Critical Care Compendium-1001 Topics

in Intensive Care & Acute Medicine

(Aug 31,
2023)_(100923742X)_(Cambridge
University Press) 1st Edition Cade
Visit to download the full and correct content document:
https://textbookfull.com/product/critical-care-compendium-1001-topics-in-intensive-car
e-acute-medicine-aug-31-2023_100923742x_cambridge-university-press-1st-edition-
cade/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Handbook of Critical and Intensive Care Medicine 4th

Edition Joseph Varon

https://textbookfull.com/product/handbook-of-critical-and-
intensive-care-medicine-4th-edition-joseph-varon/

MCQs and SBAs in Intensive Care Medicine (Oxford Higher

Special Training) (Feb 11, 2022)_(0198753055)_(Oxford
University Press) 9th Edition Consultant In Critical
Care And Anaesthesia And Senior Honorary Lecturer Lorna
Eyre
https://textbookfull.com/product/mcqs-and-sbas-in-intensive-care-
medicine-oxford-higher-special-training-
feb-11-2022_0198753055_oxford-university-press-9th-edition-
consultant-in-critical-care-and-anaesthesia-and-senior-honor/

Revision notes in intensive care medicine 1st Edition

Camporota

https://textbookfull.com/product/revision-notes-in-intensive-
care-medicine-1st-edition-camporota/

OSCEs for Intensive Care Medicine Peter Hersey

https://textbookfull.com/product/osces-for-intensive-care-
medicine-peter-hersey/
Core topics in cardiothoracic critical care 2nd Edition
Kamen Valchanov

https://textbookfull.com/product/core-topics-in-cardiothoracic-
critical-care-2nd-edition-kamen-valchanov/

Surgical Intensive Care Medicine 3rd Edition John M.

O'Donnell

https://textbookfull.com/product/surgical-intensive-care-
medicine-3rd-edition-john-m-odonnell/

Annual Update in Intensive Care and Emergency Medicine

2019 Jean-Louis Vincent

https://textbookfull.com/product/annual-update-in-intensive-care-
and-emergency-medicine-2019-jean-louis-vincent/

Critical Care Emergency Medicine 2nd Edition William

Chiu

https://textbookfull.com/product/critical-care-emergency-
medicine-2nd-edition-william-chiu/

POCUS in Critical Care, Anesthesia and Emergency

Medicine Noreddine Bouarroudj

https://textbookfull.com/product/pocus-in-critical-care-
anesthesia-and-emergency-medicine-noreddine-bouarroudj/
 Critical Care Compendium

Published online by Cambridge University Press

 Critical Care Compendium
1001 Topics in Intensive Care & Acute Medicine
J. F. Cade
Emeritus Consultant in Intensive Care, Royal Melbourne Hospital; Professorial Fellow,
Department of Medicine, University of Melbourne

Published online by Cambridge University Press

 Shaftesbury Road, Cambridge CB2 8EA, United Kingdom
One Liberty Plaza, 20th Floor, New York, NY 10006, USA
477 Williamstown Road, Port Melbourne, VIC 3207, Australia
314–321, 3rd Floor, Plot 3, Splendor Forum, Jasola District Centre,
New Delhi – 110025, India
103 Penang Road, #05–06/07, Visioncrest Commercial, Singapore
238467

Cambridge University Press is part of Cambridge University Press &

Assessment, a department of the University of Cambridge.
We share the University’s mission to contribute to society through the
pursuit of education, learning and research at the highest international
levels of excellence.

www.cambridge.org
Information on this title: www.cambridge.org/9781009237420
DOI: 10.1017/9781009237451

© J. F. Cade 2023

This publication is in copyright. Subject to statutory exception and to

the provisions of relevant collective licensing agreements, no repro-
duction of any part may take place without the written permission of
Cambridge University Press & Assessment.
previously published 9780521189415 - Acute Medicine - Uncommon
Problems and Challenges 2011
This edition published 2023
Printed in the United Kingdom by TJ Books Limited, Padstow Cornwall
A catalogue record for this publication is available from the
British Library.
Library of Congress Cataloging-in-Publication Data
ISBN 978-1-009–23742-0 Paperback

......................................................................
Cambridge University Press & Assessment has no responsibility for the
persistence or accuracy of URLs for external or third-party internet
websites referred to in this publication and does not guarantee that any
content on such websites is, or will remain, accurate or appropriate.
Every effort has been made in preparing this book to provide accurate
and up-to-date information that is in accord with accepted standards
and practice at the time of publication. Although case histories are
drawn from actual cases, every effort has been made to disguise the
identities of the individuals involved. Nevertheless, the authors, editors,
and publishers can make no warranties that the information contained
herein is totally free from error, not least because clinical standards are
constantly changing through research and regulation. The authors,
editors, and publishers therefore disclaim all liability for direct or
consequential damages resulting from the use of material contained in
this book. Readers are strongly advised to pay careful attention to
information provided by the manufacturer of any drugs or equipment
that they plan to use.

Published online by Cambridge University Press

 To my family

Published online by Cambridge University Press

 Contents

Preface page xix

A Abciximab 1 Alveolar hypoventilation 17

Abdominal compartment syndrome 1 Alzheimer’s disease 17
Abortion 1 Amanita 17
Abruptio placentae (placental abruption) 1 Amenorrhoea 17
Acanthosis nigricans 1 Aminoaciduria 17
ACE 1 Aminocaproic acid 17
Acetazolamide 1 Ammonia 17
Acetylsalicylic acid 1 Amnesia 17
Achlorhydria 1 Amniotic fluid embolism 18
Acidosis, lactic 1 Amoebiasis 19
Acidosis, renal tubular 1 Amphetamines 19
Acquired immunodeficiency syndrome 1 Amyloid 21
Acromegaly 3 Amyotrophic lateral sclerosis 21
ACTH 4 Anaemia 21
Actinomycete infections 4 Anaphylaxis 25
Actinomycosis 4 ANCA 25
Acute brain syndrome 5 Aneurysms, mycotic 25
Acute fatty liver of pregnancy 5 Angiodysplasia 25
Acute flaccid myelitis 5 Angioedema 25
Acute lung irritation 5 Angiotensin 27
Acute pulmonary oedema 6 Angiotensin-converting enzyme 27
Acute respiratory distress syndrome 7 Animal bites 28
Acyclovir 7 Anion gap 28
Addison’s disease 8 Ankylosing spondylitis 28
Adenosine 8 Anorectal infections 29
Adrenal insufficiency 9 Anorectic agents 29
Adrenocorticotropic hormone 12 Anorexia nervosa 29
Adult respiratory distress syndrome 12 Anthrax 30
Agammaglobulinaemia 12 Antibiotic-associated colitis 31
Agranulocytosis 13 Anticardiolipin antibody 31
AIDS 13 Anticholinergic agents 31
Air embolism 13 Anticholinesterases 32
Alcohol, methyl 13 Anticoagulants 33
Aldosterone 13 Antidiuretic hormone 36
Alkaloids 13 Antinuclear antibodies 36
Allergic bronchopulmonary aspergillosis 13 Antiphospholipid syndrome 36
Allergic granulomatosis and angiitis 13 Antiplatelet agents 39
Alopecia 14 Antiprotease 40
Alpha-fetoprotein 14 Antithrombin 40
Alpha1-antitrypsin deficiency 15 Aortic coarctation 41
Altitude 16 Aortic dissection 42
Aluminium 16 Aortitis 43

vii
Published online by Cambridge University Press
 Contents

Aplastic anaemia 43 Bites and stings 66

Arachnids 43 Bivalirudin 71
ARDS 43 Black cohosh 71
Argatroban 43 Bleeding 71
Arnold–Chiari malformation 43 Bleomycin 71
Arsenic 43 ‘Blind as a bat . . .’ 72
Arteriovenous malformations 45 Blisters 72
Arteritis 46 Boerhaave’s syndrome 72
Arthritis 47 Bone failure 72
Arthropathies 48 Bornholm disease 72
Arthropods 48 Botulism 72
Arthus reaction 48 Bovine spongiform encephalopathy 73
Asbestos 48 Bradykinin 73
Aspergillosis 50 Brodifacoum 73
Aspiration 51 Bromhidrosis 73
Aspirin 52 Bromocriptine 73
Asplenia 53 Bronchiectasis 73
Asthma 53 Bronchiolitis obliterans 74
Asthmatic pulmonary eosinophilia 55 Bronchocentric granulomatosis 75
Atrial natriuretic factor 55 Broncholithiasis 75
Autacoids 56 Bronchopleural fistula 75
Auto-erythrocyte purpura 56 Brucellosis 75
Autoimmune disorders 56 Brugada syndrome 75
Autoinflammatory disease 58 Budd–Chiari syndrome 76
Autonomic dysreflexia 58 Bullae 77
Avian influenza 58 Burns, respiratory complications 77
Buruli ulcer 77
B Bacillary angiomatosis 58 Byssinosis 77
Bacillary peliosis hepatis 58
Bacitracin 58 C Cadmium 77
Baclofen 59 Caeruloplasmin 77
BAL 59 Calciphylaxis 77
Barotrauma 59 Calcitonin 78
Basophilia 60 Calcium 79
Bat bites 60 Calcium disodium edetate 79
Bathing 60 Cancer 79
Bed rest 60 Cancer complications 80
Bee stings 61 Carbon monoxide 81
Behcet’s syndrome 61 Carbon tetrachloride 83
Bell’s palsy 61 Carbonic anhydrase inhibitors 83
Bence Jones protein 62 Carboxyhaemoglobin 84
Benign intracranial hypertension 62 Carcinoembryonic antigen 84
Beriberi 62 Carcinoid syndrome 84
Beryllium 63 Cardiac tumours 86
Beta2-microglobulin 63 Cardiomyopathies 87
Bicarbonate therapy 64 Cardiopulmonary bypass 89
Biliary cirrhosis 64 Cardiorenal syndrome(s) 89
Biomarkers 64 Cardiovascular disorders 90
Bioterrorism 65 CAR T-cell therapy 91
Bird fancier’s lung 65 Cat bites 92
Bird flu 65 Cat-scratch disease 92
Bismuth 65 Cathinones 93

viii
Published online by Cambridge University Press
 Contents

Cavitation 93 Coturnism 119

Cellulitis 94 Cough 119
Central pontine myelinolysis 94 COVID-19 120
Cerebellar degeneration 95 C-reactive protein 120
Cerebral arterial gas embolism 95 CREST syndrome 121
Cerebral arteritis 95 Creutzfeldt–Jakob disease 121
Cerebral salt wasting 95 Cricoarytenoid arthritis 122
Charcot–Marie–Tooth disease 96 Critical illness myopathy 122
Chelating agents 96 Critical illness neuromuscular abnormality 123
Chemical exposures 98 Critical illness polyneuropathy 123
Chemical poisoning 98 Crohn’s disease 123
Chest wall disorders 99 Crustaceans 123
Chest X-ray 99 Cryoglobulinaemia 123
Cheyne–Stokes respiration 100 Cryptococcosis 123
Chikungunya 100 Cushing’s syndrome 124
Chlorine 100 Cyanide 125
Cholangitis 100 Cystic fibrosis 126
Cholera 101 Cytomegalovirus 128
Cholestasis 102
Cholinergic agonists 102 D Dantrolene 129
Cholinergic crisis 103 Decompression sickness 129
Cholinolytic agents 103 Defibrotide 129
Christmas disease 103 Delirium 129
Chromium 103 Dementia 131
Chronic fatigue syndrome 103 Demyelinating diseases 132
Churg–Strauss syndrome 104 Dengue 134
Chylothorax 104 Dermatitis 135
Ciguatera 104 Dermatology 135
CINMA 105 Dermatomyositis 137
Circadian rhythm 105 Desferrioxamine 137
Climate change 105 Desmopressin 137
Clopidogrel 106 Dextrocardia 137
Clostridial infections 106 Diabetes insipidus 137
Clostridium difficile 107 Diaphragm 138
Coagulation disorders 108 Diarrhoea 138
Coagulation factors 110 DIC 140
Cobalt 110 Differentiation syndrome 140
Cocaine 111 Diffuse alveolar haemorrhage 140
Coeliac disease 112 Diffuse fibrosing alveolitis 141
Colchicine 113 Diffuse parenchymal lung diseases 141
Cold 114 Digoxin-specific antibody 141
Cold agglutinin disease 114 Dimercaprol 142
Colitis 114 Dioxins 142
Collagen-vascular diseases 115 Diphtheria 142
Complement deficiency 115 Dipyridamole 143
Conjunctivitis 116 Dissecting aneurysm 143
Connective tissue diseases 117 Disseminated intravascular coagulation 143
Conn’s syndrome 117 Disulfiram 144
Constipation 118 Diving 144
Copper 118 Dog bites 145
Coronavirus 119 Drowning 145
Costochondritis 119 Drug allergy 147

ix
Published online by Cambridge University Press
 Contents

Drug–drug interactions 148 Erythema multiforme 170

Drug fever 149 Erythema nodosum 171
Drugs 149 Erythrocytosis 171
Drugs and the kidney 151 Erythromelalgia 171
Drugs and the lung 152 Erythropoietin 171
Dysentery 154 Ethylene glycol 172
Dysphagia 154 Euthyroid sick syndrome 173
Dysproteinaemias 154 Exfoliative dermatitis 174
Exophthalmos 175
E Eating disorders 154 Exotic pneumonia 175
Eaton Lambert syndrome 154 Extrinsic allergic alveolitis 175
Ebola haemorrhagic fever 154
Echinacea 155 F Fabry’s disease 175
Echinococcosis 155 Factitious disorders 176
Ecstasy 156 Factor V 176
Ecthyma 156 Factor VIII 176
Ectopic hormone production 156 Faecal calprotectin 176
Eculizumab 157 Faecal lactoferrin 177
EDTA 157 Faecal transplantation 177
Eisenmenger syndrome 157 Familial hypocalciuric hypercalcaemia 177
Embolism, air 157 Familial Mediterranean fever 177
Emphysema 157 Fanconi’s syndrome 178
Empyema 157 Farmer’s lung 178
Encephalitis 157 Fasciitis 178
Encephalomyelitis 158 Favism 178
Encephalopathy 158 Feeding intolerance 178
Endarteritis 159 Felty’s syndrome 178
Endocarditis 159 Ferritin 179
Endocrinology 162 Fetal haemoglobin 179
Energy expenditure 164 Fetomaternal haemorrhage 179
Enterocolitis 164 Fever 179
Enteropathogenic E. coli 164 Fever of unknown origin 179
Enteropathy 165 Fibrinolysis 179
Envenomation 165 Fish envenomation 181
Environment 165 Fleas 181
Eosinopenia 165 Flushing 181
Eosinophilia 165 FODMAPs 181
Eosinophilia and lung infiltration 166 Folic acid deficiency 182
Eosinophilic fasciitis 167 Folliculitis 182
Eosinophilic granuloma 167 Food poisoning 182
Eosinophilic pneumonia 167 Formaldehyde 183
Epidermolysis bullosa 168 Fournier’s gangrene 183
Epididymitis 168 Frailty 183
Epidural abscess 168 Friedreich’s ataxia 183
Epstein–Barr virus 169 Frostbite 183
Eptifibatide 169 Furunculosis 184
Equine morbilliform virus 169
Ergot 169 G Gamma-hydroxybutyric acid 184
Ergotamine 170 Ganciclovir 184
Erysipelas 170 Gangrene 184
Erythema marginatum 170 Gas gangrene 186
Erythema migrans 170 Gas in soft tissues 186

