Dedication

This book is dedicated

to the sweet memories of
my parents
Sri Ananthapura Shankaranarayanayya and
Smt. Radhamma
NITTE University

(Declared as Deemed-to-be-University under section 3 of UGC Act, 1956)

Deralakatte, Mangalore-575 018
FOREWORD

I am happy to note that Dr. A.P. Krishna, Professor in the Department of

Physiology, K.S. Hegde Medical Academy has brought out this book on the
fundamentals of Physiology. This painstaking academic endeavor could not have
come at a better time for students just seeking admissions to the first year of the
MBBS course.

Physiology is a basic science subject forming part of the pre-clinical curriculum.

The functioning of the human body is a marvel of nature and its study is an
exciting journey to all, more so, the student who has just passed Pre University
and entered the portals of undergraduate learning. Dr. Krishna has made this
study easy with his presentation which is informative and yet addresses the
curriculum. The presence of diagrams, flowcharts and tables adds to the lucid
learning to the new initiate.

I commend this work and wish that Dr. Krishna adds many more books to make
this learning fruitful to the young students.

N. Vinaya Hegde
Chancellor NITTE University
PREFACE TO THE SECOND EDITION

I have written a book “Textbook of Physiology” with the intention of helping the
students of BDS, BPT, B.Sc. Nursing, BAMS, BHMS, B. Pharm. courses. The
book was well accepted and appreciated by a large group of students and
teachers. The eighth edition of the book was published in the year 2013.

After the warm response of first edition, it is a great pleasure for me to present
the revised updated second edition of Textbook of Medical Physiology. I believe
that this book may have shortcomings and mistakes. I earnestly request all the
students as well as experienced teachers to give your valuable suggestions. Your
feedback will be used for the further improvement of the book.

I place on record my sincere gratitude to Sri Nitte Vinaya Hegde, President Nitte
Education Trust and Chancellor, Nitte University for his constant
encouragement. I extend my sincere thanks to Dr. M. Shantharam Shetty, Pro.
Chancellor, Nitte University, Dr. S. Ramananda Shetty, Vice-Chancellor and Dr.
Satheesh Kumar Bhandary, Dean, K.S. Hegde Medical Academy, Mangalore for
their support and blessings.

I am grateful to colleagues in my department and many physiology teachers of

various other medical colleges. A very special thanks to my beloved students —
past, present and future.
A special appreciation to Mrs. Suman Krishna, Dr. Alka, Dr. Nikhil Joshi, Mrs.
Ankita, Mr. Santosh and Baby Vihaan

for their constant loving support. I conclude with an optimistic note that this
book will be of use for the readers. Last but not the least I am thankful to Mr.
Rajan Jain, Director of Scientific International Pvt. Ltd. and Mr. Sunil K.
Panda, Editor-cum-Coordinator for the tireless effort to bringing out the book in
a short span of time with nice get up.

1st Aug. 2014 A.P. Krishna Ph. 91-9845213997, 9480227878 E-mail:

apsnkrishna@yahoo.co.in

PREFACE TO THE FIRST EDITION

Several senior and junior teachers of physiology of many colleges motivated me
to write a textbook for MBBS students. This motivation was strongly supported
by a large number of medical students who compelled me to venture into the
task of writing a book for Medical students. This culminated in writing a
“Textbook of Medical Physiology”. I am happy to present the first edition of the
book. I believe that this book may have shortcomings and mistakes. I earnestly
request all the students as well as experienced teachers to give your valuable
suggestions. Your feedback will be used for the further improvement of the
book.

I am extremely happy to bring out this book on the year marked as Centenary
Celebration of Founder of Nitte Education Trust, Justice K.S. Hegde and on the
happy occasion of getting Deemed University status. I place on record my
sincere gratitude to Dr. Nitte Vinaya Hegde, President Nitte Education Trust and
Chancellor, Nitte University for his constant encouragement. I extend my sincere
thanks to Dr. M. Shantharam Shetty, Vice-Chancellor, Nitte University and Dr.
Arunachalam Kumar, Dean, K.S. Hegde Medical Academy, Mangalore for their
support and blessings.

I am grateful to colleagues in my department and many Physiology teachers of

various other Medical colleges. A very special thanks to my beloved students —
past, present and future.
This textbook is presented to Sri N. Vinaya Hegde, Chancellor, Nitte
University on the occasion of Centenary

Celebration of founder of Nitte Education Trust, Justice K.S. Hegde.

A word of gratitude of Mr. Nagaraja M. of Gayathri Printing Press for his role in
printing and Mrs. Suman Krishna of
M/s Suman Publications for taking the responsibility of publishing.
I conclude with an optimistic note that this book will be of use for the readers.

Mangalore 15-06-2009

Dr. A.P. Krishna

Professor
Deptt. of Physiology
K.S. Hegde Medical Academy Mangalore-18

DETAILED CONTENTS
Chapter 1 Introduction and General Physiology 1—16
Introduction to Physiology 1–6 Homeostasis—Definition, Negative and Positive
feedback mechanisms

Cell Physiology—Structure and functions of cellular organelles 6–10 Junctional

complexes
Cellular receptors, intercellular and intracellular communication

Transport across cell membrane—Active and Passive transport 11–16 Vesicular

transport process
Resting membrane potential, Action potential—Phases, Ionic basis, Properties
Osmolarity, Osmolality, Nernst equation, Gibbs-Donnan membrane equilibrium

Dehydration, Overhydration, Apoptosis 16

Chapter 2 Blood and Body Fluids 17—70

Introduction—Properties, composition and functions of blood 19–22

Plasma Proteins—Types, plasma level, functions 22–23

Red Blood Cells: Morphology, normal count, physiological variation, and

functions 23–27
Erythropoiesis: Definition, sites, hemopoietic stem cells, stages of erythropoiesis
Factors influencing erythropoiesis
Regulation of erythropoiesis—erythropoietin and other hemopoietic factors

Hemoglobin: Normal level, Physiological variations 27–30 Structure, Types,

Compounds of hemoglobin, Fate of Hb
White Blood Cells: Classification of WBC, normal values, morphology,
functions, variations 30–36 Leukopoiesis, Leukaemia

Platelet: Platelet structure, normal value, production, functions 36–42 Purpura

and Bleeding Time
Hemostasis: Major steps—Primary and Secondary, Coagulation factors
Extrinsic and intrinsic mechanisms of coagulation

Physiological mechanisms preventing intravascular coagulation—Endogenous

anticoagulant systems 43–47 Endogenous fibrinolytic systems, Intravascular
blood coagulation, Disseminated Intravascular coagulation
Anticoagulants—Types, mechanism of action and uses
Bleeding and Clotting disorders—von Willebrand disease, Hemophilia, Vitamin
K deficiency Clotting time, Bleeding time, Prothrombin time

Blood Group: Physiological basis for blood groups 47–53 The ABO system
The Rh system—Hemolytic Disease of Newborn (HDN)
Other minor blood group systems

x Contents

Blood transfusion: Indications, collection, precautions to be taken – cross

matching, screening for infections, Consequences of mismatched transfusion,
Hazards of blood transfusion, Blood bank
Significance of blood grouping, Coomb’s test

Anemia: Definition, etiological and morphological classification 53–65 Effects

of anemia on physiological systems, Signs and symptoms
Common types of anemia—Iron deficiency anemia, pernicious anemia, sickle
cell anemia,
and thalassemia—their causes and salient features
Polycythemia—Primary and secondary, physiological effects
ESR, PCV, Blood Indices, Osmotic fragility
Blood volume: Normal value, physiological variation, principles of
measurement, regulation Body Fluids and Compartments
Distribution of Total Body Water (TBW)
Principles of measurement of body fluids

Reticulo endothelial system 65–70 Odema

Immunity: Definition and types of immunity
Mechanisms (i) Cell mediated immunity (ii) Humoral immunity
Physiological basis of immunization
Autoimmune disease, AIDS, Graft rejection

Chapter 3 Cardio Vascular System 71—119

Physiological anatomy of heart 73–77 Greater and lesser circulation

Structure and properties of cardiac muscle

Functional tissues of heart—Origin and spread of cardiac impulses 77–80 Heart

block
Cardiac cycle—Definition, mechanical events during different phases of systole
and diastole 80–83 Pressure volume changes inside heart chambers and aorta

Innervation of heart 83–84

Heart Rate—Normal value, physiological variation, Regulation of heart rate 84–
87

