular inflammation, erythema nodosum, and
papulovesicular lesions, arthritis, gastrointestinal (diarrhoea)
and neurological manifestations (meningoencephalitis,
dementia) and arthritis of large joints without residual
damage. Sacroilitis and spondylitis are rare. Remissions and
exacerbations are documented. The appearance of a pustule
with erythema around it after 24 h, at the site of a needle
puncture, is diagnostic. It is HLA 85/51 associated disease
of unknown cause (?Viral)
Idiopathic
Sarcoidosis (Refer to Chapter P.U.O.)
Relapsing polychondritis It is characterised by nondeforming
polyarthritis, inflammation of cartilaginous structures (floppy
ear and saddle nose deformity and collapse of the tracheal
and bronchial cartilage rings); ocular lesions (conjunctivitis,
scleritis, iritis); cardiovascular system (aortic regurgitation
417
and vasculitis of big vessels). It is prone to recurrence and
diagnosis is confirmed by biopsy of the affected cartilage.
Palindromic rheumatism It is a rare entity characterised by
recurrent attacks of painful inflammation of multiple joints
and adjacent areas like distal phalanges, finger pads, heels
and Achilles tendons. Each attack lasts for few hours to
48 hours followed by a remission. The joints are swollen,
painful, periarticular soft tissues become red and swollen
with stretching of overlying skin. There may be a nonitching
and tender swelling over the affected muscles. Constitutional
symptoms are absent. Laboratory and X-ray finding are
not contributory.
Intermittent hydrarthrosis It is a recurrent painless joint
effusion, occurring at regular intervals and lasting for several
hours to several days. The knee joint is usually involved.
The cause is unknown and it may be a manifestation of
infective systemic disease or initial manifestation of
rheumatoid arthritis.
II. Degenerative (Mechanical)
Osteoarthritis
It is a slowly progressive noninflammatory joint disease
resulting in the loss of cartilage due to degradation of
chondrocytes and formation of osteophytes. It involves one
or more of the larger joints or distal interphalangeal joints or
spine and may be symmetrical or occasionally generalised.
The aetiology is unknown. It may be primary affecting the
elderly group or secondary to injury or congenital
abnormalities occuring in the younger group (e.g.
incongruity of joint surfaces).
Clinically, mild continuous aching pain may be localised
either to one side of the joint or generalised over the joint.
Pain may be elicited by compressing patella against femur
on active extension of knee (Shrug test). Aching pain on
movement and stiffness with rest, swollen joint due to
marginal proliferation and capsular thickening, restricted
range of movement and absence of systemic features are
the typical presentations. Examination reveals a dry creaking
sensation, tenderness and effusion. A fixed joint deformity
may result corresponding to the destruction. Muscle spasm
and atrophy and complete loss of movement are rarely
found. Heberden’s node is a typical cartilaginous and bony
enlargement on the dorsal aspect of the distal interphalangeal
joint and may occur in many fingers. The degenerative
process affects the surface of the articular cartilage initially,
and the subchondral bone becomes increasingly vascular
and thickened subsequently. The vertebral involvement may
affect the nerve roots resulting in radicular pain with sensory
 418 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
changes and motor weakness. Radiological features include
narrowing of joint space, presence of osteophytes at the
bone edges and subchondral sclerosis, sometimes with
erosions of the joint surface or bone cysts in the subchondral
bone, with absence of osteoporosis. Synovial fluid is clear
with low cellular count and sugar values. Other laboratory
findings are essentially normal.
Neuropathic joint Disease (Charcot’s joint)
The 90% of cases occur due to tabes dorsalis and the
remainder are associated with syringomyelia and peripheral
nerve lesions. The degeneration of cartilage and formation
of loose bodies occur in such neurological diseases where
there is loss of joint sense. The joints are swollen and
painless. A large amount of synovial fluid enlarges the joint
and overlying tissues become oedematous. The knee joint
in tabes and the elbow joint in syringomyelia are the joints
of predilection. Examination reveals marked irregularities
due to bony projections from articulating bones or bone
formation in the surrounding soft tissues or intra-articular
bodies in the thickened capsule. The overlying skin may be
hot. There is increased mobility and instability of the joint.
A feeling of bag of bones in the joints or a loud crepitus on
movement is familiar. Paroxysmal attacks of pain may be
complained due to intra-articular fractures. The aspirated
synovial fluid is yellow with many cells particularly
lymphocytes and clots rapidly. Other features of either tabes
dorsalis or syringomyelia are discernible. Roentgenographic
findings are marked erosions of joint surfaces with new
bone formation at the articular margins; pathological
fractures healing with considerable callus may be present.
III. Metabolic
Gout
It is characterised by recurrent attacks of acute arthritis of
sudden onset especially of the metatarsophalangeal joints
of the big toe or other joints of the feet or the ankle or knee.
It is usually monoarticular and the attacks occur during
nights heralded by severe pain in the joints and mild fever
and chills. There is marked tenderness and moderate
swelling. The attack lasts for 1 to 3 days and declines in
severity gradually in the next one week. They are precipitated
by alcoholic excess or fatty meal and emotional upsets. It is
an inherited metabolic disorder with hyperuricaemia. The
urate crystals are deposited in the articular cartilage, synovial
membrane, ligaments and capsules of the joint. When it
become chronic, painless deposits of urate crystals appear
on the ears especially at the helix areas and around the joints
of the hands. Secondary gout may occur in haematological
disorders where there is marked breakdown of nuclear
protein. Urolithiasis with attacks of renal colic may precede
the attacks of arthritis. Diagnosis is confirmed by
hyperuricaemia and demonstration of urate crystals on
synovial biopsy or within the phagocytes of the joint fluid
by polarised light microscopy. X-rays may show punched
out areas in joints or bones in the later stage of the disease,
although radiological changes may not be present in the
early cases.
Pseudogout (Chondrocalcinosis Articularis)
It may be associated with primary hyperparathyroidism.
Pseudogout may simulate acute attacks of gouty arthritis
or may manifest as chronic synovitis like rheumatoid arthritis
or degenerative joint disease like osteoarthritis. It affects
primarily large joints only (knees) or symphysis pubis. There
is chondrocalcinosis. The diagnosis is established by
demonstrating crystals of calcium pyrophosphate in the
synovial fluid. Blood uric acid is normal. X-ray of the joint
shows punctate linear calcification in the articular cartilage
and thin band of calcification of the menisci.
Ochronosis (Alkaptonuria)
It is an inborn error of metabolism with deficiency of an
enzyme homogentistic acid oxidase. Cartilaginous and severe
arthritis may result due to accumulation of homogentistic
acid which results from incomplete breakdown of tyrosine
and phenylalanine. Urine turns dark or black on standing or
at once by adding alkalies prior to development of arthritis.
Large joints and lumbosacral spine may be involved with
pain and limitation of movement. Black pigmentation of the
nose or ears may be present. Perspiration stains the clothing
brown. Homogentistic acid in the urine can be detected by
adding a drop of dilute ferric chloride solution when it turns
bluish green. Copper solutions (Benedict’s reagent) are
reduced and diabetes mellitus may be diagnosed erroneously.
X-ray of the lumbar spine is highly characteristic which
shows dense calcification of the intervertebral disc and
narrowing of the intervertebral spaces.
Hyperlipidaemia
Recurrent migratory polyarthritis affecting the knees and
small joints of the hands is a feature of familiar hyper-
betalipoproteinaemia (type-2). The attack consists of swollen
erythematous joints with formation of noninflammatory
synovial fluid and lasts for one week.
 Polyarthritis
Amyloidosis
The amyloid which is a fibrous protein may be deposited in
the synovial membrane and synovial fluid or articular cartilage
resulting in arthropathy. Small joints are involved
symmetrically. The deposition of amyloid protein may affect
any organ system. Biopsy or electrophoresis and
immunoelectrophoresis of serum and urine assist the
diagnosis.
Haemochromatosis
This iron storage disorder results in the accumulation of
iron in parenchymal tissues [liver (portal hypertension.)
heart (congestive heart failure), pancreas (diabetes mellitus)
and pituitary—testicular atrophy and skin pigmentation with
melanin]. The arthropathy is polyarthritic in nature involving
small joints and progressively affecting big joints. Calcium
pyrophosphate may be deposited in the knees as in
pseudogout. Serum iron and ferritin are raised.
Wilson’s Disease (Refer to Chapter ‘Jaundice’)
Less Common Arthritides
Hereditary (Congenital Arthropathies)
Connective Tissue Disorders: Ehrlers-Danlos Syndrome (EDS)
It is inherited as autosomal dominant and recessive and X-
linked recessive. Hypermobility of joints and proneness to
develop effusions; hyperextensible and lax skin which can
be pulled far away and restored to original position on release,
and easy bruising are the major features. Premature
osteoarthritis may occur.
Gargoilism (Hurler’s syndrome) It is a childhood disease
characterised by deposition of mucopolysaccharide in
tissues like liver. Limitation of joint movement of shoulder,
hip and fingers may be present. Contractures occur with
formation of claw hand. The other features are large head,
flat nose, thick lips, neck, kyphosis and mental retardation.
Arthrogryposis multiplex congenital Though present at birth,
it is usually diagnosed later as symmetrical joint involvement
especially of the lower limbs. Overlying subcutaneous tissues
are thick and doughy. It is painless but secondary changes
may cause discomfort later. Joint contractures occur which
may be mistaken for rheumatoid arthritis, if seen for the
first time in adulthood.
Endocrinal
Acromegaly In acromegaly, the production of excessive
growth hormone causes enlargement of the hands, feet,
419
nose and jaw. The growth of intra-articular cartilage and
soft tissue may produce joint pains, swelling and limitation
of movements especially the temporomandibular joint.
Headache and pressure effects leading to visual impairment
are other features.
The diagnosis is confirmed by:
i. Estimating growth hormonal values during a glucose
tolerance test. In acromegaly, after the ingestion of
100 g of glucose, the growth hormone values are not
suppressed to less than 5 mg/dl, as in normals.
ii. Serum phosphate levels are increased.
iii. X-ray may show enlarged sella turcica sinuses, tufting
of the terminal phalanges, and thickening of the soft
tissue of the heel (exceeds 2.2 cm.)
Hypothyroidism (Refer to Chapter ‘Oedema’).
Hyperparathyroidism (Refer to Chapter ‘Low Backache’).
Haematological
Sickle cell anaemia One or two joints may be swollen with
noninflammatory effusions especially in sickle cell crisis.
Swelling may last for about 10 days. Painful swelling of the
hands and feet, with characteristic rectangular appearance
of the bones of hands and feet in the radiographs, is
described as handfoot syndrome. Septic necrosis of the
femoral head occurs with secondary arthritis or
osteomyelitis and septic arthritis especially due to Salmonella
infections (Refer to Chapter Jaundice).
Haemophilia Big joints are commonly affected. They become
swollen and painful with limitation of movement. The
symptoms subside when bleeding ceases. Such recurrent
episodes may lead to chronic synovitis and finally may lead
to fibrous ankylosis (Refer to Chapter Bleeding Disorders).
• Henoch-Schönlein Purpura (Refer to Chapter ‘Bleeding
Disorders’).
• von Willebrand’s Disease (Refer to Chapter ‘Bleeding
Disorders’).
Neoplastic
• Carcinoma of the Bronchus (Hypertrophic Pulmonary
Osteoarthropathy)
Bronchogenic carcinoma may produce periosteal
inflammation at the distal end of the long bones and
metacarpal bones. The synovial membrane also gets
inflamed resulting in arthritis and finally clubbing. This
hypertrophic pulmonary osteoarthropathy is uncommon
in suppurative lung disease with advent of antibiotics.
• Lymphomas rarely polyarthritis may be a feature of
malignant tumours like lymphomas.
 420 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Occult Neoplasm
Occasionally polyarthritis simulating rheumatoid arthritis
may be the first manifestation of occult neoplasm.
Associated weight loss and anaemia in elderly persons
are suggestive. The arthritis may subside when the
malignant tumour is resected.
• Haemangioma
It is a rare vascular tumour of synovial membrane
occurring in young adults and usually located in the knee
joint. It is characterised by recurrent episodes of pain
spontaneously and associated with a swelling.
Movements are painful and quadriceps is wasted. Bloody
effusions may occur. The tumour is outlined by a double
contrast arthrogram and arthroscopy reveals the nature
of the growth.
• Synovial Chondromatosis
Cartilaginous or osteocartilaginous bodies develop in the
synovial membrane and protrude into the joint cavity.
Gradually the body may be extruded into the joint cavity.
The articular surfaces may be affected by these loose
bodies which cause multiple erosions and ultimately
degenerative arthritic changes.
• Lipoma
It may occur in subsynovial fat and may extend into the
joint cavity. Knee joint is affected in particular.
• Synovial Xanthoma (Pigmented villonodular synovitis)
It is an idiopathic villous overgrowth with pigmented
(brownish) synovial membrane of the knee joint due to
deposits of cholesterol and haemosiderin. The joint may
be distended by chocolate coloured nodular masses
associated with pain. Effusions occur and the aspirated
fluid may be thick orange brown colour containing
cholesterol. A double contrast arthrogram reveals a
bubbly flocculent appearance within the cavity. Synovial
biopsy shows characteristic polyhedral cells with yellow
pigment and foam cells.
• Synovioma. It is a slowly growing malignant tumour in
juxta position to synovial tissue. It occurs in young adults
invariably in the soft tissue outside the joint with
predilection to the knee joint. The swelling commences
in the periarticular site and gradually increase in size
accompanied by pain.
Traumatic Arthritis
Traumatic polyarthritis is rare. Trauma to a joint may be
direct or indirect secondary to postural strain. Direct trauma
causes the soft tissues especially the synovial membrane to
become congested and contused with increased formation
of synovial fluid, containing serum and fibrin. This usually
mainfests as swelling, pain on movement, tenderness and
spasm of the muscles. Haemarthrosis may be minimal.
Oedema may be localised over the traumatic site. The
articular cartilage may become soft and fragile and ultimately
may be worn out exposing the subchondral bone. Tearing
of soft tissue structures like ligaments and menisci may
result in an unstable joint. Abnormal mobility in a lateral
direction is suggestive of torn collateral ligaments. When
the capsular covering is contused and torn, it may become
adherent to overlying structures during healing. Consequently
the movements of the affected joint become restricted and
muscles around it may get atrophic (periarthritis). The
aspirated joint fluid which varies from amber to bloody
colour, with traumatic history is highly diagnostic. Tears of
the extensor muscles at the lateral condyle (tennis elbow)
or tears of the flexor muscles at the medial condy (Golfer’s
elbow) are commonly encountered.
Osteochondritis dessicans After repeated minor injuries, may
present as recurrent attacks of arhtritis particularly in the
knee. Elbow, hip and ankle are the other joints involved.
Sometimes sudden onset of spontaneous locking and pain
may occur due to flakes of articular cartilage with or without
portions of underlying bone. Effusions may follow.
Iatrogenic
Drugs like hydralazine and isoniazid are documented to
induce erythematosis.
Serum sickness is characterised by arthralgias,
lymphadenopathy and glomerulonephritis. It is due to
deposition of circulating drug antibody complexes over
endothelial surfaces. Complement activation and
inflammatory response occur. The drugs incriminated are
penicillin, streptomycin, sulphonamides and aspirin. May
cause serum sickness type reactions.
A frozen shoulder (capsulitis) presents as spontaneous
shoulder pain with capsular tenderness and restricted
movements. It may follow breast or thoracic surgery,
myocardial infarction, hemiplegia or consequent to rotator
cuff lesion.
CLINICAL APPROACH
Since the joints are involved due to variety of causes in
various clinical settings and almost all joint disorders result
in swelling, pain and limitation of movements, a painstaking
history and physical examination are mandatory to decide
whether it is inflammatory or noninflammatory type; and
also to determine the possible underlying cause. Since, there
are muscles around the joint and if any one of them is
 Polyarthritis
affected it may simulate joint pain/arthritis. Certain other
fallacies like a chronic joint disease simulating as paralysis
of the limb and vice versa or pain in the extremities of
different aetiology producing a stiff joint or pain arising
from juxta-articular bones (acute osteomyelitis and
epiphysitis) presenting as an acute joint disease, must be
borne in mind.
History
1. Age: (a) Younger age group (5-15 years): Rheumatic
polyarthritis or juvenile rheumatoid arthritis; (b) Young
adults: Tuberculous arthritis; (c) Older age group:
Osteoarthritis.
2. Sex: Males—Seronegative Spondyloarthropathies (SSA)
Females—Rheumatoid arthritis.
3. Onset and duration: (a) Sudden onset with a history of
recurrence over a period of months is suggestive of
rheumatoid arthritis and other connective tissue
disorders; (b) sudden attack of migratory (involvement
of second joint begins when the first joint is still under
remission) or flitting arthritis is suggestive of rheumatic
fever; (c) sudden onset with a history of recurrences
and duration of less than 10 days is gout; (d) gradual
onset, progressively becoming chronic in about two
months duration suggests osteoarthritis (if the duration
is more than six weeks, it is said to be persistent).
4. Pain: (a) Time of occurrence—Pain after midnight
continuing till the morning and preventing morning
looseness of the joints, i.e. stiffness present for at least
half an hour, is suggestive of rheumatoid arthritis; (b)
Effect of activity: Pain increases during motion and
decreases at rest as in osteoarthritis, pain decreases by
movements and does not subside at rest (rest pain) as in
rheumatoid arhtritis; (c) associated with any swelling
of the joint.
5. Symptoms: (a) Constitutional—Fever and malaise
associated with septic arthritis; (ii) systemic symptoms
like extra-articular manifestations and skin eruptions
(connective tissue disorders); conjunctivitis and urethritis
(Reiter’s); abdominal pain and diarrhoea (ulcerative
colitis); dry mucous membranes (Sjögren’s).
6. Antecedent history and familial history: (a) Antecedent
history. Past history of (i) trauma, (ii) bleeding, and (iii)
ingestion of drugs for long like hydralazine.
(b) Familial history—Suggestive of rheumatoid arthritis,
gout.
421
Physical Examination
The primary object should be to differentiate whether the
symptoms are due to articular or periarticular. If the
symptoms are due to periarticular lesions, signs of joint
tenderness or effusions or crepitus absent and painful only
on active movement unlike articular which is painful both
on active and passive movement of the joint.
Local Examination of the Joints
Inspection (from front, sides and back) Proceed from above
downwards and look at all joints comparing with the
corresponding joints.
i. Number of joints involved: Mono (one), e.g. gout,
tuberculosis, Pauci or Oligo (2-4), e.g. juvenile
rheumatoid arthritis; polyarthritis (5 and above),
rheumatic.
ii. Types of joints involved: (a) Peripheral (small joints
of hands and feet as in rheumatoid arthritis; large joints
like knee, etc. osteoarthritis); (b) axial (spine) as in
ankylosing spondylitis. Small joints are also involved
in osteoarthritis especially the distal interphalangeal
joints (DIP), which is spared in rheumatoid arthritis.
Similarly, big joints are also involved in rheumatoid
arthritis.
iii. Pattern of involvement: Symmetric of asymmetric
involvement
a. Acute symmetrical (inflammatory like rheumatic
fever).
b. Acute asymmetrical (reactive arthritis-Reiter’s).
c. Chronic symmetrical (rheumatoid and other
connective tissue disorders).
d. Chronic asymmetrical (peripheral arthritis of
ankylosing spondylitior psoriatic arthritis).
e. Intermittent symmetrical (idiopathic group vide
supra).
f. Intermittent asymmetrical (enteropathic
arthropathy).
iv. Signs of inflammation like redness over the skin
v. Swelling of the joints (inperiarticular involvement the
swelling is usually anatomically away from joint)
vi. Irregularity of the joints
vii. Any scars or sinuses
viii. Any wasting of the muscles around the joint.
Palpation
i. If the overlying skin is:
a. Warm (acute inflammation, septic arhtritis or
gout)
b. Moist(suppurative or rheumatoid arthritis)
c. Dry (gout)
 422 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
ii. Tenderness: Localised tenderness, whether it is in the
joint or over the metacarpal and metatarsal heads or
adjacent structure like mid supraspinatus muscle.
Grading of tenderness
a. Grade I: winces
b. Grade II: winces and withdraws
c. Grade III: extremely tender not allowing to touch, e.g.
gout, rheumatic fever, suppurative arthritis
iii. Any doughy feeling. If there is doughy feeling, it is
synovial or capsular thickening near the surface of
the joint.
iv. Elicit fluctuations or fluid wave (bulge sign) in a joint
effusion or patellar tap.
v. Feel for any bony outgrowth on the fingers:
Heberden’s nodes, or loose bodies in the knees.
vi. Any enlargement of the ends of the bone or disturbed
relationship of the bones in the joint (deformity).
vii. Any painful swelling in the popliteal bursa (Baker’s
cyst).
Functional state evaluation (Minimal stage to house-bound
stage)
a. Range of movement: Degree of limitation of the
movement of all joints like lumbar flexion (standing)
or flexion of knee and hip (lying) should be assessed
clinically or with a protractor or goniometer. The
limitation may be due to arthritis or muscle spasm or
ankylosis. All movements both active and passive
should be measured in degrees from a neutral position.
b. Crepitus on movement: A creaking or grating sensation
may be felt on movement, which indicates
osteoarthritis.
c. Muscle changes like wasting are appreciated by
measuring the limb on either side and assessing muscle
weakness.
d. Evidence of joint destruction with deformity.
e. Ankylosis.
f. Gait.
General Examination (Especially for Extra-articular features)
Examination of the face: Facies—Acromegalic facies.
B. Look for pallor and anaemia, generalised wasting,
lymphadenopathy, skin eruptions, butterfly rash,
subcutaneous nodules (erythema nodosum,
rheumatoid nodules, gouty trophi), mucocutaneous
lesions (oral/genital) or ocular lesions
C. Vital data: Temperature, pulse, blood pressure, etc.
Systemic Examination (For systemic features
particularly)
i. Cardiac murmurs
ii. Pleurisy or pulmonary fibrosis
iii. Hepatosplenomegaly
iv. Entrapment neuropathy.
(Multisystem involvement suggests systemic lupus
erythamatosis-SLE).
Investigations
1. Blood Tests
A. Total white cell count is reduced in SLE,
neutrophil leucocytosis in acute septic arthrits.
B. Differential count:Eosinophilia is a feature of
vasculitis.
C. ESR is markedly raised in inflammatory diseases
(infections or immunological). It is a measurement
of acute phase response.
D. Platelet count is reduced and PTT in SLE
increased.
E. Blood culture.
2. Genitourinary investigation: In suspected gonococcal
arthritis.
3. Immunological tests:
A. Rheumatoid factor: Positive in 80% of cases of
rheumatoid arthritis. (The rheumatoid factor
usually sought for is IgM which may appear at
six months to one year interval).
B. Antistreptolysin O levels (ASO titres 200 Todd
units and above significant which develops at 15
days interval), increased in rheumatic polyarthritis.
The other antibodies like antistreptokinase,
antistreptodornase, antithyalurornidase can also
be sought.
C. Antinuclear antibodies: Positive in almost all cases
of SLE. (> 1 in 80)
D. DNA antibodies: Positive in 100% of cases of
SLE.
E. LE cell: Positive in 80% of cases of SLE.
F. Anti neutrophil cytoplasmic antiobodies.
G. Paired viral antibody test may be helpful in
reactive arthritis following certain viral infections
like Epstein-Barr and hepatitis-B.
H. HLA Typing: HLA B27 is negative in rheumatoid
arthritis and normal population whereas positive
in high percentage in seronegative Spondy-
loarthropathy.
I. Cyclic citrullinated peptide antibody (CCP)
precedes symptoms of RA. Test for CCP if RF is
 Polyarthritis
negative, as CCP is positive in 100% of
Rheumatoid arthritis (Titre > 1 in 40 significant)
4. Biochemical
A. C-reactive protein raised in rheumatic fever and
rheumatoid arthritis, and yet another measure of
acute phase response.
B. Serum proteins: A.G ratio reversed in SLE.
C. Serum: Uric acid raised in gout.
D. SGPT/SGOT: Drugs like aspirin may raise it or
may be due to lupoid hepatitis.
E. Complement: Decreased in SLE especially C4
fraction and its monitoring aids follow-up of SLE.
5. Radiological
A. X-ray of the affected joints for evidence of loss
of joint space; bony erosions, juxta-articular
osteoporosis and subluxation as seen in
rheumatoid arthritis; and sacroiliac joints and bony
bridges in spinal X-rays as seen in ankylosing
spondylitis or calcification of tendon insertion sites
(enthesopathy)
B. X-ray of the foot for calcaneum spur as seen in
Reiter’s syndrome or Plantar fasciitis.
C. X-ray of the chest for any evidence of pulmonary
tuberculosis or pulmonary manifestations of
rheumatoid arthritis.
D. Arthrogram: Inject radio-opaque contrast medium
into the joint to diagnose synovial rupture or
Baker’s cyst.
6. Examination of the synovial fluid: Aspiration of the
synovial fluid from the joint under strict aspectic
conditions provides diagnositc clues.
A. Naked eye examination for assessing the signifi-
cance of the colour of the aspirate: Colourless
and clear (normal); turbid (rheumatoid arthritis,
tuberculosis and other inflammatory arthritis);
turbid and yellowish (septic arthritis and acute
gout), bloody or xanthochromic (traumatic).
B. Microscopic examination
i. Total count and differential count of the joint
aspirate. Leucocyte count<200 (normal);
<2,000 in osteoarthritis; 5000 to 50,000 in
rheumatoid arthritis and gout;> 50,000 in septic
arthritis. Neutrophil count is 75% in
inflammatory as against 25% in non
inflammatory or normal.
ii. Polarising light microscopy for crystals: Uric
acid crystals suggest gout.
423
iii. LE cell and rheumatoid factor.
iv. Joint fluid complement: Is lowered in relation
to the total protein concentration of the fluid in
rheumatoid arthritis whereas it is normal in
noninflammatory arthritis.
v. Gram’s stain, Ziehl-Neelsen’s stain for tubercle
bacilli; and culture for the organisms.
C. Mucin clot test: Acetic acid is added to the
centrifuged joint fluid. If a ropy clot is found, it is
deemed to be a good quality and indicates
presence of enough hyaluronic acid. Mucin clot
of good quality is seen in degenerative disease
whereas it is of poor quality in inflammatory joint
disease.
D. Fibrin clot: Normally the joint fluid does not clot
due to absence of fibrinogen. In inflammatory
disease, it spontaneously clots.
E. Sugar levels: Synovial glucose levels are low in
inflammations and the difference in the serum and
joint fluid in increased as against minimal
difference of 10% or no difference in the
noninflammatory or normal fluid.
F. Lactate: High levels of lactate indicate septic
arthritis.
G. Viscosity in inflammatory group.
7. Biopsy: Needle biopsy of the synovium may offer a
precise diagnosis in difficult situations.
8. Fibreoptic arthroscopy: Arthroscopic examination
especially knee is indicated for diagnosis and
assessment of articular cartilage and synovial disease,
before and after treatment since it offers a clear view
of the interior of the joint and enables early biopsy
(Fig. 27.4).
TREATMENT OF POLYARTHRITIS
A precise surmise as to the cusative mechanism of the joint
affliction must be obtained before designing the appropriate
therapy. In this exercise, an initial screening of the locomotor
system to assess whether arthralgia is due to joint disease
or due to affections of muscles and/or bones presenting as
arthralgia, is an essential step. Further an enquiry is
necessary to know whether it is (i) monoarticular or
polyarticular, (ii) of acute or chronic or acute-on-chronic
onset, (iii) inflammatory (infectious or autoimmune) or
noninflammatory and (iv) a systemic disorder or just a local
pathology (degenerative or traumatic).
 424 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

e. Indole derivatives—Indomethicin (25 mg tds)

f. Paraminophenol derivatives—Paracetamol
(1-2 gms/4)
g. Pyrazolones (not used now)
• Oxyphenbuta zone (100 mg tds)
• Phenylbutazone (100 mg tds)
h. Pyrrolo-Pyrrole-Ketorolac (10 mg 6th hrly)
NB: Salicylates: Aspirin 2-4 gms/d (better not use
as symptomatic remedy as it is specific for
rheumatic fever)
B. Selective Cox—2 inhibitors:
• Celocoxib (100 mg bd)
• Rofecoxib (12.5 mg bd)
• Valdecoxib (10 mg bd)
• Etoricoxib (60-120 mg once daily)
• Parecoxib (40 mg bd)
• Nabumetone (1-2 gm od)
• Nimesulide (100 mg bd)
Fig. 27.4: Knee arthroscopic view of villonodular synovitis with
its distinctive brownish colour (For colour version see Plate 1) As there is a wide choice, suitable agent is chosen on
the merits of the case (type of disease, convenience,
Symptomatic Treatment proneness for side effects and any other existing disease
like bronchial asthma). Since most of the drugs are likely
1. Optimum rest. to produce gastric irritation, H2 receptor antagonist may
2. Local therapy: (a) External application of heat (hot water be added.
for mentations) or wax; (b) short wave diathermy; (c) NB: Marked as • are the drugs commonly used.
rubefacients. NSAID/analgesic combinations (Topical) 4. Other drugs: (i) Weak opiods (codeine, dextropro-
3. Nonsteroidal anti-inflammatory drugs (NSAIDs), i.e. poxyphine); (ii) Muscle relaxants; and (iii) Antide-
(Non-Aspirin) pressants/anxiolytics may be considered (Refer to
These are cox (cyclo-oxygenase) inhibitors and non- Chapter Low Backache). (iv) Intra-articular steroid
opioid analgesics (Paracetamol) infection or systemic steroids in refractory cases.
(v) Physiotherapy plays a pivotal role.
The former may be either nonselective or selective.
Nonselective Specific Treatment for Specific Diseases
A. Cox Inhibitors:
a. Heterocyclin aryl acetic acid (Phenylacetic Inflammatory
acid) derivatives Infectious (microbial) arthritis: The treatment consists of
• Diclofenac sodium (50 mg tds) appropriate antibiotics based on the causative agent. The
• Diclofenac potassium (50 mg tds) choice depends on the findings from the gram film or other
• Acelofenac (100 mg bd) appropriate stains; synovial and blood cultures. However,
b. Propionic acid derivatives. initial treatment, pending the results, cloxacillin and benzyl
• Ibuprofen (400 mg tds) penicillin or cephalosporin parenterally may be given. If the
arthritis is proved to be septic, antibiotics are given at least
• Naproxen (250 mg bd)
for six weeks. Drainage or joint aspirations with local
• Ketoprofen (50 mg tds) instillation of antibiotics may be done, if necessary.
• Flurbiprofen (100 mg bd) For management of bacterial and viral infections (Refer
c. Fenamates—Mefenamic acid (250 mg tds) Chapter ‘Pyrexia of unknown origin’).
d. Oxicam Chlamydial infections are treated with Tetracycline (500
• Piroxicam (20 mg bd) mg/6 for 3 weeks).
• Texoxicam (20 mg od) Lyme disease is treated with tetracycline (250 mg/6 for
• Meloxicam (7.5 mg bd) 10-20 days).
 Polyarthritis
Sporotrichosis infection is managed with iodides and
IV amphotericin. (Refer to Chapter ‘Pyrexia or Unknown
Origin’).
Reactive/Postinfectious Arthritis
Rheumatic fever
a. Bed rest is essential for about 2-6 weeks (till ESR returns
to normal).
b. Soluble aspirin (90 mg/kg/d in divided doses). Dose is
reduced gradually and maintained till ESR is normal.
c. Corticosteroids: Prednisolone (0.5mg/kg/d in divided
doses) especially useful in the presence of carditis.
d. Antibiotics: Benzyl penicillin (600 mg i.m.) is given to
eradicate streptococci (after testing for penicillin
sensitivity.) If sensitive to penicillin, erythromysin (250
mg sixth hourly) may be given for 10 days.
e. Prophylaxis: Since the prevention of recurrences and
rheumatic heart disease is of paramount importance,
benzathine penicillin (1200000 units once in three weeks
i.m.) is given for 5 years, preferably till the age of 20
years. Or parenteral benzathine penicillin is given for
one year at least, followed by oral phenoxymethyl
penicillin (500 mg/d) for the said period. Sulphadiazine
(1 g/d orally) is the alternative for penicillin sensitive
patients. (Streptococci, fortunately, have not developed
resistance to penicillin).
Antibiotic cover before operation or dental surgery
and prompt treatment of acute upper respiratory
infections facilitate prophylaxis.
f. Treat cardiac failure if occurs (Refer to Chapter
‘Oedema’).
Reiter’s Disease
a. NSAIDs (Naproxen or indomethacin) and analgesics
(paracetamol).
b. Local cortisone injection, if necessary.
c. Cytotoxic agents in destructive arthritis.
d. Oxytetracycline (250 mg 6th hourly) for 2 to 3 weeks.
e. Conjunctivitis and urethritis subside as arthritis subsides.
If uveitis or iritis occurs, topical or systemic
corticosteroids are given.
f. In postsexual chlamydial infections tetracyclines may
help esp. to prevent PID and in postenteric cases
ciprofloxacin may be helpful esp. for yersinia infections.
Other Postinfective Types
(Refer to Chapter Pyrexia of Unknown Origin).
425
Connective Tissue Disorders (Autoimmune)
Rheumatoid arthritis
a. Medical therapy
i. Analgesics (first line of drugs to relieve pain),
aspirin and other NSAIDs (vide supra), H 2
receptor antagonists and misoprostal are
considered for gastric protection.
ii. Disease modifying drugs (second line of drugs to
reduce disease activity) indicated in active
synovitis, erosive X-ray changes and deteriorating
function with high ESR.
• Chloroquine—200-400 mg/d (maximum effect in
6 weeks to 6 months).or hydroxy chloroquine
200 mg twice daily for 3 months and then reduce
to 200 mg once daily)
• Gold salts (oral or IM)—25 mg/week, increased
gradually till response occurs (i.e.3-5 months)
when the dose is decreased so as to maintain at
50 mg monthly.
• Sulphasalazine—0.5 g increased to 2 g in the
course of four weeks.
• Methotrexate—7.5-15 mg/week.
• d-penicillamine—250 mg/d for one month. 500
mg/d for 2nd month and 750 mg/d in the 3rd
month.
• Minocyclin—(50-100 mg b.d.)
• Leflunomide: 100 mg daily for 3 days, followed
by 10-20 mg daily for two years.
iii. Corticosteroids (occasionally) intra-articular
(maximum 4 injections into one joint during one
year prevents cartilage destruction) or systemic
(avoid as far as possible).
iv. Combination treatment with disease modifying
drugs with or without corticosteroids. (gold and
chloroquine; or sulphasalazine and penicillamine;
or methotrexate, sulphasalazine and hydroxy-
chloroquine).
v. Other cytoxic and immunosuppressants in
resistant cases (if there is no response even after
one year), chlorambucil (0.1-0.2 mg/kg);
cyclophosphamide (2-3 mg/kg) azathioprine(50-
100 mg/d); cyclosporin (3-6 mg/kg/d).
vi Adjunctive drugs: Muscle relaxants; rubifacients;
antidepressants.
b. Supportive therapy (i) diet: chicken cartilage
and adequate calorie diet’ (ii) rest in optimum position;
 426 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
(iii) physical: moist heat; (iv) Physiotherapy; exercises
within limits of pain; and (v) Cryotherapy (vi) Physical
aids, orthopaedic support with metal pins or splints.
c. New biological treatment: Monoclonal antibodies against
T cell surface antigen (CD4) or against cytokines like
(tumour necrosis factor alpha, i.e. TNF inhibitors:
(Infiximab-3 mg/kg infusion every 2 months) preferably
with methotrexate or soluble TNF receptor fused to a
part of a immunoglobulin (Etanercept-25 mg twice
weekly) with methotrexate-15-25 mg/wk; (Adalimumab
40 mg s.c. every other wk) and IL-1 receptor antagonist
(Anakinra-100 mg s.c. daily or T-cell vaccination).
d. Medical synovectomy: Osmic acid or radio-colloids may
be tried to synovitis persisting despite all treatment
(Yttrium-90 silicate or Erbium-159 acetate used in
patients above 45 years).
e. Surgery: Synovectomy, tendon repair, arthroplasty or
joint replacement.
Variants of rheumatoid arthritis
a. Juvenile rheumatoid arthritis: As above ( in reduced
appropriate doses).
b. Sjögren’s syndrome: Artificial tears, nasal saline sprays,
sips of ice or plenty of water. Medical therapy as for
rheumatoid arthritis.
Systemic lupus erythematous (SLE) Treatment is aimed at
symptomatic relief and prevention of organ damage.
a. Incriminating drug, if any, should be withdrawn.
b. Fever with arthritis: Aspirin or NSAIDs.
c. Pleuritis or pericarditis: Indomethacin.
d. Skin,mucosal or joints: Antimalarials-Hydroxy
chloroquine 200 mg BD for 4 wks then O.D.
e. Occasionally prednisolone (10-20 mg/d) may be required
to suppress the symptoms.
f. If the symptoms are severe (lupus nephritis or CNS
involvement or haemolytic anaemia or thrombo-
cytopaenia) 1-2 mg/kg prednisolone/d or 1000 mg/d of
methylprednisolone for 3 days once a month or
cyclophosphamide i.v. (1 g/m2 of body surface every 3
weeks up to 3 months or cytotoxic drugs like
cyclophosphamide daily, methotrexate, chlorambucil and
azathioprine are also used in conjunction with cortisone).
Mycophenolate mofetil (1-2g/d) useful in renal lupus.
g. If unresponsive cyclosporin or plasmapheresis consi-
dered.
Vasculitis Systemic vasculitis, and giant cell arteritis are
treated with large doses of prednisolone (60-100 mg/d).
When the former is unresponsive, cyclophosphamide (2-3
mg/kg ) may be necessary. Polymyalgia rheumatica without
temporal arteritis is treated with prednisolone (15 mg/d)
and tapered to 7.5 mg/d. Pulse Methylpredniosolone is
beneficial in unresponsive polyarteritis
Progressive systemic sclerosis Since there is no curative
therapy available, symptomatic relief is sought.
Corticosteroids for inflammatory myopathy and /or arthritis
in the early phase; metoclopramide for hypomotility of GI
tract; H-2 receptor antagonists and antacids for reflux
oesophagitis; penicillamine for skin involvement; prazosin
or nifedipine for Raynaud’s phenomenon; ACE inhibitors
for hypertension are recommended.
Seronegative arthropathies
Ankylosing spondylitis Treatment is aimed to relieve pain and
facilitate skeletal mobility and prevent postural and respiratory
defects. NSAIDs like indomethacin and piroxicam are
effective drugs. Corticosteroids may be used if unresponsive
and/or associated with acute iritis. Radiotherapy is indicated
occasionally. Regular postural and breathing exercises;
sleeping on back on a bedboard without a pillow are helpful.
Surgical procedures to correct the deformities and for
rehabilitation, are adopted in selected patients.
Reiter’s syndrome and reactive arthritis (Vide supra)
• Psoriatic Arthritis: Analgesics and corticosteroids are
useful.
Out of all the disease modifying drugs used for
Rheumatoid arthritis only methotrexate is useful.
Treatment of psoriasis with coal tar, diatheranol and
salicylic acid external application; PUVA and acitretin
(25 mg/d orally) may control both joint and skin
symptoms.
• Enteropathic Arthritis- (Refer to Chapter‘Chronic
Diarrhoea’)
• Juvenile Rheumatoid Arthritis- (Vide supra)
Behçet’s syndrome Treatment is symptomatic. Arthritis
may be treated with NSAIDs. Corticosroids and
immunosuppressants are considered for major systemic
manifestations.
• Idiopathic (Refer to Chapter P.U.O.)
• Relapsing polychondritis
Treatment is with corticosteroids and cytotoxics may
be added if the disease progresses.
• Palindromic rheumatism
Treatment is symptomatic with NSAIDs. Gold salts are
used successfully.
Intermittent hydrarthrosis Treatment is symptomatic.
If necessary, aspiration may be done.
 Polyarthritis
Degenerative
Osteoarthritis The aim is to reduce pain and to improve
mobility and optimising biomechanics.
i. Pharmacological therapy
a. NSAIDs and paracetamol form the manistay and
they should be tailored to the actual needs, because
of adverse effects and possible acceleration of
the rate of cartilage loss. Topical NSAIDs gels
and others local rubs (solutions) are to be preferred
than systemic, as far as possible. Antioxidants
are beneficial.
b. Local corticosteroid injections at the tender sites
or intra-articular may be necessitated to achieve
the relief.
c. Maintain integrity of articular cartilage with intra-
articular hyaluronic acid (hyaluronan)
d. Chondroprotective agents: Cartilage loss due to
degradation of chondrocytes may be mitigated
by glucosamine sulphate, chondrotin sulphate and
methyl sulphonyl methane and manganese orally.
e. Tetracycline or Doxycycline inhibits matrix
metallo-proteinase enzymes and stimulate collagen
synthesis.
f. Inhibition of cytokines (Tumour necrosis factor
alpha and interleukin-1) useful since cytokines are
linked to loss of cartilage.
g. Colchicine (1 mg) daily is effective
h. Angiogenesis inhibitors like antagonist of integrin
V3.
ii. Appropriate physical therapy: Physiotherapy and
occupational therapy. Since quadriceps are weak.
Muscle strengthening graduated exercises (quadriceps)
and maintaining good range of joint movement and
activity, are of proven value. Change from strenous
occupation is advised, if necessary.
iii. Correct abnormal biomechanics: Provide built up
shoes to equalise the length of the legs; relieve the
weight-bearing with walking stick, fitting or rubber
heels (in soles); avoid undue trauma and physical stress
to the affected joint; reduce weight if obese.
iv. Other measures
a. Joint washout; Sterile washout of an osteoarthritic
joint may be beneficial.
b. Traction: To seprate joint surfaces and stretch
the contracted capsule;
c. Surgery and/or splinting: Arthroscopic surgery,
arthroplasty and arthrodesis are considered as and
when necessary.
427
d. Chondrocytes transplantation is a new modality
of management.
e. Gene therapy: Through adenovirus mediated
therapy.
Metabolic
Gout
i. Drug therapy: For the acute attack NSAIDs like
indomethacin (50 mg 6th hourly) naproxen (250 mg
8th hourly) or diclofenae (50 mg 8th hourly) are given
till the attack subsides and continued with lower doses
for one week. Colchicine (0.5 mg every two hours)
though very effective, causes vomiting and diarrhoea.
ii. Prophylaxis
a. Allopurinol to reduce uric acid synthesis (300-
600 mg daily in divided doses).
b. Uricosuric agents: Probenecid (0.5 gm b.d.), or
sulphinpyrazine (100 mg t.d.s.).
c. Colchicine (0.5 mg b.d.) may be preferably given
with antihyperuricaemic therapy.
d. Precipitating factors: Purine rich foods, alcohol
and obesity are to be avoided.
iii. Surgery: If the tophus is large or ulcerating, surgery
may be undertaken.
Pseudogout NSAIDs and colchicine are not as effective as
in gout. Intra-articular injection of corticosteroid is effective.
Joint aspiration may be done if necessary.
Alkaptonuria (Ochronotic arthritis) Restriction of foods
containing tyrosine and phenylalanine and administering
vitamin C in high doses facilitate decreased excretion of
homogentisic acid. There is no definite treatment for the
degenerative arthritis.
Hyperlipidaemia The treatment consists of dietary and drug
therapy. A trial of dietary therapy for at least six months is
necessary before initiation of drugs in addition.
The dietary therapy consists of high carbohydrate and
low fat diet, the fat being reduced to less than 30% of calories
(saturated fat less than 10% of calories polyunsaturated fat
not more than 10% and without restricting mono-unsaturated
fats). Dietary cholesterol must be less than 300 mg per day.
If LDL cholesterol level is not lowered to less than 160
mg% within 3 months, the saturated fat is further reduced
to less than 7% and cholesterol to less than 200 mg/d. If
there is no response, drug therapy is introduced to reduced
the LDL levels preferably to less than 130 mg% especially
in the presence of coronary heart disease or its factors.
The lipid lowering drugs used are (i) fibric acid derivatives.
 428 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Fenofibrate (200 mg once daily) Gemfibrozil-600 mg twice
daily) (ii) bile acid sequestrant or anion exchange resins
(cholestyramine and colestipol 4 g twice daily and increase
the dose up to 16 g a day supplemented by folic acid; (iii)
niacin (100 mg b.d. increased gradually to 1 g b.d.); (iv)
fish oils (1 g b.d. increased to 3 g b.d.); (v) HMG CoA
reductase inhibitors; Lovastatin (20 mg daily, increased to
40 mg b.d.); other statins are simvastatin (10-20 mg)
Atorvastation (10-40 mg) Rosuvastatin (10-20 mg)
Pravastatin (10-40 mg) (vi) probucol (0.5 g b.d.). (vii)
Policosanol (10-20 mg OD) (viii) Ezetimibe (10 mg OD)
(ix) Soluble fibre-ispaghula (9-13 gm/d)
The combination therapy with resins and niacin, lovastatin
with either resins or niacin , and gemfibrozil and lovastatin,
is effective in lowering LDL and triglycerides and raising
HDL levels. Feno fibrate with low doses of statin is also
advocated. Commonly used drugs are Atorvastatin;
Ezetimibe, Fenofibrate and Niacin.
• Amyloidosis (Refer to Chapter Chronic ‘Diarrhoea’).
• Haemochromatosis (Refer to Chapters ‘Jaundice and
Oedema’).
Less Common Arthrides
Hereditary Arthropathies
Ehlers-Danlos syndrome No specific treatment is available.
Joint ligaments may be strengthened. Cardiovascular status
and bleeding tendencies may be evaluated.
Hurler’s syndrome Genetic counselling is all important.
Antenatal diagnosis may be sought in high genetic risks.
Preventive approach is better since the management is purely
symptomatic.
Arthrogryposis multiplex congenita The fixed deformities
resembling a wooden doll are corrected, before eighteen
months and followed by stretching and splinting regimen
during the growth period.
Endocrinal
• Acromegaly The long acting dopamine agonist like
bromocriptine orally (2 mg b.d. increased to 10 mg b.d.
gradually) or octreotide (somatostatin analogue)
subcutaneously are effective. Trans-sphenoidal surgery
and/or radiotherapy (external or interstitial irradiation
with yttirium into the pituitary) are other therapeutic
approaches.
• Hypothyroidism (Refer to Chapter ‘Goitre’).
• Hyperparathyroidism Surgical removal of adenoma is
ideal (Refer to Chapter ‘Polyuria’).
Haematological
Sickle cell anaemia (Refer to Chapter ‘Fatigue’).
Haemophilia (Refer to Chapter ‘Bleeding Disorders’).
Henoch-Schonlein purpura (Refer to Chapter ‘Bleeding
Disorders’).
von Willebrand’s disease (Refer to Chapter ‘Bleeding
Disorders’).
In acute haemarthrosis, the limb is elevated and the joint
is immobilised for 24 h. Ice packs may be helpful. Pain is
controlled and mobility is restored after the deficient factor
is replaced. If unresponsive, immobilisation and replace-
ment must be continued. Small doses of corticosteroids may
be helpful. Aspiration should be avoided as far as possible.
Knee flexion contracture and deformity may be treated
appropriately by gentle traction and/or manipulation.
Chronic synovitis due to repeated haemarthroses may
require synovectomy.
In severe joint destruction, arthrodesis may be indicated.
Neoplastic
Carcinoma of the bronchus (Refer to Chapter ‘Haemoptysis’).
Lymphomas (Refer to Chapter ‘PUO’).
Traumatic Arthritis
a. Insist on rest to the affected joint. A compression
bandage and ice packs applied. Aspiration of fluid may
relieve the pain. After the swelling subsides, suitable
exercises are adopted to prevent muscle atrophy and
periarticular adhesions.
b. On ambulation, elastic compression bandage may be
necessary to prevent joint instability.
c. Orthopaedic surgical management may be necessary in
persistent and recurrent effusions.
Iatrogenic
a. Incriminating drugs should be withdrawn.
b. Serum sickness of delayed type occurring after 8th day
of injection needs only symptomatic treatment.
Nevertheless it is rewarding to make an inquiry as to
previous injections of foreign (horse) Serum and for
any history of allergic diathesis. Give trial dose of 0.2
ml sc or 0.2 ml 1 in 10 dilution) (if allergy present) and
wait for 30 mts before giving full dose.
c. Frozen shoulder (Refer to Chapter ‘Pain in the
Extremities’).
Polyarthritis 429
430 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Polyuria
28
Polyuria implies persistent increased volume of urinary
output. Urine volumes of more than three litres per day
may be considered as polyuria. Transient increase may be
induced by the ingestion of large amounts of fluids or
exposure to cold or by diuretics or after attacks of migraine
or paroxysmal tachycardia. This has to be differentiated
from frequency of micturition, which connotes passage of
small quantities of urine frequently without an increase in
the total volume as such. Normally daily output of urine is
1500 ml varying widely from 2000 to 2500 ml and secreted
more by day than during night. If the amount of urine passed
by night (Nocturia) is almost the same or more than that
during day, it is abnormal and associated with most of the
polyuric states.
PHYSIOLOGY OF URINE FORMATION
Urine formation begins with ultrafiltration of plasma. About
70% of water and sodium chloride and 80% of potassium
filtered by the glomerulus are absorbed in the proximal tubule.
The remainder of sodium chloride and water pass into loop
of Henle where most of sodium chloride is reabsorbed and
water only to some extent. So the fluid which enters the
distal tubules and collecting ducts is necessarily hypotonic
(more water and less sodium). Here the reabsorption of
water is under the influence of antidiuretic hormone (ADH)
or vasopressin of the posterior pituitary. So much so the
osmotic equilibrium of the distal tubular fluid ( isotonicity)
is achieved by increasing water permeability of the wall of
the collecting tubules, in response to ADH. Similarly
reabsorption of sodium in the distal tubule is under the
influence of adernal cortex especially aldosterone, which
process is variably coupled with potassium and hydrogen
secretions and involves exchange with potassium or
hydrogen ions (Fig. 28.1).
Thus the osmotic pressure of the plasma depends on
water balance which is regulated by ADH. If there is excess
loss of water, osmolality rises resulting in thirst, increased
secretion of ADH, and formation of concentrated urine with
high osmolality. On the other hand, if more water is taken
than necessary, osmolality falls resulting in decreased ADH
secretion and formation of dilute urine with low osmolality.
So the urine concentrating and diluting mechanism depends
on the release of ADH.
Such mechanisms of ADH secretion in relation to the
osmolality of the blood plasma and the hyperosmolality of
the medullary interstitium (due to urea and high NaCl
concentrations) enable the kidney to excrete all the waste
products of metabolism in the normal urine volume of about
1500 ml/day (1 ml per minute). So urine is formed by united
action of glomerular filtration with selective tubular
absorption.
MECHANISM OF POLYURIA
This homeostasis, i.e. renal conservation of water may be
disturbed in certain clinical settings resulting in polyuria. In
essence, it reflects (i) obligate renal water loss due to excess
water intake; (ii) diminished tubular reabsorption of water
due to vasopressin deficiency or tubular damage; and (iii)
solute diuresis after glucose or mannitol infusion, with either
low or high specific gravity of urine respectively.
CAUSES OF POLYURIA
The causes of polyuria are enlisted in Table 28.1.
 432 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 28.1: Structure of nephron

Table 28.1: Causes of polyuria Contd...

I. Polyuria with High Specific Gravity (somatic diuresis) (iv) Primary hyperparathyroidism with hypercalcaemia
1. Diabetes mellitus damaging the tubules (v) Drugs like lithium (vi) Sickle cell
anaemia
2. Hypercalcaemia
3. Primary Polydipsia (Compulsive Water Drinking)
3. Hypertonic intravenous infusions (Mannitol, High Protein
Feedings) 4. Hypokalaemia
II. Polyuria with low Specific Gravity a. Diuretics
1. Renal Dysfunction b. Corticosteroids
a. Acute renal failure: Diuretic phase c. Conn’s syndrome (primary hyperaldosteronism)
b. Chronic renal failure d. Bartter’s syndrome
c. Natriuretic syndrome e. Alkalosis
2. Diabetes Insipidus f. Renal tubular failure
a. Neurogenic: Pituitary/hypothalamic disorders
b. Nephrogenic Diabetes Mellitus (DM)
(i) Heredofamilial (ii) Renal (a) Chronic pyelonephritis It is due to diminished availability or responsiveness of
(b) Analgesic nephropathy (iii) Hypokalaemia
endogenous insulin and characterised by metabolic
Contd... abnormalities and late systemic microvascular
 Polyuria
complications. It is classified into four clinical types (1)
dysglycaemia (Prediabetes) (2) primary or idiopathic, (3)
secondary, (d) gestational.
Dysglycaemic categories. (Prediabetes)
(i) impaired Fasting Glucose (IFG)
(ii) impaired glucose tolerance (IGT) or Borderline DM.
The diagnosis is suggested when the fasting and
postprandial glucose concentrations are between the normal
values and overt diabetes mellitus. (Impaired Fasting
Glucose: 110-126 mg % and normal PP glucose, i.e. (< 140
mg%) Impaired Glucose Tolerance: - increased postprandial
glucose: 140-200 mg % and normal fasting glucose, i.e. (<
100 mg%) It is significant since the follow-up studies show
that 2-4 per cent of subjects in this group deteriorate to
unequivocal diabetic state and may develop macrovascular
complications. There is doubling of the risk of coronary
heart disease and stroke as in NIDDM. However,
microangiopathy is uncommon. The risk factors like
smoking, hypertension, obesity, physical inactivity and
hyperlipidaemia must be appropriately tackled to prevent
the complications (vide supra). Latent chemical Diabetes
mellitus connotes that cortisone GTT is abnormal. So the
stages of DM may be stated as:
1. Latent DM,
2. Prediabetes and
3. Overt Diabetes mellitus.
Primary
Type-1 diabetes (Insulin Dependent Diabetes Mellitus—
IDDM)
The term insulin dependent is considered generally as
insulin treated, although it rearly implies that a subject is
likely to develop ketoacidosis in the absence of insulin. This
usually occurs in genetically predisposed individuals between
30 to 40 years (often in childhood or adolescence, i.e.
juvenile onset). An autoimmune pathogenesis is implied in
the aetiology. It is HLA linked and primarily associated with
D-locus. The HLA DR3 and/or HLA DR4 are probably in
linkage disequilibrium with immune (Ir) genes which appear
to exist on chromosome-6 within the HLA region. These
immune responsive genes are presumed to control the
immune response to environmental factors like
coxsackievirus infections or cytotoxic agents which are
capable of damaging the beta cells directly or by immune
mechanism. It is often associated with islet cell antibodies
in 80% of newly diagnosed cases. These may be transient
as in males and persistent in females. Certain HLA antigens
like DR3 and DR4 serve as markers. The fasting insulin and
433
total C-peptide immunoreactivity are absent or very low.
Nevertheless severe ketosis prone, C-peptide negative
diabetes may occur in the remaining cases without the above
characteristics.
Type-II diabetes (Non-insulin Dependent Diabetes Mellitus—
NIDDM)
This is of four types (i) obese NIDDM, (ii) non-obese
NIDDM and (iii) maturity onset diabetes in young (MODY)
or Masson type. (iv) Low Body Weight. These subjects
usually respond to oral hypoglycaemic drugs. Although they
may require insulin for effective control of hyperglycaemia,
they do not develop ketoacidosis if insulin is withdrawn.
This is common after 40 years of age especially in obese,
people. Insulin and C-peptide are low in non-obese type-II
and high in obese type-II. Though the plasma insulin is
high, there is diminished insulin response with relative insulin
deficiency. It is not HLA linked and not autoimmune and no
islet cell antibodies are present. However, genetic factors
are more important and environmental factors like obesity,
stress, diet, inactivity and pregnancy play critical role. The
insulin gene situated in the short arm of chromosome II
appears to be the possible genetic marker. All affected
identical twin pairs are concordant for NIDDM, as compared
to only 50% of IDDM. NIDDM in the young appears to be
dominantly inherited in some families.
The hepatic production of glucose is increased and/or
peripheral utilisation of glucose is decreased besides insulin
resistance. (Abnormal insulin molecule, insulin antagonists
like adrenocortical harmones or growth hormones, and target
tissue defects like decreased number of insulin receptors,
decrease in the cellular binding of insulin to receptors and
defective insulin action distal to the receptor binding, account
for insulin resistance.) Further impaired function of cell
membrane glucose transporter proteins or phosphorylation
may also contribute to the abnormal glucose metabolism.
Although the beta cells are enlarged and numerically
increased unlike in type-I, their functions are abnormal. The
ability to secrete insulin appears to be inversely related to
the degree of hyperglycaemia. The deficit in endogenous
secretion of insulin is the initial lesion and the onset is
triggered by factors associated with insulin resistance,
physical inactivity and obesity.
Whatever the basis of aetiology, insulin deficiency is
absolute in type-I with more than 80% of beta cells being
destroyed and relative in type-II with beta cell dysfunction.
The geneticist, molecular biologist, immunologist and
epidemiologist (nutritional and toxic factors) are all
associated in the elucidation of diabetic state.
 434 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Recently low body weight type-2 diabetes mellitus is
endorsed as a distinct phenotype of NIDDM (LB-type 2
DM).
Secondary (Specific Types)
Malnutrition related diabetes mellitus (MRDM) It is prevalent
in tropical developing countries (India–South India and
Orissa; Nigeria and Brazil). There are two subtypes (a) Fibro
Calculus Pancreatic diabetes (FCPD) and (b) Protein
Deficient Diabetes Mellitus (PDDM). The latter is previously
described as Protein Deficient Pancreatic Diabetes (PDPD)
and Ketosis Resistant Young Diabetes (J Type).
The usual presenting features of MRDM are:
a. Early onset 10 to 30 years
b. Undernutrition and underweight from early childhood
c. Moderately severe hyperglycaemia
d. No ketosis
e. High insulin requirements (2 U/kg).
In addition, FCPD is characterised by abdominal pain,
steatorrhoea, pancreatic calcification and dilatation of ducts
with irregular pancreas.
In the third world countries like India, consumption of
cyanide producing glycosides in cassava (tapioca), in protein
malnutrition seems to result in pancreatic calcification and
fibrotic destruction (Z Type). Yet another type is described
as K type if it is associated with consumption of local
indigenous strong liquors.
PDDM is not localised to any particular geographical
area. It is another subtype of MRDM without pancreatic
pathology, and may be mistaken for IDDM in the young.
The human growth hormone (GH) levels and its response
to oral glucose tolerance test is valuable in the diagnosis of
PDDM, as there is paradoxical rise of growth hormone
levels (instead of expected suppression) as well as high
basal GH levels. Neither of these is seen in IDDM or
NIDDM.
Pancreatic Disorders
• Chronic pancreatitis: Recurrent abdominal pain, weight
loss, steatorrhoea, diabetes mellitus, chronic alcoholism,
and pancreatic calcification establish the diagnosis (Refer
to Chapter ‘Chronic Diarrhoea’).
• Haemochromatosis: Increased iron absorption and/or
excess parenteral iron result in deposition of iron in
organs like liver, pancreas and heart, leading to cirrhosis,
hyperglycaemia and cardiomegaly. Arthritis, testicular
atrophy and skin pigmentation (bronze diabetes) are
supportive evidences. The diagnosis is confirmed by
(i) increased serum iron and ferritin, (ii) decreased total
iron binding capacity and (iii) liver biopsy.
Endocrinopathies
• Hyperpituitarism: Hypersecretion of eosinophil cells of
anterior lobe of pituitary leads to acromegaly (after
closure of epiphysis) with increase in size of the bone,
soft tissue and viscera. About 50% of untreated cases
develop diabetes mellitus.
• Hyperadrenalism (Refer to Chapter ‘Obesity’).
• Hyperthyroidism (Refer to Chapter ‘Goitre’).
• Glucagonoma: It is characterised by dermatosis
(necrolytic erythema), stomatitis, diabetes mellitus and
high plasma glucagon levels. Most of them are malignant
(Refer to Chapter ‘Rashes’).
• Somatostatinoma: Islet tumours produce a hormone
called somatostatin which inhibits growth hormone,
gastric secretions, pancreatic secretions and insulin
release. Diarrhoea, cholelithiasis, weight loss and
hyperglycaemia are the manifestations. It is rare.
Diabetogenic drugs (a) Steroids like corticosteroids, oral
contraceptives; (b) growth hormone; (c) diuretics like
thiazide, chlorthalidone, ethacrynic acid; (d) diazoxide and
(e) Nelfinavir are documented to produce hyperglycaemia.
Genetic syndromes The clinical features are: (a) Prader-Willi,
(b) Alstrom, (c) Biemond’s syndroms (Refer to Chapter
‘Impotence’). and (d) Werner’s syndrome (premature aging,
atrophic skin, cataracts and diabetes mellitus).
Gestational diabetes mellitus (GDM) It is first diagnosed during
pregnancy in a previously euglycaemic woman. A family
history of diabetes in first degree relatives, previous foetal
loss or malformations or heavy babies, obesity are usually
associated. It is due to stress and both blood sugar as well
as amino acid levels are increased. This leads to
hyperinsulinaemia in foetus with visceromegaly and
increased fat deposition particularly after 35th weeks. Oral
Glucose Tolerance Test (GTT) is done with 75 grams and
2nd hour value > 140 mg per cent is diagnostic. In
pregnancy, IGT should be treated as GDM to avoid perinatal
or foetal jeopardy. Raised alpha feto protein suggests open
neural defect in GDM or Pre GDM (PIGT). After parturition,
glucose tolerance returns to normal. However, 15 per cent
remains as diabetes mellitus and 30 per cent develop diabetes
in the next 15 years. In pregnancy impaired glucose
tolerance (PIGT) Fasting Glucose is > 90 mg% and post
prandial is > 120 and < 140 mg%. GDM is diagnosed if
fasting is > 95 mg% and postprandial is > 140 mg %.
Clinical Features
Diabetes mellitus, in general, presents as polyuria, polydipsia,
weight loss (in spite of normal or increased intake),
 Polyuria 435

weakness, pruritus, loss of libido, nonhealing wounds and

infections (cutaneous, Balanitis) very often, it may be
discovered in the course of routine examination
(asymptomatic), and sometimes present with fatigue or
symptoms of anyone of the complications.

Mechanism of Polyuria
The insulin deficiency results in hyperglycaemia (due to
under utilisation of glucose by the peripheral tissue and
excessa amounts of glucose being released by the liver).
This excess of glucose exceeds the capacity of renal tubules
to reabsorb (renal threshold for glucose-180 to 200 mg%)
and glycosuria results which increases the osmolality of
the glomerulofiltrate and prevents reabsorption of water
resulting in polyuria and polydipsia. As the function of the
thirst centre is to ensure that polydipsia matches polyuria,
large volumes of fluid are necessarily consumed.
Fig. 28.2: Oral glucose tolerance test: Capillary blood
Diagnostic Criteria of DM
glucose curves showing normal; IGT and DM
a. Characteristic features with hyperglycaemia and (P P
plasma sugar is more than 200 mg%).
b. Fasting plasma glucose levels of more than 126 mg% NB: Plasma sugar level is 14 % above the blood sugar level
on more than one occasion. and 05551 is the system international (S1) conversion factor,
c. Abnormal oral glucose tolerance test (vide infra). i.e. about 18 mg % is equivalent to mmol/L.
Mere glycosuria may not be significant since it may be
Glycated haemoglobin (Hb A1c) Glycosylation of plasma protein
due to causes other than diabetes mellitus like renal
and haemoglobin occurs at any given plasma glucose
glycosuria. Glucose tolerance test is indicated in postprandial
concentration in any individual. As Ic fraction of
glycosuria or when fasting glucose is between 110-126 mg%.
haemoglobin gets glycosylated, (produced by glycosylation
(If the fasting sugar is less than 10 mg%, diabetes mellitus
of N-terminal valine of beta chain) the proportion of HB
is ruled out). Similarly 2 h postprandial sugar <140 mg%
A1c is a valuable indicator of blood glucose levels during
excludes 1 GT and DM.
the previous 8 to 12 weeks. Some assays measure Hb AI
Glucose tolerance test (GTT) Oral GTT is preferred to i.v. and others measure Hb AIc. This test is also very useful to
GTT since assimilation is well modulated through gut decide whether the hyperglycaemia was already pre-existing
hormones production. These hormones play a significant or temporarily induced (normal range is 4-6.5%). Useful to
role in the release of stored insulin as well as synthesis and assess long time control of DM.
release from the beta cells. (Usually 75 g of glucose is given.)
Serum insulin levels (IRI) In type-I, fasting insulin levels are
(Fig. 28.2).
low and respond poorly to glucose challenge. In type-II,
The diagnostic values are
fasting levels are normal or elevated and blunted response
Table 28.2: Categories of glucose tolerance
to glucose challenge.
C-peptide (C = connecting) Since C-peptide is secreted in
Category Fasting Plasma 2 hr Post glucose equimolar basis with insulin, its level reflects the beta cell
glucose (µg/dl) plasma glucose (µg/dl) function. Both C-peptide basal levels and glucose stimulated
Normal < 110 < 140 levels are low in IDDM. In FCPD, the basal levels may be
1 FG 110-126 < 140 normal and glucose stimulated response is high. The C-
1 GT < 110 140 - 199 peptide values are not useful in the diagnosis of NIDDM as
DM > 126 > 200 the fasting IRI is often high. However, type of diabetes
Gestational IGT > 90 120 - 140 mellitus may be determined by measuring serum insulin or
GDM > 95 > 140
C-peptide levels.
 436 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

HLA Typing Reveals certain patterns of linkage disequilibrium

for IDDM but not for NIDDM. The HLA haplotypes in
NIDDM vary between patients of different ethnic origin.
No specific haplotype has been identified for MRDM.
Islet Cell Antibody Antibodies against the cytoplasm of the
islet cells (ICA) are detected in early stage of IDDM. The
presence of such antibodies in siblings of IDDM patients or
in a susceptible community, predicts development of IDDM.