x
Published online by Cambridge University Press
 Contents

Gastric emptying 187 Heavy chains 214

Gastrinoma 187 Heavy metal poisoning 214
Gastroenteritis 187 HELLP syndrome 214
Gastroenterology 187 Helminths 215
Gastrointestinal tumours 189 Hemianopia 215
Gastroparesis 189 Hendra virus 215
Gaucher’s disease 189 Henoch–Schonlein purpura 216
Genomics 189 Heparin(s) 216
Germ warfare 189 Heparin-induced thrombocytopenia 217
Ghrelin 189 Hepatic diseases 219
Giant cell arteritis 190 Hepatic necrosis 221
Gingivitis 190 Hepatic vein thrombosis 221
Glomerular diseases 190 Hepatitis 221
Glossitis 191 Hepatocellular carcinoma 226
Glucagonoma 191 Hepatoma 227
Glucose-6-phosphate Hepatopulmonary syndrome 227
dehydrogenase deficiency 191 Hepatorenal syndrome 228
Glycocalyx 192 Hepcidin 228
Glycogen storage diseases 192 Herbicides 228
Goodpasture’s syndrome 193 Hereditary haemorrhagic telangiectasia 228
Gout 193 Herpesviruses 228
Graft-versus-host disease 196 High altitude 228
Granulomatosis with polyangiitis 196 Hirsutism 230
Graves’ disease 196 Hirudin(s) 231
Growth hormone 196 Histiocytosis 231
Guillain–Barré syndrome 196 Histocompatibility complex 232
Histoplasmosis 233
H Haemangioma 198 HIV 233
Haematology 198 Horner’s syndrome 233
Haematuria 200 Hot flushes 233
Haemochromatosis 201 Hot tubs 233
Haemodilution 203 Human bites 233
Haemoglobin disorders 203 Human immunodeficiency virus 233
Haemoglobinopathy 205 Hydatid disease 233
Haemoglobinuria 205 Hydrocephalus 234
Haemolacria 205 Hydrogen sulphide 234
Haemolysis 205 Hyperammonaemia 234
Haemolytic–uraemic syndromes 205 Hyperbaric oxygen 235
Haemophagocytic lymphohistiocytosis (HLH) 207 Hypercalcaemia 235
Haemophagocytic syndrome 207 Hyperdynamic state 237
Haemophilia 208 Hypereosinophilic syndrome 237
Haemoptysis 209 Hyperhidrosis 237
Haemostasis 210 Hyperhomocystinaemia 237
Hamman–Rich syndrome 211 Hyperparathyroidism 237
Hand–Schuller–Christian disease 211 Hyperphosphataemia 239
Hantavirus 211 Hypersensitivity pneumonitis 239
Heat 211 Hypersplenism 241
Heat cramps 212 Hyperthermia 241
Heat exhaustion/stress 212 Hyperthyroidism 241
Heat rash 212 Hypertrichosis 243
Heat shock proteins 212 Hyperuricaemia 243
Heat stroke 213 Hyperviscosity 243

xi
Published online by Cambridge University Press
 Contents

Hypocalcaemia 243 K Kaposi’s sarcoma 275

Hypoglycaemia 244 Kartagener’s syndrome 275
Hypokalaemia 245 Katayama fever 276
Hyponatraemia 245 Kawasaki disease 276
Hypoparathyroidism 246 Kennedy’s disease 276
Hypophosphataemia 246 Khat 276
Hyposplenism 247 Korsakoff syndrome 276
Hypothalamic–pituitary–adrenal axis 247 Kyphoscoliosis 276
Hypothermia 247
Hypothyroidism 250 L Lactase deficiency 277
Lactic acidosis 277
I ICU-acquired weakness 251 Langerhans cell histiocytosis 279
Idiopathic inflammatory myopathy (IIM) 252 Lassa fever 279
Idiopathic interstitial pneumonias 252 Lateral medullary syndrome 280
Idiopathic pulmonary fibrosis 252 Latex allergy 280
Idiopathic pulmonary haemosiderosis 254 Lead 280
Idiopathic thrombocytopenic purpura 254 Leflunomide 281
Immotile cilia syndrome 254 Lemierre’s syndrome 281
Immune complex disease 254 Leprosy 281
Immune thrombocytopenic purpura 255 Leptin 282
Immunodeficiency 257 Leptospirosis 282
Immunology 257 Leukocytoclastic vasculitis 282
Immunomodulation 259 Leukoencephalopathy 282
Immunothrombosis 259 Lewisite 283
Inborn errors of metabolism 259 Lice 283
Infections 260 Lichenoid skin reaction 283
Inflammatory bowel disease 263 Light chains 283
Inflammatory myeloid neoplasia 266 Lightning 283
Influenza 266 Lipoid pneumonia 283
Inhalation injury 268 Liquorice 284
Insect bites and stings 269 Listeriosis 284
Insecticides 270 Lithium 285
Insects 270 Livedo reticularis 286
Insulinoma 270 Liver abscess 287
Intensive Care Unit–acquired Loeffler’s syndrome 287
weakness 270 Ludwig’s angina 287
Interstitial lung diseases 270 Lung tumours 287
Interstitial nephritis 271 Lupus anticoagulant 288
Interstitial pneumonia 271 Lyme disease 288
Intra-abdominal hypertension 272 Lymphadenopathy 289
Iron 273 Lymphangioleiomyomatosis 289
Iron deficiency 273 Lymphocytosis 290
Iron overload disease 274 Lymphomatoid granulomatosis 290
Irritable bowel syndrome 274 Lymphopenia 291
Irukandji syndrome 274 Lyssavirus 291
Islet cell tumour 274
Isolation 275 M Macrophage activation syndrome (MAS) 291
ITP 275 ‘Mad Hatter’ syndrome 291
Magnesium 291
J Japanese encephalitis 275 Malabsorption 293
Jarisch–Herxheimer reaction 275 Malaria 294
Jellyfish envenomation 275 Malignant hyperthermia 296

xii
Published online by Cambridge University Press
 Contents

Mallory–Weiss syndrome 297 Multiple system atrophy 323

Manganese 297 Multisystem inflammatory syndrome
Marfan’s syndrome 297 in children 323
Marine vertebrate and invertebrate stings 298 Munchausen syndrome 323
Mast cells 298 Murray Valley encephalitis 323
Mastocytosis 298 Muscular dystrophies 323
May–Thurner syndrome 298 Mushroom poisoning 324
Mediastinal diseases 298 Mustards 325
Mediastinitis 299 Myalgic encephalomyelitis 325
Mediterranean fever 300 Myasthenia gravis 325
Medullary sponge kidney 300 Mycetism 327
Medullary thyroid cancer 300 Mycetoma 327
Megaloblastic anaemia 300 Mycobacterium ulcerans 327
Melatonin 300 Mycoplasma hominis 327
Meleney’s progressive synergistic gangrene 302 Mycoplasma pneumoniae 327
Melioidosis 302 Mycotic aneurysms 327
Mendelson’s syndrome 302 Myelitis 328
Meningococcaemia 302 Myelopathy 328
Meningoencephalitis 302 Myoglobinuria 328
Mercury 302 Myopathy 328
MERS 303 Myositis 329
Mesothelioma 303 Myotonia 330
Metabolic acidosis 303 Myxoedema 330
Metabolism and nutrition 303 Myxoma 330
Metastatic calcification 305
Methaemoglobinaemia 305 N Nails 330
Methanol 306 Necrolytic migratory erythema 331
Methylene blue 307 Necrotizing cutaneous mucormycosis 331
Methysergide 308 Necrotizing fasciitis 331
Microangiopathic haemolysis 308 Necrotizing granulomatous vasculitis 331
Microbiome 308 Necrotizing pneumonia 331
Microcirculation 310 Necrotizing soft-tissue infection 331
Microscopic polyangiitis 310 Nephrogenic fibrosing dermopathy 331
Microvascular dysfunction 310 Nephrogenic systemic fibrosis 331
Middle East respiratory syndrome 310 Nephrolithiasis 331
Mifepristone 310 Nephrology 332
Miller Fisher syndrome 311 Nephrotic syndrome 333
Mites 311 Neural tube defects 333
Mitochondrial diseases 311 Neurofibromatosis 334
Mixed connective tissue disease 312 Neuroleptic malignant syndrome 334
Monkey bites 312 Neurology 335
Monosodium glutamate 312 Neuromyelitis optica 337
Mosquitoes 312 Neuropathy 337
Motor neuron disease 313 Neutropenia 340
Mouth diseases 314 Neutrophilia 342
Multidisciplinary topics 315 Newcastle disease 342
Multifocal motor neuropathy 316 Nitric oxide 342
Multiorgan failure 316 Nitrous oxide 342
Multiple endocrine neoplasia 317 Nocardiosis 342
Multiple myeloma 318 Non-alcoholic fatty liver disease 343
Multiple organ dysfunction/failure 321 Non-alcoholic steatohepatitis 343
Multiple sclerosis 321 Non-respiratory thoracic disorders 344

xiii
Published online by Cambridge University Press
 Contents

Norovirus 344 Petechiae 360

Norwalk virus 344 Peutz–Jeghers syndrome 360
Nutrition 344 Phaeochromocytoma 360
Phosgene 361
O Obstetrics and gynaecology 344 Phrenic nerve 361
Occupational lung diseases 345 Phthiriasis 361
Octreotide 347 Physical exposures 361
Olmesartan 348 Pigmentation disorders 361
Oncofetal antigen 348 Pink urine 362
Ophthalmoplegia 348 Pituitary 362
Optic neuritis 348 Pituitary apoplexy 364
Oral contraceptives 348 Placental abruption (abruptio placentae) 364
Orchitis 348 Plague 364
Organophosphates 348 PLAID syndrome 365
Orthodeoxia 348 Plasmacytoma 365
Osler–Weber–Rendu disease 349 Plasmapheresis 365
Osmotic demyelination syndrome 349 Plasminogen 365
Osteomalacia 349 Platelet function disorders 366
Ovarian hyperstimulation syndrome 349 Platelets 367
Oxytocin 349 Platypnoea–orthodeoxia syndrome 368
Pleiotropic effects 368
P PADIS 349 Pleural disorders 368
Paget’s disease 350 Pleural effusion 369
Palmar erythema 351 Pleurisy 371
Pancreatic stone protein 351 Plumbism 371
Pancreatitis 351 Plummer–Vinson syndrome 371
Pancytopenia 352 Pneumatosis coli 371
Pandemics 352 Pneumoconiosis 371
Papilloedema 353 Pneumomediastinum 371
Paraganglioma 353 Pneumonia, exotic 371
Paragonimiasis 353 Pneumonia in pregnancy 371
Parahaemophilia 353 Pneumothorax 372
Paralytic shellfish poisoning 353 Poisoning 373
Paraneoplastic syndromes 354 Poliomyelitis 374
Paraquat 355 Polyarteritis nodosa 375
Parasitic infections 356 Polycystic kidney disease 376
Parathyromatosis 356 Polycystic ovary syndrome 376
Parotitis 356 Polycythaemia 376
Paroxysmal nocturnal haemoglobinuria 357 Polymyalgia rheumatica 377
Pectus excavatum 357 Polymyositis/dermatomyositis 378
Pediculosis 357 Polyneuritis 379
Pelvic inflammatory disease 357 Polyneuropathy 379
Pemphigus 358 Porphyria 379
Penicillamine 358 Portopulmonary hypertension 381
Pericarditis 358 Posterior reversible encephalopathy 381
Periodic breathing 359 Post–Intensive Care syndrome 381
Periodic fever 359 Post-transfusion purpura 382
Periodic paralysis 359 Pre-eclampsia 382
Pernicious anaemia 359 Pregnancy 384
Peroneal muscular atrophy 359 PRES 388
Persistent critical illness 359 Priapism 388
Pesticides 360 Primary alveolar hypoventilation 388