Cardiac output—Definition, normal values, Physiological variation, factors

affecting, cardiac index, 87–89
cardiac reserve
Regulation of cardiac output
Principles of measurement of cardiac output

Electrocardiogram—Principles of electrocardiography, Normal ECG 89–91

Characteristics of waves, Einthoven’s triangle and law
Significance of ECG

Heart sounds—Causes, characteristics, significance, phonocardiogram, Murmurs

91–93

Blood Pressure—Arterial blood pressure—Definition, normal values,

physiological variations, 93–103 factors affecting
Regulation of BP, Measurement of BP
Hypertension and Hypotension

Arterial pulse, venous pulse, triple response, circulation time, apex beat, Central
venous pressure 103–107
Contents xi

Haemodynamics—Peripheral resistance, blood viscosity, laminar blood flow,

turbulent blood flow, 107–109 velocity of blood flow
Poiseuille’s Law
Microcirculation—Capillary circulation, Starling forces
Local and humoral control of blood flow—Autoregulation of blood flow and
hyperemia

Regional circulation—Coronary circulation and coronary artery disease,

pulmonary, splanchnic, 109–111 cutaneous, cerebral and foetal circulation

Circulatory shock and Syncope 112–117 Cardiac failure, Cardiopulmonary

resuscitation (CPR)
Cardio vascular changes during exercise and effect of gravity on CVS,
Echocardiography, Cardiac arrythmia

Lymphatic system: Lymph-, formation, composition, circulation and functions,

lymphatic organs, 117–119 Disorders of lymphatic obstruction

Chapter 4 Respiratory System 121—154

Functional anatomy, Functions of respiratory system—Respiratory and non

respiratory functions 123–125 Physiological anatomy
Respiratory membrane

Mechanism of breathing—Respiratory muscles and their action 125–128

Intrapleural and intrapulmonary pressure changes during respiratory cycle,
Forces acting on respiratory membrane

Pressure—Volume relationships 128–130 Compliance—chest and lungs, values,

total compliance
Surfactant, Hyaline membrane disease

Spirometry—Lung volumes and lung capacities, Normal values, significance

130–137 Vital capacity and timed vital capacity—factors affecting and
significance of vital capacity
Minute repiratory volume Maximum Voluntary Ventilation Breathing Reserve
Respiratory dead space-Anatomical and physiological—Defintion and normal
value Principle of measurement
Pulmonory ventilation and alveolar ventiliation Ventilation purfusion ratio
Airway resistance
Pulmonary gas exchange—Composition of inspired air, expired air, Partial
pressures
Factors affecting gas exchange across the respiratory membrane

Transportation of oxygen in the blood 137–140 Oxygen-Hb dissociation curve

Transportation of carbondioxide in the blood
Chloride shift, Haldane effect
Respiratory Quotient

Regulation of Respiration – Neural Regulation – Respiratory centres 141–142

Hering-Bruer’s Inflation and deflation reflexes
Chemical regulation of respiration Peripheral and central chemoreceptors 142–
145 Effect of H+ conc, PCO2 and PO2 on respiration

Hypoxia—Types and effects 145–151 Cyanosis, Asphyxia, Dyspnoea, Periodic

breathing,
Acclimitization to high altitude, mountain sickness
Dysbarism Asthma, Emphysema, Apnoea, Periodic Breathing

xii Contents

Artificial respiration—Manual methods 151–154 Holger-Neilson method and

mouth to mouth breathing
Respiratory changes during exercise

Chapter 5 Excretory System 155—182

Kidney: Functional anatomy Functions of kidney, types of nephrons 157–162

Renal blood flow and its peculiarities
Juxta Glomerular Apparatus

Mechanism of urine formation, Glomerular filtration—GFR 162–165

Mechanism, factors affecting and measurement
Tubular reabsorption—Sodium, water and glucose—Tmg and renal threshold
Tubular secretion of H+

Mechanism of concentration of urine – Counter current mechanism 165–166

Role of urea, action of ADH
Micturition—Innervation of bladder, Cystometrogram 166–170 Micturition
reflex, abnormalities of micturition
Properties and composition of normal urine 170–171 Abnormal constituents of
urine

Non excretory functions of Kidneys 171–178 Acid base balance

Regulation of plasma osmalality, ECF volume
Endocrine functions Hormones acting on kidneys

Renal Function Tests—Clearance tests 178–179 Diuresis

Applied aspects—Renal failure, Artificial kidney, Nephrotic syndrome 179–182
Skin & its Appendages—Structure and function
Chapter 6 Digestive System 183—214
Introduction, functional anatomy of gastro intestinal tract and its innervations
185–187

Secretory functions of GIT

Saliva-properties, composition 188–190 Functions and regulation of secretion
and applied aspects

Stomach- functional anatomy 190–194 Gastric juice—properties, composition,

functions, mechanisms and regulation of secretion,
Experimental evidences of gastric secretion (Sham feeding and Pavlov’s pouch)
Applied aspects—Gastritis, Peptic ulcer, Zollinger-Ellison Syndrome

Exocrine Pancreas—Pancreatic juice—properties, composition, functions and

regulation of secretion 195–196 Applied aspects—Pancreatitis

Liver—Functions of liver 196–199 Bile—composition, functions and regulation

of secretion
Functions of Gall bladder
Enterohepatic circulation—Gall stones

Contents xiii

Small intestine—Functional anatomy—Succus entericus—properties,

composition, functions and 199–201 regulation of secretion
Functions of large intestine
Applied aspects

Motor functions of GIT

Mastication, Deglutition—stages—Achalasia 201–207 Gastric emptying,
Movements of stomach, Vomiting
Small intestine—movements
Large intestine—functions and movements, Defecation
Applied aspects—Diarrhea, Constipation

Jaundice, appendicitis, Steatorrhea, Irritable bowel syndrome (IBS)

Inflammatory bowel disease 207–210 (IBD), Hirschpurng’s disease, Gastro
Esophageal Reflux Disorder (GERD)

Digestion and absorption of Carbohydrates, Proteins and Lipids 210–214

Applied aspects—Malabsoption syndrome
Dietary fibres

Chapter 7 Endocrine System 215—271

Introduction—Types of chemical messengers General properties of hormones

217–221 Classification of hormones and mechanism of action
Major endocrine glands

Anterior Pituitary—Hypothalamic control of pituitary secretion 221–227

Physiological functions of growth hormone (GH), role of somatomedians on
growth, regulation of GH secretion
Abnormalities of GH secretion—Dwarfism, gigantism, acromegaly
Functions and regulation of secretion of prolactin, TSH, ACTH, Gonadotropins

Posterior Pituitary 227–230 Antidiuretic hormone—Function and regulation of

secretion
Diabetes insipidus and SIADH
Oxytocin—Functions and regulation of secretion

Thyroid gland—Synthesis, secretion, functions and regulation of secretion of

thyroid hormones 230–237 Disorders of thyroid—Goitre, Cretinism,
Myxoedema, Grave’s disease,
Thyroid function tests, Antithyroid substances

Adrenal Cortex
Synthesis and secretion of adrenocortical hormones, Functions of the
mineralocorticoids-aldosterone 237–245 Regulation of secretion of aldosterone
Conn’s syndrome
Functions and regulation of secretion of glucocorticoids—cortisol, disorders-
Addison’s disease, Cushing’s syndrome
Adrenal androgens
Adrenogential syndrome
Adrenal medulla—Biosyntheis of catecholamines
Functions of adrenal medullary hormones Alarm reaction, Pheochromocytoma

Endocrine Pancreas—Physiological functions of insulin 246–255 Mechanism of

action—Insulin receptors
Regulation of insulin secretion
Diabetes mellitus—types and pathophysiology
Glucagon—Functions and regulation of secretion
Somatostatin—Pancreatic polypeptide
Hormonal regulation of blood glucose Hypoglycemia

Parathyroid Gland—functions and regulation of secretion of PTH 255–261

Actions of PTH on regulation of plasma calcium and phosphate concentration,
Tetany
Calcitonin—Functions and regulation of secretion
Calcium metabolism—Hormonal regulation of plasma calcium level