Complications
The complications of diabetes mellitus may be acute
(metabolic) or chronic(vascular) or intermediate (infections,
etc.)
A. The acute complications are metabolic, leading to:
a. Diabetes ketoacidosis
b. Hyperosmolar non-ketoacidotic coma (seen in
maturity onset diabetes).
B. The chronic (late) complications are essentially due to Fig. 28.3B: Waxy yellowish-white deposits (hard exudates);
vascular changes which are linked esp. to postprandial oedema; leaky microaneurysms in macular region-Diabetic
hyperglycaemia (macroangiopathy-atherosclerosis, and maculopathy (For colour version see Plate 1)
microangiopathy—Small vessel disease of the kidney
and retina) and may affect any organ like
1. Ocular (microangiopathy) (Figs 28.3A to D)—
appreciated by ophthalmoscopic examination or
Fundus Fluorescein angiography.
a. Non-proliferative (exudative) retinopathy
b. Proliferative retinopathy (Leads to blindness)
c. Vitreous haemorrhage

Fig. 28.3C: Prepapillary neovascularisation

(For colour version see Plate 1)

d. Cataract (both juvenile and senile)

e. Rubeosis iridis (new vessel formation on the
anterior surface of iris)
2. Cardiovascular (macroangiopathy)
a. Coronary heart disease
b. Hypertension
Fig. 28.3A: Cotton-wool spots (soft exudates) c. Diabetic cardiomyopathy
(For colour version see Plate 1) d. Peripheral vascular disease–Diabetic foot
 Polyuria
Fig. 28.3D: Vitreous haemorrhage
(For colour version see Plate 1)
3. Renal (diabetic nephropathy), i.e. it consists of
i. Hyperfiltration. GFR elevated (mesangial
expansion) when kidney size increases;
ii. Incipient nephropathy—Microatbuminuria (GBM
thickens) GRF normal,
iii. Overt nephropathy—Macroaluinuria (Glomerulo-
sclerosis),
iv. Renal failure. (GFR decreases in iii and iv and BP
raised)
i.e. Clinical presentations are essentially those of
glomerular lesions, i.e. c, d, e, f (vide infra)
though diabetics are prone for a and b (vide infra)
a. Pyelonephritis (Chronic)
b. Papillary necrosis (complication of acute
pyelonephritis)
c. Diffuse glomerulosclerosis and nodular sclerosis
(Kimmelstiel-Wilson lesion)
d. Nephrotic syndrome
e. Renal-Retinal syndrome (Nephropathy+
Retinopathy)
f. Chronic renal failure/ESRD
4. Neurological (central and peripheral nervous system)
a. Peripheral neuropathy
b. Mononeuropathy
c. Autonomic neuropathy
d. Amyotrophy (Painful wasting of qudriceps)
e. Radiculopathy
f. Isolated cranial nerve palsy (3rd nerve or 7th
nerve)
g. Stroke
437
C. Intermediate Complications may occur in the course of
diabetic state, such as:
1. Intercurrent infections like tuberculosis, UTI,
moniliasis.
2. Dermatological
a. Staphyloccal infections folliculitis
b. Necrobiosis lipoidica diabeticorum
c. Diabetic dermopathy
d. Diabetic scleropathy.
3. Shoulder-hand syndrome
4. Fatty liver
5. Dyslipidaemias (Hyperlipoproteinaemia indicates
raised cholesterol or triglycerides which may be
primary or secondary).
6. Hyperviscosity: Major cause of ischaemia and
thrombosis, i.e. increased fibrinogen in (diabetes
mellitus) may account for the hyperviscosity of
blood.
7. Diabetic foot.
8. During pregnancy
a. Maternal
(i) Miscarriages,
(ii) Pre-eclampsia,
(iii)Progressive hydramnios
b. Foetal
(i) Foetal macrosomia
(ii) Foetal marformative neural tube defects and
respiratory distress
(iii)Retarded foetal growth
The longer the duration of hyperglycaemia, the greater
the chances of the above mentioned complications and rigid
control appears to minimise or prevent them.
Hypercalcaemia and Hypercalciuria
(Calcium Diabetes)
The calcium metabolism is controlled by :
a. Parathyroid hormone (parathyroids)
b. Vitamin-D (metabolised to 25 hydroxycholecalciferol in
the liver and converted to 1, 25 dihydroxy-cholecalciferol
in the kidney). Cholecalciferol is vitamin D3.
c. Calcitonin (thyroid) opposes the actions of parathyroid
hormone.
d. Thyroxine (thyroid) may increase calcium.
Hypercalcaemia may be seen in primary hyper-
parathyroidism, myeloma, malignancy, sarcoidosis, and
immobilisation.
The nondiffusible fraction of calcium is bound to serum
proteins. In conditions, where serum proteins are increased
 438 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
as in myeloma, serum calcium may also be raised. The
parathyroid glands control serum calcium and phosphorus
levels of the blood. The release of parathyroid hormone is
regulated by serum ionised calcium concentrations. The
parathyroid hormone maintains calcium concentrations in
the extracellular fluid. In hyperparathyroidism, the increased
parathyroid hormone increases the resorption of calcium
phosphate from the bone and increase calcium and
phosphorus excretion in the urine. The serum calcium is
usually raised and serum phosphorus is decreased due to
a. Its indirect effect of synthesis of 1, 25 dihydroxy-
cholecalciferol which in turn increases the calcium
absorption in the gut and phosphate excretion in the
urine.
b. Direct effect on the kidney resulting in increased calcium
reabsorption and decreased phosphorus resorption from
the kidney tubules. This results in the decrease of
phosphorus and increase in calcium levels.
Hypercalcaemia causes polyuria and nocturia. Though
calcium in the glomerular filtrate, which is not completely
reabsorbed in the tubules, may produce osmotic diuresis,
the polyuria can also be due to concentrating defect of the
tubules and diminished responsiveness of the tubules to
ADH, resulting in water diuresis. (vide infra). Further,
hypercalciuria results in deposition of calcium in the tubular
epithelium leading to impaired reabsorption of water.
Hypercalcaemia should be suspected if polyuria is
accompanied by weakness, loss of appetite, abdominal pain,
constipation, vomiting, confusion and weight loss.
Increased Solute Load (Hypertonic Intravenous
Infusions)
The infusion of mannitol and other hypertonic intravenous
fluids causes solute/osmotic diuresis, i.e. excretion of more
solute requires elimination of more water. So excess of
osmotically active substance in the distal tubule results in
polyuria.
Hyperalimentation with total parenteral nutrition
(consisting of solutions with 50% glucose, 4.25% amino
acids and vitamins offer 3000 calories per day) is given
through a catheter in superior vena cava in depleted
nutritional status as in malignancies. Consistent glycosuria
(++ or +++) indicates 30 per cent of the infused calories
are excreted in the urine. Hyperosmolar non-ketotic
dehydration (coma) can occur due to osmotic diuresis by
prolonged glycosuria.
Similarly protein breakdown in large haematoma may
lead to excess formation of urea which acts as a solute and
cause polyuria.
Renal Dysfunction
Acute Renal Failure
Diuretic phase sets in if the subject does not succumb during
the anuric or oliguric phase. This is due to the healing of the
renal tubules or reduction in intrarenal tension which finally
results in increased urine volumes of dilute nature (Refer to
Chapter ‘Oliguria’).
Chronic Renal Failure
It is defined as renal damage with glomerular filtration rate
< 60 ml/mt for three months or more (60-89 early renal
insufficiency; 30-59 moderate renal insufficiency; 15 to 29
severe renal insufficiency and pre-endstage renal disease;
< 15-endstage renal disease due to progressive destruction
of the renal parenchyma and fibrous replacement of many
tubules). Polyuria develops from failure of tubular
reabsorption of water besides osmotic diuresis caused by
raised blood urea and probably by artrial natriuretic hormone.
That is why the specific gravity is low and fixed at 1010
i.e. (specific gravity of glomerular filtrate is about 1010).
Chronic renal failure is not reversible unlike acute renal failure
and symptoms of uraemia (anorexia, nocturia, bone pain,
muscle weakness, cramps, serosal effusions, Refer to
Chapter ‘Oliguria’) do not appear until glomerular filtration
rate (GFR) falls to 25 per cent of normal. The sodium
excretion is restricted by the remaining nephrons which
may lead to hypertension which may also be due to distorted
renin angiotensin production. This often precedes the onset
of chronic renal failure and determines the ultimate outcome
of underlying renal disease. Apart from the signs and
symptoms due to the effects on cellular function and
metabolism (vide Chapter Coma) features of the specific
causes like diabetes mellitus, long standing hypertension,
chronic interstitial nephritis, chronic glomerulonephritis,
chronic pyelonephritis, polycystic kidney, and urinary tract
obstruction are discernible.
Congestive heart failure, pulmonary oedema, anaemia
and abnormalities in haemostasis with bleeding tendencies
are the consequences of chronic renal failure. Azotaemia
for more than three months, renal osteodystrophy and
shrunken kidney indicate the chronicity. The biochemical
parameters (S. creatinine, bicarbonate, potassium,
phosphate, blood urea), urinary abnormalities, imaging
techniques and renal biopsy confirm the diagnosis. (Urea,
creatinine, phosphate, potassium are raised whereas sodium,
calcium and bicarbonate are decreased).
 Polyuria
Natriuretic Syndrome (Salt losing nephropathy)
Greater destruction of medullary and interstitial portions of
renal parenchyma results in excessive chronic sodium loss
as in tubulointerstitial diseases or hereditary tubular disorders
(medullary cystic disease) or in diuretic stage of acute
tubular necrosis. Post-obstructive natriuresis (relief of
bilateral obstruction) is another example. Natriuresis is due
to excretion of retained urea and also due to diminished
reabsorption of salt and water in the tubules. Polyuria and
polydipsia occur.
Diabetes Insipidus (DI)
This may be pituitary (neurogenic) or nephrogenic type. In
both these conditions, there is formation of large amounts
of dilute urine, due to inadequate tubular reabsorption of
filtered water and polydipsia.
Neurogenic or Central Diabetes Insipidus (Vasopressin
Deficiency) It occurs due to damage in the region of
hypothalamic-pituitary axis affecting particularly the
posterior pituitary gland leading to decreased production of
antideuretic hormone. The causes include (a) pituitary
tumours or metastatic tumours, (b) pinealomas, (c)
granuloma, (i) eosinophilic granuloma, (ii) sarcoidosis, (d)
infections-encephalitis, (e) head injury, (f) pituitary surgery,
(g) familial and (h) idiopathic.
The onset of polyuria and polydipsia may be abrupt.
The urine volume may even exceed 15 litres per day, and
urine osmolality is less than 290 mosmol/kg. The specific
gravity is below 1010, and fails to increase with water
deprivation.
Nephrogenic Diabetes Insipidus (Vasopressin
Insensitivity)
This is a primary renal tubular defect of water reabsorption
wherein there is decreased response to ADH, although the
formation of ADH is normal. It may be a familial form (sex
linked recessive) or may be part of other renal tubular
defects like Fanconi syndrome or cystinosis, or infantile
renal tubular acidosis. Sometimes it is acquired due to
potassium depletion, chronic renal disease (pyelonephritis),
primary hyperparathyroidism, and drugs (like lithium,
dimethyl chlorotetracycline, diphenylhydantoin) or sickle
cell disease.
The cause of polyuria is differentiated by comparing
urine osmolality after dehydration (water deprivation test)
and after administration of vasopressin. In normal people,
the urine osmolality rises to 800 mosmol/kg, and the plasma
439
osmolality does not rise above 300 mosmol/kg. In diabetes
insipidus, the former does not rise (<400 mosmol/kg’) and
the later rises (>300 mosmol/kg). Vasopression corrects
the abnormality in central diabetes insipidus, i.e. urine
osmolality increases to > 600 mosmol/kg and plasma
osmolality falls but not in nephrogenic diabetes insipidus.
In psychogenic polydipsia, urine osmolality becomes > 400
mosmol/kg and plasma osmolality is normal or low (250-
290 mosmol/kg).
Primary Polydipsia
It is a characterised by passing increased amounts of dilute
urine due to compulsory water drinking. ADH release is
inhibited and medullary osmotic gradient is diminished. It
may be of psychogenic or hypothalamic or neurochemical
mechanism. There may be other hysterical symptoms along
with this psychogenic thirst. After water deprivation, the
vasopressin response helps the diagnosis, i.e. urine
osmolality increase (>400 mosmol/kg).
Hypokalaemia
Prolonged hypokalaemia is caused by (i) diuretics (loop
diuretics: (frusemide, bumetanide, ethacrynic acid; distal
potassium losing diuretics: (Hydrochlorothiazide,
chlorthalidone) (ii) corticosteroids; (iii) Conn’s syndrome;
(iv) alkalosis (metabolic); (v) Bartter ’s syndrome
(hypokalaemia due to renal potassium wasting, high renin
and aldosterone) (vi) Renal tubular failure. Polyuria, nocturia
and polydipsia occur in such states due to hypokalaemia
(Hypokalaemic nephropathy).
Diuretics or metabolic alkalosis suppress tubular
secretion of H ion resulting in excess potassium loss since
H ion competes with potassium for exchange with sodium.
The hypokalaemia which occurs in congenital disorders of
tubular transport like Bartter’s syndrome and renal tubular
acidosis reduces concentrating capacity of the kidney leading
to polyuria, besides other characteristic features of
hypokalaemia like muscular weakness (Refer to Chapter
Weak Legs).
CLINICAL APPROACH
The cause of polyuria can be determined by eliciting specific
data. Ascertain whether the polyuria is transient or persistent.
If it is transient it may not be of any significance as it is
often physiological. It may be due to
a. Exposure to cold weather
b. Excessive water drinking
c. Attack of paroxysmal tachycardia or migraine
 440 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
d. Convalescence from fevers
e. Drugs (diuretics) and beverage (tea, coffee and alcohol).
If it is persistent, the following points should be noted:
a. Any associated weight loss, weakness and recurrent
cutaneous infections suggest of diabetes mellitus.
b. Any history of haematuria or nocturia, any analgesic
drug abuse or earlier urinary problem is suggestive of
chronic renal disease.
c. Any associated abdominal pain, constipation, nausea or
vomiting is suggestive of hypercalaemia due to underlying
disease, or excessive abuse of calcium and vitamin D.
d. Any associated headache and deteriorating vision,
hypothalamic disturbances of sleep and appetite may be
due to intracranial tumour leading to diabetes insipidus.
e. Any associated history of chronic diarrhoea or drug
history of laxatives, steroids and diuretics may be due
to hypokalaemia.
f. Polyuria alone in the day and not by night is suggestive
of compulsive water drinking.
Physical Examination
General Survey
1. For evidence of marked wasting, cachexia and anaemia
(may be due to chronic renal disease or sickle cell
anaemia) or acidotic respiration or hypertension (renal
origin), or feebal peripheral pulses (arterial changes due
to diabetes mellitus).
2. Skin infections and postinflammatory pigmentation in
diabetes mellitus or pigmented yellow-brown skin as in
renal failure.
3. Fingers for any white lines or brown arcs in the nails
(chronic renal failure).
4. Lymphadenopathy for any evidence of neoplasm which
may be responsible for existing hypercalcaemia or
hypokalaemia.
5. Bones: Pain and tenderness of the bones (multiple
myeloma).
6. Eyes
a. Proptosis due to eosinophilic granuloma
b. Band keratopathy or calcification at the lateral aspect
of corneoscleral junction (hypercalcaemia)
c. Visual fields showing bitemporal hemianopia (pituitary
tumour)
d. Fundus examination for evidence of diabetic or
hypertensive retinopathy or intracranial tumour.
Systemic Examination
1. Chest examination for evidence of cardiomegaly due to
hypertension or collapse of the lung due to bronchogenic
carcinoma.
2. Abdomen: Any masses in abdomen (polycystic kidney
or enlarged kidney); any abdominal distension
(hypokalaemia).
3. Neurological examination
a. Paralysis of oculomotor nerves: Pituitary tumour
b. Muscle weakness and hypotonia and areflexia
(hypokalaemia); or tenderness of calf muscles
(diabetic peripheral neuropathy)
c. Altered modalities of sensation like loss of touch or
vibration sense (Diabetic peripheral neuropathy)
d. Diminished or absent ankle jerks (diabetic peripheral
neuropathy).
Investigations
Measurement of Fluid Intake and Output
a. If it is 3 litres and above in 24 hours it indicates chronic
renal failure, hypercalcaemia or hypokalaemic
nephropathy.
b. If it is 5 litres and above in 24 hours it is suggestive of
diabetes insipidus or primary polydypsia.
Examination of the Urine
a. Specific gravity
i. If it is low, diabetes insipidus and primary polydipsia
ii. If it is high, diabetes mellitus
iii. If it is fixed at 1010, chronic renal failure
b. Proteinuria
i. Proteinuria: Suggestive of renal disease
ii. Microalbuminuria: Urinary Albumin Excretion Rate:
20-200 ug/mt or Urinary AER: 30-300 mg/24 h
indicates glomerular vasculopathy (Normal AER is
< 30 mg/24h).
iii. Normal Urinary albumin: Creatinine ratio (mg/gm)<
30 or (mg/mmol)<3: In Microalbuminuria (mg/gm)
30-300 or Urine Albumin: Creatinine ratio; 3-30 mg/
mmol (on two samples).
c. Glycosuria: Suggestive of diabetes mellitus
d. Microscopic deposits
i. Presense of pus cells and RBCs indicate pyelo-
nephritis.
ii. Presense of casts (cylindrical structures formed by
the coagulation of protein in the renal tubules);
 Polyuria
particularly granular casts are formed by the
degeneration of the cells impressed over the
coagulated protein, or hyaline casts without the
cellular elements are found in chronic
glomerulonephritis.
e. Urine electrolytes: Sodium and potassium (estimation
of potassium in a 24 h urine helps to determine whether
hypokalaemia is due to renal loss of potassium). High
GFR leads to high loss of sodium.
f. Urine osmolality
i. If urine is isotonic with serum (renal problem).
ii. Urine osmolality greater than serum (diabetes
mellitus).
iii. If urine is hypotonic compared to serum, i.e. urine
osmolality low (diabetes insipidus or compulsive
water drinking)—Water Deprivation Test and
response to ADH (vide supra).
g. Urine electrophoresis: For multiple myeloma, wherein
Bence Jones protein (light protein) detected as a
monoclonal peak on urine electrophoresis.
h. Urinary albumin/creatinine ratio (mg/gm) < 30.
Blood
a. If plasma osmolality is normal or high it is DI where as
it is normal or low in compulsive water drinking, serum
creatinine, blood urea raised in renal failure. The osmotic
pressure of the plasma may rise if there is increased
loss of water which is measured in milliosmoles/kg
(osmolality). The plasma osmolality is estimated as
follows: 2 (Na+) + IO,i.e. hypernatraemia is associated
with increase in plasma osmolality.
b. Blood sugar: Fasting and postprandial raised in diabetes
mellitus. Hb A1c > 7% (Glycated haemoglobin) indicates
diabetes mellitus and likely risk of microvascular
complications or glycated plasma protein levels
(fructosamine) which relate to control of hyperglycaemia
over previous 8 weeks in the former and 1-3 weeks in
the later (useful in pregnancy and haemoglobinopathies
also).
c. Inflammatory markers: ESR, C-reactive protein, serum
ferritin.
d. Serum uric acid is raised esp. in chronic interestitial
nephritis.
e. Serum electrolytes: Na, K, Ca, Phosphorus, Bicarbonate
and pH of blood. (Raised serum calcium, decreased
phosphorus and increased alkaline phosphatase is
suggestive of primary hyperparathyroidism)
f. Serum proteins
441
i. Albumin and globulin ratio.
ii. Electrophoresis distinguishes paraprotein which
shows a narrow range of electrophoretic mobility.
(Paraproteins are the light chain components of
immunoglobulins and paraproteinaemia implies
proliferation of a single class of immunocytes; in
the term M band, ‘M’ indicates monoclonal and not
IgM. This M band information can be supplemented
by measuring monoclonal protein which is otherwise
known as M component. It represents the
immunoglobulin molecule (heavy or light chain)
produced by the malignant cells and is characteristic
of myeloma).
g. Serum iron B12, folate and RBC and Hb %.
h. Lipid profile for diabetic dyslipidaemia.
i. Assay of plasma ADH: it is low in cranial diabetes insipidus
or primary psychogenic polydyspsia, whereas it is raised
in nephrogenic diabetes insipidus.
j. Parathormone assay.
Kidney Function Tests
Renal function can be assessed by measuring renal clearance
and renal concentrating or diluting ability. The former is
done by endogenous creatinine clearance test for glomerular
function and the latter is done by specific gravity test for
tubular function. The other most commonly available tests
for detection of renal function are (i) serum creatinine and
blood urea (ii) routine analysis of urine including protein
estimation, estimation of urinary electrolytes and urinary
sediment analysis offer valuable information regarding renal
function (vide supra).
a. Endogenous creatinine clearance test: It is a measure of
glomerular filtration rate (GFR). The concept of
clearance is the volume of plasma completely of that
substance in unit time provided the substance is
completely cleared filtered and not absorbed in the tubule.
Since the quantity excreted in urine is equal to quantity
filtered by the glomeruli, the clearance of the substance
is equal to GFR. (Creatinine once filtered is not
reabsorbed.) The plasma creatinine levels reflect the
GFR, i.e. it rises as filtration rate diminishes. The classical
examples of low GFR are (i) acute oliguric renal failure
and (ii) long standing chronic renal failure. GFR is 20
per cent higher in pregnancy. Clearance of creatinine is
determined by collecting urine for 24 h and one sample
of blood during day time and is calculated by the
following equation:
 442 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

UV
C=
PT
C where, Clearance of creatinine
U where, Concentration of creatinine in urine in µmol/L
V where, Volume of urine in ml secreted in 24 h
P where, Concentration of creatinine in plasma in µmol/L
T where Time=1440 minutes or 24 h.
Normal value is 100 ml/minute.
Creatinine clearance values of 50 ml/minute indicate mild to
moderate renal dysfunction whereas values of 10-20 ml/
minute indicate severe dysfunction. Glomerular filtration
rate can be calculated from the following equation
140 Age × Weight (in kg)
72 × serum creatinine (mg%)
Normally physiological GFR is 90-120 ml/minute/1.73 m2.
b. Specific gravity test (Measurement of the specific gravity Fig. 28.4: Intravenous pyelogram showing dilatation of the
indicates the concentrating power of the kidney). pelvis and calyces of the left kidney with mega ureter
Withhold the fluids for 12 h and observe the specific
gravity of the urine. Normally the specific gravity should iii. Isotope renography: Renograms may show the
be 1025 or more. If the specific gravity does not exceed, characteristic pattern of obstructive uropathy.
it indicates impairment of tubular function. Apart from iv. Captopril renography to confirm renovascular
this, measurement of the ability to concentrate urine, disorders.
and the ability to dilute urine is determined by giving v. Dimethyl succinic acid scan is useful for cortical
deliberate water load. After 12 h the specific gravity is cyst, renal scarring and chronic pyelonophritis
measured, which should be 1003 or less. e. Skeletal survey for radiological changes in bone disease
(endocrine, metabolic or malignant). Isotope bone scan
Radiology may be done if bone disease is suspected (if indicated).
X-ray of:
a. Chest for carcinoma of the bronchus and sarcoidosis to Ultrasound
account for hypercalcaemia. To assess the kidney size.
b. Skull for —
i. Studying pituitary fossa for evidence of tumour like ECG
craniopharyngioma. T waves are small or inverted in hypokalaemia, and Q-T
ii. Punched out lesions of myeloma. interval is shortened in hypercalcaemia.
c. Hands for subperiosteal erosions of phalanges
(hyperparathyroidism) or renal failure induced CT Scan of Brain
osteomalacia). To confirm an intracranial space occupying lesion (if
d. Renal radiology indicated).
i. Plain X-ray of abdomen for kidney size and any
calculi. Kveim Test
ii. Intravenous pyelogram not only assesses kidney size For sarcoidosis, intradermal injection of sarcoid tissue may
but outlines the renal tract [small kidneys, show typical granulomata on biopsy after 4 to 6 weeks, in
i.e. < 10 cm with thin cortex and clubbed calyces positive cases.
seen in chronic pyelonephritis and large kidney (>14 The above described investigations can be appropriately
cms) with elongation of the calyces seen in polycystic chosen on the index of suspicion, to determine the underlying
kidney] (Fig. 28.4). cause of polyuric states.
 Polyuria
TREATMENT OF POLYURIA
The clinician should clinch the cause whether the increased
daily urine output (by actual measurement) is due to (a)
obligatory water excretion with polydipsia (primary
polydipsia and solute diuresis) or decreased tubular
reabsorption with polydipsia (central and nephrogenic
diabetes insipidus; or (b) transient without polydipsia as
such (vide supra causes). Generally it is unlikely to be of
organic origin if the polyuria is not associated with polydipsia
(of course with a few exceptions). Further, it is better
endeavoured to determine the exact mechanism of persistent
polyuria, i.e. solute related (diabetes mellitus, chronic
nephritis) or ADH incriminated (decreased secretion as in
central diabetes insipidus or decreased responsiveness of
collecting ducts to ADH as in nephrogenic diabetes insipidus,
hypokalaemia, hyperparathyroidism). It is of immense value
to see whether simple restriction of fluid intake for 24 h,
abolishes polyuria and restores normal specific gravity, as
it happens in psychogenic compulsive water drinking.
Symptomatic Relief
Fluid and Electrolyte Imbalance
Correction of these abnormalities may be necessary in late
stages rather than early stage of diagnosis.
Drugs
a. Chlorothiazide (250 mg twice a day) reduces polyuria
by inducing a sodium depleted stage.
b. Chlorpropamide (125-250 mg once a day) relieves
polyuria by enhancing the action of endogenous ADH
on the renal tubules.
c. Clofibrate (500 mg 4 times/d) results in antidiuresis by
stimulating release of residual ADH.
d. Carbamazepine (200 mg b.d.) also produces antidiuresis
in similar way.
Specific Treatment for Specific Diseases
Diabetes Mellitus
Maintaining normoglycaemia should be the primary aim as
it prevents the metabolic decompensation and possibly
vascular complications. This can be achieved by a three
point programme of diet, drugs and drill while assessing
the glycemic control periodically with glucometers and / or
estimating glycated haemoglobin (HbA 1c) levels or
fructosamine (glycated plasma protein levels).
443
Diet High carbohydrate high fibre, optimum protein and low
fat diet, meeting the calculated caloric requirements must
be planned. This key factor of the treatment programme is
so designed as to reduce weight in obese individuals or
maintain desired weight constantly in others. The ideal body
weight is calculated and adjusted accordingly in relation to
the physical activity. Mean requirement is about 30 calories/
kg body weight. The diet is appropriately constructed so as
to distribute the calories in the approximate proportions such
as carbohydrates (65%) proteins (15%) and fats (20%)
(i.e.) saturated 6% and unsaturated 14% (mono unsaturated
8% and polyunsaturated 6% (i.e.) n6 = 5% and n 3 = 1%)
n6/n3 ratio to be kept low (5-10) supplemented with high
fibre containing foods (about 50 g/d), vitamins, and
antioxidants minerals. For this purpose, the calorie value of
various foods must be ascertained, and zero calorie sugar
substitutes are advocated. Guar gum is high fibre product.
Diet therapy alone should be given a trial in newly
diagnosed diabetes mellitus before commencing drug
therapy. However, diet therapy continues to be important
even after medication.
Drug therapy Since prediabetes is associated with the risk of
DM and CAD, lifestyle and pharmacological (Metformin)
interventions are indicated.
Insulin for IDDM and oral hypoglycaemic drugs for
NIDDM are the drugs of choice. However, for the latter,
insulin may be called for at times. The dosage schedule of
the drugs depends on blood glucose levels, which is better
initiated with small doses and adjusted as per the needs slowly.
A. Oral hypoglycaemic drugs (pancreatic and extra-
pancreatic)
1. Insulin secretagogues (targeting beta-cell dys-
function).
i. Sulphonylureas
First generation—Tolbutamide (500-1000 mg/d),
chlorpropamide (100-500 mg/d) (not used now).
Second generation—short acting-Glipizide (2.5-
20 mg/d); Gliclazide (40-320 mg/d)
Long acting–Glibenclamide (2.5-20 mg/d);
Glimeperide (1-8 mg/d).
ii. Non-sulphonylureas
Repaglinide (0.5-12 mg/d), Nateglinide (60-120
mg t d s.); Meglitinide (2 mg b d)
iii. Sitagliptin-100 mg/d (increases insulin secretion
and lower glucagon secretion).
iv. Combination of oral drugs.
2. Insulin sensitisers- (facilitating glucose uptake by
peripheral tissues like skeletal muscles and adipose
tissue and reduce insulin resistance)
 444 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
i. Peroxisome proliferator activated receptor
(PPAR) agonists-
Thiazolidinediones (TZD). Rosciglitazone (4-
8mg/d); pioglitazone (15-45 mg/d).
ii. Biguanides: Metformin (0.5-3 g/d); (extended
release also) phenformin (25-100 mg/d)
(Biguanides do not produce hypoglycaemia but
lactic acidosis may result. Alcohol may increase
the risk of lactic acidosis while on phenformin).
3. Alpha glucosidase inhibitors (targeting glucose
absorption by gut)-Acarbose- (150-300 mg/d).
Miglitol (25-100 mg t. d. s) Voglibose (0.2-0.3 mg)
useful like non-sulphonylureas for controlling post
prandial hyperglycaemia.
4. Reducing hepatic glucose output
i. Biguanides
ii. Thiazolidinediones
B. Parenteral hypoglycaemic drugs (1) Insulins (2) Insulin
analogues (3) Insulin mixtures (4) Incretins
1. Insulins (Parenteral)—They are of two types i.e.
unmodified insulins (clear solutions, short acting,
conventional or purified, i.e. monocomponent
porcine or human, insulins) and modified insulins
(cloudy solutions, long acting, depot zinc
suspensions, conventional, or purified, i.e.
monocomponent porcine or human insulins). The
species of insulin are bovine, porcine and human,
i.e. recombinant DNA origin purity and action
differentiate them. Insulin available in vials, cartridges
and pumps to be used with traditional syringes,
injector pens, and preloaded syringes.
i. Short acting: Neutral soluble insulin (regular or
crystalline) and insulin zinc suspension amorphous
(semilente)
ii. Intermediate acting: Isophane insulin (NPH); and IZS
mixture of 30% in amorphous and 70% in crystalline
forms (lente).
iii. Biphasic insulin (pre-mixed 30% soluble/plain and
70% NPH) – Insulin mixture.
iv. Long acting: IZS crystalline (ultralente) and protamine
zinc insulin (PZI)
a. Unmodified regular insulin is useful in severe
hyperglycaemia (fasting blood sugar > 250 mg%),
low C-peptide levels (< 0.8 ng%), ketosis or weight
loss.
b. Modified depot insulins are usually given in moderate
diabetes, i.e. long acting drugs once daily,
intermediate acting drugs twice if necessary. DePo
insulins should not be given IV unlike regular insulins.
The dose of insulin is adjusted by examining the urine
(or blood if necessary) before breakfast, before lunch, before
dinner and at bed time. For example, if glycosuria is present
in the morning specimen (before breakfast) previous evening
dose of insulin is to be increased accordingly and so on.
The onset, peak and duration of action of different insulins
vary considerably (Fig. 28.5).
2. Insulin analogues (Parcnteral)
i. Very short acting—Insulin LisPro; insulin apart.
Insulin glulisine (These are very rapidly acting
insulins (5-15 mts and lasts for 3-5 hours).
ii. Long acting—Insulin glargine; insulin determir
3. Insulin mixture (premixed)
i. 70% NPH and 30% regular or 50% NPH and
50% regular (vide supra)
ii. 75% NPL and 25% insulin LisPro or 50% NPL
and 50% insulin LisPro (NPL is isophane
complexes of protamine with insulin LisPro, i.e.
neutral protamine LisPro)
iii. 70% insulin as part protamine and 30% insulin
as part.
4. Incretins (parenteral) Exenatide 15-10 mcg bd) SC
N.B. Long acting glargine should not be mixed with neutral
insulin as precipitation occurs instantly.
C. Combination therapy
i. Insulin and oral hypoglycaemic drugs are used
together.
ii. Both modified and unmodified insulin can be
combined as necessary and to be given
subcutaneously.
Fig. 28.5: Types of insulin and their action times
onset peak and duration
 Polyuria
iii. Oral drugs can be combined as per demands
sulphonylureas and biguanides or sulphonylureas and
thiazolidinediones or biguanides and thiazolidinediones
or sulphonylureas and thiazolidinediones as well as
biguanides.
Hypoglycaemia complication with insulin is common
and with Sulphonylureas (relatively uncommon but
serious). It is corrected by oral administration of
easily absorbable carbohydrates or intravenous 50 ml
50% glucose or
Glucagon may be given (1-mg IM) and repeated after
10 min, if necessary.
Allergy lipodystrophy and oedema are uncommon
complications (Fig. 28.6).
D. Other parenteral hypoglycaemic drugs (esp, post-
prandial hyperglycaemia by delaying gastric emptying
and inhibiting glucagon secretion) are (i) Exenatide
(5 mcg bd) (ii) Pramlintide (30 mcg bd). Pramlin tide.
(amylin analogue) like rapid acting insulin analogues
E. Other drugs
Guar gum, Glucomannan, chromium salts
F. Supportive drug therapy with vitamins, minerals,
antioxidants, alpha lipoiec acid and omega 3 fatty acids.
Drill (Exercise) Daily optimum isotonic (aerobic) exercise
(walking, playing tennis, etc.) as per the convenience of
the patient is another important component of therapy.
However, in long standing diabetics, it is not advisable to
adopt a new exercise programme because of possible silent
myocardial ischaemia.
Diet, medication and exercise must be adhered to with
fixed timings. In addition educating and motivating the patient
along with periodical check-ups must be included in the
management programme.
Complications They may be due to disease or treatment (vide
supra). The former can be prevented or retarded by good
metabolic control right from the beginning.
1. Acute complications
a. Diabetic ketoacidosis and hyperosmolar diabetic
coma (Refer to Chapter ‘Coma’).
b. Hypoglycaemia—(Vide supra)
c. Lactic acidosis. IV sodium bicarbonate along with
insulin and glucose recommended.
2. Late complications (Chronic)
a. Diabetic retinopathy; Photocoagulation or vitrectomy
(Laser treatment offered to seal leaking blood vessels
and stop growing of new blood vessels).
b. Cardiovascular
i. Coronary artery disease (Refer to Chapter ‘Chest
Pain’).
445
Fig. 28.6: Lipodystrophy subcutaneous fat atrophy in the
right deltoid region with insulin treatment
ii. Hypertension (vide infra) angiotensin 11
antagonist useful. (Refer to Chapter ‘Headache’).
iii. Cardiomyopathy: Treat as for congestive heart
failure.
iv. Peripheral vascular disease: Pentoxyfiline (400
mg twice daily). cilostazol (100 mg bd) and
Aspirin with or without clopidogrel from the
mainstary of medical therapy. Ischaemic foot
ulceration rigidly treated with appropriate
antibiotics and meticulous foot care. Revascula-
risation done either by surgical by pass
percutaneous endovascular techniques.
c. Cerebrovascular: (Refer to Chapter ‘Coma’).
d. Diabetic nephropathy: Aggressive treatment of
hypertension with ACE inhibitors and angiotensin
receptor blockers or ACE inhibitors and calcium
channel blockers to maintain blood pressure less
than130/80 mmHg besides instituting low phosphate
and protein diet. In the later stages, continuous
ambulatory peritoneal dialysis and renal trans-
plantation in selected cases considered. (Smoking
cessation may reduce risk of disease progression).
e. Diabetic neuropathy: Symptomatic treatment with
vitamins, analgesics, carbamazepine or gabapentin
along with insulin helpful. IV saline infusion bd for
one week may relieves pain. GLA (Gamma-lipoic
acid) may be beneficial. Benfotiamine (100-200 mg)
and methyl cobalamine (500-1500 ug) are beneficial.
ALA (Alpha linoleic acid). Useful in cardiac autonomic
neuropathy.
f. Autonomic neuropathy: Postural hypotension (Refer
to Chapter ‘Syncope’); Gastroparesis (Metoclo-
 446 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
pranide Itopride) impotence (Refer to Chapter
‘impotence’); neuropathic bladder (neostignine and
in dwelling catheter, occasionally resection of internal
sphincter).
Combination of Benfotiamine and L-Carnosine is
effective as adjuvant in diabetic microangiopathy.
3. Intermediate complications
a. Infections: Appropriate antibiotics as per the nature
of infection.
b. Periarthritis: NSAIDs and physiotherapy.
c. Complications during pregnancy: (Gestational
Diabetes Mellitus)- Increased calorie diet (300
calories more than actually required). Intensive
metabolic control of blood sugar levels with insulin
preferably short acting purified insulin (0.4 u/kg/d)
given 3 times daily per meal dose to achieve blood
sugar less than 120 mg. Also careful antenatal check-
ups by experienced gynaecologist with the help of
physician prevents most of the complications.
Delivery initiated usually at 34-38 weeks gestation
either by caesarean section or by normal vaginal route
following induction paediatrician’s help may also be
sought.
d. Dyslipidaemia may be corrected with statins, and /or
fibrates with nicotinic acid. Other drugs considered
are resins (probucol, soluble fibre-Ispaghulla), Bile
acid sequestrants (Cholestyramine, Colestipol),
Oestrogens, Omega 3 fatty acids, Ezetimibe useful
for lowering serum cholesterol particularly LDL
reduction which acts like bile acid sequestrant.
e. Cramps- Vitamin E 400 mg/d beneficial. Levo
carnitine is also recommended.
f. Diatetic boot—Control hyperglycaemia and
neuropathic symptoms; callous removal; regular ulcer
dressing, provide pressure offload in the feet.
Calcium Diabetes
(Hypercalcaemia and Hypercalciuria).
a. Expand extracellular fluid volume with two litres of
normal saline.
b. Administer frusemide.
c. Mithramycin (25 mg/kg iv) inhibits bone resorption.
d. Salmon calcitonin (200 iu subcutaneously tds) and
corticosteroids help some cases.
e. Treat the underlying cause accordingly.
Renal Dysfunction
Diuretic phase of Acute Renal Failure (Refer to Chapter
‘Oliguria’).
Chronic Renal Failure
A. Aim at retarding progression of chronic renal disease
by renoprotection.
Determine whether it is associated with reversible factors
(hypertension, UTI or urinary tract obstruction) or
irreversible failure. Treat reversible causes appropriately.
a. Diet: Restrict dietary proteins to 40 g/d and increase
carbohydrates and fats accordingly, so as to maintain
adequate calories. (0.6 g/d of protein with 35 calories/
kg/d. If GFR is severe reduce it to 0.2 g).
b. Fluid and electrolytes: 3 litres per day desirable unless
associated with cardiac failure or glomerular filtration
rate is < 5 ml per minute.
i. Restrict sodium and potassium (replace sodium
if salt losing nephropathy is present).
ii. Hypocalcaemia is treated with IV calcium gluconate
and 0.5 µg of alfacalcidol, or Calcitriol 0.5 µg/d.
iii. Hyperphosphataemia is treated with aluminium
hydroxide gel (1-2 g tds and restricting milk,
cheese and eggs). Aluminium accumulation may
result in encephalopathy and affect bones.
Calcium carbonate is another phosphate binder
(300-1200 mg tds); sevelamer (800-1600 µg are
other phosphate binders.
iv. Treat acidosis with 1/6 molar lactate infusion and
/or sodium bicarbonate (IV or oral)
c. Symptomatic vomiting treated with ondansetron or
domperidine; hiccups treated with chlorpromazine;
pains with appropriate analgesics; oedema with
adequate frusemide; visual loss by photocoagulation.
d. Avoid nephrotoxins and magnesium salts as well as
potassium intake.
e. Treat concomitant entities/complications: -
i. Hypertension: Blood pressure is reduced gradually
with ACE inhibitors and angiotension receptor
blockers, so as to maintain the blood pressure
preferably 125/75 or MAP maintained at 92 mm
of Hg.
ii. Diabetes Mellitus: Treated with insulin or
repaglimide or pioglitazone.
iii. Cardiac failure: Conventional treatment is
instituted adjusting the doses of digoxin and
diuretics.
iv. Anaemia: Nandrolone, erythropoietin (L-carnitine
may reduce its requirements) and packed cells
transfusion. Other causes of anaemia may be
considered and treated appropriately.
 Polyuria
v. Osteodystrophy: Treated with vitamin-D-
analogues. (serum calcium x serum phosphorus
should not exceed 55 mg. If parathyroid
harmone is raised, reduce phosphates by
appropriate diet and binders (vide supra), apart
from instituting vitamin D analogue and calcium
supplements).
vi. Dyslipidaemia—vide supra.
vii. Infections: Treated appropriately with antibiotics,
which are not nephrotoxic.
viii. Hyper homocysteinaemia if associated is treated
with folates.
f. Cortisone may reduce fibrosis or sclerosis and
rapamycin may reduce proteinuria.
B. Dialysis: Haemodialysis or continuous ambulatory
peritoneal dialysis. If serum creatinine > 7. 5, potassium
> 6 mmol/L pH<7. 2 or GFR 10-15 ml/min.
C. Renal transplantation: Renal replacement therapy
considered when persistent uraemia, refractory
hyperkalaemia, acidosis and intractable fluid overload.
Natriuretic Syndrome
Replace sodium and bicarbonate.
447
Diabetes Insipidus
Hormones: Vasopressin (10-20 u once or twice daily i.m.)
or desmopressin (10-20 µg once or twice daily intranasally
or orally 0.1 mg t.d.s) is given.
Other drugs that can be given are chlorpropamide,
clofibrate and carbamazepine.
Nephrogenic diabetes insipidus is treated with thiazide
diuretics (vide supra).
In addition to the hormonal drugs, fluids may be replaced
as necessary and the underlying cause is treated appro-
priately.
Hypokalaemia
Potassium chloride is usually given orally (8-15 g/d, i.e.
one gram of KCl contains 13.4 mmol of potassium)
supplemented by potassium rich diet like fruit juices.
Occasionally, potassium may have to be replaced IV (1.5 g
of potassium chloride in 500 ml of normal saline or glucose).
The plasma potassium may be monitored. Salt and water
depletion, if present, should primarily be treated.
448 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Pruritus
29
Pruritus is an itching sensation of the skin which evokes
motor response of scratching invariably. Scratching relieves
itching by transient damage to the nerve fibres concerned
with pruritus (itch scratch cycle). The intensity of itching
varies with the sensitivity of the skin and reactivity of mind.
Itching is an irritating cutaneous sensation without any
specific end organs. Scratch mark which is a leniar
excoriation is the sign of pruritus, and lichenification a sign
of scratching or rubbing.
PATHOPHYSIOLOGY OF PRURITUS
It is produced by the activation of receptors of itch stimuli
residing in the papillary layers of epidermis (Fig. 29.1).
The impulses transmitting pathologic pruritus pass
centrally with pain fibres through unmyelinated slowly
conducting ‘C’ group fibres to the spinal cord.
(Myelinated ‘delta A’ fibres transmit physiological itching.)
The stimuli are then carried through posterior roots and
anterolateral tracts to the thalamus, and then to postcentral
gyrus. Though pain and itch share the common stimuli,
they are felt as different modalities of sensation. Itching
appears to be caused by summation of subthreshold
stimuli too weak to cause pain. Some regard itching as
distinct sensory modality rather than subthreshold pain
modality. However itching is regarded as modified type
of pain caused by mild tissue damage. It is marked in
areas where great numbers of pain conducting fibres exist
(flexures and anogenital areas). An itch scratch centre is
presumed to be present in the floor of the 4th ventricle.
The stimuli which stimulate the itch receptor may be
exogenous or endogenous like histamine, kinin, bradykinin.
Also certain substances like bile salts or excess calcium or
xerosis (excess moisture loss due to a cutaneous lipid or
any systemic disorder) may account for itching.
CLINICAL PERSPECTIVE
Pruritus may be the symptom of primary visible skin lesions
or secondary to systemic disorders without obvious skin
disease. Predominantly, the former is localised whereas the
latter is generalised. It may be transient (physiological) or
persistent (pathological), and may even be due to a serious
underlying diseae. Significant localised forms of anogenital
pruritus (pruritus ani,pruritus of scrotum and male genitalia
or pruritus vulvae) need a special mention. The other
localised areas are eyelids, nostrils or ear canals.
The anal itching occurs when the anus is moist or soiled
as in:
1. Rectal (proctitis, thread worm infestation),
2. Anal (piles and fissures), and
3. Cutaneous (monilial infections; hyperidrosis)
Genital itching may be:
a. Scrotal pruritus (usually due to hyperidrosis and
fungus infections)
b. Genital pruritus is due to (i) infections like herpes
or moniliasis, (ii) glycosuria, and (iii) contact
dermatitis.
Pruritus vulvae may be due to:
a. Hyperidrosis and lack of personal hygiene
b. Parasitic: Trichomonas, threadworm infestation
c. Infections: Monilial, secondary to vaginitis
d. Chronic vulval dystrophies: Oestrogen deficiency
(senile atrophy), kraurosis vulvae
e. Sensitising chemicals of contraceptive appliances
f. Localised primary dermatosis (e.g.pediculosis) or
systemic disorders like diabetes mellitus (vide infra).
 450 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

1. Stratum corneum
2. Stratum granulosum
3. Stratum spinosum
4. Stratum basale
5. Epidermal cells
a. Keratinocytes constitute (90%)
b. Langerhans cell in mid-term epidermis
c. Melanocyte in stratum basale
6. Superficial vascular plexus
7. Eccrine sweat GL and
8. Eccrine sweat duct with pore
9. Sebaceous gland
10. Deep vascular plexus
11. Cutaneous innervation
a. Meissner corpuscle
b. Krause bulb
c. Ruffni endings
d. Pacinian corpuscle
12. Hair components
a. Hair papilla
b. Hair matrix
c. Hair follicle with sheaths
d. Hair shaft-visible and root (Embedded)
e. Nerve to hair follicle Fig. 29.1: Structure of normal skin
13. Branching nerve endings in dermis and epidermis
14. Fat filled cell with supporting collagen fibres.

CAUSES OF PRURITUS (TABLE 29.1)

Contd...
The causes of pruritus are enlisted in Table 29.1.
2. Systemic and other disorders
Table 29.1: Causes of pruritus
a. Infestations
I. Itching Dermatoses (With Obvious Skin Lesions–Usually i. Pediculosis corporis
Localised) ii. Filariasis: Onchocersiasis
1. Physical iii. Ankylostomiasis and other intestinal parasites
a. Climatic Effects iv. Malaria
i. Effects of heat (prickly heat) b. Hepatic disorsers: Obstructive jaundice
ii. Effects of cold. c. Metabolic and endocrinal
b. Wollen clothing i. Diabetes mellitus
2. Infestations (parasitosis and arthropoda) ii. Thyroid disorders: Hyper and hypothyroidism
a. Pediculosis (capitis or pubis) iii. Hyperparathyroidism
b. Scabies iv. Carcinoid syndrome.
c. Larva migrans d. Renal: Chronic renal failure.
d. Ankylostomiasis e. Haematological
e. Schistosomiasis i. Polycythaemia vera
f. Insects like mosquitoes and bedbugs. ii. Iron deficiency anaemia
3. Urticaria (food and drugs) iii. Leukaemia
4. Infections iv. Paraproteinaemias
a. Fungal f. Internal malignancy
b. Viral: Acute exanthemata i. Lymphomas and AILD
5. Dermatitis and eczema ii. Myeloma
6. Lichenoid Dermatosis: iii. Carcinomatosis
Lichen simplex chronicus (neurodermatitis) and lichen planus iv. Carcinoids
7. Pityriasis rosea g. Collagen disease
8. Mycosis fungoides i. Scleroderma
II. Itching Dermatoses (Without Obvious Skin Lesions-Usually ii. Dermatomyositis
Generalised) 3. Dry skin (xerosis or asteatosis) ichthyosis.
1. Physiological: Pregnancy (especially last month) 4. Senile pruritus.

Contd... Contd...
 Pruritus
Contd...
5. Food and drugs sensitivity (allergic reactions)
a. Subclinical drug sensitivity
b. Opium derivatives
c. Gold salts
d. Penicillin
e. Detergents
f. Gluten or food additives sensitivity.
6. Vasospastic disorders: Erythromelalgia
7. Psychogenic
a. Emotional
b. Delusional
c. Acarophobia.
Itching Dermatosis with Obvious Skin Lesions
(Climatic Effects)
1. Physical
Effects of heat (prickly heat) It consists of discrete pin-head
sized papulo-vesicles with erythematous base usually seen
in summer months associated with excessive sweating.
Pricking and itching are distressing. Keratin or sodden
cornified cells obstruct the orifices of the ducts of the sweat
glands, leading to the retention of sweat in the ducts which
in turn may rupture and cause miliaria. It disappears by
desquamation. Such repeated attacks may lead to chronic
obstruction of the sweat glands and tropical anhydrotic asthenia.
Effects of Cold During the winter months, exposure to cold
weather may precipitate itching (winter itch). Dry skin, hot
baths and wollen clothing may perpetuate.
2. Infestations (Parasitosis and Arthropoda)
Pediculosis Pediculosis is caused by lice (ectoparasites)
infection over occipitoparietal regions, body and pubis.
The parasites cause irritation and scratching resulting in
secondary infection. There are often blue grey macules
on the thighs at the site of the bites in phthiriasis pubis
infection. Other members of the family may be affected
by direct contact. There are three forms of lice (i) Pediculus
capitis, (ii) P. corporis and (iii) Phthiriasis pubis. The eggs
(nits) are laid over the hair of the host or inner side of
clothing. The larvae hatch out from eggs in eight days and
complete the entire life cycle of 4 to 6 weeks on the human
body.
A close watch may show 3 mm long mobile lice or
white nits obliquely attached on the shaft of the hair or
clothing.
Scabies It is caused by a mite, Sarcoptes scabiei. Itching
begins after three days of infestation and it is intense
451
particularly at night. The lesions consist of characteristic
burrows (narrow tortuous lines with dark dots which is the
site of the bites) with fine follicular papules and excoriations
over the interdigital webs, axillary folds, thighs, buttocks
usually sparing the head, face and neck. Papulo-pustules
with erythematous base develop due to secondary infection.
The lesions may be severe affecting the whole body including
face, and scalp resulting in crusting and scalling (Norwegian
scabies). Other members of the family may be affected by
intimate skin contact.
The mite is less than 0.5 mm long. The gravid female
burrows in the horny layer and lays eggs. The larvae hatch
out from eggs and develop into matured forms. The complete
life cycle takes about 10 to 15 days.
Larva Migrans This is of two types: (1) Visceral larva migrans
(toxocariasis) and (2) Cutaneous larva migrans (creeping
eruption), in which the filariform larva penetrates and
migrates in the skin. The initial red papule develops into an
irregular erythematous lenier lesion which may be seen over
the surface of the bright skin. Severe itching follows,
accompanied by secondary infection. It is caused by the
larvae of the (i) Dog hookwarm (A. brasiliense), (ii) Horse
bat fly (gasterophilus); (iii) Strongyloides stercoralis and (iv)
Necator Americans.
Ankylostomiasis When filariform larva penetrates the skin,
ancylostome dermatitis results. It causes itching followed
by papular or vesicular eruption with or without secondary
infection, (ground itch) apart from creeping eruption.
Schistosomiasis The fork-tailed cercaria penetrate the skin
of the swimmer or bather, causing cercarial dermatitis. It is
characterised by itching with formation of reddish petechiae.
Arthropoda The stings of insects like mosquitoes, bedbugs
and ants produce allergic skin reactions (urticarial weals
and papules) with itching, leading sometimes to lichenifi-
cation even.
Malaria (Refer to Chapter ‘Rashes’).
3. Urticaria (HIVES)
It is a vascular reaction of the skin (vasodilatation and
permeability) due to the liberation of histamine from mast
cells predominantly. The etiology is (i) allergic (immune
mediated: SLE; or complement mediated: Atopic diathesis,
Specific exposure to antigens), (ii) physical (thermal; cold,
heat solar) or mechanical (dermographism and prolonged
pressures) (iii) cholinergic, and (iv) idiopathic.
There are several clinical types of urticaria.
Acute Urticaria It is characterised by pruritic circumscribed
weals with erythematous borders and pale centres. They
 452 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

may coalesce to form giant weals. The wealing is

spontaneous and may be evanescent. It may be associated
with fever, generalised lymphadenopathy and swelling of
the joints. The cause of urticaria is usually allergic
(immunological) due to drugs, foods, moulds, insect bites
and parasitic infestations. If such recurrent episodes occur
for a period of six weeks or less, they are grouped as
acute.
Chronic Urticaria The eruption recur over a period of six
weeks or more. New weals continue to appear at varying
intervals as the old lesions disappear. In most cases, the
cause appears to be a plethora of mechanisms acting together
or otherwise. Immunological mechanisms seem to be of
less importance than the physical factors like heat, light
(yellow band of specturm) and prolonged pressures (tight
belts or watch straps). Cold urticaria is seen after bathing
in cold water. In severe forms it may prove a great disability,
since syncopal attacks may lead to drowning, while
swimming. Fig. 29.2: Papular urticaria

Giant Urticaria (Angioneurotic Oedema) Angio-oedema

swellings occur over the face specially eyelids and lips.
Dangerous oedema of the larynx may occur rarely. Urticaria
may be associated with angioneurotic oedema. Absence or
deficiency of CI esterase inhibitor of complement is
associated with the rare hereditary angio-oedema.
Factitious Urticaria Dermographism (triple response on
scratching) occurs without spontaneous wealing. However,
the wealing results from mechanical irritation like friction
or scratching, or firm pressure on the skin with a blunt
point. The cause is unknown but may by psychogenic or
associated with mastocytosis.
Cholinergic Urticaria It consists of small circumscribed weals
of uniform size surrounded by irregular flares chiefly over
the trunk. The attacks are provoked by exertion like exercise
or excitement like emotional disturbances or warmth or with
cholinergic drugs. Cholinergic urticaria with pruritus occurs
after sweating and severe attacks may be followed by a
refractory period of 1-2 days.
Papular Urticaria (Lichen Urticaria)
a. The lesion consists of evanescent weals replaced or
succeeded by a papule which may persist for a week
(Fig. 29.2).
b. The papules may be surmounted by vesicles.
c. They are distributed over the trunk or legs.
Insect bites or Trombicula, irritants or infections or focal
sepsis or food sensitivity are implicated.
Urticaria Pigmentosa It is a rare disorder characterised by
brownish (pigmented) macules or nodules which urticate
on scratching or friction. The lesions are found predomi-
nantly on the trunk and appear during early childhood or
adulthood. Darier’s sign is diagnostic. Residual pigmentation
which results may be fade ultimately. (vide infra)
Mastocytosis or human mast cell disease may be
cutaneous with or without systemic involvement. It may
benign or malignant. The benign generalised cutaneous form
is referred to as urticaria pigmentosa, whereas the benign
localised form is known as mastocytoma. The malignant
generalised form is malignant systemic mast cell disease
and the malignant localised form is mast cell sarcoma.
Histology shows granular mast cells in the upper dermis.
4. Infections
Fungal Infections (Superficial mycoses) Cutaneous mycotic
infections are divided into three groups: (a) Tinea versi-
color; (b) Dermatophytoses (ringworm fungi)—
Microsporon,Trichophyton, Epidermophyton; (c) Candidi-
asis (moniliasis).
i. Tinea versicolor: The lesions consist of light brown,
hypopigmented macules with fine scaling and minimal
itching on the trunk, arms and occasionally neck and
face. The outermost layers of the skin are affected with
minimal cellular response. Scales are readily obtained
by scraping, and the scraping show yeast and hyphal
forms of the causative organism of Pityrosporum
orbiculare are spores. It is seen mostly in humid warm
climate and sweating increases the susceptibility to
 Pruritus
infection. Wood’s lamp shows golden yellow fluorescene
due to a metabolic product of coproporphyrin.
ii. Dermatophytoses: It is classified according to the
anatomical site of involvement rather than the type of
fungus infection. The clinical features depend on the
keratinous structures affected.
The sources may be human.
a. Tinea capitis (ringworm of the scalp): The lesions consist
of circular, scaly (microsporon) or non-scaly
(trichophyton), apparently bald patches on the scalp with
broken hair stumps which appear as black dots. It may
vary from mild non-inflammatory type to a severe painful
boggy inflammatory mass discharging pus with crusting
and matting of hair (kerion). The term ringworm indicates
the serpiginous border of inflammation. In favus,
yellowish cup shaped crusts (scutula) with hair piercing
centrally are the characteristic lesions, and causative
organism is Trichophyton schoenleinii, Wood’s lamp
shows green fluorescence.
b. Tinea corporis or circinata (body ringworm): It is
characterised by annular lesions with raised edges
consisting of rings of small papulovesicles at the
periphery and central healing. The lesions may be
accompained by moderate degree of inflammation and
usually confined to the waistline of the abdomen. It is
caused by all the three genera and trichophyton is the
commonest.
c. Tinea cruris (Dhobie’s itch): The lesions consist of well
defined scaly macules peripherally spreading and centrally
clearing with or without vesicles; or pustules confined
to the inner aspects of the upper thigh and groins. It is
caused by any of the three genera and more common in
men.
d. Tinea pedis (athlete’s foot): The lesions consist of
irritable macerated fissures between the toes (especially
in the 4th and 5th) turning into a sodden white membrane
covering the erythematous fissured skin. The scattered
vesicles may form ulcers and develop cellulitus due to
secondary infections. A squamous hyperkeratotic lesion
affecting the soles, heels and/or sides of the feet
(Moccasin foot) is not uncommon. The lesions are
caused by trichophyton and epidermophyton.
The diagnosis of dermatophytoses is confirmed from
scrapings collected for KOH (10%) smear and culture by
Sabouraud’s medium.
iii. Cutaneous candidiasis: It usually affects (a) body folds
like axillae or groins or beneath the pendulous breasts;
(b) interdigital (toes); (c) angles of mouth (Perleche);
and (d) Vulva and intergluteal cleft. It is characterised
453
by red macerated area with undermined peripheries.
There may be satellite vesiculopustules. Whitish curd
like concretions may be present on the surface of the
lesion (especially in oral and vaginal mucous membrane).
Itching is intense. It is caused by Candida albicans.
Diagnosis is established by demonstrating pseudo hyphae
on KOH smear and culture by Sabouraud’s medium.
Viral Acute exanthemat a (Refer to Chapter Rashes.)
5. Dermatitis and Eczema
Dermatitis is a noncontagious inflammation of the skin with
erythema, oedema, oozing with or without vesiculation. It
can be classified as (a) contact (allergic) dermatitis,
(b) exfoliative dermatitis, (c) seborrhoeic dermatitis,
(d) dermatitis herpetiformis, (e) dermatitis medicamentosa,
(f) varicose dermatitis, (g) photosensitisation and solar
dermatitis, and (h) atopic dermatitis.
a. Contact dermatitis (Allergic)
Contact dermatitis sometimes is classified into:
i. Primary irritant dermatitis (appears at the site of
contact with an irritant within 1 to 2 h, e.g.industrial
irritants).
ii. Eczematous contact dermatitis or exogenous eczema
(due to topical medicines, detergents, chemicals like
nickle, kumkum dye and cosmetics, animal pollens
or protein rich products).
It is an acute inflammatory reaction of the skin due to
skin allergy usually confined to localised areas. The
characteristic lesions are erythema, oedema, vesicles
with variable amount of itching. Diagnosis is confirmed
by doing a specific patch test by applying the suspected
substance to the unaffected area, preferably back of the
chest, under an occlusive tape for about 48 h.
b. Exfoliative dermatitis (Erythroderma): This is an actively
developing generalised erythema of large areas of the
skin associated with continuous profuse scaling.
Exudation of serum may appear accompanied by
constitutional symptoms and lymphadenopathy. It may
be a sequelae to dermatitis medicamentosa or contact
dermatitis or secondary to systemic disease like
lymphomas.
c. Seborrhoeic Dermatitis: It is an acute or chronic
inflamatory scaly disease of the areas of the body where
sebaceous glands are abundant like scalp (extending to
ears and forehead), chest and body folds. It consists of
scaly erythematous plaques or folicular papulosquamous
lesions, accompanied by pruritus. Yellowish material may
extrude. Greasy scales can be rubbed off. The cause is
 454 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
unknown but presumed to be due to altered sebaceous
secretions which may predispose to secondary
infections.
d. Dermatitis Herpetiformis: It is characterised by
symmetrical polymorphic eruptions over lumbosacral
regions, scapular areas, abdomen, forearms and knees.
The primary lession is either an erythematous papule,
an urticarial like palque or a vesicle. The eruptions are
grouped in clusters associated with intense itching. The
continuous appearance and disappearance of the lesions
may leave behind pigmentary changes. Presence of IgA
deposites and C3 in apparently normal skin is highly
diagnostic. The cause is regarded in part as a
consequence of abnormally overactive immune response
to natural antigens. High incidence of HLA-B8, BRw3
and other alloantigens is documented.
e. Dermatitis Medicamentosa: It is an acute cutaneous
reaction to drugs ingested or injected (except topical
applications). The lesions consist of drug eruptions
which may include urticaria, eczema, exfoliative
dermatitis, exanthematic or fixed eruptions or
photosensitivity reactions. Occasionally the eruptions
may be bullous or lichenoid. constitutional symptoms
may be present. Diagnosis can be confirmed by
withdrawal or readministration of the drug and
intradermal or patch tests. Radioallergosorbent test
(RAST) for specific IgE antibody may be useful.
f. Varicose Dermatitis: It complicates varicose veins or
ulcers over the lower part of the leg due to hypostatis.
The itching may lead to eczema and secondary infection.
Sometimes this varicose eczema may result in
disseminated eczema due to auto sensitisation.
g. Photosensitisation and Solar Dermatitis: Photoallergic
dermatitis is an immunological reaction of delayed
hypersensitivity type initiated by ultraviolet (UV-A, 320-
400 nm wavelength). It may be due to primary sensitivity
to sunlight (UV rays) or the sunlight may secondarily
aggravate the lesion to drugs or foods or external
applications with dye and plant products. Sometimes
seborrhoea, niacin deficiency or some metabolic
disorders like porphyrias may predispose to
photosensitisation. The lesions consist of erythematous
rash with or without vesicular, papular, bullous or
lichenoid formation and subsequent pigmentation over
the exposed parts for the body. The drugs incriminated
are sulphonamides, tetracyclines, phenothiazines,
griseofulvin, nalidixic acid, thiazide diuretics etc.
h. Atopic Dermatitis Eczema (Vide Infra.): Eczema or
Eczematous dermatitis though the terms dermatitis and
eczema are used interchangeably, the conventional usage
of these terms with differing significance is desirable.
Dermatitis represents only inflammation of skin and this
term is significant particularly qualified like seborrhoeic
dermatitis. Eczema is an inflammatory response
characterised by epidermal oedema, erythema and
papulo-vesicles or pustules with subsequent weeping
and crusting, or appearance of scaling on erythematous
base during recovery or secondary effects like
pigmentary changes or lichenification (thickened skin
with pigmentation).
Eczema is classified as (a) endogenous (constitutional)
and (b) exogenous (contact)—(vide supra) based on
the internal or external causative factors respectively.
The endogenous eczema is further categoriesed as (a )
atopic, (b) nummular or discoid, (c) infective, (d)
centripetal (e) disseminated and (f) Cheiropompholyx.
• Atopic Eczema: It is a part of hay fever, asthma,
eczema syndrome. It is a superficial inflammation
of the skin characterised by pinhead sized pruritic
papular or vesicular exudative eruptions on the face,
neck as well as folds of the knees and elbows, more
or less generalised. The disease may first appear
during infancy usually in first three months and
disappears in second year. It may recur in the 5th
year and may continue up to the age of 12 with
tendency for exacerbations from time to time.
Though it is exudative in infants, it is dry and
lichenifide in children with subsequent pigmentary
changes in adults. It may be due to genetic
predisposition reacting to allergens.
• Nummular Eczema (Discoid): It is a characterised
by circular plaques of papulo-vesicles and crusting
distributed over arms, hands,thighs and legs
bilaterally.
• Infective Eczema: It develops around post-traumatic
aberrations or insect bites. It is characterised by a
well-defined patch with a crust vesiculation or
erythema which results from sensitisation to
secondary organisms.
• Centripetal Pattern Eczema: It affects the trunk,
upper portion of the chest (including scapular) and
gluteal lesions.
• Disseminated Eczema (Eczematides): It is
characterised by papular, vesicular or bullous lesions
with crusting and involves extensively including face
and eyelids. History of primary eczema may be
forthcoming earlier, to this dissemination brought
out by autosensitisation. It may be a complication of
 Pruritus
a local eczema of any type or considered as a variety
of nonatopic eczema.
• Cheiropompholyx (Dyshydrotic eczema): It consists
of vesicular eruptions with tingling and itching over
the palms and sides of the fingers and occasionally
soles. They dry up in about two weeks time with
mild scaling. Secondary infection may complicate.
Such recurrent attacks may lead to hyperkeratosis
with or without vesicles. Sweating is absent in the
affected area. It generally affects psychoneurotic
individuals with a tendency for hyperidosis of the
hands. Diagnosis is established by patch test, trigger
test (reproduction), eliminating some diet, or
presence of eosinophilia and histopathology which
shows spongiosis (intercellular oedema of epidermis).
6. Lichenoid Dermatosis
Lichen Simplex Chronicus (Neurodermatitis) A patch of lichen
simplex is shiny and usually oval with the edge fading into
normal skin. Lichenification results from prolonged and
repeated scratching of the skin and irritation thereof. The
integument becomes thick and pigmented with definite
margins. There is a tendency to become fissured and
secondarily infected. The common sites are anterolateral
aspects of legs, nape of neck, arms and anogenital area.
Emotional conflicts and menopause or a local irritation or
friction usually initiate itching. (Lichenified Eczema)
Lichen Planus It is a chronic cutaneous disorder
characterised by itchy, shiny, polygonal flat topped papules
occuring mostly on the flexor surfaces. Papules may be
arranged in circles or lines. Magnifying lens reveals linear
grey streaks on the surface of the papule. Typical distribution
is over in front of the wrist or around the ankles or on
lumbar regions. Occasionally hypertrophic plaques and rarely
bullae on the skin and erosions or ulcers on mucous
membrane, especially buccal mucosa and tongue may be
seen. The lesions leave behind pigmentation which persist
for months or years. The cause is unknown.
7. Pityriasis Rosea
It is characterised by a herald patch initially over the lower
ribs, upper abdomen or shoulders. The patch is round or
oval sharply defined and covered by fine scales. After an
interval of one week, papular, pink, or fawn or red lesions
with dry silvery grey scales develop in crops over trunk,
arms and upper third of the thighs. They disappear
spontaneously within one or two months.
455
8. Mycosis Fungoides
Mycosis fungoides is a cutaneous T-cell lymphoma which
begins as pruritic cutaneous lesion resembling erythematous
urticaria or eczema (premycotic or first stage). After
prolonged interval of years, the second infiltrative stage
appears with indurated gyrate plaques and a tendency for
central clearance. After a few months, red brown nodular
tumours (lobulated or pedunculated sometimes) appear
which eventually ulcerate (third stage). The skin biopsy
shows distinct cells identified as thymus dependent
lymphocytes (mycosis cells). Internal organs associated with
reticuloendothelial tissues like spleen, liver, lymph glands
may also be affected. Ultimately the disease may be fatal.
Sezary syndrome, another T-cell neoplasia, produces
generalised itchy erythroderma and sezary cell like mycosis
cell is diagnostic.
Itching Dermatoses
(Without Obvious Skin Lesions—Generalised)
1. Physiological: Pregnancy
Pruritus in pregnancy usually occurs during the last trimester
and it clears up after delivery with a tendency to recur with
successive pregnancies. Pregnancy rashes have a different
aetiology and they are known as pruritic urticarial papules
and plaques of pregnancy. The pruritus can occur in
pregnancy due to:
a. Herpes gestationis where symmetrical generalised lesions
resembling pemphigoid, occur in clusters.
b. Pruritus gravidarum resulting from intrahepatic
cholestasis.
c. Some women are atopics who may develop prurigo
nodules on arms and legs.
d. Acute immune progestrone dermatitis.
e. Other usual causes of pruritus.
2. Systemic and other Disorders
Infestations
• Prediculosis Corporis (vide supra.)
• Onchocerciasis: It is caused by filaria volvulus
(Onchocerca volvulus), which gains access by the bite
of female black fly (Simulium) of West Coast of Africa
or Central America. The nodule that forms at the site of
the bite is the source for microfilariae, which invade the
skin causing marked pruritus. An itchy infected papule
or lichenoid eruption results. The occular complications
are more striking. Diagnosis is based on the skin clips
 456 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
mounted on a glass slide with one or two drops of normal
saline revealing MF volvulus (it is not seen in the
peripheral blood like MF Bancrofti).
• Ankylostomiasis and other intestinal parasites (Vide supra)
• Malaria (Refer to Chapter ‘Rashes’).
Hepatic Disorders In obstructive Jaundice, itching is related
to retention of bile salts, in the blood and is directly related
to the level of concentration, rather than severity of jaundice.
(refer to chapter Jaundice.) It is an inaugral symptom in
primary biliary cirrhosis.
Metabolic and Endocrinical Diabetes mellitus Generalised
pruritus may occur at the onset of diabetes mellitus probably
due to accumulation of unused sugars in the tissues.
However, the hyperglycaemia may predispose to candida
infections and lead to pruritus ani, vulvae or balanitis. Dry
skin, due to decreased surface lipid and decreased hydrating
capacity, is also incriminated (Refer to Chapter ‘Polyuria’).
• Thyroid disorders (Hyper and hypothyroidism) In some
cases of hyperthyroidism, the skin may become
thickened, pruritic and hyperpigmented over the pretibial
area and dorsum of the feet probably due to infiltration
with a mucopolysaccharide and lymphocytes. In
hypothyroidism, the pruritus may be present due to dry
skin (Refer to Chapter ‘Goitre’).
• Hyperparathyroidism Itching is evoked due to cutaneous
calcium deposits.
Carcinoid syndrome: In carcinoid syndrome, there may
be paroxysmal cutaneous flushing attacks precipitated by
exertion, food and alcohol, besides cardiopulmonary and
gastrointestinal symptoms. Associated pruritus is probably
due to liberation of serotonin, bradykinin and histamine.
The diagnosis is confirmed by increased urinary excretion
of 5 hydroxy indole acetic acid (normal 9 mg) (Refer to
Chapter ‘Chronic Diarrhoea’).
Renal Chronic Renal Failure
In chronic renal failure, serum phosphate levels are raised
which facilitate calcium deposition in the bone. There is
also impaired ability to synthesise 1, 25 dihydroxy vitamin-
D which affects the reabsorption of calcium in the gut.
These changes contribute to hypocalcaemia and raised
plasma parathormone levels. This secondary hyperpara-
thyroidism is related to uraemic pruritus through increased
cutaneous deposition of calcium phosphate. Uraemic toxins
and dry skin also contribute to itching.
Haematological
• Polycythaemia vera: In polycythaemia vera, pruritus
may be precipitated by a hot-bath in about 20 to 50
percent of cases. This has to be differentiated from
aquagenic pruritus in which itching can be provoked by
water with any temperature. The itching is attributed to
liberation of histamine from the basophil granulocytes
and intensity is directly related to packed cell volume of
blood (Refer to Chapter ‘Cyanosis’).
• Iron deficiency anaemia: Pruritus can be a symptom
of anaemia and this is more a curiosity than of diagnostic
value. The pruritus may be attributed to tissue anoxia.
• Leukaemia Pruritus may be a presenting symptom in
chronic leukamia probably due to infiltration of the skin
with the abnormal white blood cells. However, diagnosis
is confirmed by blood picture which shows leucocytosis
with characteristic immature abnormal types of white
cells.
• Paraproteinaemias: This implies proliferation of a single
class of immunocytes. In myeloma, pruritus may occur.
Other features like bone pains and anaemia supported
by lytic lesions in the X-rays, characteristic globulin
peak on electrophoresis and plasma cells in the bone
narrow, confirm the diagnosis.
Internal Malignancy
• Lymphomas: Pruritus may be associated with 30 percent
of Hodgkin’s disease and may be the presenting symptom
of lymphomas. It is suspected by characteristic cyclical
fever of Pel-Ebstein type and lymphadenopathy with
involvement of extralymphatic organs which can be
diagnosed by lymph node biopsy and histopathological
examination. Characteristic giant cells with double or
multiple nuclei (Sternberg-Reed cells) confirm the
diagnosis of malignancy of lymphoid tissue.
• Angioimmunoblastic lymphadenopathy with
dysproteinaemia (AILD): This lymphoma-like systemic
disorder is associated with pruritus and maculopapular
rash before the onset of classical features like fever,
lymphadenopathy and hepatoplenomegaly. Lymph node
biopsy shows alternation of nodal architecture with
cellular proliferation (immunoblast lymphocytes and
plasma cells predominant) as well as vascular
proliferation. Some consider this entity as an extreme
variety of hyperimmune reaction.
• Carcinomatosis: Generalised pruritus may be a mani-
festation of carcinomatosis of the lung, gastrointestinal
tract, prostate, breast or CNS tumours. This symptom
is occasionally related to visceral carcinomas rather than
lymphomas particularly Hodgkin’s disease. Sometimes
it is associated with acanthosis nigricans in the presence
of visceral cancer like stomach.
• Carcinoids: Carcinoid tumours are slowly growing
primary neoplasms of enterochromaffin cells. Tumours
arising from ileum, stomach and bronchi may
metastasise, as compared to appendicular carcinoids
 Pruritus
which rarely metastasise. There may be no clinical
features till liver metastasis occurs or tumour itself may
cause intestinal obstruction or bleeding or acute
abdominal crisis due to necrosis. About 5 percent exhibit
carcinoid syndrome due to the hormone serotonin (vide
supra).
Collagen Diseases
• Scleroderma (Refer to Chapter Polyarthritis)
• Dermatomyositis (Refer to Chapter Paraplegia)
3. Dry Skin (Xerosis or Asteatosis)
It refers to fine accentuation of skin markings progressing
to roughened flaky skin with or without any visible scales
and associated with pruritus. Xerosis may be genetic in
origin (ichthyosis; anhidrotic type of congenital ectodermal
defect) or acquired (hypothyroidism; essential fatty acid
deficiency or environmental factors like cold weather and
low humidity or dehydration) or sensescence. Sometimes
it may be due to lymphoma without any familial history.
Artificial xerosis due to frequent usage of hot water and
soap must be borne in mind. The underlying mechanism is
decreased activity of sebaceous and/or sweat glands with
or without abnormalities of desquamation of cells.
The term asteatosis is sometimes used to denote
excessive degreasing of the skin particularly during winter
in the elderly.
4. Senile Pruritus
Senile pruritus is associated with intense pruritus in older
group (> 65 years) with dry, inelastic (atrophic) skin or
apparent emotional or climatic factors like exposure to cold
air. The sebaceous glands may be quantitatively reduced
and qualitatively defective. In cold weather and low humidity,
decreased flow of sebum may account for itching.
Degenerative (atherosclerotic) changes in the peripheral
nerves may contribute.
5. Food and Drug Sensitivity (Allergic Reactions)
The most frequent manifestation of drug sensitivity is drug
eruption. The reaction occurs within minutes to 24 h
depending on the type of allergic response elicited like:
a. Immediate or anaphylactic (type-I)
b. Cytotoxic/cytolytic reaction (type-II)
c. Arthus reaction or formation of immune complexes (type-
III)
d. Delayed hypersensitivity reaction (type-IV)
e. Autoimmune reaction evoked by drugs
457
f. Cross sensitisation: If an individual is sensitised to one
drug (Primary allergen) a reaction may result by the
administration of one or more chemically related
compounds.
Occasionally drugs may also cause cutaneous reaction
in nonallergic individuals due to liberation of vasoactive
mediators without an antigen antibody reaction. It is probably
based on genetic predisposition.
The clinical features of drug sensitivity include
generalised pruritus besides drug eruptions (exanthematous,
eczematous, fixed, urticaria, bullous, lichenoid, purpuric)
or exfoliative dermatitis or photosensitivity. Drug fever,
serum sickness (within six days) or anaphylactic shock
(immediate) are other clinical patterns. The drugs include
both topical and oral. Certain foods and food additives are
also incriminated.
6. Vasospastic Disorders: Erythromelalgia
There is paroxysmal, bilateral burning or itching sensation
of the feet and just above. The areas become warm and red
due to vasodilatation and related to increased ambient
temperature. This may be primary or secondary to
polycythemia vera and other myeloproliferative disorders.
7. Psychogenic
Generalised pruritus of psychogenic origin should be
diagnosed only after the other causes are excluded. In
psychogenic pruritus, psychogenic traits are often present
and it may result from a life style associated with stress and
strain. Sleep is not disturbed in psychogenic pruritus unlike
in other forms. This may be associated with vague
complaints like bad taste, burning tongue or feeling of insects
crawling under the skin (formication) which is a variant of
itching or delusions of parasitic infestations (acarophobia).
Emotional conflicts, anxiety and tension may aggravate
pruritus of organic causes.
CLINICAL APPROACH
The itch-scratch cycle, which constitutes scratching of an
itchy skin induced by lowered itch threshold stimuli, is not
only encountered with primary skin disease but also as a
presenting symptom of a systemic disorder. The latter is
usually conceived as generalised pruritus which refers to
the absence of cutaneous lesions except those due to
prolonged scratching or rubbing. So erroneous diagnosis
of a primary dermatological entity should not be committed
from the secondary changes of scratch marks or lichenifi-
 458 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