xiv
Published online by Cambridge University Press
 Contents

Primary ciliary dyskinesia 388 Reactive arthritis 414

Probiotics 389 Refeeding syndrome 414
Procalcitonin 389 Reiter’s syndrome 415
Proctitis 389 Relapsing fever 415
Progressive multifocal leukoencephalopathy 389 Renal artery occlusion 416
Propofol 389 Renal calculous disease 417
Prostacyclin 390 Renal cortical necrosis 417
Protein C 390 Renal cystic disease 417
Protein S 392 Renal tubular acidosis 418
Protein Z 392 Renal vein thrombosis 419
Proteinuria 393 Renin–angiotensin–aldosterone 419
Prothrombin G20210A abnormality 394 Respiratory burns 421
Prothrombin complex concentrate 394 Respiratory diseases 421
Protozoa 394 Restless legs syndrome 423
Pruritus 394 Reticulocytes 423
Prussian blue 395 Retinal haemorrhage 424
Prussic acid 395 Retrobulbar neuritis 424
Pseudogout 395 Retroperitoneal fibrosis 424
Pseudohyperkalaemia 395 Reversible posterior leukoencephalopathy 424
Pseudohyponatraemia 395 Reye’s syndrome 424
Pseudohypoparathyroidism 396 Rhabdomyolysis 425
Pseudolymphoma 396 Rheumatology 426
Pseudomembranous colitis 396 Rickettsial diseases 427
Pseudomyxoma peritonei 396 Rituximab 428
Pseudo-obstruction of the colon 396 Ross River virus disease 429
Pseudoporphyria 396
Pseudo primary aldosteronism 396 S Salicylism 429
Psittacosis 396 Salpingitis 429
Psoriasis 397 Sarcoidosis 430
Psychiatric issues 398 SARS 433
Ptosis 398 Scalded skin syndrome 433
Pulmonary alveolar proteinosis 399 Scarlet fever 433
Pulmonary hypertension 399 Schistosomiasis 433
Pulmonary infiltrates 404 Schonlein–Henoch purpura 434
Pulmonary infiltration with eosinophilia (PIE) 404 Scleredema 434
Pulmonary Langerhans cell histiocytosis 404 Scleroderma 434
Pulmonary nodules 404 Scombroid 436
Pulmonary oedema 405 Scorpion stings 436
Pulmonary veno-occlusive disease 405 Scrotal fire 436
Purpura 406 Scurvy 436
Pyoderma gangrenosum 406 Selenium 436
Pyrexia 407 Serositis 437
Pyroglutamic acid 412 Serotonin syndrome 437
Serpins 438
Q Q fever 412 Serum sickness 438
Quarantine 412 Severe acute respiratory syndrome 439
Sheehan’s syndrome 439
R Rabies 412 Short bowel syndrome 439
Radiation injury 413 Shy–Drager disease 440
Ramsay Hunt syndrome 414 Sicca syndrome 440
Rat bites 414 Sickle cell anaemia 440
Raynaud’s phenomenon/disease 414 Sideroblastic anaemia 440

xv
Published online by Cambridge University Press
 Contents
Silicosis 440
Situs inversus 440
Sjogren’s syndrome 440
Skin necrosis 441
Skin signs of internal malignant disease 442
SLE 442
Sleep 442
Sleep disorders of breathing 442
Smallpox 446
Smoke inhalation 446
Snake bites 446
Sodium nitroprusside 446
Somatomedin C 446
Somatostatin 446
Spider bites 446
Splenomegaly 446
Spondyloarthritis 447
Spotted fevers 447
Sprue-like enteropathy 447
Staphylococcal scalded skin
syndrome 447
Star fruit poisoning 447
Statins 448
Stevens–Johnson syndrome 448
Still’s disease 448
Stings 448
Stomatitis 448
Storage disorders 448
Stridor 448
Strontium 449
Strychnine 449
Sturge–Weber syndrome 449
Subacute sclerosing panencephalitis 450
Sucralfate 450
Sweating 450
Sweet’s syndrome 451
Swimming 451
Swine flu 451
Syndrome of inappropriate
antidiuretic hormone 451
Syphilis 452
Syringomyelia 453
Systemic diseases and the lung 453
Systemic lupus erythematosus 454
Systemic sclerosis 456
T Takayasu’s disease 456
Takotsubo cardiomyopathy
Tardive dyskinesia 457
Telangiectasia 457
Temporal arteritis 457
Tetanus 457
xvi
Published online by Cambridge University Press
Tetrachlorethylene 459
Tetrachlormethane 459
Tetrahydroaminoacridine (THA) 459
Tetralogy of Fallot 459
Tetrodotoxin 459
Thalassaemia 459
Thallium 459
Thermoregulation 459
Thesaurosis 460
Thiamine deficiency 460
Thrombasthenia 460
Thrombocythaemia 460
Thrombocytopenia 460
Thrombocytosis/thrombocythaemia 463
Thromboembolism 463
Thrombohaemorrhagic disorders 464
Thromboinflammation 464
Thrombolysis 464
Thrombomodulin 464
Thrombophilia 465
Thrombopoietin 466
Thrombotic microangiopathy 466
Thrombotic thrombocytopenic
purpura 466
Thymoma 468
Thyroid function 468
Thyroid storm 468
Ticks 468
Tinnitus 469
Tirofiban 469
Tisagenlecleucel 469
Tocilizumab 469
Tongue 469
Torulosis 469
Toxic epidermal necrolysis 469
Toxic erythemas 469
Toxic gases and fumes 469
Toxic shock syndrome 469
Toxoplasmosis 471
Trace elements 471
Tranexamic acid 472
Transverse myelitis 472
Trauma 472
Trauma-induced coagulopathy 473
Trauma in pregnancy 473
Trench fever 474
Trichlorethylene 474
456 Tropical pulmonary eosinophilia 474
Tuberculosis 474
Tuberous sclerosis 475
Tubulointerstitial diseases 475
Tumour-lysis syndrome 477
 Contents

Tumour markers/biomarkers 477 Von Recklinghausen’s disease 492

Tumour necrosis factor 478 Von Willebrand’s disease 492
Typhoid fever 479
Typhus 479 W Waldenstrom’s macroglobulinaemia 493
Warfare agents 493
U Ulcerative colitis 479 Warfarin 495
Ulcers 479 Wasp stings 495
Urea cycle disorders 480 Water-related accidents 495
Urticaria 480 Waterhouse–Friderichsen syndrome 495
Uveitis 482 WDHA syndrome 496
Uveoparotid fever 482 Wegener’s granulomatosis 496
Weil’s disease 497
V Valerian 482 Wernicke–Korsakoff syndrome 497
Valproate 482 West Nile virus encephalitis 498
Vaping 482 Whipple’s disease 498
Vaptans 483 Whipple’s triad 499
Varicella-zoster 483 Wilson’s disease 499
Vasculitis 484 Women’s health 499
Vasopressin 487 Woolsorter’s disease 499
Vertigo 487
Vesiculobullous diseases 487 X X-linked disorders 499
Vincent’s angina 488
VIPoma 488 Y Yellow fever 499
Viral haemorrhagic fever 488 Yellow nail syndrome 500
Vitamin deficiency 488
Vitamin B12 deficiency 489 Z Zika virus infection 500
Vitamin C deficiency 489 Zinc 500
Vitamin D deficiency 490 Zollinger–Ellison syndrome 501
Vitamin K deficiency 491 Zoonoses 501
Vitiligo 492 Zoster 502

Main entries are in bold text; cross-references are in plain text.

xvii
Published online by Cambridge University Press
 Preface
Uncommon clinical problems can present serious chal-
lenges in any medical specialty, particularly in those areas
providing acute care. These problems tend to be over-
looked even in major textbooks, they can be difficult to
identify fully elsewhere and even an experienced clinician
cannot be expected to remember all their relevant details.
Yet these problems in total can be numerous and varied,
and they may have a direct impact on patient care.
This book offers a solution. Uncommon problems
relevant to intensive care and acute medicine have been
gathered into a single volume, in which they have
been described in sufficient detail to obviate much of
the need to refer to specialized sources. The individual
topics have been arranged alphabetically, as in an encyclo-
paedia and with ample cross-referencing to facilitate
rapid access. The book is thus intended to provide an easy
and practical reference for the clinician at any level faced
with an uncommon acute medical problem at the bedside.
On the other hand, there are many things that this
book is not intended to do. It does not replace major
specialized texts, for it is not designed to cover the front-
line disorders and emergencies which underpin the care
of the acutely ill patient. Nor does it replace published
https://doi.org/10.1017/9781009237451.001 Published online by Cambridge University Press
in-depth specialist reviews or more importantly consult-
ant opinion of specialist colleagues – rather it is hoped to
be a partner with these in the large and important bound-
ary between intensive care and the many other medical
and surgical specialties which contribute to the care of the
acutely ill patient.
Recent years have seen an emphasis on intensive care
without walls and on medical emergency or rapid response
teams based in intensive care units but operating hospital-
wide. Thus, the traditional role of intensive care medicine
has become increasingly merged with acute medicine in
general, and the topics in this book reflect that overlap.
The author was fortunate to be able to persuade
Mr Ron Tandberg, one of Australia’s leading political
cartoonists, to illustrate the previous editions of this
book, and his cartoons have carried over as they are more
timeless than any text. His incisive wit has enlivened an
otherwise perhaps tedious text to the extent that his
cartoons have been referred to by some as the book’s
main attraction!
Finally, the author again thanks the editorial staff at
Cambridge University Press for their continued support
and expertise.
xix
 A
Acetylsalicylic acid See
• Aspirin.

Achlorhydria
Achlorhydria refers to the lack of secretion of gastric
acid. The diagnosis of achlorhydria may be less than
rigorous if it is based on the pH of spot samples of gastric
contents rather than on formal testing of basal or stimu-
lated gastric secretion.
Abciximab See The absence of gastric acid even after stimulation
• Antiplatelet agents. (i.e. absolute achlorhydria) has a number of associations,
including
Abdominal compartment syndrome See • gastric carcinoma,
• Intra-abdominal hypertension. • gastric polyps,
• pernicious anaemia (q.v.),
Abortion See • iron deficiency (q.v.),
• Pregnancy. • hypogammaglobulinaemia (see
See also Agammaglobulinaemia),
• Amniotic fluid embolism, • increased susceptibility to gastrointestinal infection.
• Antiphospholipid syndrome, Achlorhydria is of course also seen after
• Immune thrombocytopenic purpura,
• extensive gastric surgery or irradiation (permanently),
• Salpingitis, + +
• potent proton pump (H /K ATPase) inhibitors
• Systemic lupus erythematosus, (PPIs) (temporarily).
• Tetanus. Gastric acid is a prerequisite for peptic ulceration,
Bibliography and increased acid secretion is a feature of refractory
Levens ED, DeCherney AH. Ectopic pregnancy and or recurrent peptic ulceration (see Zollinger–Ellison
spontaneous abortion. In: Scientific American syndrome).
Medicine. Women’s Health. Hamilton: Dekker See also
Medicine. 2020. • Anaemia.

Abruptio placentae (placental Bibliography

Wolfe MM, Jensen RT. Zollinger–Ellison syndrome:
abruption) See current concepts in diagnosis and management.
• Trauma in pregnancy – Placental abruption. N Engl J Med 1987; 317: 1200.
See also
• Amniotic fluid embolism, Acidosis, lactic See
• Haemolytic–uraemic syndromes, • Lactic acidosis.
• HELLP syndrome,
• Pre-eclampsia. Acidosis, renal tubular See
Acanthosis nigricans See • Renal tubular acidosis.
• Pigmentation disorders. Acquired immunodeficiency syndrome
See also Acquired immunodeficiency syndrome (AIDS) has
• Lung tumours, become a well-recognized entity throughout all of clinical
• Paraneoplastic syndromes. medicine and beyond. The cumulative worldwide mor-
ACE See tality from AIDS pandemic has far exceeded 30 million,
with 800,000 deaths still occurring annually, as the overall
• Angiotensin-converting enzyme.
mortality has been about 40%. Nearly 40 million people
Acetazolamide See currently live with HIV infection, to which are added
about 1.7 million new cases each year.
• Carbonic anhydrase inhibitors.
See also Sophisticated computer modelling of viral phyloge-
netics has suggested that the causative virus, the human
• Benign intracranial hypertension,
immunodeficiency virus (HIV-1), originated in Africa
• High altitude,
perhaps in 1931, presumably via interspecies transfer
• Periodic paralysis.
1
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

from chimpanzees, though the first positive serology identified. Although the patient may be a risk to others,
can be dated only from 1959 in Africa and the first particularly if tuberculosis is not promptly recognized,
cases did not reach the developed world until nearly the patient is clearly also at risk of acquiring other,
10 years later. nosocomial infections while in hospital and especially
HIV infection is now regarded as a chronic condi- while in Intensive Care.
tion, and patients in the developed world at least can Respiratory infections are the most common infec-
have a relatively normal lifespan following viral sup- tions suffered by AIDS patients admitted for Intensive
pression with combined antiretroviral therapy (ART Care, but the clinical presentation is dependent on the
or cART). These ART regimens must be continued patient’s immune status, most simply assessed by the
indefinitely to prevent viral re-emergence. Current CD4 count.
antiviral therapy is so successful that HIV-AIDS • If the CD4 count is normal or nearly so, the infection
control has been effectively achieved even without is most likely to be bacterial or perhaps
the development of an effective vaccine. Moreover, tuberculosis (TB).
treated patients with an undetectable viral load (i.e. • If the CD4 count is <200/μL, the infection is most
<200 copies/mL in blood) do not pose a risk of trans- likely to be caused by, in order,
mission to others. - Pneumocystis jirovecii (P. carinii),
Pre-exposure prophylaxis (PrEP) is also available for - bacteria (especially pneumococci, but also
those at risk, e.g. in serodiscordant sexual partnerships, legionella, listeria, nocardia, salmonella),
on either a daily or an episodic basis. PrEP using a - mycobacteria (either TB or Mycobacterium avium
combination of tenofovir and emtricitabine has an effect- complex (MAC)),
iveness of over 90%, as also is post-exposure prophylaxis - fungi (candida, aspergillus),
with an effectiveness of over 80%. The widespread avail- - protozoa (toxoplasma),
ability of targeted PrEP has led to a marked fall in new - viruses (herpesviruses).
HIV diagnoses, at least in developed countries. Bacillary angiomatosis and bacillary peliosis hepatis
are serious infective complications of cat-scratch disease
(q.v.), seen in immunocompromised patients such as
Given the large number of otherwise well patients in
those with AIDS.
the population nowadays with HIV stabilized on ART
AIDS-defining neoplastic conditions remain a major
in developed countries, it is now estimated that most
clinical problem. These cancers include
such patients will be cared for in ICUs following
surgery, trauma, infection or any of the other condi- • Kaposi’s sarcoma, due to HSV8 (see Herpesviruses),
tions that prompt admission to ICU generally. In • non–Hodgkin’s lymphoma and primary
cerebral lymphoma.
addition, in patients being treated long term with
In disadvantaged communities, presenting features
combined highly active antiretroviral agents, there is
may still occasionally represent the direct effects of
an increased occurrence of a range of serious chronic
HIV infection. A very broad collection of such features
conditions, including accelerated cardiovascular dis-
may be seen, including
ease, COPD and non-AIDS-defining cancers. For all
these patients, special considerations apply in the use • an acute infectious mononucleosis-like illness
- which commonly persists for several months,
of ART if they become critically ill, and there are now
• thrombocytopenia (q.v.),
published guidelines for this.
• wasting,
• neurological disease
The traditionally most common presentation to - subacute encephalitis (q.v.),
Intensive Care, namely, opportunistic infection, has - encephalopathy (q.v.),
now been relegated to second place. Patients presenting - myelopathy (q.v.),
with these, even if their HIV status is unknown and - peripheral neuropathy (q.v.),
provided they have no other known immunodeficiency, - aseptic meningitis,
are generally not difficult to recognize as likely to • abnormalities of
have AIDS. - myocardium,
These infections are often unusually chronic, - kidneys,
recurrent, invasive or multiple. In many such patients - gut,
presenting with fever and a presumptive diagnosis - thyroid,
of infection, a specific microbiological cause is never - joints.