Other endocrine glands—Pineal gland, thymus 261–264 Local hormones—

Histamine, Serotonin, Prostaglandins, Acetyl choline, Bradykinin
GIT hormones

Growth, development and ageing 265–271

Chapter 8 Nervous System 273—357

Organization and overview of functions of Nervous system 275–277 Neuron—
Structure, classification and properties 277–278 Resting membrane potential,
Action potential, strength-duration curve
Nervefibre—Classification, conduction of impulses in myelinated &
nonmyelinated nerve fibers 279–280 Velocity of conduction of nerve impulse
Degeneration and regeneration of nervefibre, Neurotrophins 281–283 Neuroglia
—Types and functions
Sensory Receptors—Definition, Classification and Properties 283–285 Synapse
—Structure, transmission, properties, synaptic inhibition Neurotransmitters –
Definition, 285–291 types and examples
Organization of spinal cord 291–293 Reflex Action, Reflex arc, Classification of
reflexes 293–299 Properties of reflexes

Ascending Tracts—Sensory pathways—Dorsal column, lateral column 299–304

(Name of important tracts, explanation of lateral spinothalamic tract)
Anterior column
Pathway for fine touch, crude touch, pressure pain, and temperature

Physiology of Pain—Definition of pain, Pain receptors, Classification of pain

304–309 Pain pathways—fast and slow
Modulation of pain at spinal cord level
Central pain analgesic mechanisms
Referred pain, Phantom pain, Projected pain, analgesia Principles of pain
management

Descending tracts—Pyramidal and extra pyramidal pathways Origin, course,

termination and functions 309–316 Upper motor neuron lesion and lower motor
neuron lesion
Lesions of spinal cord—Complete and Hemisection of spinal cord

Gross structure and functions of—Medula and Pons 316–317

Cerebellum—Structure, connections and functions 317–322 Cerebellar disorders

Posture and equilibrium, muscle spindle and postural reflexes
Decerebrate rigidity

Contents xv
Hypothalamus—Structure, connections and functions 322–329 Thalamus—
Structure, connections and functions 329–331 Thalamic syndrome
Basal ganglia—Connections and functions 331–334 Disorders—Parkinsonism,
Wilson’s disease, Chorea
Reticular formation 334–335 Cerebral cortex, cytoarchitecture,lobes and
functions Dominant hemisphere, Disorders-Cerebral 335–340 palcy, Plegia,
Epilepsy

Limbic system, organization, connections and functions Disorders 340–342

Electroencephalogram: EEG pattern, Clinical uses of EEG 342–343

Cerebrospinal fluid, Formation, circulation, composition and functions,

Hydrocephalus-lumbar 343–346
puncture Blood Brain Barrier
Physiology of Sleep 346–350 Speech and speech disorders

Learning & Memory—Definition, types of memory 350–352 Biochemical and

physiological basis of memory
Amnesia, Alzheimer’s disease

Autonomic Nervous System , Organization and functions 352–355 Cranial

nerves 356–357

Chapter 9 Special Senses 359—384

Vision—Functional anatomy Structure of retina Rods and cones 361–363
Mechanism of formation of image—Basic optics 363

Mechanism of processing of image—Phototransduction 363–365

Refractive errors with correction
Aqueous humour, Vitreous humour, Intraoccular pressure 366

Pupillary reflexes with pathways—Light reflexes and Accommodation reflex

Argyl Robertsons 366–372 Pupil Strabismus or squint Movements of eye
Physiology of color vision and color blindness
Visual-Adaptation—light and dark, Cateract, Critical Fusion Frequency

Visual pathway with lesions at various levels, Visual acuity and Field of vision
372–375 Audition—Structure and function of external and middle ear 375–376
Structure of organ of Corti, Cochlear fluids, Cochlear potential

Mechanism of hearing, Activation of hair cell, Auditory pathway, Electrical

potentials from cochlea, 376–377 Theories of hearing
Frequency and intensity discrimination

Auditory pathway 377–379 Applied aspect: Hearing tests, Deafness, Audiometry

Vestibular apparatus: functions 379–381

Olfaction—Olfactory receptors, mechanism of stimulation, Olfactory pathway

381–384 Gustation—Modalities of taste, Taste buds
Mechanism of stimulation and taste pathway

Chapter 10 Muscle Physiology and Exercise Physiology 385—408

Muscle—Types 387–391 Comparison between skeletal, cardiac and smooth

muscles, Motor unit
Physiological anatomy of skeletal muscle, sarcomere, contractile muscle
proteins, Sarcoplasmic reticulum
Properties of skeletal muscle

Neuromuscular junction—Structure, neuromuscular transmission,

Neuromuscular blockers, 391–398 Myasthenia gravis
Excitation contraction coupling, molecular basis of muscle contraction
Experiments on properties of muscles
Chemical changes during contraction
Types of contraction—isometric and isotonic, Fast and slow muscle
Muscle dystrophy, rigor mortis

Smooth muscle—structure, types and functions, Mechanism of smooth muscle

contraction 398–399
Exercise Physiology—Isotonic and isometric exercise, gradation of exercise
400–401
Changes during exercise—Cardiovascular, respiratory, metabolic, endocrine and
nervous 401–406
Effect of training on muscular performance, health benefits of exercise 406–408

Chapter 11 Reproductive System 409—440

Introduction 411–412 Puberty—Pubertal changes in male and female

Male reproductive system—Functional anatomy 412–417 Spermatogenesis—

steps and factors influencing
Abnormal spermatogenesis, semen, Sertoli cells
Functions and regulation of secretion of testosterone
Cryptorchidism, Hypogonadism
Infertility

Female reproductive system—Functional anatomy 417–425 Oogenesis- steps

and factors influencing
Menstrual cycle—Ovarian and uterine changes
Tests for ovulation
Hormonal control of menstrual cycle
Female sex hormones, oestrogen, progesterone, relaxin

Physiology of pregnancy—Fertilization, implantation 425–432 Placenta,

hormones of placenta and functions
Pregnancy diagnostic tests
Maternal changes during pregnancy
Parturition: initiation and onset of labor
Lactation—Role of estrogen and progesterone in development of breast
Role of prolactin and oxytocin in milk ejection process
Menopause

Family planning, Physiology of contraception—Physiological basis of different

methods of 432–435
contraception in males and females
Sex determination, Sex differentiation 435–439
Chromosomal aberrations of sexual development

Question Bank 441–454

Bibliography 455
Index 457
General Physiology
Arthur C. Guyton
8-9-1919–3-4-2003
Oxford, Mississippi USA. Physiologist—Author of world’s most widely used
textbook.

Charaka
300 B.C.
Indian Physician
Known for ancient art and science of Ayurveda

Sushruta
6th Century B.C.
Indian Physician cum
Surgeon
Famous for Plastic surgery, Cataract surgery,
Rhinoplasty

William Francis Ganong Physiologist,

Endocrinologist and
Neurobiologist
 (2)

Luigi Galvani
9-09-1737–4-12-1798 Italian Physician
Known for Bioelectricity

Professor B.K. Anand 18-9-1917–2-4-2007 Indian Physiologist Known for

discovering feeding centre in
hypothalamus

Jens Christian Skou

8-10-1918
Danish Biochemist and
Doctor
Known for Sodium Potassium ATPase
Nobel Prize (1997)

Claude Bernard
12-07-1813–10-02-1878 French Physiologist Famous for the term ‘Homeostasis’

Chapter
1
INTRODUCTION AND GENERAL PHYSIOLOGY
PHYSIOLOGY
INTRODUCTION

The term “Physiology” was originally derived from a Greek

root with Latin equivalent Physiologia which means natural
knowledge. Now the term Physiology means a branch of
science dealing with the study of functions of living
organisms, as a whole or its individual parts. Physiology
deals with the study of body functions. It can be attempted
at various levels.

Cellular level or cell physiology,

Organ level,
Tissue level,
System level,
Whole body level,

Physiology aims at studying the dynamic relationship

among different organs, tissues and systems. The harmonious
functions of various organs are the basis of normal life. The
aim of physiology is to explore the sum total of functions of
these different organs and their individual actions culminating
in life.

Like in any branch of science, continuous research

activities are taking place in physiology throughout the world.
Attempts were made to understand various complex
mechanisms and their interactions. This leads to the
expansion of frontier of knowledge in physiology. This
generates the need for specialization and super specialization
of subjects. Several newer branches of physiology were
already evolved.