cation resulting from both scratching and rubbing. ii. Nikolsky’s sign: Positive in pemphigus and
Generalised pruritus is caused not ony by systemic disorders negative in dermatitis herpetiformis (Refer to
but also by local factors like infestations or dry skin. Chapter ‘Rashes’).
The term prurigo is sometimes used for a group of intense 2. Examination of other structures: Particularly hair, nails
itching conditions wherein striking physical signs include (burnished nail is a distinctive sign produced by rubbing
lichenification with pigmentary changes (depigmentation with back of the nail rather than the tip), oral and genital
with surrounding hyperpigmentation) and nodular formation mucosa.
with excoriated tops.
Evaluation of a patient with generalised pruritus includes General Examination
the detection of underlying systemic disease by a careful
history, physical examination, laboratory screening tests and 1. To look for anaemia, lymphadenopathy, jaundice or pedal
if necessary psychological assessment. Any case of oedema (as seen in exfoliative dermatitis).
generalised pruritus primarily should be screened for parasitic 2. Status of the skin: Xerosis, and pigmentary changes;
and arthropod infestation. That the generalised pruritus is 3. Any thyroid enlargement.
of psychogenic or idiopathic origin should only be made
after a scrupulous diagnostic drill. Systemic Examination
1. Evidence of pregnancy and its period
History
2. Any hepatosplenomegaly
a. Site of pruritus: Is it generalised or localised? 3. Rectal and vaginal examination
b. A clear history should be obtained whether cutaneous 4. Test for superficial sensations
lesions existed before pruritus or resulted after pruritus.
c. Is pruritus associated with rash or not? Psychological assessment
d. Precipitating factors must be identified.
e. Past dietary and drug history: Exogenous causes. If necessary (Refer to Chapters Coma and Headache)
f. History of diabetes mellitus, renal disease or worm
infestations? Investigations
g. Associated features like jaundice, anorexia, bullaemia, 1. Urinalysis: For evidence of renal disease or diabetes
flushings, weight loss, polyuria, bone pains, weakness, mellitus.
amenorrhoea, or emotional upsets (endogenous causes). 2. Stool examination: For ova, cysts or worms and ocult
h. Exposure to heat or cold or undue exercise.
blood.
3. Haematological
Physical Examination
a. Full blood count (eosinophilia is a constant finding
Local Examination of atopic dermatitis)
1. Dermatological examination (preferably by magnifying b. ESR
lens)—This should include: c. Bone marrow picture.
a. Type of primary lesions and their distribution. 4. Biochemical
b. Secondary changes if any. a. Blood sugar values especially postprandial
c. Palpation of skin to elicit tenderness (for acuteness) b. Blood urea and serum creatinine
induration (for chronicity) or dryness. c. Additional tests if necessary
d. Diascopy: Press firmly with a glass slide over the i. Liver function tests: Bilirubin, alkaline
skin to differentiate purpuric lesions from phosphatase, SGPT, SGOT.
erythematous macules. ii. Thyroid function tests: T3, T4, TSH levels
e. Wood’s lamp examination (Refer to Chapter ‘Rashes’) iii. Parathyroid assessment: Serum calcium and
f. Diagnostic signs like: phosphate levels
i. Darier’s sign: For urticaria pigmentosa (rubbing iv. Serum protein electrophoresis.
of a pigmented macule with a blunt object 5. Radiology
produces a palpable red weal within few minutes a. Chest X-ray
in urticaria pigmentosa). b. Other radiological surveys
 Pruritus
6. Skin scrapings
a. Microscopy: KOH smear for mycelia, or eggs (nits)
and adult pediculus over the hair/skin
b. Microbiological studies for fungi and secondary
organisms (culture by suitable medium)
c. IgA deposits in peri lesional cutaneous areas for
dermatitis herpetiformis.
7. Tests for allergy
i. Patch test: 0.5 cm in diameter patches of testing
material are placed at a distance of 5 cm over the
back or forearms and covered with a piece of lint
and adhesive tape firmly. Readings should be done
after 48 h. Look for:
a. Redness with normal skin (+) and with oedema
(++)
b. Redness, oedema and papules (+++)
c. Redness, oedema and vesicles (++++)
False positive patch test, irritant reaction
or excited skin state must be differentiated from
true allergy. The former gives a picture of a
chemical burn sharply defined whereas true
positives give a progressively spreading
eczematous reaction.
This test is useful to determine the cause of
contact dermatitis and the test should be
undertaken only when the lesions are under
control. Though positive skin test indicates
exposure to that particular agent, it does not
necessarily mean that the agent is responsible for
the disorder. The very same person when retested
with a positive test material, 40 percent of the
positives may become negative. Hence, accuracy
of patch testing should be viewed critically because
of the vagaries like false positive and false negative
tests.
ii. Scratch test and intradermal tests: The concerned
antigen is scratched over the skin and reactions are
read after 20 min. In case they are negative, the
drug sensitivity is assessed by intradermal test by
injecting a drop of the causative drug into the
epidermis with a sterile needle. If the test is positive,
wealing occurs within 20 min.
iii. Basophil degranulation test: Mix basophil leucocytes,
patient’s serum, antigen solution and stain on a slide.
After 10 min, it is examined under microscope when
there is rapid movement of granules inside the cell
and later outside the cells and such a reaction is said
to be positive. This test is particularly useful in food
and drug allergies.
459
8. Discontinuation of the drug or elimination of diets:
Withdrawal of the suspected agent leads to gradual
subsidence of the lesion.
9. Trigger test: Reproduction of the lesions by
readministration of the suspected offending agent after
recovery (sometimes this may prove dangerous).
10. Histopathology
i. Skin biopsy: Spongiosis is the hallmark of eczema;
or characteristic granulated mast cells closely packed
in the dermis as in mastocytosis.
ii. Lymph node biopsy: If necessary.
iii. Tzanck test: Presence of giant cells from the base
of the vesicles obtained by curettage with scalpel
and prepared with Giemsa’s or Wright’s stain; as in
herpes simplex (refer to chapter Rashes).
iv. Papanicolaou smear for cancer cells.
11. Tumour markers
12. Radioallergosorbent test (RAST) for specific IgE
antibody.
Though the list of investigations is comprehensive, one
should choose the appropriate test for routine diagnosis.
Additional investigations may be carried out if warranted.
TREATMENT OF PRURITUS
Management of this disagreeable irritating sensation, evoking
scratching (to relieve itching) is influenced by the plethora
of causes. The clinician must determine whether pruritus is
physiological (causal or transient) or pathological (primary
specific dermatologic disorder or a potential systemic
condition, dermatologically silent, but for the functional
symptom). Similarly, the treatment of anogenital pruritus
(which may or may not be a part of generalised pruritus)
calls for careful assessment of proctologic or gynaecologic
changes as well as that of the skin as such. The therapeutic
intervention is directed against the postulated peripheral
chemomediators and modulators (histamine, proteases,
opiate peptides, etc.) of pruritus.
Symptomatic Relief
1. Avoid provocative factors like rough clothing, stress,
hot baths (lukewarm bath preferred), disagreeable dietary
articles.
2. Apply cold damp cloth over the pruritic areas.
3. Topical applications with lotions containing menthol
(0.5%), phenol (1%) and camphor (2%) or calamine
lotion may be of value. Drying agents like talc (powders)
are useful if the skin is moist. Topical anaesthetic or
antihistaminic agents are better avoided because of
possible sensitisation.
 460 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
4. Emollient substances may be used after bath as softners.
5. Systemic treatment with antihistamines like
diphenhydramine (25 mg) or hydroxyzine (25 mg) or
mebrophenhydramine (25 mg) or Cetrizine (10 mg) or
loratadine (10 mg) cyproheptadine (4 mg) in repeated
doses as needed, alleviates pruritus effectively.
6. Psychotropic agents like doxepin (25 mg) or
chlordiazepoxide (20 mg) are beneficial if depression or
anxiety is associated.
7. Cholestyramine (5 mg b.d.) is helpful.
8. Phototherapy with ultraviolet B light, three times per
week is considered in some cases.
Specific Treatment
Pruritus with Primary Dermatologic Affections
Physical: Climatic Effects
• Prickly heat
a. Avoid causes inducing perspiration like hot spicy
food; physical exertion, working and living conditions
in a hot environment; and tight-fitting rough
garments.
b. Local applications with soothing lotion like calamine
or antiprickly heat powders consisting of equal parts
of boric acid, zinc oxide and starch. If the affected
areas are small chlorhexidine lotion and 1 percent
salicylic acid may be applied.
Antihistamine may be prescribed.
c. Secondary infection with abscesses of the sweat
glands (periporitis) may be treated with appropriate
antibiotics.
• Winter itch Improve general health, avoid exposure to
cold, use warm clothing, adopt suitable environment.
Local application with cold cream or antipruritic agents
or emollients are some of the soothing measures.
Infestations
Pediculosis The treatment includes application of 1 percent
gamma benzene hexachloride lotion with or without cetrimide
(0.1%) and massaging gently of the affected areas (P capitis
or P pubis). This may be repeated after a week, if necessary.
The hair should be washed after 12-14 h. This may be
repeated after 7-10 days. The other preparations used are
malathion and pyrethrins (Permethrin).
Bed clothes and under clothing should be sterilized,
combs should be soaked in 2 percent lysol or pediculicidal
lotions for one hour, to prevent reinfection. Secondary
complications with crusts require soap and water cleansings
and appropriate antibiotics. All the members of the family
are better treated.
Infestation of the eyelashes may be treated with ointment
consisting of physostigmine (0.25%), or petrolatum twice
daily.
Pediculosis corporis may be treated with benzyl benzoate
emulsion or gamma benzene hexachloride or crotamiton.
All clothing should be thoroughly sterilized and ironed, or
the garments may be immersed in 2 percent emulsion of
DDT. Encouraging hygienic living, avoiding overcrowding
are other measures.
Scabies Disinfestation with benzyl benzoate emulsion 20
to 35 percent is applied from neck down overnight after a
thorough scrub with soap and water and change all clothing
including bed linen next morning. It may be repeated, if
necessary, after one week. All infected persons in the family
must be treated simultaneously. Alternative drugs are gamma
benzene hexachloride or crotamiton. Secondary infection,
if present, is treated with systemic antibiotics. Personal
hygiene is an important preventive measure.
Insect bites The bites may excite transient reactions but
occasionally macular and papular lesions, sometimes
pigmented, may persist. Topical steroids are helpful in
alleviating the sensitivity reaction. Avoiding insect bites or
using insect repellents are preventive measures.
Larva migrans
a. Cutaneous larva migrans (Refer to Chapter Rashes.)
b. Visceral larva migrans (Vide infra)
Urticaria
a. Eliminate causes like food and drug allergy or parasitic
infestation and focal sepsis or physical or psychological
stress.
b. Antihistamines (vide supra): These H1 antihistamines may
be unsuccessful since H2 receptor sites also may be
present in the cutaneous blood vessels which also calls
for treatment with H2 receptor antagonists.
c. A short course of prednisolone given with gradually
declining doses over a week.
d. Sympathomimetics like epinephrine 0.2 ml 1 : 1000, s.c.
sequentially may be an additional measure, if not
contraindicated. Resistant cases may respond to
terbutaline.
e. Tranquilisers (vide supra) considered.
f. Cromoglycate blocks release of mediators. Since this is
poorly absorbed, doxantrazole is preferred to suppress
histamine relese, in cold urticaria.
 Pruritus
g. Solar urticaria is treated with cyproheptadine (4 mg b.d),
topical corticosteroids and graded exposure to sunlight.
Resistant cases need PUVA photochemotherapy.
h. Hereditary angiooedema responds to either methyl
testosterone buccal tablets (10 mg) or oxymethalone
(25 mg). Danazol may be effective.
i. Angioneurotic oedema is treated with antihistamines,
epinephrine or corticosteroids. If the glottis is involved,
emergency tracheostomy may be necessary.
j. Chronic urticaria: Drugs, foods, parasitic infestations
and such incriminating factors are to be identified and
eliminated. Antihistamines for long periods,
autohaemotherapy and tranexamic acid are useful.
Systemic corticosteroids are to be reserved. Antibiotics
or anthelmintics or tranquilisers may be useful in some
cases of chronic idiopathic urticaria (diagnosed after
exclusion as the case may be).
k. Factitious urticaria needs no active treatment. If
necessary, antihistamines or corticosteroids may be
considered.
l. Cholinergic urticaria: Antihistamines for long periods of
several months may be necessary.
m. Papular urticaria: The treatment is on the same line as
for urticaria. If trombicula irritans is the underlying
cause, crotamiton application offers cure.
n. Urticaria pigmentosa (Mastocytosis): Skin lesions
respond to psoralen, photochemotherapy with long wave
UV irradiation (PUVA). Disodium chromoglycate and
cimetidine beneficial to alleviate clinical manifestations.
Steroids control blister formation.
o. Hyposensitisation may be useful in case of inhalant
allergy.
p. Prevention of urticaria is possible by avoiding ingestion
of exogenous urticariogenic materials or other pruritus
stimuli.
Infections
Fungal Infections These are treated by employing anti fungal
agents topically and systemically.
• Tinea versicolor: Old external remedies like 20 percent
sodium hyposulphite, 3 percent salicylic acid in 70
percent alcohol, sulphur ointment 2 percent and
Whitfield’s ointment are replaced by tolnaftate 0.5 to 1
percent, propylene glycol 50 percent in water, haloprogin,
clotrimazole 1 percent, miconazole nitrate 2 percent and
econazole 1 percent. Selenium sulfide application kept
overnight weekly and then every three months may
reduce possible recurrences.
461
Cream or Ketoconazte orally (200 mg daily for three
weeks and then daily for three days in a month for three
months) or fluconazole (100-200 mg once daily for 2-4
wks) is of value.
• Dermatophytoses
a. Tinea capitis: Micronised griseofulvin orally (10 mg/
kg/d for six weeks) is very effective. Selenium sulfide
shampoo twice weekly is an adjunctive therapy.
Intralesional triamcinolone or a short course of oral
prednisolone is useful for kerions. Antibiotics may be
administered if secondary bacterial infection occurs.
b. Tinea corporis or circinata: Miconazole, clotrimazole,
tolnaftate or terbinafine applied twice daily is effective.
Oral griseofulvin, terbinafine or itraconazole may be
necessary in extensive infections. Antifungal dusting
powders are useful.
c. Tinea cruris: External applications of clotrimazole or
or tolnaftate or terbinafine may be curative in about
three weeks. Loose underwears, keeping the areas
dry by aeration, avoiding excess physical activity, and
bland dusting powders are useful to avoid relapse.
Imidazoles (Ketoconazole, Miconazole, Econazole) or
Triazoles (Flucanazole, Itraconazole) are effective.
Oral griseofulvin is necessary in extensive and resistant
cases.
d. Tinea pedis: Tolnaftate or clotrimazole or miconazole
creams or powders applied twice daily. Griseofulvin
may be required in long standing cases. Antibiotics
(topical or systemic) may be utilised if secondary
bacterial infection or cellulitis supervenes. Relapses
are prevented by promoting dryness and good hygiene.
e. Cutaneous candidiasis: Nystatin as a topical
medicament or imidazoles (miconazole, clotrimazole,
econazole) applied twice a day are effective in intertrigo
(body folds), and interdigital lesions. Amphotericin B
topically in superficial candidiasis and i.v. in chronic
mucocutaneous and systemic infections are useful.
Apply nystatin cream 100000 units four times a day for
a week as curative for oral mucosal lesions. In refractory
cases, 0.5 percent aqueous solution of gention violet is
swabbed over the affected areas twice daily.
Vulvovaginal candidiasis is treated by inserting
intravaginally one tablet of nystatin containing 100000 units
for 1-2 weeks. Oral nystatin tablets (500000-1000000 units
2 or 3 times a day) may be necessary to suppress gastro-
intestinal reservoir of candidiasis to prevent reinfection (Not
commonly used now). Other drugs used are miconazole
cream or clotrimazole suppository vaginally for seven days
 462 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
are also useful. Ketoconazole 200 mg od or preferably Fluco-
nazole (150 ml once daily orally) is effective in candidiasis.
Viral Infections (Refer to Chapter ‘Rashes’).
Dermatitis
a. Contact (allergic) dermatitis or chemical eczema: Topical
corticosteroids like mometasone are effective, when
massaged gently. Prednisolone may be necessary for
the acute stage of severe contact dermatitis, with adequate
doses and rapidly tapered over the weeks. Prevention
of allergent, by screening the contactant-checklist
contact, is very essential. Hyposensitisation or
desensitisation may be helpful for contact allergy.
b. Exfoliative dermatitis (erythroderma): Systemic
corticosteroids should be instituted and long term
administration in low doses may be required in some
cases. Systemic antibiotics are necessary in many cases.
Topical therapy includes the application of bland,
nonirritating lotions after a lukewarm bath. The
underlying cause may be treated accordingly.
c. Seborrhoeic dermatitis: Cetrimide or selenium sulphide
or ketoconazole shampoo may be necessary to maintain
the scalp healthy, especially in winter. Anti-seborrhoeic
remedies commonly used are salicylic acid, sulphur and
tar. When it is associated with inflammatory component,
a topical steroid (hydrocortisone) with neomycin or
framycetin are useful. Greasy bases like ointments or
creams should be avoided at this stage. Thick adherent
seborrhoeic scaling needs a tar gel application twice
weekly at night. Internal administration with
antihistaminics or corticosteroids or antibiotics may be
considered, if necessary. Ultraviolet therapy combined
with liquor picis carb paint may be beneficial at times.
Autohaemotherapy is useful sometimes. Low
carbohydrate, fat diet, fresh air and relaxation may be
supportive.
d. Dermatitis herpetiformis (Duhring’s disease): Dapsone
100 mg/d initially is effective. In some patients, higher
daily doses may be needed and in others weekly treatment
is sufficient to suppress the features. It is advisable to
opt for minimum dosage levels. If dapsone is intolerable
sulphapyridine 1 g daily is prescribed.
Strict adherence to a gluten-free diet will not only
ameliorate the lesions but reduce the dapsone
requirements.
e. Dermatitis medicamentosa: (Refer to Chapter ‘Rashes—
Drug Eruptions’).
f. Varicose dermatitis: Avoid long hours of standing,
elevating the legs during rest periods, foot exercises,
elastic stockings or crepe bandages are conservative
measures. Injection treatment or surgery may be
considered. Factors like itching and secondary infection
treated symptomatically.
g. Photosensitisation and solar dermatitis: Avoid exposure
to sun. Apply anti-actinic lotion or cream. Either short
UV or full spectrum UV and visible light sun screen
containing para-aminobenzoic acid (PABA) esters with
benzophenone or presun15 titanium dioxide respectively
are advocated.
Systemic and topical corticosteroids, and antihistamines
may be considered, if necessary. Sometimes chloroquine
orally (150 mg daily) is given for few months.
In resistant cases, PUVA photochemotherapy thrice
weekly followed by once weekly is an effective option.
h. Atopic dermatitis or atopic eczema: (vide infra).
Eczema or Eczematous Dermatitis
• Atopic Eczema
a. Avoid exacerbating factors, and/or psychosomatic
stresses.
b. Topical therapy with 2.5 crude coal tar or 1 to 5%
ichthammol, and topical either potent (1% hydro-
cortisone ointment or 0.5% triamcinolone ointment)
or highly potent (betamethasone dipropionate or
clobetasol propionate) mometasone are effective.
c. Associated ichthyosis is treated with emollients like
petrolatum.
d. Systemic therapy with steroids in flare-ups and/or
antihistamines with sedative effect are useful.
e. Antibiotics may be given if secondary infection exits.
f. For acute oozing (weeping) lesions use Condy’s lotion
(potassium permanganate) or Burow’s solution
(aluminium acetate); for subsiding (drying lesions
use calamine lotion and for chronic dry lesions
ointments containing steroids or tar or hydroxy-
quinoline useful.
• Nummular eczema (Discoid)
a. Avoid exacerbating factors.
b. Topical therapies.
c. Ultraviolet therapy.
d. Correct psychosomatic factors.
e. Avoid dry skin by massaging with oils.
f. Support skin as per morphological stage of the
disease.
• Infective eczema: The affected parts are painted with
gentian violet. When it dries, any medicated paste like
Lasser’s paste (zinc oxide) is applied. When once
infection starts clearing, gentian violet is discontinued.
Antibacterial creams may be employed with discretion.
Systemic antibiotics as per the needs are considered.
 Pruritus
• Disseminated eczema (Eczematides): In the acute stage,
simple lotions like boric acid 2 to 4% with or without
Burow’s solution are effective. Following these
compresses or soaks, ointments containing corticos-
teroids or tar or iodochlorhydroxyquin can be applied
during the drying stage. Constitutional symptoms like
fever or pain may be treated symptomatically. A short
therapy with systemic corticosteroids may be necessary
in disabling cases. If secondary infections (pyoderma)
occur, appropriate antibiotics may be given. Avoidance
of causal mechanism like powerful sensitising agents is
the preventive step.
• Cheiropompholyx (Dyshidrotic eczema): The local
measures consist of application of alum or Burow’s
sulution or hydrocortisone lotion. Antihistamines with
sedative component may be useful. Underlying causes
like emotional stress or focal sepsis are corrected.
Lichenoid Dermatosis
• Lichen simplex chronicus (Neurodermatitis): Local
inunction of hydrocortisone ointment is of value.
Intralesional injection of a corticosteroids is considered,
if neccessary. Patient must be educated that preventing
of scratching offers a cure. Tanquillisers may be given.
Dermabrasion normalises the cutaneous appearance.
• Lichen planus topical corticosteroids fluocinolone
(0.05%) or clobetasol (0.05%)] are helpful for localised
lesions. Topical 0.1% isotretinoin (retinoic acid-vitamin
A acid is effective for hyperkeratotic and oral lesions.
For extensive lesions 1% phenol in calamine lotion or
0.1% phenol 0.5% menthol in zinc cream may be used.
If necessary, predinisolone (15-20 mg daily for about
six weeks) is given and tapered gradually. Topical
trioxsalen followed by longwave ultraviolet light exposure
(PUVA) may also be beneficial in some cases.
Antihistamines are useful to control pruritus. Griseofulvin
(500 mg four times a day for four weeks) appears to be
of value. Topical immunosuppressants like Tacrolimus
or Pimicrolimus are yielding encouraging results.
Reassurance, relaxation (avoiding undue stress) and
removal of offending agents are indicated.
Pityriasis Rosea Treatment is symptomatic. Soothing lotions
like calamine minimises drying or irritation. Topical
corticosteroids in a hydrophilic cream base may be required.
Severe cases need systemic corticosteroids (prednisolone).
Antihistamines are beneficial. Reassure about its duration
(approximately two months). Ultraviolet light therapy is
considered in chronic cases.
Sulphone therapy is empirical.
463
Mycosis Fungoides If it involves skin only, PUVA, topical
nitrogen mustard, radiation therapy teleroentgen or electron
beam therapy) are indicated. Cytotoxic agents (antineoplastic
drugs) are considered if there is systemic involvement.
Pruritus without Dermatologic Affections Per Se
• Physiological: Pregnancy
• Herpes gestationis: Treatment include corticosteroids
(if not contraindicated as in the first trimester of
pregnancy) antihistamines, or dapsone.
• Pruritus gravidarum: The generalised itching due to
intrahepatic cholestasis is relieved in most of the cases
by cholestyramine, a nonabsorbable synthetic ion
exchange resin.
• Prurigo gestationis: The treatment consists of corticos-
teroids (locally or systematically discriminately).
Nevertheless the lesions which appear in the last
trimester of pregnancy tend to clear in the postpartum
period leaving behind postinflammatory hyperpigmen-
tation.
• Acute immune progesterone dermatitis: General palliative
and local treatment is indicated. The lesions increase
when progesterone containing drugs are given and
decrease on withdrawal.
Systemic and other Disorders
Infestations Pediculosis corporis (Vide supra)
Onchocerciasis (Refer to Chapter Rashes)
• Visceral larva migrans (toxocariasis): Thiobendazole
(50 mg/kg as a single dose) or levamisole (2.5 mg/kg as
a single dose) is usually recommended. Diethylcarbam-
azine can be tried. Corticosteroids or antihistamines or
analgesics are used for symtomatic relief.
Periodic treatment of puppies (for three weeks at
weekly intervals and then biannually) and avoiding soil
contamination are the preventive measures.
• Ankylostomiasis: Treatment includes mebendazole (100
mg b.d. for three days) or albendazole (400 mg for one
day) or pyrantel pamoate (11 mg/kg daily for three days),
or bephenium hydroxynaphthoate (5 g of the granules
for one day for A duodenale and for three days a Necator
Americans).
Consequent anaemia is treated with iron
preparations. Bare feet walking is avoided to prevent
hookworm infection.
• Schistosomiasis (Refer to Chapter ‘Rashes’)
• Malaria (Refer to Chapter ‘Rashes’)
 464 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Hepatic disorders Obstructive Jaundice (Refer to Chapter
‘Jaundice’)
Metabolic and endocrinal
• Diabetes mellitus (Refer to Chapter ‘Polyuria’)
• Thyroid disorders (Hyper and hypothyroidism: (Refer to
Chapter ‘Goitre’)
• Hyperparathyroidism
i. Treatment of primary hyperparathyroidism is surgical
removal of the adenoma of the affected gland(s).
Postoperative tetany, if occurs, is treated with calcium
and magnesium. There is no satisfactory medical
treatment for primary hyperparathyroidism.
However, if unwilling or unsuitable for surgery, it is
best managed by:
– Forcing fluids 3-4 litres a day and salt 8-10 g/d.
– Avoid immobilisation, calcium salts and thiazide
medication.
– Add phosphate preparations if renal function is
good.
– Consider ethinyl oestradiol (30 µg/d) to lower
serum calcium or calcitonin.
ii. Secondary hyperparathyroidism due to hyperplasia
usually consequent to chronic renal failure with
phosphate retention (raised parathyroid hormone is
appropriate to calcium levels) is treated with dietary
restriction of phosphates, aluminium hydroxide and
judicious supplements of vitamin-D as calcitriol
(0.25-2 µg/d). If calcium is low, oral calcium and
alfacalcidol (0.5-5 µg/d) given. (Avoid this treatment
till phosphate is normal lest metabolic calcification
should occur.)
iii. Tertiary hyperparathyroidism, which is consequent
to secondary hyperparathyroidism, leading to
adenoma is treated as for primary hyper-
parathyroidism.
iv. Hypercalcaemic cirsis: Aminohydroxypropylidene
diphosphanate (APD-30 mg i.v. in saline) is effective
in lowering calcium within two days and normalises
within six days. If not available other therapeutic
approach may be resorted to (Refer to Chapter
‘Weight Loss and Polyuria’)
• Carcinoid syndrome (Refer to Chapter ‘Chronic Diarrhoea’)
Renal Chronic renal failure (Refer to Chapter ‘Polyuria’)
Haematological
• Polycythaemia vera (Refer to Chapter ‘Fatigue’)
• Iron deficiency (Refer to Chapter ‘Fatigue’)
• Leukaemia (Refer to Chapter ‘Bleeding Disorders’)
• Paraproteinaemias (Refer to Chapter ‘Bleeding Disorders’)
Internal malignancy
Lymphomas (Refer to Chapter ‘Pyrexia of Unknown Origin’)
Angioimmunoblastic lymphadenopathy with disproteinaemia
(Refer to Chapter ‘Rashes’)
Carcinomatosis (Refer to Chapter ‘Weight Loss’)
Carcinoids Symptomatic theray is directed against humoral
mediators. Flushing is relieved with both H1 and H 2
antagonists or phenoxybenzamine (20-200 mg per day) or
phenothiazines. Diarrhoea may be controlled with loperamide
(2 mg 3-4 times a day) or cyproheptadine (4 mg tds) and
methyserzide (2 mg tds) are helpful. Cyproheptadine may
also be useful for pruritus.
Somatostatin is beneficial for flushing, diarrhoea and
bronchospasm. Symptoms due to bronchial carcinoids
respond better to corticosteroids. Niacin may be necessary
to prevent pellagra. Hypotension, if occurs, should be treated
with volume expanders and/or methoxamine or angiotensin
infusions (drugs with adrenergic activity must be avoided).
Surgical removal may be curative. In metastases and
when resection is not feasible, pallation is achieved with
chemotherapy (5 fluorouracil with or without and interferon-
alpha streptozocin is current choice. Doxorubicin and
cyclophosphamide are other drugs).
Collagen disease
Scleroderma (Refer to Chapter ‘Polyarthritis’)
Dermatomyositis (Refer to Chapter ‘Paraplegia’)
Dry Skin (Xerosis or Asteatosis)
General treatment Warm moist climate is to be advised.
Encourage sweat baths in steam rooms. Simple hypertonic
saline baths reduce scaling. use mild toilet soaps or
superfatted soaps. Gentle massage with mineral oil or
soothing emulsion may be beneficial as it impedes the water
loss from the stratum corneum. 10% urea and 5% lactic
acid ointment in vaseline base is useful.
Treat the underlying cause, if any, in acquired forms.
(In the congenital disorder, no causal treatment is possible.)
Pharmacotherapy Fat soluble vitamins like vitamin-A
(50,000-1,000,00 units) prescribed. Small doses of thyroid
may be useful. Antipruritic lotions may be incorporated.
Senile Pruritus Avoid physical exciting causes. Oil massage
and antipruritic lotions helpful. Antihistamines and
tranquilisers orally may be given as needed. Hormonal therapy
with androgens for males and oestrogens for females is
beneficial. Any obvious cause of pruritus, if present , specific
treatment may be adopted.
Food and Drug Sensitivity The therapy includes immediate
withdrawal of the offending agent. In severe cases,
antihistamines or steroids orally may be necessary. Local
bland applications as mentioned above are recommended.
 Pruritus
If metals are incriminated, British anti-Lewisite (BAL-
Dimercaprol-3 to 6 mg/kg-1 to 3 times a day for 10 days)
administered.
Prophylaxis is achieved by taking proper history of prior
sensitisation to drugs. If necessary, an intradermal sensitivity
test may be considered. Drugs used systemically are avoided
for topical purpose.
Erythromelalgia Avoid warm environment. Elevate the
affected part and use cold compresses. Aspirin may be
beneficial. If unresponsive and troublesome, surgical therapy
is considered, i.e. nerve block or nerve section or
sympathectomy. Treat if any secondary cause like
myeloproliferative disorder is identified.
Psychogenic The patient is taken into confidence and made
to ventilate, underlying associated guilt. The role of emotional
factors, frustrations must be explained. If there is any
restlessness, agitation or depression, appropriate anxiolytics
and/or antidepressants are prescribed. Supportive
psychotherapy or analytical psychotherapy, relaxation
techniques, abreaction are beneficial to facilitate emotional relief.
Anogenital Pruritus Pruritus ani Anal hygiene is of primary
importance. Thorough cleansing after a bowel movement
is mandatory. Any source of irritation, if present, should be
removed. Avoid spicy foods. Keep the area dry and clean.
Sitz baths with or without equal amounts of baking soda
and starch or mild antiseptics recommended for any subacute
465
inflammations. One percent hydrocortisone ointment
topically may be helpful, for acute inflammation.
Local causes like skin disease surgical ailments (fissure
etc.), parasitic infestations (thread worms) or systemic
disease must be identified and treated appropriately.
Pruritus vulvae identify the source of irritation and
sensitisation. Keep the affected and neighbouring parts clean
and dry to mitigate the itching due to spreading cutaneous
disease from neighbouring areas. Vulvar infections or
infestations like trichomonas, enterobius vermicularis,
scabies, pediculoses, candidiasis, and skin infections like
tinea are treated appropriately. Clotrimazole, metronidazole,
povidone iodine pessaries are beneficial.
Noninfective vaginitis like senile vaginitis responds better
to hormones but emollients are necessary for the external
genitalia (topical oestrogens may not be so effective).
Gynaecological conditions like cervicitis or cystocele,
if present, accordingly managed. Systemic disorders like
diabetes mellitus must be effectively controlled. Pruritus in
pregnancy may respond to progesterone.
Localised neurodermatitis associated with any psychic
component needs psychogenic therapy.
Sitz baths or topical hydrocortisone therapy may be
useful.
Pruritus scrotum and penis Same principles of treatment
as above are applicable.
466 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Pruritus 467
 Chapter
Pyrexia of
30 Unknown Origin
Pyrexia of unknown origin (PUO) is not pyrexia of unknown
origin but undetermined origin wherein proper evaluation
or renewed evaluation may be made to determine the cause
that is not obvious and resolve the enigma of temperature
chart. It is defined as a prolonged fever lasting three weeks
or more with >101.2°F in coarse of the day which has
resisted diagnosis or escaped detection, in spite of meticulous
clinical approach.
It may be:
1. An uncommon presentation of a common disorder.
2. A manifestation of a uncommon disease.
3. Prolonged fever where significant clues are unwittingly
missed.
4. A simultaneous or sequential occurrence of different
diseases.
Nevertheless, it does not include short fevers (of 10 days
duration or less with or without obvious cause) and
prolonged fevers wherein the cause is obvious.
The exact upper level of normal body temperature is
variable in normal individuals and is much less influenced
by external stimuli than other vital signs. Oral temperature
of more than 99°F (37.2°C) is taken as fever and >106°F
(41.1°C) is considered as hyperpyrexia. 109.4°F (43°C) is
malignant hyperpyrexia (complication of anaesthesia). Body
temperature exceeding 114°F (45.6°C) may not be
compatible with life. Normal temperature is 98-99°F, below
98°F (36.7°C) is subnormal and below 95°F (35°C) is
hypothermia. Core (rectal) temperature of >33°C is mild
hypothermia and <33°C (91.4° F) is moderate-severe.
Fevers are usually described as continuous; (not touching
normal) with one hr fluctuation; remittent; (not touching
normal) with 2 hrs variation; intermittent (Touches normal
many times in 24 hrs) [when occurs daily (quotidian); on
alternate days (tertian); and every 4th day (quartan)];
relapsing (periodic). When it does not conform to any of
these patterns, it is termed as irregular fever.
PATHOGENESIS OF FEVER
Fever is often a sign of infection. Sometimes, it is sequelae
of tissue damage or malignancy.
Bacterial endotoxins, toxic substances or immunological
reactions, or drugs in sensitised persons, stimulate synthesis
of endogenous pyrogens (EP) (interleukin I) by monocytes,
macrophages, tumour cells and release into circulation. It
also initiates immune response by activating T cells to
synthesise interleukin II which causes expansion of
responding T cells. EP passes into CNS, stimulates synthesis
and release of prostaglandins of E series from preoptic
hypothalamic area, 3rd and 4th cerebral ventricles. These
increase cyclic AMP resulting in increased heat production.
Sometimes, dietary induced thermogenesis takes place (10%
of ingested energy). Simultaneously, heat loss is decreased
by cutaneous vasoconstriction. This heat conservation
disturbs hypothalamic thermoregulatory centre by shifting
the thermostat setting upward from 37°C. Thus, fever
results which reflects an imbalance between heat production
and heat loss.
CAUSES OF PYREXIA OF UNKNOWN ORIGIN
The causes of PUO include a list of “prolonged fevers” and
some of them may be PUO at least initially (Table 30.1).
Table 30.1: Causes of PUO
1. Infections
A. Bacterial
a. Infective endocarditis
b. Sepsis (pelvic, perinephric, subphrenic, hepatobiliary and
sinuses)
c. Brucellosis
d. Typhoid relapse
e. Tuberculosis: Miliary type and obscure extra-pulmonary
f. E. coli (UTI)
Contd...
 Pyrexia of Unknown Origin 469

Contd... Contd...

B. Chlamydial psittacosis e. Inherited

C. Viral i. Familial mediterranean fever
a. Cytomegalovirus ii. Hyperlipidaemia type-I
b. Infectious mononucleosis (glandular fever) iii. Cyclical neutropenia
c. Acquired Immuno deficiency Syndrome (AIDS) iv. Fabry’s disease
D. Parasitic v. Anhidrotic ectodermal dysplasia
a. Hepatic amoebiasis NB: Infections, neoplasms, hypersensitivity to drugs, and connective
b. Kala-azar dissue disorders are important.
c. Toxoplasmosis
d. Trypanosomiasis
N.B: Malaria untreated may continue for > 3 wks as periodic Infections (may be Systemic or Localised)
intermittent fever (recurrent).
Bacterial
E. Rickettsial: Q fever and other typhus fever
F. Spirochaetal: Leptospirosis Infective Endocarditis Any fever of more than seven days
G. Mycotic (systemic)
duration with a cardiac murmur is in variably to be considered
a. Histoplasmosis
b. Disseminated candidiasis as bacterial endocarditis. Other associated features like
c. Pneumocystitis Carinii Pneumonia (PCP) splenomegaly, haemorrhages, painful areas on the toes and
H. Nosocomial (Hospital acquired) soles or fingers and palms (Osler’s nodes), microscopic
2. Neoplastic (Malignant or Benign) haematuria and a positive blood culture offer the clue.
a. Lymphomas Sepsis Pyogenic infections of the hepatobiliary or pelvic
b. Carcinomas (hypernephroma, hepatoma)
inflammations or perinephric regions or prostatic abscess,
c. Sarcomas
d. Atrial myxoma sinusitis, comprise appreciable percentage of any group with
3. Connective Tissue Disorders pyrexia of unknown origin.
a. SLE Brucellosis Arthralgia and myalgia with a temperature chart
b. Polyarteritis nodosa showing alternative febrile and afebrile periods with a positive
c. Giant cell arteritis blood culture and a raised antibody titre are suggestive of
d. Rheumatic fever
brucellosis.
e. Rheumatoid arthritis
4. Vascular Diseases Typhoid Relapse Though typhoid fever is not considered to
a. Recurrent pulmonary embolism be a cause of pyrexia of unknown origin as such, typhoid
b. Deep venous thrombosis relapse has to be borne in mind specially when the blood
c. Pelvic thrombophlebitis cultures and specific antibodies are not conclusive.
5. Granulomas Sometimes, chloromycetin or ciprofloxacin or any other
a. Sarcoidosis
drug resistant typhoid fever poses the same enigma.
b. Crohn’s disease
c. Granulomatous hepatitis Tuberculosis (Miliary Type and Obscure Extrapulmonary Types)
6. Liver Cirrhosis; Hepatocellular Failure, Chronic Active hepatitis Acute miliary tuberculosis or extrapulmonary lesions
7. Hypersensitivity to Drugs involving bones and joints, urinary tract and peritoneum
Drug fever may be the underlying cause, for fever which may not be
8. Haematological detected, until late during the course of the disease. Diagnosis
a. Aplastic anaemia can be established by radiological and bacteriological
b. Leukaemia examinations with a positive tuberculin test. Initial X-ray
c. Agranulocytosis chest may be normal but few weeks later X-ray may show
d. Febrile neutropemia
miliary tuberculosis.
9. Other Causes
a. Aetiocholanolone fever E. coli (UTI) (Refer to Chapter ‘Haematuria’)
b. Factitious fever
c. Habitual hyperthermia Chlamydial
d. Thyroiditis
Psittacosis (Chlamydia psittaci) A non-productive cough with
Contd... myalgia and abdominal pain, gastrointestinal symptoms with
 470 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
nontender hepatosplenomegaly, in persons dealing with birds
(parrots or pigeons) suggest the diagnosis. It is established
by single or multiple segmental opacities in the skiagram
chest and isolating the organism from the blood or bronchial
secretions or serological studies or rising titre of complement
fixing antibodies (Rarely nephritis, meningoencephalitis).
Viral
Cytomegalovirus This may be congenital or acquired. The
former may be seen in new borns with major organ
involvement causing respiratory distress, jaundice,
encephalitis, pathological fractures of long bones, purpura,
elevated IGM, and specific CMV antibody. Acquired
infections may be seen as sore throat, arthralgias,
pneumonitis or pericarditis, hepatitis with icterus, purpura,
diarrhoea and retinitis. Isolation of the virus and
demonstration of rising antibody titres are diagnostic.
Infectious Mononucleosis (Glandular Fever) Sore throat,
lymphadenopathy, bilateral supraorbital oedema,
hepatosplenomegaly with absolute increase in lymphocytes
and monocytes and presence of heterophil antibodies which
agglutinate the erythrocytes of sheep (heterophil antibody
tests, e.g. mono spot test)—Paul-Bunnel test and specific
antibodies against Epstein-Barr virus like IgM or IgG-VCA
(viral capsid antigen) are diagnostic spreads through saliva,
Droplets.
AIDS (Refer Appendix IV) A person having one or more of the
underlying features, with no known cause is considered to
be suffering from ARC (AIDS related complex).
1. Unexplained weight loss at least 10 percent of total body
weight
2. Fatigue, malaise of at least four weeks duration
3. Prolonged fever for at least four weeks
4. Diarrhoea for two weeks or
5. Palpable lymphadenopathy involving one or more
extrainguinal sites of at least three months duration.
It can be excluded if there is negative result for serum
antibodies against HIV (This antibody test is done with
serological test kits, viz. ELISA test and the ‘Western Blot’
test is used as a confirmatory test for all ELISA positive
sera). A glandular fever like illness occurs at the time of
sero-conversion.
Parasitic
Hepatic amoebiasis (Refer to Chapter ‘Jaundice’)
Kala-azar Prolonged fever with hepatosplenomegaly and
emaciation without toxic appearance should rouse the
suspicion of kala-azar especially in endemic areas. It is cause
by Leishmania donovani and spread by sandflies.
The diagnosis can be confirmed by:
a. Gel test: One drop of 40 percent formalin added to 1 cc
of serum when a solid whitish opalesance occurs within
one or two minutes and solidify within 20 min.
b. Chopra test: Few drops of blood of the subject should
be added to 5 drops of 2 percent potassium acetate.
Four percent of solution of pentavalent antimony
compound is allowed to flow down the tube till it settles
below the blood mixture when a flocculent precipitate is
seen at the junction within 20 min and remains for 24 h.
c. Demonstration of protozoan parasite in bone marrow
aspirates.
d. k 39 strip test (testing for antibody to leshmania antigen
k 39.
Toxoplasmosis It is a rare disease with prolonged fever,
meningoencephalitis, lymphadenitis, myocarditis,
pneumonitis, choriodoretinitis and maculopapular rash.
X-ray of the skull may show calcified areas and the
definitive diagnosis is made by the isolation of the toxoplasms
gondii from the subject and indirect complement fixation
test with a titre of 1:128. It is also seen in infants if the
foetus is infected early in pregnancy.
Trypanosomiasis African type caused by T gambiense tsetse
fly through and American type by T cruzi (Refer to Chapter
‘Rashes’).
Rickettisial (Refer to Chapter ‘Rashes’)
Q Fever and Other Typhus Fevers (Refer to Chapter ‘Rashes’)
This is known as ‘Query’ fever and the fever is prolonged
with severe headache and bradycardia. Majority of cases
will have pneumonitis. Majority of cases will have
pneumonitis. In some cases hepatitis with jaundice,
endocarditis with aortic valve involvement may be present.
Diagnosis is made by isolation of the organism, Coxiella
burnetii, or by agglutinin test or by a raised complement
fixing antibody titre to phase 1 antigen. Preserve of phase I
antigen indicates chronic infection as against phase II which
indicates, acute infection.
Scrub Typhus (Mite-borne Typhus) Fever with rash on the
5th day with a primary eschar leaving an ulcer and regional
adenitis is highly characteristic. There may be signs of
bronchitis and deafness as a constant feature.
Diagnosis is confirmed by:
a. A positive Weil-Felix reaction which shows agglutination
of OXK strains (from day 10).
b. Isolating Rickettsia tsutsugamushi from the peritoneal
smears (by grinding up blood clot with normal saline
and centrifuging; then 0.3 ml supernatent fluid is
innoculated intraperitoneally into mice).
 Pyrexia of Unknown Origin
c. There may be speckling of the lymphocytes with
azurophilic granules.
Spirochaetal
Leptospirosis There is febrile stage with vomiting, headache
myalgia, conjunctival suffusion and irregular fever. There
may be jaundice, Haemorrhages, renal involvement. Though
fever subsides by lysis on 12th day with disappearance of
jaundice, the recurrence of high fever may occur on 16th
day lasting for 2 to 3 weeks.
The diagnosis is confirmed by demonstrating
spirochaetes in the blood in the first week and the urine in
the second and third weeks. The agglutination test is positive
if the titre is above 1 in 300 or a rising titre. Microscopic
agglutination test, or ELISA 1gM and slide agglutination
tests may be employed.
Mycotic
Histoplasmosis Fever and pneumonitis with middle lobe
collapse with hilar lymphadenopathy and hepatosplenomegaly
are typical features. The chest X-ray may show miliary
pattern or apical infiltrates or progressive fibrosis.
Disseminated Candidiasis It is caused by yeast like fungus
candida (C. albicans). Mucocutaneous candidiasis or
oesophageal lesions or genitourinary lesions are fairly well
documented. However, haematogenous dissemination
presents with fever and toxicity. Pulmonary candidiasis or
endocarditis or meningitis or retinal abscesses may occur.
The diagnosis is confirmed by demonstration of hyphae on
wet smear or culture of the blood, CSF or by biopsy.
Pneumocystic Carinii
It causes pneumonia particularly in immunocompromised
or severe malnourished patients. The physical findings are
scanty in spite of radiological evidence of extensive
pulmonary involvement. The diagnosis depends upon
demonstration of protozoan-like cysts in respiratory
secretions or lung tissue. X-ray of the chest shows alveolar
infiltrates spreading from the hilum or nodular infiltrates or
cavitation (This is classed now as Fungus).
Nosocomial
Nosocomial PUO may be due to nosocornial (Hospital
acquired) infections like thrombophlebitis, colitis or drug
fever.
471
Neoplastic (Malignant or Benign)
Certain neoplasms like lymphomas, sarcomas of the bone
or carcinomas of the kidney or liver may cause fever. The
principal symptom is lymphadenopathy with Pel-Ebstein type
of fever in Hodgkin’s disease and other lymphomas. The
diagnosis is confirmed by lymph node biopsy (Refer to
Chapter ‘Bleeding Disorders’).
Primary liver cell carcinoma (hepatoma) may be
associated with fever with hard tender hepatomegaly with
or without jaundice. Ultrasound and CT scan are useful in
diagnosis and biopsy confirms.
Although painless haematuria is the first symptom in
75% of cases of hypernephroma, it may be associated with
fever, emaciation, and a palpable tumour without a definite
edge, below the 12th rib posteriorly. The diagnosis is
confirmed by radiological, cystoscopic, exploratory
laparotomy, ultrasonography, and/or isotope scanning with
99 Tcm-DTPA or 99 Tcm-MAG3 (Renography) which
provides functional information (uptake and excretory pattern
of each kidney).
Atrial myxoma is an uncommon entity and presents itself
with fever, arthralgia, changing heart murmurs with or
without peripheral embolism. It may mimic mitral stenosis,
tricuspid stenosis depending on the involvement of the atria.
The diagnosis is confirmed by echocardiography or selective
angiocardiography.
Connective Tissue Disorders
Systemic Lupus Erythematosus (SLE): Refer to Chapter
‘Polyarthritis’.
Fever may be the principal manifestation in SLE with
migratory arthralgia or erosive arthritis.
The classical butterfly rash over the cheeks and nose
along with features of visceral involvement in this order are
characteristic.
a. Anaemia
b. Lymphadenopathy
c. Renal involvement (nephritis and nephrotic syndrome)
d. Pleuritis
e. Pericarditis/Endocarditis
f. Central nervous system abnormalities (like convulsions
and psychosis)
g. Hepatomegaly
h. Retinopathy (Retinal cytoid bodies present)
i. Haemorrhagic tendency (purpuras or clotting defects)
or thrombosis due to antiphospholipid syndrome.
j. Vasculitis with Raynaud’s phenomenon.
 472 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
This primary necrotising vasculitis can be diagnosed by
the presence of :
a. Antibodies to nuclear antigens (especially antinuclear
factor and antibody to double-stranded DNA).
b. LE cells (polymorphs which contain denatured nucleii).
(Normal leucocytes when incubated in serum of SLE
subjects extrude nuclear material which is phagocytosed
by other leucocytes because of the presence of abnormal
globulin with an affinity for the nucleii of the cells) (Refer
to Chapter ‘Polyarthritis’) (See Fig. 27.3).
Polyarteritis Nodosa (PAN)
Fever with arthralgias are the initial complaints. The
progressive necrotising inflammation involving the vessels
of various organs reflect in varienty of clinical features like
haematuria, abdominal pain, angina, mononeuritis multiplex,
and tender subcutaneous nodules. Hypertension may occur
early even when the renal function is normal. Sometimes
lung involvement may produce asthma of late onset. The
diagnosis is confirmed by biopsy of tender muscles and
renal biopsy. Churg-Strauss syndrome (CSS)/Allergic angitis
and granulomatosis is a multisystemic vasculitis involving
skin and lungs most often. Kidney involvement is less
common and less severe unlike PAN. No granuloma
formation in PAN unlike CSS (Refer to Chapter ‘Polyarthritis’)
Giant Cell Arteritis
It is seen in elderly persons and manifests as fever of low
grade type with high ESR. It is characterised by aching
pain on the neck and shoulders or the hips and tender
muscles. Intense headache, scalp tenderness and visual
disturbances may be associated along with intermittent pain
of the jaws with mastication. The vessels of the skull
especially temporal arteries are involved which are thickened
and tender. The diagnosis is confirmed by temporal artery
biopsy and with a raised ESR (Refer to Chapter ‘Polyarthritis’).
Vascular Diseases
• Recurrent Pulmonary Embolisms (Refer to Chapter
‘Chest Pain’)
• Deep Venous Thrombosis.
Venous thrombosis may account for unexplained fever
or tachycardia besides pain and oedema of the legs. Dilated
veins and increased warmth of the affected limb may be
present. Forceful dorsiflexion of the foot may cause pain
(Homan’s sign). Precipitating factors are congestive cardiac
failure or prolonged recumbency or postoperative periods
and pregnancy.
Doppler ultrasound and plethysmography are useful in
diagnostic manoeuvres. Contrast venography, radioactive
fibrinogen uptake and radionuclide venography with
simultaneous lung scanning are further investigating
procedures.
Pelvic Thrombophlebitis
Thrombophlebitis is venous thrombosis with or without
inflammation of the venous wall. Local pain, tenderness
may be accompanied by constitutional disturbances like
fever, malaise and tachycardia. It may be encountered usually
in the deep veins of the legs and pelvis in postoperative or
postpartum or post-traumatic periods. The thrombotic
process may start in progress to the pelvic veins.
Thrombosis of the ilio femoral veins presents as a rapidly
developing swelling of the whole limb. It is not evident as a
tender cord unless it extends below the inguinal ligament.
Engorged collateral veins may be present in the upper portion
of the thigh. When suppuration occurs in the affected vein,
fever associated with chills may occur. The diagnosis is
confirmed by venography or ultrasonography or peripheral
colour Doppler.
Granulomas
Sarcoidosis
It may present as fever, arthralgia of the knees and ankles,
erythema nodusum, hilar lymphadenopathy or insidiously
with cough and progressive dyspnoea. There may be
generalised lymphadenopathy, isolated cranial nerve
involvement and peripheral neuritis, cystic lesions in the
phalanges, keratoconjunctivitis sicca, lacrimal gland
enlargement uveitis. It is a non-caseating granuloma. Acute
sarcoidosis is known as Lofgren’s syndrome.
The diagnosis is confirmed usually by:
a. A positive kveim reaction (subcutaneous inoculation with
1 cc of human sarcoid tissue like spleen or lymph nodes
produces papular lesion, the biopsy of which at 4 to 6
weeks shows sarcoid granuloma with well formed
epithetoid tubercles).
b. (i) Biopsy of the palpable lymph node or blind scalene
node.
(ii) Liver biopsy.
c. Hypercalcaemia and hypergammaglobulinaemia.
d. Serum angiotensin converting enzyme is elevated.
e. X-ray of chest shows hilar lymphadenopathy and
symmetrical pulmonary fine coarse nodular lesions
(mottling) or diffuse fibrosis esp. upper lobes.
f. CT chest shows perivascular nodularity of lungs.
g. Gallium 67 scanning (increased uptake).
 Pyrexia of Unknown Origin
Crohn’s Disease
It presents as abdominal pain with diarrhoea and fever.
Tender mass in the right iliac fossa is a cardinal physical
sign. There may be signs of malabsorption, fistula and
perianal abscesses, oral genital ulcers, uveitis, and arthritis.
In some cases, fever may be striking than the gastrointestinal
manifestations.
The diagnosis is confirmed by:
a. Sigmoidoscopy
b. Radiological evidence of fissuring or rose thorn ulcers
with intervening oedema (cobble-stones) or involvement
of small bowel with narrow terminal ileum (string sign)
(Refer to Chapter ‘Chronic Diarrhoea’).
Granulomatous Hepatitis
Hepatic granulomatous lesions occur in sarcoidosis,
tuberculosis, and mycotic infections. They consist of
epitheloid cells with surrounding lymphocytes, giant cells,
and central areas of necrosis, usually in the region of portal
tracts. Though the lesions are not specific, the course of
the disease with the possible demonstration of underlying
organism, clinches the diagnosis. In addition, granulomatous
hepatitis of unknown cause with prolonged pyrexia is also
documented and diagnosis is facilitated by liver biopsy.
Liver Cirrhosis
Fever may occur due to the products of necrosing and
autolysing liver cells disturbing thremoregulatory centre
(Refer to Chapter ‘Jaundice’).
Hypersensitivity to Drugs
Drug Fever (More than One Drug)
Hypersensitivity to drugs as a cause of PUO is a significant
factor where the drugs themselves may cause fever with
relative bradycardia; drug resh, leucocytosis/eosinophilia or
sometimes perpetuate the fever long after the
commencement of therapy. Fever subsides within days after
discontinuing the drugs. Antibiotics, sulpha drugs,
antihistamines, methyldopa, barbiturates, and phenytoin are
some examples (Refer to Chapter ‘Pruritus’).
Haematological
Aplastic Anaemia (Bone Marrow/Stem Failure)
The bone marrow contains few cells in a gelatinous and
fatty matrix due to hypoplasia of the erythroid, myeloid and
473
thrombopoietic elements. Consequently, there is
pancytopenia. This hypoplasia or aplasia may be primary or
secondary. The term refractory anaemia is confined to
pancytopenia with normal cellular or hypercellular marrow.
Sometimes, there may be myelodysplasia with abnormal
maturation. The clinical features are those of progressive
anaemia. Fever may be present without inflammatory signs
in spite of infections due to neutropenia. Oral ulcers and
petechiae or mild bleeding may be associated. The diagnosis
is confirmed by sternal puncture which shows diminished
formative elements and examination of peripheral blood
which reveals pancytopenia. Other causes of pancytopenia
are hypersplenism, SLE megaloblastic anaemia (Refer to
Chapter ‘Bleeding Disorders’).
Leukaemia (Refer to Chapter ‘Bleeding Disorders’)
Agranulocytosis It is characterised by marked leucopenia
with severe reduction of polymorphonaclear leucocytes due
to idiosyncrasy to drugs or an integral part of aplastic
anaemia. General malaise, weakness, fever and sore throat
with or without ulceration may be encountered several weeks
or months after exposure to the offending agent. The
leucopenia with granulopenia (WBC 2000 per C > mm and
granulocytes 20 to 30 %) may be persistent or recurrent.
The diagnosis is confirmed by examination of the blood
and bone marrow.
Febrile neutropenia A reduction in neuoutrophil count i.e.
neutropenia predominantly is drug induced particularly
cancer chemotherapy other causes are infections, SLE,
drugs and kostnanis syndrome.Clinical features may be
asymptomatic or symptomatic. Fever may be the only
presentation with soar throat or skin inflamation leading to
even septicaemia with shock. Absolute neutrophil count is
less than 1000/mm 3 . The neutropenic patients are
succeptible to an array of microbial infections even less
virulent. This demands immediate empiric antimicrobial
therapy. The therapy includes extended spectrum pencillians
with betalactamase inhibitors and aminoglycosides is
warranted without waiting for microbiological
documentation. Treatment is to be continued for 5 days
after the fever has resolved. Pathogens (bacterial, viral,
fungal) identified may need appropriate management.
The colony stimulating factors are useful for preventing
severe neutropenic complications. The role of glanulocyte
transfusion is an exciting and emergent therapy. Prophylaxis
includes isolation, acceleration of granulocyte recovery and
judicious prophylactic use of antimicrobials.
 474 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Other Causes
Aetiocholanolone Fever
Seventeen ketosteroids, androsterone, epiandrosterone and
aetiocholanolone are derived mainly from metabolism of
testosterone, besides oestrone to a minor extent.
Aetiocholanolone has no androgenic activity but possesses
pyrogenic effects. This is found in excess in some cases of
adrenogenital syndrome and periodic fever.
Factitious Fever (False Fever)
Certain individuals or Munchausen syndrome patients,
usually women, try to produce false elevations of the body
temperature by their own ways and means so as to achieve
their purpose.
Habitual Hyperthermia (Psychogenic fever)
The subject may have temperature set at a higher level than
the normal range especially in young women with vague
complaints of the nature of psychoneurosis. This may be a
manifestation of an underlying organic disease or without
any significance. This is suspected after careful observation
for a reasonable period, without any support from the
investigational study.
Thyroiditis
It may be acute, subacute (granulomatous and lymphocytic)
and chronic. Fever is associated with acute or subacute
granulomatous thyroiditis. Acute thyroiditis results usually
from bacterial infection of the thyroid gland with features
of fever, tenderness and swelling of the thyroid gland. The
thyroid scan may show area of decreased uptake in the
affected portion.
Subacute granulomatous thyroiditis follows a viral
infection. It is characterised by painful enlarged thyroid gland
associated with fever and chills, neck pain or dysphagia.
There may be signs of hyperthyroidism of short duration.
The radioactive iodine uptake is low with a poorly visualised
thyroid gland.
In subacute lymphocytic thyroiditis or chronic thyroiditis
(Hashimoto’s and Riedel’s thyroiditis), fever is not a clinical
feature (Refer to Chapter ‘Goitre’).
Inherited
Familial mediterranean fever It is an inherited disorder seen in
certain races (Jewish and Armenian). The episodes of fever
may be prolonged or recurrent with few days or couple of
weeks interval. Abdominal pain or pleuritic pain or joint pain
may be associated due to peritoneal, pleural or joint
inflammation.
Hyperlipidaemia Type-1 The deficiency of enzyme lipoprotein
lipase leads to a block in the metabolism of chylomicrons,
leading to high levels even after fat-free diet or fasting. The
recurrent attacks of abdominal pain (pancreatitis), eruptive
xanthomas, hepatosplenomegaly, white retinal vessels may
also be associated with fever. The diagnosis is suggested
by:
1. Observing pale and creamy plasma,
2. High plasma triglyceride levels (> 2000 mg per 100 ml),
3. Type-1 lipoprotein pattern on electrophoresis, and
4. Heparin infusion fails to increase the lipoprotein lipase
levels.
Cyclic Neutropenia Neutropenia occurs in cycles of
approximately three weeks with fever, malaise, oral ulcers
and cervical adenopathy. The neutrophils return to normal
levels within few days. This is a familial occurrence and
the cyclic phenomenon is due to a defective stem cell.
Fabry’s Disease It is an inborn error of glycosphingolipid
metabolism characterised by intermittent fever,
telangiectases, hypohidrosis, corneal opactities, agonising
pain and paraesthesiae of hands and feet. As age advances
involvement of the coronary arteries and renal vessels may
result in angina and hypertension. Lymphoedema of the legs
and episodic diarrhoea may be present. The diagnosis is
confirmed by demonstration of deficient alpha-
galactosidase-A activity in plasma and increased amounts
of globotriaosylceramide in plasma.
Anhidrotic Ectodermal Dysplasia It is inherited as X-linked
recessive trait, with a triad of defects anhidrosis, anodontia
and atrichosis. It may be associated with prolonged
intermittent fever. Deficient sweating, hair and teeth will
differentiate it from tropical anhidrotic asthenia in children
especially during summer months.
CLINICAL APPROACH
For the assessment of pyrexia of unknown origin, the
following must be enquired:
a. Eliciting when and how the fever started?
b. Any associated symptoms like rigors, body aches and
joint pains, dysuria or cough or convulsions, weight
loss, skin sores
c. Drug history (antibiotics, sulpha, barbiturates, phenytoin,
methyldopa, antihistamines)
d. History of any exposure to infections
e. Occupation and contacts with animals.
 Pyrexia of Unknown Origin 475

Physical Examination o. Limbs

Hands: Look for
a. Temperature: Recording temperature every four hour
i. Clubbing of the fingers (Hippocratic fingers)
and maintaining temperature charts meticulously
ii. Osler’s nodes
(continuous, remittent, intermittent, relapsing charts).
iii. Splinter haemorrhages
b. Pulse: Observe the pulse rate and its relationship with iv. Transverse white bands of the nails (Beau’s lines)
temperature (relative bradycardia or proportionate v. swelling of the small joints.
tachycardia). vi. Deep venous thrombosis.
c. Blood pressure: Hypertension in pyelonephritis or p. Chest
polyarteritis
Lungs
d. Respiratory rate: Respiratory rate and the pulse
i. Percussion of the chest for any dullness (pleural
respiration ratio
effusion) or check for diaphragmatic movements.
e. General appearance: Is the patient looking toxic or
ii. Auscultate for change in breath sounds (like
normal in spite of fever or dull and inactive?
cavernous breath sounds for a cavity) and any
f. Sensorium status
accompaniments like pleural rub or crepitations.
g. Skin: Any generalised flushing or petechiae,
Heart: Any evidence of pericardial rub or cardiac
haemorrhages or rash or eschar or any infective wounds
murmurs
or herpetic vesicles on the lips. Any nodules which can q. Abdomen: Look for evidence of
be demonstrated about their attachment to deeper i. Ascites
structures. ii. Hepatomegaly
h. Lymph glands: Palpate for enlarged lymph glands over iii. Splenomegaly
the neck, axillary regions, epitroclears, groins and note
iv. Localising signs of any abscess like perinephric or
whether single or multiple, consistency, tenderness,
subphrenic
discrete or matted.
r. Pelvic: Rectal and vaginal examinations.
i. Bones and joints: Any swelling or impaired mobility of
s. Look for changing signs.
a joint or joints, any tenderness of the long bones or
vertebrae.
j. Face Investigations
i. Butterfly rash First Stage
ii. Parotid gland enlargement
iii. Any cranial nerve paralysis Basic Investigations
k. Eyes 1. Urinalysis including microscopic examination for pus
i. Conjunctiva for anaemia cells and RBCs.
ii. Sclera for jaundice 2. Haematology
iii. Uveitis A. Total white cell count
iv. Fundus exam for any papilloedema, choroidal a. i. Leucocytosis (pyogenic bacteria)
deposits, or candle wax dripping appeance (due to ii. Leukaemia
perivascular cuffing of retinal veins) b. Leucopenia (Brucellosis)
l. Head and neck: Look for: B. Differential count
i. Tenderness of the scalp a. Lymphocytosis, e.g. Glandular fever
ii. Tenderness of the temporal artery b. Eosinophilia, e.g. Parasitic infections, connective
iii. Neck rigidity tissue disorders
iv. Evidence of cyanosis and c. CD4 lymphocyte count (low in AIDS)
v. Evidence of mastoiditis. C. Blood smear examination: For abnormal white blood
m. Oral cavity: Dental or oropharyngeal sepsis corpuscles
n. Tongue D. NBT test
i. Pallor of the tongue This test is used to differentiate bacterial and
ii. Any ulcers or typhoid tongue (central coating, free nonbacterial illnesses. The percentage of absolute
margins and tremulousness) number of leucocytes, which makes colourless
 476 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

nitroblue tetrazorium dye to blue black deposits, is 3. Biochemical

increased in bacterial infections. A. T4 and radioactive iodine uptake levels
E. ESR B. Tumour markers—Alpha fetoprotein (Raised in
It is increased (more than 50 mm in one hour) in hepatoma)
lymphomas, connective tissue diseases and infections C. Immunoglobulins—It is raised in certain diseases.
like pulmonary tuberculosis. The examples are:
3. Microbiology (culture and sensitivity) i. IgA—Crohn’s disease
A. Urine culture for E. coli—A sterile pyuria may be ii. IgG—Systemic lupus erythematous
suggestive of tuberculosis. iii. IgM—Primary biliary cirrhosis; Rheumatoid
B. Faeces culture if indicated. arthritis.
C. Blood cultures for aerobic and anaerobic organisms. 4. Radiology
D. Throat swab culture. Contrast Radiography
E. Sputum culture. A. Intravenous pyelogram
F. CSF culture. B. Barium studies of the GI tract.
G. Tuberculin test (Mantoux). 5. Ultrasonography
A. Abdomen—It is possible to demonstrate
H. HIV detected by PCR (Refer to Appendix IV).
abnormalities of liver or retroperitoneum.
4. Serology
B. Cardiac—Echocardiography including colour
A. Antibody test for infections like typhoid, brucellosis,
doppler.
leptospirosis, glandular fever (rising titres are very
diagnostic), K39 strip test for visceral leishmaniasis
by testing for antibody to Leishman antigen K39.
Third Stage
B. Acute and convalscent sera for paired titres. Advanced Investigations
5. Biochemical 1. Radiology and Imaging Procedures
A. Liver function tests for liver disorders. A. Endoscopic Retrograde Cholangio Pancreatography
B. Alkaline phosphatase estimation—It is raised in bone (ERCP).
or liver diseases. B. Computed Tomography (CT) Scan
C. Blood urea and serum creatinine for assessing renal i. Abdomen: Especially useful in obese people, in
function. retroperitoneal lesions or differentiating intra-
D. CSF analysis. hepatic fluid collections and hepatic mass lesions.
6. Skin tests ii. Total body scan: If indicated.
7. Radiology C. Magnetic Resonance Imaging (MRI) of the spinal
A. Chest X-ray for apical inflitrates, hilar shadows and cord or pelvis as indicated.
diaphragm abnormalities. D. Radionuclide Scanning
B. Abdomen X-ray—Look for abnormal shadows and Different scanning procedures by using radiolabelled
loss of psoas shadow. compounds allow accurate assessment of
C. X-ray of the sinuses. inflammatory or neoplastic processes, parenchymal
8. ECG changes in the viscera and biliary patency.
i. 99 m Technetium sulphur colloid liver-spleen
Second Stage scans
ii. 99 m Tc-HSA lung scan
Further Investigations If diagnosis is still uncertain redo iii. 99 m Tc-MDP bone scan
history taking and physical examination everyday and review iv. 67-Gallium scan for osteomyelitis localising
the charts. Withhold each drug one after another for 48 hours abscess, primary or metastic tumour.
(each to be considered). v. 99T m labelled WBC for abdominal abscess.
1. Microbiology: Animal inoculation test. E. Abdominal aortography.
2. Serology: Antibody test for immune disorders like F. Lymphangiogram.
rheumatoid factor, antinuclear antibodies especially DNA 2. Endoscopic examination (as appropriate, depending on
antibody test, antistreptolysin titres. the lesion suspected).
 Pyrexia of Unknown Origin
A. Gastroduodenoscopy
B. Colonscopy
C. Bronchoscopy.
3. Relevant biopsy studies
A. Lymph gland
B. Muscle
C. Bone marrow
D. Liver
E. Kidney.
Fourth Stage
Conclusive investigations If the disease remains still a riddle
despite exhaustive investigations or if the patients condition
is deteriorating then:
1. Explorative laparotomy for occult cancers or preferably
laproscopy may be considered, before diagnostic
laparotomy for occult cancers.
2. Therapeutic trial: Treatment is better avoided ideally until
diagnosis is established wherever possible. If this is not
feasible, then specific drug trial towards the highly
suspected condition or employing drugs with limited
spectrum of activity like AKT; is a logical step, as the
risk of untreated disease vastly outweighs the risk of
drugs. Further caution must be exercised, if diagnostic
delay is going to adversely affect the prognosis in
conditions like intra-abdominal infections.
Nevertheless, it should be possible to diagnose about
90% of all PUOs with a proper diagnostic evaluation, i.e.
interrogating the patient at frequent intervals for any new
symptoms or physical signs as elicited by repeating physical
examination as often as possible supported by appropriate
investigations as and when necessary. Most of the PUOs
may be due to occult infections or malignancies or
connective tissue disorders. Quite often the remaining 10%
will recover and all that is required in such patients, is a
watchful non-interference, and thorough reassurnce.
Passage of time and progress of underlying disease may
throw light sooner or later.
TREATMENT OF PYREXIA OF UNKNOWN ORIGIN (PUO)
The disoredered thermoregulation with raised body
temperature for > 3 weeks or undiagnosed even after one
week of comprehensive investigations, is a challenging
enigma to the clinician. The difficulty in diagnosis is primarily
obviated by eliminating common infections like that of urinary
tract. It is to be realised that causes of prolonged fever may
vary considerably from place to place such as resurgence
477
of an erstwhile common disorder in a region. Further it is
to be reckoned that more than one cause (vide supra) may
be responsible for the riddle. However, the aetiology of fever,
whether it is due to an infection or neoplasm or connective
tissue disorder or an obscure cause (drug fever, thyroiditis,
cryptic haematoma, thromboembolism ) must be determined
as quickly as possible lest deleterious effects should occur.
The practice of administering antipyretics routinely must
be discouraged (as it affects the temperature chart and
encourages undesirable ambulation) unless the temperature
shoots beyond 102° F (39° C). The therapeutic trials
preferably with single antibiotic should be the last recourse
or when the patient is critically ill (it is better to give, after
sending the blood, etc. for appropriate cultures). Partially
treated casually with inadequate dosage schedule, is the
biggest problem, faced by clinician now.
Symptomatic/Supportive Treatment
1. Bed rest
2. Temperature: High temperatures must be lowered by:
a. Tepid sponging, or ice caps.
b. Immersion in a tub of cold water, if the temperature
is very high (108° F or 42.2° C).
c. Cooling blankets.
d. Antipyretic drugs: Paracetamol (0.5 g every 4 hours),
aspirin (0.3 to 0.6 g every 4 hours) are used
discriminately. Sweating with abrupt fall of
temperature is met with adequate fluids.
e. Associated rigors are treated with blankets and
chlorpromazine (20 mg).
Dantrolene (1 mg/kg every 5 mts IV upto 10 mg/kg
may be tried in hyperthermia)
3. Associated symptoms
a. Body pains/headache: Non-narcotic analgesics,
paracetamol, NSAIDs.
b. Restlessness: Diazepam, or chlordiazepoxide.
c. Insomnia and delirium: Hypnotic-sedatives may be
given.
d. Other symptoms like cough, seizures, anaemia, may
be treated appropriately.
4. General care of the mouth and skin.
5. Diet: Fluids must be given in such amounts as to ensure
urine output or more than 1500 ml/d. Light diet with
adequate calories (such as milk or proprietary
preparations of milk, bread, biscuits, glucose and fruit
juice) to reduce work load of the internal organs.
6. Watch for any complications like cardiac or circulatory
failure and treat promptly as they arise.
 478 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Specific Treatment for Specific Diseases
Infections
Bacterial Infections
• Infective endocarditis
i. Suitable antibiotics are given for 4 to 6 weeks
depending on the causative organism, such as—
a. S viridans: Penicillin G (10-20 million units/d
indevide doses or cefazolin (2 g i.v. 8th hourly).
b. Enterococcus: Penicillin as above or ampicillin
(2 gm every 6 hours i.v.), and gentamicin (1 mg/
kg twice daily).
c. Pneumococcus: Penicillin G (6-12 million units/
d) or cefazolin as above or ceftriaxone (1 gm bd).
ii. Any obvious source of infection should be removed.
iii. Associated anaemia or cardiac failure must be treated
appropriately.
iv. Cardiac surgery if indicated (valvular disease,
prosthetic valves) must be undertaken.
• Sepsis Suitable antibiotic and surgical drainage, if
necessary, are imperative.
• Brucellosis Tetracycline (500 mg 6 hourly) together with
rifampicin (600 mg/d) or streptomycin (1 gm) for one
month prevent relapses.
• Typhoid Specific chemotherapy includes ciprofloxacin
(500 mg twice daily) or co-trimoxazole (2 tablets twice
daily) or chloramphenicol (250 mg 4-hourly) or
amoxycillin (750 mg 6-hourly), which should be
continued for about 10 days after the temperature
touches normal. Relapses are likely to occur if the
chemotherapy is started or stopped too early and
inadequate. The chronic carrier state is treated with
ciprofloxacin for four weeks and cholecystectomy may
be done if necessary.
• Tuberculosis (Refer to Chapters ‘Haemoptysis and
Chronic Diarrhoea’).
• Antibacterials:
1. Beta-lactam antibiotics
A. Penicillins (Parenteral and oral)
i. Penicillinase sensitive:
Benzyl penicillin (Penicillin-G) procaine penicillin and
Benzathine penicillin
ii. Penicillinase (Betalactamase) vesistant penicillins:
Cloxacillin; Methacillin, Flucloxacillin.
iii. Betalactamase inhibitors clavulanic acid, Sulbatum
and Tazobactam
iv. Broad spectrum: Aminopenicillins—Ampicillin and
Amoxycillin)
v. Piperacillins:
vi. Oral Penicillins (Penicillin-V)
B. Cephalosporins:
i. First generation: Cephalaxin, Cefadroxil, cefazolin
ii. Second generation: Cefuroxime, Cefaclor
iii. Third generation: Cefotaxime, Ceftriaxone,
Cefoperazone, Cefpodoxime, Ceftizoxime, Cefdinir
iv. Fourth generation: Cefepime
C. Monobactam: Aztreonam
D. Carbapenens: Imipenum, Meropenum
2. Aminoglycosides - Gentamicin, Amikacin,
Streptomycin, Kanamcin, Tobramycin, Netilmicin
3. Macrolides - Erythromycin, Azithromycin,
Roxithromycin, Clarithromycin, Spiramycin
4. Quinolones -
i. Nalidixic acid
ii. Fluroquinolones - Norfloxacin, Ciprofloxacin,
Ofloxacin, Levofloxacin, Sparfloxacin,
Moxifloxacin, Gatifloxacin
5. Tetracyclines - Tetracycline, Oxytetracycline,
Demeclocycline, Doxycycline, Minocycline
6. Nitroimidazoles - Metronidazole
7. Glycopeptides - vancomycin, telcoplanin
8. Oxazolidinones - Limezolid
9. Lincozamides - Lincomycin, clindamycin
10. Chloramphenicol
11. Rifamycins - Rifampicin, Rifabutin
12. Others - Co-trimoxazole, Nitrofluramtoin, Fusidic
acid, Polymyxin
Viral Infections
• Psittacosis Tetracycline (500 mg 6-hourly orally or 500
mg i.v.) for 10 days is effective.
• Cytomegalovirus infection Ganciclovir (5 mg/kg/12 hrs/
VI) is given only in severe infections since it is toxic.
Foscarnet (24 mg per ml in saline infusion).
• Infectious mononucleosis Treatment is symptomatic and
short course of corticosteroids may be given for airway
obstruction or dysphagia or thrombocytopenia or severe
haemolytic anaemia.
• AIDS Since there is no specific therapy, prevention is
all important. However, antiviral drugs like zidovudine
(azidothymidine) or dideoxycytidine are known to
suppress the virus and alter the course of the disease.
Opportunistic infections and Kaposi’s sarcoma are
treated appropriately. (refer Appendix IV).
• Antiviral agents
1. Nucleoside analogues
Aciclovir, Valaciclovir, Fanciclovir, Ganciclovir,
Cidofovir
2. Ribavirins
 Pyrexia of Unknown Origin
3. Adamantanes - Amantadine
4. Interferons - INF-alpha and Pegylated INF-alpha
5. Pyrophosphate analogues - Foscarnet
6. Zanamivir, Oseltsaivir
7. Lamivudine
8. HAART (Refer to Appendix-IV).
Parasitic Infections
• Kalaazar (Visceral leishmaniasis) Pentavalent antimonials
like sodium stibogluconate (10-20 mg Sb/kg up to 850
mg i.m. or i.v. daily for 3-4 weeks), pentamidine (3-4
mg/kg once or twice per week), or amphotericin (0.5
mg/kg in 1.5 % glucose i.v. infusion slowly for six hours
and may be increased gradually to 1 mg/kg and given or
alternate days for four weeks) considered, if
unresponsive to antimonials.
• Toxoplasmosis Sulphadiazine (1 g 6-hourly) and
pyrimethamine (100 mg b.d x 48 h. followed by 25 mg/
d) together with folinic acid (10 mg/d) given for four
weeks, orally.
• Malaria (Refer to Chapter ‘Rashes’).
Rickettsial Diseases Q fever Chloramphenicol (50 mg/kg 6-
hourly) or tetracycline (25 mg/kg 6-hourly) given for two
weeks. If endocarditis is present, tetracycline and
clindamycin or rifampicin given for prolonged periods.
Other typhus fevers Chloramphenicol or tetracycline is
given till temperature remains normal for two days.
Spirochaetal: Leptospirosis (Refer to Chapter ‘Jaundice’).
Mycotic Infections
• Histoplasmosis Amphotericin (0.5 mg/kg in 5% glucose
i.v. infusion slowly for six hours and may be increased
gradually to 1 mg/kg for three months) is indicated in
seriously ill patients. A short course of prednisolone is
given if dyspnoea is present. For nonmeningeal cases,
ketoconazole (200-400 mg/d) is given for one year.
• Disseminted candidiasis Amphotericin is indicated as
above with or without flucytosine (100 mg/kg/d).
• Pneunomocystis carinii Trimethoprim and
sulphamethoxazole 20-100 mg/kg/d 6-hrly oral or IV
for 2 wks or pentamidine 4 mg/kg/d parenterally for
2 wks) are advocated.
• Antifungal Agents
1. Azoles
a. Imidazole — Miconazole, Ketoconazole,
Clotrimazole, Econazole
b. Triazole — Fluconazole, Itraconazole
2. Morpholines — Griseofulvin
3. Allylamines — Terbinafine
4. Pyrimdine — Flucytosine
479
5. Polyenes — Amphotericin B, Nystatin
6. Echinocandins — Caspofungin
NB Systemic antifungal drugs in use are Amphotericin B,
Flucytosine, Fluconazole, Intraconazole, Ketoconazole.
Neoplasms (Malignant or Benign)
Lymphomas
Hodgkin’s limphoma The teatment recommended for early
stage one and two of classic group is radiotherapy for 1
month. For advanced stage (Three and four) disease
systemic chemotherapy is the treatment of choice for 6-9
months. Radiotherapy, combination chemotherapy or both
offer a cure rate of 70%. There are various chemotherapy
protocols. CHL VPP regimen is usually adopted, i.e.
chlorambucil (5 mg b.d. for two weeks), vinblastine (10 mg
the 1st day and 8th day i.v.), procarbazine (150 mg for two
weeks), prednisolone (40 mg for two weeks) are given on
a four week cycle, for 6 to 9 pulses. MOPP (Mustine,
Vincristine procarbazine, prednisolone in advanced disease,
and in those who do not respond, it may be beneficial to
alternate CHL VPP with adriamycin (doxorubicin),
bleomycin, vinblastine and dacarbazine. This ABVD regime
is likely to prevent second malignancy like acute leukaemia.
The other variety, i.e. nodular lymphocyte predominant
responds to radiotherapy.
Non-Hodgkin’s lymphoma Radical radiotherapy may cure
early stages. The palliative radiotherapy with chemotherapy
either single agent (chlorambucil) or combination
chemotherapy, i.e. (CHOP) cyclophosphamide,
hydroxydaunorubicin, oncovin/vincristine and prednisolone
in cycles) indicated in advanced stages. Fludarabine is
effective. Rituximab (Anti-CD 20 monoclonal antibodies)
375 mg/m2 in N. Saline with or without chemotherapy
promising.
Carcinomas (Refer to Chapters ‘Weight Loss and
Haematuria’).
Osteosarcoma Radical amputation and chemotherapy with
adriamycin, methotrexate and citrovorum factor.
Atrial Myxoma Surgical removal of the tumour is indicated.
Connective Tissue Disorders
• SLE
•
•
Polyarteritis Nodosa
Giant Cell Arteritis } (Refer to Chapter ‘Polyarthritis’)
Vascular Diseases
• Recurrent Pulmonary Embolism (Refer to Chapter ‘Chest
Pain’).
 480 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Deep Venous Thrombosis (Refer to Chapter ‘Oedema’).
• Pelvic Thrombophlebitis (Refer to Chapter ‘Oedema’)
Granulomas
• Sarcoidosis
• Prednisolone 20 to 40 mg daily for one month, followed
by a maintenance dose of 10 mg daily is effective. When
corticosteroids are contraindicated, hydroxy chloroquine
is preferred.
• Crohn’s Disease (Refer to Chapter ‘Chronic Diarrhoea’)
Granolomatous Hepatitis (Vide supra—Infections and
Sarcoidosis.)
Liver
Hepatic Cirrhosis (Decompensated) (Refer to Chapter
‘Jaundice’).
Drug fever
Discontinue the incriminating drugs.
Haematological
Aplastic Anaemia (Refer to Chapter ‘Fatigue’).
Leukaemia (Refer to Chapter ‘Bleeding Disorders’).
Agranulocytosis
The incriminating agent (drug idiosyncrasy or toxicity) must
be withdrawn. The possible infections/septicaemia should
be treated aggressively with antibiotics and supportive
measures.
Febrile Neutropenia
Febrile neutropenia: Recombinant granulocyte colony
stimulating factor-GCSF (FILGRASTIM) stimulates
neutrophil production.
Other Causes
Thyroiditis (Refer to Chapter ‘Goitre’).
Inherited
• Familial mediterranean fever 0.6 g of colchicine t.d.s.
prevents fever.
• Hyperlipidaemia Dietary measures (low fat and low
cholesterol diet) plus avoiding sucrose and alcohol with
or without nicotinic acid or gemfibrozil or statins may
be helpful (Refer to Chapter ‘Polyarthritis’).
• Cyclical neutropenia (Periodic fever) It is prone to
spontaneous remissions. Though various therapies are
proved to be ineffective, lithium carbonate yields result
in some cases. Haemopoietic growth factors like G-
CSF improves neutrophil counts and periodicity.
• Fabry’s disease Treatment is symptomatic for this rare
X-linked lysosomal disorder. Carbamazepine relieves
agonising pains and paraesthesiae. If renal failure occurs,
dialysis or renal transplantation considered.
Pyrexia of Unknown Origin 481
482 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Rashes
31
The term rash includes all cutaneous eruptions with or
without fever. The skin is considered to be a mirror of
systemic diseases. Cutaneous manifestations of systemic
diseases are well documented, like butterfly rash, erythema
nodosum, erythema marginatum, splinter haemorrhages and
spider naevi. A symmetrical or generalised rash of sudden
onset is pathognomonic of an endogenous disorder whereas
an asymmetrical and localised eruption is suggestive of an
exogenous origin. These cutaneous eruptions may be due
to (i) exanthemata, (ii) leutic lesions, (iii) drug allergy, (iv)
haemorrhagic eruptions (purpura), (v) malignancy or (vi)
classical skin disorders per se like acne, pityriasis, lichen
planus, urticaria. The description of all such eruptions may
be out of place in this context. Hence generalised eruptions
associated with infections, immune-mediated entities and
drug ingestion deserve description.
Any cutaneous eruption generally consists of a primary
(elementary) specific lesion from which secondary lesions
may evolve. Certain terms are used in the dermatologic
vocabulary to express the morphology of different skin
lesions, the interpretation of which requires concept of
minute characteristics of the rash.
The primary lesions are divided into (1) flat lesions
(macules and haemorrhages) and (2) raised lesions (a) solid
lesions without fluid (papules and weals) and (b) lesions
with fluid (vesicles, bullae and pustules).
TERMINOLOGY
Macule or Spot
It is a small circumscribed area neither appreciably raised
nor depressed with altered colour (depigmented,
hypopigmented or hyperpigmented or erythematous or
purpuric macules) and not palpable. The term macule
connotes lesion of any size. (In the past it was restricted to
lesions less than 1 cm in diameter and the term patch was
applied for lesions more than 1 cm diameter.)
Haemorrhages
These are extravasations of blood (petechiae < 1 mm in
diameter; purpuric spots > 2 mm; ecchymoses > 5 mm).
Papule
It is a solid circumscribed raised palpable lesion of <1 cm
in diameter (usually 0.5 cm). The terms nodule or tubercle
and tumour are used to connote, increasing diameters of
> 1 cm and deeper involvement. Plaques are coalesced papules
occupying relatively large irregular area ( >2 cm). A papule
may become vesicular or pustular or break into an ulcer.
Maculopapular
Maculopapular lesions are raised spots differing in colour
from the surrounding skin.
Weal
It is a slightly elevated, solid, palpable, oedematous lesion,
the centre of which is paler than the periphery. It is
surrounded by a zone of erythema (flare) and the lesion is
evanescent (often fading in minutes to hours) leaving no
trace behind, or succeeded by a papule. The weal may be
as small as a match-head or a palm size even.
Vesicle
It is circumscribed elevated lesion containing usually clear
fluid (often serous) of 0.5 cm or less diameter with or
without an erythematous base. Occasionally, the contents
may be blood, lymph or extracellular fluid.
Bullae
Bullae or blebs are merely large vesicles of > 0.5 cm diameter.
Blister is a generic term used to describe either a vesicle
or a bulla.
 484 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Cyst ii. Fissures or rhagades are deep linear cracks in the

epidermis of varying length with no breadth due to
A cyst is a epithelium lined cavity with fluid or semisolid
stretched skin, consequent to inelasticity and thickening.
matter.
PATHOGENESIS
Pustule
The exanthems are due to:
It is a circumscribed elevated lesion of 0.5 cm or less
1. Direct invasion of the skin by the micro-organism and
diameter containing pus. It may be pustular from the onset
multiplication therein.
or may develop from a vesicle. Larger collections of pus
2. Microbe being carried in plasma or blood cells into dermal
are termed fruncles (boils).
blood vessels.
A cluster of boils with surrounding cellulitis and multiple 3. Immunological injury (antigen-antibody reaction to
drainage points accompanied by sloughing of skin antigen derived from microbe)
subcutaneous tissues, is described as carbuncle.
The secondary lesions occur as sequelae or mechanically. CAUSES OF RASHES (GENERALISED ERUPTIONS)
(TABLE 31.1)
Desquamation
Table 31.1: Causes of rashes
A scale (a flake of horny skin) is found if a primary lesion is
a dry one, whereas a scab or a crust may be found from a I. Infections
moist lesion like a vesicle or pustule, due to coagulation of 1. Viral
a. Varicella
serum and blood.
b. Variola
c. Vaccinia
Pigmentation d. Measles
e. Rubella
Pigmentation may occur around a primary lesion (post-
f. Herpes zoster
inflammatory lesion). Pigmentation is often associated with g. Herpes simplex
lichenification, i.e. thickened skin and exaggerated skin lines. h. Arbo viruses
i. Enteroviruses
Ulcer j. Others
i. Exanthem subitum
It is a break in the continuity of the skin surface associated ii. Erythema infectiosum
with destruction of a part with definite length and breadth, iii. Infectious mononucleosis
depth and characteristic edges. iv. AIDs-Acute seroconversion.
2. Bacterial
Scar a. Streptococcus: Group-A (Scarlet fever)
b. Staphylococcus pyogenes aureus.
It is a connective tissue replacement, following destruction c. Tuberculosis
of the basal layer of the epidermis or underlined corium and d. Hansen’s disease
they may be thin or thick, freely movable or adherent, pitted e. Typhoid fever
f. Gonorrhoea
or pigmented.
g. Meningococcal meningitis
3. Chlamydial: Psittacosis
Atrophy 4. Spirochaetal
a. Leutic infection
It is thinning of the skin and may develop due to destruction
b. Rat bite fever
of hair follicles, sweat glands and connective tissue. c. Leptospirosis
5. Rickettsial
Mechanical a. Spotted fevers
i. Rocky mountain spotted fever
i. Excoriation: Excoriations are superficial or deep linear ii. Rickettsialpox.
markings caused by scratching. New lesions may
develop in scratch areas (Koebner phenomena) Contd...
 Rashes 485