2
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Bibliography
Barbier F, Mer M, Szychowiak P, et al. Management of
HIV-infected patients in the intensive care unit. Intens
Care Med 2020; 46: 329.
Brookmeyer R. Reconstruction and future trends of the
AIDS epidemic in the United States. Science 1991;
253: 37.
Cheruvu S, Holloway CJ. Cardiovascular disease in
human immunodeficiency virus. Intern Med J 2014;
44: 315.
Dickson D. Tests fail to support claims for origin of AIDS
in polio vaccine. Nature 2000; 407: 117.
Karpatkin S, Nardi M, Green D. Platelet and coagulation
defects associated with HIV-1 infection. Thromb
Haemost 2002; 88: 389.
Korber B, Muldoon M, Theiler J, et al. Timing the
ancestor of the HIV-1 pandemic strains. Science 2000;
288: 1789.
Levine SJ, White DA. Pneumocystis carinii. Clin Chest
Med 1988; 9: 395.
Mann JM. AIDS – the second decade: a global
perspective. J Infect Dis 1992; 165: 245.
Miller R. HIV-associated respiratory diseases. Lancet
1996; 348: 307.
Panlilo AL, Cardo DM, Grohskopf LA, et al. Updated
U.S. public health service guidelines for the
management of occupational exposures to HIV and
recommendations for postexposure prophylaxis.
MMWR 2005; 54: 1.
Pitman MC, Lewin SR. Towards a cure for human
immunodeficiency virus. Intern Med J 2018; 48: 12.
Rosen MJ. Pulmonary complications of HIV infection:
a review. Respirology 2008; 13: 181.
Suffredini DA, George JM, Masur H. Management of
antiretrovirals in critically ill patients: great progress
but potential pitfalls. Crit Care Med 2018; 46: 663.
Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral
treatment of adult HIV infection:
2010 recommendations of the International AIDS
Society-USA panel. JAMA 2010; 304: 321.
Yarwood T, Russell DB. HIV: almost gone, but still
forgotten. Intern Med J 2020; 50: 269.
Acromegaly
Acromegaly is a rare condition, produced in adults by
excessive growth hormone which is usually derived from
a pituitary adenoma. Its incidence is about 4 per million
of the population per year, and its prevalence is about
50 per million of the population.
The pituitary adenoma usually arises from somatic
mutation of the gene coding for part of a regulatory
G protein, thus causing the production of growth
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
hormone to become continuous instead of varying
greatly during the day as it normally does in response
to many stimuli, including exercise, stress, hypogly-
caemia and adrenergic influences. Excessive growth
hormone in children may produce gigantism as an
occasional phenomenon.
Growth hormone (GH, somatotropin, somatropin) is
a 191 amino acid peptide, which is secreted by the anterior
pituitary and which acts by stimulating the hepatic pro-
duction of somatomedin C (or insulin-like growth factor
1, IGF-1), one of the body’s many growth factors which
circulate and bind to target cell receptors. IGF, which as
an ultimate anabolic agent was called the wonder drug of
the late twentieth century, is now described as a system
and is the subject of an extensive literature.
The pituitary secretion of growth hormone is regulated
by two neuropeptides secreted by the hypothalamus into
the pituitary portal circulation, namely, growth hormone–
releasing hormone (GHRH) which is stimulatory and
somatostatin (q.v.) which is inhibitory. Acromegaly may
thus also occur from excessive pituitary stimulation by
GHRH either from the hypothalamus or ectopically from
tumours, particularly benign foregut tumours such as
bronchial carcinoid (q.v.) or pancreatic adenoma.
The clinical features of acromegaly include both local
(mechanical or parasellar) and distal (hormonal)
changes, as for all pituitary tumours.
• Local (mechanical or parasellar) features include
headache and visual impairment (both of fields
and of acuity).
• Distal (hormonal) features include acral and soft
tissue overgrowth (affecting especially the face,
hands and feet), increased bodily hair (see
Hirsutism), sweating (q.v.) and odour, sleep
apnoea (q.v.), husky voice, diabetes and skin tags
(fibroma molluscum). Concomitant vascular
disease may occur, with both atherosclerosis and
microvascular dysfunction (q.v.).
Most patients have sleep apnoea (q.v.), and both the
obstructive and central forms of this condition
may occur.
Since the hormonal changes of acromegaly which
lead to clinical recognition tend to develop slowly,
the adenoma is generally a macro-adenoma (i.e.
>10 mm) and parasellar features are usual when the
diagnosis is made.
Investigations show an elevated plasma growth hor-
mone level which is not suppressed after a glucose load
(i.e. >3 μg/L, despite glucose 75 g 1–2 hr previously in a
3
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
standard oral glucose tolerance test). The plasma soma-
tomedin C level which reflects average growth hormone
activity is increased. The sella itself is best imaged by CT
or MRI. If pituitary hyperplasia rather than a discrete
adenoma is present, the source of GHRH should be
sought either in the hypothalamus or an ectopic site.
Treatment of a pituitary adenoma is usually by trans-
phenoidal resection.
• Postoperative radiotherapy is required if the GH and
IGF-1 remain elevated, as is often the case.
• If GH levels still remain elevated, symptoms may be
improved by medical treatment, using agents such as
bromocriptine (a dopamine agonist, given in a dose of
2.5–10 mg bd) or octreotide (a synthetic analog of
somatostatin, given in a dose of 200 mcg SC bd or tds).
Bromocriptine is particularly useful in patients with
prolactin-secreting tumours (but see Ergot).
• Second-generation dopamine agonists (e.g.
cabergoline), somatostatin analogs (e.g. pasireotide)
and growth hormone receptor antagonists (e.g.
pegvisomant) provide newer pharmacological options
for biochemical control when surgery is not feasible or
is incomplete. More recently, a long-acting analog of
somatostatin-release-inhibitor factor (SRIF) has been
found to be effective in resistant cases.
Pituitary apoplexy is an emergency condition which
can complicate any pituitary tumour.
It presents with headache, coma, shock and abnor-
mal eye signs.
It requires urgent treatment with corticosteroids
and surgery.
See also
• Pituitary.
Bibliography
Bach LA. The insulin-like growth factor system: basic and
clinical aspects. Aust NZ J Med 1999; 29: 355.
Burt MG, Ho KKY. Newer options in the management of
acromegaly. Intern Med J 2006; 36: 437.
Bills DC, Meyer FB, Laws ER, et al. A retrospective
analysis of pituitary apoplexy. Neurosurgery 1993;
33: 602.
Colao A, Ferone D, Marzullo P, et al. Systemic
complications of acromegaly: epidemiology,
pathogenesis, and management. Endocr Rev 2004;
25: 102.
Cheung NW, Taylor L, Boyages SC. An audit of long-
term octreotide therapy for acromegaly. Aust NZ
J Med 1997; 27: 12.
4
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
Lamberts S, van der Lely AJ, de Herder WW, et al.
Octreotide. N Engl J Med 1996; 334: 246.
Melmed S. Medical progress: acromegaly. N Engl J Med
2006; 355: 2558.
Randeva H, Schoebel J, Byrne J, et al. Classical pituitary
apoplexy: clinical features, management and outcome.
Clin Endo 1999; 51: 181.
ACTH See
• Adrenocorticotropic hormone.
See also
• Adrenal insufficiency.
• Aldosterone,
• Conn’s syndrome,
• Cushing’s syndrome,
• Ectopic hormone production,
• Hirsutism,
• Paraneoplastic syndromes.
Actinomycete infections See
• Actinomycosis,
• Nocardiosis,
• Whipple’s disease.
Actinomycosis
Actinomycosis is due to infection with a Gram-positive
bacterium, Actinomyces israelii, previously thought to be
a fungus because of its filamentous hyphae-like appear-
ance. It is an obligate anaerobe, related to Nocardia (q.v.)
and often part of the normal oral flora.
Infection arises when there is injury to the mucosal
barrier, especially in association with necrotic tissue or a
foreign body. Most infections are facio-cervical, but occa-
sionally the infection may involve the lungs or become
disseminated. It is also an uncommon cause of pelvic
inflammatory disease in women.
It is a chronic deep granulomatous infection with
sinus formation. Inspection of exuded material may show
the characteristic ‘sulphur granules’, tiny pale particles
which on microscopy are masses of filaments.
Laboratory identification can sometimes be difficult,
as the organisms on smear may fragment to give cocco-
bacilli appearing like diphtheroids and on culture they
are slowly growing under anaerobic conditions.
Treatment is with penicillin 7.2–14.4 g (12–24
million U) IV per day in divided doses for 2–4 weeks, then
orally in reduced dose for 3–6 months. In penicillin-
sensitive patients, tetracycline may be used.
• Surgical clearance may be required, and hyperbaric
oxygen should be considered in severe infections.
The prognosis is generally good.
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Bibliography
Systemic effects may also be seen on occasion,
Weese WC, Smith IM. A study of 57 cases of
including
actinomycosis over a 36-year period. Arch Intern Med
• fever,
1975; 135: 1562.
• chills,
Acute brain syndrome See • leukocytosis.
• Delirium.

Acute fatty liver of pregnancy Bronchiolitis (q.v.), pulmonary oedema (q.v.) and sub-
sequent bronchopneumonia are possible consequences of
Acute fatty liver of pregnancy (AFLP) is a rare and acute lung irritation.
potentially fatal condition of the third trimester and is
usually associated with pre-eclampsia. It presents with
nausea, vomiting, abdominal pain and jaundice. Toxic gases and fumes include
Liver function tests are abnormal, and there is usually • ammonia,
a coagulopathy. Hypoglycaemia can be severe and sus- • chlorine (q.v.),
tained. The liver biopsy shows diffuse panlobular fatty • sulphur dioxide,
change (i.e. steatosis). • oxides of nitrogen,
Treatment is with emergency delivery and Intensive • ozone,
Care support. • hydrogen sulphide (q.v.),
See also • isocyanates
• HELLP syndrome, - which may also cause occupational asthma
• Pre-eclampsia. (q.v.),
Bibliography • osmium tetroxide,
Chang MS, Rutherford AE. Liver disease in pregnancy. • metal fumes
In: Scientific American Medicine. Hepatology. - especially oxides of copper (q.v.), magnesium
Hamilton: Dekker Medicine. 2020. (q.v.) and zinc (q.v.),
- also oxides of antimony, beryllium (q.v.),
Acute flaccid myelitis See cadmium (q.v.), cobalt (q.v.), iron (q.v.),
• Poliomyelitis. manganese (q.v.), nickel, selenium (q.v.), tin,
tungsten and vanadium,
Acute lung irritation • mercury (q.v.),
• platinum salts,
Acute lung irritation can be produced by a large number • polymer fumes (Teflon degradation products),
of chemical pollutants in the form of noxious gases and • warfare agents (q.v.).
fumes (see Occupational lung diseases). Irritation gener-
ally occurs in the upper respiratory tract (and often
elsewhere, such as the skin), as well as in the lung. The treatment of toxic gas exposure is focussed on
Water-soluble gases (e.g. ammonia, sulphur dioxide) par- airway protection, intubation and lung protective modes
ticularly affect the upper airway and produce immediate of mechanical ventilation. Corticosteroids have not been of
symptoms, whereas less soluble gases (e.g. oxides of value acutely, though benefit has been reported during the
nitrogen, ozone) primarily affect the peripheral airways later reparative phase. Interestingly, simple drugs such as
and may produce delayed symptoms (i.e. about 12 hr aminophylline, ibuprofen, N-acetylcysteine, nebulized hep-
later). Heavy exposure to any agent causes effects arin and salbutamol have been recommended, but formal
throughout the entire respiratory system. documentation of their efficacy is lacking.
Systemic abnormalities are also produced following
the inhalation of
Clinical features of acute lung irritation thus include • carbon monoxide (q.v.),
• sneezing, rhinorrhoea, lacrimation, • cyanide (q.v.).
• stridor (q.v.), Asphyxia may be caused by excess
• cough, • carbon dioxide,
• wheeze, • nitrogen,
• dyspnoea. • methane.