1. Animal physiology and comparative animal

physiology.
2. Experimental physiology.
3. Clinical physiology.
4. Psychophysiology or Behavioural physiology.
5. Neurophysiology.
6. Environmental physiology.
7. Sports physiology.
Physiology in general is the discipline that deals with the bodily functions and
their control. It is a mechanistic view of life and it tries to explain life in terms of
different physical and chemical processes. In physiology we mostly discuss
normal body functions. However, a student who later is likely to become a
member of a medical team in life deals with abnormal people – or patients.
Therefore it is quite natural to have a doubt about the need of studying normal
physiology. It is a must to know what are the normal functions and activities of a
body and parts of a body, then only one can detect any deviation from normal.
Without knowing what is normal. One cannot say what is abnormal. It is also
needed to evaluate the extent of variation, the cause for it, to decide a means of
bringing back the situation to the normalcy by a suitable treatment. By the term
normal we do not mean a single rigid figure or a fixed line. It always means a
range, for example one may say normal body temperature is 98.6°F, but it does
not mean that fixed figure. Even in a healthy person, body temperature may vary
from 97.6°F – 99.6°F. This type of variation is physiological variation. Body has
a built-in mechanism to bring back the deviated condition to the normal state. It
is a complex feed back control mechanism which maintains a constant internal
environment. Maintenance of a constant internal environment is termed as
milieu interieur in French Later Walter Cannon coined by Claude Bernard.
Human body is a mass of living cells. These cells are bathed in extracellular
fluid ECF and these cells are filled with intracellular fluid ICF. The composition,
volume osmolality, pH, and temperature of ICF and ECF are kept constant,
inspite of changes in the environmental factors. There are factors which try to
destabilize it. As long as body is able to maintain its constant internal
environment, there is no disease and there is no need of any treatment. The
moment this mechanism fails, external intervention is needed in terms of
treatment – physical, chemical or surgical.
Hormone
Gland Target tissue Inhibition

with a mechanism to correct the variable. The elevation in body temperature can
be detected by thermoreceptors present in the body, they send this information to
hypothalamus. Hypothalamus in turn initiates corrective steps so that the
increased body temperature is brought down to normal. Corrective measures
may include sweating, vasodilatation etc. As long as this homeostatic control
mechanism is functional no disease or disorder. If it fails it will result in
dysfunction.
Product —Negative feedback mechanism

Hormone Internal stimuli Homeostasis

Normal state

Constant physiological and biochemical state External stimuli

Gland Target tissue Disturbance or upset in balance
+
Product

—Positive feedback mechanism Alteration in

physiological & biochemical variables

Fig. 1.1
Feedback mechanism
Homeostasis regulatory mechanisms

Homeostasis is the stability of the internal environment. But there are various
environmental and physiological parameters that influence the destabilization of
the constancy of internal body environment. Imbalance in the constant internal
environment may lead to some organ or system dysfunction. Therefore, in our
body there are various controlling mechanisms which tend to maintain the
homeostatic state of the body. Among that negative and positive feedback
mechanisms play prominent role.

Homeostasis

It is very important to know how the homeostasis of various physiological and

biochemical variables is achieved. It is also required to understand how the
disturbances in these homeostatic regulations may result in various dysfunctions
and disorders. Once this fundamental mechanisms are understood it will be
easier to interfere and manipulate the variables so that homeostasis is brought
back to the normal. That is the guiding principle of treatment of a disease or
disorder.

Usually homeostatic regulatory mechanism has got two components. First one to
detect the deviation in the physiological variables. Secondly to correct the
variables, so that normally is restored. For example, when body temperature
increases beyond the normal level, normal level is commonly referred as set
point, there should be a mechanism to detect the change in the variable followed
Change in variables is detected by receptors

Response by organ or Organs

Altered variable is brought back to normal state

If fails Homeostasis reestablished Leads to disease or disorder

Needs treatment that is external

support to restore normally

Fig. 1.2

Positive feedback: This feedback mechanism is known to exaggerate the rate of

process or reactions. Therefore, this control mechanism does not operate to
provide homeostasis.

For example, during the process of child birth (delivery), the head of fetus
presses the cervix, this stimulus distend the cervix, which in turn send the
feedback to the posterior lobe of pituitary gland, after analyzing the signals
pituitary gland releases the hormone oxytocin, which increases the force of
uterine muscle contraction this helps to further pushing of the fetus towards
cervix, this cycle increases the secretion and release of more and more oxytocin
till the fetus is delivered.
In positive feedback mechanism the stimulus and the response or the cause and
the effect are operating in the same direction. In such mechanisms an increase in
a particular physiological variable respond which further increases the variable.
This type of control mechanism do not operate to provide homeostasis classical
example. During irreversible stage of haemorhagic shock. Cardiac output has
diminished to a very low level. Coronary blood flow falls— oxygen supply to
cardiac muscles decreases. This will further decrease the force of contraction of
heart, decrease stoke volume, further decrease cardiac and put—go on and on
leading to death.

Some other examples for positive feedback mechanism. 1. Luteinizing hormone

secretion: During preovulatory phase oestrogen stimulates this secretion of LH
from anterior pituitary

2. Action of trypsin: Once a small quantity of trypsin is formed from trypsinogen

in the small intestine, all remaining inactive enzymes are activated

3. Activation of blood clotting factors one after the other.

Negative feedback: This feedback mechanism is known to slow down the rate
of process or reactions. Therefore, homeostatic regulation is generally achieved
through negative feedback mechanism.
For example: If particular hormone concentration in blood increased beyond the
normal level, this immediately send the negative signals to that specific
endocrine gland to cease the further secretion of that hormone so as to maintain
the normal hormonal level in the blood. This mechanism also called as
corrective mechanism because it initiates the action which directly opposes a
variation from normal limits.
Another example for negative feedback mechanism is restoration of body fluid
volume. Suppose a person plays outdoor game under hot sun. He will be losing
water leadsing to dehydration. This will increase the osmotic concentration of
blood. Elevation of osmotic concentration will stimulate the osmo receptors of
hypothalamus. This will produce the sense of thirst. Thirst leads to water intake.
Absorption of water from the intestine to blood restores the fluid. Increase in the
osmotic concentration of blood is the stimulus. Drinking of fluid is the response.
Response nullifies the stimulus. This is a negative feedback mechanism.
The secretion of most of the hormones are controlled by negative feedback
mechanism.
For example hypothalamus secretes a small peptide— Thyrotropin Releasing
Factor, TRF. This will stimulate the anterior pituitary to secrete more of thyroid
stimulating hormone TSH. TSH in-turn stimulate and increase the secretion of
thyroxin from thyroid gland. Increase in the plasma concentration of thyroxin
will in-turn exhibit inhibition at the level of hypothalamus and anterior pituitary.
Because of this secretion of all the hormones in this hypothalamo-hypophyseal-
thyroid axis are inhibited.
Hypothalamus
– TRF
Anterior pituitary
–
TSH
+ Thyroid gland
Thyroxine
Fig. 1.3

The common approach of studying Physiology is system wise. System is a group

of organs and structures concerned with a common body functions.

1. Circulatory system or Cardiovascular system

2. Respiratory system
3. Excretory system
4. Digestive system
5. Endocrine system
6. Nervous system
7. Special senses
8. Musculo-skeletal system
9. Reproductive system
Each system is composed of a set of inter connected and interdependent organs
which act together for a common purpose, which is not possible by any one of
them alone. However, it should be remembered that any system can perform
their designated duties only with harmonious coexistence with other systems but
cannot do anything in isolation.

An organ, e.g., heart, is a structural unit of the body. An organ is composed of

different tissues and serves a specific function. Tissues are a group of similarly
specialized cells which together perform a certain specific function. Basically
there are four types of tissues—Muscular, Neural, Epithelial and Connective
tissue. Tissues are made of cells and function of tissues is function of cells.

GENERAL PHYSIOLOGY
Body is made of several individual systems. Human physiology is studied by
dealing with the study of one system after another. All these systems function on
the basis of some fundamental physical and chemical principles and processes
which are common to all of them. General physiology includes these
fundamental principles which help to understand the activities of individual
systems.

Cell Physiology
A typical cell, Cell membrane, Cell organelles.

Membrane transports: Diffusion, Osmosis, Active and Passive transport,

Endocytosis, Exocytosis, Phagocytosis.

Membrane potentials
Resting membrane potential, Action potential, properties, Phases, Ionic basis.
Osmolarity, Osmolality, Nernst equation, Equilibrium, GibbsDonnan membrane.
Apoptosis, dehydration derhydration.

Cell Physiology

Cell is the basic structural and functional unit of the body. This concept was first
proposed by Schleiden and Schwann. Living organism is a society of cells. At
birth number of cells is about 2 × 1012 and in adult number of cells is about 6 ×
1013.