Contd... of rash is confined to face and peripheral portions of the

b. Epidemic typhus.
limbs. The lesions are macules which develop into papules
c. Endemic typhus. within few hours. This stage lasts for 2 to 3 days. The
6. Fungal: Cryptococcosis conversion of papules into vesicles which are deep seated
7. Parasitic and multiloculated then commences in the next 24 hours.
a. Toxoplasmosis After about two days, vesicles become purulent. This
b. Trypanosomiasis evolution of pustules is universal by the tenth day of fever.
c. Malaria The lesions develop with regular sequence and present as a
d. Filariasis
e. Other parasites
single stage of development in any area at one time. The
II. Immunologic fever which subsides after development of rash, reappears
1. Hypersensitivity (cell mediated immunity) with pustular formation and toxicity supervenes. The vesicles
a. Erythema nodosum may be observed in the mucous membrane which leave
b. Erythema multiforme behind ulcers. The pustules slowly dry up and form black
c. Stevens-Johnson syndrome scabs which separate after several days, leaving pock marks
d. Behcet’s syndrome (Pitted scars).
e. Lyell’s syndrome
f. Angio-immunoblastic lymphadenopathy with Vaccinia (Cow-pox) It is the result of accidental inoculation
dysproteinaemia (AILD) of the hands of milkers from the udders or primary
g. Henoch- Schonlein purpura. vaccination with calf lymph. They go through the stages of
2. Autoimmunity (Antibody mediated or Humoral immunity) erythema, papulation, vesiculation, crusting and scarring.
a. Polyarteritis nodosa This vaccinia may be generalised in atopic individuals.
b. Rheumatic fever
III. HLA Related Diseases (Genetic Components Involved in
Measles (Rubeola) It is usually seen in children with prodromal
Autoimmunity) features like fever and running of the nose, small white
1. Systemic lupus erythematosus spots surrounded by red areolae on the inner side of the
2. Pemphigus vulgaris cheeks at the parotid duct opening (Koplik’s spots) appear
IV. Tumours: Glucagonoma before the rash. The eruptions occur on the fourth day of
V. Drug Eruptions fever, commencing behind the ears and spreading on the
VI. Idiopathic: Mucocutaneous Lymph Node Syndrome (Kawasaki’s face, neck, trunk and extremities. The type of lesion is
Disease)
maculopapular only and becomes confluent forming typical
blotchy appearance. As the rash appears, the Koplik’s spots
Infections fade. Itching may accompany the rash. Catarrhal symptoms
Viral and fever are maximum along with stomatitis at the height
of the eruption. The rash disappears in two or three days,
Varicella (Chickenpox) The characteristic presentation is fever when the temperature falls abruptly. Since the lesions are
and rash on the very first day. The distribution is only dry without fluid collections, the rash fades into
predominantly central (centripetal), confining to the trunk, brownish staining. Ultimately there is fine desquamation
axillae and neck. The lesions and their evolution are macules without scars.
appear first and within few hours become papular and then
Rubella (German measles) The features are like measles except
vesicular; then they become pustular within 24 to 48 h. The
eruptions appear in crops and all the said evolving lesions that the premonitory symptoms are mild and the rash appears
are appreciated in any one area at the same time. The on the first day of the illness without Koplik’s spots and
uniloculated vesicles are also seen in the mucous membrane disappears without staining or desquamation. Striking tender
which may rupture leaving behind ulcers. The pustules may lymphadenitis of the posterior cervical glands is distinctive,
rupture or dry up without rupturing in a few days and form and lymphadenopathy may be generalised. The whole illness
scabs. Since the lesions are superficial, they leave no scars. lasts for about three days. This entity is otherwise known
Though earlier lesions dry up and form crusts, fresh crops as German measles (German being Germane which
appear with fever. Pruritus may be intense. connotes closely akin to or pertinent to).
Variola (Smallpox) It is of only historical interest as there is Herpes zoster (Shingles) Herpes Zoster (Shingles) is closely
global eradication. The rash starts on the 3rd day of fever. related to varicella (Reactivation of the dormant virus causes)
The distribution is peripheral (centrifugal) and the density and hence it is termed as varicella zoster virus. It is presumed
 486 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
to result in semi-immune states. The attack starts with pain
in the segmental distribution of the nerve root due to invasion
of posterior root ganglia or for that matter any other ganglia
followed by rash over the distribution of the same nerve
root, after three days. Fever may accompany the pain. The
rash consists of a group of vesicles on an erythematous
base along the dermatome. They develop in crops, each
crop lasting for about a week. Later the vesicles rupture or
dry up forming crusts leaving behind scars and pigmentation.
The pain usually subsides as the eruption fades, and
intractable neuralgia may occasionally result, which may
last even for years. The affected dermatome may become
anaesthetic or segmental muscle wasting may be seen. The
other ganglia affected are geniculate ganglion (facial paralysis
with vesicles on the auditory meatus and the soft palate) or
it may be Gasserian ganglion (involving the face and cornea).
The virus sometimes involves nerve roots which are already
affected by tumours or lymphomas or injury or toxic states
(symptomatic herpes). Occasionally, generalised herpes
zoster may be encountered. Smears from the vesicles show
multinucleated giant cells.
Herpes simplex (HSV) This exists in two forms—Type-I and
type-II, i.e. HSV-1 and HSV-2. Though the latter is
responsible for genital herpes, which is painful, all other
clinical varieties are due to type-I only. Usually, it is
associated with malaria or pneumonia. It starts on the very
first day with burning or itching with erythematous and
macular formation on which small vesicles erupt with clear
fluid inside. Later they collapse, ulcerate and become crusted.
Occasionally, generalised vesicular eruptions may occur.
The clinical course lasts for about 1 to 2 weeks usually
leaving no scars or pigmentary changes. Herpes simplex
infection may be recurrent at the same site. Sometimes the
infection may be generalised or systemic (fever, sore throat,
lymphadenopathy and hepatitis) or manifest as gingivo-
stomatitis or keratoconjunctivitis or herpes whitlow Eczema
herpeticum and occasionally meningitis, encephalitis myelitis.
It may lie dormant in ganglion cells and reactivated which
accounts for recurrent HSV.
Arboviruses Arthropod-borne viruses are many and some of
them are mosquito-borne like dengue fever or chikungunya
with fever and rash. Sometimes dengue fever is associated
with petechial rash and haemorrhages of the gastrointestinal
tract. Certain tick-borne viruses like crimean haemorrhagic
fever may also be associated with petechial rash and
gastrointestinal bleeding.
Dengue fever or break-bone fever is characterised by
severe body pains associated with fever and rash. The
eruption appears on the 3rd to 5th day. It may be
morbiliform, maculopapular or petechial and is distributed
on the trunk and extremities (first appears on dorsum of
hands and feet). It may be pruritic and fades with
desquamation which lasts for about two weeks.
Haemorrhagic manifestation may vary from easy bruising
to spontaneous bleeding and may progress to shock. The
other features are injected sclera and nontender
lymphadenopathy. The temperature chart is characteristic
with a biphasic curve (initial phase 3-4 days; remission 12
h to two days and second phase 1-2 days), which is
described as saddle-back chart. Detection of antidengue
immunoglobalin (IgM) and virus genomic sequence by PCR
are diagnostic. Platelets are reduced. Dengue haemorrhagic
fever and dengue shock syndrome are severe presentations.
Chikungunya is like dengue fever with additional features
of arthralgia and arthritis of the interphalangeal joints or big
joints. The fever lasts for 1 to 6 days or may have biphasic
character and the rash is maculopapular.
Enteroviruses These include coxsackie viruses and
echoviruses, polio, reo and rota viruses.
Echoviruses of type 9 and 16 (Boston exanthem) may
be associated with fever, sore throat and rash of the rubella
type and aseptic meningitis. The fever lasts for a day or
two. The rash appears during the fever which is
maculopapular in type and lasts for about a week. Orchitis
may occur. A petechial rash or a vesicular eruption with
crust formation may occasionally be seen with type-9.
Coxsackie viruses especially of group-A cause
herpangina, aseptic meningitis, hepatitis, myopericarditis and
cutaneous eruptions. However, coxasackievirus-16 may
produce febrileness, hepatitis and cutaneous vesicular
eruption on the hands and feet (hand foot and mouth disease).
Others
• Exanthem subitum (Roseola Infantum): It is seen in
children below two years and present as high pronounced
fever lasting for four days. Then temperature drops to
37°C. Face is usually involved. A maculopapular rash
appears on the trunk and extends on to the thighs. The
rash lasts for about a day or two.
• Erythema Infectiosum: It commences as low grade fever
with red flush cheeks. A maculopapular rash with a
confluent tendency may be distributed over the
extremities and trunk on the next day or so. The rash
lasts for a week fading at the centre of the eruption
leaving behind lace like appearance or may show a
waxing and waning character persisting for several
weeks.
 Rashes
• Infectious mononucleosis: It is characterised by fever,
sore throat, lymphadenopathy, maculopapular rash. The
fever is prolonged. The rash which is erythematous,
maculopapular type appears on the trunk and extremities
during 4th to 10th day, in 50 percent of cases only. The
eruption fades before 3rd week of illness when the glands
usually appear (Refer to Chapter ‘Pyrexia of Unknown
Origin’).
• HIV: Acute seroconversion illness presents as fever,
maculopapular rash, myalgia, lymphadenopathy.
(Refer appendix IV)
Bacterial
Streptococcus: Group-A (Scarlet fever) The erythrogenic strain
of the Group-A haemolytic Streptococci produce a specific
exotoxin responsible for the rash, which occurs on the
second day of fever. The eruption consists of generalised
punctate erythema with pinpoint macules which blanch
on pressure. It appears first behind the ears and spreads
on to the trunk, neck and extremities, which is most
intense in the flexures of the arms and legs. The rash fades
in about one week and the subsequent desquamation is a
prolonged process. Inflammation of the fauces with
tonsillitis, tender lymphadenopathy and “strawberry tongue”
(initially furred with red papillae resembling unriped
strawberry and subsequent disappearance of furr leaving
the red papillae appear like a ripe strawberry), are the
associated features.
Erysipelas is a red spreading patch due to local
inflammation of the skin and oedema of subcutaneous tissue
caused by haemolytic streptococci (superficial cellulitis).
Vesicles and bullae may form.
Staphylococcal infection Staphylococcus aurerus infections
also produce erythema and subsequent development of
bullae.
Tuberculosis Tuberculosis of the skin may be (i) localised
(lupus vulgaris, lupus verrucosus, scrofuloderma,
tuberculosis cutis) and (ii) disseminated (tuberculides,
erythema nodosum, papulonecrotic tuberculosis). Erythema
nodosum starts with constitutional disturbances like fever
and body pains with painful nodules on the pretibial surface
of the legs and forearms. They appear in crops bilaterally
and present as red tender nodular swellings. In 6 to 8 weeks
time, they clear spontaneously leaving behind an appearance
of a contusion. They never ulcerate or undergo induration.
The lesions are due to hypersensitivity reactions of the
subcutaneous vessels. The other sensitizing causes are
487
streptococcal infections, Hansen’s disease, mycotic
infections and occasionally drugs.
Papulonecrotic tuberculosis is not common and may
appear as discrete papulo-nodular lesions on the extensor
aspect of the forearms, legs, back of the hands and feet.
They undergo necrosis and ulceration and heal with pitted
scarring.
In some cases of acute generalised miliary tuberculosis,
there may be cutaneous lesions of maculopapular type, or
papular lesions (which undergo necrosis and ulcer
formation). It is caused by Mycobacterium tuberculosis.
Hansen’s disease
It is usually classified as:
a. Stable
i. With high resistance (tuberculoid)
ii. With low resistance (lepromatous)
b. Unstable (borderline): Borderline lepromatous,
borderline tuberculoid, indeterminate maculoan-
aesthetic or polyneuritic).
The reactions in leprosy (lepra reaction) may be acute,
accompanied by fever with exacerbation of existing lesions.
The nerves become swollen with tenderness and neuralgic
pains. Multiple macules or nodules surrounded by oedema
appear on the body at the same time (erythema nodosum
leprosum). In some cases, subcutaneous tender nodules
may form. The nodules become pustular, break up with
ulceration and scar formation. In extreme cases, these form
bullae and ulcerative lesions (lucio phenomena) leaving
behind thin angular scars. This may last for few days and
occasionally prolonged for weeks or months. The
desquamating epithelium covers the lesions as and when
the reaction subsides. The other manifestations include
arthritis, orchitis, lymphadenitis, neuritis and iritis. The
reaction may be triggered during treatment per se due to
increased drug concentration in the tissues or any intercurrent
infection. It is caused by Mycobacterium leprae.
Typhoid fever It is characterised by fever of continuous type
with relative bradycardia. The tongue is centrally coated,
sparing the margins and the tremulousness may be obvious.
The rash consists of pale pink slightly raised spots (rose
spots) distributed over the abdomen, back and sides of the
trunk, which are probably due to capillary seeding of bacteria
into capillaries. They appear at the end of the first week and
fade in about 3 to 4 days, leaving behind a transient brownish
stain. The rash is usually scanty and is uncommon. Enlarged
liver and spleen are the other classical presentations. The
diagnosis is confirmed by widal reaction and positive culture
for Salmonella typhi.
 488 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Gonorrhoea Gonococcal infection may take a diseeminated
turn when it is characterised by fever, asymmetrical arthritis
and cutaneous lesions which consist of papular or petechial
or pustular necrotic lesions on the distal portions of the
extremities. The organisms may be demonstrated from the
skin lesion (Refer to Chapter ‘Polyarthritis’).
Meningococcal meningitis Meningococcal infections usually
herald with fever, headache, vomiting followed by meningitis.
The rash may be macular eruption or rose spots or petechial
rash distributed over the distal extremities, axillae and flanks.
The eruptions occur during the first week. These petechial
or purpuric eruptions are widespread and may be associated
with shock due to haemorrhage into adrenal cortex
(Waterhouse-Friedrichsen’s syndrome. The skin lesions
slough during recovery process. The demonstration of
meningococci in CSF or blood culture is diagnostic.
Chlamydial: Psittacosis
Chlamydia psittaci causes psittacosis (contacted from
parrots) or ornithosis (pigeons) wherein low grade fever,
myalgia and pneumonia are the main features. Macular rash,
like rose spots of typhoid fever, may be present (Horder’s
spots). A rising titre of antibody is diagnostic.
Spirochaetal
Leutic infection The rash is seen in secondary stage which
usually occurs 4 to 8 weeks after the primary genital sore.
It may be macular or papular affecting the trunk, extremities,
palms and soles. It is bilaterally symmetrical, discrete and
coppery in colour with pleomorphic character. Itching is
strikingly absent and on palpation, the papules feel indurated.
They may be seen arranged in circles over the hair margins
on the face. The lesions may become papulo-squamous
with scaly formation or papulo pustular with central necrotic
spot or whole papule may break and pustule may from with
subsequent crust formation. Vesicles are never formed. The
lesions over the palms and soles may undergo pigmentary
changes. Fever and malaise may develop when the rash
appears. The other manifestations are adenitis, mucous
patches (round greyish white patch over lips and fauces
with subsequent formation of snail track ulcers or any other
mucous membranes like nose or genitalia), bone pains, acute
iridocyclitis and occasionally joint swelling. The rash may
last for about three weeks and take another three weeks to
decline. It is caused by Treponema pallidum. This entity is
uncommon now.
Rat-bite fever A relapsing type of fever with febrile periods
of about four days alternating with afebrile periods of same
duration followed by the bite of a rat due to Spirillum minus
and Streptobacillus moniliformis. The rash occurs after 1
to 3 days of fever. It is macular or papular, purplish or
brownish in colour and distributed over the extremities
predominantly.
Leptospirosis (Weil’s disease) It is caused by Leptospira
icterohaemorrhagiae and spreads by contact with urine of
the infected rats. Leptospira survive for months in swimming
pools and damp soil. The entry is through abrasion of skin
or respiratory tract or GI tract. In the first stage, the
constitutional symptoms like severe headache, muscle pains,
and chills are followed by high temperature. The rash may
be maculopapular or papular or purpuric, distributed over
the trunk. Other manifestations are jaundice,
hepatosplenomegaly, lymphadenopathy, haemorrhages like
haemoptysis, meningitis, myocarditis and renal involvement.
Fever subsides by lysis on the 12th day with the
disappearance of jaundice. It may recur on the 16th day
and lasts for 2 to 3 weeks. The diagnosis is confirmed by
demonstrating spirochaetes in the blood in the first week
and urine in the 2nd and 3rd weeks. The agglutination test
is positive, if the titre is above 1 in 300 or a rising titre.
Leptospira Canicola causes aseptic meningitis (Canicola
fever).
Rickettsial
Spotted fevers
• Rocky mountain spotted fever: It is caused by Rickettsia
rickettsii transmitted by ticks and characterised by
sudden onset of fever (which lasts for 2 to 3 weeks)
with chills and headache. On the 4th day of illness, the
rash appears on the wrists, palms, forearms, ankles and
soles extending centrifugally. Rash is macular or
maculopapular. Brownish discolouration may persist for
several weeks over the site of rash. In severe cases,
rash may be ecchymotic and subsequently form indolent
ulcers. Seizures and athetoid movements may occur with
or without coma. Hypotension and cyanosis are
common. A feeble Weil-Felix reaction occurs with
proteus vulgaris OX19 and OX2.
• Rickettsialpox: It is caused by Rickettsial akari and
transmitted by mites. After the initial lesion of the mite
bite, (which starts as an erythematous patch developing
into a vesicle with a central eschar) fever starts after 3
to 7 days and lasts for about 1 to 7 days. The skin rash
appears on the second day over the body sparing palms
and soles, in the form of maculopapular and vesicular at
a later stage. Subsequently the vesicles dry with scab
 Rashes
formation and scaling, leaving behind pigmentary spots.
Weil-Felix reaction is negative.
Epidemic typhus: It is caused by Rickettsia prowazeki and
transmitted by louse. It is characterised by fever (which
lasts for 14 days) headache, chills and the rash appears on
the 5th day of fever. The rash is macular type starting in the
axillary region and spreading into the trunk and limbs. It
may become petechial and confluent. There may be browny
desquamation towards the end of the 3rd week. The strongly
positive Weil-Felix reaction to OX19 strain of proteus, with
negative agglutination to OXK and OX2 antigens, (especially
rising titre) is diagnostic (1 in 200 to 1 in 500).
Endemic typhus: It is caused by Rickettsia mooseri
transmitted by rat flea. It resembles the epidemic typhus
fever but is milder. The rash is macular type turning
maculopapular unlike epidemic typhus where it remains
macular only, and petechiae are uncommon. Serology is
also as for epidemic typhus.
Fungal
Cryptococcosis (Torulosis): It is caused by encapsulated,
budding yeast like fungus, cryptococcus neoformans, by
inhalation. The characteristic clinical manifestations are
meningoencephalitis and granulomatous inflammation of the
lungs, with consolidation or cavitation or pleural effusion
rarely. The rash is uncommon and is in the form of few
tiny papular lesions which enlarge slowly and soften in the
centre forming ulcers. Demonstration of the organism on
an Indian ink staining either in the CSF or sputum and by
skin biopsy is diagnostic.
Parasitic
Toxoplasmosis: It is caused by intracellular protozoan, i.e.
Toxoplasma gondii which exists in three forms during its
life cycle (a) trophozoites (invasive); (b) cysts (animal
tissues ingested); (c) oocysts (cats). The mode of
transmission may be transplacental by an infected mother
(congenital) or acquired by ingestion of oocysts from
infected cat faeces or cysts from animal tissues (beef, pork,
lamb) when the trophozoites are liberated and invade (oral)
or through blood transfusions (parenteral). The acquired
variety may present as acute febrile episode with generalised
maculopapular rash sparing the palms and soles like typhus
fever.
There may be disseminated myositis, pneumonitis,
encephalitis and myocarditis. There is enlargement of lymph
glands, specially cervical nodes are usually discrete, firm
and tender. The congenital variety is characterised by fever,
489
jaundice, choroidoretinitis and meningoencephalitis. Purpura
may occur infrequently.
Diagnosis is confirmed by (i) rising titre values over
three weeks even up to 1 in 1000; (ii) identification of
organisms (a) by isolating toxoplasma in mice inoculated
with blood or CSF; (b) demonstration of trophozoites in
tissue sections, or bone marrow aspirate or in body fluids
like CSF.
Trypanosomiasis (Chagas’ disease) South American
trypanosomiasis is caused by a protozoan Trypanosomia
cruzi. The infection is transmitted to humans by reduvid
bugs. The flagellated organism is ingested by the bug while
biting. After multiplication, they are discharged in the faeces.
The infection is supposed to occur through contamination
of the bite wound with faeces. It is characterised by fever,
lymphadenopathy, facial oedema and hepatosplenomegaly.
After the primary lesion of chagoma formed at the site of
inoculation of the organisms, morbiliform rash may occur
in the acute phase over the chest and abdomen without
itching and fades within 7 to 10 days. Myocarditis
(congestive cardiomyopathy) is common whereas
meningoencephalitis is rare. There may be gastrointestinal
sequelae like megacolon or megaoesophagus. The diagnosis
is established by demonstrating trypanosomes in the wet
and stained blood films or CSF or lymphnode aspirate.
African Trypanosomiasis caused by T. Gambiense or
T. Rhodesiense transmitted by tsetse fly is characterised by
fever, lymphadenopathy (posteior cervical) oedema,
subcutaneous chanare and erythematons rash over trunk.
Later CNS features develop (sleeping sickness). Organisms
demonstrated in blood, lymph gland or CSF.
Malaria In the recent times, infection with Plasmodium vivax
transmitted by anopheles mosquito presents as urticaria or
papular urticarial rash with high fever and rigors. The rigor
(cold stage) is preceded by steadily rising fever and coincides
with escaping of parasites into the blood by rupture of host
red blood cells (merozites). This stage may lasts for 15 min
to 1 hour. The second stage consists of (hot stage) high
fever when the parasites invade new red cells and fever
lasts for 6 to 10 hours. The last stage (wet stage) consists
of profuse sweating which lasts about two hours when the
fever rapidly subsides. This typical clinical picture with
splenomegaly is highly suggestive of malaria and
demonstration of malarial parasites in the peripheral blood
smear and Q.B.C. or rapid tests confirms the diagnosis.
Untreated cases may run prolonged courses.
Filariasis Early clinical manifestations are allergic in nature
and consist of urticaria or papular urticarial rash with or
 490 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
without recurrent low grade febrile episodes. It may be
associated with lymphangitis and lymphadenitis. The
diagnosis is confirmed by demonstration of microfilaria in
the blood and Q.B.C. for microfilaria. It is caused by either
Wuchereria bancrofti or W. malayi (refer to Chapter
Polyarthritis).
Other Parasites
Though parasitic infetions like onchocerciasis,
schistosomiasis and larva are also associated with rashes,
they are not associatd with febrile episodes. (Refer to
Chpater Pruritus.)
Immunologic
Hypersensitivity (Cell Mediated Immunity)
• Erythema Nodosum: Red lender nodules on the legs and
occasionally forearms appear due to hypersensitivity
resulting in inflammation of the vessel walls. (Vide supra-
Tuberculosis and Hansen’s disease).
• Erythema Multiforme: The onset is acute with fever
and well defined maculo-erythematous lesions with
symmetrical distribution on the distal parts of the
extremities including palms and soles, and face. The
mucosa of the mouth and genitalia may also be involved.
The lesions become indurated. The central area of the
circular lesion is paler than the periphery and may contain
a bulla (iris or target lesion). The lesions may be
polymorphic (maculo-erythematous, papulo-vesicular,
bullous and haemorrhagic) with or without itching. The
term multiforme signifies these different lesions. The
cutaneous lesions end in fissures and scales followed
by peeling, whereas the mucosal lesions may ulcerate.
The other associated features are fever, arthritis and
albuminuria. The lesions are due to lymphocytic
inflammatory infiltration around the dilated dermal blood
vessels and are related to infections like haemolyticus
streptococcus, mycoplasma pneumonia, herpes simplex,
or drugs like penicillin and sulphonamides. The eruptions
usually last for about 2 to 3 weeks and recurrences are
common.
• Stevens-Johnson Syndrome: It is an acute fulminating
type of erythema multiforme, characterised by extensive
bullous eruptions of the skin, oral cavity, conjunctiva
and cornea of the eye, which may rupture and form an
inflammatory area leading to pannus and blindness even.
It may be accompanied by fever and prostration.
Tracheobronchial mucosa may be involved leading to
respiratory infection and atelectasis. The prognosis is
bad and may prove fatal, especially with associated
visceral involvement.
• Behcet’s Syndrome (Refer to Chapter ‘Polyarthritis’).
• Lyell’s Syndrome: Lyell’s syndrome or toxic epidermal
necrosis is characterised by acute onset, severe
constitutional symptoms, flaccid bullae, epidermal
suppuration and a positive Nikolsky’s sign (superficial
detachment of the epidermis after light pressure on the
skin). It may be due to untoward effects of the drugs
like penicillin or sulphonamides or barbiturates or due to
bacterial toxins like staphylococci.
• Angio-immunoblastic Lymphadenopathy with
Dysproteinaemia (AILD) (Refer to Chapter Pruritus.)
• Henoch-Schönlein Purpura (Refer to Chapter Bleeding
Disorders,)
• Autoimmunity (Antibody Mediated or Humoral
Immunity)
• Polyarteritis Nodosa (Refer to Chapter Polyarthritis.)
• Rheumatic Fever (Refer to Chapter Polyarthritis.)
HLA Related Diseases
(Genetic Components Involved in Autoimmunity)
• Systemic Lupus Erythematosus (Refer to Chapter
Polyarthritis.)
• Pemphigus Vulgaris
It is characterised by an insidious onset of bullae in crops.
The lesions appear on the oral mucosa and/or over the skin
of the limbs and trunk. They are painful and mostly seen at
the sites of pressure and trauma and become rapidly erosive.
The intervening skin is normal. Severe constitutional
disturbances may be present. Sliding pressure with the
thumb, over unaffected skin, causes easy separation of the
epidermis (Nikolsky’s sign). This is demonstrated by another
way (vide infra).
The diagnosis is further confirmed by Tzanck’s test (a
smear is taken from the base of the bulla and stained with
Giemsa’s stain and the appearance of disruption of epidermal
intercellular connections is unique—acantholysis).
There is an association with HLA (Human Leukocyte
Antigen) system or Major histocompatibility complex (MHC)
and 95 percent of the patients are positive for HLA DR4.
(The MHC is located on the short arm of chromosome 6.)
IgG deposits, present on the surface of the keratinocytes
in the epidermis, are derived from circulating autoantibodies.
This is to be differentiated from other bullous lesions
such as pemphigoid, wherein the lesions are in the dermis
and the bullae are not easily broken. It is diagnosed by the
 Rashes 491

absence of (i) mucosal ulcerations (ii) acantholysis and (iii) The causes of macular eruptions are:
Nikolsky’s sign and (iv) constitutional disturbances. a. Exanthemata: Measles (first disease), scarlet fever
(second disease), rubella (third disease), Duke’s
Tumours disease (fourth disease of historical interest and in
retrospect appears an expression of viral disease),
Glucagonoma (Glucagon Secreting Tumour)
erythema infectiosum (fifth disease), exanthem
This tumour of pancreatic alpha cells, seen in late middle subitum or roseola infantum (sixth disease); varicella
age presents as diabetes mellitus, intermittent diarrhoea, (chickenpox) and variola (smallpox).
anaemia, stomatitis and weight loss besides erythema,
b. Drug reaction
migrating outwards from the perineum with blisters healing
c. Lupus erythematosus
centrally. The lesions may spread on to the lower abdomen.
d. Erythema multiforme
The diagnosis is confirmed by raised plasma glucagon levels.
e. Vasculitis (Purpuric—dark red)
f. Tuberculoid Hansen
Drug Eruptions
g. Tinea versicolor
Drug eruptions are cutaneous eruptions resulting from a h. Vitiligo
systematic use of the drug and not by topical application. i. Post-inflammatory hyperpigmentation (pigmented)
Usually it is bilaterally symmetrical and may be generalised j. Sun-induced (pigmented).
except in fixed drug eruption. The type of rash may be N.B. a to e — Erythematous (Red)
morbilliform, scarlatiniform; urticarial, vesiculo-bullous, f to h — Discoloured (depigmented)
erythema multiforme. Sometimes, other features like I to J — Pigmented.
arthritis, jaundice, and blood dyscrasias may be associated 2. Papules
(Refer to Chapter Pruritus). These may be (i) of any colour (red or yellow or white);
(ii) localised or generalised; or (iii) of epidermal or dermal
Idiopathic Causes origin (vide supra).
Mucocutaneous Lymph Node Syndrome (Kawasaki’s The causes of papules or eruptions passing through
Disease) papular stage are:
It is usually seen in children manifesting as fever, a. Exanthemata: Chickenpox and smallpox (pink or skin
conjunctivitis, cervical adenitis with maculo erythematous coloured)
rash over the limbs between 3rd to 5th day of fever. b. Acne vulgaris (red or skin coloured with a black
Desquamation of the eruptions starts after one week. dot, i.e. comedo)
Arthritis, hepatitis, myocarditis, meningitis may also occur. c. Eczema (red or brown)
ESR and C-reactive protein are elevated. d. Erythema multiforme (red)
e. Erythema nodosum (red)
CLINICAL APPROACH f. Scabies (skin coloured)
g. Lichen planus (violaceous)
The striking similarity of cutaneous eruptions, looking alike h. Pityriasis rosea (fawn)
in many clinical situations of different origin, calls for a i. Cutaneous tuberculosis (reddish brown)
diligent approach, to interpret the correct morphology of j. Secondary leutic stage: Lues (copper red)
the lesion and the disorder. So one should get an insight of
k. Adenoma sebaceum (yellow)
the (i) type of rash (macules, etc.); (ii) colour; (iii) time of
l. Urticaria (pink or white surrounded by red flare)
appearance; (iv) distribution; (v) evolution of lesions; and
m. Molluscum contagiosum (white)
(vi) possible causes of different types of eruptions.
3. Maculopapules
(i) Exanthemata (vide supra); (ii) adenoviruses;
Differential Diagnosis of Eruptions
(iii) arbovirus (dengue); (iv) enteroviruses (echo
1. Macules and coxsackie); (v) infectious mononucleosis; (vi)
These may be (i) of any colour (erythematous, purpuric rickettsial diseases; (vii) drug eruptions; (viii) poly-
and discoloured or depigmented); (ii) localised or morphous light eruptions; (ix) erythema marginatum;
generalised; or (iii) arise from epidermis (vide supra). and (x) erythema multiforme.
 492 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

4. Vesicles g. Exanthemata
Vesicles which are moist lesions may be (i) transparent;
(ii) localised or generalised; (iii) discrete or grouped; or
(iv) occur within or beneath epidermis (vide supra).
The causes of vesicles or eruptions passing through
vesicular stage are:
a. Miliaria and sudamina
i. Smallpox
ii. Chickenpox.
h. Rickettsial pox
i. Pustular psoriasis
j. Drug eruptions
} Generalised

}
k. Behcet’s syndrome.
b. Eczema 7. Weals
c. Contact dermatitis Localised These are flat-topped solid elevations which are
d. Herpes simplex and zoster characteristic of urticaria. They are reddish initially or
e. Tinea corporis or circinata whitish surrounded by a red flare; localised or
f. Pompholyx generalised; evanescent due to focal oedema of the upper
layer of the dermis, consequent to dilatation and
g. Exanthemata varicella
h. Scabies
i. Dermatitis herpetiformis
} Generalised permeability of cutaneous capillaries. If the deeper
vessels are involved, subcutaneous angio oedema occurs
(vide supra). Weals are of four varieties (i) spontaneous
N.B. a to f - localised wealing (urticaria and angioneurotic oedema); (ii)
g to j - Generalised provoked wealing (dermographism); (iii) followed by
j. Drug eruptions papules (insect bites) and (iv) associated with painless
5. Bullae or Blebs swellings (loiasis) (refer to Chapter Pruritus).
Bullae or blebs possess the same characteristics as the The causes of weals are:
vesicle (both in contents and origin) but larger in size. a. Dermographism
The causes of bullae are b. Insect bites
a. Trauma (friction, chemical, thermal) c. Physiological response to caning (Localised area a to e)
b. Insect bites d. Angioneurotic oedema (giant urticaria)
e. Urticaria
c. Dermatitis artefacta (Localised are a to f)
d. Foxed drug eruptions
e. Bullous impetigo and toxic epidermal necrolysis
(Lyell’s syndrome)
f. Drug allergy
g. Food allergy
h. Parasitic infestations
} Generalised

8. Petechiae and Purpura

f. Epidermolysis bullosa Purpuric eruptions arise in the dermis. They may be macular
g. Porphyria cutanea retarda (a) without inflammation, i.e. tiny (petechiae) or extensive
h. Pemphigus vulgaris
i. Bullous pemphigoid
j. Erythema multiforme
k. Dermatitis herpetiformis
6. Pustules
} Generalised
macules (ecchymoses) and (b) palpable (papular) with
inflammation. This type of eruption demands immediate
enquiry for its cause (refer to Chapter Bleeding Disorders).
The causes of purpuric eruptions are:
a. Infections (subacute bacterial endocarditis, Echo and
They may develop from vesicles (which become purulent coxsackie viruses, Rickettsial diseases) and viral
due to secondary infection) or from papules. The colour haemorrhagic fevers
varies from yellow or cream or green. They may be b. Idiopathic thrombocytopenic purpura
localised or generalised and arise on the normal skin or c. Allergic vasculitis
in the hair follicles or around sweat pores (vide supra). d. Drug hypersensitivity
The causes of pustules are: Hence a rational approach to the diagnosis of an eruption
with or without fever, is obtaining
a. Folliculitis
1. Proper dermatological history along with history of
b. Furunculosis (boils or perifollicular abscesses
present illness, past history and personal/family
c. Pyoderma (impetigo) (Localised are a to f) history;
d. Pustular miliaria 2. Examination of the skin in good light (preferably by
e. Pustular acne hand lens) supported by systemic examination in
f. Dermatophyte (pustular ringworm) general; and
 Rashes
3. Supporting laboratory aids, intradermal tests (patch
as well as biological) and histological studies if
necessary.
History
Dermatological history of:
a. Use of drugs
b. Occupation for any chemical sensitization
c. Any extramarital exposure
d. Evolution of the eruptions (i) the day of appearance of
the rash after febrile episode (as it is distinctive for
different diseases), (ii) whether the rash and fever are
associated with orderly evolution like maculo-papular,
vesicular, pustular or all types of lesions exist in any one
area (iii) whether vesicles and bullae have appeared
without macules and papules, (iv) whether the rash is
appearing all at one time or in crops and (v) manner of
spread
e. Whether itching is associated or not?
f. Any accompanying constitutional symptoms?
g. Any dietary aberrations or emotional upsets?
h. Whether same type of illness is experienced by other
members of the family?
Physical Examination
Dermatological Examination
This offers more valuable information than history, and a
spot (instant) diagnosis is possible in the majority of cases.
1. Inspection (preferably with a hand lens)
a. Skin
i. Survey the skin from head to foot.
ii. Interpretation of the morphology of different
lesions and their characteristics.
iii. Distribution of the eruption, exact anatomical
location and whether symmetrical or
asymmetrical (confined to one site) or follow a
dermatome distribution.
iv. Compare the fresh lesions with the older lesions.
v. Progression of lesion: Whether cutaneous
eruption is modified from primary lesion to super
added secondary lesions?
vi. Whether contiguous area of the skin like nails,
hair, mucocutaneous junctions are also involved?
b. Oral cavity for any lesions (exanthemata)
c. Genitalia for any lesions
2. Palpation by hand and if necessary by blunt probe
a. Consistency: Smooth or rough, dry and firm or moist
and soft
493
b. Any tenderness
c. Any secondary changes like induration or infiltration,
etc
d. Finger pressure
i. Whether the maculo-papular lesions disappear on
pressure (erythema) or persist (purpura)?
ii. Whether the light pressure over the bullae enlarge
it?
iii. Whether the integument is easily detachable when
pressure is applied over uninvolved skin.
iv. Whether the skin is elastic or not? (Skin is elastic,
if it flattens immediately after pinching and
releasing.)
v. Any pitting oedema (recognised by formation of
a pit after pressure for about 20 s over the skin
and subcutaneous tissue preferably against
underlying bone). Pitting may not be seen if the
oedema is long standing and due to lymphatic
obstruction or myxoedema.
e. Transillumination: To assess the nature and extent
of the eruption precisely.
f. Diascopy: It consists of study of lesions by applying
pressure with a clear glass slide which drains away
the blood from the lesions. (If the redness of the
macule is due to erythema consequent to dilatation
of capillaries, it turns pale on pressure whereas
purpura due to extravasated blood does not turn
pale).
g. If necessary the contents of the lesion can be
identified by aspirating with a needle.
h. Nikolsky’s sign: If an intact bulla can be moved along
in the skin, by pushing it with one thumb while the
other hand anchors the adjacent skin, it is said to be
positive as seen in pemphigus. However it is negative
in erythema multiforme and dermatitis herpetiformis.
General Examination
a. Toxic or not?
b. Type of temperature chart.
c. Temperature: Pulse ratio, and respiratory rate.
d. Record blood pressure.
e. Any lymphadenopathy.
Systemic Examination (Necessary if systemic disease is
suspected.)
a. Chest
i. Heart: Intensity and duration of the heart sounds and
any murmurs.
ii. Lungs: character of breath sounds and
accompaniments.
b. Abdomen: Any organomegaly.
 494 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
c. Neurological: Particularly sensory system.
d. Locomotor system: Any involvement of the joint; if so,
mono or polyarticular?
Investigations
Generally dermatological diagnosis is more sound, on
physical examination only supported by history, rather than
by the investigations.
Special Investigations
1. Wood’s Lamp Examination
It consists of mercury vapour lamp with a special filter
made up of nickel oxide and silica. When the long wave
ultraviolet passes through the filter and impinges on the
skin, a fluorescence is produced at 360 nm. The different
colours of fluorescence light are characteristic of
different dermatological conditions. It is particularly
relevant in eruptive fevers when associated with
infections like Pseudomonas when a greenish white
colour is appreciated.
2. Microscopic Examination
i. Oil mount preparation of skin scraping of an itchy
papule with burrows for identifying scabies mite.
ii. Scrapings of roof of the vesicle are snipped to
differentiate the bullae by the presence of pemphigus
cell.
iii. Tzanck smear test for herpetic vesicle (refer to
Chapter Pruritus).
iv. Obtain a smear from the pustule or bulla and stain
appropriately (Gram’s stain) for the evidence of
bacteria.
v. Dark-field examination of the material from the ulcers
of genitalia may show Treponema pallidum.
vi. Scrapings of scales for dermatophyte infections by
potassium hyroxide preparation to identify the hyphae
especially in the cellular area which appear as
branching refracted threads (material plced in a drop
of 10 to 20 percent of aqueous KOH and examined
after 30 min). In addition, 10 percent KOH
preparation is usual for demonstrating molluscum
bodies.
vii. Skin biopsy: The exact diagnosis of uncertain dermal
lesions is established by histological examination.
viii.Direct immunofluorescence detects abnormal
deposits of immunoglobulins and complement in the
biopsied tissue.
ix. Blister fluid for macromolecules which are
anticomplementary, i.e. low complement.
3. Microbiological Studies (Refer to Chapter ‘Pyrexia of
Unknown Origin’).
i. Bacterial cultures
a. Material from pustules or bullae obtained for
culture.
b. Crusts, if present, are removed and the underlying
exudate can be swabbed for culture.
c. Skin biopsy specimen cultured, if necessary.
ii. Fungal cultures: In superficial infections, scales are
scraped from the lesions and the systemic fungal
infections involving the skin, tissue is obtained from
the border of the lesion by punch biopsy and cultured
to establish the implicating species of fungus
(Sabouraud’s Glucose-agar or Beerwort-agar
medium).
iii. Viral cultures: If necessary, at specialised centres.
4. Test for Allergy (Refer to Chapter ‘Pruritus’)
5. Blood Tests (Refer to Chapter ‘Pyrexia of Unknown
Origin’).
i. Blood counts and ESR
ii. Serological (a) VDRL (leutic infections) (b) Weil-
Felix (Rickettsial diseases) (c) Complement fixation
(viral and Rickettsial infections) (a) HIV
iii. Staining blood films for haemoparasites
iv. LE cell and anti-nuclear antibodies. (Refer to Chapter
‘Polyarthritis’).
v. Antistreptolysin titre: (Refer to Chapter ‘Polyarthritis’)
vi. Serum antibody studies: IgG antibody present in
pemphigus
vii. Bleeding/Clotting profile (if necessary).
Appropriate investigations may be considered and tailored
to confirm a clinical suspicion or process the available data
so as to decipher whether the rash is of systemic origin or
dermatological per se, and arrive at an exact diagnosis.
TREATMENT OF RASHES
The primary effort of the clinician is to interpret correctly
the specific type of rash, arising from epidermis and
subepidermal region (primary lesions like macules, papules,
vesicles, pustules, bullae) or arising from dermis without
epidermal change (lesions like erythema, vasculitis, weal
and petechiae); aided by the day of its appearance along
with plethora of clinical signs, before considering the
therapeutic options. Determining the underlying cause calls
for clinical skill, since the eruptions are common to many
etiologic agents (microbial, parasitic, autoimmune and drugs)
though some are unique in its presentation to a particular
 Rashes
microbe. The therapeutic approach becomes easier, if one
realises that an infinite variety of types of drug reactions
are devoid of prodromal symptoms and signs usually.
Symptomatic Treatment
Infectious rashes need more supportive care than
noninfectious rashes.
1. Prevent itching with antipruritic agents.
2. Use dusting powder over the rashes to allay irritation.
3. Mouth washes are helpful for oral lesions.
4. Associated fevers with rashes need
a. Isolation and rest.
b. Good nursing care, tepid sponging and hygiene of
the eyes, ears and skin.
c. Antipyretics in hyperpyrexia.
d. Optimum calories: Nutritious, easily digestible diet
to reduce the work of internal organs. Rough diet is
avoided in cases of exanthemata.
e. Fluids: Fluid balance maintained.
5. Other accompanying symptoms like sleeplessness,
cough, vomiting etc., may be appropriately treated.
Specific Treatment for Specific Diseases
Infections
Viral
• Varicells: The treatment is symptomatic and supportive.
Antiviral agents like vidarabine or acyclovir are useful in
severe cases of immunocompromised patients, during first
five days. Secondary bacterial infections and other
complications treated accordingly. Aspirin should not be
used as it may precipitate Reye’s syndrome.
Hyperimmune zoster gamma globulin may prevent it, if
administered within seven days of exposure. It can be
prevented by administering chicken pox vaccine.
• Variola: It is eradicated totally. If a case is suspected,
bring it to the notice of the public Health Authority.
• Vaccinia Generalised vaccinia and eczema vaccinatum
is treated with vaccinia immune globulin (0.5 ml/kg i.m.),
methisazone is effective in some cases of progressive
vaccinia. Secondary infection may be treated with
antibiotics.
• Measles The treatment is symptomatic and supportive.
Secondary bacterial infection of the lungs is treated by
appropriate antibiotics. It is effectively prevented
through immunisation, between 9-12 months of age.
• Rubella The treatment is symptomatic and supportive.
It is prevented through immunisation. If the infection is
495
confirmed during early pregnancy, medical termination
is advised to prevent intrauterine hazards.
• Herpes zoster Analgesics are beneficial. Prednisolone
40 mg/d with declining doses later, is considered.
Vidarabine may aid cutaneous healing and relieve the
pain apart from shortening the course of disease. In
immunocompromised patients, acyclovir (15 mg/kg
daily IV over 12 h or 800 mg orally five times a day)
Famciclovir is an alternative given (500 mg tds)
valaciclovir is another alternative (1 gm tds) is
recommended. Local measures with dusting powder and
a dry dressing done during eruption. Calamine lotion is
often of value. Idoxuridine 4 percent relieves pain when
used topically. Atropine and topical antivirals mentioned
above are prescribed in zoster ophthalmicus.
Postzoster neuralgia is a distressing complication. It may
respond to intercostal neural block. Amitriptyline may be
helpful. Triamcinolone parenterally may give prompt relief
of the post-herpetic pain. Gabapentin is beneficial Hourly
eye drops of 0.1 per cent Idoxuridine in saline useful in eye
lesions.
• Herpes simplex (Refer to Chapter ‘Paraplegia’)
• Arboviruses The treatment is symptomatic and
supportive. Haemorrhagic episodes may need transfusion
of fresh blood and if shock arises treat it as a medical
emergency. Prevention is by implementing permanent
anti-mosquito measures and amoxycillin 500 mg b.d.
• Enteroviruses Treatment is purely symptomatic.
Complications like myocarditis due to coxsackie virus
infection is treated as for heart failure or cardiogenic
shock.
Others
• Exanthem subitum Treatment is symptomatic.
Erythema infectiosum (fifth disease) Treatment is
symptomatic.
• Infectious mononucleosis (Refer to Chapter Pyrexia of
Unknown Origin.)
• HIV (Refer to Appendix IV)
Bacterial
• Streptococcus Group-A (Scarlet fever) Prompt treatment
with benzathine penicillin G (1.2 million units as a single
dose) or procaine penicillin G (0.3 million units i.m. daily
for 10 days) or erythromycin (250 mg four times a day
for 10 days) for penicillin sensitive patients, prevents
the onset of acute rheumatic fever or glomerulonephritis.
• Staphylococcal Topical antibiotic treatment supported
by personal hygiene may suffice; otherwise systemic
therapy with cloxacillin (500 mg 4 times) platelet
 496 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
transfusions confident if the platelets are critically low.
Gamma globulin IV beneficial in some cases of Dengue
fever or erythromycin (250 mg 4 times) or ciprofloxacin
(250 mg 4 times) is indicated.
Treatment of toxic shock syndrome associated with
fever and sun burn rash is directed against shock and
renal failure, and DIC if present.
• Tuberculosis (Refer to Chapters Chronic Diarrhoea and
Haemoptysis.)
• Hansen’s disease (Chemotherapy of Hansen’s disease
depends upon the clinical type. Lepromatous type is
treated with rifampicin 600 mg along with 300 mg
clofazimine monthly and 100 mg of dapsone with 50 mg
of clofazimine daily of two years followed by dapsone
monotherapy for five years.
Tuberculoid type is treated with 600 mg of
rifampicin monthly and 100 mg of dapsone daily for six
months. It may be followed by dapsone monotherapy
for three years, if possible.
Borderline and indeterminate types are treated like
repromatous and tuberculoid respectively. Supervisory
control is necessary for monthly therapy with rifampicin
and clofazimine.
If lepra reaction occurs, withhold the treatment
and institute corticosteroids. Thalidomide is beneficial
(if not pregnant).
Apart from chemotherapy, surgery and
physiotherapy may be required in some cases.
Prevention may be facilitated by immunising children
with BCG vaccine.
Erythema nodosum leprosum (ENL) is treated with
60 mg of prednisolone daily and taper the dose over a
period of 2 to 4 weeks. Clofazimine 100 mg twice daily
for few weeks may be necessary in chronic ENL cases,
and maintain with prednisolone in tapering doses as the
former commences to act (which requires 3-4 weeks
to attain effective levels). Antipyretics and analgesics
may be administered, if necessary. Antimalarials like
chloroquine are another alternative.
Lucio phenomena is also managed with
corticosteroids.
Neuritis with or without any associated reaction
needs high doses of corticosteroids.
• Typhoid fever (Refer to Chapter Pyrexia of Unknown
Origin.)
• Gonorrhoea: Therapy of uncomplicated gonorrhoea
includes benzyl penicillin 5 million units i.m. with 1 gm
probenecid orally or amoxycillin 3 g with probenecid 1
gm orally or ceftriaxone 250 mg IM, followed by
tetracycline 0.5 g 6th hourly for one week. However,
complicated infections need cefotaxime 1 to 2 g
parenterally daily for one week or ceftriaxone 1 g iv or
IM daily for one week. Endocarditis or meningitis may
require treatment for 2 to 4 weeks. Treatment of pelvic
inflammatory disease is detailed in Chapter Acute
Abdominal Pain.
• Meningococcal Meningitis: Benzyl penicillin 12-24
million units per day for seven days is advocated. In
penicillin allergic patients, chloramphenicol (0.5 g 4 or
6 hourly) is an alternative. Recently rifampicin 600 mg/
12 h orally for two days is preferred (refer to Chapter
Headache—Pyogenic Meningitis). Associated shock, if
any, is treated with hydrocortisone.
Chlamydial: Psittacosis
Tetracycline 0.5 g 6th hourly for at least 10 days is effective.
Spirochaetal
• Leutic infection Benzathine penicillin 2.4million units as
one dose IM in early leutic infection (primary, secondary
or early latent infections) is the prescribed treatment.
Tetracycline orally 0.5 g 6 hourly for 15 days is an
alternative in penicillin allergic patients. Late latent
infection of more than one year duration requires 2.4
million units of benzathine penicillin every week for three
consecutive weeks. Tetracycline 0.5 g every six hours
orally for four weeks is the alternative. The treatment
for cardiovascular or neurological involvement is that
of acute leutic myelitis (Refer to Chapter Paraplegia).
• Rat bite fever Procaine penicillin six lac units twice daily
IM is given for 7 to 10 days. If penicillin allergy exists,
erythromycin or tetracycline 0.5 g 6 hourly is an
alternative.
• Leptospirosis (Refer to Chapter Jaundice.)
Rickettsial Diseases (Refer to Chapter Pyrexia of
Unknown Origin.)
Fungal: Crytococcosis (Torulosis) IV amphotericin B (0.3 mg/
kg/daily) along with flucytosine (150 mg/kg/daily) or
amphotericin alone (0.6 mg/kg/d) is prescribed for a period
of six weeks. Fluconazole (200-400 mg/d) or ketoconazole
(400-800 mg/d) is an alternative.
Parasitic
• Toxoplasmosis [Refer to Chapter Pyrexia of Unknown
Origin] (PUO).
• Trypanosomiasis (Chagas’ disease)
Nifurtimox (2 mg/kg/daily 6th hourly for two months)
is advocated in acute disease state. Primaquine
phosphate (26.3 mg salt) may be tried for 10 days.
 Rashes
Prevention is better by using insecticides to eliminate
the reduviid bugs. Allopurinol reduces parasitaemia
sleeping sickness: Suramin 20 mg/kg IV weekly
Melarsopral 0.4 mg/kg IV 3 d/wk for 4 wks
recommended. Chronic cases treated symptomatically.
• Malaria: Uncomplicated Plasmodium vivax, P. ovale,
P. malariae should be treated with oral Chloroquine
(600 mg followed by 300 mg after 6h, 24h, and 48h
later). If necessary, Chloroquine parenterally given (200
mg 6 hourly) and followed with oral therapy as soon as
possible (total dose 25 mg/kg) is administered. Radical
cure is obtained with primaquine (7.5 mg bd orally for
14 days) which is administered after Chloroquine to
eradicate hepatic hypnozoites and prevent relapse in
P. vivax and P. Malariae. (It is active also against
gametocytes of P. Falciparum). Bulaquine is other
alternative, uncomplicated p.falciparum infection is
treated with chloroquine (25 mg/kg every 4 hours i.m
or 10 mg/kg infusion over 8 hours followed by 15 mg/
kg over 24 hours to a total 25 mg/kg) or as in oral
regimen as above.
In chloroquine resistant cases, (pyrimethamine
(25mg) and sulfadoxine (500 mg) per tablet 3 tablets as
single dose once only, with or without quinene for five
days or quinine sulphate (600 mg t. d. s for seven days)
with doxycycline 100 mg/d or tetracycline 500 mg four
times a day for 7 days) are administered. The alternate
therapy is Mefloquine (20 mg /kg in 2 doses 8 hours
apart upto total 1. 5 g with our without artemether 80
mg for three days or atovaquone and proguanil 4 tablets
daily for 3 days or halofantrine (8 mg/kg 6 hourly for 3
doses-total upto 1.5 g) with or without artesunate.
In multidrug resistant cases, artesunate (120 mg 1st
day then 60 mg for four days IM/IV) plus tetracycline or
Clindamycin if necessary.
N.B. Drug resistance is indicated if parasitaemia has not
declined by 75 per cent after two days or not cleared after
seven days of treatment.
In complicated or severe p. falciparum infections like
cerebral malaria, quinine salt (10 mg/kg i.v infusion for 4-8
hours tds for 7 days) is administered. Oral therapy can be
started as soon as possible. Additionally tetracycline for 7
days given/pyrimethamine + sulfadoxine 3 tab stat.
In quinine resistant cases, artemesinin derivatives, like
artesunate (2 mg/kg by IV or IM on the 1st day then 1 mg
/kg daily for next four days) or orally 100 mg bd. 1st day
and 50 mg bd for next 4 days is advocated. Artemether 150
mg daily IM for 3 days is an alternative.
Symptomatic therapy and supportive therapy warranted
during management. Malarial vaccine is in offing.
497
Prevention: Personal protection from mosquito bites with
insect repellent or using mosquito nets apart from mosquito
eradication by insecticides are the strategies.
Chemoprophylaxis: one week before exposure and continued
for four weeks after exposure is advocated with chloroquine
(300 mg base weekly). In chloroquine resistant areas
mefloquine (250 mg weekly) and continued for 4 wks after
return advocated or chloroquine (300 mg weekly one week
before exposure and proguanil (200 mg daily) two days
before exposure, and continued for 4 weeks after exposure,
is another option. Alternative therapy is doxycycline (100
mg daily) two days before exposure is suggested, and
continued for four weeks after return from the malarious
areas or atovaquone and proguanil (malarone) 1 tablet daily
for 2 days before exposure upto one week after return.
• Filariasis DEC i.e. Diethylcarbamazine (2 mg/kg tds
for three weeks) is effective to eliminate the microfilariae.
Since adult worms are not fully affected, microfilarial
relapses may occur once in 3-12 months, which need
repeated courses accordingly. Concurrent administration
of an antihistamine is beneficial to prevent allergic
reactions. Ivermectin 400 mg/kg with or without
albendazole 400 mg is effective orally (Single dose).
Coexisting bacterial infection is dealt with appropriate
antibiotics. Repeated episodes ineffectively treated may
lead to elephantiasis (refer to Chapter Oedema).
Prevention is possible by effective vector control and
yearly single dose therapy with DEC and albendazole
preferally for 5 years is recommended.
Other parasites
a. Onchocerciasis: Same as filariasis.
b. Schistosomiasis: Praziquantel (Refer to Chapter ‘Weight
Loss’) is advocated.
c. Larva migrans: Cutaneous larva migrans is trated by
eliminating the strongyloides larvae with thiabendazole
(25 mg/kg bd three days) or mebandazole (100 mg bd
for three days), or albendazole (400 mg once daily for
three days).
Immunologic
Hypersensitivity (Cell Mediated Immunity)
• Erythema nodosum: It is a self-limited disease lasting
for about 3-6 weeks. General measures like bed rest,
hot or cold compresses, leg elevation, anti-inflammatory
analgesics and systemic therapy against the underlying
cause are insituted. In severe cases, intralesional
triamcinolone or prednisolone tapering over three weeks
is beneficial, unless contraindicated (vide supra).
 498 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Erythema multiforme: Local measures like wet dressing
or soothing lotions (calamine lotion) are helpful.
Antihistamines may be given for pruritus. Buccal lesions
are treated with antiseptic mouth rinses, and local
application of hydrocortisone-antibiotic ointment and
viscus lidocaine (2%), if necessary. Ocular lesions need
special ophthalmic care. Parenteral fluids may be given.
Specific measures may be directed against the underlying
cause like acyclovir for herpes simplex.
Corticosteroids may be tried though they remain
controversial. Disease subsides uneventfully in 2 to 3
weeks.
• Stevens-Johnson syndrome: Calamine lotion for the skin,
steroid drops for the eye lesions and systemic steroid
therapy may be helpful for this variant of erythema
multiforme, associated with visceral involvement
carrying a bad prognosis.
• Behcet’s syndrome (Refer to Chapter ‘Polyarthritis’)
• Lyell’s syndrome Maintain fluid and electrolyte balance
and supplement proteins. Local care with silver nitrate
(0.5%) dressings and debridement of necrotic tissue
are helpful. Secondary infection may be treated with
appropriate antibiotics. Corticosteroids in high doses may
be tried, though questionable. Any incriminated drug may
be withdrawn.
• Angio-Immunoblastic lymphadenopathy with
dysproteinaemia (AILD): The treatment is initiated with
corticosteroids. Levamisole may be combined to
stimulate T-cell function. If unresponsive, combination
chemotherapy as for lymphomas may be instituted. Local
lesions are managed with radiotherapy.
• Henoch-Schonlein purpura (Refer to Chapter ‘Bleeding
Disorders’).
Autoimmunity (Antibody mediated or humoral immunity)
• Polyarteritis nodosa (Refer chapter Polyarthritis)
• Rheumatic fever (Refer to Chapter Polyarthritis.)
HLA Related Diseases (Genetic Components Involved
in Autoimmunity)
Systemic lupus erythematosus (Refer to Chapter
‘polyarthritis’)
Pemphigus vulgaris Systemic glucocorticoids (60 mg/d to
be increased if necessary) for 2 months. The other drugs
to be considered are azathioprine (1 mg/kg) or cyclophos-
phamide (1 mg/kg) and methotrexate (25 mg/week) instead
of azathioprine.
In resistant cases, dapsone (100 mg/d) may be
beneficial. Plasmapheresis may be combined. Appropriate
supportive therapy with bed rest, anaesthetic troches,
intravenous feeding and local soothing applications may be
adopted.
Tumours
Glucagonoma: Resection is the treatment of choice.
Drug Eruptions
Refer to Chapter ‘Pruritus’.
Idiopathic
Mucocutaneous lymph node syndrome (Kawasaki’s disease)
The outcome is uneventful in most of the cases and aspirin
is advocated in both acute and recovery stages.
Rashes 499
500 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Shock
32
Acute circulatory failure occurs due to sudden reduction in
cardiac output and consequent reduction in tissue perfusion,
with impairment of vital organ system. This may be central
cardiac failure or peripheral circulatory failure. The central
cardiac failure results from inadequate cardiac filling or
emptying. The peripheral circulatory failure is a sudden
reduction in the circulating blood volume associated with
diminished venous return. The peripheral circulatory failure
is used synonymously with shock, although the clinical
picture is similar, in both central and peripheral failures.
Shock, syncope and sudden cardiovascular collapse are
forms of acute circulatory failure differing only in the rapidity
of the onset of the circulatory failure, i.e. shock is not as
sudden as syncope. Generally, there is acute hypotension
(systolic pressure <90 mm of Hg) in shock apart from cold
clammy skin, fast thready pulse, cyanosis and mental
obtundation. Any patient who develops shock may go
through three stages:
Stage-I (mild)—Compensatory mechanisms set in.
Blood pressure is normal or slightly reduced and
hypoperfusion to nonvital organs occurs, with cold skin
and tachycardia.
Stage-II (moderate)—In spite of compensatory
mechanisms, blood pressure falls and hypoperfusion of vital
organs like kidney and liver begins, with oliguria.
Stage-III (severe)—Compensatory mechanisms fail.
Blood pressure progressively falls with evidence of
hypoperfusion of vital organs especially brain and heart with
restlessness, mental torpor, cardiac irregularities and
irreversible stage.
PATHOPHYSIOLOGY OF SHOCK
The basic mechanism of shock reflect haemodynamic
defects, with circulatory stress (reversible) and cellular injury
(irreversible).
Reversible Stage
The initial disturbance of sudden fall of blood pressure, due
to fall in cardiac output or vasodilatation, accelerates the
sympathetic outflow, by activating the pressor receptors.
This leads to vasoconstriction (most marked in skin and
gut) which tries to maintain the blood pressure and
redistribute the blood by increasing the peripheral resistance.
Besides this neuromechanism, a humoral role comes into
play wherein adrenal secretions (epinephrine and
aldosterone) and pituitary secretions (ADH and ACTH)
increase along with renin secretions from the kidney and
participate in the restoration of arterial pressure and tissue
perfusion. Thus blood pressure is maintained at the cost of
hypoxia in the vasoconstricted areas.
Irreversible Stage
If this stage of vasoconstriction is prolonged, the medullary
vasomotor centre is affected with depressed vasomotor
activity, leading to vascular atony and capillary stasis. This
pooling of blood in the atonic small vessels accelerates the
already deficient venous return and diminished cardiac
output, with progressive fall of arterial pressure (Fig. 32.1).
Prolonged tissue hypoperfusion leads to microcirculatory
failure, tissue anoxia, endothelial damage, cellular membrane
dysfunction and cellular damage. Some metabolic
derangements like anoxia, hypercapnia, lactic acidosis, result
from the diminished perfusion of the tissues with indirect
effect on the energy requiring systems of the cell membrane.
There is depletion of high energy phosphates and release of
lysosomal enzymes, leading to cellular dysfunction and injury,
which results in further hypovolaemia due to loss of blood
from capillaries, precipitating irreversible shock. There is
necrosis of the gastrointestinal mucosa, decreased
myocardial contractility; tubular necrosis in the kidneys;
and generalised endothelial damage with disseminated
intravascular coagulation.
 502 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Decreased Blood Pressure results from decreased 1. Hypovolaemic Shock (Volume loss)
Venous return and fall in Cardiac Output. Hypovolaemia results from decreased volume within
The decreased tissue perfusion is not only due to the intravascular compartment due to fluid loss and
hypotension but also the decreased cardiac output in turn reduced venous return.
and microcirculatory failure further, accentuate hypoperfusion A. Loss of blood from
leading to impairment of vital organ systems (the cardiac i. Gastrointestinal bleeding (Refer to Chapter
output is reducd due to (i) decreased venous return (ii) ‘Haematemesis’).
metabolic acidosis and (iii) reduced coronary perfusion). ii. Complications of surgery
Thus, haemodynamic mechanism of shock essentially
iii. Complications of pregnancy, ectopic pregnancy
deals with:
(Refer to Chapter ‘Acute Abdominal Pain’).
1. a. Cardiac factors and
b. Vascular factors (resistance to blood flow, iv. Trauma.
microcirculation and transcapillary exchange) B. Loss of Plasma
2. Cellular injury depends upon the availability of a. Burns
substrates and oxygen to the mitochondria (ATP is b. Crush injuries
synthesised by mitochondria providing the high energy C. Loss of fluid and electrolytes from
phosphate needs of the cell and hypoxia reduces the I. GI Tract
rate of ATP synthesis). i. Vomiting
CLASSIFICATION AND CAUSES ii. Diarrhoea
iii. Acute intestinal obstruction
Shock is classified clinically as (1) hypovolaemic, (2)
distributive, (3) cardiogenic and (4) extracardiac obstructive. iv. Acute pancreatitis
The former two are essentially due to reduction in venous II. Urinary Tract
return (peripheral), whereas cardiogenic is due to primary i. Diabetic acidosis
reduction in the cardiac output (central). ii. Addison’s disease (rare)

Decreased Blood Pressure (Systolic BP mmHg < 90)