5
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Bibliography 3. Decreased plasma oncotic pressure

Dennekamp M, Abramson MJ. The effects of bushfire
smoke on respiratory health. Respirology 2011; 16: 198.
Kales SN, Christiani DC. Acute chemical emergencies.
New Engl J Med 2004; 350: 800.
Schwartz DA. Acute inhalational injury. Occup Med
1987; 2: 297.
Acute pulmonary oedema
Pulmonary oedema is defined as an increased amount of
extravascular fluid (water and solute) in the lung, where it
may be interstitial or alveolar or both.
Pulmonary oedema is one of the commonest respira-
tory disorders and may follow a wide variety of local and
systemic insults. Although pulmonary oedema due to left
heart failure is the classical clinical picture, pulmonary
oedema also occurs in a number of other common set-
tings. In these, the left atrial pressure may be normal or
even low.
These non-cardiac settings include
• serious medical or surgical illness in the form of the
acute respiratory distress syndrome (ARDS) (q.v.),
• an important component in
- viral pneumonia,
- aspiration pneumonitis (q.v.),
- respiratory burns (q.v.),
- uraemia,
- endotoxaemia (a systemic inflammatory response
syndrome),
- drowning (q.v.),
- head injury,
- severe upper airway obstruction (see Asthma),
- altitude-related illness (see High altitude).
Pulmonary oedema may therefore present in diverse
settings with different pathogenetic mechanisms and thus
with different therapeutic implications.
The causes of pulmonary oedema are
1. Increased capillary hydrostatic pressure
• cardiogenic (left heart failure),
• blood volume overload,
• pulmonary veno-occlusive disease (q.v.).
2. Increased capillary permeability
• acute respiratory distress syndrome (ARDS)(q.v.),
• viral and other pneumonia,
• inhaled toxic substances (including oxygen),
• circulating toxic agents (including sepsis),
• disseminated intravascular coagulation (q.v.),
• uraemia, radiation (q.v.), burns (q.v.), non-fatal
downing (q.v.),
• vaping-associated respiratory disease after using
e-cigarettes (see Vaping).
• hypoalbuminaemia.
4. Decreased tissue hydrostatic pressure (i.e. negative-
pressure pulmonary oedema)
• rapid lung re-expansion, after
- drainage of a pneumothorax or large pleural
effusion,
- pneumonectomy,
• laryngospasm (and other causes of acute upper
airway obstruction, when associated with strong
inspiratory effort).
5. Decreased lymphatic drainage
• lymphangitis carcinomatosa,
• lymphangioleiomyomatosis (q.v.),
• lung transplantation.
6. Uncertain mechanisms
• high altitude (q.v.),
• neurogenic (raised intracranial pressure),
• drug overdose (especially IV heroin),
• pulmonary embolism,
• maximal exercise (occasionally),
• scuba diving, usually in cold water
(occasionally).
In practice,
• the first two groups of causes are by far the most
commonly encountered,
• the third group is probably not a cause in its own
right, but lowers the threshold for pulmonary
oedema from other causes,
• groups four, five and six are less common.
Bibliography
Adir Y, Shupak A, Gil A, et al. Swimming-induced
pulmonary edema: clinical presentation and serial
lung function. Chest 2004; 126: 394.
Albertson TE, Walby WF, Derlet RW. Stimulant-induced
pulmonary toxicity. Chest 1995; 108: 1140.
Bhattacharya M, Kallet RH, Ware LB, et al. Negative-
pressure pulmonary edema. Chest 2016; 150: 927.
Busl KM, Bleck TP. Neurogenic pulmonary edema. Crit
Care Med 2015; 43: 1710.
Colice GL. Neurogenic pulmonary edema. Clin Chest
Med 1985; 6: 473.
Esper A, Martin GS, Staton GW. Pulmonary edema.
In: Scientific American Medicine. Pulmonary & Critical
Care Medicine – Pulmonary. Hamilton: Dekker
Medicine. 2020.
Gehlbach BK, Geppert E. The pulmonary manifestations
of left heart failure. Chest 2004; 125: 669.

6
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Harms BA, Kramer GC, Bodai BI, et al. Effect of It should be remembered that even later definitions of
hypoproteinemia on pulmonary and soft tissue edema ARDS (e.g. Berlin 2012) have limited accuracy and that
formation. Crit Care Med 1981; 9: 503. its differential diagnosis includes a number of other con-
Kollef MH, Pluss J. Noncardiogenic pulmonary edema ditions associated with diffuse alveolar changes (see
following upper airway obstruction. Medicine 1991; Pulmonary infiltrates). The syndrome thus incorporates
70: 91. considerable heterogeneity.
McConkey PP. Postobstructive pulmonary oedema. See
Anaesth Intens Care 2000; 28: 72. • Acute pulmonary oedema.
Richalet JP. High altitude pulmonary oedema: still a place
Bibliography
for controversy? Thorax 1995; 50: 923.
Beitler JR, Schoenfeld DA, Thompson BT. Preventing
Scherrer U, Vollenweider L, Delabays A, et al. Inhaled
ARDS: progress, promise, and pitfalls. Chest 2014;
nitric oxide for high-altitude pulmonary edema.
146: 1102.
N Engl J Med 1996; 334: 624.
Esper A, Martin GS, Staton GW. Pulmonary edema. In:
Schoene RB. Pulmonary edema at high altitude: review,
Scientific American Medicine. Pulmonary & Critical
pathophysiology, and update. Clin Chest Med 1985;
Care Medicine. Hamilton: Dekker Medicine. 2020.
6: 491.
Guerin C, Thompson T, Brower R. The ten diseases that
Schwarz MI, Albert RK. ‘Imitators’ of the ARDS:
look like ARDS. Intens Care Med 2015; 41: 1099.
implications for diagnosis and treatment. Chest 2004;
Jaber S, Slutsky AS, eds. Mechanical ventilation in
125: 1530.
intensive care. Intens Care Med 2020; 46: Special Issue.
Sibbald WJ, Cunningham DR, Chin DN. Non-cardiac or
Rittayamai N, Brochard L. What’s new in ADRS (clinical
cardiac pulmonary edema? Chest 1983; 84: 452.
studies). Intens Care Med 2014; 40: 1731.
Simon RP. Neurogenic pulmonary edema. Neurol Clin
Thompson BT, Chambers RC, Liu KD. Acute respiratory
1993; 11: 309.
distress syndrome. N Engl J Med 2017; 377: 562.
Sporer KA, Dorn E. Heroin-related noncardiogenic
Various. ARDS birthday issue. Intens Care Med 2016;
pulmonary edema. Chest 2001; 120: 1628.
42: 637.
Steinberg KP, Hudson LD. Acute lung injury and acute
respiratory distress syndrome: the clinical syndrome. Acyclovir
Clin Chest Med 2000; 21: 401. Acyclovir (aciclovir) is one of the most important antiviral
Taylor JR, Ryu J, Colby TV, et al. drugs. It replaced vidarabine (ara-A), the first available
Lymphangioleiomyomatosis. N Engl J Med 1990; antiviral agent for systemic use in serious infections. It is a
323: 1254. synthetic purine nucleoside analog, structurally related to
Timby J, Reed C, Zeilender S, et al. Mechanical causes of guanosine. Its unique mechanism of action inhibits DNA
pulmonary edema. Chest 1990; 98: 973. synthesis and thus viral replication, so that it does not
affect the latent virus. There is a low incidence of develop-
Acute respiratory distress syndrome ment of resistance, but unwarranted use is unwise.
The antiviral effects of acyclovir are particularly rele-
Acute respiratory distress syndrome (adult respiratory
vant for herpesviruses (q.v.), as follows. It is
distress syndrome, ARDS) has been recognized as the
• especially effective against herpes simplex virus
hallmark respiratory complication of critical illness since
(HSV) types 1 and 2,
its first description in 1967. Its pathogenesis, clinical
• less effective but still very useful for varicella-zoster
features, diagnosis and management have been exten-
virus (VZV) (q.v.),
sively described, studied and reviewed in the literature
• of intermediate efficacy against Epstein–Barr virus
over the past four decades.
(EBV) (q.v.),
It has become apparent that there has been a major
• ineffective against cytomegalovirus (CMV) (q.v.), but
decline (about 4-fold) in the incidence and mortality of
the related agent, ganciclovir, is however effective
ARDS over the past 20 years. This decline has been
against CMV – see below.
attributed to improved resuscitation and early treatment
of sepsis, trauma and other precursor conditions, to more
The greatest value of acyclovir is in HSV encephalitis,
restrictive fluid and blood product practices, and to
in which trial results have shown a survival rate of
improved ventilator protocols focussed on lung protec-
about 80% and complete neurological recovery in
tion. This improvement has occurred despite the failure of
about 50%.
any specific pharmacological measure to alter its outcome.