Major types of cells are nerve cell, muscle cell, red blood cell, gland cell and
immune cell.
Cell is composed of cell membrane surrounding the protoplasm cell.
Cell = Cell membrane plus protoplasm. Protoplasm = Cytoplasm plus nucleus.
A typical cell:
Cell membrane: It is a thin, elastic semipermeable membrane, enveloping the
cell. It separates extracellular fluid from intracellular fluid. It is also called
plasma membrane. It has a thickness of 7.5–10 nm.

Compostion:
- Lipid bilayer.
- Protein (intrinsic, and extrinsic and transmembrane).
- Carbohydrates [5%].
Smooth endoplasmic reticulum
Centrioles Ribosomes

Mitochondrion Smooth
endoplasmic reticulum

Lysosome

Rough endoplasmic reticulum

Nuclear membrance Nucleus Nucleolus

Fig. 1.4
Normal cell structure
Extrinsic Extracellular fluidproteins Carbohydrate Golgi
apparatus
Microvilli
Hydrophilic head
Transmembranous Intrinsic protein

Cytosol Phospholipid bilayer

Fig. 1.5 Plasma membrane

Hydrophobic tail
Lipid Bilayer

The two major lipids are phospholipids and cholesterol. The lipid layer is fluid in
nature, floats and substances dissolved in it also floats along with it.

Lipid bilayer is amphipathic layer

Phospholipid molecule is composed of polar hydrophilic head and non-polar,
hydrophobic, hydrocarbon tail end. The tail ends of two layers are facing each
other at centre.
Functions:

1. Contributes to semi-permeability and selective permeability nature of cell

membrane.
It is permeable to fat soluble substances like oxygen, carbon dioxide etc.
It is impermeable to water soluble substances like glucose, urea, ion etc.

2. Cholesterol: It gives structural stability to cell membrane.

Carbohydrate layer: Carbohydrates are found in combination with lipid or

protein and hence called glycolipids or glycoproteins respectively. It is called
Glycocalyx.
Carbohydrates may be also present in the form of proteoglycans.

Functions:
1. It forms connection for adjacent cells and links adjacent cells together by
membrane junctions. 2. This layer is negatively charged. Hence repels

negatively charged substances.

3. They form receptors for binding of some hormones.
4. They take part in immunological reactions.
5. Carbohydrate present on RBC membrane help to form blood group antigen.

Protein layer
Intrinsic—attached to inner surface of membrane. Extrinic—present at outer
surface.
Transmembrane—extends from outside to inside. Functions:

1. They consist of protein channels for the permeability of ions and water soluble
substances.
2. Help in transmission of impulses.
3. Provide structural integrity to cell.
4. Some proteins function as enzymes.
5. Some proteins form receptors for hormone.
6. Some proteins act as carriers for the transportation of substances from one
side to other side.

Overall Functions of Cell Membrane

1. Forms protective covering of cell.

2. Shows selective permeability and semipermeability. Detect chemical

messengers arriving at the cell surface.

3. Determines the shape and size of cell.

4. Helps in generation and maintenance of transmembrane potential.
5. Facilitates in exchange of gases.
6. Also help in transport of macromolecules (pinocytosis and phagocytosis).
7. Absorption of nutrients and excretion of metabolic wastes.
8. Regulate the passage of substances into and out of the cells.
The plasma membrane is not solid but fluid structure. The proteins embedded in
it gives it the mosaic appearance and hence this model of cell membrane is
called Fluid mosaic model. (Singer and Nicolson 1972)
Cytoplasm is the fluid present inside cell.
Cytoplasm consists of:
1. Cell organelles
2. Chemical contents
(a) Water — 70–85%
(b) Protein — 10–20%
(c) Carbohydrate 6%
(d) Fats — 2–4%
(e) Electrolytes — small amounts. e.g., K+, sulphates which help in maintaining
membrane potential across the cell.

1. Mitochondria

It is called power house of cell.

Shape : The mitochondria is rod shaped or oval. Size : Size varies from 0.2–0.5
micron. Number : It varies. A single cell of liver may have

as many as 2,500 mitochondria

Structure : Double layered membrane. Inner layer has folds called cristae which
increase surface area for enzymatic reaction.

– The stalked particles attached to mitochondria are called Racker’s particles.

– Matrix contain RNA and mitochondrial DNA Functions:
– It plays a very important role in cellular respiration and generation of energy as
ATP.
– Various metabolic reactions take place in mitochondria, e.g., Krebs cycle, Urea
cycle.

2. Endoplasmic reticulum (ER)

It is the extensive network of interconnected sacs or tubes

found in cytoplasm of majority of Eukaryotes. It is lined by a single layered unit

membrane.
Endoplasmic reticulum of muscle cells is called Sarcoplasmic reticulum.
Classification: There are two types based on presence or absence of ribosomes
attached to their surface.
Outer
membrane Inner membrance Cristae Ribosomes Secretary vesicles
Cisternae
Mitochondrion
Golgi body
DNA Matrix
Nucleolus Ribosome
Small subunit Nucleo plasm Nucleo pores Nucleus
Large subunit Ribosome Rough endoplasmic reticulum
Fig. 1.6
Cell organelles

1. Rough endoplasmic reticulum (RER) Ribosomes are attached to their

surface and thus makes the surface rough.
– Since ribosomes are present the major function

is biosynthesis of protein.
2. Smooth endoplasmic reticulum
Ribosomes are absent—Cholesterol synthesis takes place here.

Functions of endoplasmic reticulum

1. Biosynthesis of protein (RER).
2. Synthesis of cholesterol and other steroids (SER).
3. The tubular space within the ER functions as a intracellular transport system
for ions within the cell.
4. It provides site for storage of product.
5. It functions as cytoskeleton.

3. Golgi body
It consists of a few flattened sacs and tubes placed one over other. Flattened sac
is called Cisternae.

Functions: 1. Processing of protein synthesized by ribosomes and

ER. It modifies and packs the protein.

2. It later give rise to acrosome in male germ cells.
3. It give rise to lysosomes.

4. Lysosomes

They are called suicide bags of cell. They are vesicle—like organells present
through out the cell. They arises from the Golgi body. They contain digestive
enzymes called hydrolases.
Functions:
– Digestion of nutrients intracellularly
– Destruction of bacteria and other foreign body. Thus

protects the cell.

– Digestion and removal of old, worn out and dead
cells of the tissue (Auto digestion).

5. Ribosomes
Ribosomes are called protein factory of cells. There are two types:
1. Bound ribosomes (attached to RER) and 2. Free ribosomes.

Ribosomes size: It is expressed in Svedberg unit. It is 70S for prokaryotes and

80S for eukaryotes. Each 80S ribosome is made up of two subunits of 40S

and 60S.
Function: It plays a very important role in translation process of protein
synthesis

6. Centrioles
They are two cylindrical rods which appear during cell division.
Functions: It helps in the formation of spindle fibres and direct the
chromosomes during cell division.
7. Cytoskeleton
Plays a very important role in maintaining the structure and shape of the cell.

It is a complex set of rods that act as supporting structure

They are of two types 1. Microfilament 2. Microtubules.

Microtubules: Made up of protein called tubulin. Functions:

1. Formation of spindle fibre.
2. Structural stability to cells.
3. Intracellular transport of ions.

Microfilament: Made up of action and myosin filament. These are contractile

proteins and plays a very important role in muscle contraction.

8. Nucleus
It is the master of cell organelles. The nucleus is spherical and situated at the
centre of the cell.
Nuclear membranes: Double layered membrane with pores called nucleopores.

Exchange of materials between nucleus and cytoplasm occur through these

pores.

Nucleoplasm
It is the ground substance of nucleus. It is called karyolymph or nuclear sap. It
contains enzymes and other substances required for synthesis of RNA and DNA.

DNA: It is the genetic material which contain stored hereditary information.

RNA and DNA are together responsible for protein synthesis.
DNA contains information for the protein to be synthesized and hence direct the
protein synthesis and RNA regulates the synthesis of protein.