Fig. 32.1: Sequence of events in shock

 Shock
III. From the skin
Excessive sweating
Effects of heat—Heat stroke
2. Distributive (Venous Pooling)
It represents pooling of blood in small vessels without
decrease in intravascular volume, and the reduction
in the venous return is due to vasodilatation. This may
be: (i) neurogenic or (ii) vasogenic in origin (septic)
or (iii) Anaphylactic.
i. Neurogenic
a. Pain from any cause like perforation of peptic
ulcer or acute pancreatitis
b. Blow on abdomen (solar plexus) and testicle
c. Spinal injury
d. Neurogenic drugs—anaesthetics, narcotic over
dosage, psychotropic drugs
ii. Vasogenic (Infections)
a. Gram-negative septicaemia
b. Gram-positive septicaemia
c. Nonbacterial organisms
d. Toxic shock syndrome (Staphylococcus aureus
toxin).
iii. Anaphylactic Shock (Vascular Pooling and
Decreased Intravascular Volume)
This results from reduction in venous return due
to release of histaminic and consequent
vasodilatation with vascular pooling as well as
decreased intravascular volume.
a. Drugs like penicillin, local anaesthetics,
iodinated contrast diagnostic agents
b. Sera and vaccines
c. Incompatible blood transfusion (haemolytic
reaction)
d. Insect stings.
3. Cardiogenic Shock (Pump Failure)
Primary reduction in the cardiac output is due to acute
deficiency in (a) cardiac filling (pericardial effusion
with cardiac tamponade or severe tachycardias); and
(b) cardiac emptying (myocardial infarction).
a. Cardiac arrhythmias
b. Intracardiac obstruction (valvular stenosis, atrial
myxoma)
c. Myocardial infarction
d. Pericardial tamponade
e. Aortic dissection
f. Dilated cardiomyopathy/Severe congestive heart
failure (CHF)
g. Rupture of ventricular septum or ventricular wall
or ruptured aortic aneurysm
503
4. Extracardiac obstructive
i. Pulmonary embolism
ii. Tension pneumothorax
CLINICAL FEATURES OF SHOCK
The symptoms and signs are attributed to the diminished
cardiac output and the compensatory mechanisms which
ensue to retrieve the catastrophe. The decrease in blood
volume necessitates redistribution of blood essentially to
the vital organs and maintain optimum blood pressure. In
this endeavour, vasoconstriction occurs in nonvital regions
like skin and splanchnic area.
1. Appearance—may be restless or apathetic, extreme
weakness and mental torpor are variable.
2. Skin
a. Excessive sweating with pale, cold and clammy
skin (coldness and pallor marked in the hands
and feet frequently with cyanosis).
b. Superficial veins are collapsed.
3. Vital Data
a. Pulse—Rapid thread pulse
b. Blood pressure—Hypotension (systolic blood
pressure below 90 mm of Hg and also reduced
pulse pressure)
c. Respirations—Deep and rapid
d. Temperature—Usually subnormal
4. Heart—Heart sounds are feeble. The first sound is
soft probably due to low filling pressure. Cardiac
arrhythmias or features of underlying cardiac disorder
may be elicited.
5. Lungs—Evidence of pulmonary infection or embolism
may be present.
6. Abdomen—Liver may be enlarged and tender.
Auscultation of the abdomen may show either
excessive sounds (intestinal obstruction) or may
be absolutely silent (general peritonitis or intestinal
ileus.)
7. Urine—Urinary output is diminished (oliguria or
anuria), < 20 ml/hr.
8. Blood—Haemoconcentrations is due to dehydration
or haemodilution is due to haemorrhage. In addition,
characteristic physical signs of the underlying cause
of shock can also be elicited.
Complications like (i) Multiorgan failure, i.e. cardiac,
respiratory and/or renal. (ii) Gastrointestinal (iii)
Disseminated intravascular coagulation. (iv) Infections
should be looked for.
 504 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
SPECIFIC TYPES OF SHOCK
1. Hypovolaemic Shock
Loss of Blood (Vide supra)
Loss of plasma (Vide supra)
Loss of fluid and electrolytes from Gl tract
a. Vomiting (Refer to Chapter Vomiting).
b. Diarrhoea (Refer to Chapter Chronic Diarrhoea).
c. Acute intestinal obstruction (Refer to Chapter Acute
Abdominal Pain).
d. Acute pancreatitis (Refer Chapter ‘Acute Abdominal
Pain’).
Loss of fluid and electrolytes from urinary tract (a) Diabetic
Acidosis: In Diabetes mellitus, insulin insufficiency results
in certain metabolic derangements. Removal of blood
glucose is reduced by the peripheral tisues, and glycosuria
occurs (when plasma level rises above the original threshold
limits of 180 mg %). In spite of renal loss, the blood glucose
is still high by neoglucogenesis because of the excessive
amounts of glucose being released from the liver, by the
breakdown of proteins especially alanine.
Insulin deficiency affects the fat metabolism also by the
cessation lipogenesis and increased lipolysis resulting in
release of free fatty acids into circulation. The increased
free fatty acid availability leads to accumulation of acetyl
CoA (each unit of fatty acid gives rise to 8 units of acetyl
coenzyme). The accumulation of acetyl coenzymes-A due
to the mounting breakdown of fats, is disproportionately
greater than the body can utilise. Condensation of two acetyl
CoA molecules form aceto acetyl CoA, the precursor of
aceto acetate. Glucagon or change in the glucagon/insulin
ratio activates the fatty acid oxidative sequence. Thus aceto
acetic acid, and its derivatives—betahydroxy butyric acid
and acetone begin to appear in excessive amounts in the
blood, producing ketosis. This ketogenesis begets metabolic
acidosis, which perpetuates further sodium loss in the urine
(besides the excessive loss of salt together with water
already occurring in the osmotic diuresis in diabetes
mellitus). As a consequence of the acidosis and salt depletion,
the volume of extracellular fluid is diminished leading to fall
in blood pressure and glomerular filtration rate with
consequent oliguria. This shock further aggravates metabolic
acidosis, due to hypoxia of the tissues and accumulation of
organic acids.
The diagnosis can be clinched by history of missing
insulin injections, infections in a known diabetic with
dehydration, air hunger, weak pulse, low blood pressure
and ocular tension with or without coma supported by (i)
hyperglycaemia; (ii) Presence of sugar and ketone bodies
(acetone and acetoacetic acid) in the urine; (iii) low serum
bicarbonate and (iv) high free fatty acids (Refer to Chapter
Polyuria).
(b) Addison’s Disease: In Addison’s disease salt depletion
occurs due to the failure of kidney to conserve salt because
of inadequate hormonal control (due to aldosterone
deficiency and raised vasopressin). This affects primarily
the volume of extracellular fluid including the plasma,
resulting in dehydration. The decrease in the blood volume
leads to a drop in blood pressure and glomerular filtration
rate with oliguria. The hyponatraemia may also be due to
loss of sodium from the vascular compartment into tendons
and cartilage.
Weakness, weight loss, hyperpigmentation along with
low cortisol and high ACTH in plasma and decreased
production of cortisone by the adrenal, both in the basal
and stimulation states, are confirmatory. Short and prolonged
ACTH stimulation test is a further exercise. This may be
autoimmune (associated with insulin dependent diabetes
mellitus, Grave’s disease, ovarian failure) or idiopathic in
origin.
Addisonian crisis (shock) occurs in known Addison’s
disease or noncompliance of medication, while on long-
term steroids. Infection, surgery or trauma may precipitate.
Loss of fluid and electrolytes from the skin (Excessive
sweating, heat stroke) Hyperthermia (41 to 44°C) causes
tissue injury with selective thermal damage to the brain.
High humidity in the range of 60 to 80 percent is another
prerequisite. After prolonged exposure to high temperature,
homeostatis of the body fluids and electrolytes is disturbed,
till a stage when the sweat glands cease to function (sweat
fatigue).
The activation of sympathoadrenal system and the alpha
mediated effects of catecholamines impair heat dissipation.
Thus the heat regulating centre is deranged and fails to
maintain body temperature at the optimum level by cessation
of sweating. This heat stress increases intestinal permeability
and loss of mucosal integrity resulting in increased leakage
of endotoxins (lipopolysaccharides). The impaired hepatic
detoxification of endotoxins further results in high levels of
endotoxins in systemic circulation. This leads to
redistribution of blood from central to peripheral circulation
resulting in hypovolaemia, hypotension and circulatory
failure. The pre-existing salt depletion and hypohydration
due to excessive sweating, aggravate the circulatory failure
leading to hypoxia, acidosis and disseminated intravascular
coagulation.
Hyperpyrexia (even up to 44°C), dry skin, and absence
of sweating, with or without premonitory symptoms
 Shock
proceeding to impaired consciousness and convulsions,
during mid summer period with urinary chlorides below 3
g in a 24 h collection are highly diagnostic. It usually follows
exposure to high environmental temperatures or excessive
exertion under hot humid climatic conditions.
2. Distributive Type
Neurogenic Shock (Vasodilatory Shock/Vasoplegia
Syndrome)
This type of shock occurs due to vasomotor collapse leading
to reflex vasodilatation and vascular pooling especially in
the splanchnic area and reduced peripheral resistance,
without loss of fluid or blood or plasma as such. The
vasodilatation occurs predominantly in the capillaries and
small vessels (postarteriolar vessels). The fall in arterial blood
pressure due to vasodilatation, precedes reduction in the
cardiac output; Pain from perforation of peptic ulcer or
acute pancreatitis leading to shock is also based on reflex
vasodilatation due to neurogenic impulses (Refer to Chapter
Chest Pain).
Vasogenic Shock (Bacteraemic/Septicaemic)/Systemic
Inflammatory Response Syndrome (SIRS)
In this type, the release of toxins (endo/exo) affect the
vascular tone directly and facilitate vascular pooling. The
endotoxin from gram-negative organisms like E. coli is a
component of bacterial cell membrane and can also be
liberated from the dead bacteria. It is a lipopolysaccharide
with lipid A chain whose moiety is the endotoxic principle.
It causes arteriolar vasoconstriction with expanded venous
capacitance (pooling). The interaction of this moiety with
the host cell (macrophage) results in secretion of various
mediators of shock like inflammatory mediators; Platelet
activity factor (phospholipid) tumour necrosis factor
(cachetin), cytokines, activation of complement and
coagulation pathways, endogenous opiates (endorphins),
excess of nitric oxide.
All these pathophysiological steps are responsible for
the biological effects of septic shock syndrome. This type
of septic shock can be caused by gram-negative and
positive organism or nonbacterial organisms like malaria
(Falciparum) or viruses. It is characterised by fever, with
chills, tachypnoea, gastrointestinal disturbances, changes
in mental status and hypotension.
The term “toxic shock syndrome” is indistinguishable
from “septic shock” except that for a characteristic macular
rash, blanching on pressure, and inflamed mucosa
505
(conjunctivitis, pharyngitis and vaginitis) in addition to the
above features. This toxic shock is usually due to
Staphylococcus aureus, whose toxic principle is teichoic
acid. It is presumed that the presence of a vaginal tampon,
facilitates bacterial proliferation and the endometrium may
become the site of toxin absorption.
In profound shock, widespread disseminated
intravascular coagulation in the bowel, kidney, etc. affects
the microcirculation. The resulting ischaemia leads to
breakdown of mucosal barrier, facilitating entry of bacteria
and their toxins into circulation. These act as vasodilators,
overcoming the compensatory vasoconstriction, with a
further fall in blood pressure and thus perpetuates shock.
Anaphylactic Shock
It is due to the reaction of antigen (a drug or serum) with
antibody whose union takes place on the surface of the
mast cells (The antibody is IgE type which adheres to the
surface of the mast cell in the skin, gut and bronchial
mucosa and the antigen is usually serum or drug). This
results in degranulation of the cell and release of vasoactive
compounds like histamine, serotonin, bradykinin and slow
reacting substances. Histamine, the most important
substance, impairs the vascular tone leading to vasodilatation
(venous and arteriolar) and vascular permeability, besides
bronchial constriction. Arteriolar dilatation with reduced
perfusion pressure and increased capillary permeability with
loss of intravascular fluid, may lead to hypovolaemia (loss
of plasma volume with simultaneous increase in the
haematocrit and haemoglobin). The shock state may be
associated with or without urticaria or respiratory distress,
which is in the form of air way obstruction due to mucosal
oedema presenting as stridor, acute asthma and a feeling of
lump in the throat.
3. Cardiogenic Shock (Pump Failure with Intact
Intravascular Volume)
The most common cause is acute myocardial infarction
especially the anterior and arterioseptal types with loss of
viable myocardium and/or haemodynamic complications like
cardiac arrhythmias or rupture of the papillary muscle or
myocardium. The fall in blood pressure is primarily due to
failure of heart acting as a pump to maintain circulation
(pump failure). Rapidly developing pericardial effusion and
above mentioned haemodynamic complications precipitate
the onset of shock. It may be not only due to primary
reduction of cardiac output but also influenced by factors
like pain and ischaemic cardiac damage. The increase in
 506 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
left ventricular filling pressure as reflected in pulmonary
artery occlusive pressure or ventricular and diastolic to more
than 18 mm of Hg, and reduction of cardiac index are the
haemodynamic features of cardiogenic shock, i.e. raised
pulmonary capillary wedge pressure is suggestive of left
ventricular failure, as against low pulmonary capillary
pressure 6 mm of Hg in hypovolaemia. The critical size of
the total infarct area is 40 per cent of left ventricular mass,
at which shock will set in. Vasoconstriction which occurs
to maintain blood pressure increases systemic vascular
resistance, which in turn increases the myocardial after load,
thereby affecting cardiac performance. It is an expression
of severe left ventricular failure.
i. Cardiac arrhythmias (Refer to Chapter ‘Palpitations’).
ii. Intracardiac obstruction (Refer to Chapter
‘Syncope’).
a. Critical aortic stenosis (the aortic valve area is less
than 0.7 cm2 as against normal range of 2.6 to 3.6
cm2)
b. Atrial myxoma
iii. Myocardial infarction (Refer to Chapter ‘Chest Pain’).
iv. Pericardial tamponade (Refer to Chapter ‘Chest Pain’).
v. Aortic dissection—(Refer to Chapter ‘Chest Pain’).
vi. Dilated cardiomyopathy (Refer to Chapter
‘Palpitations’).
vii. Rupture of ventricular septum or ventricular wall
(Refer to Chapter ‘Chest Pain’).
Fig. 32.2: Pulmonary embolism—Deep S wave in L1 and Q in L3 with inverted T in L3 and V1 to V3
4. Extracardiac Obstructive (Fig. 32.2)
i. Pulmonary embolism
Refer to chapter—Chest Pain
ii. Tension pneumothorax }
CLINICAL APPROACH
Shock is a medical emergency. This acute haemodynamic
disorder varies in its presentation depending on the loss of
blood volume. Ten to 20 per cent of the loss of blood volume
may be mild, 20 to 40 per cent of blood loss may be moderate
and more than 40 per cent of blood loss is of severe clinical
state. The clinician must be vigilant to recognise quickly
the severity of shock by assessing the peripheral perfusion
and resuscitate rapidly to prevent slipping into an irreversible
stage of shock. Previous cardiac history, bleeding episodes,
and drug history are all of prime importance.
History
1. A few details in the history should be quickly elicited as
one should not lose much time. Elicit whether there is
any haematemesis and malaena, haemoptysis or diarrhoea
or vomiting prior to the onset of shock.
2. Any history of drug administration, insect bites.
3. Any history of agonising pain either in the chest or in
the upper abdomen or elsewhere.
4. Any history of acute febrile episodes.
5. Any history of injury.
 Shock
6. Any past history of diabetes mellitus or effort dyspnoea
or dyspepsia.
7. Excessive indulgence of alcohol or heavy meals.
8. Any history of bleeding from anywhere.
Physical Examination
General Examination
1. Appearance—Apathy, restlessness and prostration.
2. Skin
a. Note the upper level of coldness of the limbs,
below or above the knee
b. Cold and clammy sweating
c. Pallor
d. Dehydration
e. Bleeding points (from old venipuncture sites).
3. Any cyanosis due to anoxia
4. Any jaundice due to septicaemia
5. Pupils—Dilated and sluggish
6. Legs—Thrombosis of the leg veins
7. Vital data
a. Pulse—Is it rapid and feeble or unequal or fading
on inspiration
b. Blood pressure—Below 90 mm of mercury
c. Respiration—Tachypnoea and shallow
d. Temperature—Subnormal or normal.
Systemic Examination
1. Cardiovascular system
a. Neck veins—Examine the neck veins for jugular
venous pressure (if raised suggestive of cardio-
genic or obstructive shock and if JVP is reduced
it is hypovolaemic or Anaphylactic, whereas JVP
is variable in others).
• Is JVP raised on inspiration paradoxically?
b. Heart
i. Any abnormal heart sounds?
ii. Any murmurs?
iii. Any evidence of cardiac tamponade (rising
venous pressure, falling arterial blood pressure,
muffled heart sounds and pulsus paradoxicus
2. Respiratory system
a. Lungs—Any adventitious sounds, acidotie
breathing
b. Evidence of any consolidation.
3. Alimentary system
a. Oral cavity—Dry tongue
b. Any abdominal rigidity or rebound tenderness
507
c. Any tender hepatomegaly
d. Rectal examination.
4. Evidence of damage to organ systems
a. Gastric bleeding occurring after shock
b. Altered cerebral function
c. Renal shut down.
Investigations
As per the index of suspicion about the underlying cause of
shock, the following appropriate investigations can be
undertaken.
Urine
i. Measure the volume of the urine
ii. Chemical examination Albumin, sugar, acetone and
bile pigments
iii. Microscopic—For cells and casts
iv. Osmolality
v. Electrolytes
vi. Culture and sensitivity.
Blood
a. Biochemical
i. Blood urea
ii. Serum creatinine
iii. Blood sugar
iv. Serum electrolytes—(Bicarbonate, sodium,
potassium, chloride phosphorus and calcium)
v. Serum lactate (normal 0.4 to 1.8 mmol/L) elevated
in shock—Higher the value greater the fatality.
vi. Serum enzymes (Liver enzymes—SGPT, SGOT;
muscle—creatinine phosphokinase; pancreas—
amylase; cardiopulmonary—LDH)
vii. Serum bilirubin
viii. Blood gases—pH, pO2, pCO2
ix. S. cortisol
b. Haematology
i. Coagulation screen—Clotting time, prothrombin
time and partial thromboplastin time; fibrinogen,
fibrin degradation products (Blood may not clot
in a bottle in disseminated intravascular coagu-
lation).
ii. Haematocrit (raised in peritonitis and lowered in
haematemesis) and PCV falls about 3 to 4 per
cent for every 500 ml of blood loss.
iii. Full blood count and ESR; haemoglobin and red
cell count, total white cell count and differential
 508 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
count (Neutrophilia, and lymphopenia) and platelet
count.
iv. Blood film—for any fragmented RBC
(schistocytes) as seen in DIC.
v. Blood volume.
c. Culture
i. Blood culture for gram positive organisms
ii. Culture of sputum if any.
d. Endotoxin detection by the limulus lysate test indicates
poor out come.
Radiology
a. X-ray chest for any unsuspected pneumonia.
b. X-ray abdomen for any gas under the diaphragm
(perforation) or fluid levels (intestinal obstruction).
ECG
For any evidence of myocardial infarction or pulmonary
embolism (Fig. 32.2).
• Further Investigations, if necessary
• Haemodynamic Measurements
a. Central venous pressure
b. Left ventricular filling pressure
c. Pulmonary artery occlusive pressure (pulmonary
capillary pressure, technically pulmonary wedge
pressure)
d. Mixed venous oxygen tension of the blood samples
from the pulmonary artery or right atrium which is
an index of tissue oxygenation
e. Cardiac output
• ECHO: For cardiac tamponade or CHF.
• The 2, 3-diphosphoglycerate (DPG) elevated in
hypoxia.
TREATMENT OF SHOCK
Tissue hypoperfusion with circulatory and respiratory
compromise must rapidly be combated, while the search is
being made for the underlying cause. An early treatment,
indeed, is the key to a successful outcome. Hence, the
clinician must envisage a timely provision for an (i) adequate
ventilation, (ii) optimum fluid replacement and (iii) effective
circulation, apart from directing treatment towards the cause/
type of the shock state. As there is an interplay of several
ongoing haemodynamic mechanisms in shock syndrome,
continuous monitoring of various parameters reflecting
cardiovascular function and consequent metabolic after
effects, is imperative. Clinical factors unfavourably
influencing the prognosis are coma, anuria, heart disease,
acidotic breathing or severe sepsis.
General Measures
1. Raise the foot end of the bed to facilitate venous return
and maintain adequate cerebral circulation.
2. Warmth may be applied to conserve body heat and
further dilate the peripheral vessels.
3. Allay apprehension by reassurance and diazepam if
necessary.
4. Maintain an adequate air way and administer 100
percent oxygen either by mask or by nasal catheter
so as to maintain an arterial pO2 of at least 60 mm of
Hg even at 12 L/mt (Vide infra)
5. Establish venous access for therapeutic (fluid challenge
and vasoactive drugs to correct haemodynamic
abnormalities—vide infra) as well as biochemical
monitoring.
6. Nutritional supplementation, skin care, etc.
7. Other drugs
a. Appropriate analgesics for pain relief.
b. Effective antibiotics for nosocomical infection.
c. Parenteral hydrocortisone (100 mg 4th hourly IV)
for improving cardiac output and perfusion as well
as immunologic mechanisms and metabolism.
d. Chlorpromazine 10-25 mg IM useful to control
shivering.
e. Pantoprazole for stress ulcer
f. To prevent DVT aspirin my be considered support
hosiery is useful.
8. Continuous monitoring
a. Clinical monitoring—Temperature, pulse and
respiration (TPR monitor)
b. Urine output (by sterile catheterization > 30 ml/h)
c. Biochemical monitoring—pH, PaO2, PaCO 2,
serum lactate, serum electrolytes, serum creatinine
and blood urea
d. Pulse oximetry to detect fluctuations in arterial
oxygenation
e. Continuous electrographic monitoring
f. Haemodynamic monitoring
i. Monitor blood pressure (raised to 100 mm of
Hg or above) or >75 mmHg of mean arterial
blood peressure (MAP)
ii. Central venous pressure (CVP) is monitored
continuously if possible, as a guide to the fluid
replacement. (Normal < 4 of water) Low
central venous pressure demands fluid
replacement. (3 cm of water = 1 mm of Hg)
 Shock
iii. If facilities permit, pulmonary artery wedge
pressure also called pulmonary capillary wedge
pressure may be done (Normal value—mean
PCWP is 12 mm of Hg). Fluids are to be
administered, if PCWP is low so as to maintain
it at 18 mm of Hg.
iv. Fluid challenge—Fluid is administered at the
rate of 100 ml over a period of 10 minutes. If
the CVP or PCWP remains low or normal
during this interval, it connotes hypovolaemia
as a cause of shock and the infusion may be
continued at the same rate. If the CVP is >
15 cm of water or the PCWP is >20 mm of
Hg, it connotes pump failure and the infusion
must be stopped.
Specific Measures
Adequate Ventilation (Respiratory Support)
The primary principle in the resuscitation of a patient in
shock is to ensure adequate ventilation. Oxygen must be
administered by nasal catheter or endotracheal tube
depending on the severity of hypoxaemia but keeping in
mind the danagers of oxygen toxicity (higher PaO2) and
carbon dioxide retention (respiratory acidosis). Arterial blood
gas analysis is highly contributory to clinical evaluation which
alone may be inadequate. Positive pressure ventilation may
be required to ensure adequate oxygen exchange. (Positive
pressure ventilators are preferred—pressure preset and
volume preset—to maintain artificial ventilation). If PaO2
fails to rise, shock lung must be suspected when assisted
ventilation with positive end-expiratory pressure (PEEP) is
employed. Continuous positive airway pressure (CPAP) is
another mode of improving oxygenation. Oxygen may be
given even upto 12 L/mt especially in injuries.
Optimum Fluid and Electrolyte Replacement /Inotropic
Agents (Haemodynamic Support)
The sole aim is to correct the abnormalities of fluid,
electrolyte and acid-base balance. The choice of fluid to be
replaced is determined by the type of fluid loss, i.e. whole
blood, plasma, water and electrolytes. Replacement may be
monitored by simple parameters like haematocrit (rises in
plasma loss and falls in blood loss haemoglobin (better to
maintain at 12 gm% and above for effective oxygen
transport) and osmolality. Cross-matched whole blood only
to be used. If unmatched, ORh -ve, blood may be used.
Two types of fluids are used to resuscitate the patient,
i.e. crystalloids (0.9% sodium chloride, 5% dextrose, Ringer
509
lactate or acetate solution) and colloids (blood, plasma,
serum albumin or plasma subsitutes like haemaccel or
dextran are useful in haemorrhage or burns and not in septic
or sustained hypovolaemic shock due to fluid loss). Low
molecular weight dextran is relatively short-acting and does
not usually affect the coagulation mechanism and blood
typing/cross-matching unlike dextran. It decreases blood
viscosity, red cell sludging and platelet adhesiveness. The
volume expansion is aimed not only by replacement but
also by maintaining the optimum blood volume. It is better
to estimate the circulatory volume loss (Fluid loss may be
assessed by parameters like body weight, blood pressure-
supine and erect, pulse rate and clinical features like altered
sensorium, etc.). The rate of replacement depends on the
needs, and an undesirable fluid overload with pulmonary
complications must be avoided.
Usually, the quantity of crystalloids needed is four times
the estimated circulatory volume loss since 2000 ml of
crystalloids increase only 500 ml of vascular volume as the
other three parts enter the extravascular space. This ratio
may be altered even up to 8:1, if the treatment of shock is
delayed.
The response to hydration is appreciated by restoration
of normal blood pressure (without postural changes) and
clinical profile, increase in urine output of >30 ml/h and
elevation of the CVP up to 10 cm of water and fall of elevated
lactate levels.
Any metablic imbalance like metabolic acidosis may be
treated appropriately with IV sodium bicarbonate (Refer to
Chapter Coma). Alkalosis must be avoided.
Effective Circulation
The other endeavour is to maintain proper pump function
for effective circulation. Pharmacotherapy is the mainstay
to correct the haemodynamic changes apart from
mechanical support with circulatory assist devices.
Drug Therapy
a. Vasoactive drugs
Vasopressors—The choice of vasopressors depends
upon the haemodynamic status of the subject. They
are given by IV infusion. Vasopressors should be used
along with or after vigorous volume load. They are
effctive especially in hypotensive shock without
decrease in blood volume.
i. Dopamine (2 to 20 mg/kg/min in 5% dextrose)
ii. Dobutamine (2.5-1.5 mg/kg/min in dextrose
infusion (currently favoured adrenergic inotropic
510 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
agent) useful in LV dysfunction or shock esp
septic.
iii. Levarterenol (norepinephrine)—24 mg in 500 ml,
i.e 2-20 µg/min (considered in the absence of
response to either dopamine or dobutamine.
iv. Mephentermine—5-20 mg
v. Metaraminol—15-100 mg IV infusion
vi. Isoproterenol—1 mg (i.e) 1-5 µg/min in dextrose
infusion
vii. If tissue oxygen consumption is decreased,
N-acetylcystein (150 mg/kg/d) or Prostacyclin
(5-10 mg/kg/min) counteracts the side effect.
b. Other inotropic agents:
i. Digitails glycosides are not generally preferred.
However, it is found to be beneficial in septic
shock especially when the low blood pressure
persists despite raised CVP or PCWP (0.5 mg
initially followed by 0.25 mg as needed).
ii. Amrinone/Milrinone—Apart from positive
inotropic action, it is also a potent vasodilator and
is useful in lowering the pulmonary capillary wedge
pressure (0.5 mg/kg as initial bolus followed by IV
infusion at a dose of 5-10 µg/kg/min).
c. Vasodilators: Vasodilators have a limited role and are
not beneficial for patients with bacterial or
hypovolaemic shock. They are useful if pulmonary
oedema is associated with shock.
i. Nitroglycerin (25 µg/min initially and increased
by 20 mg/min every 5 minutes until haemo-
dynamics improve, i.e. PCWP at 15-18 mm of
Hg or blood pressure (systolic) at 90 mmHg.
ii. Soium nitroprusside (10 mg/min initially and the
dose is increased every 5 min until haemo-
dynamics improve or the systolic blood pressure
does not fall > 10 mm Hg or below 90 mmHg.
Contraindicated in severe hypotension). It is
followed by:
iii. Oral vasodilators like ACE inhibitors (enalapril 2.5-
5 mg/d).
d. Glucogon is a drug of choice for hypotension due to
betablockers.
e. Antibiotics (vide infra)
f. Steroids (vide supra)
g. Heparin Heparin may be effective to improve the
microcirculation, since intravascular coagulation
occurs due to microcirculation damage especially in
septic or traumatic shock (2500-5000 units IV every
4-6 h). It is not to be considered as a routine measure.
h. Adjuvant therapy with antiendotoxin agents,
antimediator agents and inhibitors of nuclear factor
kappa-B, are entertained.
• Intra-aortic balloon counterpulsation Circulatory
assist devices with intra-aortic balloon pump is
beneficial in the management of cardiogenic shock
as coronary blood flow is augmented in diastolic
inflation and left ventricular overload is decreased
by systolic deflation; and arrangements may be
made for any surgical measure in the intervening
period, i.e. PCI and CABG for revascularization.
Treatment of Complications of Shock
Renal Failure
The urine output may be decreased due to inadequate renal
perfusion, when vigorous fluid therapy must be instituted
to increase the output to acceptable limits (if necessary,
with frusemide after restoring the volume status) and
prevent acute tubular necrosis to develop (Refer to Chapter
Oliguria).
Cardiac Failure
Acute cardiac failure occurs especially in septic shock even
without pre-existing heart disease, due to myocardial
depression factor and presents clinically as left ventricular
failure (Refer to Chapter Dyspnoea).
Respiratory Failure
Even after the correction of haemodynamic or other
abnormalities, non-cardiogenic pulmonary oedema due to
increased capillary permeability may develop and progress.
(Refer to Chapters Dyspnoea and Cyanosis).
Gastrointestinal Complications
Ulceration of the GI tract with haemorrhage or infarcted
bowel needs surgical intervention.
Disseminated Intravascular Coagulation
(Refer to Chapter Bleeding Disorders)
Infections
When the source is from an open viscous or abscess, prompt
surgical measures are imperative as antibiotics alone may
not suffice.
 Shock
Multiorgan dysfunction syndrome (MODS) is
derangement of function in two or more organs in critically
ill-patients which is contributed by shock, sepsis or trauma.
Treatment of Different Types of Shock
Apart from the steps mentioned above, additional precise
measures for different clinical shock states may be outlined
as given below.
Hypovolaemic Shock
Repletion of intravascular volume by appropriate fluid
challenge rapidly so as to raise the systolic blood pressure
to >100 mmHg is the primary therapy. Careful watch is to
be directed at the jugulars and lung bases. Circulatory
overload is unlikely if CVP is maintained below 15 cm of
water and PCWP below 18 mmHg or lung bases are clear.
Vasopressors may be helpful in those with inadequate
vasoconstrictor response. However, when the peripheral
vasoconstriction is severe, they are often ineffective, since
the tissue perfusion is further reduced, dopamine preferred.
The underlying cause of either loss of blood or plasma
or fluid and electrolytes must also be treated appropriately.
(Specific gravity of urine of 1020 and urinary sodium
of <10 mEq/L indicates significant hypovolaemia).
Distributive
Neurogenic Shock
Alpha-adrenergic stimulators like methoxamine or
phenylephrine are the drugs of choice. Nevertheless,
expansion of blood volume may suffice most often since
sudden pooling of blood in the venous bed reduces the
effective blood volume, although there is no loss of blood,
plasma or fluids as such. Aprotinin may be considered for
pancreatogenic shock (vide infra).
Septic (Bacteraemic) Shock
a. Antibiotic therapy is instituted promptly to control the
infection. (Combination of antibiotics like cefuroxime
IV 1 gm t.d.s, gentamicin 1 mg/kg twice daily IM and
metronidazole 500 mg as IV infusion tds).
vancomycin, lmipenem are other preferred antibiotics.
b. Fluid replacement.
c. Vasopressors administered, if shock persists even after
volume expansion.
d. Glucocorticoids—Soluble hydrocortisone (100 mg
every 4-6 hours) may be of value.
511
e. Consider Aprotinin for endotoxic shock (70 mg initially
followed by 28 mg fourth hourly).
f. Immunotherapy with human antiserum to the
lipopolysaccharide core of endotoxin from heat treated
E. coli.
g. Naloxone (1 mg bolus to be repeated till a maximum
dose of 0.1 mg/kg is reached) may be beneficial (as
an opiate antagonist to the released endogenous opiate
b-endorphin).
h. Digoxin (Vide supra).
i. Nitric oxide inhibitors like low doses of L-NMMA
(L-N-Monomethyl arginine), Hydroxycobalamine
(Selectively blocks nitric oxide derived from
endothelium).
j. Oxygen therapy to maintain tissue oxygen delivery
k. Inhibit toxic mediators.
l. Activated Protein C (rhAPC) considered in severe
sepsis with end organ dysfunction.
m. Treat complications like DIC as they arise.
Toxic Shock Syndrome
Prompt removal of packings in the closed spaces like vaginal
tampons and antistaphylococcal antibiotics are the mainstay
of therapy.
Anaphylactic shock
a. The choice of drug is adrenaline (0.5 ml of 1 in 1000
SC and repeat every 15 minutes as needed).
b. Antihistamines—Chlorpheniramine 10 mg parenterally
or diphenhydramine 1 mg/kg up to 50 mg IV or IM.
c. Soluble hydrocortisone 200 mg IV every 4.6 hours;
taper the dose later.
d. Fluids—IV infusion of isotonic crystalloid solution
with dobutamine, if necessary, titrating to the
acceptable blood pressure limits.
e. Aminophylline 500 mg in dextrose given as IV infusion
to relieve the bronchospasm.
f. Tourniquet is applied above the injection site to delay
the absorption of the offending drug and additional
adrenaline 0.3 ml 1 in 1000 into the drug injected site,
may be given.
Cardiogenic shock: After adequate fluid and electrolyte
corrections, tissue perfusion must be improved along with
inotropic agents/vasopressors besides optimal oxygenation.
(If systolic blood pressure is <70 min Hg Noradrenaline
and if BP is between 70-90 mmHg, dopamine infusions
administered. If dopamine needs are more, noradrenaline
considered. If BP. is >90 mmHg, dobutamine is preferred.
 512 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Noradrenaline may be given with dobutamine, if necessary). Nonischaemic Causes

If there is no response or excessive tachycardia develops,
i. Cardiac arrhythmias (Refer to Chapter ‘Palpitations’).
milrinone-(noncate cholamine phosphodiesterase III
ii. Intracardiac obstruction—Balloon valvuloplasty for
inhibitor)—is added for ionotropic support. Vasodilators like
valvular stenosis; beta-adrenoreceptor and calcium
sodium nitroprusside may be given with dopamine or
channel blocking agents for hypertrophic cardiomyo-
dobutamine to increase cardiac output and maintain blood
pathy; and emergency surgery for ball-valve thrombus
pressure. Withhold nitrates, betablockers, ACE inhibitors
or atrial myxoma.
till BP stabilises. Vasodilators also should be withheld if the
iii. Dissecting aneurysm—(Refer to Chapter ‘Chest Pain’).
cardiogenic shock is due to right ventricular infarction and
iv. Dilated cardiomyopathy (Refer to Chapter ‘Palpitations’)
only IV fluids administered in addition to inotropes. Intra-
v. Rupture of ventricular septum or wall (Refer to
aortic balloon counterpulsation, if needed (Refer to Chapter
Chapter ‘Chest Pain’).
Chest Pain) correct arrhythmias. Circulatory assist devices
and revascularisation attempts can be initiated, if warranted.
4. Extracardiac Obstructive (Vide supra)
Ischaemic Causes i. Pulmonary embolism
i. Myocardial infarction (Refer to Chapter ‘Chest Pain’). ii. Tension pneumothorax }
Refer to Chapter—Chest Pain
Shock 513
 Chapter

Syncope
33
Syncope (Greek—syn = with; koptein = to cut off) is a 3. Vascular Insufficiency of Outgoing Vessels to the Brain
sudden, transient and complete loss of consciousness due a. Hypersensitive carotid sinus.
to decreased cerebral blood flow to less than half of the b. Carotid artery obstruction.
normal for about 3 to 4 seconds. If the reduced cerebral c. Subclavian steal syndrome-(Refer to Chapter –
perfusion is prolonged for more than 5 seconds, a Vertigo).
convulsion occurs (isolated fit). This is a form of hyper d. Cervical Spondylosis-(Refer to Chapter – Vertigo).
acute circulatory failure with consequent anoxia and 4. Vascular insufficiency of cerebral vessels: Cerebral
disturbed brain metabolism. It may be preceded by nausea syncope
with clouding of visual fields and generally followed by full 5. Metabolic disturbances: Hypocapnia as in hyper-
recovery within minutes. It is not usually associated with ventilation
any organic disease of the brain as such. 6. Anoxaemia: Obstruction to blood flow due to sudden
The term faintness or blackout is sometimes used gravitational effects of anoxia from sudden decom-
synonymously with syncope. pression (e.g. aviation).
The cerebral blood flow or the cerebral perfusion
pressure depends on (i) cardiac output, (ii) arterial blood TYPES OF SYNCOPE
pressure and (iii) resistance of the cerebral arteries. An acute 1. Neurocardiogenic syncope
in crease in cerebrovascular resistance leads to cerebral A. Vasovagal syncope (Vasodepressor)
vasoconstriction and increase in intracranial pressure. B. Reflex syncope
i. Carotid sinus syncope
AETIOPATHOGENESIS ii. Postural syncope
The decreased blood flow to the brain may result from: 2. Cardiac syncope
3. Cerebral syncope
1. Inadequate venous return and cardiac filling
4. Metabolic
a. Loss of vasomotore tone with dilatation of systemic
5. Anoxic syncope
arterioles and sudden fall of peripheral resistancs as
6. Psychogenic
in vasovagal synocope and postural synocope .
b. Hypovolaemia as in acute heamorrhage.
c. Severe cough or breath holding spells.
1. Neurocardiogenic Syncope
d. Severe pulmonary embolism. This represents an abnormal autonomic response with
e. Pericardial tamponade. bradycardia and hypotension.
2. Inadequate cardiac output
a. Cardiac arrhythmias. VASOVAGAL SYNCOPE (VASODEPRESSOR)
b. Obstruction to left ventricular outflow tract (aortic It is the commonest form of Neurocardiogenic Syncope,
stenosis and hypertrophic obstructive cardio- which includes the common faint. It is mediated by Bezold-
myopathy). Jarisch reflex (increased vagal tone). The predisposing
c. Acute myocardial infarction. factors are extreme exertion, prolonged standing, sudden
 Syncope
painful or emotional stimuli like fright, environment heat or
crowding in hot stuffy room. This is most often due to
sudden depression of vasomotor centre with loss of
vasomotor tone, resulting in pooling of peripheral blood,
and consequent fall of blood pressure. The subject is
invariably standing still before the sudden attack. The onset
is not instantaneous (over seconds). Weakness, nausea,
sweating. Dimness of vision, and ringing in the ears, precede
before the subject gradually sinks to the ground without
any injury. There is pallor of the body with prespiration.
The skeletal muscles are relaxed and flaccidity is elicited.
The pulse rate is usually slow and feeble. The systolic blood
pressure is around 60 mm of Hg and the respirations are
slow and shallow. Pupils are dilated with sluggish light reflex.
Tonic convulsions are not usually associated but limbs may
jerk and the sphincter tone is intact without urinary
incontinence. The duration is usually measured in seconds
to minutes (< 2 minutes) and recovery is complete without
any residual symptoms like headache, drowsiness or
confusion. The history of such episodes under similar
circumstances is contributory for the diagnosis.
It will not occur while lying down. (Autonomic
dysfunction results in bradycardia and hypotension and
cerebral hypoperfusion accounts for unconsiousness)
Reflex Syncope
Carotid sinus syncope This result from hypersensitivity of
the carotid sinus. which contains sensory end organs
(baroreceptors) whose axons are connected with the nerves
from the carotid body. The slightest pressure whether due
to tight collar or turning the head to one side results in
syncope. The attack always occurs in the standing upright
position. In a normal person pressure over the carotid sinus
causes a slight reduction in the pulse rate of 6 beats per min
and a slight fall in the blood pressure of 10 mm of mercury.
In the carotid sinus hypersensitivity the pressure over the
sinus may result in two types of responses.
a. Cardiac slowing (vagal type).
b. Fall of blood pressure with no effect in the pulse rate
(vasodepressor type).
The latter is less common than the former and the symptoms
may last longer, say, for a few hours.
The carotid sinus syndrome may be associated with an
identifiable lesion like carotid sinus tumour or cervical
lymphadenopathy or scars. The diagnosis is confirmed by
gently applying light pressure on one side in the region of
carotid sinus at the level of superior border of thyroid
cartilage for 20 sec at a time, in supine position; and recording
515
the abnormal responses like (a) sinus bradycardia or even
ventricular asystole of 3 sec duration, and (b) a decrease in
systolic arterial blood pressure to the extent of 50 mm of
Hg and above.
Carotid sinus stimulation is not usually associated with
any complications. Nevertheless it may result in cardiac
standstill and hemiplegia, particularly in the elderly
hypertensive patients with cerebral vascular disease.
Postural syncope Here the syncope occurs when the subject
suddenly stands up from a recumbent position, due to
impairment of autonomic control of peripheral vasculature.
The consequent inadequate reflex vasoconstriction leads to
an abrupt fall of blood pressure (postural or orthostatic
hypotension). The pulse remains unchanged although
orthostatic tachycardia may be associated. The pallor and
nausea associated with vasovagal syncope are absent.
This may occur after exercise or a sumptuous meal. In
young women upright posture assumption may result in
tachycardia with insignificant change in blood pressure
(postural orthostatic tachycardia syndrome). It is a long-
standing reproducible symptom.
The mechanism underlined is pooling of blood in the
lower extremities, which is normally prevented by
a. Pumping action of the muscles to facilitate the venous
return,
b. Reflexes which constrict the peripheral arterioles and
venules, and
c. Acceleration of the heart through carotid and aortic
reflexes.
The postural syncope is likely to occur after acute blood
loss, in debilitating illnesses, because of use of hypotensive
drugs or diuretics; or near term pregnancy may obstruct
inferior vena cava (supine hypotensive syndrome). This may
be chronic in certain neurological disorders like diabetic
neuropathy or syringomyelia or primary autonomic
insufficiency (chronic orthostatic hypotension). The postural
hypotension in chronic idiopathic orthostatic hypotension
is associated with hypohidrosis, impotence, sphincter
disturbances, asymmetrical pupils and without compensatory
tachycardia. The lack of prespiration may be partial or
complete, unilateral or bilateral. There is response (sweating)
to pilocarpine although heat does not. Degeneration of post-
ganglionic and pre-ganglionic neurons is striking. This may
occur as part of multisystem atrophy or associated with
Parkinson’s disease.
Secondary orthostatic hypotension occurs in neurological
disorders as cited above, which involve the autonomic
nervous system resulting in autonomic dysfunction. The
autonomic insufficiency is suggested by unchanging pulse
rate, in spite of hypotension.
 516 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

This impairment of autonomic control of peripheral

vasculature causing postural hypotension is diagnosed by:
a. Recording the blood pressure in the supine position
as well as standing position (after recumbency for
10 min, standing BP is recorded at 3 min intervals)
when the systolic blood pressure falls by more than Fig. 33.1A: Second degree heart block (Mobitz II)—Ventricular
10 mm of Hg and diastolic falls by more than 4 mm response to every second sinus impulse only, with constant
of Hg on standing. PR interval (2 : 1 block)
b. Valsalva manoeuvre—The subject in supine position
exhales for at least 10 s aginast a closed glottis forcibly
when the intrathoracic pressure is elevated. It can
also be done by blowing up the column of mercury
so as to maintain the pressure at 40 mm of Hg for 10
sec. Normally the blood pressure falls and pulse rate Fig. 33.1B: Second degree heart block with Wenckebach
rises during the strain, and there is an over shoot (i.e. phenomenon (Mobitz I)—Progressive increase in PR intervals,
rise of arterial pressure) as well as a reflex bradycardia until ventricular complex is dropped. The same sequence is
when the strain is released. In postural hypotension, repeated
there is no overshoot of arterial pressure and reflex
bradycardia after releasing the strain due to impairment
of autonomic reflexes, although the blood pressure
which continues to fall during the manoeuvre, gradually
returns to original level subsequently.
Visceral reflex syncope (Micturition) Micturition syncope is
a type of postural syncope wherein the elderly person empties Fig. 33.2: Third degree (Complete) heart block—Ventricular
his distended bladder after arising from a recumbent position. rate is less than the atrial rate. NO constant relationship
Post-tussive syncope After a paroxysm of cough specially in between the QRS complexes and P waves, as atria and
ventricles contract independently
obstructive pulmonary diseases the loss of consciousness
occurs due to high intrathoracic pressure, may be even 300
mm of mercury, which is well above the arterial pressure.
This results in the total impediment of venous return to the
heart and consequent fall of the cardiac output. Simultaneously
the intracranial pressure is increased. Both these factors
Fig. 33.3A: Ventricular tachycardia—Run of abnormal (wide)
produce reduction in the pressure of the cerebral vessels
and uniform (monomorphic) QRS complexes with
with precipitous impairment of cerebral perfusion. approximately regular rhythm. P waves are obscured by
ventricular complexes
2. Cardiac Syncope
In this group the cardiac output falls as a result of underlying
heart diseases like
a. Cardiac arrhythmias, i.e. sick sinus syndrome, heart
block or paroxysmal techycardia (Figs 33.1 to 33.3).
Fig. 33.3B: Ventricular tachycardia degenerates into ventricular
b. Obstruction to outflow tracts, i.e. Aortic or pulmonary fibrillation: Rapid oscillations, varying in amplitude and width,
stenosis and hypertrophic obstructive cardiomyopathy. representing QRS complexes with an undulating base line
c. Cyanotic heart disease, e.g. Fallot’s tetralogy and absence of apparent isoelectric interval
d. Ischaemic heart disease, e.g. acute myocardial
infarction Cardiac Arrhythmias (Refer to Chapter ‘Palpitations’)
e. Pericardial tamponade In Stokes-Adams syndrome the cerebral blood flow ceases
f. Intracardiac masses, e.g. myxoma or clots due to ventricular asystole, resulting in syncopal attacks
g. Pulmonary embolism. within 3 seconds. The asystole may be either due to AV
 Syncope
Block or Ventricular tachycardia/ fibrillation. Occasionally,
sinoatrial block (sick sinus syndrome) and sensitive/
compressed carotid sinus in a normal heart can also result
in asystole. Breathing continues even though the heart has
stopped (pallor without pulses). i.e. cardiac standstill. If
the heart does not restore its function within 10 seconds,
convulsions will occur due to cerebral anoxia and may prove
fatal if the asystole is prolonged for 2 min. Nevertheless,
spontaneous recovery is usual. Cardiac syncope of this type
due to reduced cardiac output is paroxysmal, even occurring
several times in the day or at longer intervals.
Tachyarrhythmias may reduce the cardiac output resulting
in syncope.
Obstruction to Outflow Tracts
In severe pulmonary stenosis effort syncope occurs, due
to inadequate filling of left ventricle disproportionate to
increased demands. In aortic stenosis, there is maximal
cardiac output and adequate blood flow at rest but on exertion
further increase in cardiac output does not take place and
the effort syncope results. In hypertrophic obstructive
cardiomyopathy, syncope results from inadequate cardiac
output during or after exertion. It occurs in erect position,
after prolonged standing, or after paroxysms of cough.
Cyanotic Heart Disease
In tetralogy of Fallot, the syncope is not related to decreased
cardiac output but due to increased right to left shunt caused
by a fall in systemic resistance or infundibular spasm
resulting in arterial hypoxia.
Ischaemic Heart Disease
Syncope may be the preseting manifestation in some cases
of myocardial infarction due to intense visceral pain and a
fall in cardiac output.
Pericardial tamponade
Refer to Chapter Dyspnoea
Intracardiac Masses
Mechanical obstruction at the mitral orifice due to left atrial
thrombus may account for syncope, specially when there
is concomitant mitral stenosis. So is the case with myxoma.
Pulmonary Embolism
Syncope may result in pulmonary embolism due to acute
circulatory obstruction and involvement of the vagal
reflexes.
517
3. Cerebral Syncope (Neurologic)
Syncope due to cerebrovascular disease is usually caused
by transient occlusion of either carotid arteries or vertebral
system or vascular spasm of the cerebral arteries (TIA).
Compression of the verebral arteries by cervical spondylitis
can cause syncopal attacks specially when there is abrupt
movement of the neck. Diminished cranial arterial blood
flow may account for syncope in migraine.
4. Metabolic origin
Hyperventilation may be associated with syncope which
usually develops gradually. Other symptoms of
hyperventilation syndrome like numbness and tingling or
tetany may be elicited. Forced breathing results in decreased
cerebral blood flow due to vasoconstriction caused by carbon
dioxide wash out and consequent low carbon dioxide tension
(hypocapnia). This is usually a hysterical phenomenon or
may follow a valsalva’s manoeuvre. These stereotyped
attacks can be reproduced by forced breathing, which can
be used as a test for syncope. Sometimes hypoglycaemia
may be incriminated (Neuroglylopenia).
5. Anoxic Syncope
This occurs (a) at high altitudes, (b) with extreme exertion
or exercise in chronic pulmonary disease or congenital heart
diseases or (c) when flying high or during ascent of a plane
from a sharp dive (aviation). The reduction of arterial oxygen
saturation with consequent cerebral anoxia is the underlying
mechanism for syncopal attacks. Inability to increase the
cardiac output on demand and consequent decreased
cerebral perfusion which occurs during exertion or exercise,
due to the associated cardiac disorders, may be contributory.
Anoxaemia is due to lowred O2 in arterial blood or venous
blood with increased AV difference or deficient O2 carrying
power of blood.
6. Psychogenic
Hysteria; Anxiety (Refer to Chapters ‘Coma and palpitation’)
CLINICAL APPROACH
Usually in cases of syncope, physical examination during
the attack may not be feasible. Nevertheless, careful history
taking and examination may be contributory to the diagnosis
of syncope. Whether neurocardiogenic or cardiogenic.
Methods of Enquiry
1. Predisposing factors (like emotional stress, blood loss
esp-G.I bleeding, exertion, change of posture, rotation
of neck, diabetes mellitus or intake of drugs).
 518 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
2. Type of onset (symptoms developing, gradually over
a period of few seconds or minutes (vasovagal) or
sudden or abrupt without any premonition (cardiac).
3. Decubitus at the onset (usually prolonged standing
still in vasovagal) or standing suddenly from supine
position as in postural or any position as in cardiac
arrhythmias.
4. Duration of attack (few seconds to few minutes in
vasomotor, more than few minutes in
hyperventilation).
5. Associated features like striking pallor (vasovagal);
dyspnoea, palpitations, cyanosis and signs of
underlying cardiac disorder (cardiac syncope); tingling
and numbness or tetany (in hyperventilation type);
other neurological features like hemiparesis, diplopia,
vertigo, thick speech, and slow stertorous breathing
(cerebral).
6. Situational (i.e.) related to mictirution or cough.
History from an eye-witness regarding syncopal episode
may be complementary for the diagnosis.
Physical Examination
General
a. Look for any clubbing or cyanosis, or anaemia.
b. Feel all the pulses and asses rate and rhythm.
c. Take blood pressure in both arms and legs, recumbent
and standing positions.
d. Simultaneous pulse and heart rates and blood pressure
response to carotid sinus pressure.
e. Whether turning movements of the head produce any
syncope.
Systemic Examination
Cardiovascular System
a. Auscultate for neck bruits (vascular obstruction).
b. Examine the heart for any valvular disease or any
congenital heart disease.
Respiratory system It examines for evidence of:
a. Acute cor pulmonale (pulmonary embolism), and
b. Chronic copulmonale.
Central Nervous System
Examine for any evidence of:
a. Cerebovascular disease especially for vertebrobasilar
system;
b. Features related to structures of posterior fossa (visual,
auditory and vestibular); and
c. Neurological diseases associated with paralysis of
circulatory reflexes.
1. In clinical practice, syncope has to be differentiated
from Epilepsy:
Though there are no tonic clonic convulsions in
syncope, occasionally few clonic twitches are seen
after becoming unconscious, especially in heart block
or cardiac standstill. The characteristic features of
epilepsy are:
(a) The seizures can occur in any position either
during the day or by night during sleep; (b) aura
present; (c) the attack is abrupt onset; (d) personal
injury invariably present after the fall due to loss of
protective reflexes; (e) tonic and clonic convulsions
with rolling of the eyes upwards usually precede loss
of consciousness; (f) biting of the tongue; (g)
incontinence of urine; (h) absence of pallor and
presence of rigidity; and (i) postictal state of confusion
and drowsiness.
In akinetic seizures the subject falls to the ground
without any warning and becomes unresponsive with
generalised muscular hypotonia. Unawareness of the
fall is the only evidence for brief loss of consciousness.
2. Hysterical fainting or malingering occurs in hysterical
personalities with acute anxiety state. Absence of any
obvious physical signs especially changes in blood
pressure, pulse rate or skin colour will be diagnostic.
3. Drop attacks—The subject often falls to the ground
often injuring himself without interruption of
consciousness and gets up at once.
The underlying cause is postulated to be basilar
artery ischaemia;
Alcoholic blackouts.
4. Post-concussion amnesia following brief loss of
consciousness.
5. Hypoglycaemia can produce brief confusional states,
sympathetic overactivity, twitching of muscles,
incoordination followed by loss of consciousness
which is usually prolonged. Diagnosis depends upon
detection of blood sugars of less than 40 mg
percent during the attack or after prolonged fasting
for 72 h.
6. Acute intracranial hypertension may produce brief loss
of consciousness in colloid cysts of 3rd ventricle
which obstruct the cavity intermittently or produce
plateau waves.
 Syncope
Investigations
Haematology
Red blood cell counts; haemoglobin percentage and packed
cell volume.
Biochemical Evaluation
a. Normally norepinephrine increases on assuming upright
position, much above the supine levels whereas in
orthostatic hypotension, there is little or no rise.
b. Glucose tolerance test for evidence of diabetes mellitus
or hypoglycaemia.
c. LDH levels for coronary thrombosis or pulmonary
embolism.
d. Serum sodium levels.
ECG
Syncope of cardiac origin may invariably reveal changes of
either hypertrophic cardiomyopathy, ischaemic pattern or
arrhythmias. Twenty four hours ECG especially during the
routine activities is useful for effectively detecting cardiac
arrhythmias (Holter monitoring), exercise testing.
• Skiagram of Chest
• Evaluation of Autonomic Function
a. Standing position normally may result in a fall of
systolic blood pressure by less than 20 mm of Hg
with a modest tachycardia whereas in autonomic
dysfunction the fall will be more than 20 mm of Hg
with an unaltered pulse.
b. Deep breathing results in more than 10 heart beats
per min normally. The loss of this respiratory variation
of heart rate (< 10) indicates autonomic neuropathy
due to vagal degeneration.
c. Valsalva manoeuvre (autonomic procedure) vide supra.
d. Pupillary reaction: Instilling either 0.1% adrenaline or
2.5% methacholine does not result in dilatation or
constriction respectively if normal.
Pharmacological Tests
a. When nitroglycerine is given in autonomic failure blood
pressure, falls, without reflex tachycardia.
b. Noradrenaline infusion shows hyposensitivity in
autonomic failure.
c. Pilocarpine induces sweating which may reveal the
abnormal sweat pattern of hyperhidrosis on one side
and anhidrosis on other side in autonomic dysfunction.
d. Isoproteronol and adenosine also used to induce
vasovagal syncope through Bezold-Jarisch reflex.
519
Reproducing Attacks of Syncope
a. By applying pressure or massage over carotid sinus
so as to activate the vasomotor reflexes (Contra-
indicated if carotid bruit is present).
b. Hyperventilation—Rapid and deep breathing for 2 to
3 minutes.
c. Head-upright tilt table test (HUT)—In those who can
not stand at all tilt table can be used to put the subject
in upright position by tilting the table to +60° for 45
minutes or more (monitor ECG and BP) when positive
response results in syncope (reproduced) due to
defective vasomotor reflexes and consequent increased
fall of blood pressure (normally BP falls but stabilises
at a lower level), backing up neurocardiogenic
syncope. If symptoms/signs appear, they are reversed
by adopting flat position. If they do not develop,
provocative tests done with Isoprenaline (slow
infusion) or glyceryl trinitrate (inhaled) and tilt is
repeated.
This test is contraindicated in coronary artery disease, mitral
stenosis, left ventricular outflow obstruction.
Further Investigations
If Indicated.
EEG In the majority of cases, EEG shows some changes in
the interval between seizures whereas in syncope it is normal.
Twenty four h EEG may prove useful. EEG reveals slow
waves (2-5 sec) of high voltage during loss of consciousness
followed by flattening of the record transiently.
• Cerebral Angiography
• CT Scanning or MRI brain
Useful to differentiate other causes of brief loss of
consciousness.
• Echocardiography
• Intracardiac Electrophysiologic Studies
(It may be utilised judiciously for delineating some of
the syncopal episodes, which elude exact diagnosis)
Disorders like Epilepsy, (Syncope is more gradual both onset
and cessation; without convulsive movements, and limp
instead of rigidity) or Drop attacks (Though falls on ground,
there is no warning, no unconsciousness no vertigo and no
confusion after recovery) must be carefully distinguished.
So is the case with meniere’s disease.
TREATMENT OF SYNCOPE
Episodic impaired consciousness with a feeling of
momentary weakness and slipping on to the ground
 520 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
motionless may be really alarming. Such fainting attacks
must be carefully delineated from attacks of fits. Any
ordinary episode of syncope needs only little treatment since
it is self limited.
However, critical approach to ascertain the aetiology of
syncope inclusive of predisposing and precipitating factors
must be pursued and measures must be undertaken to
prevent future attacks.
Symptomatic Relief
a. Place the patient in a horizontal position with the head
low or legs elevated.
b. Loosen tight clothing and facilitate fresh air.
c. Keep smelling salts (aromatic spirits of ammonia) near
the nostrils.
d. Sprinkle cold water over the face.
Such elementary measures restore consciousness usually
in patients with simple (common) faint or rarely vasopressors
or atropine may be required.
Specific Treatment for Specific Causes
1. Inadequate Venous Return and Cardiac Filling
Vasovagal syncope (Simple Fainting, Vasodepressor
Syncope; Neurocardiogenic syncope)
a. Avoid prolonged standing, hot stuffy rooms or extreme
exertion.
b. Leg bandages and/or abdominal binders help venous
return.
c. Adequate hydration and salt intake to be increased.
d. Beta-blockers indicated, if Bezold-Jarisch Reflex is
incriminated.
e. Anti-cholinergics are beneficial if resting bradycardia is
present.
f. Midodrine (Alpha-I adrenergic agonist - 5 to 15 mg tds)
causes vasoconstriction.
Carotid sinus syncope (vide infra)
Postural hypotension and syncope
a. Tilt the head up by 6 to 10 inches while sleeping.
b. Caution the patient to rise slowly from supine to sitting
position and wait for a couple of minutes before
standing.
c. Increase daily salt intake—Sodium chloride 4 to 10 g/
day (1 gm of NaCl contains 17 mEq of sodium).
d. Withdraw or reduce the dosage of hypotensive drugs
or other offending drugs.
e. Elastic stockings and/or abdominal binders may be
helpful.
f. Nine-alpha fludrocortisone (0.1 mg twice daily) and/
or indomethacin (up to 75 mg daily) or adrenergic
drugs like ephedrine (up to 75 mg daily) may control
attacks in the early stage.
g. Encourage exercises like plantar dorsiflexion, tensing
abdominal muscles, isometric exercise of upper limbs
before and after standing.
h. Correct the underlying cause of autonomic
dysfunction if the orthostatic hypotension/syncope is
chronic.
i. Sympathomimetics like midodrine are worth trying in
dysautonomia.
j. Orthostatic training.
Hypovolaemia Postural syncope due to hypovolaemia is
corrected by volume replacement with appropriate fluids.
Tussive syncope Severe bouts of cough can be suppressed
with cough suppressants (like linctus codeine or noscapine
or dextromethorphan) and antibiotics, if necessary.
Severe Pulmonary Embolism (Refer to Chapter – Chest Pain.)
Cardiac tamponade Pericardial fluid under pressure leading
to tamponade can be dealt with pericardiocentesis or
pericardiotomy or pericardiectomy. If possible,
pericardiocentesis may be done in conjunction with
haemodynamic measurements. Malignant pericardial
effusion causing cardiac tamponade can be managed not
only with pericardiocentesis, but radiation therapy and local
or systemic chemotherapy. Purulent effusions with
tamponade need surgical extensive drainage and effective
antibiotics.
2. Inadequate Cardiac Output (Cardiac Syncope)
Cardiac arrhythmias Refer to Chapter – Palpitations.
Disturbances in impulse conduction
i. Sick sinus syndrome: Though life span is not affected,
the treatment is indicated in the presence of disturbing
symptoms. Drug therapy with atropine or isoproterenol
is beneficial only in a few patients and even in these
cases the side effects prohibit long term treatment.
(Isoproterenol is not desirable in myocardial ischaemia).
Permanent pacemaker implantation is effective if
symptomatic, in controlling troublesome symptoms
Tachycardia may be treated with anti-arrhythmic drugs
after implantation. (Figs. 33.4a and b). (Refer to
Chapter ‘Palpitations’).
 Syncope
Fig. 33.4a: Sick sinus syndrome: Sinus arrhythmia (non-phasic)
with intermittent sinus pauses. (The longest R-R interval is
prolonged by greater than 40% of the shortest R-R interval)
Fig. 33.4b: After pacing (permanent): Each vertical line (pacing
impulse) is immediately followed by wide ventricular QRS
complex
ii. AV block: (second and third degree)
Drug treatment with sympathomimetic drugs like isuprel;
ephedrine or cholinergic blocking drugs like atropine, has
relatively little benefit though prescribed especially to prevent
Stokes-Adams attacks. The survival rate can be greatly
improved by long term treatment with permanent pacemaker
implantation even if asymptomatic.
For the immediate treatment of complete heart block
with asystole i. e Stokes-Adams syndrome (if pulseless for
5 seconds (Dizziness); more than 5 sec (loss of
consciousness); 10 sec/seizures); 2 min/unevenful recovery
unlikely); 4 min (irreversible brain damage).
Deliver a vigorous blow over the precordium and elevate
both ledgs to 90 for 15 seconds. If the heart does not
commence beating immediately, cardiopulmonary
resuscitation must be started within 2 minutes, lest
irreversible cerebral damage should occur.
Drug therapy simultaneously-Asystole due to ventricular
techycardia or fibrillation must be excluded before instituting
the following drug regime. (Refer tp Chapter Palpitations)
a. Isoproterenol (0.2 mg or every 3 hours or 1-2 mg in
5% dextrose infusion). Isoproterenol is not desirable
in ischaemia or
Adrenaline (0.2 ml 1 in 1000 every 1 to 2 hours sc
or 3 ml 1 in 1000 i.e. 3 mg in dextrose infusion) may
be effective. If necessary, intracardiac injection of
adrenaline (5 ml 1 in 10,000) is given. The entry of
the needle itself may stimulate the heart to beat again.
b. Atropine (0.6 mg IV initially to a maximum of 3 mg)
may be an useful adjunct to improve AV conduction.
c. Calcium gluconate 10 percent 10-cc IV may be
beneficial. (Avoid sodium bicarbonate line).
521
d. Correct acidosis (50 ml of 8.4 percent of NaHCO3
iv), hypoxaemia and/or hypokalaemia, appropriately.
Recovery from seizures is spontaneous, seldom
requiring specific treatment.
e. Temporary pacing electrode can be inserted in the
mean while.
It the attack is prolonged CPR must be commenced.
Cardiopulmonary Resuscitation (CPR)
Basic Life Support-ABC
A. Air way—Open the airway by hyperextending the chin
and clear the same, by lifting the tongue from the
back of the throat and extracting the solid or liquid
debris with the index and middle fingers covered with
handkerchief.
B. Breathing—Mouth to mouth breathing (breathing
through Brooks airway or AMBU system, if available)
must be done at the rate of 12 to 15 per minute
(Keeping the nostrils closed), if there is no spontaneous
breathing. Initially, give two full breaths, each lasting
for 2 seconds and continue.
C. Circulation —Look for signs of circulation for not
more than 10 seconds. If circulation is present, rescue
breathing may be continued. If circulation is absent,
chest compressions (external cardiac massage) and
simultaneous rescue breathing to be done as follows.
(cardiopulmonary resuscitation sequences).
The 100 chest compressions (by placing one hand over
the other, above the xiphisternum at a rate of 100 per
minute, with 4 cms depth of compression) at a sequence of
15 compressions to two breaths alternatively if alone, or
5 compressions to one breath, if two persons are available
(pausing after every 5th compression while the other inflates
the lung) are to be accomplished. Chest compressions and
mouth to mouth breathing should not coincide so as to avoid
high intrapulmonary pressure and rupture).
Check for the return of the pulse. If pulse continues to
be absent, sequences must be repeated for at least 30
minutes till the patient resumes breathing and heart starts
beating again, with previously dilated pupils remaining
constricted.
The effectiveness of the procedure is to be checked
intermittently (feel for the carotid pulse every minute)
without interruption of the cardiopulmonary resuscitation
as far as possible (however, better not interrupt CPR for
> 7 seconds, either to give shocks in ventricular
tachycardia/ventricular fibrillation or to incubate or gaining
IV access).
 522 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Advanced Cardiovascular Life Support
A. Place defibrillator on chest, checking the electrodes
and paddle positions;
B. Set up monitor to assess the cause of asystole whether
it is due to ventricular tachycardia/fibrillation or
complete heart block.
C. IV access maintained for administration of drugs like
adreneline or lignocaine or sodium bicarbonate,
D. Endotracheal intubation.
E. Set up suction and oxygenation.
F. If electrical activity does not appear, pacing is to be
done. (external or endocardial).
G. If the patient is not fully conscious even after
successful treatment, dexamethasone 4 mg i. v every
6 hours is to be given to reduce carebral oedema.
H. After prolonged resuscitation, severe acidosis may
occur for which 50 ml of 8. 4 percent sodium
bicarbonate given iv.
N.B. CPR is indicated in cardiopulmonary standstill
(pulseless, apnoea, unconsciousness) which may occur in
myocardial infarction, cardiac arrhythmias; metabolic
disturbances (hypothermia, hypoxia, hypercapnia); drugs
sensitivity; operations/anaesthesia; electrocution.
b. Obstruction to Left Ventricular Outflow Tract
i. Aortic stenosis: Aortic valvotomy or valve replacement
can be considered. Balloon valvuloplasty is a palliative
measure. Similarily valvotomy, for pulmonary stenosis,
can be accomplished.
ii. Hypertrophic obstructive cardiomyopathy: Beta
adrenoreceptor blocker is the mainstay of medical
management. Calcium antagonists like diltiazem
improve diastolic filling and function. Disopyramide
or amiodarone may be beneficial for arrhythmias.
Antibiotic prophylaxis for endocarditis may be
considered. Digitalis, diuretics, nitrates and beta
receptor stimulants are better not entertained. Severe
exercise must be avoided. Surgical septal myotomy—
myectomy is utilised if refractory to medical treatment.
Septal ablation is an alternative.
c. Acute Myocardial Infarction (Refer to Chapter – Chest
Pain.)
3. Vascular Insufficiency of Outgoing Vessels to the Brain
Hypersensitive carotid sinus (Reflex syncope/Carotid syncope)
Carotid sinus syncope If the carotid sinus is hypersensitive,
minimum doses of belladonna and/or ephedrine may be
necessary. Strict caution must be offered not to wear tight
collars and avoid sudden turning of the head. A majority of
patients require implantation of pacemaker. Mixed
cardioinhibitory and vasodepressor carotid sinus
hypersensitivity may require either radiation therapy or
surgical denerrvation of the sinus.
Carotid artery obstruction Carotid endarterectomy may be
considered, if > 70 percent stenosis present at the origin of
internal carotid artery. The operative risk of a stroke or a
fatality has to be weighed against syncopal episodes.
Extracranial-intracranial anastomosis (superficial temporal
artery to the middle cerebral trunk) may be beneficial.
Subclavian steal syndrome (Refer to Chapter Vertigo)
Cervical spondylosis (Refer to Chapter Vertigo)
4. Vascular Insufficiency of Cerebral Vessels
Cerebral syncope Inadequacy of the brain circulation due to
cerebrovascular diseases (including extracranial vascular
insufficiency like vertebrobasilar or carotid artery disease)
or any other predisposing intracranial pathology like recent
head injury or intracranial tumours or vascular
malformations leading to displacement or insufficiency of
cerebral circulation must be probed and managed
appropriately.
5. Metabolic disturbances
If the hyperventilation with hypocapnia results in cerebral
vascular insufficiency, oxygen and 5 percent CO 2 or
rebreathing his own CO2 by breathing into a paper-bag is
beneficial. Calcium intravenously is given if tetany is present.
Sometimes metabolic abnormalities like hypoglycaemia
may be the underlying cause when parenteral glucose is to
be administered.
6. Anoxic Syncope
i. High altitudes: Initial manifestations (dizziness,
drowsiness, dyspnoea, syncopal episodes) may be
relieved by oxygen administration. If symptoms are
severe and persistent, returning back to the lower
altitudes is required.
ii. Aviation: There is no specific treatment except the
same principles being applied as on ground. However,
flying at greater heights or positive acceleration in the
long axis of the body are better avoided as they can
precipitate cerebral anoxia.
iii. Exertion in congenital heart disease or decompensated
chronic pulmonary disease. Increased arterial oxygen
unsaturation or inability to increase the cardiac output
on exertion (in congenital heart diseases or
decompensated chronic pulmonary disease) with
 Syncope 523

consequent cerebral circulatory insufficiency and
cerebral anoxia, is better prevented by avoiding
unwarranted exertion.
Although oxygen administration may be beneficial,
the fact that inhalation of oxygen in cor pulmonale
may lead to syncope (due to respiratory depression
and consequent hypercapnia) must be borne in mind.
iv. Extreme exertion: Excessive muscular activity during
exercise makes the venous blood leaving the muscles
become more unsaturated with oxygen. When this
blood joins the systemic circulation, arterial oxygen
saturation gets lowered. The consequent syncope due
to cerebral anoxia is prevented by avoiding undue
exertion.
524 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter

Vertigo and Dizziness

34
The term vertigo is derived from the latin word ‘Vertere’ and cerebellum) or (b) central vestibular apparatus (central
which means ‘to turn’. It refers to disturbance of equilibrium connections) rather than visual or somato sensory disorders
with an illusory sensation of movement, either of the self or (Fig. 34.1).
surroundings. It is usually rotatory. Thus, it is defined as an
“awareness of disordered orientation of body in space”. If Table 34.1: Causes of vertigo and dizziness
it is severe the subject may even be thrown on to the ground.
It is usually episodic and may be associated with reflex I. Causes of vertigo
autonomic discharge like pallor, cold, sweating, nausea and 1. Otological (Peripheral)
a. External ear: Wax, Otitis external
vomiting.
b. Middle ear
The terms dizziness and giddiness strictly do not cover i. Eustachian tube block
vertigo as there is a mere sensation of unsteadiness/ ii. Suppurative otitis media
imbalance only without a sense of turning or falling iii. cholesteatoma
(nonrotatory) and without reflex autonomic discharges but iv. Barotrauma
with abnormal sensation in the head (light headedness). c. Internal ear (vestibular end organs and vestibular nerve)
Orderly orientation of the body in space and a balanced i. Acute labyrinthitis
posture is maintained by peripheral and central mechanisms. ii. Toxic labyrinthitis (drugs like streptomycin or salicylates)
iii. Positional vertigo
The afferent impulses from (a) the retina of the eyes; (b) the iv. Meniere’s syndrome
labyrinths of inner ears; and (c) proprioceptors of the muscles v. Motion sickness (physiological)
and joints of the neck, trunk and limbs are of prime vi. Trauma
importance. These impulses from the sensory end organs vii. Peri lymph fistula
are inter linked to the central mechanisms—nuclei of the d. Vestibular nerve: Vestibular neuronitis
brainstem (vestibular nuclei, oculomotor nuclei and red 2. Neurological (Central)
nuclei), basal ganglia, medial longitudinal bundle and a. Cortical
i. Aura of epileptic attack (Vestibular epilepsy)
cerebellum. These constitute the reflex pathways, playing ii. Migraine (Basilar)
the pivotal role in the maintenance of equilibrium. From these iii. Tumour
centres, the impulses reach the cerebral cortex, superior iv. Atherosclerosis
temporal and inferior parietal lobes, which in turn affect the b. Brainstem
voluntary movements through motor centres in mid brain i. Vetebrobasilar insufficiency (atherosclerosis), TIA
and spinal cord to adjust balanced posture (Table 34.1). ii. Subclavian steal syndrome
The disturbance of spatial orienttion is not only due to iii. Tumour
iv. Multiple sclerosis
disordered function of the peripheral and central c. Cerebellar (Flocculo-nodular lobe which is linked closely to
mechanisms but due to decreased blood flow to the vestibular system)
concerned parts. Nevertheless vertigo is usually due to i. Tumors
diseases of vestibular apparatus which consists of (a) ii. Thrombosis of the posterior inferior cerebellar artery.
peripheral vestibular apparatus (labyrinth, i.e. semicircular ii. Trauma
canals, and vestibule, i.e. utricle and saccule utricle and
saccule) and the vestibular nerve till it enters the brainstem Contd...
 526 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Fig. 34.1: The labyrinth and vestibular pathways (Vestibular apparatus)

Contd... Contd...

d. Eighth nerve b. Sudden fall in cardiac output

i. Acoustic neuroma c. Postural hypotension
ii. Basal meningitis d. Cardiac arrythmias
e. Head injury e. Valvular heart disease
f. Alcohol and drugs 2. Adverse Reactions of Drugs
3. Ocular a. Hypotensive drugs
a. Standing at unusually high place (Height vertigo)— b. Psychotropic drugs
physiological c. Antihistamines
b. Ocular muscle paralysis d. Excess alcohol
c. Using strong lenses for the first time 3. Haematological
4. Cervical a. Anaemia
a. Cervical spondylosis b. Hyperviscosity
b. Whiplash injury 4. Metabolic: Hypoglycaemia, Hyperventilation
5. Psychogenic: Hysteria 5. Neurological
(The common causes of vertigo are labyrinthopathies and vascular a. Autonomic neuropathy
disturbances in the head and neck leading to ischaemia in the vestibular b. Tumours
system.) c. Cerebrovascular accidents
II. Causes of dizziness d. Head injury
1. Cardiovascular 6. Failing Eye Sight
a. Hypertension 7. Psychogenic: Anxiety Neurosis
Contd...
 Vertigo and Dizziness
Vertigo
Otological Causes
External ear
• Otitis externa It can present as vertigo and otorrhoea.
Acute otitis media may be associated with ear discharge,
ear-ache and mild labyrinthitis with vertigo.
Middle ear
• Chronic otitis media There may be conductive deafness
with vertigo if there is extension into the labyrinthine
structures besides a foul smelling purulent discharge.
• Cholesteatoma In the temporal bone may present itself
as vertigo with squamous debris in external auditory
canal. It may be seen in cerebellum or cerebellopontine
angle.
Internal ear
• Acute labyrinthitis: The symptoms of acute vestibular
disturbances like vertigo, nausea, vomiting, nystagmus,
ataxia of the limbs on the affected side with rapidly
progressive deafness and pain in the ear will be noticed.
The subject will be lying on the sound side. The affected
ear will be uppermost. Nystagmus is coarser, on looking
to the side of the lesion.
• Toxic labyrinthitis: Drug toxicity especiaaly streptomycin
may result in vertigo due to damage of the fine hair cells
of the vestibular end organs and the damage may be
permanent in elderly. Sometimes food allergy may result
in vertigo.
• Positional vertigo: This occurs when the head is placed
in a recumbent, position on either side. Two types are
documented. One usually comes at night, while turning
in the bed and is called benign positional vertigo. The
other occurs when head is tilted back while standing,
(positioning) Which is described as paroxysmal posional
vertigo. It may be due to peripheral or central lesions. If
peripheral, it is commonly due to the disease of the otolith
organ, or folllows usually head injury to the labyrinth or
a free floating clot within endolymph on posterior
semicircular canal or vestibular neuronitis or ear
infection, BPPV lasts for less than one minute. This
peripheral group is described as Benign Paroxysmal
Positional Vertigo (BPPV) related to posture as compared
to the central positional vertigo due to lesions of the
fourth ventricle. It differs from other vestibular disorders
in which vertigo is increased by head motion, which is
present at other times as well, unlike in BPPV.
Vertigo will be severe if the head is positioned in
one specific movement (lowered) and passes off, if the
527
head is maintained in the same position. Any movement
of head may cause it.
Paroxysmal positional vertigo can be elicited by
moving the head suddenly (Hallpikes’s Test) or by
changing the position from sitting to recumbency with
the head turned to one side. After a delay of ten seconds,
vertigo and unidirectional nystagmus occur and lasts
for less than one minute. It can be reversed by moving
from recumbency to sitting position. This can be
reproduced by repeated manoeuvers with symptoms
becoming less marked with repetition. This reproduction
in a specific pattern and reversibility is highly specific
to benign peripheral group and not seen in malignant
central vertigo of posterior fossa tumours.
If central, vertigo is mild and persist as long as the
head is maintained in the position causing vertigo. There
is no question of vertigo or nystagmus becoming less
or passing off as there is no adaptation and fatiguability
(unidirectional mystagnum is usually not a feature of
central lesions). It is usually due to posterior fossa
(cerebeller) tumour or multiple sclerosis. (vide infra–
Positional tests.)
• Menieres syndrome The vertigo is recurrent, associated
with vomiting, ‘roaring’ tinnitus and progressive hearing
loss due to nerve deafness. The episode lasts for half an
hour to many hours and can be incapacitating. Between
the attacks there may be tinnitus and fluctuating hearing
loss in the affected ear. It is due to failure of the
mechanism regulating production and disposal of
endolymph, which results in dilatation of the endolymph
system of the internal ear. This leads to degeneration of
the fine vestibular hair cells. The disease runs over some
months or years. Otosclerosis may give rise to similar
paroxysmal vertigo but the deafness is obstructive
(conduction) or mixed. Drop attacks may be
encountered rarely. Episodic vertigo without auditory
symptoms is called as “Recurrent vestibulopathy”.
• Motion sickness (physiological) Vertigo, vomiting with
or without nausea, abdominal discomfort, blurring of
vision and autonomic disturbances like sweating,
flushing, and pallor may be associated. This
physiological disturbance of visceral function is
encountered in any form of motion sickness; be it travel
in cars, planes, ships (sea-sickness). Abnormal
stimulation of the labyrinth is the prime factor with
irregular excitation of the vertical canals leading to
disturbance of equilibrium.
Trauma Vertigo may result from either injury of
the temporal bone or postoperatively. The latter may be
associated with neural deafness and perilymph fistula.
 528 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Perilymphatic fistula (Leakage from inner ear into tympanic
cavity via round/oval window) caused by barotrauma or
cholesteatoma. Precipitation of vertigo by straining is the
clue and can be simulated by performing valsalva manoeuvre.
d. Vestibular nerve: Vestibular neuromitis
Vestibular neuronitis (Acute vestibular failure) Vertigo is abrupt
in onset and lasts for somedays, following upper respiratory
infection. The hearing is not affected and there is no tinnitus.
Vomiting may be present and staggering gait may occur. It
usually recovers in three weeks time. Recurrence may be
there but in a milder form. Caloric test shows diminished
response or canal paresis on the affected side like Meniere’s
syndrome (Fig. 34.2).
Neurological Causes
Cortical lesions Vertigo occurs in an aura of epileptic fit
and when the patient recovers consciousness, the
vertigo disappears. Similarly, it may be in the aura of
migraine and lasts for several minutes before the onset of
the headache.
Intracranial tumours may be associated with vertigo
depending on the anatomical location. The general
symptoms atributed to increased intracranial pressure like
headache, projectile vomiting, papilloedema, disturbances
of pulse rate, blood pressure and respiration will offer the
clue.
Brainstem lesions (Central positional vertigo) vide supra In
the pontine tumour, vertigo is common along with occipital
headache. Ocular symptoms like diplopia, paralysis of
conjugate deviation and weakness of the lateral rectus are
usually seen. Nystagmus and slight ataxia of the limbs
present, though cerebellum is not affected. Crossed paralysis
with variable sensory loss elicited.
The acoustic neuroma in the cerebello-pontine angle
usually presents itself with tinnitus as first symtom followed
by advancing deafness besides giddiness. Loss of responses
to calorie test, loss of corneal reflex on the side of the
deafness, occipital headache, weakness of the lateral rectus
muscle, facial weakness and cerebellar signs will be
diagnostic.
In the vertebrobasilar insufficiency, vertigo is due to
reduction of blood supplyto the brainstem and usually
associated with diplopia, dysphagia, dysarthria, dysaesthesia,
deafness, ataxia and other corresponding neurological signs.
(Hemi-or quadriplegia with sensory symptoms). Drop
attacks may occur.
In subclavian steal syndrome there is occlusion of the
subclavian artery proximal to the origin of vertebral artery,
wherein pulse and blood pressure are reduced in the affected
arm when compared to normal side. Blood from the
contralateral vertebrobasilar system is used to feed the distal
subclavian artery via anastamotic channels. Exercise of the
affected arm leads to further fall in blood pressure followed
by retrograde vertebral blood flow to that arm (steal)
resulting in brainstem ischaemia and consequent vertigo.
This exercise induced vertigo and the difference of blood
pressure of more than 20 mm of Hg between the arms with
or without a bruit over the affected subclavian artery
(supraclavicular space) are diagnostic.
Cerebellar lesions (Central Positional Verligo-Vide Supra)
tumour involving flocculonodular lobe causes vertigo as it
is linked with vestibular system. Symptoms of cerebellar
deficiency are marked on standing and that of increased
intracranial pressure occur early.
The onset of thrombosis of the posterior inferior
cerebellar artery is associated with severe vertigo and
vomiting, dysphagia, cerebellar deficiency on the side of
the lesion, ipsilateral paralysis of the palate and pharynx,
and dissociated sensory changes (analgesia and as well as
thermoanaesthesia) on the ipsilateral face, and the trunk as
well as limbs on contralateral side are characteristic.
In multiple sclerosis due to patches of demyelination,
vertigo may be complained of. Features of nystagmus,
dysarthria, intention tremor and ataxic paraplegia are
classical. (direction of cerebellar nystagmus is towards side
of lesion)
Eighth nerve
i. Acoustic neuroma (vide supra)
ii. Meningeal: Basal Meningitis
It is due to inflammation of the leptomeninges at the
base due to infections like leutic and may involve the cranial
nerves while passing through the meninges. Usually chiasmal
region and cranial nerves (3rd, 6th, 7th and 5th nerves in
the order of frequency) are affected. If the 8th nerve is
involved, there will be vertigo and deafness.
Head injury Previous history of injury will be contributory in
certain cases of vertigo since persistent disabling symptoms
like headache, vertigo and mental disturbances are common
as a sequelae.
Alcohol and drugs Alcohol intoxication or Barbiturate or
Phenytoin intoxication cause vertigenous spells Foetor and
Blood levels confirm.
Ocular (Central)
Vertigo due to ocular muscle paralysis is usually associated
with diplopia. Erroneous projection of the visual field is
always in the normal direction of action of the affected
 Vertigo and Dizziness
muscle, i.e. diplopia in gaze towards the paralysed muscle.
When this produces sufficient spatial disorientation, vertigo
occurs.
Individuals wearing glasses for the first time may develop
vertigo due to alteration and distortion of images from the
abnormalities of the dioptric apparatus.
Height vertigo produced on looking down from a height
is due to abolition of the usual vanishing point which
disappears after sitting or visually fixing a nearby fixed
object. The other examples of perceptual distortion is looking
from the platform at a fast moving train.
Cervical
In cervical spondylosis, the blood supplied to the brain is
diminished by the movement of the neck due to the
compression of the vestibular artery by protruding
degenerated intervertebral discs.
Whiplash (flexion-extension) injury to the neck causes
neck pain associated with vertigo and positional nystagmus.
The mechanism involved is impairment of the vestibular
function or vertebrobasilar insufficiency.
Psychogenic
Vertigo may occur as a symptom of conversion reaction of
hysteria. The mode of production of this symptom is by a
suggestion and entertaining the symptom to gain the
purpose. The symptoms usually do not occur when the
individual is alone but get exaggerated in the presence of
sympathetic audience. The subject may be indifferent to
the symptoms, although they may be incapacitating.
Invariably, there will be no of evidence of any organic
disease.
Dizziness
Cardiovascular
Giddiness is common in untreated hypertensives due to
selective vasoconstriction and disturbed cerebral blood flow,
impairing the supply of necessary nutrients like oxygen and
glucose. Similarly, the cerebral blood flow will be diminished
due to an abrupt fall in cardiac output as occurs in
hypovolaemia due to haemorrhage, coronary occulsion,
cardiac arrhythmias or valvular disease of the heart. A
significant reduction of cerebral blood flow usually 50
percent may result, if the arrhythmias last for about 4
seconds.
Diminished effective cerebral blood flow can also occur
with postural hypotension resulting in ischaemia and
529
consequent giddiness. Anaemia usually produces dizziness,
unless it is acute from haemorrhage when vertigo results,
due to sudden fall in cardiac output.
Drugs
The most common adverse reaction of drugs is unsteadiness
experienced with antihistamines streptomycin and
psychotropic drugs. It may also arise as a result of
hypotensive drugs reducing the pressure impairing the
cerebral perfusion. Drugs like methyldopa can result in
postural hypotension, with dizziness. Hypo glycaemic drugs
may cause unsteadiness with or without other features of
hypoglycaemia.
Haematological
Anaemia (Refer to Chapter ‘Fatigue’).
Metabolic
i. Hypoglycaemia (Refer to Chapter ‘Coma’).
ii. Hyperventilation (Refer to Chapter ‘Dysphoea’).
Neurological
A feeling of unsteadiness with a tendency to fall on stooping
may be associated with increased intracranial pressure as
occurs in an intracranial tumour.
Similarly, cerebral infarction or transient ischaemic
attacks of the brainstem or in obvious stroke may result in
dizziness, accompanied by vomiting, headache and other
neurological features.
Postconcussional syndrome may present as giddiness,
headache and nervous instability. Looking to one side
or in the upward direction may cause a feeling of
imbalance. The nervous instability may be restlessness,
failure to concentrate, feeling of apprehensions and
tenseness.
Autonomic Neuropathy
Loss of pupillary reflexes, mydriasis, diminished lacrimation
and sweating, impotence, bowel and bladder paresis are the
associated features due to degeneration of non-medullated
autonomic nerve fibres. Sometimes diabetic neuropathy may
be associated with disturbance of autonomic function
resulting in dizziness. esp. postprandial period (Autonomic
neuropathy may be primary or secondary to drugs/part of a
polyneuropathy/ageing).
 530 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Failing Eye Sight
It may be an isolated event or combined with deterioration
of proprioception or vestibular deterioration, as seen
frequently in elderly patients complaining of dizziness.
Psychogenic
Usually sufferers from anxiety neurosis will experience
giddiness only without any sensation of rotation. The
symptoms of overactivity of the sympathetic nervous system
and features of anxiety and tension will be obvious.
CLINICAL APPROACH
It is of immense value to allow the patient to describe his
symptoms without any interruption, to begin with. Specific
questioning can be adopted to elicit the history precisely.
1. Determine whether it is vertigo or dizziness or entirely a
different problem like syncope or ataxia. If it is true
vertigo, elucidate its origin whether vestibular or
nonvestibular. If vestibular, is it pathological (peripheral
or central) or merely a physiologic vertigo (height vertigo
and bending vertigo or motion sickness.
2. Periodicity
a. Recurrent—Meniere’s syndrome, Migraine Vertebro-
basilar ischaemia.
i. If rotational—Direction of rotation, severity and
nature of subsequent effects.
ii. Is there any sensation of falling or a fall? Any
warning features, any loss of consciousness (loss
of consciousness in vertigo is exceptionally rare
except in temporal lobe epilepsy).
iii. Any features of a seizure?
iv. Any symptoms of transient ischaemic attacks.
b. Persistent, e.g. chronic ear disease, ototoxic drugs,
posterior fossa tumour, acoustic neuroma, brainstem
lesions.
c. Acute—Vestibular neuronitis, brainstem infarct,
drugs, cerebellar lesion.
3. Duration of attack
a. Several seconds, e.g. benign positional vertigo
b. Several minutes to hours Meniere’s syndrome
c. Several days, e.g. vestibular neuronitis
d. Permanent, e.g. brainstem infarction.
4. Intensity: Marked in Peripheral and mild in central vertigo.
5. Directions of Spin: Towards quick phase in peripheral
and variable in central vertigo.
6. Aggravating factors (relationship to posture and
position)—Movements of the head or neck, sudden
upright posture from supine position; food allergy or
intolerance. If exacerbated by loud noise and valsalva
manoeuvre, it indicates peripheral inner ear disorder with
a perilymphatic fistula (otolith-tullio phenomenon).
7. Associated features
a. Aural (hearing loss, tinnitus, suppuration)
b. Visual (diplopia)
c. Autonomic (nausea, vomiting, sweating, hyper-
ventilation)
d. Headache
e. Any neurological features.
8. Past history
a. Ear discharge
b. Upper respiratory infections
c. Head injury
d. Epilepsy
e. History of taking any ototoxic drugs, and recent
alcohol bouts
f. Hypertension or diabetes mellitus
g. Any unaccustomed activity like mountain climbing,
sea bathing results in vertigo due to barotrauma.
Physical Examination
It is an exercise aimed at neuro-otological evaluation. During
an attack, observe the position of the patient in bed (usually
inclined to one side); e.g. (In Meniere’s disease patient lies
on sound side) elicit inclination to stand and walk without
support (unable to do so in vertigo).
General Examination
a. Look for pallor of mucous membranes.
b. Record blood pressure
i. In both supine and standing positions (after standing
still for 3 minutes).
ii. In both upper arms (after exercising the arms).
c. Examine pulse rate, rhythm, and volume; palpate the
carotid pulse and also look for any vascular bruits.
Systemic Examination
Neurological examination (with special reference to 8th
cranial nerve and nystagmus)
a. Assess any cranial nerve dysfunctions (including
fundus examination).
b. Elicit abnormal motor and sensory long tracts signs
or lesions of the brainstem.
c. Cerebellar signs
d. Reflexes—Corneal, plantar and deep reflexes
e. Gait
f. Autonomic nervous system
 Vertigo and Dizziness
8th cranial nerve Test for both divisions of the nerve.
1. Auditory division measures hearing threshold and ascer-
tain whether deafness is conductive or perceptive by:
a. Voice test—Normal hearing should be possible at 18
feet distance with a forced whispered voice; if not
heard conversation voice is tested.
b. Tuning fork tests—(Frequency used 256 or 512 Hz)
i. Rinne’s test—In conductive deafness, it is
negative (bone conduction is better than air
conduction) and it is positive (air conduction is
better than bone conduction) in nerve deafness
and normal individuals.
ii. Weber’s test—In conductive deafness the
vibrations are localised in the affected ear
whereas in nerve deafness it is better heard in
the normal ear or more often heard in the midline
itself. In normal persons the vibrations are heard
in the middle line.
iii. Audiometric test—Vide infra.
2. Vestibular division—Vide infra.
Nystagmus (Involuntary rhythmic oscillation of the eyes)
This is a physical sign of paramount importance in the
analysis of symptom of vertigo. If vertigo is
accompanied by nystagmus it is postional vertigo. It
can be spontaneous or induced either by movement or a
particular position of the head or by caloric stimulation.
It may be:
a. Vestibular (peripheral—labyrinth or vestibular nerve;
and central—vestibular nuclei in the brainstem or
cerebellar connections);
b. Non-vestibular (retinal, ocular, congenital) in origin.
To test for nystagmus the patient is asked to (i)
look straight and observe whether the eyes are steady
at rest or oscillations present; (ii) look in all four
directions within the area of binocular vision, after
waiting at least 5 seconds at each position for
nystagmus to occur; and (iii) assume different
positions of the head to see for nystagmus to develop
(positional nystagmus).
If nystagmus is present ascertain its character.
i. Pendular (horizontal oscillations, at equal amplitude
and speed of movement, on either side of the midline
and there is no quick phase) is usually non-vestibular.
ii. Jerky (quick in one direction followed by a slow
movement in the other and can be in one plane, i.e.,
horizontal or vertical or more than one plane, i.e.
rotatory. It may be present at rest or on deviation of
the eyes. The quick movement indicates direction
of nystagmus is usually of vestibular origin, or
cerebellar.
531
iii. Ataxic or dissociated (different response in each eye)
is usually due to lesions of the brainstem.
Nystagmus is said to be severe, if present even on looking
to the side of the slow component. If nystagmus is of
vestibular origin it has to be differentiated whether it is of
peripheral or central origin.
The characteristic of peripheral type of vestibular
nystagmus are:
i. Unidirectional
ii. Direction of nystagmus opposite to the affected
labyrinth (Horizontal or rotatory)
iii. Never vertical or rotatory
iv. Conjugate character (Two eyes move in identical
manner)
v. Vertigo marked
vi. Visual fixation inhibits nystagmus and vertigo; and
enhanced by loss of fixation
vii. Duration of symptoms temporary, varies from
minutes to 3 weeks and recurrent
viii. Tinnitus or deafness may be present
ix. Tendency to fall in the direction of the slow
component (affected side)
The characteristics of central type of vestibular nystagmus
are:
i. Bidirectional, (Nystagmus directed to right on looking
to right and vice versa) (i.e. changes the direction
with changes of position).
ii. Direction of nystagmus is towards the side of the
lesion as in cerebellum
iii. May be vertical in midbrain and medulla
iv. Dissociated character [i.e. Nystagmus is more
marked and coarse, horizontal in abducking eye
whereas it is fine and less marked in the other eye
which is slow to adduct (Brainstem lesion)].
v. Vertigo mild or absent
vi. Visual fixation does not inhibit
vii. Duration of symptoms permanent
viii.Tinnitus or deafness may be absent
ix. Tendency to fall may be variable.
Nystagmus may occur at extremes of lateral gaze or
on looking at a moving train (Physiological).
Otological examination
a. Look for accumulated wax or any discharge from
the external meatus.
b. Examine the tympanic membrane with auriscope.
c. Test for auditory function.
d. Vestibulometry is used for evaluating vestibular
system.
 532 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
i. Nystagmus including positional and induced
ii. Specific tests
iii. Romberg’s and other tests (Vide infra)
[Vestibule, i.e. utricle and saccule concerned with position
of head whereas semicircular canals with movement of
head].
Cardiovascular Examination
a. Any arrhythmias, and
b. Valvular diseases.
Posture tests
a. Positional test (Dix and Hallpike)—Make the patient
seated on a couch, hold his head and lay it briskly so
as to position it 30° below the couch level and rotate
it 30-45° towards the examiner. Normally there is
no nystagmus or vertigo. If severe vertigo and
nystagmus occur towards the downmost ear, i.e.
affected ear and last for several seconds, it is
suggestive of benign positional vertigo due to
degeneration of otolith apparatus. Similar episode
may be seen in less intensity on returning to sitting
position and disappears on repetition of the
manoeuvres. The nystagmus persists with mild or
absent vertigo in central lesions (posterior fossa or
brainstem.)
b. Cervical posture test—Movements of cervical spine
are done by positioning the neck in all four directions
gently and observing the symptoms thereof (limitation
of movement, vertigo and nystagmus of cervical
origin). This identifies the underlying cervical
spondylosis or vertebral atherosclerosis.
c. Body posture test—Make the patient stoop for a
minute and straighten up to provoke the attack.
d. Doll’s eye movements—(Refer to Chapter ‘Coma’)
e. Head shaking test (not routinely employed)—The
head is shaken fairly rapidly from side to side 20
times. If nystagmus develops towards the opposite
side, it indicates vestibular lesions causing loss of
lateral canal responses on caloric test.
f. Romberg’s and other tests
i. Romberg’s test: Ask the patient to stand with both
the feet drawn together (both heels and toes
touching) and close the eyes. Look for the
direction of swaying or tendency to fall. Usually
the patient tends to fall to the side of the peripheral
lesion. There is no swaying in normal persons.
ii. Sharpened Romberg test: It comprises standing
tandem with eyes closed on either leg with arms
folded across the chest for 30 secs. If performed
it excludes organic neurologic disease.
iii. Other tests:
• Walking with eyes closed.
• Standing on one leg with eyes closed.
• Tandem walking—Ask the patient to walk
with the great toe touching the heel, with eyes
opened and closed.
• Any disequilibrium while conducting these
clinical tests indicates vestibular dysfunction.
In clinical practice, unsteadiness has to be differentiated
from:
1. Sensory or cerebellar ataxias, where the disequilibrium
is due to impairment of coordination of movements of
the limbs without any rotatary movement of the body.
In vertigenous ataxia, coordination of the movements
of the limbs is not affected although staggering is present.
2. Oscillopsia wherein surrounding objects appear moving
in cases of coarse nystagmus of central origin or
opsoclonus (irregular, conjugate dancing movements of
the eyes).
3. Hypoglycaemia wherein the low blood sugar may result
in unsteadiness due to the affect on cerebral function
and associated with sweating, apprehension, tachycardia,
etc due to adrenaline stimulation (Refer to Chapter ‘Coma’)
4. Hyperventilation syndrome—(Refer to Chapter
‘Dyspnoea’).
Investigations
i. Blood
a. Studies like RBC, haemoglobin percentage,
WBC, differential count and ESR
b. Serology—VDRL
c. Chemistry—Blood sugar, serum cholesterol
fractions and triglycerides
ii. Radiology
a. X-ray of mastoids, middle ear
b. X-ray of the skull, internal auditory meati
c. X-ray of the cervical spine for spondylitic
changes or any calcified arteries
d. X-ray of the chest.
iii. ECG
Routine and ambulatory monitoring
iv. CSF Analysis
v. EEG
vi. Audiometric tests
• Pure Tone audiometry This is done to measure
the hearing acuity. Pure-tone audiometer delivers
tones of variable frequency and intensity to the
ears by ear phones and audiograms are recorded.
The normal hearing level is zero decibel of
 Vertigo and Dizziness 533