7
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
It is also of value in oral-labial, genital, rectal and
neonatal HSV infections.
In VZV infections, it is helpful in
• the elderly, especially those with widespread lesions or
trigeminal involvement,
• herpes zoster encephalitis,
• varicella pneumonia,
• immunocompromised patients (in whom interferon
alpha and/or VZV immune globulin are also useful).
Acyclovir
• is not indicated in infectious mononucleosis, except
perhaps in severe cases,
• is not indicated in cytomegalovirus infections, except
for prophylaxis after bone marrow transplantation in
seropositive patients, in whom it is effective when
given in high dosage, i.e. 500 mg/m2 tds IV for the
first month),
• is not effective in the chronic fatigue syndrome (q.v.).
Acyclovir is not protein-bound but is distributed
evenly throughout the total body water, except in the
CSF in which the level is 25–50% of that in plasma. The
urinary concentration is about 10 times the plasma con-
centration. It has a half-life of about 3 hr, which rises 6-
fold in severe renal failure, since it is primarily excreted
in the urine. It is 60% removed by dialysis. It is probably
not mutagenic or carcinogenic. Although fetal risk has
not been shown, it crosses the placenta and should be
used in pregnancy only if there is a strong maternal
indication. It is excreted into breast milk.
It is available as a powder for IV administration, as
capsules for oral use and as an ointment for mucocuta-
neous lesions or keratitis. Intravenously, it is given as
5–10 mg/kg 8 hrly for 5–10 days. Typically, 500 mg are
reconstituted in 20 mL, diluted to 100 mL and adminis-
tered over 1 hr, giving a mean steady-state peak plasma
concentration of 20 mcg/mL.
Although the solution is widely compatible, it
undergoes irreversible crystallization if refrigerated.
Intravenous acyclovir is normally well tolerated, but it is
potentially phlebitic because of its alkaline nature
unless given diluted and slowly, and it can sometimes
give rise to nausea or a rash. Rarely, reversible encephal-
opathy or renal dysfunction may occur from very
high concentrations.
Later nucleoside analogs include
• valacyclovir (a prodrug of acyclovir) and famciclovir,
which are useful alternative agents,
• foscarnet, which may be used in chronic acyclovir-
resistant HSV type 2 infections.
8
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
Ganciclovir is structurally similar to acyclovir and is
given in similar dosage. Its chief difference is that it is
active against cytomegalovirus (q.v.). It is therefore used,
often with immune globulin, in CMV retinitis or pneu-
monia, for example after bone marrow transplantation.
Unlike acyclovir, it can produce bone marrow depres-
sion. It is teratogenic and mutagenic in animals. The
usual dosage is 5 mg/kg IV 12 hrly.
Valganciclovir is a prodrug of ganciclovir with much
higher bioavailability.
See also
• Bell’s palsy,
• Encephalitis.
Bibliography
Dwyer DE, Cunningham AL. Herpes simplex and
varicella-zoster virus infections. Med J Aust 2002;
177: 267.
Ernest ME, Franey RJ. Acyclovir and ganciclovir-induced
neurotoxicity. Ann Pharmacother 1998; 32: 111.
Hirsch MS. Herpesvirus infections. In: Scientific
American Medicine. Infectious Diseases. Hamilton:
Dekker Medicine. 2020.
Jackson JL, Gibbons R, Meyer G, et al. The effect of
treating herpes zoster with oral acyclovir in preventing
postherpetic neuralgia: a meta-analysis. Arch Intern
Med 1997; 157: 909.
Jacobson M. Treatment of cytomegalovirus retinitis in
patients with the acquired immunodeficiency
syndrome. N Engl J Med 1997; 337: 105.
Laskin OL. Acyclovir: pharmacology and clinical
experience. Arch Intern Med 1984; 144: 1241.
Prentice HG, Gluckman E, Powles RL, et al. Impact of
long-term acyclovir on cytomegalovirus infection and
survival after allogenic bone marrow transplantation:
European Acyclovir for CMV Prophylaxis Study
Group. Lancet 1994; 343: 749.
Addison’s disease See
• Adrenal insufficiency.
Adenosine
Adenosine is an autacoid (q.v.). It is an endogenous
purine nucleoside of molecular weight 267 Da, and it
has receptors (A1 or A2) on most cell membranes. It is
released when ATP is used and may thus help maintain
the balance between oxygen availability and utilization. It
is involved in many local regulatory processes, and in
particular it is a vasodilator and an inhibitor of neuronal
discharge. Adenoreceptors are present on phagocytes as
well as in cardiac myocytes, and there is evidence that
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
their modulation may prevent tissue injury in ischaemia
and sepsis.
Its cardiac effects were first recognized in 1929 and are
extensive. They especially involve decreased conduction
and ventricular automaticity, coronary vasodilatation and
the blunting of the effects of catecholamines. On balance,
it is thus ‘cardioprotective’. Both A1 and A2 receptors are
present in the heart – A1 in the cardiomyocytes and A2 in
the endothelial cells and vascular smooth muscle cells.
Clinically, its particular use is in the diagnosis and
treatment of tachyarrhythmias.
• It is of most value in the treatment of
supraventricular tachycardia, especially that
associated with the WPW syndrome, with an
average time to termination of arrhythmia of
30 sec.
• It has no effect in atrial fibrillation or atrial flutter.
• It is not of value in ventricular tachycardia unless
catecholamine induced.
Its effects are antagonized by theophylline and
potentiated by dipyridamole, but it may be administered
without altered efficacy in the presence of other cardiac
drugs or in liver or renal disease.
It is of potential clinical use in electrophysiological
studies, in cardiac stress testing and in the assessment of
coronary blood flow reserve. It has no useful effect on
coronary ischaemia.
Since its half-life is only 10 sec, it is given as a rapid IV
bolus of 3–6 mg. A further bolus of up to 12 mg may be
given 1–3 min later if necessary.
It can produce unpleasant and marked though transi-
ent side-effects, including flushing (q.v.), sweating (q.v.),
tingling, headache, light-headedness, nausea and appre-
hension. Bronchospasm may be precipitated in asthmat-
ics. It can also produce cardiac pain, which is angina-like
but not in fact ischaemic.
Bibliography
Belardinelli L, Linden J, Berne RM. The cardiac effects of
adenosine. Prog Cardiovasc Dis 1989; 167: 1186.
Cronstein BN. Adenosine, an endogenous anti-
inflammatory agent. J Appl Physiol 1994; 76: 5.
McCallion K, Harkin DW, Gardiner KR. Role of
adenosine in immunomodulation: review of the
literature. Crit Care Med 2004; 32: 273.
Adrenal insufficiency
Acute adrenal insufficiency is an uncommon condition
and is usually due to haemorrhage (especially from
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
heparin – q.v.), hypotension or shock (as in the
Waterhouse–Friderichsen syndrome – q.v.).
It thus occurs mostly in seriously ill patients, in whom
it should remembered as an uncommon cause of the
hyperdynamic state (q.v.).
The clinical features include nausea, weakness and
abdominal pain, as well as circulatory failure. Typically,
there is hyponatraemia (q.v.) with hyperkalaemia, and
the plasma urea may be elevated.
Relevant investigations include failure of the plasma
cortisol level to increase after the injection of synthetic
ACTH (see below) and direct imaging with CT.
Treatment is with physiological doses of hydrocorti-
sone IV.
Relative adrenal insufficiency (RAI) refers to a clin-
ical scenario that has been increasingly recognized in
seriously ill patients since the 1990s, though there remains
controversy about its definition, its relevance and even its
existence. Unlike (absolute) acute adrenal insufficiency
(see above), it is probably frequent, but it has no particu-
lar set of clinical features. Instead, it represents an exacer-
bation of the responses to severe illness or injury and is
chiefly manifest in retrospect as circulatory improvement
in catecholamine-dependence after physiological doses of
hydrocortisone, particularly in sepsis. Presumably, like
other organs and pathways, the hypothalamic–pituitary–
adrenal (HPA) axis (q.v.) has been impaired in this set-
ting, although paradoxically the basal cortisol levels in
critically ill patients are generally high and independent
of the usually low ACTH level at this time (probably
because some cytokines have ACTH-like activity).
A task force developing consensus guidelines in 2008
(and updated in 2017) coined the term critical illness–
related corticosteroid insufficiency (CIRCI) to reflect the
additional concept of an inadequate cellular or tissue
response to endogenous corticosteroid contributing to the
severity of the patient’s illness. However, since the diagno-
sis of tissue corticosteroid resistance remains difficult,
practical diagnosis relies on the principles described below.
The identification of relative adrenal insufficiency
requires a high level of suspicion and the demonstration
of an abnormal synthetic ACTH test (see below).
However, like most laboratory tests which have been
developed in well subjects or stable patients, the inter-
pretation of this test can be controversial, especially in
seriously ill patients, i.e. the very ones in whom the test is
most important. This difficulty is compounded by
• hypoalbuminaemia, because most circulating total
cortisol is protein-bound and it is the free cortisol
9
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
which is active (but which is not currently measurable
in most laboratories), and
• a commonly blunted ACTH response, presumably
because of existing maximal stimulation.
Nevertheless, the practical implication is that physio-
logical doses of glucocorticoid appear to be of therapeutic
benefit, especially in improving inotrope responsiveness in
circulatory failure. This is an area of ongoing clinical
research. A common practice has been that if the synthetic
ACTH is not clearly normal (see below), a therapeutic trial
of hydrocortisone (e.g. 100 mg IV 8 hrly or 200 mg per day
by IV infusion) can be warranted. However, given the
controversy about the ACTH test in this situation (see
above), those who prescribe hydrocortisone in such cases
most commonly do so empirically and without a prior
ACTH test. Such cases include septic shock, ARDS, trauma,
community-acquired pneumonia, bacterial meningitis, car-
diopulmonary bypass and after cardiac arrest. However,
given the heterogeneity of steroid-responsiveness among
patients with these conditions, it is likely that genomic
studies will be needed to clarify optimal treatment regimens.
An additional point of interest in this area is that the
greatly increased risk of relative adrenal insufficiency in
patients who have been given the sedative agent, etomi-
date, now provides a contraindication to the use of that
drug in Intensive Care practice.
Chronic adrenal insufficiency (Addison’s disease) is
due to
• autoimmune disease (sometimes polyglandular),
• a space-occupying lesion, typically a metastasis or
granuloma (e.g. TB),
• pituitary deficiency, due to
- global hypopituitarism (when hypothyroidism
(q.v.) is also typically present), or
- previous administration of corticosteroids in
pharmacological doses (when diabetes is
commonly associated),
• HIV infection (q.v.), with associated CMV adrenal
infection,
• drugs, such as ketoconazole, rifampicin.
Clinical features comprise
• weakness,
• weight loss,
• pigmentation (q.v.), especially in body creases,
• hypotension,
• hypovolaemia (except that blood volume remains
normal in pituitary deficiency (q.v.), since
aldosterone secretion is primarily controlled by the
renin–angiotensin system (q.v.)).
10
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
Investigations show mild hyperkalaemia and prone-
ness to hyponatraemia (q.v.) from water overload. In
patients who are sufficiently hypovolaemic to have pre-
renal renal failure, there is more marked hyperkalaemia
with hypoglycaemia, raised plasma urea and raised
haematocrit.
Specific testing shows a low plasma cortisol, which
fails to rise after synthetic ACTH 250 mcg IV (normal
>150 nmol/L and a rise at 30 min by at least 300 nmol/L
to a peak of >550 nmol/L). This short synthetic ACTH
stimulation test is simple and safe. In septic patients, the
cortisol rise rather than the basal level has correlated best
with outcome (but see above).
If adrenal insufficiency is clinically overt and cortico-
steroids have been commenced, confirmatory testing is
very difficult, unless dexamethasone can be temporarily
substituted and then ceased pending a long (i.e. 3-day)
synthetic ACTH stimulation test.
The plasma ACTH level is >20 pmol/L in primary
adrenal failure, but in hypopituitarism it is low (as are the
other pituitary hormones – q.v.). A rise in plasma cortisol
still occurs in hypopituitarism following ACTH, though
this may be subnormal due to chronic ACTH deficiency.
Treatment of adrenal insufficiency is urgent if there is
circulatory failure (i.e. adrenal crisis), with hydrocortisone
100 mg IV then 10–15 mg/hr, together with fluids, electro-
lytes and glucose. Chronic treatment requires maintenance
therapy with cortisone (approximately 35 mg per day given
about 2/3 in the morning and 1/3 in the evening), together
with fludrocortisone 100 mcg per day.
Patients with adrenal insufficiency exposed to stress
require increased doses of corticosteroids.
Typically, double the usual dose is used for minor
stress and hydrocortisone 100 mg IV 8 hrly for severe
stress, though recently it has become recognized that
these doses are excessive. In fact, doses of 25–150 mg
of hydrocortisone per day for a maximum of 3 days
are adequate.
Hypothalamic–pituitary–adrenal (HPA) (q.v.) func-
tion is suppressed by previously administered corticoster-
oids in pharmacological doses (even in the inhaled form
in children).
• This may not recover for a year or more after such
steroids are ceased.
• There is no simple and accurate prediction of
hormonal reserve function, based on the previous
dose or duration of steroid treatment.
• Prophylactic hydrocortisone (as above) is also
routinely recommended in such patients exposed to
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
stress. This cover is continued for 2 days, and then
if the clinical situation is satisfactory it is tapered over
the next few days.
If time permits, the cortisol response to ACTH may
be assessed prior to anticipated stress, such as elective
major surgery, but a normal value after ACTH does not
necessarily imply a normal response to other stress.
A more relevant adrenal assessment used to be provided
by the cortisol response to insulin-induced hypogly-
caemia, but this test is nowadays considered to be unsafe.
Bibliography
Al-Kurd A, Mazeh H. The endocrine system: adrenal
glands. In: Scientific American Medicine. Organ
Systems: Anatomy & Physiology. Hamilton: Dekker
Medicine. 2020.
Amrein K, Martucci G, Hahner S. Understanding adrenal
crisis. Intens Care Med 2018; 44: 652.
Annane D, Pastores SM, Rochwerg B, et al. Guidelines for
the diagnosis and management of critical illness-
related corticosteroid insufficiency (CIRCI) in
critically ill patients (Part 1): Society of Critical Care
Medicine (SCCM) and European Society of Intensive
Care Medicine (ESICM) 2017. Crit Care Med 2017;
45: 2078 and Intens Care Med 2017; 43: 1751.
Annane D, Pastores SM, Arlt W, et al. Critical illness-
related corticosteroid insufficiency (CIRCI): a
narrative review from a Multispecialty Task Force of
the Society of Critical Care Medicine (SCCM) and the
European Society of Intensive Care Medicine
(ESICM). Crit Care Med 2017; 45: 2089 and Intens
Care Med 2017; 43: 1781.
Annane D, Sebille V, Charpentier C, et al. Effect of
treatment with low doses of hydrocortisone and
fludrocortisone on mortality in patients with septic
shock. JAMA 2002; 288: 862.
Claussen MS, Landercasper J, Cogbill TH. Acute adrenal
insufficiency presenting as shock after trauma and
surgery: three cases and review of the literature.
J Trauma 1992; 32: 94.
Cohen J, Venkatesh B. Relative adrenal insufficiency in
the intensive care population; background and critical
appraisal of the evidence. Anaesth Intens Care 2010;
38: 425.
Editorial. Corticosteroids and hypothalamic-pituitary-
adrenocortical function. BMJ 1980; 280: 813.
Hamrahian AH, Oseni TS, Arafah BM. Measurement of
serum free cortisol in critically ill patients. N Engl
J Med 2004; 350: 1629.
Jung C, Inder WJ. Management of adrenal insufficiency
during the stress of medical illness and surgery. Med
J Aust 2008; 188: 409.
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
Keller-Wood M. Hypothalamic-piuitary-adrenal axis-
feedback control. Compr Physiol 2015; 5: 1161.
Ligtenberg JJM, Zilstra JG. The relative adrenal
insufficiency syndrome revisited: which patients will
benefit from low-dose steroids? Curr Opin Crit Care
2004; 10: 456.
Lipiner-Friedman D, Sprung CL, Laterre PF, et al.
Adrenal function in sepsis: the retrospective Corticus
cohort study. Crit Care Med 2007; 35: 1012.
Loriaux DL. The polyendocrine deficiency syndromes.
N Engl J Med 1985; 312: 1568.
Loriaux DL. Adrenal insufficiency. In: Scientific
American Medicine. Endocrinology & Metabolism.
Hamilton: Dekker Medicine. 2020.
Malerba G, Romano-Girard F, Cravoisy A, et al. Risk
factors of relative adrenocortical deficiency in
intensive care patients needing mechanical ventilation.
Intens Care Med 2005; 31: 388.
Marik PE. Unravelling the mystery of adrenal failure in
the critically ill. Crit Care Med 2004; 32: 569.
Marik PE, Pastores SM, Annane D, et al.
Recommendations for the diagnosis and management
of corticosteroid insufficiency in critically ill adult
patients: consensus statements from an international
task force by the American College of Critical Care
Medicine. Crit Care Med 2008; 36: 1937.
Marik PE, Zaloga GP. Adrenal insufficiency in the
critically ill: a new look at an old problem. Chest 2002;
122: 1784.
Marik PE, Zaloga GP. Adrenal insufficiency during septic
shock. Crit Care Med 2003; 31: 141.
Pastores SM, Annane D, Rochwerg B, et al. Guidelines for
the diagnosis and management of critical illness-
related corticosteroid insufficiency (CIRCI) in
critically ill patients (Part 2): Society of Critical Care
Medicine (SCCM) and European Society of Intensive
Care Medicine (ESICM) 2017. Crit Care Med 2018;
46: 146 and Intens Care Med 2017; 43: 1751.
Peeters B, Meersseman P, Perre SV, et al. Adrenocortical
function during prolonged critical illness and beyond:
a prospective observational study. Intens Care Med
2018; 44: 1720.
Puar TH, Stikkelbroeck NM, Smans LC, et al. Adrenal
crisis: still a deadly event in the 21st century. Am J Med
2016; 129: 339.
Rai R, Cohen J, Venkateash B. Assessment of
adrenocortical function in the critically ill. Crit Care
Resusc 2004; 6: 123.
Rygard SL, Butler E, Granholm A, et al. Low-dose
corticosteroids for adult patients with septic shock: a
systematic review with meta-analysis and trial
sequential review. Intens Care Med 2018; 44: 1003.
11
 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Salem M, Tainsh RE, Bromberg J, et al. Perioperative
glucocorticoid coverage: a reassessment 42 years after
emergence of a problem. Ann Surg 1994; 219: 416.
Szalados JE, Vukmir RB. Acute adrenal insufficiency
resulting from adrenal hemorrhage as indicated by
post-operative hypotension. Intens Care Med 1994;
20: 216.
Vance ML. Hypopituitarism. N Engl J Med 1994;
330: 1651.
Vella A, Nippoldt TB, Morris JC. Adrenal hemorrhage:
a 25-year experience at the Mayo Clinic. Mayo Clin
Proc 2001; 76: 161.
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive
glucocorticoid therapy in patients with septic shock.
N Engl J Med 2018; 378: 797.
Venkatesh B, Prins J, Torpy D, et al. Relative adrenal
insufficiency: match point or deuce? Crit Care Resusc
2006; 8: 376.
Vita JA, Silverberg SJ, Goland RS, et al. Clinical clues to
the cause of Addison’s disease. Am J Med 1985; 78: 461.
Volbeda M, Wetterslev J, Gluud C, et al. Glucocorticoids
for sepsis: systematic review with meta-analysis and
trial sequential analysis. Intens Care Med 2015;
41: 1220.
Webb SAR. Relative adrenal insufficiency exists and
should be treated. Crit Care Resusc 2006; 8: 371.
Zaloga GP, Marik P. Hypothalamic-pituitary-adrenal
insufficiency. Crit Care Clin 2001; 17: 25.
Adrenocorticotropic hormone
Adrenocorticotropic hormone (corticotropin, ACTH)
is the main controlling factor for the adrenal production
of cortisol and androgens. It is produced in the
anterior pituitary by cleavage of a large and complex
polypeptide (241 amino acids) called propiomelanocor-
tin (POMC), which also includes melanocyte-stimulating
hormone (MSH), beta-endorphin, met-enkephalin, beta-
lipotropin and a number of other peptides of currently
unknown function.
The secretion of ACTH is controlled primarily by the
hypothalamus-derived corticotropin-releasing hormone
(CRH) and secondarily by catecholamines and vasopres-
sin. ACTH release is also stimulated by stress and by
hypoglycaemia. CRH production and ACTH release are
inhibited by both natural and synthetic corticosteroids,
which suppress mRNA for POMC synthesis. ACTH is
released in pulses, especially in the mornings, thus
explaining the diurnal rhythm of cortisol secretion.
The normal level of ACTH is 1.3–16.7 pmol/L.
See
• Adrenal insufficiency,
• Aldosterone,
12
https://doi.org/10.1017/9781009237451.002 Published online by Cambridge University Press
• Conn’s syndrome,
• Cushing’s syndrome,
• Ectopic hormone production,
• Hirsutism,
• Paraneoplastic syndromes.
Bibliography
Editorial. Corticosteroids and hypothalamic-pituitary-
adrenocortical function. BMJ 1980; 280: 813.
Imura H. Control of biosynthesis and secretion of
ACTH: a review. Horm Metab Res 1987; 16
(suppl.): 1.
Orth DN. Corticotropin-releasing hormone in humans.
Endocr Rev 1992; 13: 164.
Adult respiratory distress syndrome See
• Acute respiratory distress syndrome.
See also
• Acute pulmonary oedema.
Agammaglobulinaemia
Agammaglobulinaemia (Bruton’s agammaglobulinae-
mia) was the first described immunodeficiency disorder
(q.v.). It is a congenital X-linked condition, caused by
mutations in the BTK gene on the long arm of the
X chromosome which encodes for a tyrosine kinase
expressed in pre–B cells.
• There is a lifelong susceptibility to infection
- particularly with encapsulated pyogenic
microorganisms,
- less so with viruses, fungi and even most Gram-
negative bacteria (except for Haemophilus
influenzae).
• Infections, particularly of the respiratory tract,
show a(n)
- increased frequency,
- increased severity,
- increased recurrence rate,
- decreased responsiveness to treatment.
Chronic meningoencephalitis, due to an echovirus,
can be a particularly troublesome complication (see
Encephalitis).
In about 30% of patients, agammaglobulinaemia is
associated with a rheumatoid arthritis-like disease and
sometimes with dermatomyositis (q.v.), probably due to
an enterovirus.
On investigation, all the immunoglobulins are
decreased (with IgA, IgM and IgD often undetectable
Another random document with
no related content on Scribd:
natural relationship of one idea to another—and its conscious
recognition at the time of observation, or later, during reflection, that
one’s memory is aided. This is what psychologists have always
called “the law of the association of ideas.” It is a natural law, which
even a child unconsciously recognizes. The baby subconsciously or
instinctively knows that food and its pleasant sensations of comfort
are associated with its mother’s breast. Star and sky, sea and ship,
automobile and swift travel, gun and war, cyclone and disaster, are
instances of natural and simple association that all people recognize.
In the cultivation, discipline, strengthening of the powers of the
memory, this natural law can be made to render marvelous service.
For not only can man avail himself of faculties of the mind
unconsciously exercised, he has the additional power of consciously
directing their exercise. Just as our domestic water systems are the
result of the conscious direction of the self-flowing water in the
course we wish it to flow, so is the enlarged power of our memories
the result of the conscious and purposeful direction of our
observation, reflection, and thought-linking to that end. Drawn from
personal experience there are five methods of thought-linking which
have proved themselves of great help. These are: First, Incidental.
Second, Accidental. Third, Scientific. Fourth, Pictorial. Fifth,
Constructive.