Nucleoli
It is darkly stained structure within the nucleus. It is the site for synthesis of
ribosomes.
Cell junctions
In between the adjacent, epithelial cells there is usually an association, this is
known as a junction. The junctions between the two adjacent cells can be of
several types such as:
Gap junction

The membranes of adjacent cells lie very close to each other, and this gap is
filled with densely packed particles through each of which are connected by a
sort of channel. It permits movements of molecule from one cell to another cell.
Gap junctions mainly found in cardiac and smooth muscles which facilitate rapid
propagation of electrical changes from one cell to another cell.
Gap junction

Fig. 1.7
Gap junction
Desmosome

In between the two membranes of the adjacent cells, there is small gap; this gap
is filled with accumulation of dense proteins and the fibers extending from the
each membrane. This type of junctions mainly present in skin, which is regularly
subjected for tensile stress (physical stretching).
Extra cellular space
Cell membrance

Fig. 1.8
Desmosome
Tight junctions

The cell membranes of the adjacent cells are fused together. This type of the
junctions acts as a barrier and prevents the movements of ions or molecules from
one cell side to the other cell. Tight junctions mainly present at choroid plexus,
intestinal mucosal layer and renal tubules.
Tight Proteinjunction
ridges

Fig. 1.9
Tight junction Cellular receptors

Cells receive information from outer environment through a class of proteins

known as receptors. Notch is a cell surface protein that functions as a receptor.
Animals have a small set of genes that code for signaling proteins that interact
specifically with Notch receptors and stimulate a response in cells that express
Notch on their surface. Molecules that activate or in some cases, inhibit these
receptors can be classified as hormones, neurotransmitters, cytokines, growth
factors but all of these are called receptor ligands. The details of ligand-receptor
interactions are fundamental to cell signaling.

Other signaling molecules are unable to permeate the hydrophobic cell

membrane due to their hydrophilic nature, so their target receptor is expressed on
the membrane. When such signaling molecule activates its receptor, the signal is
carried into the cell usually by means of a second messenger such as cAMP.

Cell signaling

Cell signaling is part of a complex system of communication that governs basic

cellular activities and coordinates cell actions. The ability of cells to perceive
and correctly respond to their microenvironment is the basis of development,
tissue repair, and immunity as well as normal tissue homeostasis. Errors in
cellular information processing are responsible for diseases such as cancer,
autoimmunity, and diabetes.
Intercellular communications

Cells communicate with each other via direct contact known as juxtacrine
signaling, over short distances called as paracrine signaling, or over large
distances and/or scales termed as endocrine signaling.

Some cell-to-cell communication requires direct cellcell contact. Some cells can
form gap junctions that connect their cytoplasm to the cytoplasm of adjacent
cells. In cardiac muscle, gap junctions between adjacent cells allows for action
potential propagation from the cardiac pacemaker region of the heart to spread
and coordinately cause contraction of the heart. Many cell signals are carried by
molecules that are released by one cell and move to make contact with another
cell. Endocrine signals are called hormones. Hormones are produced by
endocrine cells and they travel through the blood to reach all parts of the body.
Specificity of signaling can be controlled if only some cells can respond to a
particular hormone. Paracrine signals target only cells in the vicinity of the
emitting cell. Neurotransmitters represent an example. Some signaling molecules
can function as both a hormone and a neurotransmitter.

Intracellular communications

Receptor activation caused by ligand binding to a receptor is directly coupled to

the cell’s response to the ligand. The entire set of cell changes induced by
receptor activation is called a signal transduction mechanism or pathway. A more
complex signal transduction pathway involves changes of protein-protein
interactions inside the cell, induced by an external signal. Many growth factors
bind to receptors at the cell surface and stimulate cells to progress through the
cell cycle and divide. Several of these receptors are kinases that start to
phosphorylate themselves and other proteins when binding to a ligand. This
phosphorylation can generate a binding site for a different protein and thus
induce protein-protein interaction.

Other signaling molecules are unable to permeate the hydrophobic cell

membrane due to their hydrophilic nature, so their target receptor is expressed on
the membrane. When such signaling molecule activates its receptor, the signal is
carried into the cell usually by means of a second messenger such as cAMP.
Signal transduction pathways provide opportunities for feedback, signal
amplification, and interactions inside one cell.
TABLE 1.1
Different Transport Mechanism
Passive transport Active transport Transport of macromolecules
Diffusion Osmosis Primary Secondary
Pinocytosis Phagocytosis
Simple Facilitated diffusion diffusion Sodium Sodium counter cotransport
transport
Membrane Transport
Membrane
The major types of mechanisms for transport across the cell membrane are:

1. Passive transport—which requires no energy.

2. Active transport—requires energy.
3. Macromolecular transport.
Passive transport may be in the form of diffusion or osmosis.
Diffusion: Movement of solute particles from a region of higher solute
concentration to a region of lower solute concentration along the concentration
gradient due to the

Brownian movement of molecules. It is down hill movement and does not

require energy. Diffusion is of two types:

(a) Simple
(b) Facilitated.
Simple diffusion is without the involvement of any

carrier proteins, by random movement of particles through lipid layer or protein

channels [membrane pores or gaps].

Facilitated diffusion: Substance binds with a carrier protein and conformational

changes occur in that protein molecule and then the substance will diffuse.
Plasma Cytoplasm
Carrier
D-glucose
Sugar / carrier complex

Fig. 1.10 Facilitated diffusion

Simple diffusion through lipid layer

Fat soluble substances (like O2, CO2) diffuse through the lipid layer.

Factors determining diffusion

1. Permeability: Which inturn, depends on (a) Thickness—more thick
membrane less diffusion.

(b) Cross sectional area—directly proportional. (c) Presence of protein channels.

(d) Molecular weight of substance to be diffused

—More the molecular weight more will be the resistance for its movement and
hence less permeability.

(e) Diffusion coefficient (expression for permeability) D = permeability × area

of cross section.

(f) Temperature—Increase in temperature increases the thermal motion of the

molecules and hence increases the permeability.

(g) Solubility—Fat soluble substance can be easily diffused.

2. Concentration gradient
More the concentration, gradient more is the diffusion.
Other types of gradient are pressure gradient and electrochemical gradient.

3. Ionic charge: Increase in negativity decreases the permeability and hence

decreases the rate of diffusion. It is true for positivity too.
dcFick’s law J = −DA dx

J = rate of diffusion
A = area of cross section
X = thickness
D = diffusion coefficient
C = concentration

Diffusion through protein channels

Membrane protein provides aqueous pathways for different ions.

They are of two types:

1. Leak channels 2. Gated channels
Leak channels are always open and diffusion through them cannot be
controlled. e.g., K+ leak channels.
Gated channels: They open and close when required and diffusion through
them can be controlled. They are:
1. Voltage gated channels [influenced by change in voltage]
2. Ligand gated channels [influenced by hormones]
3. Mechanically gated channels.
Factors affecting are: 1. Molecular weight 2. Rate of kinetic movement of
substance.
Facilitated diffusion (for water soluble substances and substances with larger
molecular weight), it is also called carrier mediated diffusion.
Example: Transport of glucose and other monosaccharides and amino acids in
proximal convoluted tubules.

Properties:

1. Carrier proteins with binding sites are specific for transport of a particular
substance.
2. Saturation: Rate of diffusion increases with increase in solute concentration
upto a certain extent after which it shows saturation.
3. Inhibition (competitively)
Osmosis—Definition: Movement of water and other solvent molecules from a
region of lower solute concentration to a region of higher solute concentration
across a semipermeable membrane.
Or, Movement of water or other solvent molecules from a region of higher
solvent concentration to a region of lower solvent concentration across a
semipermeable membrane. In the cell plasma membrane act as semipermeable
membrane for osmosis.
Osmotic pressure: It is the hydrostatic pressure required to stop osmosis from
one compartment to another. It is directly proportional to number of solute and
inversely proportional to volume of solvent. It is also influenced by the
temperature.
Solvent drag: During bulk flow of solvent it carries along with it some solutes
(ions) passively and this is called solvent drag.

TABLE 1.2
Comparison between diffusion and osmosis
S.No. Diffusion Osmosis
1. Movement of ions or particles from a region of higher Movement of solvent
particles from its region of higher concentration to a region of lower
concentration. concentration to the region of lower concentration through a
semipermeable membrane. It is diffusion through semipermeable membrane.

2. It can be facilitated by using a carrier (Carrier– mediated). It cannot be

facilitated.
3. It can be stopped only by separating the two media when It can be stopped by
applying a suitable pressure (osmotic the gradient is present. pressure).

4. Concentration difference, or electric potential difference Concentration

difference for solvent across a membrane or pressure difference are mainly
responsible for impermeable to solute is responsible for osmosis. diffusion.

Active transport
Movement of solute particles from a region of higher

concentration to a region of lower concentration is called active transport.

It requires energy expenditure. Energy is supplied by break down of ATP. It

occurs against concentration gradient and hence called uphill movement. It
requires carrier protein.