intensity at all frequencies of sound waves in (normal) and reduced on left side (affected) to
cycles per second (from 125 to 6000). In hot water or vice versa with cold water, which
conductive deafness, bone conducted hearing is indicates left sided central lesions like, left
better than air conducted and both low and high cerebral hemisphere and vice versa (Fig. 34.2).
tones are equally affected. In nerve deafness air Reduced nystagmus is the hall mark in this test.
conducted hearing is better than bone conducted • Electronystagmography (ENG) It enables
and only high tones are significantly affected. detection of nystagmus even though it is not seen
Recruitment The phenomenon of loudness on naked eye examination. The permanent record
recruitment is increase of loudness of sounds of nystagmus on paper further facilitates
more rapidly with increasing intensity of sounds measurement of its amplitude duration. A
in the affected ear as compared to the normal complete ENG consists of series of tests which
ear (quiet sounds cannot be heard). This is usually include eye movements with eyes open, eyes
due to destruction of the outer hair-cells in the closed and caloric testing. The electrodes are
cochlea. It helps in localising the site of a lesion placed at each outer canthus and on the forehead
in sensory neural deafness, since the presence
of recruitment is associated with cochlear lesions
than the lesions of acoustic nerve or central
connections.
vii. Vestibular Tests (Specific)
Nystagmus is induced by thermal, visual, rotational
stimulation and analysed.
• Bithermal caloric tests This test assesses the
labyrinthine function of each ear. The patient lies
with the head at 30° above the horizontal level
when the lateral semicircular canals lie in a vertical
plane. Tests are carried out on each ear with both
cold water (30°C) and hot water (44°C). 250 cc
of water is allowed to flow into the external
auditory meatus for 40 seconds. Five minutes
are allowed between the irrigations. The patient
is asked to open his eyes and fix at an object
over the ceiling. This produces horizontal
nystagmus which lasts for about 2 to 3 minutes
in a normal person (the horizontal nystagmus
elicited with cold water will have its fast phase
to the opposite side, whereas with hot water the
response is reversed). A lesion in the peripheral
vestibular apparatus (vestibule or vestibular
nerve) results in absent or diminished response
(i.e., duration of nystagmus is reduced) to both
hot or cold irrigations on the affected side, be it
left or right canal paresis. Meniere’s disease and
acoustic neurinoma are classical examples.
Nystagmus may be more readily induced
in one direction in some cases and this is known
as directional preponderance which may be to Fig. 34.2: Caloric tests (a) Normal, (b) Canal paresis—
the right or left. It occurs towards the normal Peipheral lesions (Meniere’s disease and 8th nerve lesions),
ear usually. A right directional preponderance (c) Central lesions (central connections of a labyrinth or
means a nystagmus increased on right side brainstem or cerebral hemispheres)
534 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
between the eyes. In peripheral vestibular
disorders, nystagmus is not caused with optic
fixation but a regular nystagmus may be revealed
or accentuated when eyes are closed and in
darkness, the amplitude of which is large towards
the direction of quick phase. In central lesions,
nystagmus is irregular and abolished by eye
closure and in darkness.
• Rotation test The labyrinth may be stimulated
by rotating the patient in a revolving chair. It
has limited clinical application since both
labyrinths are stimulated simultaneously.
Revolve the chair for about 10 times in 20
seconds in either direction. For instance, if the
rotation is directed towards the right, the normal
response is nystagmus being to the right during
acceleration with a sense of rotation to the right
(i.e., same side), when the chair is decelerated
nystagmus is seen in the left with a sense of
rotation to the left, i.e. opposite direction of
rotation, though the head and body are at rest.
The response is more marked if the rotation is
carried on the direction of affected labyrinth
than when rotation is carried out in the opposite
direction. There will be no response if the
vestibular activity is deficient bilaterally as
occurs in congenital deafness or ototoxicity due
to drugs.
Fistula test After fitting an ear piece tightly into
the meatus, the air pressure is raised in the meatus
by sqeezing the attached rubber bag. Nystagmus
induced on releasing the bag, is in the direction
of the affected side in a case of fistula, which
may follow surgical trauma or sudden changes
of pressure.
viii. Other Tests
• Glycerol test This test is useful in fluctuant
sensoryneural loss due to Meniere’s disease.
Glycerol is given orally with equal amount of
saline. If the hearing is improved, it is said to
be positive; whereas there may be a poor
response or a negative result, even if the patient
is in a remission stage with good hearing.
• Hyperventilation test Ask the patient to
hyperventilate for 3 minutes and if the
complained symptoms are experienced, it
indicates that hyperventilation may be the
underlying factor, thus helping the diagnosis.
Special Investigations
1. CT scanning of the brain for temporal bones and
posterior fossa.
2. Magnetic resonance imaging.
3. Vertebral angiography.
4. Dizziness stimulation battery.
• In the evaluation of vertiginous patients, they should
be initially classified into
a. Sensation of rotation (vertigo)
b. Sensation of light headedness or feeling of
unsteadiness/swimming or floating in the head
(dizziness)
c. Sensation of imbalance or feeling of unsteadiness in
the limbs (ataxia)
d. Sensation of impending loss of consciousness (faint)
If it is vertigo, it is fruitful to subdivide them
into the following three groups so as to enable one
to arrive at a positive diagnosis.
a. Vertigo per se (without aural symptoms), e.g. benign
positional vertigo, vestibular neuronitis.
b. Vertigo with aural symptoms or nausea and vomiting,
e.g. labyrinthitis, Meniere’s disease.
c. Vertigo with clinical features of intracranial lesions,
e.g. vertebrobasilar insufficiency, intracranial
tumours.
TREATMENT OF VERTIGO AND DIZZINESS
Specific spotting of the different disorders giving rise to
disequilibrium (dizziness and vertigo) is imperative to choose
the therapeutic options. The list of disorders appended (vide
supra) comprises organic (otological, neurological, ocular,
cervical and general medical disorders) and psychogenic
aetiologies.
In most of the cases, the disease processes involve
either (i) labyrinth (inner ear), vestibular portion of 8th
nerve or its connections (peripheral vertigo) or (ii)
cerebrum or brainstem, cerebellum (central vertigo). The
latter is relatively less common. The former is acute
episodic in character (an impression of external
objects rotating around the individual) whereas the
latter is chronic persistent or recurrent. Hence the
management depends upon the case on hand, whether it
pertains to (i) an acute vertigenous episode or recurrent
episodes with labyrinthine damage or (ii) chronic recurrent
attacks or chronic persistent disequilibrium with central
affections.
 Vertigo and Dizziness
Therapeutic Options
The therapeutic options are (i) pharmacotherapy, (ii)
counselling and (iii) surgery.
Pharmacotherapy
The available drugs are classified as (a) drugs for
symptomatic relief and (b) drugs to modify the underlying
pathophysiology.
a. Drugs for symptomatic relief are (i) antihistamines; (ii)
antiemetics; (iii) anticholinergics and (iv) sympathno-
mimetics: (ephedrine 25 mg/day) (v) psychotropics.
b. The drugs to modify the underlying pathophysiology
are (i) vasodilators; (ii) diuretics; (iii) cerebroactive
drugs; (iv) corticosteroids and (v) antibiotics.
Anti-vertigo drugs (Symptomatic relief)
a. Antihistamines (labyrinthine suppressants): (i) cinnarizine
(15 mg tds); (ii) dimenhydrinate (50-100 mg tds); (iii)
promethazine theoclate (25 mg tds); (iv) cyclizine (50
mg tds for severe attacks) and (v) meclizine (25-50
mg).
b. Antiemetics: (i) prochlorperazine (5 mg tds) acts directly
on the brainstem (suppresses central vestibular
pathways) and controls emesis associated with vertigo.
It is not recommended for long use because of
extrapyramidal side-effects; (ii) other drugs—(refer to
Chapter Vomiting).
c. Anticholinergics: (i) atropine sulfate (0.4 mg i.m.); (ii)
hyoscine hydrobromide (0.6 mg 3 hourly) is useful for
aborting vertigenous attack due to endolymphatic
hydrops. It acts by blocking afferent impulses coming
to the vomiting centre. Scopolamine transdermal Patch.
d. Psychotropics: Including tranquilisers (both minor and
major) and sedatives are used by virtue of their GABA-
nergic action of suppression of central vestibular
pathways. (Diazepam 2.5 mg 1-3 times/day) However,
they are better avoided since they interfere with the
normal compensatory mechanisms, which enable
recovery from vestibular dysfunction.
N.B: Chronic use not advocated.
Accessory drugs
a. Vasodilators: (i) cinnarizine (25 mg tds) prevents
vasospasm and reduces blood viscosity; (ii) betahistine
(8 mg tds) improves blood flow to the labyrinth and
brainstem; (iii) cyclandelate (200-400 mg bd); (iv)
papaverine (60-300 mg SC); (v) pentoxyphylline (400
mg bd) improves RBC flexibility and decreases blood
viscosity and (vi) nicotinic acid (100 mg 6th hourly).
b. Diuretics: For decreasing intralabyrinthine fluid pressure;
(i) frusemide (20-40 mg orally or iv); (ii) hydro-
535
chlorothiazide (25-100 mg) and (iii) glycerol (1 oz 6th
hourly).
c. Cerebroactive drugs for metabolic activation and
neurotransmitter modulation via GABAnergic or cyclic
AMP mechanisms: (i) ergot derivatives (dihydro-
ergocristine) 1 mg tds; (ii) pyritinol (100-200 mg tds);
(iii) piracetam (400-800 mg tds); (iv) vitamin B6 (50
mg), A (1000 units), E (200 mg); and (v) carbamazepine
(200 mg tds) for temporal lobe giddiness.
d. Corticosteroids: Prednisolone (5 mg 6th hourly) for
nonsuppurative labyrinthitis.
e. Appropriate antibiotics for suppurative labyrinthitis.
Counselling
a. Patient should be explained about the nature of the
balance disorder and assured that there is no underlying
sinister life-threatening disease.
b. Adaptation exercises (Cawthorne-cooksey head and
balance exercises—Eye movements, head and neck
movements, shoulder and trunk movements, standing
up exercises and lying down exercises). Encourage one
exercise at a time to be performed for 3 minutes three
times a day and increase progressively up to 30 minutes.
These exercises are of particular value only in chronic
peripheral vestibular disorders. BPPV is self limited and
if persistant repositioning exercise programme yields
good results.
Surgery
Those cases which fail to respond to medical therapy are
considered for surgery. The conservative surgery (shunt
operations, vestibular nerve section) is indicated if the
hearing is good or it is the only hearing ear. Destructive
surgery (labyrinthectomy, translabyrinthine VIIIth nerve
section) is indicated when the hearing loss is severe and
other ear is normal.
Specific Treatment for Specific Diseases
Otologial (Peripheral)
External ear
• Impacted cerumen (Wax) It is cleared through the
speculum if readily removable. It is painful, irrigate with
water (37°C) or if necessary, soften the mass repeatedly
with olive oil drops or glycerin (70%) or hydrogen
peroxide (3%) and then irrigate after a couple of days.
• Otitis externa Systemic antibiotics and analgesics may
be necessary if there is lymphadenopathy or fever.
Topical antibiotic ointments may be applied to the ear
canal followed by ear drops (preferably after clearing
 536 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
debris either by wiping with a cotton wick or carbamide
peroxide in anhydrous glycerol).
• Malignant external otitis due to Pseudomonas aeruginosa
in elderly diabetics must be treated vigorously with
affective antibiotics parenterally and tight control of
diabetes mellitus.
Middle ear
• Eustachian tube catarrh Politzer’s method is beneficial.
The nozzle of the politzer’s bag is inserted into one nostril
and both nostrils are closed firmly. Then the patient is
asked to swallow when simultaneously the air from the
bag is pumped into the nose to facilitate air gushing into
the tube. This inflation improves the subjective
symptoms. Alternatively the Eustachian catheter can also
be used. (Introduce the nozzle of the Politzer’s bag into
the catheter and perform inflation).
Suppurative otitis media (Refer to Chapter ‘Vomiting’).
• Cholesteatoma A common complication of chronic otitis
media with perforation resulting information of a mass
of desquaminated epithelium with cholesterol crystals
and inflammation of the attic in the middle ear. Ultimately
it grows and erodes middle ear structure, invades mastoid
antrum and penetrates the bony wall of horizontal semi-
circular canal with fistula formation or intracranial
complications (brain abscess). Cholesteatoma almost
always requires surgery.
Internal ear
• Acute labyrinthitis
a. Nonsuppurative labyrinthitis—Insist on bed rest till
symptoms subside. Antivertigo drugs like
antihistamines (vide supra) are indicated. If any
infection of the middle ear or mastoid bone is
associated, appropriate antibiotics may be given.
Prednisolone may be beneficial.
b. Suppurative labyrinthitis following otitis media and
mastoiditis, need effective antibiotics and surgical
drainage.
• Toxic labyrinthitis Remove the offending agent and
symptomatic relief may be given.
• Benign positional vertigo Reassurance, symptomatic
relief with vestibular sedatives. Vestibular adaptation
exercises are beneficial. Better watch for any intracranial
tumour developing subsequently. It may be treated with
Canalith (floating clot) repositioning procedure (Epley
manoeuvre) in posterior semicircular canal, accounting
for BPPV.
• Meniere’s disease
a. Acute attack
i. Bed rest (lie on sound side)
ii. Salt and fluid restricted
iii. Antihistamines (cinnarizine), antiemetics
(prochlorperazine), if necessary frusemide IV
and diazepam IM/IV
iv. Symptomatic tinnitus responds to carbamzepine
or tocainide
In more severe attacks prochlorperazine 12.5 mg IM or
cyclizine may be given.
b. Long-term treatment and prophylaxis
i. Restriction of salt and fluid intake
ii. Abstinence from tobacco
iii. No driving or swimming allowed
iv. Betahistine helps to control vertigo, relieves
tinnitus and restricts hearing loss.
c. Recurrent disabling attacks with progressive
deterioration require surgery on the labyrinth or
vestibular nerve (vide supra). or surgical endolymph
drainage. Chemical labyrinthectomy with Gentamicin
injection into middle ear.
• Motion sickness Antihistamines are beneficial. Lying
down eyes closed helps. Hyoscine (as transdermal patch)
or 1.5 mg and/or antiemetics promethazine theoclate
may be used, if necessary. Attacks may be prevented
with mild sedatives and by limiting movements
stimulating the vertical canals.
• Perilymphatic fistula Surgery vestibular neuronitis
treated with bed rest bed rest and labyrinthine
suppressants as for Meniere’s disease. Appropriate
antibiotics may be given, if any respiratory infection
exists. Diazepam may be useful.
Neurological (Central)
It may be acute (VBI) or recurrent (migraine, temporal lobe
epilepsy and VBI) or chronic (basal meningitis, intracranial
tumour and multiple sclerosis).
Cortical
• Aura of epileptic attack (Refer to Chapter Epileptic
Seizures.)
• Atherosclerosis (Refer to Chapter ‘Epilepitc Seizures’).
Migraine (Refer to Chapter ‘Headache’).
Tumour (Refer to Chapter ‘Headache’).
Brainstem
• Vertebrobasilar insufficiency (VBI) TIA of the
vertebrobasilar territory (< 24 hours duration) or minor
stroke of the brainstem whose duration is 1 to 2 weeks
is treated with antiplatelet agents (low doses of aspirin
and/or clopidine) apart from symptomatic therapy.
Anticoagulants (heparin for 3 days and subsequently
oral warfarin) may be used if there is a clear embolic
 Vertigo and Dizziness
source or if the antiplatelet agents fail or recurent attacks
are not controlled. However, it is better to display them
only after a CT scan (as there is a risk of bleeding into
the lesion if the infarction is established). Low molecular
weight heparin prefered.
• Subclavian steal syndrome The symptoms usually
subside in course of time without specific treatment. If
necessary, surgery may be considered for occlusion of
the proximal left subclavian or innominate artery by
employing bypass grafts in the neck connecting
subclavian artery to the ipsilateral carotid artery, or
endarterectomy by an experienced surgeon.
• Multiple sclerosis Corticosteroids (dexamethasone 2 mg
tds for 10 days) may be beneficial in acute exacerbations.
Cytotoxic immunosuppressive therapy with cyclophos-
phamide and azathioprine alone or in combination with
corticosteriods may be given. Interferon betal-b is
beneficial in relapsing remitting multiple sclerosis and
for slowing its progress. Symptomatic management for
spasticity (baclofen 5-20 mg tds) or dantrolene (25-100
mg tds or diazepam (2 mg 6th hourly) or tizanidine
(2 mg tds); dysaesthesia (carbamazepine 200 mg tds),
ataxia (clonazepam 2 mg tds), urinary symptoms like
retention (bethanechol 20 mg tds), or hyperreflexia
(propantheline 15 mg 6th hourly), tremor (isoniazid 200
mg bd along with pyridoxine 50 mg or clonazepam or
propranolol) may be considered (Refer to Chapter
‘Paraplegia’).
Cerebellar
Thrombosis of the Posterior Inferior Cerebellar Artery
(Lateral Medullary Syndrome)
a. Medical therapy—Osmotic agents (mannitol) and
corticosteroids (dexamethasone) for cerebral oedema if
any; antiplatelet agents; anticoagulation with heparin to
be considered if basilar insufficiency ensues (preferably
given after a CT scan); and symptomatic therapy for
dysphagia, vertigo and vomiting given as indicated.
b. Surgical therapy—Surgical decompression considered,
if necessary. Occipital to posterior-inferior bypass
grafting recommended, if vertebral thrombotic lesion
proximal to the posterior-inferior cerebellar artery exists.
c. Appropriate measures adopted for a good functional
recovery.
• Trauma Postconcussional syndrome resulting in
vertigo especially on sudden head movement or
change of posture needs essentially rehabilitation,
apart from symptomatic therapy. Any underlying
blood clot, if present, requires surgical evacuation
sooner or later.
537
Eighth nerve
Acoustic neuroma Surgical removal is the treatment of
choice.
Basal meningitis (Refer to Chapter ‘Headache’).
Ocular
a. Avoid situations causing vertigo (Vide supra).
b. A shade or a frosted glass when used, relieves diplopia
and vertigo in ocular palsy and orthoptic exercises may
be beneficial.
c. Primary cause of ocular palsy is treated appropriately.
Cervical
i. Movements of the neck must be limited by applying a
cervical collar or traction in established cervical
spondylosis.
ii. The underlying mechanism of cervical vertigo may be
corrected by vestibular sedatives and/or vasodilators like
cinnarizine supplemented with cyclandelate.
Psychogenic
Therapeutic approach is essentially oriented towards the
patient and not merely the symptom. Allay the patient’s fright
and anxiety (panic attacks) with anxiolytics. If necessary,
antipsychoitics (chlorpromazine or haloperidol) or
antidepressants are used. Reassurance, psychotherapy,
behavioural therapy besides medication may be met with
success (Refer to Chapter ‘Headache’).
Treatment of General Medical Disorders
Causing Dizziness
The various systemic disorders enumerated under causes
of dizziness are to be identified and treated appropriately.
Cardiovascular
a. Hypertension (Refer to Chapter ‘Headache’).
b. Sudden Fall in Cardiac Output (Refer to Chapter ‘Shock’).
c. Postural Hypotension (Refer to Chapter ‘Syncope’).
d. Cardiac Arrhythmias (Refer to Chapter ‘Palpitations’).
e. Valvular Heart Disease
The causes of the valvular disease, be it stenosis or
regurgitation, due to congenital or acquired causes or senile
degeneration may be treated medically as per the needs (refer
to Chapter Haemoptysis and the Oedema) or a definitive
surgical treatment (valvotomy or balloon valvuloplasty or
valve replacement) is to be undertaken.
 538 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
Adverse Reactions of Drugs
If drugs are incriminated, withdrawal of the same is helpful.
• Haematological
i. Anaemia (Refer to Chapter ‘Fatigue’).
ii. Hyperviscosity (Refer to Chapter ‘Bleeding disorders’).
• Anaemia (Refer to Chapter ‘Fatigue’).
• Metabolic
i. Hypoglycaeuria (Refer to Chapter ‘Coma’).
ii. Hyperventilation (Refer to Chapter ‘Dyspnoea’).
• Neurological
a. Autonomic neuropathy (Refer to Chapter ‘Syncope’).
b. Intracranial Space Occupying Lesions (Refer to
Chapter ‘Headache’).
c. Cerebrovascular Accidents (Vide supra.) (Refer to
Chapter ‘Coma’).
d. TIA: In TIA aspirin (150 mg) is advocated for life.
Oral anticoagulants considered if recurrent attacks
are not controlled. Carotid endarterectomy may be
considered if > 70% stenosis present at the origin of
the internal carotid artery control risk factors for
stroke.
e. Head Injury (Vide supra)
• Failing Eye Sight
Correct the errors of refraction or treat any other cause
of failing eye sight.
• Psychogenic (Anxiety Neurosis) (Vide supra) Refer to
Chapter ‘Fatigue’.
Vertigo and Dizziness 539
 Chapter
Vomiting
35
Vomiting is a forceful expulsion of stomach contents through
mouth, with or without nausea or retching. Nausea is an
unpleasent subjective sensation of desire to vomit (usually
experienced in the throat or epigastrium) which is due to
altered motility of the small intestinal tract associated with
diminished gastric activity (tonicity) and may be
accompanied by pallor, sweating and/or salivation. Retching
is laboured rhythmic contractions of the respiratory and
abdominal muscles with closed mouth and sometimes
without explusion of gastric contents. Most often emesis is
accomplished in successive three stages of nausea, retching
and vomiting.
PATHOPHYSIOLOGY
The act of vomiting consists of:
1. Movement of gastric contents into the oesophagus
a. Forceful contractions of the abdominal muscles
against fixed diaphragm (in inspiratory position)
resulting in sudden rise of intra-abdominal pressure.
b. Simultaneous spasm of the pylorus and contraction
of the walls of the stomach with relaxation of the
cardiac sphincter, facilitating movement of gastric
contents into the oesophagus.
2. Movements of gastric contents from oesophagus into
the mouth.
Reversed peristalsis in the oesophagus and increased
intrathoracic pressure results in further movement of
gastric contents into the mouth.
3. Expulsion of gastric contents
The soft palate is reflexly elevated (prevents contents
entering into the nasopharynx) and the glottis is closed
(prevents aspiration of contents into the lungs), finally
completing the oral explusion of gastric contents.
Vomiting is under the control of two centres in the
medulla (1) the vomiting centre is located at the floor of the
4th ventricle adjacent to the nucleus of vagus, respiratory
centre, vasomotor centre, salivary centre and vestibular
centre, with which interconnections are established through
lateral reticulation, and (2) chemoreceptor trigger zone
(blood-stream chemosensor) is situated more superficially
and lies close to the vomiting centre. The vomiting centre
receives afferent stimuli from the gastrointestinal tract,
cerebral cortex and limbic system, labyrinthine apparatus
and chemoreceptor trigger zone. The efferent pathways
are phrenic nerves (to diaphragm), spinal nerves (to thorax
and abdominal muscles), the efferent nerve fibres in the
vagus (supplying the stomach and oesophagus).
The chemoreceptor trigger zone does not produce
vomiting by itself but when activated by many stimuli
(including drugs), it sends efferents to the vomiting centre
and initiates emesis. It is the vomiting centre which is
responsible for the act of emesis when excited by the stimuli
from different afferent channels. Neurotransmitters and their
receptors are present in the emetic centre as well as in the
gastrointestinal tract and blocking of the actions of one or
more of these transmitters, alleviates emesis.
CAUSES OF VOMITING
The causes can be conveniently grouped into (Table 35.1):
1. Those acting directly on the emetic centre (central):
Toxic and neuropsychiatric causes.
2. Those acting reflexly on the emetic centre (reflex):
Visceral and Otological causes.
Central Causes
Toxic
Drugs and chemicals These may produce nausea and vomiting
as side effect due to local irritation or directly stimulating
the chemoreceptor trigger zone. Irritating drugs like
 Vomiting 541

Table 35.1: Aetiology of vomiting salicylates and alcohol may act locally whereas drugs like
digoxin, morphine and anaesthetics directly stimulate the
I. Central Causes
chemoreceptor trigger zone. Vomiting in cancer patients
1. Toxic (Toxi-infective and Toxi-Metabolic)
a. Drugs and chemicals, e.g. alcohol, medications (anticancer
depends on the emetic potential of the anticancer drugs and
therapy, theophylline, digoxin, morphine), anaesthetics. may be chemotherapy dose related or may be due to radiation
b. Infections (toxins) or metastasis in the brain or alimentary tract. Sometimes
i. Systemic infections not involving GI tract directly drugs in normal dosage cause vomiting in sensitive
ii. Infections of GI tract: Food poisoning (gastroenteritis), individuals due to idiosyncrasy.
cholera.
Systemic infections Toxins formed by the microbes may
c. Metabolic: Uraemia, diabetic ketoacidosis, hypercalcaemia
d. Pregnancy: Hyperemesis gravidarum, eclampsia
produce vomiting stimulating the medullary emetic
e. Cylical vomiting in children. mechanism. It is common especially in children at the onset
2. Neurological
of acute infections. Other clinical features pertaining to the
a. Special senses: Unpleasant smells and repulsive sights
infection offer clues to account for the vomiting.
b. Increased intracranial pressure: Meningitis, intracranial tumours Food poisoning It is ingestion of contaminated food by a
c. Cerebral: Migraine single group of persons with similarity of clinical features
d. Radiation sickness like vomiting, diarrhoea, abdominal pain, dehydration with
3. Psychogenic or without collapse. The vomiting starts within half an hour
Emotional disturbances and functional or hysterical vomiting. after ingestion (chemical poisoning), within an hour
II. Reflex Causes (bacterial toxins), within 24 h (poisonous fungi), within 12
1. Visceral to 48 h (Salmonella). It is usually due to:
i. Abdominal a. Food contaminated with chemicals (antimony or zinc).
a. Gastric b. Ingestion of foods containing fungi (mushroom) or sea
i. Irritant foods and chemicals, idiosyncrasy foods (shellfish).
ii. Gastritis c. Infections with Salmonella group, Shigella and E. coli
iii. Peptic ulcer
iv. Pyloric obstruction Bacterial food poisoning may be infection type or toxin type.
v. Afferent loop syndrome • Infection type: The common Salmonella infections are
vi. Acute dilatation of the stomach Salmonella typhimurium and Salmonella enteriditis. The
vii. Venous congestion: Congestive liver and cirrhosis. infection occurs usually from contaminated milk or meat
b. Intestinal or ducks’ eggs or infected excreta or rats and mice.
i. Appendicitis The organisms multiply in the intestines and infecting
ii. Intestinal parasites
dose is directly related to the severity of clinical features.
iii. Paralytic ileus
iv. Intestinal obstruction.
• Toxin type
c. Peritoneal: Acute peritonitis. a. Staph. pyogenes: The source of infection is a food
d. Hepatobiliary system handler with septic lesion or who is a carrier. The
i. Viral hepatitis organisms multiply in the food and produce exotoxin
ii. Acute cholecystitis which is resistant to heat.
iii. Biliary colic. b. Clostridium botulinum: Clostridia produce exotoxin
e. Pancreas: Acute Pancreatitis.
which is absorbed from the gut. The source of
f. Kidney
i. Renal colic
infection is usually canned food (anaerobic). The
ii. Dietl’s crisis. vomiting is inconstant with minimal gastrointestinal
ii. Cardiopulmonary disturbances and striking neurological features
a. Acute myocardial infarction (diplopia, dysphagia, ataxia and muscular weakness
b. Congestive heart failure and respiratory embarrassment).
c. Pertussis Generally chemical or toxin type of food poisoning is of
2. Otological sudden onset and explosive in nature causing collapse
a. Labyrinthine disturbances
without fever whereas in infection type, it is slow in
i. Meniere’s disease
ii. Motion sickness. onset associated with fever.
b. Middle-ear disease: Infection • Vibrio cholerae infection is less common. Unlike in
gastroenteritis, the vomiting occurs, after copious rice
 542 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
water stools and marked dehydration develops rapidly.
The powerful exotoxin activates adenylate cyclase and
the increased concentration of cyclic adenosine
monophosphate in the wall of the gut, results in the
hypersecretion of water and chlorides as well as
diminished sodium reabsorption.
Metabolic (Refer to Chapter—Coma)
Pregnancy: Vomiting of early pregnancy (morning
sickness) occurs in about 75 per cent of pregnant
women, mostly primipara, after the first missed period,
(usually during the 6th week). If the nausea and vomiting
is severe and persistent, it is termed hyperemesis
gravidarum. Generally, it ceases after 4th to 5th months
of gestation. If this is unchecked it leads to dehydration,
jaundice and may prove fatal. Uterine bleeding at 6th or
8th week associated with nausea and vomiting may be
due to hydatidform mole which is a hydropic degenerative
disorder of the chorionic villi. The examination may show
unduly enlarged uterus, than that of a normal pregnancy
of same duration. Absence of foetus and placenta by
ultrasonography is diagnostic.
Vomiting in late pregnancy is due to toxaemia of
pregnancy which generally occurs in the last trimester or
within seven days of delivery. Oedema, proteinuria,
hypertension form the triad of symptoms in preeclampsia
and if convulsions occur it is described as eclampsia.
Epigastric distress with nausea and vomiting may occur
due to congestion of the liver, wholly caused by generalised
disorders of the vessels resulting in seepage of blood into
peri-sinusoidal spaces.
Cyclical or Recurrent Vomiting in Children This occurs at
regular intervals. The attack comes on suddenly with
headache, sometimes pyrexia, followed by abdominal pain
with ketonuria. Predisposing causes are family history of
allergy or migraine, overexertion or overfatigue or any acute
infection.
Neurological
Increased Intracranial Pressure
• Meningitis, intracranial tumours (Refer to Chapter
‘Headache’).
• Migraine (Refer to Chapter ‘Headache’).
Radiation Sickness: It may cause immediate effect on normal
tissues (skin, mucous membrane, bone marrow and viscera)
or systemic reaction (radiation sickness). Nausea, vomiting,
anorexia, weakness or prostration may occur depending on
the number of units of absorbed dose (number of units of
radiation dose, i.e. rad/gray/rem/sievert or roentgen) and
the site of radiation therapy given. The psychological
repurcussions of the underlying illness may contribute.
Psychogenic (Hysterical Vomiting)
Vomiting may be a visceral expression of some emotional
disturbance like vague feeling of fear or disgust. It is usually
not associated with nausea or abdominal pain and occurs
even after consuming digestible articles. Though the
vomiting is said to be severe and frequent, the weight and
nutritional status often remain good. The other hysterical
manifestations may be elicitable in these patients (usually
women). Anorexia nervosa, is a part of psychic disturbance
associated with not only anorexia but also vomiting, which
may be under control of the will. Vomiting may become
habitual.
Reflex Causes
Visceral
Abdominal
• Gastric
a. Irritant foods and poisons may cause vomiting
immediately after swallowing and are accompanied
by epigastric pain. Alcoholic drinks or consumption
of foods to which one is allergic (like shellfish) may
cause vomiting. Careful history, chemical analysis
of matter vomited and relevant clinical features
pertaining to the various types of acute poisoning
offer the clue.
b. Gastritis: Bile reflux gastritis (bilious vomiting): The
reflux of duodenal contents after peptic ulcer surgery
may produce abdominal discomfort, bilious vomiting
and endoscopy shows bile in the stomach and diffuse
gastritis (Refer to Chapter ‘Haematemesis’).
c. Peptic Ulcer: (Refer to Chapter ‘Haematemesis’).
d. Pyloric obstruction: In pyloric obstruction, the
vomiting occurs regularly after food, associated with
pain due to violent peristalsis of the stomach in order
to overcome the obstruction. Frequent vomiting
prevents the overdistension of the stomach. At a later
stage, dilatation supervenes if the obstruction
progresses and large quantities are vomited several
times. The vomiting contains food consumed many
hours before, with offensive odour. Splashing after
four hours or more after the last meal and visible
gastric peristalsis are diagnostic. It is usually caused
by peptic ulcer or pyloric carcinoma.
 Vomiting
Persistent vomiting in infants (after birth up to four
months) with infrequent stool, palpable tumour in
the epigastrium are highly suggestive of hypertrophic
pyloric stenosis.
e. Afferent loop syndrome: After Billroth II gastrectomy,
the patient may develop postprandial pain (30 min
later) which is relieved by vomiting of bilious fluid.
This is caused by partial obstruction of the afferent
loop at the anastomosis, due to free passage of food
from stomach into efferent loop and as well as
increased pancreatic and biliary secretions.
The accumulated bile suddenly overcomes the
obstruction and bile is flooded into the empty
stomach.
f. Acute dilatation of the stomach: Large amounts of
dark fluid are vomited and the abdomen may be
overdistended. The dilatation is due to loss of tone
and occurs after operation or acute infection.
g. Venous congestion: Gastric venous congestion may
be associated with congestive heart failure. Passive
congestion of the liver results when the blood flow
from the hepatic vein is hindred towards the right
side of the heart. This in turn results in congestion
of organs like stomach, drained by portal veins
leading to anorexia, postprandial discomfort, nausea
and vomiting. Vomiting in congestive heart failure
due to drugs should not be ignored. Venous
congestion in the stomach can also occur in cirrhosis
and eclampsia.
• Intestinal
a. Intestinal parasites: Intestinal parasites may cause
vomiting especially in children due to reflex irritation.
A classical example is ascaris which inhabits in the
jejunum and may normally creep up into the stomach
and find its way in the vomit giving rise to an alarm
to the patient.
b. Appendicitis
c. Paralytic ileus (Refer to Chapter ‘Acute
d. Intestinal obstruction Abdominal Pain’).
• Peritoneal
• Acute peritonitis (Refer to Chapter ‘Acute Abdominal
Pain’).
• Hepatobiliary System
a. Viral hepatitis: (Refer to Chapter ‘Jaundice’)
b. Acute cholecystitis (Refer to Chapter
c. Biliary colic ‘Acute Abdominal Pain’).
• Pancreas Acute pancreatitis (Refer to Chapters ‘Acute
Abdominal Pain’ and ‘Chest Pain’)
543
• Kidney
i. Renal colic (Refer to Chapter ‘Acute
ii. Dietl’s crisis Abdominal Pain’).
Cardiopulmonary
• Acute myocardial infarction (Refer to Chapter ‘Chest
Pain’).
• Congestive heart failure (Refer to Chapter ‘Oedema’).
• Pertussis Whooping cough or pertussis is an acute
infection caused by Haemophilus pertussis. It is
characterised by catarrh of the respiratory tract
associated with paroxysmal cough and usually an
inspiratory laryngeal spasm (whoop). The cough may
be so severe as to produce suffusion of the face and
retching or vomiting. The disproportion between the
violent fits of coughing and the physical signs over the
chest may be elusive for diagnosis but the whoop and
the bacteriological diagnosis are confirmatory.
Otological
Labyrinthine Disturbances
• Meniere’s disease (Refer to Chapter ‘Vertigo’).
• Motion sickness (Refer to Chapter ‘Vertigo’).
Middle Ear Disease Infection Acute otitis media may occur
due to infection spreading from nasopharynx along the
eustachian tube to the middle ear. There may be pain in the
ear, pyrexia and vomiting. The pain may be relieved when
once the perforation of the drum and otorrhoea occur.
Obstructive deafness is appreciable and tinnitus or vertigo
may be present when chronic otitis media sets in, which
may be associated with either auditory tube (eustachian)
disease or mastoid disease.
The painful stimulation of afferent nerves of the
abdominal viscrea as described above, causes reflex
vomiting. Similarly, the reflex resulting from stimulation of
semicircular canals as in motion sickness (sea or air or car
sickness especially car travel up the hills) or involvement of
semicircular canals in Meniere’s disease and pharyngeal
irritation leading to prolonged hawking, account for vomiting.
CLINICAL APPROACH
Evaluation of vomiting, centres around
1. Careful analysis; whether (a) it is a feature of simple or
a serious organic disease or a functional disease,
depending upon the associated symptoms, character of
vomitus, its frequency and duration; (b) any
complications of vomiting like electrolyte disturbances
(dehydration, hypokalaemia, metabolic alkalosis,
 544 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
malnutrition, aspiration pneumonia, oesophageal mucosal
tears or rupture of the oesophagus) exist and
2. Differentiating it from (a) effortless explusion of acid
gastric juice or bile acids and/or food contents of the
lower oesophagus or stomach (regurgitation); (b)
regurgitating stomach contents, voluntarily into the mouth
and ejecting the same or swallowing once again
(rumination); and (c) fluid suddenly filling in the mouth
from both regurgitation and excessive salivation (water
brash).
Regurgitation, rumination and water brash (Pyrosis) are
not usually accompanied by nausea or retching or
abdominal and diaphragmatic contractions).
History
1. Drug history: Any drug ingestion like digoxin or alcoholic
bouts?
2. Time of occurrence: Vomiting occurring predominantly
in the morning may be due to alcoholic gastritis or
incipient uraemia or early pregnancy. Vomiting occurring
shortly after food may be due to gastric ulcer. Vomiting
occurring after 4 to 6 hours may be due to pyloric
obstruction
3. Duration: Short duration denotes infection or errors of
diet or intestinal obstruction whereas long duration
indicates peptic ulcer.
4. Preceding nausea or retching: Vomiting is always
preceded by nausea in toxic or visceral causes, especially
alimentary disorders. Vomiting is not preceded by nausea
in intracranial tumours (projectile vomiting). Nausea
without vomiting is present in chronic gastritis and
chronic cholecystitis.
5. History of similar past episodes
i. As in cyclical vomiting in children
ii. Associated with digestive distress, emotional upsets
or hysterical behaviour
iii. Vomiting associated with motion sickness as occurs
in ship or car travel.
6. Associated symptoms like pain, headache, vertigo, fever,
constipation or diarrhoea.
i. Vomiting following or relieving episodes of epigastric
pain is due to peptic ulcer. Unilateral abdomianl pain
due to biliary or renal colic may be associated with
vomiting. Vomiting associated with precordial pain
and sweating suggests acute myocardial infarction.
ii. Periodic vomiting preceded by headache with
photophobia suggests migraine.
iii. If vomiting is associated with vertigo, it indicates
labyrinthine disturbances.
iv. If associated with fever, it may be due to systemic
infections.
v. If vomiting is associated with constipation and
abdominal pain, it is intestinal obstruction.
vi. If associated with diarrhoea and abdominal pain, it
is usually acute gastroenteritis.
7. Character of vomitus
a. Nature: (What is vomited and how does it look like?)
i. Presence of mucus suggests gastritis.
ii. Presence of blood or altered blood with dark
brown colour (coffee ground due to haemoglobin
being converted into haematin) suggests bleeding
from oesophagogastroduodenal areas (Refer to
Chapter ‘Haematemesis’).
iii. Anchovy sauce: Amoebic abscess of the liver
rupturing into the stomach.
iv. Presence of residues of food taken many hours
before, with sour or foul odour and froth on the
surface on standing suggests pyloric stenosis.
v. Presence of free hydrochloric acid: If absent in
an elderly person suggests gastric carcinoma.
vi. Presence of bile may be due to biliary, pancreato-
duodenal reflux, after operations interfering with
pyloric function or obstruction below the
ampulla of Vater. If vomit contains dark green
bile, it may resemble vomit with blood which
can be differentiated by adding water when the
green colour becomes more obvious, whereas
the bloody vomit remains dark.
vii. Faecal vomit is brownish black in colour and
resembles blood but the faecal odour is the
differentiating feature. This occurs in intestinal
obstruction and gastrocolic fistula (Refer to
Chapter ‘Acute Abdominal Pain’).
b. Quantity: How much is vomited?
c. Frequency: How often the emesis occurred?
d. Odour
i. Lack of odour is suggestive of achalasia or
achylia gastrica
ii. Vomitus with odour (vide supra).
Physical Examination
Vital Data
a. Blood pressure: If it is high, it may be due to hypertension
with uraemia or hypertension with congestive heart
failure.
b. Respiration: If the respirations are Kussmaul type, it
may be due to metabolic acidosis from vomiting and
 Vomiting
associated diarrhoea. To determine whether it is due to
bicarbonate loss or acid retention, calculation of anion
gap helps since it is normal in the former and increased
in the latter. Hypoventilation may be seen in metabolic
alkalosis from prolonged vomiting so as to retain carbon
dioxide for providing more carbonic acid.
c. Pulse: If there is rapid feeble pulse, it may be due to
dehydration with hypovolaemia.
d. Temperature: If pyrexia is present, it indicates systemic
infection.
Examinations of the Body Parts
Examination of the face For any evidence of chronic
alcoholism such as bloated face with injected eyes and baggy
eyelids.
Examination of the eyes For any yellow discolouration of
eyes for evidence of jaundice; fundus examination for
papilloedema which indicates intracranial tumour; and tension
of the eyeball is reduced in diabetic ketoacidosis.
Examination of ears For any evidence of middle ear infection
and deafness.
Examination of the tongue The colour of the tongue may be
brownish and dry as seen in uraemia.
Examination of the neck Nuchal rigidity with vomiting,
headache and fever suggest meningitis.
Examination of the abdomen Inspection of the abdomen for
any visible peristalsis or doughy distension of the abdomen;
or any swelling in the epigastric region. Also look for the
abdominal movements with respirations (if absent, suggests
peritonitis).
Palpate the abdomen for any tenderness and board like
rigidity (peritonitis) or hepatomegaly or enlarged gallbladder,
or any other intra-abdominal masses. Percuss for any
diminished or absent liver dullness (tympany anteriorly over
the liver may be due to distended loops of bowel or due to
perforation of a hollow viscus), and for evidence of fluid in
the peritoneal cavity or tympanitic abdominal distension
(intestinal obstruction).
Auscultate for any borborygmi. They may be entirely
absent in peritonitis or intestinal ileus. Excessive borborygmi
may be heard in intestinal obstruction.
Examination of the chest
i. For any evidence of cardiac lesions leading to congestive
heart failure.
ii. For evidence of chronic bronchitis and emphysema with
any intercurrent infection.
545
Investigations
Vomiting which occurs after dietary indiscretion or alcoholic
excess or poisoning or vomiting of pregnancy does not
probably require extensive investigatory approach.
Nevertheless, an endeavour must be exercised to determine
the cause of vomiting where it is not obvious. For this,
appropriate investigations, depending on the index of
suspicion of possible aetiology must be attempted.
Urine
Urine tested for albumin deposits (uraemia); sugar and
acetone (diabetic ketoacidosis); bilirubin (jaundice); and for
pregnancy.
Blood
a. TC, DC and ESR for evidence for any infection.
b. Biochemical: Blood urea, glucose; serum bilirubin serum
electrolytes (Na, K, chlorides, bicarbonate); pH (acid
base disturbances); Gamma Glutamyl Transpeptidase
(GGT) (alcoholic liver).
Motion
It is tested for occult blood.
CSF
Lumbar puncture if there is no contraindication and look
for biochemical changes in CSF.
Radiology
a. Plain X-ray of abdomen—For evidence of abnormal gas
shadows.
b. Cholecystogram for any caliculi and cholecystitis.
c. Barium meal series to assess the motility of
gastrointestinal tract and mucosal status.
d. X-ray of skull for any evidence of increased intracranial
tension.
Imaging Procedures (If indicated)
a. Ultrasonography for alimentary conditions, like acute
appendicitis.
b. CT scan and MRI for increased intracranial pressure
like intracranial tumour.
Eighth Nerve
a. Audiogram—To assess conductive or perceptive
deafness.
b. Caloric test for labyrinthine disturbances.
 546 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
TREATMENT OF VOMITING
Control of emesis depends on whether it occurs per se or
concurrently with any other symptom (like headache,
abdominal pain, diarrhoea or vertigo). The timing, quantity,
character of vomitus and other associated features may
enable the physician to uncover and treat the underlying
cause.
Acute simple vomiting due to errors of diet or drugs
other than cytotoxics need no aggressive treatment except
correction of dietary measures and withdrawal of the
offending drug or any other aggravating factor.
Vomit with faecal odour or bloody colour (Refer to
Chapters ‘Acute Abdominal Pain and Haematemesis’), or
sudden vomiting with headache, fever, and photophobia
(Refer to Chapter ‘Headache’) demands intensive approach.
Prolonged severe vomiting requires critical management.
If not treated appropriately, it may lead to fluid-electrolyte
and acid-base disturbances. However, persistent vomiting
without loss of weight needs only psychotherapy.
Ultimately the therapeutic approach is related to the type
and cause of emesis (abdominal or extra-abdominal) by
offering symptomatic relief, with anti-emetic drugs, and
fluid replacement, besides correction of the specific cause.
Symptomatic Treatment
Anti-emetic Drugs
1. Dopamine antagonists
a. Phenothiazines
i. Prochlorperazine 5 mg (indicated in labyrinthine
disorders and migraine)
ii. Chlorpromazine 10 to 25 mg (postoperative
vomiting, uraemia, malignancy and radiation
sickness)
iii. Triflupromazine 10 mg [same as (ii)]
b. Metoclopramide 10 mg—(Also increases the tone
of the gastro-oesophageal sphincter, metabolic,
gastric or any other cause and cancer chemotherapy).
c. Domperidone (10 mg) does not cross the blood brain
barrier unlike metoclopramide [indicated as in (b)].
2. Serotonin receptor antagonist—Ondansetron (8 mg i.v/
i.m.) is beneficial in vomitings due to cancer
chemotherapy with drugs like cisplatin. Granisetron (1-
2 mg once daily orally or 1 mg diluted to 5 ml iv bd for
chemotherapy related, Radiation or PO emesis).
Palonosetron (0.25-0.75 mg) iv is advocated in cancer
chemotherapy induced emesis.
3. Antihistamines (useful in labyrinthine disturbances)
a. Meclizine (25 mg)
b. Hydroxyzine (25 mg)
c. Dimenhydrinate (50 mg)
d. Cinnarizine (25 mg)
e. Promethazine hydrochloride (25 mg)
f. Promethazine theoclate (25 mg).
4. Anticholinergics act on the vomiting centre and also
reduce gastrointestinal overactivity. Hyoscine used
externally as transdermal patch 1.5 mg (motion sickness).
5. Cannabinoids 1 mg to control emesis due to cytotoxic
drugs.
6. Non-phenothiazine psychotropic drugs
a. Tranquilisers: Lorazepam (1-2 mg)
b. Butyrophenones—Haloperidol (2-6 mg).
7. Other drugs
a. Antacids (gastritis, peptic ulcer)
b. Pyridoxine 10 mg thrice daily (vomiting of pregnancy
and irradiation)
c. Betahistine 8 mg (Meniere’s syndrome).
Replacement of Fluid and Electrolytes
Maintain adequate hydration and correct chloride and
potassium depletion and possible metabolic alkalosis by
intravenous fluids as needed like.
1. The 5 to 10 per cent of dextrose in saline solution.
2. Normal saline (2-4 litres per day) with or without
potassium (17-40 mmol/L)
3. ‘Gastric solution’ containing sodium chloride 63 mmol/L,
potassium chloride 17 mmol/L and ammonium chloride
90 mmol/L.
(Whether isotonic saline only or supplemented with
potassium chloride or additional amonium chloride also
should be given, depends on the degree of alkalosis, i.e.
increase in bicarbonate). Refer Chapter ‘Coma’.
Diet
Temporarily withhold all foods while maintaining with i.v.
fluids. When oral feeding is permitted, milk, barley, whey,
glucose in iced water or fruit juice and crackers or biscuits
are given. Then step up with small feedings of palatable
foods based on the individual preferences.
Specific Treatment for Specific Diseases
Central Causes
1. Toxic
• Drugs and chemicals Prompt withdrawal of the
offending agent and if necessary, symptomatic treatment
may be given.
 Vomiting
• Infections
a. Systemic infections not involving GI tract directly:
Appropriate antibiotic(s) in effective doses,
adminstered.
b. Infections of GI tract
i. Food poisoning (gastroenteritis)—If it is due to
a chemical or poisonous food, stomach wash
may be given and the contents may be kept for
analysis. Replace fluids and electrolytes orally
or parenterally as per the needs.
Withhold diet till acute symptoms subside.
Loperamide, Domperidone is useful in controlling
diarrhoea or vomiting as the case may be.
ii. Cholera—Replacement of the fluids to maintain
circulation is of utmost importance. The ideal
fluids include sodium chloride (isotonic saline),
Ringer lactate or sodium bicarbonate, potassium
chloride and supplemented by glucose (5%) after
correction of dehydration. Tetracycline (250 mg
6th hourly) or furazolidone (100 mg 6th hourly)
for three days or doxycycline (300 mg as single
dose) is valuable. If renal failure sets in, it is
treated accordingly. Cholera is prevented by
observing strict personal hygiene, with emphasis
on boiled water for drinking and clean
environment. Vaccination provides immunity for
a limited period.
• Metabolic
a. Uraemia—(Refer to Chapters ‘Oliguria and Polyuria’).
b. Diabetic Ketoacidosis—(Refer to Chapter ‘Polyuria’).
c. Hypercalcaemia—(Refer to Chapter ‘Polyuria’).
• Pregnancy
a. Hyperemesis gravidarum—Pyridoxine (50-100 mg)
is beneficial. If drug therapy is needed
prochlorperazine or Domperidone or Doxylamine
with Pyridoxine Preferably is given. Correct any fluid
and electrolyte disturbances. If condition deteriorates
despite therapy, therapeutic abortion is considered
especially when anuria, jaundice or haemorrhage
occurs.
b. Eclampsia—(Refer to Chapter ‘Epileptic Seizures’).
Cyclical vomiting in children The attacks which
occur at regular intervals of a few weeks need only
symptomatic treatment. Precipitating factors like
allergy, constipation, overstrain at school, any
associated infection must be treated accordingly.
Vigilant watch must be maintained to prevent acidosis/
ketosis.
547
2. Neurological
• Meningeal (Refer to Chapter ‘Headache’).
• Intracranial tumours (Refer to Chapter ‘Headache’).
• Migraine (Refer to Chapter ‘Headache’).
• Radiation Treatment is symptomatic and supportive.
Distressing vomiting is preferably treated with
dimenhydrinate, piperazine derivatives like prochlor-
perazine or perphenazine. (1 h before and 4 h after
radiation therapy or 6th hourly). Ondansetron is beneficial
Fluid and electrolyte balance must be maintained. Whole
blood transfusion may be necessary in some cases.
Appropriate antibiotics may be considered if secondary
infection occurs.
3. Psychogenic Psychotherapy helps emesis with psychic
basis. Isolate the patient and avoid unpleasant psychic stimuli
such as unpalatable foods or drugs or emesis basins. Patient
should be impressed that something is being done (passing
a nasogastric tube) while the psychic basis is evaluated
simultaneously. Reassurance and advice (to avoid
predisposing situations causing emotional disturbances and
to adjust social network) are often rewarding.
Anxiolytics like benzodiazepines (diazepam 5-10 mg;
Alprazdam 0.5 mg tid; clobazam 10 mg bd chlor-
diazepoxide10-20 mg; lorazepam 1-2 mg; triazolam 0.25-1
mg), meprobamate (400-800 mg) or buspirone (5-10 mg)
may be given.
Abreactive therapies like carbon dioxide therapy may
help recovery.
Reflex Causes
1. Visceral
• Abdominal
a. Gastric
i. Gastritis: (Refer to Chapter ‘Dyspepsia’).
ii. Peptic ulcer: (Refer to Chapter ‘Haematemesis’).
iii. Pyloric obstruction: (Refer to Chapter ‘Weight
Loss’).
iv. Afferent loop syndrome: (Refer to Chapter
‘Chronic Diarrhoea’).
v. Acute dilatation of the stomach: Aspirations done
continuously so as to keep the stomach empty.
Nothing should be given by mouth. Fluids must
be given i.v. adequately so as to replace the
aspirates. If there is no satisfactory response in
3 or 4 days time, jejunostomy may be considered
to facilitate feeding through the stomach till the
stomach regains its normal tone and size.
vi. Venous congestion: (Refer to Chapters ‘Oedema
and Jaundice’).
 548 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
b. Intestinal
i. Appendicitis, paralytic ileus, and intestinal
obstruction: (Refer to Chapter ‘Acute Abdominal
Pain’).
ii. Intestinal parasites: Piperazine (100 mg/kg body
weight) or levamisole (5 mg/kg body weight)
or pyrantel pamoate (10 mg/kg body weight)
given as a single dose is effective in ascariasis.
Albendazole (400 mg single dose) or
mebendazole (100 mg b.d. for 3 days) are other
popular alternatives. Ivermectin is a recent
molecule recommended for intestinal nematodes
(one dose of 200 µg/kg body weight on two
successive days; with or without one dose of
Albendazole). If obstruction occurs, worms may
be milked past the obstruction, failing which they
may be removed by enterostomy.
c. Peritoneal (Acute peritonitis): (Refer to Chapter
‘Acute Abdominal Pain’).
d. Hepatobiliary system
i. Viral Hepatitis: (Refer to Chapter ‘Jaundice’).
ii. Acute Cholecystitis: (Refer to Chapter ‘Acute
Abdominal Pain’).
iii. Biliary Colic: (Refer to Chapter ‘Acute
Abdominal Pain’)
e. Pancreas (Acute Pancreatitis) (Refer to Chapters
‘Shock’ and ‘Acute Abdominal Pain’ )
f. Kidney
i. Renal colic:
ii. Dietl’s crisis: (Refer to Chapter ‘Acute Abdominal
Pain’).
• Cardiopulmonary
a. Acute Myocardial Infarction: (Refer to Chapter ‘Chest
Pain’).
b. Congestive Heart Failure: (Refer to Chapter ‘Oedema’).
c. Pertussis (Whooping cough): Erythromycin is
effective if given in the catarrhal stage, and is
continued for two weeks. Methadone is useful in
controlling paroxysms of cough. Supportive care
with supplemental oxygen and gentle suction of the
secretions may be necessary in the presence of
cyanosis. Adequate nutrition must be maintained by
frequent feeding especially after vomiting which
usually follows the paroxysms of coughing. If
vomiting attacks interfere, nasogastric feeding or
intravenous fluid may be considered. Occasionally
seizures may require anticonvulsants, Childhood
immunisation with inactivated vaccine is a preventive
measure though fits can occur very rarely (1 in more
than 3,00,000 cases).
Disease contacts may be given prophylactic
erythromycin.
2. Otological
• Labyrinthine Disturbances
• Meniere’s disease (Refer to Chapter ‘Vertigo’).
• Motion sickness (Refer to Chapter ‘Vertigo’).
• Middle Ear Disease:
• Infection Acute otitis media is treated with systemic
antibiotics and analgesics. The nasal passages must be
decongested as often as possible. In acute catarrhal
(secretory) otitis media incision of tympanic membrane
may be required.
Chronic otitis media requires eradication of nasal sepsis.
The defect in tympanic membrane may be corrected by
applying a skin graft to improve the hearing.
Severe (serous) otitis media with perforation of the ear
drum or attic membrane needs the services of an aural
surgeon. The resulting complications like acute labyrinthitis
require effective antibiotic therapy and radical
mastoidectomy, after recovery from the acute phase.
Vomiting 549
550 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
 Chapter
Weight Loss
36
Loss of weight without dietary restriction (involuntary)
poses a problem to the clinician. This has to be differentiated
from underweight due to enforced dieting or constitutional
leanness or hyposthenic somatotype wherein there is no
appreciable loss in weight. In fact, any loss of 10 percent
or more of the normal body weight is significant, and the
underlying cause must be sought, which may be organic or
psychogenic. If the loss of weight occurs rapidly, it is likely
to be organic. The weight loss may involve body fluids or
tissue mass or both as the body weight is essentially made
up of body fluids and body mass (water forms 60% of the
total body weight and skeletal muscle forms about 30% of
the lean body mass). Emaciation (weight loss) associated
with anaemia and pallor of the skin is referred as cachexia.
Correctness of weight is an important factor and its
significance must be assessed against the height and build
of the patient. Since the caloric value of tissue is said to be
7.7 calories per gram, it is presumed that loss of 1 kg in
body mass requires a deficit of 7,700 calories.
BASIC PRINCIPLES
Normally the standard weight is maintained by striking a
balance between caloric intake and expenditure. The calories
are provided by the consumption of energy yielding foods
like carbohydrates and fats as well as by body building foods
like proteins. The energy requirements are approximately
35 to 45 calories per kg body weight, i.e. a man weighing
60 kg requires 2100 to 2700 calories depending on the
nutritional status and type of activity of the individual.
Basal metabolism is the calories required for the body
during absolute resting conditions. About 50 to 60 percent
of the total intake of calories daily is utilised for basal
purposes. The basal energy requirement is one calorie per
hour per one kg body weight, i.e. a man weighing about 60 kg
requires a caloric intake of about 1440 calories (60 × 24).
On the contrary, the basal energy expenditure averages 1400
calories and is calculated by the following equation:
66 + (13.7 × ideal body weight in kg) + (5 × height in
cm) – 6.8 × age
Apart from this expenditure, daily energy output includes
specific dynamic action (calories required for food
absorption) and physical activity.
The specific dynamic action of food consumed, averages
10 percent of the total intake of calories. Physical activity
may be nonoccupational like standing, sitting, dressing,
bathing, etc. and occupational purposes. For moderate
activity, about 40 to 50 percent of the daily intake or 30
percent for sedentary activity have to be added.
Only 93 percent of caloric intake is utilised as 7 percent
account for urine and faecal loss. So the estimated energy
requirement for zero balance will be 107 percent of the
caloric output. Thus there will be weight loss if the intake
of calories is less than the daily caloric expenditure.
In children, failure to gain weight may be equivalent to
loss of weight. In old age, shrinkage of tissue mass is
progressive which is a normal process of ageing
(physiological).
The mechanism of weight loss revolves around:
i. Anorexia (occult malignancy or infection or congestive
heart failure)
ii. Accelerated tissue metabolism (thyrotoxicosis,
phaeochromocytoma)
iii. Excessive loss of calories in urine or faeces (diabetes
mellitus and malabsorption syndrome or chronic
diarrhoea)
iv. Simple dieting
Weight loss is inevitable, if there is decreased appetite
and consequent decrease in the intake of food. On the
contrary, weight loss may be associated with increased
appetite as occurs in accelerated metabolism or any loss
through urine and/or faeces. Sometimes, the loss of weight
 552 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

in the clinical setting of a normal appetite and intake may be 1. Gastrointestinal