The Incidental Method

The events, the incidents, of the day occur in a natural order: one
follows another. The days of the week with their respective incidents
follow in natural sequence. A full recognition of this fact is of far
greater help to the memory than one would believe on first thought.
Many a man has been able to recall a particularly important event by
going back, step by step, incident by incident, over the occurrences
of the day. It is related of Thurlow Weed, the eminent statesman,
that, when he entered political life, he had so poor and wretched a
memory that it was his bane. He determined to improve it, and,
realizing the importance of observation and reflection, he decided
upon the following method: As the incidents of the day followed each
other, in natural sequence, he would consciously note how they
followed. Then at the close of the day he sat down with his wife, and
relating the incidents exactly in the order they occurred, he would
review the events of the day, even to the most trivial and
inconsequential act. At other times he would relate the incidental
order backwards. It was not long before his memory so improved
that he began to be noted for it. Before he died, he had the
reputation of possessing a phenomenal memory. One will find this
same method a great help in seeking to recall a sermon, a lecture or
speech. There is a natural sequence in all well-thought-out
addresses, and the listener, carefully noting the change from one
thought to another—the progress of the address—will find it aid his
memory development wonderfully to take the last thought given, say,
and in reverse order, bring up the thoughts, the ideas given. Then let
the address be “incidentally” gone over from the first thought to the
second, the third, and so on to the end. Thus it can be recalled and
put away in the memory securely for future use.

The Accidental Method

Another natural method is what may be termed accidental. It is
purely accidental that Pike’s Peak is 14,147 feet high, but see how
this fact enables you to fix the figures in your mind. There are two
fourteens and the last figure is half of fourteen, namely, seven. It is a
purely accidental fact that the two Emperors of Germany died in
1888, but the fact that they did die in that year, the one year in the
whole century when the three eights occur, indelibly fixes the date in
mind. Again the year 1666 might have passed by unnoticed were it
not for the fact that that was the date of the Great Fire in London.
Now let us see how this accidental association may fix a relative
date for many other important events. The Great Fire purged the city
of London of the horrors caused by the Great Plague. This plague
was made the basis for Eugene Sue’s graphic novel, “The
Wandering Jew.” Wherever he went—so ran the legend—the plague
followed as the result of Christ’s curse. It was the Great Plague that
brought into existence the peculiar custom of all the Latin, as well as
the English, peoples exclaiming, “God bless you!” or its equivalent,
upon hearing one sneeze. The reason for the custom is that
sneezing was one of the first symptoms of the fearful plague, and
one, hearing his friend sneeze, immediately felt afraid he was seized
with the dread disease, and gave vent to this pious exclamation. The
custom persists to this day, but few know its origin. This plague also
brings to mind a noble example of heroism that is worthy of
enshrinement in every heart. It was found by those who watched the
progress of the plague that it went from place to place, dying out
here as soon as it appeared elsewhere. It was this phenomenon that
gave to Eugene Sue the dramatic element in his novel, for it
appeared to the ignorant people of those days that the plague
actually followed the cursed Jew. A country pastor, an humble but
devoted and true servant of God, in a little Derbyshire village, had
observed this fact. Although isolation for contagious diseases was
not thought of by physicians at that time, this man seemed to grasp
the idea. He determined that if ever the disease reached his village
he would endeavor to isolate his people from all others so that it
would stop there and no longer continue to slay its helpless victims.
In due time the plague did appear in his village. He had already
aroused in his simple-minded flock the spirit of true heroism, and
they pledged themselves to second his endeavors. Food was
brought from a near-by town and deposited near a watering-trough,
in which a small stream was continually flowing. In this flowing water
the villagers placed the money in payment for their food supplies.
Thus there was no contact of peoples, no contamination. The
villagers kept to themselves, no one going away and no one coming
in. The result was that in a very short time the plague was stayed,
and Europe breathed a great sigh of relief, attributing its cessation to
the goodness of God, when we now know it was owing to the self-
sacrificing wisdom of men.
But we are not yet through with our associations with the
accidental date of 1666. The most remarkable account we have of
the Great Plague is Daniel DeFoe’s “Journal of the Plague,” which
for many years was regarded as the genuine diary of an eye-
witness. As DeFoe, however, was not born until 1661, five years
before the plague, he could have had but the faintest and most
childish remembrances of that dread event. But it was he who wrote
the world-famous, ever-enjoyable “Robinson Crusoe.” This appeared
in 1719, and, while the association of this date with that of 1666 is
remote, it does approximately fix the date of the appearance of that
masterpiece.
Another literary masterpiece appeared, however, much nearer the
time of the plague. That was John Bunyan’s “Pilgrim’s Progress,”
which was written in Bedford Jail during the actual year of the plague
and fire.
One of the greatest lawyers of England was Sir Matthew Hale, and
it is a help to fix approximately the time he was on the bench when
we recall that it was he who sentenced John Bunyan to the twelve
years’ confinement that gave to the world his “Pilgrim’s Progress.”
On the other hand, Hale was a great personal friend of Richard
Baxter, who, at about the same time, wrote the well known “Saints’
Everlasting Rest.” Here, then, hung on to this accidental peg of the
year 1666, we find the following facts: First, the Great Fire; second,
the Great Plague; third, Eugene Sue’s novel “The Wandering Jew;”
fourth, the custom of saying “God bless you;” fifth, the heroism of the
Derbyshire villagers that stopped the plague; sixth DeFoe’s writing of
the “Journal of the Plague” and “Robinson Crusoe;” seventh,
Bunyan’s writing of “Pilgrim’s Progress;” eighth, Sir Matthew Hale on
the English bench; ninth, Richard Baxter’s writing of the “Saints’
Everlasting Rest.”
Every novelist uses this law of accidental association, for it is
habitually used by every class of people. Who is there who does not
recall certain events because they happened on days when other
and perhaps more important events occurred which fixed the date in
the mind? For instance, if an event occurred on the day of her first
child’s birth, and the mother was aware of it, you may rest fully
assured she would have no trouble recalling the date of the event. Its
accidental association will guarantee its remembrance.
Lawyers use this law constantly in seeking to extract evidences
from their witnesses. The dates of certain events are surely fixed in
the mind. Other events, less securely remembered, occurred at, or
about, the same time. The association once clearly established, the
memory invariably responds.

The Scientific Method

This method is merely a phase of reflection, for during that
process one naturally classifies his ideas, received through
observation. As David Pryde says in his “How to Read”:

See every fact and group of facts as clearly and distinctly

as you can; ascertain the fact in your past experience to
which it bears a likeness or relation, and then associate it with
that fact. And this rule can be applied in almost every case.
Take as an example that most difficult of all efforts, namely,
the beginning of a new study, where all the details are
strange. All that you have to do is to begin with those details
that can be associated with your past experience. In science,
begin with the specimens with which you are already familiar,
and group around them as many other specimens as you can.
In history and geography, commence with the facts relating to
the places and scenes which you actually know. And in
foreign languages, start with the words and phrases for the
most familiar objects and incidents of every-day life. In this
way you will give all your mind a clear and safe foundation in
your own experience.... The mind cannot master many
disconnected details. It becomes perplexed and then
helpless. It must generalize these details. It must arrange
them into groups, according to the three laws of association—
resemblance, contiguity, and cause and effect. This, it will be
granted at once, must be the method in all rigidly systematic
studies, such as the sciences, history, biography, and politics.
But it is valuable to ordinary people as well to know that the
same plan can be used in all kinds of descriptions. Every
collection of details can be arranged in groups in such a way
that they can be clearly understood and remembered. The
following is the manner in which this can be done: In studying
any interesting scene, let your mind look carefully at all the
details. You will then become conscious of one or more
definite effects or strong impressions that have been made
upon you. Discover what these impressions are. Then group
and describe in order the details which tend to produce each
of the impressions. You will then find that you have comprised
in your description all the important details of the scene. As
an instance, let us suppose a writer is out in the country on a
morning toward the end of May, and wishes to describe the
multitudinous objects which delight his senses. First of all, he
ascertains that the general impressions as produced on his
mind by the summer landscape are the ideas of luxuriance,
brightness and joy. He then proceeds to describe in these
groups the details which produce these impressions. He first
takes up the luxuriant features, the springing crops of grain
completely hiding the red soil; the rich, living carpet of grass
and flowers covering the meadows; the hedge-rows on each
side of the way, in their bright summer green; the trees
bending gracefully under the full weight of their foliage; and
the wild plants, those waifs of nature, flourishing everywhere,
smothering the woodland brook, filling up each scar and
crevice in the rock, and making a rich fringe along the side of
every highway and footpath. He then descants upon the
brightness of the landscape; the golden sunshine; the pearly
dew-drops hanging on the tips of every blade of grass, and
sparkling in the morning rays; the clusters of daisies dappling
the pasture-land; the dandelion glowing under the very foot of
the traveler; the chestnut trees, like great candelabra, stuck
all over with white lights, lighting up the woodlands; and lilacs,
laburnums, and hawthorne in full flower, making the farmer’s
garden one mass of variegated blossom. And last of all, he
can dwell upon the joy that is abroad on the face of the earth:
the little birds so full of one feeling that they can only trill it
forth in the same delicious monotone; the lark bounding into
the air, as if eager and quivering to proclaim his joy to the
whole world; the bee humming his satisfaction as he revels
among the flowers; and the myriads of insects floating in the
air and poising and darting with drowsy buzz through the
 floods of golden sunshine. Thus we see that, by this habit of
generalizing, the mind can grasp the details of almost any
scene.
This desire to unify knowledge, to see unity in variety, is
one of the most noted characteristics of great men in all
departures of learning. Scientific men in the present day are
eager to resolve all the phenomena of nature into force or
energy. The history of philosophy, too, is in a great measure,
taken up with attempts to prove that being and knowing are
identical. Emerson can find no better definition of genius than
that it is intellect constructive. Perhaps, he says, if we should
meet Shakspere, we should not be conscious of any great
inferiority, but of a great equality, only that he possesses a
great skill of using—of classifying—his facts, which we
lacked.

Herbert Spencer was a master at the classification of facts. By the

classification of all the known languages of the world, the scientists
are seeking to find out accurately, as never before, the relationships
of mankind. Men have been writing the different languages of widely
diverse people for centuries, but never before has an attempt been
made on so vast a scale to bring all this isolated knowledge to bear
upon the solution of one great question—the origin of the human
race. All scientific knowledge is based upon the association of
isolated and detached facts. These are then reflected upon, and,
finally, theories begin to form themselves in the mind of the student,
the philosopher. He then brings his facts and theories into close
relationship and sees whether they “fit.” If he is assured that they do,
he presents his thought to the world, and, according to its
reasonableness, it is received or rejected.

The Pictorial Method

Most children make mental pictures with great ease, but,
unfortunately, as they grow older, they allow this faculty to lose its
power by disuse. In the cultivation and use of the memory, however,
it can be of the greatest possible help. All books of travel and
description, all novels, all history, are made up of a series of word
pictures. Do not be content merely to read the words of these
pictures. Go further! Actually picture each scene in your imagination
and you will thus materially aid your original power of observation.
Let your pictures be definite, positive, explicit as to details, for the
more careful you are in making a picture real to your mind, the easier
it will be recalled.
Now, if you desire to recall the whole course of a book, you will
find these vividly-made mental pictures have a natural order of
sequence, and one will recall the next following, and so on. There is
great joy in learning to make pictorial thought-links, and then in the
ability they give to the memory to recall them.

Methods of Constructive Thought-Linking

We now come to the active making of artificial links as aids to the
memory where none naturally appear. A thought-link of this type is
the generally known doggerel:

Thirty days hath September,

April, June and November,
All the rest have thirty-one
Save February which alone
[18]Has twenty-eight, and one day more
We add to it one year in four.

In like manner how do we remember the order of the prime colors?