Two types: 1. Primary active transport

2. Secondary active transport Primary active transport

In primary active transport the transport occurs by the direct utilisation of energy
(hydrolysis of ATP and other high energy bonds).

Example: Sodium Potassium ATPase pump.

The carrier protein of Sodium Potassium ATPase pump has six binding sites,
three for sodium, two for potassium and one for ATPase which breaks down the
ATP.

Transfer of three sodium ions occur in exchange for two potassium ions with
expenditure of energy. Sodium moves from inside of the cell to outside and
potassium moves in.

This is responsible for generation and maintenance of membrane potential and

hence this pump is called Electrogenic pump.

Mechanism of transport
The substance (molecule or ion) to be transported first attaches itself or binds to
the carrier protein which activates ATPase and ATP is hydrolysed.

This causes conformational changes in the protein molecule and outer surface of
the protein faces inside and inner surface faces outside and the substance is
liberated.

Secondary active transport: Also called exchange transport.

Transport of molecules or ions in opposite direction with the help of carrier
protein with the utilisation of energy.
Example: 1. HCO− and Cl− counter transport3

2. Na+ and H+ counter transport Co-transport of ions can also exist in similar
manner e.g., Na+ and glucose co-transport.
Transport protein ADP ATP
Extracellular Pifluid
Pi
Membrane
Intracellular fluid
Transported solute
Fig. 1.11 Primary active transport
Extracellular fluid
High Na+ Low glucose Intercellular fluid
Low Na+ High
glucose Extracellular fluid
High Na+ Low glucose Intercellular fluid
Low Na+ Low H+
Co-transport Counter transport Fig. 1.12 Carrier mediated transport
TABLE 1.3
Comparison between active and passive transport
S.No. Active transport Passive transport 1. Transport is against concentration
gradient. Transport is along the concentration gradient. 2. Incurs expenditure of
energy. Energy is not required. 3. Shows saturation.
4. Specificity: Specific for particular molecules.

5. Shows competitive inhibition. Related molecules can inhibit transport of

another molecule by this process. No saturation. The process continues till an
equilibrium is obtained except in facilitated diffusion.

No such specificity.
No such competitive inhibition is seen.
Transport of macromolecules Endocytosis and exocytosis are two types of
mechanism for transport of macromolecules.
Extracellular fluid Solid material
Plasma membrane Phagosome Liquid
material Plasma membrane Pinosome
Plasma membrane
Cytoplasm Cytoplasm Cytoplasm
A. Phagocytosis
Fig. 1.13
Transport of macromolecules
B. Pinocytosis

Endocytosis (into the cell) is of two types:

1. Pinocytosis—Cell drinking
2. Phagocytosis—Cell eating
Pinocytosis: The macromolecule to be transported binds to receptors on the cell
membrane. The membrane then dips or invaginates. The membrane finally
covers it. The substance is now enclosed by a part of membrane as a bubble. It is
called pinocytic vesicle which breaks off from cell membrane and later acted
upon by lysosomes. Phagocytosis: It occurs in the same way as pinocytosis. The
bubble is called phagocytic vesicle. The process is seen in protozoans (e.g.,
amoeba) and lower metazoans (e.g., sponges). In man such a process is used by
white blood cells (WBCs) and connective tissue called phagocytes. Exocytosis:
By this process the intracellular substances are released into the surrounding
tissue. Example—is the release of neurotransmitters (which is stored as secretory
granules in vesicles) from nerve endings.
The molecule binds to the inner surface of plasma membrane. At this place the
cell membrane evaginates forming vesicle which is later pinched off.

+30 Spike potential

+20 Overshoot
+10

0
–10
–20

–30
–40
–50 Firing
–55 level
–60 Point of
stimulus

–70
After deporisation

Latent After
period hyperpolarisation
Time (ms)
Absolute refractory Reflectiveperiod refractory period

Fig. 1.14
Action potential

It is a property shown by nerves and muscles. Excitability is defined as ability to

respond to a stimulus by way of generating an action potential. Stimulus means a
change in the energy level. Resting membrane potential (RMP) is defined as the
potential difference or voltage difference existing between inside and outside of
a nerve membrane when it is at rest. Normal RMP is –70 mv to
–90 mv. RMP is due to unequal distribution of ions between inside and outside
nerve membrane. There is more sodium ions and chloride ions outside the nerve
membrane whereas K+ and negatively charged protein ions are more inside the
membrane. This unequal distribution of ions are due to the following reasons:

1. Operation of sodium potassium pump—It is an active transport mechanism. It

involves carrier proteins and requires energy expenditure.

2. Permeability of membrane to potassium ions is greater than sodium ions.

3. Presence of net negatively charged non-diffusable protein ions inside the
membrane.
When the nerve is stimulated the permeability of membrane changes. It becomes
more permeable to sodium ions. Na+ rush from outside to inside of membrane.
This is known as sodium influx. Entry of positively charged ions make the inside
of the membrane more and more positive, less and less negative. The polarity is
lost. This phase is depolarisation. For a fraction of a second the inner side of the
membrane becomes positive (+30 mv.) But once again polarity is reestablished.
This phase is known as repolarisation. Action potential is defined as a changing
potential taking place across the membrane with depolarisation followed with
repolarisation spreading along the length of nerve membrane.
One osmol is the osmotic pressure exerted by one molar solution.
Osmolarity—Number of osmoles per liter of solution. Osmolality—Number of
osmoles per kilogram of solvent.
Osmolarity is important for regulation of cell volume. If a cell is surrounded by a
solution the osmolarity of which is lower than that of the intracellular fluid
(hypotonic solution) water enters the cell. Swelling it up and sometimes
rupturing it. On the other hand, if the cell is surrounded by a hypertonic solution.
Water leaves the cell making it shrunken. Therefore the cell should always be
surrounded by an interstitial fluid the osmolarity of which is the same as that of
the intracellular fluid (isotonic solution). The homeostatic mechanisms for
regulation of body fluid volume and osmolarity are coupled.
Relationship between osmolarity and osmotic pressure. At 37°C, 1
milliosmole/L. Hence their osmotic pressure = 300 × 19.3 = 5790 mmHg.
However, the actual osmotic pressure is about 6% less. i.e., about 5500 mmHg.
The reason for the discrepancy is that many oppositely charged ions, e.g.,
sodium and chloride ions, attract each other. Therefore a sodium chloride
molecule actually exerts slightly less than double the osmotic pressure exerted
by one molecule of an unionised molecule.

Nernst equation

One useful application of the Nernst equation is determining ion concentration.

If you know the concentrations of all but one species and the voltage, you can
get the concentration of the final species. This is how pH meters work: the
unknown concentration is (H+), and they simply measure the voltage in the cell.

The Nernst equation isIF

E = E0 –

RTJ ln (Q)H
nFK

The reaction quotient Q has the form and value PH2*Fe+2

Q =+ 2H
+ 2 Where, if the temperature of the reaction at 25oC, the
Q = 10500 H

term RT/F is 0.0257 V.F I bgGRTJ lnE = E0 −

HF
nFK I F05 I
0.389 = 0.409 – G0 0257J*lnG[H+]2J F

H2
05

K
I HK
1.556 = lnG[H ]+ 2J
HK
054.74 =[H+]2
[H+] = 0.325 M Gibbs-Donnan Equilibrium

The Gibbs–Donnan equilibrium is a phenomenon of solutions that contributes to

the formation of an electrical potential across a cell membrane. The Gibbs-
Donnan equilibrium (Donnan effect) is a name for the behavior of charged
particles near a semi-permeable membrane to sometimes fail to distribute evenly
across the two sides of the membrane. The usual cause is the presence of a
different charged substance that is unable to pass through the membrane and thus
creates an uneven electrical charge. For example, the large anionic proteins in
blood plasma are not permeable to capillary walls. Because small cations are
attracted, but are not bound to the proteins, small anions will cross capillary
walls more readily than small cations.

Dehydration
Dehydration occurs when the amount of water leaving the body is greater than
the amount being taken in. The body is very dynamic and always changing. This
is especially true with water in the body. The body is able to monitor the amount
of fluid it needs to function. The thirst mechanism signals the body to drink
water when the body is dry. As well, hormones like anti-diuretic hormone
(ADH) work with the kidney to limit the amount of water lost in the urine when
the body needs to conserve water.