probably due to excessive physical or mental activity, or an
Deficient Intake of Food
underlying disease itself (Table 36.1).
Dysphagia: Refer to Chapter ‘Dysphagia’.
Table 36.1: Causes of weight loss
Anorexia Anorexia is the lack of a general desire for food
1. Gastrointestinal
with marked decrease of hunger (unpleasent sensation
a. Deficient intake of food
localized in epigastrium) or appetite (a pleasent sensation
i. Ill-fitting dentures, calorie malnutrition; food fadism
ii. Dysphagia
felt usually in the mouth or palate depending more on the
iii. Anorexia odours relating to olfactory activities).
iv. Pyloric stenosis due to long standing peptic ulcer Normally, food intake depends upon two centres in the
b. Impaired absorption or utilisation hypothalamus
i. Partial gastrectomy i. Laterally situated feeding centre
ii. Chronic diarrhoea
ii. Medially situated satiety centre
iii. Steatorrhoea
iv. Intestinal parasites The satiety centre inhibits the feeding centre. In some
v. Previous gut surgery. cases, appetite may be present but fear of eating
2. Endocrine and Metabolic (sitophobia) may be there due to postprandial
a. Thyrotoxicosis discomfort.
b. Adrenal insufficiency Anorexia accounting for weight loss may be due to:
c. Panhypopituitarism
i. Smoking leading to gastritis or chronic bronchitis
d. Diabetes mellitus.
3. Cardiopulmonary ii. Chronic congestive heart failure
a. Cardiac failure (Cardiac cachexia) iii. Uraemia
b. Emphysema (COPD) iv. Cirrhosis of the liver
4. Chronic renal failure
v. Malignancy (commonly gastric cancer and anorexia
5. Infections/immunological
may be the first symptom)
a. Tuberculosis
b. Chronic bronchitis vi. Chronic infections
c. Suppuration vii. Drugs like digoxin
d. Acquired immunodeficiency syndrome (AIDS) viii. Psychic: Anorexia nervosa (vide infra).
e. Occult infections and prolonged fevers.
f. Connective tissue disorders (vasculitis syndrome)
• Pyloric stenosis Refer to Chapter ‘Vomiting’.
6. Malignant Neoplasms
Impaired Absorption or Utilisation
a. Carcinoma of breast
b. Alimentary: GI Tract, liver, pancreas Partial Gastrectomy: Dumping or postcibal syndrome
c. Genito-urinary following surgery for peptic ulcer may be early or late in
d. Respiratory onset. The early dumping syndrome consists of symptoms
e. Haematological: Lymphoma and leukaemia like drowsiness, asthenia, inclination to lie down and
f. Bones tachycardia developing within 30 min after a meal. These
g. Occult. symptoms are attributed to rapid emptying of the gastric
7. Substance (Drugs and Alcohol) Abuse
contents into the small intestine. The intestinal distension
a. Drugs
stimulates autonomic reflexes or release gut hormones like
i. Illegal: Drug addiction
ii. Therapeutic: Amphetamine, fenfluramine, digoxin, drugs
serotonin and peptides (vasoactive, intestinal and gastric
affecting bacterial flora (antibiotics). inhibitory). The late dumping syndrome may occur after 1
b. Alcohol: Chronic alcoholism 1/2 to 3 h especially after a rich carbohydrate meal. The
c. Tobacco smoking symptoms of dizziness, palpitations, sweating and sometimes
8. Psychogenic fainting may occur. It is attributed to insulin release and
a. Anorexia nervosa consequent hypoglycaemia.
b. Depressive illness Chronic diarrhoea (Refer to Chapter ‘Chronic Diarrhoea’).
c. Schizophrenia.
Steatorrhoea (Refer to Chapter ‘Chronic Diarrhoea’).
 Weight Loss
Intestinal Parasites
i. Protozoa
a. Amoebiasis: (Refer to Chapter ‘Chronic Diarrhoea’).
b. Giardiasis (Refer to Chapter ‘Chronic Diarrhoea’).
ii. Helminthes
a. Nematode: Enterobius vermicularis; Strongyloides
stercoralis (hyperinfection)
b. Cestoda: Taenia saginata
c. Trematode: Schistosomiasis mansoni;
Schistosomiasis japonicum
• Enterobius vermicularis: The mode of infection is
through ingestion of eggs from contaminated food and
fingers. After ingestion the larvae are liberated from eggs
and develop into either a male or female worm. The
fertilised female migrates down the caecum and colon
and deposits the eggs. This infection is common
especially in children. Apart from perianal itching,
vulvovaginitis, and frequent micturition, gastrointestinal
symptoms like anorexia, abdominal discomfort may
develop. The diagnosis is obvious if there is any history
of passing small white worms in the faeces or nocturnal
perambulations of worms around the anal region or
microscopic examination for ova.
• Strongyloides stercoralis: The mode of infection is by
the filariform larvae, penetrating through the skin into
the venous circulation and developing into adult males
or females in the alveoli of the lung. Then they migrate
to trachea and epiglottis and are swalloed. The fertilised
females burrough into intestinal mucous membrane and
oviposit. As soon as the eggs are laid, the rhabditiform
larvae hatch out from the mucous membrane into the
lumen and are passed in the faeces. This larva may
mature into an adult and continue progeny in the soil
(copulation—second batch of rhabditiform larvae—
filariform larvae) or metamorphose directly into filarifom
larvae, without sexual phase, which constitutes the
infective stage. In hyperinfection, the filariform larvae
penetrate the intestinal epithelium and reach the lungs
via portal circulation (internal reinfection). With heavy
infection, it may result in intestinal catarrh leading to
gastrointestinal upsets and diarrhoea. The diagnosis is
confirmed by detecting the rhabditiform larvae in the
fresh sample of faeces.
• Taenia saginata: The mode of infection is by eating
undercooked beef containing cysticercus bovis. The
eggs in the human faeces are swallowed by the cattle
while grazing. The oncospheres (hexacanth embryos)
are liberated in the alimentary canal of the cattle and
penetrate through the gut wall and reach the striped
553
muscles through circulation, which is metamorphosed
into a cysticercus (larval) stage. After the consumption
of infected beef, the head (scolex) evaginates in the
human alimentary canal and anchors in the gut wall by
the four circular suckers and develops into an adult,
expelling the terminal gravid proglottides in the stool.
The symptomatology constitutes abdominal discomfort
and indigestion apart from passing proglottides. There
is often ravenous (increased) appetite associated with
loss of weight. The diagnosis is confirmed by
macroscopic (naked eye) examination for the whitish
segments (proglottides) and microscopic demonstration
of eggs of T saginata in the faeces.
• Schistosomiasis mansoni: The mode of infection is by
cercariae invading the human skin or mucous membrane
in contact with infested water and reaching the portal
system where they mature. The parasite deposits ova in
the colon and liver and also to a lesser extent in the
small intestine, stomach and pancreas. These ova escape
via the faeces and on contact with water miracidia
emerge which invade the intermediate molluscun host
(snail) wherein the sporocyst and cercariae develop (The
latter invade the skin). Thus, the cycle is from man to
snail through water and from snail to man through water
again. This parasite occurs in parts of Africa and South
America. The clinical features are predominantly intestinal
involving the sigmoidorectal region with colicky
abdominal pain, and dysentery. Later, visceral
manifestations like periportal cirrhosis and splenomegaly
with ascites may supervene.
• Schistosomiasis japonicum: In it the life cycle is similar
to Schistosomiasis mansoni but the lesions are much
more pronounced. It is found in the far east (Japan,
China and Philippines).
Apart from the dysenteric symptoms, the changes
in the liver are striking in the portal tract. It consists of
pseudotubercle around the eggs liberated which are
ultimately replaced by fibrous tissue giving a picture of
periportal cirrhosis. The haematin pigment liberated in
the worm is deposited in the Kupffer’s cells. The chronic
stage with cirrhosis is characterised by emaciation,
weakness and hepatic insufficiency. The diagnosis is
confirmed by demonstration of lateral-spined eggs in
the faeces.
Previous Gut Surgery Intestinal resection may result in short
bowel syndrome. If the proximal duodenum and distal half
of the ileum are spared, even 50 percent of the resection of
the small bowel may be tolerated. On the other hand, if the
ileum and ileocaecal valve are resected, diarrhoea and
 554 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
malabsorption state may result even on removal of less than
30 percent of the small intestine.
2. Endocrine and Metabolic
• Thyrotoxicosis (Refer to Chapter ‘Goitre’).
• Adrenal Insufficiency (Refer to Chapter ‘Shock’).
• Panhypopituitarism (Simmonds’ Disease)
The destruction of the anterior lobe of the
hypophysis due to infarction as a sequel to postpartum
shock (Sheehan’s syndrome), injuries, infections,
nonfunctioning tumours or surgery, result in pituitary
cachexia (loss of body weight, apart from loss of axillary
and pubic hair and striking pallor, hypogonadism,
amenorrhoea, impotence). Panhypopituitarism in
childhood is called infantilism.
• Diabetes Mellitus (Refer to Chapters ‘Polyuria and
Shock’).
3. Cardiopulmonary
• Cardiac Failure
• Emphysema (Refer to Chapter ‘Dyspnoea’).
4. Renal
Chronic Renal Failure (Refer to Chapter ‘Polyuria’).
5. Infections/Immunological
• Tuberculosis (Refer to Chapters ‘Chronic Diarrhoea and
Haemoptysis’).
• Chronic bronchitis
• Suppuration (Subacute/Chronic) (Refer to Chapters
‘PUO and Shock’).
• Acquired Immunodeficiency Syndrome (AIDS) (Refer
to Appendix IV)
• Occult Infections and Prolonged Fevers (Refer to
Chapter ‘PUO’)
• Connective tissue disorders (Refer to Chapter
‘Polyarthritis’).
6. Malignant Neoplasms
Tumourigenesis
The term malignant tumour or cancer denotes an abnormal
growth of cell invading normal tissue and formation of
abnormal mass of new tissue which may spread to distant
organs (metastasis). The discovery of new growth control
system is a breakthrough in understanding molecular biology
of cancer cell, Newer concepts have emerged regarding
aetiology apart from predisposing factors which include
age, environmental influences, diet, smoking habits, heredity,
and acquired pre-neoplastic disorders. Numerous genes are
discovered (whose encoded products are essential for
regulation of normal growth) while dissecting cancer cell,
into its molecular components and comparing it with normal
counterpart. Their disruption can lead to malignancy.
Oncogenes Oncogenes are the first set of genes to be
identified. It appears that all aetiologic factors ultimately
affect two sets of genes, i.e. proto-oncogenes (precursors
of oncogenes) and cancer suppressor genes (antion-
cogenes). These oncogenes, indeed, are a family of unique
sequences of DNA. All mammalian cells contain proto-
oncogenes, activation of which may lead to malignancy or
by inactivation of genes, which normally suppress the
proliferation of cells. C-oncogenes are cellular genes whose
abnoraml expression is associated with development of
cancer cell behaviour. The products of oncogenes (growth
factors—extracellular proteins receptors for growth factors,
protein kinases, nuclear oncoproteins) may be involved in
the control of cell cycle.
Viral Oncogenes The element of virus genome responsible
for rapid transforming capabiity is known as viral oncogene
(V-oncogene). Tumour viruses are of two types (i) DNA
virus ad (ii) RNA virus. V-oncogenes are introduced into
the cells by viruses. The RNA tumour viruses possess
three genes and the reverse transcriptase gene converts
viral genomic RNA into DNA which then integrates into
the host’s genome. This genetic information is translated
into a protein, which ultimately may lead to malignant
transformation.
Hormones Hormonal stimulation continuously may lead to
cancer as there is a relationship between hormonal action
and oncogenesis. Oestrogen therapy is useful especially in
genetically susceptible individuals and in those with benign
breast lesions.
• Immune deficiencies: Like infections, tumours are
common in immunodeficiencies, which are generally
resistant to treatment and prone for recurrence.
However, regression occurs in immune suppressed
patietns, following correction of underlying immune
deficiency.
• Autoimmunity: In systemic lupus erythematosus,
Sjögrens syndrome, renal transplants, AIDS are some
of the classical examples which are likely to develop
malignant tumours.
Though molecular biology of cancer is elucidative,
cancer induction is presumptive. Genetic composition,
viruses, carcinogens (environmental and therapeutic),
 Weight Loss
hormones and immunological factors are all contributory.
Tumour classification: It is based on histological analysis of
tumours according to their tissue of origin. Those from
mesenchyme are called sarcomas; epithelial origin are
carcinomas (basal, squamous, adenocarcinoma) and from
embryonic germ cell is described as teratoma. Cytokeratins
are found by immunohistology in epithelial tumours; glial
fibrillary proteins in gliomas and collagen fibrils in connective
tissue tumours.
Metastasis About 1 in 1000 cancer cells metastasise from
primary tumour. The propensity for metastasis is facilitated
by degrading the matrix by (i) urokinase and tissue
plasminogen activator enzymes; and (ii) overexpression of
epidermal growth factor receptors. The pattern of gene
expression within a tumour ultimately identifies its biological
behaviour. Thus, the pattern of expression of growth control
proteins determines whether early metastasis has occurred
or not at the time of commencement of therapy as in breast
cancer. Metastatic detection is in the offing by the Radio
Labelled Monoclonal Antibody Scanning.
Tumour Markers
Sera from tumour patients contain elevated levels of
circulating oncoproteins (tumour markers) which may
prove useful for the diagnosis and monitoring tratment.
i. Oncofetal antigens which are products of gene
expression during foetal tisue differentiation, e.g.
carcinoembryonic antigen for Colorectal Carcinoma
pancreatic oncofetal antigen and alpha fetoprotein for
Hepatocellular Carcinoma.
ii. Hormones—Placental hormones, ectopic hormones.
iii. Enzymes—Acid phosphatase.
iv. Immunoglobulins (macroglobulinaemia).
v. Neurone specific enolase for Small Cell Carcinoma of
lung
vi. Prostate specific antigen for Prostatic Cancer
Combined monoclonal antibody and oncogene
technology may enable to discover new kind of tumour
markers (vide infra).
Such neoplastic diseases of the gastrointestinal tract
(refer to Chapter Haematemesis) genitourinary tract (Refer
to Chapter ‘Haematuria’), respiratory (Refer to Chapter
‘Haemotysis’), lymphoma and myeloma (Refer to Chapter
‘Bleeding Disorders’) or any occult malignancy may cause
weight loss and careful search must be made to exclude the
underlying malignancy by screening through the pertaining
characteristic clinical features and imaging studies.
555
7. Substance (Drugs and Alcohol) Abuse
Drug Abuse
It is the self-administration of any drug in a manner away
from the approved medical or social pattern. This may lead
to intensive pattern of use in terms of frequency or quantity,
landing in dependence or compulsive drug use (drug
addiction). It is characterised by an overwhelming
involvement in the acquistion of drugs; or tendency to
increase the dosage to derive the desired effects or
occurrence of annoying symptoms on withdrawal of the
drugs.
There are three forms of drug abuse—
a. Benign: Pain killers.
b. Borderline: Nicotine and alcohol.
c. Malignant forms: The abuse is excessive or persistently
used beyond a point. It includes (i) Stimulants: Cocaine;
(ii) Depressants: Diazepam and barbiturates;
(iii) Narcotics: Opium, heroin, pethidine, morphine;
(iv) Canabinoids: Cannabis (Marijuana—Cannabis sativa
or hemp plant, and tetrahydrocannabinol is the chemical
involved); (v) Hallucinogens: Lysergic acid diethylamide
(LSD) and mescaline.
These different drugs produce different reactions in the
human body which may be too obvious to be reckoned
with (mood variations, restlessness, disjointed thinking, loss
of self-control, blood shot eyes, lack of appetite and loss of
weight).
Alcoholism
Alcoholism is a social problem with medical complications.
It consists of two phases:
1. Symptomatic phase (problem drinking)
2. Addiction phase (alcohol addiction).
The former is repeated or chronic use of alcohol to
resolve social tensions or emotional problems. An intermittent
irresistible desire to consume large quantities of alcohol sets
in (dipsomania). This usually progresses to addiction with
excessive use of alcohol and psychological dependence,
without which he cannot carry on his routine life. Eye
openers (drinking in the morning), behavioural changes
(fidgety and tics), injected conjunctiva, trembling lips,
tremors, and lack of appetite set in. Ultimately the
pathological changes occur in the organs like liver (cirrhosis),
stomach (chronic gastritis), nervous system (Korsakoff’s
syndrome, cerebellar deterioration, peripheral neuritis), and
cardiovascular system (hypertension and cardiomyopathy).
The other features include psychotic symptoms like
 556 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
hallucinations or withdrawal syndrome like delirium tremens.
This regular alcoholic indulgence with dislike for food
eventually leads to loss of weight. The probable markers
for alcoholism are raised gamma glutamyl transpeptidase,
raised mean corpuscular volume and hyperuricaemia.
Tobacco Smoking
Tobacco smoke contains particulate phase (nicotine,
aromatic hydrocarbons) and gas phase (carbon monoxide
and nitrosamines). Smoking acts like tranquilisers giving
rise to a feeling of relaxation. Ninty percent of nicotine is
absorbed in inhaled smoke and about 50 percent only when
drawn into the mouth. Average cigarette may yield about 6
to 8 mg of nicotine. In general, excessive smoking causes
loss of appetite and lessens gastric motility which may
ultimately lead to loss of weight. The other ill-effects are
peptic ulcer, ischaemic heart disease, cardiac arrhythmias,
Buerger’s disease, carcinoma (bronchogenic, laryngeal and
oral), chronic obstructive pulmonary disease and amblyopia.
8. Psychogenic
Anorexia Nervosa
This is usually due to psychological dysfucntion like
depression or emotional conflict although hypothalamic
dysfunction is also incriminated. It is usually seen in young
unmarried women. Anorexia or aversion to eat without
discriminating the component factors of hunger, appetite
and taste for food is characteristic. There may be associated
phobia of becoming obese. Emaciation sets in following
anorexia. Sometimes, there may be self-induced vomiting.
Associated amenorrhoea may precede anorexia. No other
medical illness as such is discernible. Despite striking wasting
and anorexia, there is retention of axillary and pubic hair,
unlike hypopituitarism. Basal luteinising hormone and follicle
stimulating hormone levels are low.
Depressive Illness
The depressive illness produces somatic as well as psychic
changes. The common physical symptoms are anorexia,
loss of weight, vague body pains and easy fatiguability. The
psychic symptoms include unexplained fears and haunting
ideas with anxiety, insomnia (like waking after 2 or 3 hours
of sleep), diurnal variations of mood, ideas of guilt, loss of
interest and lack of concentration, and hypochondriacal
tendencies. The depression may alternate with mania
(bipolar) or depression may be alone (unipolar). It is prone
for relapse and remissions. Depressive illness in its remission
phase is to be entertained to acount for the weight loss,
when there is no discernible organic cause.
Schizophrenia
In schizophrenia, personality is not intergrated with
discrepant thinking, emotion and conduct. The basic
psychotic symptoms are thought disorder including delusion,
emotional incongruity, hallucinations and disturbed conduct
with lack of insight. Loss of weight and vasomotor
distrubances are the associated features. There are four
varieties of schizophrenia—
1. Simple (insidious withdrawal from reality, inappropriate
moods and behaviour).
2. Hebephrenic (abnormal conduct, thinking disturbances).
3. Paranoid (hallucinations and delusions of suspiciousness,
persecution and splendour).
4. Catatonic (akinetic or hyperkinetic with acute outbrusts).
CLINICAL APPROACH
In the evaluation of weight loss, it is pertinent to know
whether the weight loss is rapid or gradual. The loss may
involve either body fat or fluid. The more rapid the weight
loss, the more it is likely to be due to an organic disorder.
Underweight, which is due to underdevelopment of fatty
tissue or leanness must be clearly differentiated before
assessing loss of weight. An endeavour must be made to
clinch the cause of weight loss whether it is exogenous or
endogenous, intentional or unintentional. The significant
factor to be considered is appetite and precise dietary history
thereof.
History
During history taking, specific complaints may indicate the
system, primarily at fault.
1. Age and sex: Wasting in middle or old age, malignancy
should be suspected. Weight loss in young women may
be due to anorexia nervosa.
2. Degree and extent of weight loss: Previous records
may help.
3. Dietary details: Qualitative or quantitative intake of food.
4. Any difficulty to swallow.
5. Appetite: If there is loss of appetite asociated with weight
loss, it is likely to be inflammatory disease, malignancy,
psychiatric problem or failure of vital organs like kidney
or chronic cardiopulmonary disease. If the weight loss
is associated with increased appetite, it is likely to be
due to diabetes mellitus or thyrotoxicosis or
malabsorption or parasitic infestation.
 Weight Loss
6. Any vomiting or diarrhoea or indigestion.
7. Any fever (infections) or bone pains (myeloma).
8. Any cough, haemoptysis and dyspnoea indicate cardiac
or pulmonary disease.
9. Any history of neurosis or depression.
10. Type of personality and life style: Involving stress,
anxiety and more working hours.
11. Alcoholism and excessive smoking.
12. Drugs: Any drug therapy with diuretics or digoxin or
any drug addiction.
Physical Examination
Genreal Examination
1. Face: Sunken orbits or cheeks; proptosis of the eyes
2. Evidence of anaemia.
3. Any lymphadenopathy or thyroid enalrgement.
4. Skin: Loose skin folds, pigmentation, dehydration.
5. Hands: Fine tremours of the outstretched hands or
sweating of the palms.
6. Record temperature and other vital data.
7. Assessment of nutritional status.
Actual body weight
a. Body weight = × 100
Ideal body weight
(Normal value: 100)
b. Measurement of triceps skin fold with skin calipers
at mid point indicates adipose tissue (Normal value:
Men 8-23 mm; Women 10-20 mm).
c. Lean body mass (Refer to Chapter ‘Obesity’).
i. Midarm muscle circumference is calculated as
follows:
Midarm circumference = 0.314 × triceps skinfold
(midarm circumference: Normal value—men
29.3 cm; women 28.5 cm). Midarm muscle
circumference: Normal value for adults—men
25 cm; and women 23 cm.
ii. 24 h urine creatinine (mg) (Normal value for
Height in cms
men 10.5 and women 5.8)
d. Serum albumin (normal 4 g%).
(Since skeletal muscle forms 30% and visceral
compartment 20% of lean body mass, estimation of
ratio of urinary creatinine excretion to height, reflects
the size of skeletal muscle mass and serum albumin
indicates status of visceral protein pool.)
e. Body mass index. If it is below 18.5 (under weight)
and above 24.9 (over weight)
557
Systemic Examination
1. Chest: Look for
a. Any lumps in the breast.
b. Any cardiac enlargement or murmurs (anaemia,
valvular disease).
c. Lungs: Any impaired movements of the chest, or
dullness, altered breath sounds and accompaniments
(tuberculosis and malignancy).
2. Abdomen: Look for (a) scars; (b) tenderness; (c) masses
(d) ascites (e) Rectal and Pelvic examination.
3. Psychiatric examination and analysis of (i) symptom
complex displayed (clinical); and (ii) conflicts and
stresses responsible for the underlying psychosis
(dynamic).
Investigations
1. Routine urine examination: Physical, chemical,
microscopic and bacteriological (for renal infections or
malignancy).
2. Blood examination
a. Full blood count, and ESR
b. Blood sugar
c. Blood urea and serum creatinine
d. Gama glutamyl transpeptidase and A:G ratio and S
bilirubin for chronic liver disease
e. Serum T-3 and T-4 levels; Plasma cortisol; LH and
FSH (if indicated)
f. Blood culture for any underlying infection
g. Serum proteins.
3. Motion
i. Microscopic: Is it bulky, pale, large and offensive or
watery?
ii. Microscopic: For parasites (Impaired absorption or
utilisation).
4. Radiology
a. Skiagram of the chest (for pulmonary tuberculosis
or malignancy) or sinuses.
b. Barium meal and/or enema series (for inflammatory
or malignant bowel disease or pyloric stenosis due
to peptic ulcer).
c. IVP (for renal infection or malignancy).
5. Ultrasonography: Abdomen for any underlying pathology
6. Endoscopy: Upper gastrointestinal endoscopy for
evidence of any occult malignancy or colonoscopy.
7. Ascitic fluid analysis: For evidence of (i) exudative
pathology (cell count including type of cell, specific
gravity and protein content); (ii) malignant cells;
(iii) adenosine deaminase (Higher values indicate
tuberculous abdomen).
 558 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
8. Biopsy of the lymph node: Done if lymphadenopathy is
present for confirmation of any lymphomas.
9. Tumour markers like carcinoembryonic antigen (CEA)
for GI, lung and breast; cancers; alpha fetoprotein
(Hepatoma, germ cell tumor of gonads); PSA (Prostateana
Breast); βHCG (GI, lung, teratoma, choriocarcinoma)
CA 125 (ovary) CA (Pancreas, G.I.); CA 153 (Breast)
and LDH reflects turnover burden/necrosis.
10. CT scan: Liver scan or bone scan (if indicated)
Thus patients with weight loss merit investigations,
pertaining to the index of suspicion of the underlying cause
whether endocrinal, gastrointestinal, infections, malignancy
or psychiatric, as outlined above.
TREATMENT OF WEIGHT LOSS
The therapeutic approach for weight loss should be governed
by the various mechanisms involved, i.e. (1) decreased
calorie intake, (2) increased caloric loss, (3) increased
metabolic rate and (4) psychological factors.
The caloric needs for most of the patients are estimated
as either basal energy expenditure ×1.75 calories per day or
multiplying the desirable body weight by 30-40 kcal per kg
depending on the sex and physical activity. Energy needs
may be increased in situations like sepsis. For clinical
purposes, basal metabolic rate is deemed equal to basal
energy expenditure, which is calculated by using the formula
(vide supra). The calories thus, obtained are to be translated
into a dietary plan.
So the treatment of weight loss should be so designed
as to rectify the deranged mechanisms (vide supra) by
symptomatic and specific measures.
Symptomatic Measures
1. Frequent oral feedings (if necessary liquid diets with
high calorie density like 1 cal/ml).
2. Special nutritional support by:
a. Enteral feeding (tube feeding is better tolerated by
keeping the patient in right lateral position with head
of the bed elevated at 30°).
b. If tube feeding is not tolerated, parenteral nutritional
support is instituted by peripheral or central vein.
The delivery system, for the peripheral infusion needs
either a pump or a drip chamber whereas for the
latter single lumen catheters are utilised for
cannulating the subclavian or internal jugular veins.
The parenteral fluids used are dextrose, amino acid
solution (1 g of nitrogen is equivalent to 6.25 g of
protein), lipid preparations (10%) along with vitamins
and minerals, trace elements and electrolytes yielding
1 kcal/ml. Approximately carbohydrates 55%,
proteins 15% and fats 30% of the total daily calories
may be obtained by this venous alimentation.
(Glycerol if used as energy source, yields 4.3 kcal/
g.) However, complications like fatty liver or
hyperglycaemia, or glucose related hypercapnia or
hypertriglyceridaemia are to taken cognisance of,
when these parenteral formulations are contemplated.
3. Besidees correction of calorie deficiency, nutritional
deficiencies are to be treated if present (preferably
prevented by dietary supplementation of micronutrients).
4. Pharmaco therapy: Cyproheptadine and/or nandrolone
or Melatonin.
Specific Treatment of Underlying Causes
Facilitate Increased Calorie Intake
Gastrointestinal
A. Correct causes of deficient intake of food
i. Ill-fitting dentures? Avoid these to facilitate proper
chewing.
ii. Dysphagia: (Refer to Chapter ‘Dysphagia’).
iii. Anorexia: The underlying cause of anorexia with
weight loss (infections tuberculosis; malignancies
carcinoma of the stomach; systemic diseases like
uraemia or cirrhosis of the liver; endocrinal
disorders; drugs like amphetamines, metoclo-
pramide; excessive alcohol and somking; anorexia
nervosa) when effectively treated, the appetite may
be restored to normal. Symptomatic treatment with
drugs like cyproheptadine, buclizine, vitamin B12
may be tried for marginal benefit.
iv. Pyloric stenosis due to long standing peptic ulcer:
Gastic lavage to remove all food debris followed by
aspiration every secod hourly for 3 to 4 days is
indicated. Adequate decompression restores gastric
tone. Oral fluids are encourged if volume of the
aspirate declines. Dehydration and associated
metabolic alkalosis are to be treated. Ultimately when
the patient’s general condition improves, elective
surgery (vagotomy and pyloroplasty or partial
gastrectomy) can be undertaken.
B. Correct causes of impaired absorption and utilisation
i. Partial gastrectomy: Weight loss due to post-
gastrectomy complications is treated as follows:
a. Dumping syndrome (vide supra). Both forms
are treated with dietary measures, which include
 Weight Loss
frequent small meals, avoding fluids at meal time,
glucose and/or guar gum.
b. Small stomach (diminished intake of food
because of discomfort following meals) is treated
with high energy small meals.
c. Afferent loop syndromes (abdominal distension
with nausea and vomiting after food due to
obstructed afferent loop or malabsorption due
to stasis with bacterial overgrowth within the
afferent loop) are treated with revisional surgical
correction of afferent loop or gastroduodenal
anastomosis. Anaemia due to inadequate
absorption and osteomalacia due to vitamin D
and calcium malabsorption are treated
appropriately. Metronidazole or oxytetracycline
can be prescribed.
d. Bile reflux (anorexia, nausea and substernal
distress due to reflux of bile) is treated by
diverting the duodenal contents with Roux-en-
Y procedure.
e. Post-vagotomy diarrhoea is treated with
loperamide (2 mg t.d.s.) or codeine (30 mg
t.d.s.).
f. General malabsorption and nutritional
impairment (malabsorption due to rapid gastric
emptying with poor mixing of gastric contents,
reduced bile concentrations and pancreatic
juices, bacterial overgrowth; steatorrhoea) is
treated with appropriate adequate replacement
of B12 and other micronutrients, pancreatic
enzymes. Tetracycline (250 mg every 6 hours
orally for one week) may be given and if
necessary, it may be repeated once in two
months for coexisting bacterial overgrowth. Low
fat diet with medium-chain triglycerides may
ameliorate steatorrhoea.
If malabsorption is severe, parenteral alimentation may
be required.
i. Chronic diarrhoea: (Refer to Chapter ‘Chronic
Diarrhoea’).
ii. Steatorrhoea. (Refer to Chapter ‘Chronic Diarrhoea’).
iii. Previous gut surgery: (Refer to Chapter ‘Chronic
Diarrhoea’).
iv. Intestinal Parasites
a. Protozoa
– Amoebiasis: (Refer to Chapter ‘Chronic
Diarrhoea’).
– Giardiasis: (Refer to Chapter ‘Chronic
Diarrhoea’).
559
b. Nematodes
– Enterobius vermicularis: Pyrantel pamoate
(11 mg/kg a single dose); Albendazole (400
mg single dose); mebendazole (100 mg single
dose) may be given and repeated after two
weeks to control autoinfection. If necessary,
every member of the family may be given
mebendazole and repeated after ten days.
Personal hygiene and laundering of night
clothes and bed linen must be emphasized as
a control measure.
– Strongyloides stercoralis (hyperinfection):
Thiabendazole (25 mg/kg twice daily for 2-5
days) or mebendazole (100 mg twice daily
for three days) or albendazole (400 mg single
dose for three days) is given.
c. Cestodes (Taenia saginata): Praziquantel (10 mg/
kg as single dose) is given or albendazole (400
mg once daily for 3 consecutive days) is an
alternative.
d. Trematodes (Schistosomiasis japonicum:
Schistosomiasis mansoni): Praziquantel (30 mg/
kg twice daily for one day) or oxamniquine
(15 mg/kg twice daily for two days) is given.
Endocrinal Addison’s disease Replacement therapy with
cortisone (20 mg morning, 10 mg evening) and
fludrocortisone (0.05-0.1 mg daily) indicated. Underlying
cause like tuberculosis is treated accordingly. If adrenal crisis
occurs, hydrocortisone hemiscuccinate (100 mg 6th
hourly) along with i.v. dextrose saline given. Precipitating
cause like infection is treated appropriately.
Panhypopituitarism (Refer to Chapter ‘Gynaecomastia’).
Cardiopulmonary—(Refer to Chapters ‘Dyspnoea and
Oedema’).
Substances (Drugs and Alcohol) Abuse Early abstinence from
commonly abused drugs like marijuan, cocaine and others
is usually complicated by withdrawal symptoms.
Psychotherapy (individual and groups), family therapy, peer
group aid programmes are beneficial. Antidepressants or
anxiolytic drugs or antipsychotic drugs like haloperidol are
of value. Hospitalisation may be required during
detoxification and stage of initial drug abstinence.
Alcoholism (Refer to Chapter ‘Fatigue’).
Psychogenic
• Anorexia nervosa: The aim of therapy is to restore normal
body weight by encouraging the patient to take the
controlled diet with persuasion and insistece. Supervision
may be necessary during meal time and little later to see
 560 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
that vomiting is not induced. The target of weight gain
should be about 1 kg per week. Hospitalisation may be
required in some cases. Clomiphene may be given to re-
establish menstruation. Other modes of therapy are
psychotherapy, individual therapy and family therapy to
ensure freedom from social and emotional pressures.
• Depressive illness (Refer to Chapters ‘Fatigue and
Coma’).
• Schizophrenia: The pharmacotherapy with neuroleptic
drugs is the mainstay of treatment. The usual drugs
prescribed are phenothiazines (chlorpromazine 100-1000
mg/d, thioridazine: 50-500 mg/d. fluphenazine: 20-100
mg fortnightly), butyrophenones (haloperidol 5-30 mg/
d), thioxanthines (flupenthixol: 40-200 mg fortnightly).
Risperidone (2-6 mg/d), olanzapine (5-10 mg/d)
Quetiapine (200-400 mg/d); Clozapine (300-450 mg/d);
Aripiprazole (10-15 mg/d), amiswpride (50-300 mg/d
as a single dose) are introduced and effective. The
initiation of therapy should be at a low dose and gradually
increased so as to avoid troublesome extrapyramidal side
effects. In nonresponsive patients, neuroleptic treatment
may be augmented with either lithium, carbamazepine
benzodiazepines and Dival Proexna.
The treatment may be tapered after 12 months and
stopped completely. If necessary, maintenance therapy
is continued indefinitely. Antiparkinsonian drugs
(beneztropine 2-6 mg/d or procyclidine 5 mg t.d.s) may
be given, if necessary.
Psychosocial measures including the patient, his
family and environment (general and social) facilitate
stabilisation. The behaviour of the members of the family
towards the patient may be modified to create a congenial
atmosphere for the patient.
2. Prevent the Calorie Loss
• Diabetes mellitus (Refer to Chapter ‘Polyuria’).
• Malabsorption (Refer to Chapter ‘Chronic Diarrhoea’).
Correct the Increased Metabolic Rate
Infections Tuberculosis (Refer to Chapter ‘Haemoptysis’).
Suppuration Effective antibiotics in adequate dosage
schedule adopted.
Occult infections and prolonged fevers (Refer to Chapter
‘Pyrexia of Unknown Origin’).
Endocrinal Hyperthyroidism (Refer to Chapter ‘Goitre’).
• Physiological: Physical Exertion
Avoid strenuous physical activities. (However,
significant weight loss due to increased physical activity
per se is rare.)
4. Deal Psychological Factors
Psychotherapeutic Strategies (Vide supra.)
Prevent Cachexia
Malignant Neoplasms – Discreet Treatment.
Malignant neoplasms The treatment is directed towards the
control of tumour (cure) as well as the symptoms (care)
wherein all the mechanisms of weight loss may be operating
leading to cachexia. It consists mainly of three pronged
attack, i.e. (i) surgery, (ii) radiotherapy (teleptherapy,
branchytherapy, fractionation of dose) and (iii)
chemotherapy apart from hormonal and biological
approaches (monoclonal antibodies; inhibitors of oncogene
products) along with supportive treatment.
Radiobioconjugates With biological moites and
Radioimmune therapy with radioactive isotopes targeted
therapy is emerging as fourth modality of cancer therapy.
Chemotherapy (Cytotoxics) The aim of cancer chemotherapy
is to destroy malignant cells, minimising damage to normal
cells and facilitating prolonged remission or cure. The
concept of antibody targetting of cancer chemotherapeutic
agents enabled development of monoclonal antibodies for
drug delivery in cancer chemotherapy.
An effective drug or a combination of drugs should be
chosen as per the type of malignancy. The adverse effects
must be properly weighed as per the risks and benefits.
Cytotoxics These are broadly divided into four groups.
a. Decreasing DNA Synthesis (DNA Damaging and
Inhibiting DNA Repair)
i. Alkylating agents: Cyclophosphamide, Ifosfamide,
Chorambucil, busulfan, melphalan, nitrogen
mustard, thiotepa
ii. Nitrosoureas: BCNU, TCNU, CCNU (lomustine)
iii. Antibiotics: Doxorubicin, daunorubicin, acti-
nomycin, bleomycin, mitomycin, mithramycin
(pliamycin)
iv. Topoisomerase antagonists
Type I (Irinotecan) and Type II (Itoposide).
v. Platinum compounds: Cisplatin, carboplatin
vi. Purine analogues: Fludarabine: Cladribine
b. Interfering Nucleotides Synthesis (from purines and
pyrimidine)
i. Antimetabolites; methotrexate, 6-mercaptopurine, 6-
thioguanine, 5-fluorouracil, cytosine arabinoside.
ii. Purine analogues: Fludarabine, Cladribine
c. Inhibiting Cell Division
i. Plant alkaloids (vincristine, vinblastine)
ii. Taxanes (Paclitaxel; Docetaxel)
 Weight Loss 561

d. Miscellaneous: c. Treatment of pain: Relief of pain is attained by displaying

i. Hydroxyurea various range of analgesics (non-narcotics and
ii. Procarbazine narcotics) like paracetamol, dextropropoxyphene,
iii. Dacarbazine NSAID, ketorolac, chlorpromazine, pentazocine, opiates
iv. L-Asparaginase and opioids or cocaine or nerve blocks depending on
v. Cytarabine the grade of pain.
vi. Letrozole d. Treatment of metabolic syndromes like hyperuricaemia
e. Cyto protectants: with allopurinol or hypercalcaemia with 2-3 L of normal
i. Amifostine saline, frusemide, prednisolone, mithramycin and
ii. Mesna calcitonin or hyperkalaemia with glucose and insulin.
e. Nutritional support with parenteral alimentation, if
Endocrine therapy
necessary.
i. Hormones and Analogues
f. Psychological support with drugs and adjusting psycho-
a. Androgens
social problems specially in terminal stages.
b. Antiandrogens (cyprotenone)
c. Oestrogens Treatment of Certain Malignancies
d. Antioestrogens (tamoxifen) (Listed Under Causes)
e. Progestogens;
f. Adrenocorticosteroids Carcinoma of Breast: It is best managed by (i) Surgical
g. Aromatase inhibitors (anastrozole) removal followed by (ii) Chemotherapy and (iii)
ii. Somatostatin Analogues: Octreotide (Hormone treatment Radiotherapy. Chemotherapy consists of Adriamycin,
offers potential therpeutic benefit for carcinoma of the Fluorouracil, Cyclophosphamide and sometimes
breast, prostate, endometrium and thyroid). Methotrexate. Tamoxafen (used in oestrogen receptor
Biological therapy positive cases). Anastrazole (in postmenopausal causes);
a. Cytokines goserelin (in premenopausal cases); Docitaxel (in metastases)
i. Interferons: Interferon alfa-2a, Interferon alfa-2b • Carcinoma of oesophagus. 5-Fluorouracil, and cisplatin
ii. Interleukins: Recombinant Interleukin-2 and Radiotherapy
iii. Granulocyte/colony stimulating factor (G-CSF) • Carcinoma of the Stomach
iv. Granulocyte-Macrophage colony stimulating factor • Carcinoma of the cardia or fundus is better managed by
(GM-CSF) endoscopic yttrium-aluminium-garnet laser or a large
b. Immunotherapy heater probe therapy (Refer to Chapters ‘Haematemesis
i. Monoclonal antibodies (Rituximab) either alone or and Melaena’). Gamma globulin is beneficial for stomal
tumours.
in combination with chemotherapy (immuno-
• Carcinoma of the Colon
chemotherapy) or coupled with a Radionucleide
Colectomy is indicated. Radiotherapy is of minimal
(Radioimmunotherapy).
benefit. Combination chemotherapy, i.e. levamisole and
ii. Vaccines: BCG vaccine; cancer vaccine.
5-fluorouracil, vincristine and methyl CCNU (Semustine)
c. Inhibitors of proteins of oncogenes and intracellular signal
after surgery may improve overall survival time.
pathway: Tyrosine Kinase inhibitor (Imatinib). Other
• Hepatoma (Hepatocellular Carcinoma)
novel agents: Gefitinib, Erlotinib.
Surgical removal is indicated, if cirrhosis is not
d. Gene therapy-Antisense sequence of DNA bases directed associated. Palliative therapy may be given with
against BCI-2 oncogene. cytotoxics. Liver transplantation is of limited value due
Supportive therapy to recurrence of the tumour. Local tumour ablation
a. Transfusions if necessary, are given especially when therapy with percutaneous injection of ethanol or acetic
the haemoglobin concentration falls below 7 g per cent. acid; transarterial chemoembolisation (adriamycin,
Other transfusions (platelets or granulocytes) considered, cisplatin); coagulation by microwave laser are adopted
if required. for cancers <5 cm. Radiolabelled polyclonal antiferritin
b. Treatment of infections with appropriate antibiotics antibody besides external beam radiation therapy and
(isolation by conventional barrier techniques to be chemotherapy can regress tumour up to 50 per cent
encouraged). with localised types.
 562 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
• Carcinoma of the Pancreas
Whipple operation (removal of duodenum and head
of the pancreas) is desirable. Palliative surgery with
cholecystojejunostomy or endoscopic insertion of stent
through the length of the obstructed bile duct ameliorates
obstructive jaundice. Gastroenterostomy prevents
duodenal obstruction.
• Carcinoma of the Kidney
Radical nephrectomy is better performed since it
is resistant to radiotherapy and chemotherapy. However,
palliation of bone pain by radiotherapy and chemotherapy
with vinblastine for metastasis may be considered.
Immunotherapy with interferon is promising for
metastatic renal cell carcinoma. (Refer to Chapter
Haematuria.)
• Carcinoma of Prostate is treated by androgen deprivation
with Gn releasing hormone analogue Goserelin,
Lev Prorelin as depo monthly.
• Bronchogenic Carcinoma (Refer to Chapter
‘Haemoptysis’).
• Haematological malignancies
Leukaemias (Refer to Chapter ‘Bleeding Disorders’).
Lymphomas (Refer to Chapter ‘Pyrexia of Unknown
Origin’).
Myeloma (Refer to Chapter ‘Low Backache’).
• Malignant Bone Tumours
Chondrosarcoma: Amputation is indicated
Osteogenic sarcoma: Surgical (radical amputation)
megavoltage radiotherapy, and chemotherapy with multiple
drug protocol (cyclophosphamide and doxorubicin,
methotrexate, vincristine) may result in an increase in the
five years survival rate.
Ewing’s sarcoma: Ablative surgery, megavoltage
radiotherapy and chemotherapy are effective.
Fibrosarcoma: Amputation is advocated.
For those who are beyond the curable stage, terminal
care must be designed to relieve pain, ensure optimum
nutrition and psychological support. Nevertheless, the basic
approach to cancer control is by primary prevention
(avoiding precipitating factors) and secondary prevention
(early diagnosis and treatment).
Weight Loss 563
 Appendices

APPENDIX I: LABORATORY REFERENCE VALUES

Normal Haematological Values

• Red blood cell count Males: 5-6 million per mm3
Females: 4.2-5.5 million per mm3
Haemoglobin Males: 14-17 g. per 100 ml
(100 % = 14.6 g per 100 ml) Females: 12-15 g. per 100 ml
RDW 13.4 ± 1.2%
Erythrocyte indices
Mean corpuscular haemoglobin 27-32 pg
Mean corpuscular haemoglobin
concentration 32-38%
Mean corpuscular volume 78-94 µ3
Packed cell volume (haematocrit), i.e. Males: 40-54%
% of volume of blood occupied by RBC Females: 37-47%
Reticulocytes 0-5-2%
Erythrocyte Sedimentation Rate (ESR) Males: 0-9 mm in 1 h
Females: 0 to 20 mm 1 h (increases with age)
Osmotic fragility of red cells Haemolysis commences at 0.45% saline
and is complete at 0.30%
• White blood cell count 4,800-10,800 per mm3
Neutrophil polymorphs 40-75%
Eosinophil 1-6%
Basophil 0-2%
Lymphocyte 20-45%
Monocyte 2-10%
• Platelet count 1,50,000-4,00,000 per mm3
• Coagulation studies
Bleeding time 2-7 min
Coagulation time 4-9 min
Prothrombin time 12-14 s (INR < 1.8)
Partial thromboplastin time 24-36 s
Thrombin time 12-18 s
Clot retraction time Commences in 1 to 3 h and completes in 24 h
Fibrinogen 200-400 mg/100 ml
FDP < 8 µg/ml
Antithrombin (ATIII) 5 -15 µg/L (50 - 150%)
Bone Marrow: (Contains all nucleated cells)
• Total nucleated cell count: 20,000 – 100,000 per c. mm
• Differential cell count (averge %)
I. Haemocytoblast 0.5
II. Other cells:
(A) Erythroid cells
Proerythroblasts 2
Normoblasts
 566 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Early 9.5
Late 13
(B) Myeloid cells:
Myeloblasts 1
Promyelocytes 3
Myelocytes 7
Metamyelocytes 9.5
Neutrophils 35
Eosinophils 2
Basophils 0.5
(C) Lymphocytes 14
(D) Monocytes 1.5
(E) Plasma cells 0.5
(F) Reticulum cells 0.5
(G) Megakaryocytes 0.5

Normal Blood Chemistries (Refer Appendix II also)

Aldolase 0-8 µ/L (0-130 nmol nmol/L)
Ammonia 80-110 µg/100 ml (47-65 µmol/L)
Amylase 60-180 U/L (13-53 nmol/L)
Angiotensin II 10-30 pg/ml (10-30 nmol/L)
Antistreptolysin titre 150-200 U/ml
Alpha-antitrypsin 85-213 mg/100 ml (0.8-2.1 g/L)
Alpha fetoprotein < 30 ng/ml (<30 µ/L)
Bilirubin: Total 0.3-1 mg/100 ml (5.1-17 µmol/L)
Direct 0.1-0.3 mg/100 ml (1.7-5.1 µmol/L)
Indirect 0.2-0.7 mg/100 ml (3.4-12 µmol/L)
CA19.9 0-25 µ/ml
CA125 35 U/ml
CEA 4-7 ng/ml
C-Peptide 0.8-4.0 ng/ml
C-reactive protein < 10 mg/L
Carbon dioxide content (Total) 21-30 mEq/L (21-30 mmol/L)
(bicarbonate+carbon dioxide)
Catecholamines: Epinephrine < 0.1 µg/L
Norepinephrine < 0.5 µg/L
Ceruloplasmin 27-37 mg/100 mL (1.8-2.5 µmol/L)
Cholesterol (total)
Desirable < 200 mg/(< 5.2 mmol/L)
Borderline 200 – 231 mg (5.20 – 6.18 mmol/L)
Desirable LDL cholesterol < 130 mg% (< 3.36 mmol/L)
Borderline LDL cholesterol 130 – 159 mg% (3.36 – 4.11 mmol/L)
Desirable HDL cholesterol > 60 mg% (> 1.55 mmol/L)
Borderline HDL cholesterol 35–60 mg% (0.9 – 1.55 mmol/L)
Cholesterol esters 90-150 mg/100 ml (2.3-3.9 mmol/L)
Complement
C3 55-120 mg/100 ml (0.55-1.2 g/L)
C4 20-50 mg/100 ml (0.2-0.5 g/L)
 Appendices 567

Copper (Free and Bound) 70-140 µg/100 ml (11-22 µmol/L)

Creatine 0-17-0.93 mg/100 ml
Creatine kinase (CK) Males: 25-195 U/L (0.4-1.51 mmol/L)
Females: 25-170 U/L (0.17-1.18 mmol/L)
Creatine kinase (MB) < 6% of total CK.
Creatinine < 1.5 mg/100 ml (< 133 µmol/L)
Electrolytes
Bicarbonate 21-28 mEq/L (21-28 mmol/L)
Calcium 9-10.5 mg/100 ml (2.2-2.6 mmol/L)
Chlorides 98-106 mEq/L (98-106 mmol/L)
Magnesium 1.3-2.1 mEq/L (0.8-1.3 mmol/L)
Phosphorus 3-4.5 mg/100 ml (1-1.4 mmol/L)
Potassium 3.5-5 mEq/L (3.5-5 mmol/L)
Sodium 136-145 mEq/L (1.36-145 mmol/L)
Fatty acids (free) < 18 mg/100 ml (<0.7 mmol/L)
Ferritin 12-200 ng/ml (12-200 µg/L)
Folate 2.1-2.8 µg/L (5-6.3 nmol/L)
Gamma glutamyl transferase 4-60 U/L
Glucose: Fasting < 110 mg/100 ml (<6.1 mmol/L)
i.e. 72-108 mg/100 ml (4-6 mmol/L)
Glucose (postprandial) < 140 mg/100 ml (< 7.8 mmol/L)
Glucose-6 phosphate dehydrogenase 5-10 U/g Hb
Glycosylated (Glycated Haemoglobin (HbA1c) 4-6.5%
Haptoglobin 30 – 200 mg%
Homocystein 5-15 µmol/L
Hormones: (Vide Appendix II.)
(β-HCG) Human chorionic gonadotrophin
men and nonpregnant women < 3 m U/ml (< 3 IU/L)
β-Hydroxy butyrate 72 – 182 U/L
Immunoglobulins
IgA 90-325 mg/100 ml (0.9-3.2 g/L)
Igd 0.8 mg/100 ml (0-0.08 g/L)
IgE < 0.025 mg/100 ml (< 0.00025 g/L)
IgG 800-1500 mg/100 ml (8-15 g/L)
IgM 45-150 mg/100 ml (0.45-1.5 g/L)
Insulin (F1): 6 – 26 µU/ml
Insulinlike growth factor 123-463 ng/ml)
Iron 80-180 µg/100 ml (4-32 µmol/L)
Iron-binding capacity 250-460 µg/100 ml (45-82 µmol/L)
Lactate 5-15 mg/100 ml (0.6-1.7 mmol/L)
Lactic acid 0.6-1.8 mEq/L
Lactate dehydrogenase (LDH) 110-250 mU/ml (1.83-4.17 µmol/L)
Lactate dehydrogenase isoenzymes
Fraction 1 14-26% of total (0.14-0.25)
Fraction 2 29-39% of total (0.29-0.39)
Fraction 3 20-26% of total (0.2-0.25)
Fraction 4 8-16% of total (0.08-0.16)
Fraction 5 6-16% of total (0.06-0.16)
Lead < 20 µg/100 ml (<1 µmol/L)
568 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Lipase 0 – 160 U/L

Lipids (total) 450-1000 mg/100 ml
Lipoproteins
Beta lipoproteins (LDL) 60-70%
Prebeta lipoproteins (VLDL) 8-20%
Alpha lipoproteins (HDL) 17-25%
Lipoprotein (a) 12-22 mg/100 ml
Myoglobin 19-92 ng/L
5-Nucleotidase 0.3-2.6 U/100 ml (27-233) nmol/L
Osmolality 285-295 mosm/kg of serum water
Oxygen content
Arterial blood 17-21 volume%
Venous blood 10-16 volume%
Oxygen saturation
Arterial blood 97% (0.97 mol/mol)
Venous blood 60-80% (0.6-0.85 mol/mol)
Phosphatase acid 0.2-1.8 IU/L (3-30 nmol/L)
Phosphatase alkanine 30-120 IU/L (0.5-2 µmol/L)
Phospholipid 150-250 mg/100 ml (48-81 mmol/L)
pH 7.35-7.45
PO2 (oxygen tension) 80-100 mmHg (11-13 kPa)
PCO2 (carbon dioxide tension) 35-45 mmHg (11-13 kPa)
Prostate specific antigen (PSA) 0-4 ng/ml (0-4 µg/L)
Proteins-Total 5.5-8 g/100 ml (55-80 g/L)
Albumin 3.5-5.5 g/100 ml (35-55 g/L)
Golbulin 2-3.5 g/100 ml (20-35 g/L)
Protein electrophoresis
Alpha1 0.2-0.4 g/100 ml (2-4 g/L)
Alpha 2 0.5-0.9 g/100 ml (5-9 g/L)
Beta 0.6-1.11 g/100 ml (6-11 g/L)
Gamma 0.7-1.7 g/100 ml (7-17 g/L)
Protein-C 71-716%
Protein-S 76-178%
Pyruvate 0.5-1.5 mg/100 ml (0.06-0.17 mmol/L)
Renin activity 1-4.8 ng/ml/h (more in the upright position and on low
sodium diet or decreased renal blood flow)
Serotonin (5 hydroxy tryptamine) 0.05-0.2 µg/ml
SGOT (Serum Glutamic-Oxaloacetic Transaminase) or
AST (Aspartate-Aminotransferase) 10-40 Karmen units/ml (100-300 µmols/L)
SGPT (Serum Glutamic-Pyruvic Transaminase) or
ALT (Alanine-Aminotransferase) 10-40 Karmen unit/ml (50-430 µmols/L)
Sulphate 0.5-1.5 mg/100 ml
Transferrin 200-400 mg% (2-4 gm/L)
Transferrin saturation 25-40%
Triglycerides <160 mg/100 ml (<1.8 mmol/L)
Troponin-I < 0.05 ng/ml
Troponin-T < 0.01 ng/ml
Urea nitrogen-creatinine ratio 10 : 1
Urea 15-45 mg% (2.5-7.5 mmol/L)
 Appendices 569

Urea nitrogen 10-20 mg/100 ml (3.6-7.1 mmol/L)

Uric acid Men: 3.5-8 mg/100 ml (210-480 µmol/L)
Women: 2.5-6 mg/100 ml (150-360 umol/L)
Vitamin B12 200-600 pg/ml (148-443 pmol/L)
Zinc 75-120 µg/100ml (11.5-18.5 µmol/L)

Normal Urinary Chemistries (Refer Appendix II also)

Albumin (mg) < 30 mg/24h or < 20 µg/min
Microalbuminuria 30-300 mg/24h or 20-200 µg/mt
Albumin (mg)/Creatinine (mmol) ratio < 2.5 mg/mmoL
Ammonia 30-50 mEq/24 h(30-50 mmol/24 h)
Amylase 35-260 somogyi units/dl
Calcium < 150 mg/24 h (< 3.8 mmol/24h)
Chlorides 5-15 g/24 h
Copper 0-25 µg/24 h (0-0.4 µmol/24 h)
Coproporphyrin 100-300 µg/24 h (150-460 nmol/24 h)
Cortisol (free): < 280 nmol/24 h
Creatine Men: <50 mg/24 h (< 380 pmol/24 h)
Female: <100 mg/24 h (< 760 pmol/24 h)
Creatinine 1-1.6 g/24h (8.8-14 mmol/24h)
Cystine 10-100 mg/24 h
Glucose 50-300 mg/24 h (0.3-1.7 mmol/24h)
Hormones (Vide Appendix II.)
5-Hydroxyindoleacetic acid (5-HIAA) 2-9 mg/24 h (10-47 µmol/24 h)
Hydroxymethylmandelic acid: 16 – 48 µmol/24 h
Ketones 50.5 ± 30.7 mg/24 h
Lead < 80 µg/24 h (<0.4 µmol/24 h)
Meta adrenalines: 59 – 335 mg/24 h (0.3 – 1.7 µmol/24 h)
Osmolality 350-1000 moSm/kg
Oxalate 0.2-0.54 mmol/24 h
pH 4.6-8
Phosphorus 0.8-2 g/24 h
Prophyrins
Copro porphyrin <96 µg/24h
Uro Porphyrin <46 µg/24h
Potassium 25-100 mEq/24 h (25-100 mmol/24 h)
Protein < 150 mg/24 h (< 0.15 g/24 h)
Sodium 100-260 mEq/24 h (100-260 mmol/24 h)
Specific gravity 1015-1025
Sulphate 50 mmol/24 h
Urea 15-35 g/24 h
Uric acid 600-700 mg/24 h
Urobilinogen 1-3.5 mg/24 h (1.7-5.9 µmol/24 h)

Normal Faeces
Bulk Dry weight 66.4 g/24 h
Wet weight < 197.5 g/24 h
Calcium up to 610 mg/24 h (upto 15.4 mmol/24 h)
 570 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Coproporphyrin 400-1000 µg/24 h (600-1500 nmol/24 h)

Fat (total) < 6 g/24 h
Nitrogen < 1.7 g./24 h (Ig.N = 6.5 g protein)
Trypsin < 40 U
Urobilinogen 40-280 mg/24 h (68-470 µmol/24 h)
Water About 65%

Normal Cerebrospinal Fluid

Cells (lymphocytes) 0-5 per c.mm
Chlorides 116-122 mEq/L (116-122 mmol/L)
Globulin 0-6 mg/100 ml (0.06 g/L)
Glucose 40-70 mg/100 ml (2.2-3.9 mmol/L)
Osmolality 285-295 mosmol/kg (285-195 mosmol/L)
pH 7.34-7.43
Pressure 7-20 cm of water
Protein (lumbar) 15-45 mg/100 ml (0.15-0.45 g/L)
Protein (cisternal) 15-25 mg/100 ml (0.15-0.25 g/L)
Protein (ventricular) 5-15 mg/100 ml (0.05-0.15 g/L)
Specific gravity 1003-1008
Total volume 60-150 ml
Ig G Index < 0.65

Normal Seminal Fluid

Count (spermatocyte) 50-100 million/c.cm
Liquefaction Complete in 15-30 min
Morphology > 50% of normal forms
Motility > 60% of motile forms
Volume 2-6 ml
Specific gravity 1028
pH 7.35-7.5
Acid phosphatase 2500 kA/ml

Body Fluids
Total volume 50-70% of body weight
Intracellular 30-40% of body weight
Extracellular 20-30% of body weight

Blood Volume About 80 ml/kg body weight: of this RBC volume is 42%
(34 ml/kg) and Plasma volume is 58% (46 ml/kg)
N.B.
i. Microgram (µg)=1/1000000 of a gram (10–6)
ii. Nanogram (ng)=1/1000000000 of a gram (10–9)
iii. Picogram (pg)=1/1000000000000 of a gram (10–12)
iv. Mole=6×1023 molecules (Mole is molecular weight of the substance expressed in grams)
v. Millimole=1/1000 of a mole. (mmol) (It is molecular weight of ion in milligrams)
vi. Micromole (µmol)=1/1000000 of a mole
 Appendices 571

vii. Conversion of milligrams (mg)/dl into milliequivalents (mEq)/L

mg/dl ×10 × Valence
mEq/L =
Atomic weight
viii. Conversion of mEq/L into mg/dl
mEQ/L × atomic weight
mg/dl =
10 × valence
ix. Conversion of mg/dl into mmol/L: All monovalent radicals have the same amounts of mg/dl; mEq/L or mmol/L. But
it is different for divalent radicals. However, it is calculated as follows:
mg/dl ×10
mmol/L = × mmol/L
Atomic weight
• For example, normal value of serum phosphorus is 3-4.5 mg/dl (0.9-1.45 mmol/L)
3 × 10/31 (Atomic Weight)=0.9 mmol/L
4.5 × 10/31=1.45 mmol/L, i.e. normal value of serum phosphorus is 0.9-1.45 mmol/L
 APPENDIX II: FUNCTION TESTS OF DIVERSE ORGANS

Cardiovascular
1. Clinical assessment (normal values a. From lying to standing position:
in function tests of cardiovascular (i) Rise in pulse rate: > 10/mm
autonomic status) (ii) Rise in blood pressure: < 10 mmHg
b. Heat rate variation in deep breathing (6/min): Maximum-mini-
mum heart rate: >10/min
c. Breath-holding test: >30 s
d. Valsalva ratio: >1.2
Ratio of longest and shortest R-R intervals in ECG taken during
valsalva manoeuvre.
e. Record blood pressure continuously while the subject is stand-
ing for 10-20 min, when the systolic blood pressure should not
fall by 20 mmHg or more.
f. Diastolic blood pressure responds to sustained hand grip (for
2-3 min): >16 mmHg
g. Exercise tolerance test: Heart rate increases rarely over 150/min
and rapidly returns to normal after ceasing exercise
(a, b, c and d are tests for parasympthetic nervous system and e, f
and g are tests for sympathetic nervous system.
2. Resting ECG Provides accurate information about the state of myocardium
3. Stress testing Exercise ECG shows
(i) No significant ST depression
(ii) Decreased amplitude of ‘R’ wave in V5
4. Circulatory and related measurements Cardiac output: 2.5-3.6 L/sq. m of body surface area/min
Circulation time: Arm to lung: 4-8 s
Arm to tongue: 10-16 s
Stroke volume
Ejection fraction, i.e. = 0.55 – 0.78
End-diastolic volume
End-diastolic volume: 75 ± 15 ml/m2 (EDV)
End-systolic volume: 25 ± 8 ml/m2
LV Work: Stroke work index: 30-110 (gm)/m2
Systolic time intervals: (PEP; LVET; Qs2)
Pre-ejection period (PEP): 131 millisec
Left ventricular
ejection time (LVET): 413 millisec
Total electromechanical systole
(Qs2): 546 millisec.
PEP
Ratio of = 0.35 ± 0.04
LVET

5. Haemodynamic studies
6. Other special investigations (apart
from cardiac catheterisation studies
—vide supra)
Endocrinal
1. Pituitary function
Appendices 573
(a) Flows:
Cardiac output
Cardiac index Body surface area = 2.4 – 3.8 /L/min/sqm
(b) Pressures
Central venous pressure: < 4 cm
Right atrium: 2-6 mmHg
Left atrium: 2-12 mmHg
Right ventricle
Systolic (peak) 15-30 mmHg
End-diastolic: 2-7 mmHg
Pulmonary artery
Systolic (peak): 15-30 mmHg
End-diastolic: 2-7 mmHg
Pulmonary capillary wedge pressure:
<15-18 mmHg
Left ventricle
Systolic (peak): 100-140 mmHg
End-diastolic: 3-12 mmHg
(on exercise: 12 mmHg)
Arterial (systemic): Aorta
Systolic (peak): 90-140 mmHg
End-diastolic: 60-90 mmHg
Mean: 70-105 mmHg
(c) Resistances
Systemic vascular
resistance: 770-1500 (dyn.s)/cm5
Pulmonary vascular
resistance: 20-120 (dyn.s)/cm5
Total pulmonary
resistance: 100-300 (dyn.s)/cm5
(D) Oxygen consumption: 110-150 L/min/sqm
Arteriovenous oxygen differnece: 30-50 ml/L
Echocardiography: For measuring dimensions of chambers and
aorta; assessing movements of septum, valves and left ventricular
wall; and function
Doppler echocardiography (measures blood flow velocity directly)
Angiography
Radionuclide angiography
(i) Blood pool scanning: Peak LV filling rate (PFR) = 2.5-
4.2 EDV/s
Time to PFR = 58-161 millisec (derived from LV time
activity curve which was obtained from equilibrium
radionuclide angiography)
(ii) Myocardial scanning
(a) Basal function tests
(i) Measurement of pituitary hormones, serum ACTH (corticotro
phin) < 80 ng/L (< 18 pmol/L)
574 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Growth hormone: < 15 – 20 mU/L)

TSH; FSH; LH (vide infra)
Prolactin: 60-390 mU/L
ADH (vasopressin): 0.9-4.6 pmol/L
Oxytocin: 1.25-5 ng/L (1-4 pmol/L)
(ii) Measurement of target organ secretion (thyroid, adrenal,
gonads)- (Vide infra).
(b) Dynamic Test: (Insulin hypoglycaemia test): A fall of blood
sugar to <40 mg% after administering-insulin IV (0.1-0.2
U/kg) stimulates hypothalamic pituitary axis. Then serum
cortisol, growth hormones, ACTH and blood sugar are
measured every 1/2 for 2 h.
2. Adrenal function (a) Basal fucntion tests
(i) Measurement of adrenal steroids (serum)
Cortisol (hydrocortisone)
8 am 5-25 µg/100 ml (140-690 nmol/L)
4 pm 3-12 µg/100 ml (80-330 nmol/L)
(Cricadian rhythm—cortisol secretion more in the morning)
II-deoxycortisol: <1 µg/100 ml (<30 nmol/L)
Aldosterone: <8 ng/100 ml (<220 pmol/L)
Dehydroepiandrosterone (DHEA) 0.2-.9 µg/100 ml
(7-31 nmol/L)
Dehydroepiandrosterone sulfate (DHEA sulfate)
50-250 µg/100 ml (1.3-6.7 µmol/L)
17-hydroxyprogesterone
Women: 0.02-0.1 µg/100 ml (0.6-3 nmol/L)
(higher in luteal phase)
Men: 0.006-0.3 µg/100 ml (0.2-9 nmol/L)
(ii) Measurement of adrenosteroids: (urine)
Cortisal (free): 20-100 µg/24h (55-275 nmol/24 h)
17-hydroxy corticosteroids: 2-10 mg/24 h (5.5-28 µmol/24 h)
Aldosterone: 5-19 µg/24 h (14-53 nmol/24 h)
17-oxogenic steroids
Men: 10-19 mg/24 h
Women: 5-13 mg/24 h
17-oxosteroids (ketosteroids)
Men: 7-25 mg/24 h (24-88 µmol/24 h)
Women: 4-15 mg/24 h (14-52 µmol/24 h)
(iii) Measurement of urinary catecholamines
Free catecholamines: <100 µg/24 h (< 590 nmol/24 h);
Epi nephrine: < 50 µg/24 h (< 275 nmol/24 h)
Vanillyl mandelic acid (VMA) < 8 mg/24 h (<40 µmol/24 h)
(b) Dynamic tests
(i) Dexamethasone suppression test
1 mg of dexamethasone orally given at 10 pm Serum cor
tisol estimated at 8 am and it should be < 5 µg/100 ml in
normal persons.
 Appendices 575

(ii) Insulin hypoglycaemia test (vide supra).

(iii) Metyrapone test
Administration of metyrapone blocks cortisol formation
by adrenal under normal conditions. In turn ACTH is released
which results in increased adrenocortical steriod production
other than cortisol which is indicated by increased urinary
17-hydroxycorticosteroids.
(iv) Tertracosactrin (synacthen) test
ACTH or its synthetic analogue (synacthen) is given (250 mg
IM.) and serum cortisol response is observed. The initial level
should be over 5 µg/100 ML and after 30 min over 20 µg/100
ml and the difference between them not less than 7 µg/100 ml
in normal persons.
3. Testicular function (a) Hormonal
Serum testosterone (secretion more in the morning)
Men: 300-1000 ng/100 ml (10-35 nmol/L)
Women: <100 ng/100 ml (< 3.5-7 nmol/L)
Prepubertal (both sexes): 5-20 ng/100 ml (0.17-0.7 nmol/L)
Androstenedione
Men : 80-130 mg/100 ml (3-5 nmol/L)
Women: 100-200 ng/100 ml (3.5-7 nmol/L)
Etiocholanolone: <1.2 µg/100 ml
Gonadotrophins
LH (ICSH): Secretes androgens and oestrogens
Men: 5-20 mIU/ml (5-20 IU/L)
Women: 5-25 mIU/ml (5-25 IU/L)—much higher at ovulation
period and postmenopausal period.
FSH (spermatogenesis)
Men: 5-20 mIU/ml (5-20 IU/L)
Women : 5-20 mIU/ml (5-20 IU/L)–Higher at ovulation and
postmenopausal period.
Prepubertal (both sexes): < 5 mIU/ml (< 5IU/L)
(b) Reproductive—seminal analysis (vide Appendix-I)
(c) Stimulation test with Gonadtrophic Releasing Hormone (GnRH)
or clomiphene or hCG—may be necessary if the hormonal
levels are on the border line.
4. Ovarian function (a) Hormonal
(i) Serum values
oestriol <0.2 µg/100 ml
oestradiol—Women: 20-60 pg/ml (70-220 pmol/L)
(raised at ovulation)
Men : < 50 pg/ml (< 180 pmol/L)
Progesterone-Women: > 5 ng/ml ( > 16 nmol/L) (Luteal)
Men, and preovulatory, postmenopausal and prepubertal
females: 2 ng/ml (6.4 nmol/L)
Testosterone 0.12 – 0.81 ng/ml (0.4 – 2.8 nmol/L)
FSH 2 – 8 U/L
LH 3 – 16 U/L
Testosterone-oestradiol ratio 15-17.
576 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

(ii) Urine values

Oestrogens (oestradiol)
Men: <50 pg/mL (< 180 pmol/L)
Women: 20-60 pg/mL (70-220 pmol/L)
Pregnanetriol: 0.2-3.5 mg/24 h
(b) Basal body temperature: Useful to determine the ovulatory
cycles. A rise of about 0.5—1° F is suggestive of progester
one secretion by corpus luteum following ovulation. This
biphasic temperature pattern is normal.
5. Thyroid function (a) Basal function tests
(i) Hormones
Thyroid stimulation hormone (TSH): 0.4-5 mU/L (0.4-5 m U/L)
Triiodothyronine (T3): 70-190 ng/100 ml (1.1-2.9 nmol/L)
Thyroxine (T4): 5-12 µg/100 ml (64-154 nmol/L)
Free thyroxine: 0.8-2.4 µg/100 ml (10.2-30.6 nmol/L)
Free thyroxine index: 1.3-5.1 units
Effective thyroxine ratio: 0.58-1.1%
Protein bound iodine: Indicates amount of circulating inorganic
Iodine mostly in the form of thyroxine (3-8 µg/100 ml).
Thyroid binding globulin: 7-17 mg/L
Thyroglobulin (3-42 ng/ml)
TSH receptor antibodies (< 7U/L)
T3 (resin) uptake: 25-35% (The amount of T3 not bound to
protein and removed on the resin is measured)
Reverse triiodothyronine (rT3): 10-40 ng/100 ml (0.15-0.61
nmol/L)
Calcitonin (< 0.1 µg/L)
(ii) Uptake: Studies radioactive iodine (131 I) uptake: 5-35% in
24h
(iii) Thyroid scaning:
A dose of radio-iodide or technetium is administered and the
activity over the gland is mapped. (Normal: 5×2 cm)
(b) Dynamic tests of homeostatic control
(i) T3 suppression test: When T3 (40 µg t.d.s.) is given for one
week, pituitary TSH is suppressed and consequently thyroid
uptake of radio-iodine in a normal person.
(ii) TSH stimulation test: When TSH is given (5-10 units IM)
daily for 3 days, there is no or little increase in the uptake of
radio-iodine if hypothyroidism is due to thyroid failure.
(iii) TRH test: TRH (200 µg) given IV and TSH measured before
and after one hour. In hypothyroidism, TSH response is exag-
gerated (rise is > 2 mU/L) whereas in hyperthyroidism the
TSH response is contrary (<2 MU/L). However in, hypothy
roidism due to pituitary disease, there may be reduced response.
(iv) Perchlorate discharge test: 131 I is given and after four hours
when the counts are stable perchlorate is given orally and up
take measurements are done hourly. 10-15% reduction in
counts is normal.
 Appendices 577

6. Parathyroid function (a) Basal function tests

(i) Hormones
Parathormone <0.1-0.73 µg/L (<0.8-8.5 pmol/L)
(ii) Biochemical
Serum calcium and urinary calcium
Serum phosphate and urinary
phosphate
Serum alkaline phosphatase
(iii) Dynamic test
} (Vide Appendix-I)

(i) Parathyroid hormone infusion test–Measures

tubular response to the hormone regarding
reabsorption of phosphate.
7. Pancreas (endocrine) (a) Hormones:
Glucagon: 50-100 pg/ml (14-29 pmol/L)
Proinsulin (5.78-6.9 Pmol/L)
Insulin (fasting): 6-26 u/ml (43-186 pmol/L)
C-Peptide (0.8-4.0 ng/ml)
(b) Sugar tolerance test: After giving 75 g of glucose orally, blood
sugar should not be > 180 mg/100 ml (> 10 mmol/L) within
two hours.

Gastrointestinal
1. Oesophageal (i) Resting pressure
Upper oesophageal sphincter (UES): +30 mmHg; Lower
oesophageal sphincter (LES): +15 mmHg
(ii) Swallowing pressure: Increases more than twice (> 60
mmHg) in the UEs and less than twice (< 30 mmHg) in
the LES
2. Gastric (i) Intragastric pressure: + 5 mmHg
(ii) Gastric juice
Volume: 2-3 L/d
Reaction: pH 1.6-1.8
Basal acid output
Ratio = Maximal acid output = 0.6

(iii) Serum gastrin 60-200 pg/ml

3. Intestinal (A) Absorption tests
(i) D-xylase: 25 g of xylase given orally after fasting over-
night. Serum should contain 25-40 mg/100 ml after one
hour and urine collected after five hours should contain
5.8 g.
(ii) Vitamin: A: After 200000 units of vitamin A in oil given
oraly after fasting, the serum level should rise to twice
that of fasting level in 3-5 h.
(iii) Vitamin B12: B12 labelled with cobalt58 is given orally to-
gether with a further dose of B12 labelled with cobalt57
bound to intrinsic factor and a dose of B12 1000 µg also
given at the beginning of the test. 24 h urine collection is
then assayed, when more than 10% of the dose should
be excreted within 24 h.
 578 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

(B) Colonic flora: Normal jejunum contains 101-103 organisms. (Any

contamination/overgrowth is indicated by breath hydrogen test,
i.e. end-expiratory breath samples, at intervals of 30 min for
two hours, show a rise of > 20 ppm above base line as mea-
sured by breath hydrogen metre, after an overnight fast, on
administering 50 g of glucose orally in 200 ml of water.)
(C) Stool: (Vide Appendix I)

Hepatobiliary and Pancreatic (Exocrine)

1. Liver (A) Excretory
(i) Biliary
Serum bilirubin: Total: 0.3-1mg/100 ml (5.1-1.7 µmol/L)
Direct: 0.1-0.3 mg/dl (1.7-5.1 µmol/L)
Indirect: 0.2-0.7 mg/dl (3.4–12 µmol/L)
Urinary bilirubin: Absent normally
Urinary urobilinogen: 1-35 mg/24 h (1.7–5.9 µmol/24 h)
Faecal stercobinogen: 40-280 mg/24 h (68–470 µmol/
24 h)
(ii) Bromosulphthalein excretion: 5 mg/kg IV when given
< 5% of the dose is retained in serum after 45 min (not
useful in the presence of jaundice)
(iii) Cholesterol (serum): < 200mg (< 5.2 mmol/L)
(iv) Enzymes: Serum alkaline phosphatase: 30-120 IU/L
(0.5–2 µmol/L)
(B) Integrity of hepatocytes
Enzymes
(i) Aspartate aminotransferase (AST, SGOT): 10-40 Karmen
units/ml (100–300 mmol/L)
(ii) Alanine aminotransferase (ALT, SGPT) 10-40 karmen
units/ml (50-430 mmol/L)
(C) Other enzymes
(i) Gamma glutamyltranspeptidase (4-60 U/L)
(ii) 5-nucleotidase: 0.3–2.6 Bodansky units/100 ml (27-233
nmol/L) (useful to confirm isolated rise in serum alkaline
phosphatase of suspected liver origin)
(D) Metabolic function
(a) Proteins
(i) Albumin: 3.5-5 g/dl
(ii) Globulin: 2-3.5 g/dl
(iii) Flocculation tests
Thymol turbidity: 0-4 U
Zinc sulphate turbidity: 4-12 U
(iv) Prothrombin: 60-100%
(v) Ammonia (test for hepatic detoxification) 80-110 µg/dl
(b) Fats
Cholesterol esters (about 60% of cholesterol is esterified nor-
mally by the liver)
90-150 mg/100 ml (2.3–3.9 mmol/L)
 Appendices 579

(c) Carbohydrates: Galactose tolerance (2.5 g/kg in 50%

solution when given i.v., disappears from blood in two
hours): no longer used
2. Gallbladder (A) Oral cholecystography: The gallbladder should contract to one
half of its original size at least, after a fatty meal (not under-
taken in jaundice).
(B) Cholangiography: Useful to determine normal patency of the
bile duct
3. Pancreas (Exocrine) (A) Examination of the urine amylase (diastase) levels: Normally
35-260 somogyi units/h
(B) Examination of the stool:
(i) Faecal fat content should not exceed 10% of the fat in-
take
(ii) Faecal nitrogen does not exceed 1.5 g representing 10 g
of protein
(iii) Microscopy: Partially digested few muscle fibres present
(C) Examination of the blood:
(a) Enzymes
(i) Serum amylase: 60-180 somogyi units/100 ml (13-53
mmol/L)
(ii) Serum lipase: 0.2-1.5 U
(iii) Serum alkaline phosphatase: 30-120 IU/L (0.5-2 mmol/L)
(b) Coagulation
(i) Serum calcium: 9-10.5 mg/dl (2.2-2.6 mmol/L)
(ii) Prothrombin: 60-100%
(iii) Antithrombin III: 80-120%
(D) Study of duodenal juice:
(i) Yellow or yellowish green bile stain
(ii) pH > 8
(iii) Pancreatic enzyme content
(iv) Secretory tests
(a) Secretin test (1U/kg body weight)/Pancreozymin/
Cholecystokinin IV (seldom employed)
(i) Volume of pancreatic juice: >2 ml/kg in 80 min
(ii) Bicarbonate output: >10 mEq in 30 min
(iii) Bicarbonate concentration: >80 mEq/L
(iv) Pancreatic enzyme content increased
(b) Lundh test meal (liquid form of carbohydrate, pro-
tein, fat): Duodenal contents assayed for
concentration of pancreatic enzymes
(E) Bentiromide test: 500 mg of bentiromide orally given and
p-aminobenzoic acid measured in
(i) Plasma >3.6 (± 1.1) µg/ml at 90 min
(ii) Urine > 50% recovered in 6 h
(F) Radiology: ERCP (Endoscopic Retrograde Cholangio
Pancreatography): Pancreatic cytology and pancreatic juice
analysis can also be done, besides visualising biliary tree and
pancreatic duct.
580 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Pulmonary
1. Ventilatory (A) Spirometry Women Men
Forced vital capacity (FVC) ≥3L ≥4L
Forced expiratory volume (FEV1) >2L >3L
in one second
FEV1/FVC=FEV1% > 60% > 70%
Maximal mid-expiratory flow (MMF): > 1.6 L/s > 2 L/sec
Maximal expiratory flow rate (MEFR) >3L/s >3.5L/sec
Pulmonary ventilation (Respiratory minute volume): 6 L/min
Alveolar ventilation: 4.2 L/min
Maximal voluntary ventilation (MVV): 125-170 L/min
Peak Expiratory Flow rate with 300-500 L/min 450-
700 L/min weights flow meter (PEFR) First ten second
of expiration.
(B) Lung Volumes Women Men
Total lung capacity (TLC) 4.2 L 6L
(IRV+TV+ERV+RV)
Vital capacity (VC) 3.1 L 4.8 L
(IRV+TV+ERV)
Inspiratory capacity (IC) 2.4 L 3.8 L
(IRV+TV)
Functional residual capacity (FRC): 1.8 L 2.2 L
(ERV+RV)
Inspiratory reserve volume (IRV) 1.9 L 3.3 L
Expiratory reserve volume (ERV) 0.7 L 1.0 L
Tidal volume (TV) 0.5 L 0.5 L
Residual volume (RV) 1.1 L 1.2 L
(Minute volume is TV × Rate of respiration which measures
air entering or leaving respiratory tract at mouth)
2. Gas exchange (A) Arterial blood gases
Arterial oxygen tension (PaO2): 80-100 mmHg (11-13 kPa)
Arterial oxygen saturation (SaO2): 95-99%
Alveolar oxygen tension (PaO2), i.e.

PaCO 2
PaO2 = PIO 2 = 94 – 100 mmHg
0.8
(PIO2 is inspired pressure of O2 which is 149.7 mmHg)
Alveolar-arterial oxygen difference (A-a)O2 = ≤ 20 mmHg
larger gradients suggest impaired gas exchange leading to
decrease in PaO2 (Hypoxaemia)
F1O2 (Fraction of O2 in the inspired air) is 0.21
Arterial carbon dioxide tension (PaCO2): = 35-45 mmHg (4.7-
6 kPa)
Arterial bicarbonate (HCO3): 21-28 mEq/L (21-28 mmol/L)
Arterial blood pH: 7.35-7.45
(N.B. 7.6 mmHg = 1 kPa), where kPa = Kilopascals.
(B) Diffusing capacity for carbon monoxide uptake (DL CO)—
Gas exchanging capacity or transfer factor. At rest: 19 ± 3.9/ml
 Appendices 581

CO/min/mmHg; On exercise: 27± 3.9 ml CO/min/mmHg (N.B:

Reduced duffusing capacity causes reduced oxygenation of
arterial blood as in emphysema gas transfer measured by as-
sessing CO uptake).