Few there are who do not know the coined word, made from the
initial letters of Violet, Indigo, Blue, Green, Yellow, Orange, Red—
Vibgyor. Again, the student of geology, who forgets the order of his
great epochs or eras, might recall them by formulating a sentence
that presents the initial letters of the names of these epochs. Thus,
“Careful men pay easily,” suggests Cenozoic, Mesozoic, Paleozoic,
Eozoic. Of course no one of common sense presumes to assert that
these constructive thought-links are any other than crutches,
footbridges over streams too wide to stride or jump unaided. They
should frankly be recognized as such, and only reverted to in case of
necessity, or as a last resort. But it is equally foolish in view of the
testimony of their almost universal usage and helpfulness, to deny
that they are an aid to most memories.

Think of the Impressions

To “think of the impressions.” This is the final admonition of
Stokes’s golden rule of memory. One word conveys his idea—
review. The things to be remembered must be thought over. They
must be re-collected—again collected. You will thus re-observe
them, re-reflect upon them, re-strengthen your original mental
impressions and the ideas that have grown around them. Experience
demonstrates that all memory impressions are lasting. One may
have forgotten something for twenty, thirty, forty years, when
suddenly a chance word, sound, sight, or even odor, will recall it with
an intensity and reality that are startling. All works on mental
philosophy give illustrations of this asserted fact. The practical need
of all men, however, is to cultivate the ability to call up mental
impressions at will.
Ready recollection is the great desideratum. Hidden knowledge is
of slight use. It is as if one had a fortune stored away in some hidden
dungeon, carefully locked up, but he had lost the key. Availability,
readiness, promptness are essentials to efficiency. The hat-boy at
the hotel dining-room would be useless did his memory not act
promptly, instantly. To-morrow will not do. Now is the accepted time.
This efficient, prompt, responsive memory is the one you need and
desire. It is worth striving for. The prospector wanders over the
mountains, canyons, deserts, for years, seeking the precious ore in
most unlikely places. He is always buoyed up with the hope, some
day, of striking it rich. Are you as earnest in your desire for memory
development as he? If so, careful, systematic, daily exercise of the
various faculties of the mind and memory will give to you this golden
possession. Reread here what has been quoted earlier from David
Pryde’s “What Books to Read and How to Read.” The hints therein
contained are worth their weight in gold to the really earnest student.
But rest assured of this: If you would have a good memory, you must
work for it. Give your whole attention to whatever you read or hear.
Concentrate. Compare the parts of the composition with the whole.
Seek its excellencies, study its deficiencies. Reflect upon it from
every angle. Write out in your own language the facts, or the ideas of
what you have heard or read. Then use daily what you have gained.
Knowledge stored away in the mind is not only useless, it is
positively injurious. Use is the law of life. Give your knowledge, your
ideas, your reflections away. Tell them to your intimates, your friends.
Write them to your correspondents. For the more you give the more
you will find you have. There is a giving that increases and a
withholding that impoverishes, and in nothing is this more apparent
than in the giving of the riches of the mind or memory. Each time one
recites a well-liked poem for the benefit and blessing of others, the
more firmly he fixes it in his own mind. “There is that which
scattereth, and yet increaseth.” In the scattering of your gems of
mind and heart, you are increasing your own store.
Not only give freely, but give often. The daily use of what you have
gained is an advantage. Avail yourself of every reasonable
opportunity to use your newly acquired powers, and your newly
acquired knowledge. Let me repeat, use is the law of life. To learn
something new daily is a good motto, but to use what you have
learned is even better. You gain ease of recollection by daily
exercising the faculty of recollection. And if your memory balks,
refuses to act, compel it to obey you. If you make a demand upon it
and it fails to respond—you cannot remember—do not let the matter
go by. Demand of the memory that it bring back that which you
require. Keep the need before you.
In this constant, persistent, cheerful, willing use of the memory lies
great happiness and content. “It is more blessed to give than to
receive.” The more, in reason, the athlete uses his muscles the
stronger they become. And think of the radiant joy that is the natural
accompaniment of a healthy, vigorous body. What constant pleasure
is his who calls upon a physical body which readily and willingly
responds! Equally so is it with the memory and all the mind. Activity
keeps it in health. In this glorious condition it readily responds to all
calls, it is radiantly alive, and I know of no joy greater that can be
given to man than that in body, mind, and soul he is a radiating
center of activity, receiving and giving on every hand.
In conclusion, here are a few practical words upon the other side
of the question, on forgetting, for there is a forgetting that is of great
help to the power of remembering. Fix these precepts firmly in your
mind:
Forget evil imaginations.
Forget the slander you have heard.
Forget the meanness of small souls.
Forget the faults of your friends.
Forget the injuries done you by your enemies.
Forget the misunderstandings of yesterday.
Forget all malice, all fault-finding, all injuries, all hardness, all
unlovely and distressing things.
Start out every day with a clean sheet. Remember only the sweet,
beautiful and lovely things, and you will thus be as a human sun of
righteousness, with healing in your rays.
 FOOTNOTES
[1] Entered according to Act of Congress, in the year 1884, by
George Wharton James, in the office of the Librarian of Congress,
at Washington, D. C.
[2] Entered according to Act of Congress, in the year 1885, by
George Wharton James, in the office of the Librarian of Congress,
at Washington, D. C.
[3] Scripture, “Stuttering and Lisping,” p. 3.
[4] Pauline B. Camp, “Correction of Speech Defects in a Public
School System.” “The Quarterly Journal of Public Speaking” for
October, 1917, p. 304.
[5] By contact is meant the point of greatest resistance of the
vocal organs to the column of air.
[6] Lawyer, Senator from Nebraska, 1895—born at Montpelier,
Vt., 1847.
[7] Pronounced “Sombray.”
[8] Adobe, pronounced A-do´by, a thick clay of which sun-dried
bricks are made.
[9] Robert Lloyd was an English poet of the middle eighteenth
century.
[10] This remarkable poem relates to revelry in India at a time
when the English officers serving in that country were being
struck down by pestilence. It has been correctly styled “the very
poetry of military despair.”
[11] Some of the greatest literature of this war has been written
by British Tommies—in the trenches or in hospitals; but nothing
finer or better interpreting the psychology of the men at the front
has yet appeared in print than this poem by Bombardier B.
Bumpas, of the Australian contingent, wounded at Gallipoli and
while convalescing in a hospital at Cairo, minus a leg and an eye.
[12] From “Madrigali.”
 [13] From Hiawatha.
[14] Mr. Miller gives the following interesting note to the above
poem:
“We had been moving West and West from my birth, at Liberty,
Union County, Indiana, November 10, 1841 or 1842 (the Bible
was burned and we don’t know which year), and now were in the
woods of the Miami Indian Reserve. My first recollection is of
starting up from the trundle-bed with my two little brothers and
looking out one night at father and mother at work burning brush-
heaps, which threw a lurid flare against the greased paper
window. Late that autumn I was measured for my first shoes, and
Papa led me to his school. Then a strange old woman came, and
there was mystery and a smell of mint, and one night, as we three
little ones were hurried away through the woods to a neighbor’s,
she was very cross. We three came back alone in the cold, early
morning. There was a little snow, rabbit tracks in the trail, and
some quail ran hastily from cover to cover. We three little ones
were all alone and silent, so silent. We knew nothing, nothing at
all, and yet we knew, intuitively, all; but truly the divine mystery of
mother nature, God’s relegation of His last great work to woman,
her partnership with Him in creation—not one of us had ever
dreamed of. Yet we three little lads huddled up in a knot near the
ice-hung eaves of the log cabin outside the corner where
mother’s bed stood and—did the new baby hear her silent and
awed little brothers? Did she feel them, outside there, huddled
close together in the cold and snow, listening, listening? For lo! a
little baby cry came through the cabin wall; and then we all rushed
around the corner of the cabin, jerked the latch and all three in a
heap tumbled up into the bed and peered down into the little pink
face against mother’s breast. Gentle, gentle, how more than ever
gentle were we all six now in that little log cabin. Papa doing
everything so gently, saying nothing, only doing, doing. And ever
so and always toward the West, till 1852, when he had touched
the sea of seas, and could go no farther. And so gentle always!
Can you conceive how gentle? Seventy-two years he led and
lived in the wilderness and yet never fired or even laid hand to a
gun.”
[15] There is a Scandinavian legend that Siegfried, the “Viking,”
feeling that he was at the point of death, caused himself to be
placed on the deck of his ship; the sails were hoisted, the vessel
set on fire, and in this manner he drifted out to sea, alone, and
finished his career.
[16] In the “days of old, the days of gold, and the days of ’49,”
water was brought from the Sierran heights in wooden viaducts,
or “flumes,” to be used in the mines. The fifth stanza refers to the
process of hydraulic mining, where the water, projected through
huge nozzles (somewhat after the fashion used by fire-engines),
washed down the mountain-sides into the sluice-boxes where the
dirt was washed away and the gold retained. Now the flume’s
waters are mainly diverted to purposes of irrigation.
[17] “‘The Arrow and the Song’ came into my mind and glanced
on to the paper with an arrow’s speed—literally an improvisation,”
said Longfellow. The poem has been exceedingly popular, both
when recited and also when sung to the beautiful music
composed for it by the Italian song-writer, Ciro Pinsuti.
[18] Here is a variant of the last two lines:

“Has twenty-eight and this in fine

One year in four has twenty-nine.”
 INDEX
All titles to chapters are in capitals.
All titles to selections are in italics.
Names of authors are given in ordinary type.

A
Abraham Lincoln Walks at Midnight, 520
Adams, Charles F., 338, 393
Advance, The Great, 534
Adventure, A Startling, 150
” An Unexpected, 258
AFTER DINNER SPEAKING, 711
Ain’t It the Truth (exercise), 35
Aldrich, Thomas B., 490, 665
All in the Emphasis, 311
Alexander, S. J., 641, 642, 643
Alexandra, A Welcome to, 633
Americanism, Creed of, 677
America and Its Flag, 559
” Music of, 21
Analysis, Progressive, 112
Ancient Mariner, 49
Andersen, Hans C., 191
Anderson, Alexander, 427
” John, My Jo, 574
Annabel Lee, 430
” The Lover of, 431
Apostrophe to the Ocean, 536
Apple Blossoms, 588
Arena, A Combat in the, 272
Arrow and the Song, The, 630
ARTICULATION EXERCISES, 27 et seq.
As I Came Down from Lebanon, 587
Aspirates, 28
As You Like It (quoted), 658-59
At Grandma’s, 391
Authors, Study Great, 2
Author’s Thought, Getting the, 7

B
Baby, Rocking the, 434
Bacon, Francis, 49
Bad Night, A, 131
Ballad of the King’s Singer, The True, 498
Banishment Scene, 662
Bansman, William, 538
Barnes, W. H. L., 683
Barrett, Wilson, 187
Bashford, Herbert, 414, 416, 456, 460, 612, 624
Battle Field, The Children of the, 452
Beecher, Henry Ward, iv, 100
Belief, Author’s Purpose, 113
Bedford-Jones, H., 337
Bell Buoy, The, 70
Bells of San Gabriel, 631
” of Shandon, 636
” The Minaret, 621
Bennett, Henry Holcomb, 525
Beside the Dead, 433
Betty Botter, 30
Bill and His Billboard, 35
Billee, Little, 360
Bishop and the Convict, The, 220
Bishop, Justin Truitt, 142
Black Sailor’s Chanty, The, 408
Blacksmith of Limerick, The, 503
Bland, Henry Meade, 568
Blossom Time, In, 607
Blossoms, Apple, 588
Booth, Gov. Newton, 678
Boy Wanted, A, 285
” The Whistling, 358
Bosher, Kate Langley, 132
Bravest Battle, The, 519
Break! Break! Break!, 433
Breath Sounds, 28
Brook and the Wave, The, 590
Brook, Song of the, 603
Brooks, Fred Emerson, 331, 343, 345, 348, 357, 358, 385, 408,
481
Brookside, The, 579
Brotherhood, 540
Browne, J. Ross, 131, 146, 150, 245
Browning, Elizabeth, 19, 442, 539, 542
Browning, Robert, 57, 63, 64, 66, 99, 304, 305, 321, 429, 548,
627
Brother, Little, 177
Brown Wolf, 183
Bryant, William Cullen, 53
Bullets, The Song of the, 644
Bumpas, Bombardier B., 423
Bunner, Henry C., 336
Burdette, Robert, 24, 148, 157, 158
Buried Heart, The, 434
Burns, Robert, 547, 574, 617
Butterfly, To a February, 642
Byron, Lord, 536

C
Cable, George W., 204
California, 606
Camp-Meeting at Bluff Springs, 142
Camp, Pauline B., 76
Captain, O, My Captain, 171
Carleton, Will, 507
Carmichael, Sarah B., 67, 453
Carruth, W. H., 469
Cary, Alice, 334, 609
Castles, Irish, 344
Catacombs of Palermo, 146
Cavalier’s Song, The, 473
Cave, The Tiger’s, 239
Champlain, Legend of Lake, 207
Channing’s Symphony, 324
Chapman, Arthur, 587
Charge, Pickett’s, 481
Charlie Jones’s Bad Luck, 412
Cheney, Annie Elizabeth, 600, 606
Chesterfield, Lord, 27
Child, R. W., 250
Child of My Heart, 613
Child’s Almanac, A, 392
Children of the Battlefield, The, 452
Chip of the Old Block, A, 193
Christmas at Sea, 510
” in India, 634
” Present for a Lady, A, 137
Christmas Ring, The, 348
Cicely, 332
Clarence, The Dream of, 501
Clark, James Gowdy, 452, 594
Classification of Selections, 113
Clearness and Precision in Speech, 85 et seq.
Clearness of Thought, 113
Coleridge, S. T., 49
Colloquial Selections, 327 et seq.
Colum, Padraic, 616
Columbus, by Joaquin Miller, 626
” Analysis of, 105
” by A. H. Clough, 340
Combat in the Arena, A, 272
Combination Sounds, 29
Co’n Pone’s Hot, When the, 397
Conversational Style, 672
Convict, The Bishop and the, 220
Cooke, Edmund Vance, 396, 404
Coolbrith, Ina, 433, 535, 538, 604, 605, 607
Cooper, Peter, 585
Copper Sin, A Son of, 262
Cornwall, Barry, 533
Coronation, 521
Correct Speech, 12
Corson, Hiram, 97, 101