Renal
1. Glomerular (A) Clearance tests for measuring glomerular filtration rate (GFR)
Creatinine clearance test: 75-125 ml/min
Insulin clearance test: 100-150 ml/min
Urea clearance test: 60-100 ml/min
(N.B: Normal GFR in men is about 125 ml/min, or 180 L/day,
and 10% lower in women as against normal urine volume of
2 L/day, i.e. 99% of filtrate is reabsorbed normally)
GFR
(B) Filatration fraction (FF) = = 17 to 21%
RPF
(RPF = Renal plasma flow)
(C) Urine volume: 800-2500 ml/day
(D) Substances depending on filtration for their excretion
Urea: 15-40 mg/100 ml (2.5–6.7 mmol/L)
Creatinine: 0.7-1.5 mg/100 ml (62-133 µmol/L)
(E) Renin activity=0.9-3.3 ng/ml/hr.
2. Tubular function (A) Urine specific gravity (for assessing distal tubular function)
Water concentration test: > 1025 (after 12 h of water restric-
tion)
Water dilution test: < 1003 (after 12 h of liberal water intake)
(B) Phenolsulphonephthalein (PSP) excretion test for assessing
proximal tubule—Proximal tubular transport measured by the
15 minute excretion determination and also serves as a clinical
measurement of renal plasma flow (6 mg parenterally).
> 25% excreted in 15 min
> 40% excreted in one hour
> 60% excreted in two hours
(C) Urea concentration test
Urine urea concentration: > 2 g/100 ml
(D) Tubular reabsorption of phosphorus: 79-94%
3. Both glomerular and tubular (A) Urine
Specific gravity: 1002-1028
pH: 4.6-8
Acid load test: Ammonium chloride given (0.1 g per kg body
weight) when pH should become < 5.3
Osmolality: 350-1000 mOsm/kg
Protein excretion: < 150 mg in 24 h
Other chemical constituents (inorganic, e.g. sodium and
organic, e.g. urea)
Deposits: Under high objective (1/6 in)
Cells: Pus cells (2-4), RBC (1-2) epithelial cells (occasional)
Casts: Hyaline (occasional)
 582 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

(B) Blood
Anion gap = Na-(HCO3 + Cl)=10 ± 2 mEq/L or mmol/L
Osmolality = 2Na mEq/L + BUN mg/dl + Glucose mg/dl
2.8 18
= 285-305 mOsm/kg
Urine osmolality
Serum osmolality = > 3
Bicarbonate: 21-28 mEq/L (21-28 mmol/L)
Renin activity 0.9 – 3.3 ng/ml/hr
(C) Effective renal plasma flow
Para-aminohippuric acid clearance: 490-820 ml/min
(D) Radiology: Intravenous pyelogram
(E) Isotope clearance procedures
(F) Isotope renography (renogram)
(G) Renal scintigraphy (scan)
N.B.: Osmolality is number of osmoles per kg of solvent. Osmolarity is number of osmoles per litre of solution.
 APPENDIX III: TOXICOLOGY (SPECIFIC POISONS)
Poisons can be grouped as (1) Alcohols (2) Corrosives (3)
Drugs (4) Metals (5) Pesticides and (6) Miscellanea: (i)
Mushroom (ii) Petroleum distillates (iii) plants (iv) Toxic
gases and fumes
The principles of management of poisoning:
A. Elimination by
i. Emesis or Gastric lavage (contraindicated in acids
or alkalies or petroleum distillates poisoning) Preserve
Gastric contents.
ii. Inactivation with universal antidote i. e. activated
charcoal (50-100 gm through the lavage tube).
iii. Bowel irrigation by oral Polyethelene glycol-
electrolyte at a rate of one litre per hour till rectal
effluent is clear.
iv. Alkaline Diuresis.
v. Dialysis/Haemoperfusion
B. Specific antidotes/management
C. Supportive therapy to maintain Circulation, Respiration,
Urine output and Temperature.
D. Symptomatic therapy for pain, Electrolyte imbalance.
E. Treat complications if any (Pulmonary Oedema, Cerebral
Oedema, Renal Failure, Cardiac Arrhythmias).
F. General care of Coma, Convulsions and infections.
G. Monitoring Serum drug levels and Biochemical
parameters.
H. Psychiatric counseling after recovery.
1. Alcohols:
a. Ethyl alcohol-10% Dextrose, Thiamine (100 mg),
Sodium bicarbonate IV; Dialysis if alcohol levels in
the blood is more than 350 gm %. Diazepam is given
to control seizures.
b. Methyl alcohol-Ethanol 50 gm (125 ml of Whisky
or Gin). To maintain Ethanol concentration at 100-
200 mg; Sodium Bicarbonate IV for acidosis; Dialysis
if necessary Methyl Pyrazole is the specific
alternative.’
c. Ethylene glycol: Fomepizole (methylpirazole) is
antidote or ethanol (vide supra)
2. Barbiturate-Hasten excretion-forced alkaline diuresis
with Saline, Glucose and 1/6th Molar lactate 500 ml
each (or 1.26% of Sodium Bicarbonate). Repeat after 4
hrs. Also 400 ml of 20% Mannitol and 40 mg Frusemide
Plus 3gms of Potassium Chloride daily, increase the
output. Consider dialysis or preferably haemoperfusion,
if meeded.
3. Belladona alkaloids (DATURA)-Physostigmine (0.5 –
2 mg) IM/IV, external cooling for controlling
hyperthermia.
4. Benzodiazepines-Flumazenil 0.5 mg –2 mg for respiratory
cessation. Forced Alakaline Diuresis, if required.
5. Carbon Monoxide-100% Oxygen. Diazepam for
convulsions. Blood transfusion with packed cells if
needed.
6. Corrosives (Acids and Alkalies):
a. Acids-Aluminium hydroxide.
b. Alkalies-Weak acids like citric acid
For both dilute with water/saline egg white, butter, milk
are beneficial as demulcents. Analgesics if necessary.
Steroids to prevent stricture may be considered.
7. Cyanide-initially amylnitrite inhalations till Sodium Nitrite
of 10 ml of 3% solution IV started; then Sodium
thiosulphate 25% -2.5-5 ml per minute IV. Dicobalt
edetate 300 mg IV indicated only if Cyanide poisoning
is definite vit B12 may be beneficial.
8. Detergents and disinfectants:
a. Cationic detergents include antiseptics of the
quarternary type-Treat shock, or Respiratory
embarrassment appropriately. Diazepam is given for
convulsions.
b. Anionic or Nonanionic detergents need treatment as
for alkalies.
c. Disinfectants like phenol is corrosive. Skin burns
and eyes washed with saline. Analgesics, Respiratory
support, demulcents given. Endotracheal intubation
or Tracheostomy if there is oedema of pharynx or
larynx. Follow up for any stricture formation and
treat accordingly.
9. Hypotensives:
i. β-blockers-Glucagon 5-10 mg IV given.
ii. Calcium channe blockers calcium gluconate IV
advocated.
 584 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
10. Metals
i. Lead: Sodium calcium edetate (50 mg/kg in Saline
IV/day for 5 days). Dimercaprol (BAL)-5 mg/kg IM
4 hrly for 2 days followed by half dose twice daily
for 1-2 weeks). Dimercaptosuccinic acid (DMSA)-
analogue of BAL) is more specific 30 mg/kg body
orally and likely to replace Sodium Calcium edetate.
ii. Mercury: Oral Dimercapto Propane Sulphonate
(DMPS)-analogue of BAL is beneficial in the
treatment of inorganic mercury poisoning. (30 mg/
kg) orally.
iii. Arsenic: Both the analogues of BAL are alternatives.
iv. Copper (Copper Sulphate)-BAL and D-Penicillamine,
Steroids, blood transfusion. Treat acute renal failure
or hepatic failure if occurs.
v. Iron: Desferrioxamine (as for Aluminium).
vi. Thallium-Prussian blue (Potassium, Ferihexa-
cyanoferrate). 10 gm bd orally.
11. Mushrooms: Toxic mushrooms account for 1-2% of
thousands of mushroom species. Amanita phylloids
ingestion is responsible for most of the fatal mushroom
poisonings.
Treatment is supportive with fluids. Benzyl penicillin
and silymarin for inhibiting amatoxin uptake by liver cells.
Treat hepatic encephalopathy if occurs, appropriately.
Treat cholinergic muscarine symptoms with atropine
and anticholinergic symptoms with physostigmine. CNS
excitement is controlled with Diazepam. Dialysis can be
considered if warranted.
12. Naphthalene-Promote excretion of haemoglobin by
alkalinazation, Diazepam for convulsions if any. Blood
transfusion if required.
13. Oleander-Electrolyte fluid balance to be maintained
especially monitoring hyperkalaemia and acidosis. Sinus
bradycardia treated with atropine or Pacing. Ventricular
Tachycardia treated with lidocaine. Digoxin-specific-Fab
antibody binding fragments (6 mg/kg) is an antidote as
for Digoxin.
14. Opiates (Morphine Heroin and Pethidine)-Naloxane 0.4
mg IV. If no response in 3 minutes, 0.8 mg IV to be
given. To be repeated till arousal. Vasopressors if
necessary (assisted ventilation required if Naloxane is
not available immediately).
15. Paracetamol- N- Acetylcysteine orally 140 mg/kg
followed by 70 mg/ kg 4 hrly for 17 doses (or) 300 mg/
kg IV in Dextrose 5% over 20 hrs. Oral Methionine 2.5
gm 4-hourly upto 10 gms. VIT K for bleeds and Mannitol
for Cerebral Oedema. Treat Renal or Hepatic failure if
develops, despite full treatment.
16. Pesticides: (Cholinesterase inhibitors)
a. Insecticides:
i. Organochlorine (DDT)- Cholestyramine 16 gm
per day in divided doses. Diazepam for
convulsions.
ii. Organophosphates- (i) Atropine 2 mg IV/IM
every 15 minutes till atropinasation occurs (ii)
Cholinesterase reactivatiors (Pralidoxime-PAM
1-2 gm IV every 15 minutes and repeat in one
hour if necessary.
Intermediate syndrome of Organophosphorous
poisoning-mostly weakness/paralysis occurs in
treated cases which are inadequately Atropin after
chloinergic crisis is over and feeling better.
Endotracheal intubation and Ventilatory support
indicated besides atropine adequately.
iii. Carbamates: Same as (ii) but PAM is not
indicated.
b. Fumigants:
i. Aluminium Phosphide poisoning-Gastric lavage
cautiously with Potassium Permangnate. Antacids
helpful.
Spot diagnosis by Silver Nitrate impregnated
paper test to Gastric fluid is 100% positive.
Cardiogenic shock treated with fluids and
inotropes and hydrocortisone.
Cardiac arrhythmias treated with amiadarone or
DC shock 6 IV Magnesium Sulphate may be
helpful.
Metabolic acidosis treated with IV sodium
bicarbonate (300-500 ml). Oxygen if necessary.
ARDS- Ventilatory support instituted.
Dialysis- Considered if necessary.
ii. Zinc phosphide treatment is supportive.
c. Rodenticides:
i. Zinc phosphide
ii. Anticoagulants Vit. K. is antidote
d. Herbicides:
Paraquat used as weedicide.
Supportive treatment advocated and supplemental
O2 is with held unless PO2 is less than 70 mmHg
17. Petroleum distillates: (Hydrocarbon poisoning) use of
lavage or inducing emesis is nor recommended. Activated
charcoal considered if it contains toxic solutes. Observe
for aspiration Pneumonia for 8 hrs and appropriate
antibiotic administerid if warranted. Watch for
arrhythmias and treat accordingly. Bronchodilators used
cautiously due to risk of arrhythmias.
18. Phenothiazines: Procyclidine or Orphenadrine for extra-
pyramidal symptoms.
 Appendices
Diazepam for convulsions.
Forced Alkaline Diuresis or Dialysis if Forced Alkaline
Diuresis Contraindicated. Neuroleptic Malignant
Syndrome (Hyperthermia, rigidity, confusion and coma)
is treated with Dantrolene IV. 1 mg/kg every 5 mts up to
10 mg/kg.
19. Salicylates (Aspirin):
Sodium bicarbonate (1-3 mEq/kg) IV.
VIT K 75 mg Parenterally if haemorrhages occur.
Forced Alkaline Diuresis or Dialysis, if needed.
20. Seafood Poisoning Replace fluid and electrolyte losses
with IV saline. Anaphylactoid reactions treated with
diphenhydramine and H2 blockers or hydrocortisone IV or
epinephrine. Rapidly progressive muscle weakness leading
to respiratory paralysis should be appropriately managed.
Mannitol 1 gm/Kg/IV is beneficial.
21. Stings and bites
a. Scorpion sting: Infiltrate around the bitten area.
Cocktail (Chlorpromazine 50 mg., promethazine 50
mg. and pathidine 100 mg. in 50 ml of 5% dextrose)
may be given in a dose of 0.3 ml/kg. per dose every
2 hours. Prazosin 500 microgram every 3 hours
orally is effective to counter the catecholamine
induced autonomic storm. Haemodynamic support
with dobutamine, analgesics for pain management
and other symptomatic measures may be undertaken.
Scorpion antivenom IV, though specific for sting,
may not be effective to prevent or alleviate cardio-
vascular morbidity.
b. Bee/wasp sting: Remove the sting barb by scarpping
and apply cold compresses. Apply mild acids like
venegar to bee stings and mild alkali to wasp stings.
Antihistamines or prednisolone may be beneficial.
Treat anaphylactic shock appropriately.
Bites
a. Snake bite
i. Immobilise bitten area with crepe bandage and
the limb by splinting.
ii. Tourniquet applied just above the bite releasing it
very 15 minutes, for 1 minute, till Anti snake
venom is given.
iii. Wash the wound with KMnO4 solution.
iv. T.T. and appropriate antibiotics administered,
preferably after removing the slough.
v. Reassure and if necessary diazepam may be given.
vi. Don’t incise/use local ASV/Ice packs/Heparin
(as it worsens coagulopathy)
585
vii. Specific treatment with anti snake venom is given.
Poly valent anti snake venom is only available in
India which is given IV diluted with dextrose saline
(50-200 ML of ASV is advocated depending on
the swelling and the speed with which swelling
progresses). Repeated doses are required 6 hourly
for 2-3 days depending on the clotting time (skin
test is mandatory before starting treatment). If
hyper sensitivity occurs, de-sensitisation is carried
out starting with small doses, keeping adrenaline,
antihistamines and corticosteroids ready.
viii. Other measures:
a. Neurotoxicity-treated with Neostigmine (0.5
every ½ hour upto 2.5 mg. IV and repeat at
2-12 hour intervals). It is preceded by IV
atropine (0.6 mg).
b. Bleeding and DIC-(Refer to Chapter ‘Bleeding
Disorder’).
c. Respiratory failure-ventilatory support with
tracheostomy and oxygen therapy.
d. Hypotension and shock (Refer to Chapter
‘Shock’).
e. Renal failure-(Refer to Chapter ‘Oliguria’).
f. Cardiotoxicity-Cardiac arrhythmias-(Refer to
Chapter ‘Palpitations’)
g. Compartmental syndromes-If swelling in bitten
area causes sub-fascial oedema, fasciectomy
advocated, while ASV continues.
B. Spider bite: Early excision of the bite sites may prevent
local necrosis. Pain may be relieved with narcotic
analgesics and oral corticosteroids beneficial. Calcium
gluconate IV relieves muscle rigidity.
22. Theophylline: Repeated administration of activated
charcoal (gut dialysis) consider haemodialysis if serum
levels > 100 mg/L Treat Seizures with Diazepam and
tachycardia with betablockers.
23. Toxic gases and fumes: Oxygen inhalations to be given
Bronchodilators for chlorine or ammonia fumes
administered Humidified oxygen is beneficial.
24. Tricyclic Depressants-sodium bicarbonate is antidote,
watch for arrhythmias and treat appropriately
Physostigmine 2 mg to be repeated if necessary.
Diazepam given for convulsions.
N.B: It is advisable to observe all patients of poisoning for
one week after instituting general as well as specific
principles of treatment for poisoning.
 APPENDIX IV: HIV/AIDS—FAST FACTS
Basic Considerations
Acquired immunodeficiency syndrome (AIDS) is an overt
end-stage manifestation of prolonged infection with Human
immunodeficiency virus (HIV). It was first described in
1981 in USA and in 1986 in India. There are 40 million
people infected world wide (95% in developing countries
and 5% in developed countries). About 16000 new cases
are added everyday. Hence, the importance of prevention
and control, is all the more significant.
HIV is a retrovirus from lentivirus family. It was isolated
in 1983 and proved that it was the causative agent in 1984.
It is probably derived from one of the African simian
immunodeficiency viruses (AIDS originated from African
Chimpanzees).
There are two strains of HIV, i.e. types HIV-1 and HIV-
2 of which the former accounts for most of the HIV
infections and the latter which is confined to West Africa,
is less transmissible. HIV is transmitted with horizontal
spread through sexual contacts (either bilateral heterosexual
or homosexual) and blood transfusion/needles and vertical
transmission from the infected mother to the child.
This virus affects the core immune system
T lymphocytes. The entry of the virus into the cell occurs
by binding to the host’s CD4 receptors in helper T
lymphocytes via outer envelope gp 120 receptor fusion and
uncoating of the virus occurs by gp41 binding to cell
chemokine core receptors, thereby facilitating entry
chemokine receptors CCR5 and CXCR4 are important for
entry of the virus. Infact HIV earlier infection is R5 tropic
virus as against dual/mixed tropic virus, which emerges
later as infection. Progress by utilising either R5 or CXCR4
co-receptors. Then once the virus enters the cell, it replicates.
The viral RNA is translated into DNA by the enzyme reverse
transcriptase (RT). HIV integrates into host target cell DNA,
mostly CD4 lymphocytes in the lymphoid tissue through
viral integrase enzyme (Integrated virus is known as provira
DNA). Viral DNA programmes host cell DNA, to produce
viral proteins (VPs) as large polypeptides which are cleaved
by viral protease enzyme into building blocks of virus.
Protease enzyme cuts VPs into small pieces. A day or so
after infection, the CD4 cell dies and completed virions are
released from the cell in billions (viral load) and exist free in
plasma for about six hours before infecting new CD4 cells
and the process is repeated. Daily turnover of infected CD4
cells is also in billions. This results in fall of CD4 count and
lymphopenia. The number of circulating viruses (viral load)
and the low CD4 counts predict the progress of the disease
(CD4 cells refer to all cells bearing CD4 receptors in T
lymphocytes). Other cells in the immune network which
are infected are macrophages, monocytes and some B
lymphocyte lines.
Clinical Spectrum
HIV infection and the resultant AIDS consists of three
stages—Acute infection, latent infection and chronic
infection (spreading over 15-25 years).
Acute Infection (Acute Retroviral Syndrome)
The primary infection usually occurs 2 to 6 weeks after
exposure. The initial infection may be asymptomatic or
symptomatic. The presenting symptoms are fever, sore
throat, myalgia, maculopapular rash, progressive generalised
lymphadenopathy (PGL). This non-specific glandular fever
like illness; unusually with oral ulcers or transient involvement
of nervous system (Meningoencephalitis), following recent
HIV infection is known as acute sero conversion. It usually
lasts for up to three weeks and recovery is complete. In
about one-third of patients, it may be totally silent.
Diagnosis is based on: (1) detecting virus by PCR. P24
antigen test is positive even before antibodies develop. HIV
RNA in serum is raised up to one million copies/ml even,
(2) CD4 cell count falls up to 500 cells/cmm (Normal 1000)
CD4: CD8 ratio is reversed (3) Lymphopenia,
thrombocytopenia raised liver enzymes are the other
findings, (4) Antibodies to HIV absent is early stages of
infection (Period between HIV infection and development
of specific HIV antibodies is known as ‘‘window period’’
which is usually 3-12 weeks; when it is infectious to others
but seronegative). However, immunoblot assay (antibodies
developing to early proteins) may be highly beneficial.
 Appendices
Not all those who become positive progress to AIDS.
However, those who experience seroconversion illness may
have a more rapidly progressive course.
Latent Infections (Asymptomatic stage)
HIV infects may target cells in the body predominantly having
CD4 receptors and chemokine co-receptors, i.e. CD4-T
cell lymphocytes with a direct cytopathic effect. About 10
billion particles of HIV (various-new infectious viruses) are
produced by infected cells and cleared everyday in these
infected individuals for 2 to 7 years or more. This clinical
latency lasting for about 7 years or more is asymptomatic
except for possible generalised lymphadenopathy. Virus
specific CD8 T cell lymphocytes develop, which control
the HIV replication after infection. Further progress is
assessed by means of an increasing viral load (HIV RNA),
i.e. if it is more than 100000 molecules/ml progression to
AIDS in three years, if > 300000/ml progression in one
year and 10000 molecules, progression is likely in 3 to 19
years. and decreasing CD4 counts (less than 350). A decline
of 50 CD4 cells/year is know to occur. This is the dangerous
period pertaining to the spread of the disease.
Chronic Infection: (Early Stage and Advanced Stage-
Symptomatic and Complicated Stages)
When the host’s ability to replenish CD4 cells wanes,
immunodeficiency manifests with HIV effects. Early
acquired immunodeficiency stage consists of systemic
symptoms like fever and/or nonbloody diarrhoea of more
than one month duration, weight loss more than 10% of the
previous body weight, oral candidiasis or leucoplakia and
persistent lymphadenopathy (more than 1 cm) involving
one or more extrainguinal sites of three months duration,
thrombocytopenia and anaemia. This spectrum corresponds
to AIDS related complex (ARC), i.e. Stage III. In this stage,
the CD4 count will be varying between 500-200 cells/cmm.
Aproportion of those ill-patients will progress to full-blown
AIDS (Advanced Immunodeficiency stage), when CD4
count will be < 200 cells/cmm i.e. Stage IV.
AIDS is defined as development of one or more AIDS
indicating illnesses in the presence of confirmed HIV
infection and CD4 count less than 200 cells/cmm. The
clinical features depend upon AIDS indicating clinical
conditions and complications of HIV related infections
affecting virtually every organ either due to HIV itself or
opportunistic, infections, besides HIV related malignancies
(Kaposi’s sarcoma, Lymphoma).
587
AIDS indicating conditions are organ specific—
1. Pulmonary (Pneumocystis Pneumonia and lymphoid
interstitial pneumonitis.
2. Gastrointestinal (oral lesions like hairy leukoplakia,
candidiasis, oesophageal candidiasis, Mycobacterium
avium intracellular, malabsorption and granulomatous
hepatitis).
3. CNS syndromes
a. Cryptococcus neoformans (meningitis), Toxoplasma
Gondi, Tuberculous, cytomegalovirus infections.
b. Dementia
c. Progressive multifocal leukoencophalopathy
d. Vascular myelopathy.
4. Renal (Glomerulosclerosis and mesangial proliferation)
— Nephrotic syndrome.
5. Skin (Viral infections of the skin and bacillary
angiomatosis)
6. Eye (Cytomegalovirus retinitis).
The opportunistic infections are:
Pneumocystis carinii, Toxoplasmosis, Cryptococal,
Cytomegalovirus, Herpes infections. Candidiasis, and
Mycobacterium avium complex.
HIV related malignancies are:
Tumours (Kaposi’s sarcoma, non-Hodgkin’s lymphoma
and cervix and anal cancers).
Thus, the HIV not only has direct effects (Serocon-
version illness, small bowel enteropathy, CNS illnesses, renal
dysfunction), but also invites opportunistic infections due
to immunodeficiencies and HIV induced malignancies as
complications.
N.B: Recently, the disease is categorised into three groups—
Category ‘A’ corresponds to Acute and latent infections
(CD4 > 500 cells/cmm)
Category ‘B’ corresponds to AIDS related complex (CD4
200-499 cells/cmm)
Category ‘C’ corresponds to AIDS indicating conditions
(CD4 < 200 cells/cmm).
Diagnosis of HIV Infection and AIDS
i. Clinical, i.e. proper history of exposure and sero
converting illness;
ii. Serological, i.e. specific tests like HIV ELISA antibody
test or rapid spot test or simple test, which is confirmed
again by western blot;
iii. Antigen assays—Nucleic acid based;
iv. Virological—Virus is detected by PCR even before
seroconversion and P24 antigen is high. Quantitative
level of plasma RNA virus i.e. HIV RNA measured;
 588 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine
v. Immunological, i.e. CD4 cell count (The lower the
CD cell count, the more the opportunistic infections
and malignancies). If CD4 cell count test is not possible,
the total lymphocyte count of less than 1200 cells/cm
is diagnostic.
N.B: The increased viral load and low CD4 count strongly
predict progress of HIV infection.
Management of the HIV Infection and AIDS
Counselling before testing and after testing, as well as HIV
infected partners and family members, is indicated before
resorting to antiretroviral therapy (ART). This ART is to be
considered when HIV RNA exceeds 55000 copies/ml and
CD4 counts is less than 350 cells/cmm. (< 1200
lymphocytes/cmm) or all symptomatic patients regardless
of cell counts/plasma viral load level. Seroconversion illness
merits discrimination of ART and there is increasing interest
in ART, so as to preserve anti HIV T cell response and
lower the viral set point. ART is indicated in asymptomatic
patients when (a) CD4 is < 350 (b) CD4 > 350 and HIV
RNA load > 55000 copies/ml. (c) Mandatory if CD4 is less
than 200. HAART (highly active antiretroviral treatment) is
deferred in CD4 is > 350 and viral load < 55000. It is advisable
to follow such patients periodically (3-6 months).
All HIV positive patients should not be given ART as
soon as the diagnosis is made especially if CD4 is >
350/mm3. It is better to rule out presence of associated
opportunistic infections (IOs) and if present, treat
accordingly before ART. (Refer to Chapter ‘RASH’ and
‘PUO’).
Antiretroviral drugs (enzyme inhibitors) are classified
into five groups.
i. Reverse transcriptase inhibitors (RTs)
ii. Protease inhibitors (PI)
iii. Fusion (entry) inhibitors:
(a) Enfuvirtide (90 mg SC, twice daily)
(b) CCR5 antagonists
iv. Integrase inhibitors and
v. Maturation inhibitors.
The first antiretroviral agent is discovered in 1987.
i. Reverse transcriptase inhibitors are further divided into
inhibitors three groups.
a. Nucleoside reverse transcriptase inhibitors (NRTI)—
Lamivudine (LAM), Stavudine (STV), Zidovudine
(ZDV), Didanosine (DDI), and abacavir.
b. Non-nucleoside reverse transcriptase inhibitors
(NNRTI)—Efavirenz, (EFV) and nevirapine (NVP).
c. Nucleotide analogue (NT)—Tenofovir.
ii. Protease inhibitors are—Indinavir, nelfinavir, ritonavir,
saquinavir, lopinavir.
HAART is the principle hope now and its options are
as follows: (3 Antiretroviral drugs)
a. 2 NRTI (Lamivudine-150 mg b.d. and Zidovudine-
350 mg bd) or Didanosine-200 mg bd and ZDV or
Didanosine and Stavudine plus one PI, i.e. Indinavir-
600 mg tds or Nelfinavir-750 mg tds or Ritonavir-
600 mg bd or Saquinavir-1200 mg tds soft gel or
boosted PI like Lopinavir/Ritonavir-100/400 mg bd.
b. 2 NRTI (ZDV+LAM or STV+LAM) plus one
NNRTI like Nevirapine 200 mg/d for two weeks,
Later 200 mg bd; or Efavirenz 600 mg/d. This is
the Indian scenario (i.e.).
(ZDV + LAM + NVP;
ZDV + LAM + EFV;
STV + LAM + NVP;
STV + LAM + EFV)
iii. One NRTI plus one NNRT plus one PI.
iv. 3 NRTI (LAM, ZDV, and Abacavir 300 mg bd)
N.B:
1. ZDV should not be combined with STV as it is an
incompatible combination.
2. Some OIs and NNRTIS (except Efavirenz) react with
Rifampicin and this is not the case with NRTIS.
3. EFV and STV and DDI are avoided in pregnancy.
4. Ruling out OIs or adequate control of OIs, if present, is
necessary before starting ART.
For advanced cases 4 drug therapy may be contemplated
such as 2 NRTIS plus 2 PIs. The treatment must be
monitored frequently once in three months for side effects
or CD4 counts and continued for six months at least and
switch over to lesser potent regimen, if the counts are
favourable, for 6 months more.
ART is stopped, if toxicity or life threatening inflam-
matory response or drug interactions or persistent viral
replication occurs.
In associated tuberculosis infection, either defer ART
or give ATT if CD4 is more than 200 cells/cmm. In case
ART has to be given, EFV is used with rifampicin safely
since possible drug reactions occur with other PIs and
NNRTIS.
Immunocompromised patients i.e. CD4 <200 cells/cmm
invite opportunistic infections (OIs) or malignancies.
Treatment of opportunistic infections appropriately form
the main stay of HIV therapeutics besides ART. Prevention
of opportunistic infections with chemoprophylaxis forms
primary prophylaxis with lower dosage of the same drugs
used for OIs therapy, i.e.
 Appendices
Fungal
1. Pneumocystis carinii pneumonia (PCP)—Trimethoprim
TMP 160 mg and sulfamethoxazole (SMX) 800 mg
thrice daily for 14 to 21 days,
2. Orogenital candidiasis—Fluconzole 100-200 mg/d for
10 to 14 days
3. Cryptococcal meningitis—Amphotericin B IV (0.3 mg/
kg/d) and Fluocytosine (150 mg/kg body weight for 6
weeks) or fluconazole for milder cases (400-800 mg/d).
Bacterial
1. Mycobacterium avium complex—Azithromycin 1.2 g per
week or Rifabutin 300 mg orally daily for 6 to 12 months.
2. Tuberculosis—Isoniazid 300 mg/d for one year.
Viral
1. Varicella zoster virus-VZIG-5 vials (1.25 ml each) IM
given within four days or exposure.
2. Cytomegalovirus-Ganciclovir 0.5 mg/kg IV bd or
foscarnet 90 mg/kg/d IV for 2-3 weeks and continue
maintenance treatment lifelong.
3. Hepatitis virus A; prevented by appropriate vaccines.
4. Hepatitis virus B
Parasitic
1. Toxoplasma gondii—Pyrimethamine 50-100 mg/d +
Sulphadiazine 4 to 6 mg/d + Folinic acid 15 mg/d for 4
to 8 weeks.
Secondary prophylaxis is continuing the prophylactic
measures lifelong, even after full treatment of opportunistic
infections with or without half doses.
N.B: HAART has resulted in dramatic decline in the
incidence of OIs and better response to their treatment.
Malignancies Kaposi’s Sarcoma: Doxorubicin and
Paclitaxel for refractory cases after HAART. Radiation or
surgery, if necessary, may be considered.
589
Lymphoma—Refer to Chapters ‘Bleeding Disorders’ and
‘PUO’.
Others: Anaemia, Erythropoietin; for Neutropenia G-CSF
and for depression appropriate antidepressants are
advocated.
Supportive treatment may be designed by appropriate
measures with proper nutrition, vitamins like B12, micro-
nutrients and antioxidants in a healthy environment.
Post exposure prophylaxis (PEP) is advocated with ZDV,
LAM and indinavir or nelfinavir for four weeks preferably
within 1 to 2 hours of exposure. So is the case with high
risk occupational exposure.
Apart from HAART and opportunistic infections
prophylaxis, enhancing immune system may be entertained
with interleukin-2 which is a cytokine capable of mobilising
CD4 cells and increasing their production.
Prevention and Control
1. Education and awareness;
2. Encouraging safer sex practices including microbicides—
local ART (gels);
3. Screaning for blood donors.
4. Changing needles.
5. Antenatal screening for HIV antibodies and treatment
with ZDV if warranted. Other drugs preferred are
nevirapine and nelfinavir.
6. Postpartum care—(a) No breast feeding (b) ZDV is given
for 6 weeks to infants within two days after birth.
Initiation for PCP prophylaxis at 4 to 6 weeks. Determine
the HIV infection status periodically upto six months of
age.
7. Vaccine development against AIDS is slow and possible
only after 7-10 years, though first trial was made in
1999.
 Suggested Reading
General Texts
1. Bouchier. French’s Index of Differential Diagnosis.
Butterworth-Heinemann, London, Boston; 13th edn; 1996.
2. Christopher Bunch. Horizons in Medicine. Royal College
of Physicians of London; Bailliere Tindall/WB Saunders,
London, Philadelphia; No. 1, 1989 and Subsequent
Horizons Series.
3. Edwards CRW Bouchier IAD. Davidson’s Text Book of
Principles and Practice of Medicine. ELBS with Churchill
Livingstone, Edinburgh; 17th edn; 1995.
4. Goodman Gilman A; Goodman and Gilman’s. The
Pharmacological basis of Therapeutics; Maxwell
MacMillan, New York; 8th edn; 1991.
5. Gurmukh S Sainani. API Textbook of Medicine. The
Association of Physicians of India, Mumbai; 5th edn; 1992.
6. James B Wyngaarden, Lloyd H Smith Jr, J Claude Bennett.
Cecil Text Book of Medicine; WB Saunders Co,
Philadelphia, London; 19th edn; 1992.
7. Kurt J Isselbacher et al. Harrison’s Principles of Internal
Medicine. McGraw-Hill Book Co. New Boston, London;
27th edn; 1992.
8. Michele Woodler, Alison Whelan. Manual of Medical
Therapeutics. Little Brown and Company, Boston, London;
27th edn; 1992.
9. Weatherall DJ, et al. Oxford Textbook of Medicine. Oxford
University Press, New Delhi and Mumbai; 3rd edn; 1996.
Texts of Medical Specialities
10. Anthony Seaton, Douglas Seaton A, Gordon Leitch.
Crofton and Douglas’s Respiratory Diseases. Oxford
University Press, New Delhi, Mumbai; 4th edn; 1989.
11. Barry M Brenner. Brenner and Rector’s The Kidney. WB
Saunders Co, Philadelphia, London; 5th edn; 1996.
12. Eugene Braunwald. Heart Disease. WB Saunders Co,
Philadelphia, London; 5th edn; 1997.
13. Frank Firkin et al. de Gruchy’s Clinical Haematology in
Medical Practice; Oxford University Press, New Delhi and
Mumbai; 5th edn; 1989.
14. Jean D Wilson, Daniel W Foster. Williams Text Book of
Endocrinology. WB Saunders Co, Philadelphia, London;
8th edn; 1992.
15. John Walton. Brain’s Disease of the Nervous System;
Oxford University Press, New Delhi, Mumbai; 10th edn;
1994.
16. Kaplan HI, Sadock BJ; Textbook of Psychiatry; Williams
and Wilkins, Baltimore, Maryland; 6th edn; 1995.
17. Kelly WN, Harris Jr ED, Ruddy S and Sledge CB; Textbook
of Rheumatology; WB Saunders Co, Philadelphia, London,
4th edn; 1993.
18. Ronald Kahn C, Gordon, C. Weir Joslin’s Diabetes Mellitus.
Lea and Febiger, Philadelphia, London; 13th Edn; 1994.
19. Sheila Sherlock James Dooley. Disease of the Liver and
Biliary System; Blackwell Scientific Publications, Oxford;
9th edn; 1993.
20. Thomas B. Fitzpatrick et al. Dermatology in General
Medicine; McGraw-Hill Inc., Health Professions Division,
New York and New Delhi; 4th edn; 1993.
21. William S. Haubrich, et al. Bocus Gastroenterology; WB
Saunders Co, Philadelphia, London; 5th edn; 1995.
Texts of Other Specialities
22. Alang G Kerr, Dafydd Stephens. Scott-Brown’s
Otolaryngology, Volume two—Adult Audiology
Butterworth International Edition Kent, UK, 5th edn; 1987.
23. Behraman Kliegman, Arvin. Nelson Textbook of
Paediatrics; WB Saunders Co, Philadelphia, London; 15th
edn; 1996.
592 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

24. Martin L. Pernoll. Current Obstetric and Gynaecologic
Diagnosis and Treatment. Appleton and Lange/Prentice-
Hall Medical Publications, London; 8th edn; 1994.
25. Ronald G Grainger, David J. Allison; Diagnostic Radiology:
An Anglo-American Textbook of Imaging; Churchill
Livingstone, Edinburgh, New York; 2nd edn; 1992.
26. Samuel L Turek. Orthopaedics Principles and their
Application, JB Lippincott Company, Philadelphia, New
York, London; 4th edn.
27. Seymour I. Schwartz, G Tom Shires, Frank C Spencer.
Principles of Surgery. McGraw-Hill Book Co, New York,
New Delhi; 6th edn; 1994.

A mountain sickness 141
Abdomen 45, 85, 241
Abdominal
angina 15
colic 185
crisis 5
hernias 2, 6, 15
migraine 262
pain 1
Abetalipoproteinaemia 64
Absence seizures 161
Absorption tests 67
Accelerated destruction 21
Achlorhydria 63, 109, 115
Acidification test 243
Acquired
autoimmune haemolytic anaemia 291
valvular diseases 382
Acrocyanosis 95
Acromegaly 419
Acute
abdominal pain 1
anxiety 46, 55
appendicitis 1, 2, 11
arterial occlusion 373
asthma 148
brachial neuritis 373
bursitis 7, 18
cauda equina lesions 403
cholecystitis 1, 2, 7, 13
circulatory failure 501
cor pulmonale 43
coronary syndrome 42, 53
cystitis 232
distension 14
dyspepsia 108
gastric erosions 217
gastroenteritis 1, 2, 13
glomerulonephritis 245
hepatitis 295, 304
indigestion 45, 55
intermittent porphyria 6
interstitial nephritis 236
lymphatic leukaemia 34
mesenteric lymphadenitis 1, 3, 14
metabolic complications of diabetes
mellitus 88
Index
Alzheimer’s disease 158, 169
myeloid leukaemia 34 Amoebiasis 58, 221
myocardial infarction 2, 6, 7, 50, 382 Amoxycillin 115
pancreatitis 1-3, 7, 12, 14, 18, 46, 48, 55 Ampicillin 104
pharyngitis 120
Amyloidosis 64
poliomyelitis 396
Anaemia 174
porphyria 2, 18
Analysis of pain 7
posthaemorrhagic anaemia 186
postinfectious 234 Anaphylactic shock 511
pulmonary oedema 132 Anaphylactoid purpura 38
pyelonephritis 1, 3, 233 Androgen resistance 208, 212
pyelthanonephritis 245 Aneurysm of
renal aorta 219, 225
artery occlusions 361 ascending aorta 254
failure 352, 438 Aneurysms 53
vein occlusions 361 Angina 2
respiratory distress syndrome 14, 46, 149 pectoris 39, 49, 369
restrictive lung disease 139
Angiography 282
severe attack 147
Angiomatous malformation 157
thyroiditis 196, 202
tonsillitis 120 Angioneurotic oedema 452
tubular necrosis 360 Anhidrotic ectodermal dysplasia 474
urticaria 451 Ankylosing spondylitis 316, 416
Addison’s disease 177, 187, 504 Ankylostomiasis 451
Adenosine diphosphate 19 Anorexia nervosa 556
Adjunct therapy 114 Anoxaemia 173, 265
Adolescent 9 Anoxic syncope 517, 522
gynaecomastia 206 Antegrade pyelography 244
Adrenal Anterior oesteophytes 121
carcinoma 208
Anti Koch’s therapy 169
cortex 331, 336
Antiandrogenic drugs 209
Adulthood 164
Antibody mechanism 26
Aetiocholanolone fever 474
Anticoagulant drugs 23
Affective psychosis 179
Anticonvulsant drug therapy 167
Afferent loop syndrome 64
Airway cooling 137 Antidopaminergics 114
Alcohol 6, 81,190 Antiepileptic drugs 168
Alcoholic myopathy 400 Antiflatulents 114
Aldosterone deficiency 177, 187 Antihaemophilic globulin 20
Alimentary
Antiplatelet drugs 51
affections 45
Antispasmodics 114
obesity 330
Anxiety 189, 244, 272
Allergic 71
reactions 457 disorders 152
stomatitis 120 neurosis 180
Alport’s syndrome 238 state 143
Alstrom’s syndrome 332 Aortic
Altered CSF flow 265, 271 aneurysm 43, 258
Alveolar oedema 132 stenosis 135
 594 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Aortitis 43, 53 Benign Burkitt’s lymphoma 25

Aphthous stomatitis 119 hypertrophy 232, 244 Burr cells 176
Aplastic intracranial hypert 271 Bursitis 366
anaemia 21, 25, 184 neoplastic nodules 197
crises 185 papilloma 237 C
Appendicitis 9 thyroid nodule 203
Appendix 110, 116 Benzodiazepines 81 Caisson disease 393
Berger’s disease 234 Calcified faecolith 11
Arch of aorta 254
Beriberi 342 Calcitonin assay 201
Arm raising test 199
Bernard Soulier syndrome 21, 24, 36 Calcium
Arterial obstruction 100
Bernstein’s test 46 diabetes 437, 446
Arteriovenous malformations 219 stones 247
Biemond’s syndrome 332
Arthritic pain 408 Calculus 231, 233, 244
Bile salt deficiency 61
Arthrogryposis multiplex congenita 419, 428 Caloric response 84
Biliary
Articular pain 372 colic 1, 2, 5, 7, 13, 46 Calve’s disease 318, 324
Asphyxia 160, 173 obstruction 2, 14 Campylobacter pylori 218
Aspiration tract 1, 2, 13 Capillary
pneumonia 141, 151 Biochemical tests 182 endothelial defects 38
pneumonitis 141 Biopsy studies 68 endothelium defects 21, 27
Asteatosis 457 Bleeding 244 resistance test 31
Asthenic syndromes 180, 190 diathesis 254, 255, 258 Carbon
Atherosclerosis of large pelvic vessels 279 disorder 19, 82, 238 dioxide retention 103
Atonic seizures 161 time 31 monoxide 81
Atresias 97 Blood 10, 545 Carcinoid
Atrial diseases 219 syndrome 263
myxoma 146 dyscrasis 120 tumour 62
septal defect 96, 97 gases 145 Carcinoma 178, 197, 232, 233, 245
tachyarrhythmias 378 loss 175 Carcinoma of
Atrioventricular block 381 sugar 10 bowel 178
tests 243, 358, 385 stomach 115, 218, 225
Atypical absence seizures 161
transfusion 256 Carcinomatous
Aural vertigo 165
urea 10 myopathy 400
Autoerythrocyte sensitisation 28, 38
Boas sign 10 ulcer 120
Autoimmune
Body fluids 85 Cardiac
chronic active hepatitis 296 arrhythmias 52, 377, 386
Bone marrow
diseases 316 asthma 132
defect 24, 25, 34
Automatic component 161 failure 52
depression 35
Autonomic examination 31 markers of myocardial damage 48
feature 160 Bone pains 372 oedema 340
neurogenic reflexes 137 Bornholm disease 2, 5, 15 silhoutte 48
neuropathy 279 Brachial neuritis 368 syncope 516
Breakdown of haemoglobin 287 tamponade 53
B Breath Cardiogenic
Backache 311 holding fits 160, 173 pulmonary oedema 146
Bacteria 243 tests 67 shock 52, 505, 511
Bacterial arthritis 410 Breathing exercises 103 Cardiopulmonary resuscitation (CPR) 521
Baker’s cyst 367 Bromsulphalein excretion 302 Cardiovascular
Ball valve thrombus 135, 146 Bronchial changes 194
Banti’s disease 21, 26, 36 adenoma 253, 258 disorders 178, 188
Barium asthma 136, 147 examination 371
enema 11 Bronchiectasis 251, 257 system 144
meal 11 Bronchogenic carcinoma 44, 54, 252, 257 Carotid artery obstruction 522
Basic thyroid function tests 199 Brucellosis 469 Carotid sinus
Basilar artery migraine 262 Brudzinski’s sign 78 pressure 385
Basophil degranulation test 459 Buccal smear 281 syncope 515, 522
Bedide manoeuvres 101 Budd-Chiari syndrome 5, 15 Carpal tunnel syndrome 368
Behçet’s syndrome 119, 409, 417 Bulbocavernous reflex latency 282 Carpenter’s syndrome 332
 Index 595

Caruncle 231, 244 Certain diseases 7 posthaemorrhagic anaemia 186

Cataplexy 165 Cervical pulmonary
Catarrhal stomatitis 120 disc herniation 367 fibrosis 139
Cauda equina lesions 312, 397, 404 fibrositis 263, 270 hypertension 43, 54
Causes of spondylitis 121 renal failure 208, 438, 446
acute abdominal pain 1 spondylosis 263, 270, 367, 522 thyroiditis 196, 203
backache 311 Charcot’s joint 418 uraemia 64
chest pain 39 Charcot-Leyden crystal 59 urticaria 452
chronic dyspepsia 108 Chelation therapy 18 Chvostek’ sign 159
coma 75 Chemotherapy 256 Circulating anticoagulants 23, 33
cyanosis 96 Chest Circulation time 101
dizziness 526 examination 164 Circulatory failure 107
dysphagia 119 pain 39 Cirrhosis 280, 296
dyspnoea 133 wall 151 Cirrhosis of liver 209
erectile dysfunction (ED) 276 Cheyne-Stokes respiration 83, 132 Clarithromycin 115
goitre 192 Childhood 164 Classification of haemorrhagic disorders 21
gynaecomastia 206 paroxysmal vertigo 262 Climacteric gynaecomastia 206
haematemesis 216, 219 Chlamydia trachomatis 411 Clindamycin 14
haematuria 230 Chloridorrhoea 64 Clinical types of cyanosis 95
haemoptysis 250 Cholangiogram 11 Clonic seizures 162
headache 261 Cholangitis 1, 2 Clostridium botulinum 541
jaundice 289 Cholecystitis 9, 46, 55 Clot retraction time 31
melaena 219 Cholelithiasis 46, 55 Clotting time 31
oedema 340 Cholera 80, 91 Cluster headache 263, 269
oliguria 353 Cholinergic urticaria 452 CNS disorders 344, 349
pain 364 Chondrocalcinosis articularis 418 Coagulation
palpitations 376 Christmas defects 22
paraplegia 391 disease 22, 32 inhibitory system 20
polyuria 431 factor 20 system 19
pyrexia 468 Chronic Colitis 1, 2
rashes 484 active hepatitis 296 Collagen
thrombocytopathy 27 alcoholism 190 diseases 240, 457, 464
thrombocytopenia 24 anxiety 46, 55 vascular disease 100
thrombocytosis 27 appendicitis 110 Collapse of lung 138, 149
Ceftazidime 104 arterial occlusion 368, 373 Colon obstruction 9
Cellulitis 366, 372 asthma 148, 149 Colonic
Central bronchitis 138, 149, 251, 257 carcinoma 63
cardiac failure 178 cholecystitis 110, 116 distension 45, 55
cyanosis 94, 95, 96 cystitis 232 Coma 74, 75
diabetes insipidus 439 diarrhoea 57, 178, 552 Complete testicular feminisation syndrome
nervous system 518 dyspepsia 108, 178 208
positional vertigo 528 fatigue syndrome 180, 190 Complex partial
Cephalalgia 261 gastritis 115, 218 seizures 161
Cephalosporin 13 hepatitis 178, 296, 306 status 163
Cerebellar lesions 528 interstitial Complications of obesity 332
Cerebral cystitis 232 Condy’s solution 32
abscess 157, 265, 271 nephritis 236 Congenital
arteriosclerosis 157 intestinal ischaemia 4, 15 adrenal hyperplasia 208
diplegia 396 liver disease 30 anorchia 206, 212
haemorrhage 87 lymphatic leukaemia 34 arthropathies 419
malaria 80, 90 mountain sickness 141 diplegia 158, 169
syncope 517, 522 myeloid leukaemia 34 disorders 330, 332
venous thrombosis 88 obstructive pulmonary disease 103, 104, heart disease 96, 100, 104, 135, 382
Cerebrovascular 138, 178 Meckel’s diverticulum 220, 226
accidents 87, 219 pancreatitis 110, 116 syndromes 330
lesions 75 persistent hepatitis 296 Congestive heart failure 136, 280, 296
 596 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Connective tissue disorders 178, 419, 471, 479 paralysis 139, 140, 50 pregnancy 4, 7, 15
Consequent to systemic diseases 116 pleurisy 2, 6 rhythms 377
Constitutional obesity 330 Diet 334 Eczematous dermatitis 462
Continuous positive airway pressure (CPAP) Dietl’s crises 2, 4, 247 Effects of
102, 103 Diffuse cold 451
Contrast films 11 sclerosis 158, 169 heat 451
Cord 369 toxic goitre 195, 202 Ehlers-Danlos syndrome 21, 27, 38, 419, 428
compression 393, 394, 403 Dilutional coagulopathy 26 Eisenmenger’s syndrome 43, 97
infarctions 393 Direct thrombin inhibitor 52 Electroencephalography (EEG) 166
Corneal reflex 84 Disaccharidase deficiency 65 Electrolyte disorders 79, 90
Costochondritis 44 Disc prolapse 312 Electrophoresis 101
Courvoisier’s sign 10 Disorders of adipose tissue 330, 332 Electrophysiological testing 386
Cresentic glomerulonephritis 234 Dissecting aneurysm 43 Emphysema 138, 150
Crigler-Najjar syndrome 293 Disseminated Empty Sella syndrome 331
Crohn’s disease 60, 61, 69, 220, 473 candidiasis 471 Encephalitis 78, 331
Cryptosporidium parvum 60 intravascular coagulation 21, 23, 26, 33 Endobronchial tamponade 256
Crystals 242 sclerosis 395 Endocrinal obesity 330
Cullen’s sign 9, 46 vasculitis 235 Endogenous depression 179
Cushing’s Distal Endometriosis 64
disease 21, 38 ileum 226 Endoscopic retrograde cholangiopancreato-
syndrome 28 muscular dystrophy 399 graphy 11, 113
Cutaneous candidiasis 461 Disturbances in impulse Endoscopy 67, 303
Cyanosis 94 conduction 380 Entamoeba histolytica 59
Cyanotic heart disease 517 formation 386 Enterobius vermicularis 553
Cyclic neutropenia 474 Diverticulitis 1, 2, 9, 60 Enteropathic arthropathy 417
Cyst 484 Diverticulosis 220 Entrapment neuropathies 368, 373
Cysticercus cellulose 156 Doppler test 101 Epidemic dropsy 342
Cystine stones 247 Doxycycline 14 Epilepsy 78, 155
Cystitis 232, 245 Drowsiness 75 Epileptic seizures 155
Cystometrogram 282 Drug 6, 240 Epiloia 158, 170
Cystoscopy 244, 359 fever 473 Epstein-Barr virus 411
induced dysfunction 284 Erb’s paraplegia 395, 403
D screen 86 Erect position 11
Da Costa’s syndrome 46, 55, 190 Dry skin 457 Erectile dysfunction 276
Decreased Dubin-Johnson syndrome 297 Erythema nodosum leprosum 409
androgen secretion 206 Ducey-Driscoll syndrome 293 Erythrocyanosis 95
cardiac output 107 Duodenal ulcer 115 Erythromelalgia 368, 373
production of red cells 183 Duodenitis 115 Escape rhythm 377
survival of platelets 21, 24, 26, 36 Duodenum 109, 115 Ethanol 81
Deep venous thrombosis 372 Dye reduction spot test 358 Ethyl alcohol 81
Defective secretions 69 Dysentery 9 Euglobulin clot lysis time 31
Deficiency disorders 395 Dyshormonogenesis 194, 202 Euthyroid 193
Degree of obesity 329 Dyspepsia 108 goitre 193
Depression 272 Dysphagia 119 Ewing’s sarcoma 562
Depressive Dyspnoea 132 Examination of
illness 556 Dysproteinaemias 28, 235, 246 abdomen 9, 112, 545
psychiatric states 82 Dystrophia adiposogentalis 330 chest 10, 112, 545
Dercum’s disease 332 CNS 10
Diabetes E ears 545
insipidus 439, 447 eyes 545
mellitus 9, 63, 142, 177, 187, 239, 279, 432 Ebstein’s anomaly 98 face 545
Diabetic ECG 11, 101, 182 neck 545
acidosis 78 Echinococcus granulosus 239 sputum 144
ketoacidosis 2, 6 Echocardiography 101 tongue 112, 545
nephropathy 246 Echoencephalography 166 Exercise test 385
Diabetogenic drugs 434 Ectopic Exertional dyspnoea 132
Diaphragmatic hormone secreting tumours 208 Expiratory dyspnoea 132
 Index 597

Extensive pneumonia 104 Formation of Glucose-6-phosphate dehydrogenase deficiency

Extra-alimentary 111, 116 bilirubin 287 185
Extracorporeal membrane oxygenation fibrin 20 Glycated haemoglobin 435
(ECMO) 102 prothrombinase 19 Goitre 192
Extrahepatic obstructive jaundice 298 thrombin 20 Goitrogens 194, 202
Extrasystoles 377 Fowler position 12 Goitrous
Extrinsic Fractional test meal (FTM) 218 Hashimoto’s thyroiditis 196
allergic alveolitis 139, 150 Fragmented red blood cells 23 hyperthyroidism 193
pathway 19 Friedreich’s ataxia 404 Gonadotrophins 209
Fröhlich’s syndrome 330 Gonads 331
F Fulminant hepatitis 305 Gonococcal arthritis 410
Functional Goodpasture’s syndrome 235, 246, 254
Fabry’s disease 474 Grading of coma 75
colonopathies 64, 71
Facial reflexes 84 Gram stain 85
state evaluation 422
Facioplegic migraine 262 Granulomatous
Fungal
Factitious 71 gaint cell thyroiditis 196
infections 452
urticaria 452 hepatitis 473
lung disease 252, 257
Failing eye sight 530 Graves’ disease 193, 195, 202
Fusiform bacilli 119
Fallot’s tetralogy 96, 135 Grey Turner’s sign 9, 46
Familial mediterranean fever 474 Guillain-Barre
Fanconi’s anaemia 21, 24, 35 G polyneuritis 397
Fatigue 174, 272 Gaisbock’s syndrome 99 syndrome 405
Fatty Gallbladder dyspepsia 112 Gum bleeding 32
hernia of linea alba 6 Gallstones 9, 11 Gynaecomastia 206
infiltration of liver 110, 116 Gamma amino butyric acid (GABA) 155
Febrile neutropenia 473 Gas stoppage sign 8 H
Felty’s syndrome 415 Gastrectomy 64
Ferric chloride test 85 Habitual hyperthermia 474
Gastric Haemangioma 219, 233
Fever 244 flatulence 109, 115 Haemarthrosis 32
Fibrin peristalsis 9 Haematemesis 9, 32, 216, 224
clot 20 Gastritis 109 Haematochezia 9
degradation products 31 Gastroduodenal causes 217 Haematoma of rectus sheath 6, 15
stabilising factor deficiency 22 Gastrointestinal disorders 178, 188 Haematuria 32, 230
Fibrinogen Gastrojejunostomy 64 Haemobilia 219, 225
concentration 31 Gastro-oesophageal reflux 46 Haemoglobin abnormalities 95, 98
deficiency 22, 23, 33 Gaucher’s Haemoglobinurias 292
degradation products 20 cell 24 Haemolytic
Fibrinolytic system 20 disease 21, 24 anaemias 186
Fibrosing alveolitis 140 Genetic 64, 71 jaundice 289, 304
Filarial encephalitis 80, 91 predisposition 194 transfusion reaction 186
Filariasis 239 syndromes 434 uraemic syndrome 26
Flaccid paraplegias 396, 403 Gentamycin 14, 104 Haemophilia 22, 419
Fluid and electrolyte disturbances 177, 187 Gestational diabetes mellitus 434 A 22, 32
Fluids 18 GI endoscopy 11 B 22, 32
Focal and segmental Giant Haemoptysis 32, 250
glomerulonephritis 246 cell arteritis 263, 472 Haemorrhage 1, 483
glomerulosclerosis 236 platelet 24 Haemorrhagic
Focal proliferative glomerulonephritis 235 urticaria 452 cystitis 232
Folate deficiency 184 Giardiasis 59 disease of newborn 226
Foley’s catheter 32 Gilbert’s disease 293 fevers 239
Folic acid 119 Glandular fever 470 Haemorrhoids 221
Follicular carcinoma 197 Glanzmann’s disease 21, 24, 27, 36 Hansen’s disease 207, 487
Food Glasgow coma scale 75 Hartnup disease 65
intolerance 110, 116 Globulin deficiency 63 Hasen’s disease 212
poisoning 541 Glomerulopathies 233, 236 Hashimoto’s thyroiditis 196, 203
Foreign body 253, 258 Glucose tolerance test 67, 182, 435 Head injury 78, 88, 271
 598 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Headache 45, 261 Hypersensitivity pneumonitis 139 diarrhoea 58

Heart failure 99 Hypersplenism 26 disorders 178, 187
Heat hyperpyrexia 80, 91 Hypertension 263, 269 Infratentorial lesions 74
Heimlich manoeuvre 104 Hypertensive encephalopathy 77, 88 Injury 232
Helicobacter pylori 114, 218 Hyperthyroidism 194, 209, 279 Insect bites 460
Hemangioma of stomach 226 Hypertonic intravenous infusions 438 Insomnia 179, 189, 272
Henoch-Schönlein purpura 21, 28, 29, 38, Hypertrophic obstructive cardiomyopathy Inspiratory dyspnoea 132
235, 246 43, 53 Intensive coronary care units 50
Hepatic Hyperventilation syndrome 143, 152 Intermittent
Hyperviscosity syndrome 82 hydrarthrosis 417
cirrhosis 347
Hypocalcaemia 79 therapy 114
disorders 456, 464
Hypogammaglobulinaemia 65 Interstitial nephritis 236
edema 341
Hypoglycaemia 79, 89 Interventional therapy 247
Hepatocellular Intestinal
Hypoglycaemic agents 332
failure 79 Hypokalaemia 177, 187, 447 amoebiasis 109
jaundice 293, 304 Hyponatraemia 79 colic 1, 3
Hereditary Hypophosphataemia 177, 187 flatulence 109, 115
arthropathies 428 Hypopituitarism 80, 187 giardiasis 110
biosynthetic defects 194 Hypoproteinaemic states 342 hurry 70
capillary fragility 27, 38 Hypothalamic pituitary disorders 330 obstruction 2, 3, 14
disorder 21 Hypothyroid 193 parasites 109, 115
haemoglobinopathies 289 Hypothyroidism 80 tuberculosis 69
haemorrhagic telangiectasia 27, 38 Hypovolaemic shock 511 Intracardiac masses 517
nephritis 238 Hypoxaemic spells 104 Intracranial tumour 157, 264, 271
spherocytosis 185, 289 Hypoxia 95 Intradermal tests 459
Herniorrhaphy 15 Hysteria 82, 393 Intrahepatic obstructive jaundice 297
Herniotomy 15 Hysterical seizures 164 Intraperitoneal sepsis 4
Herpes Intrinsic pathway 20
I Invasive fibrous thyroiditis 197
simplex 119
Involutional purpura 38
zoster 2, 45, 55 Idiopathic Iodide induced hyperthyroidism 202
Hess’s test 30, 31, 222 cyclic oedema 343 Iron deficiency anaemia 183
Hiatus hernia 55, 142 thrombocytopenic purpura 21, 26 Irritable bowel syndrome 64, 111, 116
Hip joint disease 2, 7, 18 Iliopsoas sign 10 Ischaemia 1
Hippocratic facies 9 Immune thrombocytopenic purpura 36 Ischaemic
His bundle electrocardiograms 386 Immunological test 201, 302 colitis 15, 220
HLA related diseases 490 Impaired haemoglobin synthesis 183 heart disease 39, 517
Hodgkin’s Inadequate flow of lymph or blood 62 strokes 87
disease 25 Incompatible blood transfusion 292 Islet cell antibody 436
lymphoma 25 Increased Isoimmune haemolytic anaemias 186
Hollow organ 1 capillary permeability 344 Isotope
Holter monitoring 40, 166 central venous pressure 341 renogram 243
Hormonal and nutritional deficiencies 184 conversion of androgens to oestrogens scan 243
Horner’s syndrome 44 209 Itching dermatoses 451, 455
destruction of red cells 185
Horton’s syndrome 263
Hurler’s syndrome 419, 428
oestrogen secretion 208, 212 J
venous pressure 343
Hutchison’s pupil 84 Jaccoud’s arthritis 409, 412
Indices for metabolic effects of thyroid 200
Hydrocephalus 271, 396 Individual factors assays 31 Jacksonian-minor motor status 163
Hyperabduction syndrome 45, 55 Jaundice 9, 287
Infancy 164
Hypercalcaemia 79, 177 Joint 319
Infantile hemiplegia 158, 170
Hypercapnia 265, 266 pains 372
Infarction 2
Hyperkinetic circulatory states 136 Infections 27, 293 symptoms 408
Hypermagnesaemia 177 Infectious arthritis 410 Junctional tachycardias 379
Hypernatraemia 79 Infective endocarditis 469
K
Hyperosmolar nonketotic diabetic coma 78 Inflammatory
Hyperpnoea 133 arthritis 410 Kansas haemoglobin 99
Hyperprolactinaemia 278 bowel disease 57, 69, 220 Kawasaki’s disease 498
 Index 599

Kehr’s sign 5 Lower Measurement of

Ketogenic diet 167 gastrointestinal lesions 220 blood gas tensions 101
Kidney function tests 441 endoscopy 11 nocturnal penile tumescence 282
Klinefelter’s syndrome 206, 212, 278 intracranial pressure 87 Mechanism of
Knee Lumbar arthritic pain 408
chest position 96 canal stenosis 324 cyanosis 95
joints 367 disc herniation 323 dyspnoea 133
puncture 166 fatigue 174
L spondylosis 313, 367 headache 261
stenosis 317 pain 364
Labyrinthine disturbances 543 Lumbosacral Mediastinal emphysema 2, 6, 44, 54
Lactic acidosis 78 Medullary
disc herniation 367
Lactose tolerance test 67 carcinoma 197, 203
strain 319
Laparoscopy 303 sponge kidney 237
Lung
Large bowel instruction 9
abscess 251, 257 Megaloblastic anaemia 21, 25, 35, 184
Larva migrans 451, 460
biopsy 253, 258 Melaena 9, 216, 226
Laryngeal obstruction 104
contusion 253, 258 neonatorum 220
Lateral chest pain 49
Lyell’s syndrome 490, 498 Membranous glomerulonephritis 235, 246
Lawrence-Moon-Biedl syndrome 332
Lyme disease 412 Mendelson syndrome 141
Lead 82
Lymphangitis 368 Meninges 369
palsy 7
Lymphocytic Meningioma of falx cerebri 396
poisoning 2, 6
lymphomas 25 Meningitis 78
Left
thyroiditis 196 Meningococcal meningitis 488
atrial myxoma 135
Lymphogranuloma venereum 411 Menopause 331
heart failure 133, 146, 253, 258
Lymphoma 25, 178, 197 Meralgia paraesthetica 368, 373
lateral decubitus film 11
Meropenem 104
lower quadrant 7
M Mesengial proliferative glomerulonephritis
upper quadrant 7
246
Leptospira canicola 488
M. pneumoniae 411 Mesenteric
Leptospirosis 471
M. tuberculosis 409 angina 4, 15
Leriche’s syndrome 279
MacBurney’s point 2 apoplexy 15
Lesions of vertebral column 312
Macrocytic anaemia 175 infarction 5
Less common arthritides 419
Maculopapular 483 vascular insufficiency 220
Leucocytes 182
Maintenance therapy 114 Mesentery 3
Leutic infection 488
Leutinising hormone (LH) 278 Malabsorption syndrome 57, 60, 69 Metabolic
Levodopa 188 Malaria 239 acidosis 80, 142, 152
Leydig cells 278 Male sexual dysfunction 275 alkalosis 79
Lichen Malignant disturbances 522
planus 455 carcinoma 237 myopathies 397, 399
simplex chronicus 455 cells 243 origin 517
urticaria 452 goitre 197 Metabolism of bilirubin 287
Lichenoid dermatosis 455, 463 hypertension 361 Metals 6, 81
Limb girdle type 399 neoplastic nodules 197 Methaemoglobinaemia 98, 104, 177
Lipid profile 48 Mallory-Weiss syndrome 217 Methanol 81
Liquid stool 57 Malnutrition 178, 187 Methods to estimate body fat 329
Liver related diabetes mellitus 434 Methotrexate 150
biopsy 302 Mammary dysplasia 46 Methyl alcohol 81
cirrhosis 473 Marble bone disease 21, 24 Metronidazole 13
disease 24, 33 Marrow Microcytic anaemia 175
function tests 166 depression 21, 24, 25 Middle ear disease 543
Local failure 21, 184 Migraine 165, 261
anaesthetics 114 infiltration 21, 24, 25 Migrainous neuralgia 263
cyanosis 107 Massive Miller-Abbott’s tube 13
urinary tract diseases 230 pulmonary embolism 104 Minimal change
Low transfusion 21, 26 disease 246
fat diet 13 Mastitis 46, 55 glomerulonephritis 236
molecular weight heparin 51 Maturation defect 21, 24, 25 Mite-borne typhus 470
 600 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Mitral Nephrolithiasis 236 Oculocephalic reflex 84

stenosis 253, 258 Nephrotic syndrome 246 Oculovestibular reflex 84
valve prolapse 43, 53 Nerve entrapment 2, 5, 15 Oedema 339
Mixed Nervous Oesophageal
connective tissue disease 416 diarrhoea 64 carcinoma 217
cyanosis 95 dyspepsia 111, 116 motility disorders 45
Mondor disease 45, 55 Neuritides 270 rupture 46, 55
Monge’s disease 141 Neurocardiogenic syncope 514 spasm 55
Moniz syndrome 83 Neurocirculatory asthenia 143, 152, 180, 190 Oliguria 352
Morphine 13, 81 Neurocysticercosis 156 Omental torsion 2, 4, 15
Motion 10, 545 Neurogenic shock 511 Ophthalmoplegic migraine 262
Motor Neurologic amyotrophy 368 Opium 81
component 161 Neurological Oral
manifestations 160 diseases 179, 188 cholecystogram 11
neuron disease 395, 397, 403, 404 disorders 208 sepsis 112
Mountain sickness 151, 152 Neuropathic joint disease 418 Orthopnoea 132
Movable kidney 238, 247 Neuropsychiatric examination 164 Orthostatic dyspnoea 96
Moynihan’s disease 111, 115 Neurotic depression 179 Osler-Weber-Rendu syndrome 27
Multiple Neurovascular causes 55 Osteitis of cranial bones 264, 270
lipomata 332 Newborn 206 Osteoarthritis 367, 417
myeloma 317 Nicotinic acid 119 Osteoarthritis of spine 313
sclerosis 395 Noisy abdomen 9 Osteochondritis dessicans 420
Multislice computed tomography 48 Noncardiogenic pulmonary oedema 146 Osteomyelitis 315
Mumps orchitis 207 Nongastrointestinal disorders 226 Osteopetrosis 21, 24
Munchausen syndrome 7 Nongoitrous hypothyroidism 196 Oxalate stones 247
Murphy’s sign 10, 110 Non-Hodgkin’s lymphoma 25 Oxaluria 247
Muscle 366 Nontoxic goitre 193 Oxygen therapy 102
pains 372 Nonulcer dyspepsia 111, 116
Myasthenia 142 Noonan’s syndrome 207, 212 P
gravis 179, 188, 398 Normal
Mycosis fungoides 455, 463 haemostasis 19 Pachy meningitis 369
Myelofibrosis 35 platelet count 28 Paget’s disease 315
Myeloproliferative disorders 26 Normocytic anaemia 175 Pain 244, 364
Myelosclerosis 25, 35 Nutritional Pain in
Myocardial deficiencies 119 lower extremities 364
infarction 40, 48 oedema 342 upper extremities 364
ischaemia 39, 49 Painless thyroiditis 196
Myoclonic seizures 161 O Palindromic rheumatism 417
Myxoedema 196 Pancreatic
coma 90 Obesity 328 calcification 11
Obliterative bronchiolitis 138, 149 cholera 64
N Obstruction in upper airways 136, 147 function tests 67
Obstruction of Pancreatitis 7
N. gonorrhoeae 14 airways 104 Papillary
Narcolepsy 165 lower airways 136 carcinoma 197
Narcotic analgesics 13 Obstructions 99 necrosis 361
Narcotics 81 Obstructive Papilloma 233
Nasal intermittent positive pressure colics 1 Papular urticaria 452
ventilation 104 jaundice 297, 307 Papule 483
Natriuretic syndrome 439, 447 Obturator sign 10 Paralytic ileus 4
Necrotising vasculitis 29, 38 Occlusive arterial disease 100 Paraplegia 391
Neighbouring visceral disease 240 Occult infections 178 Parasagittal meningioma 396
Neonatal gynaecomastia 206 Occupational Parasites 243
Neoplasia 178, 188 asthma 140 Parasitic
Neoplasms 9, 208 lung diseases 139 infections 80
Neoplasms of colon 221 Ochronotic arthritis 428 lung diseases 257
Nephrogenic diabetes insipidus 439 Ocular signs 194 Parkinsonian syndrome 179, 188
 Index 601

Paroxysmal Pityriasis rosea 455, 463 testicular failure 206, 283

cold haemoglobinuria 292 Plasma thyrotoxicosis 195, 202
nocturnal thromboplastin component 20 Prinzmetal’s angina 49
dyspnoea 132 volume decreased 99 Proctitis 221
haemoglobinuria 292 Plasmodium falciparum 80 Prognostic stratification 53
Partial Platelet Progressive systemic sclerosis 416, 427
gastrectomy 552 aggregation 31 Prolactinogenic 209
lipodystrophy 332 defects 21, 24, 33 Proliferative
seizures 160, 161 Platypnoea 132 mesangial glomerulonephritis 235
thromboplastin time 31 Pleural effusion 141, 150 mesangiocapillary glomerulonephritis 234
Particularly caecum 178 Pleurisy 44, 54 Prophyalxis 247
Patent ductus arteriosus 97 Pleuritic pain 49 Prostatic enlargement 362
Pellagra 63 Pleurodynia 45 Prostatitis 232, 244
Pelvic Pleuropulmonary disease 48 Protein 242
inflammatory disease 1, 3, 14 Plummer’s disease 195 losing enteropathy 62, 70
organs 1, 2 Pneumoconiosis 139, 150 Prothrombin time 31
thrombophlebitis 472 Pneumocystic carinii 471 Pruritus 449
Pelvi-ureteric junction 2 Pneumonia 2, 6, 44, 54, 251 Pseudoerythrocytosis 99
Pemphigus vulgaris 498 Pneumothorax 2, 6, 7 Pseudohaemophilia 21
Penile index 282 Pointing sign 113 Pseudohypertrophic muscular dystrophy 399
Pentazocine 13 Poisons 142 Pseudotoxaemia syndrome 185
Peptic ulcer 1, 2, 9, 13, 113, 218 Poliomyelitis 142 Pseudotumour cerebri 265, 271
Perchlorate discharge test 201 Polyarteritis nodosa 253, 472 Pseudoxanthoma elasticum 219, 226
Percutaneous transluminal coronary angioplasty Psoriatic arthritis 416
Polycystic
49 Psychic
kidney 237, 247
Perforated peptic ulcer 7, 46 component 161
ovaries 331
Periarthritis of symptoms 160
Polycythaemia 99, 104, 177
left shoulder joint 45 Psychogenic 179, 517
Polycythalaemia 186
shoulder joint 366 fever 474
Polymyalgia rheumatica 399
Periarticular pain 372 headache 266
Polymyositis 399
Pericardial pain 1, 7
Polyuria 431
effusion 42, 53 depression 189
Porencephaly 158, 170
tamponade 135, 146, 517 Psychometric examination 164
Pericarditis 42, 53 Porphyria 79 Psychotherapy 168
Perifollicular purpura 28 Portal hypertension 216 Psychotic depression 179
Perilymphatic fistula 528 Positive end-expiratory pressure 14 Puberal hypogonadism 278
Peripheral Positron emission tomography (PET) 48 Pulmonary
circulatory failure 178 Postgastrointestinal surgery 64, 71 alveolar proteinosis 140, 150
cyanosis 94, 95, 99 Posterolateral infarction 42 arteriovenous fistula 98, 104
nerves 373 Postherpetic neuralgia 270 atresia 97
neuropathy 279 Postinfarction angina 52 embolism 43, 54, 133, 151, 517
Peritoneal fluid 11 Postinfectious arthritis 412 eosinophilia 252
Peritonsillar abscess 120 Post-lumbar puncture 265, 271 fibrosis 104
Peroneal muscular atrophy 397 Postpuberal hypogonadism 278 function tests 138, 144
Peyronie’s disease 279, 284 Post-traumatic sympathetic dystrophy 368 haemosiderosis 254
Pharyngeal pouch 121 Postural hypertension 253, 258
Phenol-sulphon-phthalein test 243 strain 319 infarction 5
Phenothiazines 81 syncope 515 oedema 104, 132
Phenylketonuria 158, 171 Pott’s disease 372 receptor stimulation 133
Phosphatic stones 247 Prader-Willi syndrome 332 stenosis 96
Physiological Pregnancy 331, 542 tuberculosis 141, 151, 178, 251, 256
dysfunction 284 Prevention of reinfarction 53 Pulse oximetry 101, 166
gynaecomastia 206 Prickly heat 451 Purpura
jaundice 304 Primary fulminans 28
Pick’s disease 158, 169 absorptive disorders of small bowel simplex 28, 38
Pituitary mucosa 61 Pustule 484
hypothalamic disorders 208 atrophic thyroiditis 196 Pyelonephritis 14
tumours 330 fibrinolysis 33 Pyloric obstruction 9
 602 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Pyogenic Replacement of fluid and electrolytes 546 Scurvy 28, 240

arthritis 410 Respiratory Second level studies 101
meningitis 270 acidosis 80 Secondary
Pyridoxine deficiency 160 disease 178, 188 absorptive defects 62
failure 102 deposits 317
Q system 143 depression to illness 179
Q fever 470 Restricted testicular failure 207, 212, 284
Qualitative platelet defects 38 chest movements 141, 151 thrombocytopenia 36
lymphatic flow 344 thyrotoxicosis 195, 202
R Restrictive lung disease 150 Secretion 192
Retention of salt and water 341 Segmental
Rabies 142, 152 Retinal migraine 262 glomerulonephritis 234
Radiation Retrocaecal appendicitis 8 glomerulosclerosis 246
cystitis 232 Retroperitoneal fibrosis 361
sickness 542 Semen analysis 281
Retropharyngeal abscess 121, 142, 152
Radicultis 368 Senile
Rh incompatibility 292
Radioimmune assay 68 pruritus 457
Rheumatic fever 412
Radiological tests 385 purpura 29, 38
Rheumatoid
Radionuclide ventriculography 48 Sepsis 469
arthritis 316, 367, 413, 426
Rapidly progressive glomerulonephritis 245 Sequestration crises 185
spondylitis 316
Rat-bite fever 488 Rib pressure syndrome 369 Serology 166
Raynaud’s Riboflavin 119 Seronegative arthropathies 427
disease 100, 368 Rickets 159 Serum
phenomenon 100, 107, 373 Riedel’s thyroiditis 197, 203 electrolytes 166
RBC mass 99 Right insulin levels 435
Reaven’s syndrome 332 lower quadrant 7 Severe anaemia 342
Recurrent upper quadrant 7 Shock 99
pulmonary embolism 151 ventricular infarction 52 lung 138
vomiting in children 542 Rigors 165 Shoulder-hand syndrome 368
Referred pain 1, 6, 265, 271, 319 Ringer lactate 12 Sicca syndrome 415
Reflex Rothera’s test 85 Sick sinus syndrome 381
headache 265 Rotor’s syndrome 297 Sickle cell
sympathetic dystrophy 368, 373 Ruptured anaemia 185, 289, 419
syncope 515 aortic aneurysm 2, 5, 15 crisis 2, 5, 15
Refractory ectopic pregnancy 2, 5, 15 disease 238
anaemia 186 graafian follicle 2, 5, 15 preparations 10
ulcers 115 mesentery 2, 5, 15 Silent abdomen 9
Reifenstein’s syndrome 208, 212 spleen 2, 5, 15 Simmond’s disease 177, 187
Reiter’s Simple
disease 425 S easy bruising 38
syndrome 416
goitre 193, 201
Relapsing polychondritis 417 Sacralisation of 5th lumbar vertebra 317
obesity 330
Relative polycythaemia 99 Sacroiliac
partial seizures 160
Renal joints 319
Single outflow tract 97
arterial occlusion 237 strain 319
Sinoatrial
artery aneurysm 237 Salmonella enterocolitis 10
biopsy 244, 359 Salt depletion 177, 187 block 380
calculi 11 Sarcoidosis 140 disease 381
colic 7 Scabies 451 Sinus
dysfunction 446 Scarlet fever 487 bradycardia 377
failure 280 Scheuermann’s disease 318, 324 rhythm 377
function tests 243 Schistosomiasis 239, 451 tachycardia 377
insufficiency 142 japonicum 553 Sjögren’s syndrome 120, 415
oedema 341 mansoni 553 Sleep
pain 4 Schizophrenia 556 apnoea syndrome 133
trauma 247 Scratch test 459 attacks 165
vein thrombosis 237, 246 Screens defect in platelet function 31 paralysis 165
 Index 603

Small Subacromial bursitis 45 Though laryngismus stridulus 159

bowel syndrome 62, 70 Subacute Three glass test 241
intestinal bacterial endocarditis 239 Thrombin clotting time 31
resection 64 thyroiditis 196, 202 Thrombocytes 182
obstruction 9 Subarachnoid haemorrhage 77, 87, 264 Thrombocytopenia 33
intestine peristalsis 9 Subclavian steal syndrome 522 Thrombophilia 82
vessel vasculitis 254 Subdural Thrombophlebitis 368
Smooth muscle spasm 1 haematoma 265, 271 Thromboplastin generation test 31
Soft tissue bleeds 32 haemorrhage 88 Thrombotic thrombocytopenic purpura 21,
Solid organs 1, 2 Sugar 242 26
Somatosensory seizure 160 Sulphaemoglobinaemia 99 Thyroid
Somnolence 75 Superficial mycoses 452 biopsy 201
Space-occupying lesions 78, 157 Suppurative pneumonia and lung abscess 141 cancer 203
Spastic paraplegias of acute onset 392 Suprarenal cortical failure 80, 90 function 192
Special blood tests 243 Supratentorial lesions 74 growth immunoglobulin 194
Specific Supraventricular tachyarrhythmias 378 imaging 201
gravity 241, 243 Surface inadequacy 62 nodules 198
treatment for specific diseases 12, 68, Swollen joints 409 stimulating
104, 113, 146, 346 Symptomatic hormone 192
Spina bifida occulta 317, 324 cholelithiasis 14 immunboglobulin 201
Spinal purpuras 27 storm 195
anaesthesia 397, 403 therapy 68 suppression test 200
cord 312 Synchronised intermittent mandatory ventilation Thyroiditis 193, 196, 202
injuries 393 103 Thyrotrophin releasing hormone 192, 200
lesions 2 Syncope 164, 514 Thyroxine binding globulin 192
nerves roots 368, 373 Syndrome X 332 Tietze’s syndrome 44
tumours 312 Systemic Tinea
Spirometric tests 144 diseases 284 capitis 461
Spirometry 101, 144 hypertension 253, 258 corporis 461
Splenic infections 541 cruris 461
defect 21, 24, 26, 35 lupus erythematosis 21, 26 pedis 461
infarction 5, 15 thrombo-haemorrhagic disorder 23 Tonic
Spondylitis 44 Systolic anterior motion 43 clonic seizures 162
Spondylolisthesis 318, 324 seizures 162
Spondylolysis 318, 324 T Torsion of
Spontaneous pneumothorax 44, 54, 150 Tabes dorsalis 142, 152 ovarian cyst 4, 15
Sprue syndrome 110, 116 Tabetic crises 142, 152 testicle 2, 6, 18
Sprung back 319 Tachyarrhythmias 43, 53 Toxaemia of pregnancy 159, 239
Spurious diarrhoea 65 Tachypnoea 133 Toxic
Stable angina 49 Taenia saginata 553 goitre 194
Stage of spinal shock 396 Telangiectasia 219 multinodular goitre 193
Staph. pyogenes 541 Temporal lobe lesions 279 nodular goitre 195, 202
Status Temporomandibular joints 271 shock syndrome 511
asthmaticus 147 Tendonitis 366 uninodular goitre 193
epilepticus 162 Tenosynovitis 366 Toxoplasmosis 80, 91
Steatosis 116 Tension headache 263, 270 Transient ischaemic 164
Stein-Leventhal syndrome 331 Terminal haematuria 245 Transillumination test 199
Stevens-Johnson syndrome 498 Testicular Transposition of
Stokes-Adams syndrome 381 failure 277 great vessels 97
Stomatitis 119 feminisation 212 pulmonary veins 98
Stool 182 tumours 208 Trauma 45, 233, 238, 245, 248
Storage pool deficiency 21, 36 Tetanus 165 Traumatic arthritis 420
Stress test 47 Tetany 159 Treadmill stress test 385
String test 223 Thematic apperception test 82, 181 Treatment of
Strongyloides stercoralis 553 Therapeutic starvation 334 acute abdominal pain 12
Strongyloidiasis 110 Thoracic outlet bleeding disorders 32
Struvite stones 247 compression syndrome 45, 55 chest pain 49
Stupor 75 syndrome 100 chronic diarrhoea 68
 604 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

coma 86 Typhoid 219 septal defect 97

cyanosis 102 fever 80, 91, 315, 487 tachyarrhythmias 380
different types of shock 511 relapse 469 tachycardia 380
dyspepsia 113 Typhus fevers 470 Vertebrobasilar insufficiency 164
dyspnoea 146 Vertigo 525, 527
epileptic seizures 167 U Vesical calculi 245
gynaecomastia 211
Ulcer dyspepsia 113 Vibrio cholerae 541
haematemesis 223
haematuria 248 Ulcerative colitis 60, 69 Viral
haemoptysis 256 Ultrasonography 201, 359 encephalitis 88
headache 268 Unclassified epileptic seizures 162 meningitis 271
insulin resistance syndrome 335 Unstable angina 40 Virus fever 45
jaundice 304 Upper gastrointestinal lesions 219 Visceral
low backache 322 Uraemia 28, 79 hypersensitivity 112
melaena 223 Ureteric reflex syncope 516
nontoxic goitre 201 calculus 238, 248
Vitamin
obesity 334 colic 2, 4, 15
D deficiency rickets 159
oedema 346 lesions 248
trauma 238 D resistant rickets 160
oliguria 359
Ureterocele 238, 248 K deficiency 22, 33
pain in extremities 371
palpitations 386 Urethral von Willebrand’s
paraplegia 401 stricture 362 disease 21, 22, 24, 27, 32, 36, 409
polyarthritis 423 tumours 362 factor 22
polyuria 443 valves 362
pruritus 459 Urethritis 244 W
rashes 494 Urethroscopy 244
specific types of jaundice 304 Uric acid crystals 361 Water
status epilepticus 168 Urine 10, 182, 545 excretion test 182
toxic goitre 202 examination 241 retention 158, 170
vomiting 546 formation 431 Weber’s syndrome 76
Trepopnoea 132 Urticaria 460 Wegener’s granulomatosis 250, 254, 258
TRH test 200 pigmentosa 452 Weil’s disease 488
Tricuspid atresia 97 Weiss syndrome 332
Trigeminal neuralgia 270 V Wernicke’s encephalopathy 81, 91, 160
Tropical
Vagotomy 64 Whipple’s disease 62
eosinophilia 138, 149, 257
Valvular Wilm’s tumour 247
infections 80
neurasthenia 180, 190 disease 100, 135 Wilson’s disease 306, 419
Trousseau’s sign 159 heart disease 135 Winter itch 460
True Varicose veins 343 Wiskott-Aldrich syndrome 21, 24, 35
hermaphroditism 208 Vas deferens 276 Wolff-Parkinson-White syndrome 380
polycythaemia 99 Vascular Wood’s lamp examination 458, 494
Truncus arteriosus 98 defects 38
Trypanosomiasis 80 diseases 472 X
Tube casts 242 factor 19
Tuberculoma 157 haemophilia 21, 22, 24, 32 Xerosis 457
Tuberculosis 58, 178, 220, 315 headache 261, 268 Xiphoidalgia 44
Tuberculous obstructions 107
disease 178 occlusion 151 Y
meningitis 271 purpuras 27, 38
Tuberous sclerosis 158 Vasculitis 246, 416, 426 Yersinia 59
Tumours 220, 244, 245, 248, 369 Vasogenic shock 505
like angioma 232 Vasospastic disorders 457 Z
Tumours of ureter 238 Vasovagal syncope 514
Types of Vegetable poisons 293 Zenker’s diverticulum 121
obesity 329 Venous obstruction 99 Ziehl-Neelsen stain 85
seizure 165 Ventricular Zollinger-Ellison syndrome 57, 61, 63, 115,
syncope 514 fibrillation 380 225