Effects may include headaches similar to what is experienced during a hangover,

muscle cramps, a sudden episode of visual snow, decreased blood pressure
(hypotension), and dizziness or fainting when standing up due to orthostatic
hypotension. Untreated dehydration generally results in delirium,
unconsciousness, swelling of the tongue and in extreme cases death.
Dehydration symptoms generally become noticeable after 2% of one’s normal
water volume has been lost. Initially, one experiences thirst and discomfort,
possibly along with loss of appetite and dry skin. This can be followed by
constipation. Athletes may suffer a loss of performance of up to 30% and
experience flushing, low endurance, rapid heart rates, elevated body
temperatures, and rapid onset of fatigue.

Symptoms of mild dehydration include thirst, decreased urine volume,

abnormally dark urine, unexplained tiredness, irritability, lack of tears when
crying, headache, dry mouth, dizziness when standing due to orthostatic
hypotension, and in some cases can cause insomnia. In moderate to severe
dehydration, there may be no urine output at all. Other symptoms in these states
include lethargy or extreme sleepiness, seizures, sunken fontanel (soft spot) in
infants, fainting, and sunken eyes.

Overhydration
Overhydration occurs when the body takes in more water than it loses.
Overhydration can occur, for example, when athletes drink excessive amounts of
water or sports drinks to avoid dehydration, or when people drink much more
water than their body needs because of a psychiatric disorder called psychogenic
polydipsia. The result is too much water and not enough sodium.

Apoptosis

Apoptosis is a process of programmed cell death in which body cells die and get
absorbed. Sometimes it is called as cell suicide.

Apoptosis, or programmed cell death, is a normal component of the development

and health of multicellular organisms. Cells die in response to a variety of
stimuli and during apoptosis they do so in a controlled, regulated fashion. This
makes apoptosis distinct from another form of cell death called necrosis in which
uncontrolled cell death leads to lysis of cells, inflammatory responses and,
potentially, to serious health problems. Apoptosis, by contrast, is a process in
which cells play an active role in their own death that’s why apoptosis is often
referred to as cell suicide.
Upon receiving specific signals instructing the cells to undergo apoptosis a
number of distinctive changes occur in the cell. A family of proteins known as
caspases is typically activated in the early stages of apoptosis. These proteins
breakdown or cleave key cellular components that are required for normal
cellular function including structural proteins in the cytoskeleton and nuclear
proteins such as DNA repair enzymes. The caspases can also activate other
degradative enzymes such as DNases, which begin to cleave the DNA in the
nucleus.

Apoptosis is a natural phenomenon which plays an important role during

embryonal development such as degeneration of many tissues like web in the
fingers, death of neurons during brain development. Also in adulthood, apoptosis
responsible for shedding of villi of small intestine and in female it helps in
cyclical shedding of endometrium during the time of menstruation. Uncontrolled
apoptosis may lead to number of degenerative diseases and cancers.
Blood
Karl Landsteiner
14-06-1868–26-6-1943 Austrian Biologist & Physician
Discovered ABO and Rh Blood group
Nobel Prize (1930)

Erik Adolf Von Willebrand 01-02-1870–12-09-1949 Finland Medical Doctor

Famous for his study of blood clotting disorders Von Willebrand disease

Metnikoff
16-5-1845–15-7-1916 Russian microbiologist Famous for immune system-
phagocytosis Noble Prize (1908)
 (18)

Paul Oskar Morawitz

03-04-1879–01-07-1936 Famous for Study of blood coagulation, clotting
factors, blood transfusion without the benefit of blood typing

Robert Gwyn Macfarlane 26-06-1909–26-3-1987 British Physician

Famous for the study of Blood Clotting cascade and haemophilia

Paul Ehrlich
14-03-1854–20-08-1915 German Immunologist Famous for Autoimmunity
Nobel Prize (1908)

Chapter
2
BLOOD AND BODY FLUIDS

Introduction—Properties, composition and functions of blood.

Plasma Proteins—Types, plasma level, functions. Red Blood Cells:
Morphology, normal count, physiological variation, and functions.
Erythropoiesis: Definition, sites, hemopoietic stem cells, stages of
erythropoiesis.
Factors influencing erythropoiesis.
Regulation of erythropoiesis—erythropoietin and other hemopoietic factors
Hemoglobin: Normal level. Physiological variations,
Structure, Types, compounds of hemoglobin, Fate of Hb.
White Blood Cells: Classification of WBC, normal values morphology,
functions, variations, Leukopoiesis, Leukaemia.
Platelet: Platelet structure, normal value, production, functions.
Purpura and Bleeding Time.
Hemostasis: Major steps—Primary and Secondary, Coagulation factors.
Extrinsic and intrinsic mechanisms of coagulation. Physiological mechanisms
preventing intravascular coagulation—Endogenous anticoagulant systems.
Endogenous fibrinolytic systems, Intravascular blood coagulation, Disseminated
Intravascular coagulation. Anticoagulants—Types, Mechanism of action and
uses.
Bleeding and Clotting Disorders—von Willebrand disease, Hemophilia, Vitamin
K deficiency. Clotting time, Bleeding time, Prothrombin time. Blood Group:
Physiological basis for blood groups The ABO system.
The Rh system—Hemolytic Disease of Newborn (HDN).
Other minor blood group systems.
Blood transfusion: Indications, Collection, Precautions to be taken—cross
matching, screening for infections, Consequences of mismatched transfusion,
Hazards of blood transfusion. Blood bank.
Significance of blood grouping.
Anemia: Definition, etiological and morphological classification.
Effects of anemia on physiological systems. Signs and symptoms.
Common types of anemia—Iron deficiency anemia, pernicious anemia, sickle
cell anemia, and thalassemia—their causes and salient features. Polycythemia—
Primary and secondary, Physiological effects.
ESR, PCV, Blood Indices, Osmotic fragility. Blood volume: Normal value,
Physiological variation, Principles of measurement, regulation. Body Fluids and
compartments.
Distribution of total body water (TBW). Principles of measurement of body
fluids. Effect of dehydration and overhydration. Reticulo endothelial system.
Odema.
Immunity: Definition and types of immunity. Mechanisms (i) Cell mediated
immunity (ii) Humoral immunity.
Physiological basis of immunisation.
Autoimmune disease, AIDS, Graft rejection.

BLOOD
Cardio vascular system comprises of heart, blood and blood vessels.
The branch of physiology dealing with blood is called hematology. “Blood is a
fluid connective tissue of the body”.

Blood connects different parts of the body. It connects different parts by virtue of
circulation.
Sir William Harvey was the scientist who discovered the circulation of blood.
Hematology includes the study of blood and blood disorders. The proper
analysis of blood may help in the diagnosis and management of blood disorders
as well as many other diseases. Hematological investigation is very routine and
important in medical practice. Many bodily dysfunctions can be detected by
noting the alternations in blood even in their early stage. These laboratory
findings of blood parameter are fairly reliable in the diagnosis and prognosis of
diseases collection of blood samples and investigation is very easy. Therefore
hematological investigation has become an integrated part of medical practice.

Properties of Blood
1. Volume of blood present in the body is 5-6 litres

2. The colour of blood is red. This is due to the presence of oxyhaemoglobin.

3. The pH of blood is 7.4. Slightly alkaline.
4. Specific gravity is the relative density of blood compared to water = 1.060
5. Viscosity means thickness of any fluid compared to water. Viscosity of blood
is 5 times greater than water. Blood is thicker than water.

Composition of Blood
Blood is divided into two major components—Plasma and formed elements or
cells.
COMPOSITION
Blood
Blood cells - 45% formed elements
Plasma 55%

Erythrocytes or RBC
5 million/c.mm Leukocytes or WBC
4000-11000/c.mm Platelets or Thrombocytes 2-4 lacs/c.mm Water Solids 91% 9%

Granulocytes Agranulocytes Organic 8%

Inorganic 1%
Neutrophils Basophils 40-70% 0-1% Eosinophils Lymphocyte Monocyte 1-5% 25-40% 2-8%

1. Plasma proteins (a) Albumin

(b) Globulin
(c) Fibrinogen
(d) Prothrombin

2. Amino acids
3. Glucose
4. Fats and lipids (a) Free fatty acids Cations Anions ++ –Na K Cl, HCO3 Ca

++Mg++PO––, SO–– 44 Mn++, Fe++

(b) Mono/Di/Tri glycerides
(c) Cholesterol
(d) Phospholipids

5. Vitamins
6. Hormones
7. Nitrogenous waste products
(a) urea (b) uric acid (c) creatinine, Bile pigments, xanthine.

Fig. 2.1 Composition of blood

1. Plasma

It is the liquid portion of blood in which various types of blood cells are
suspended. By volume plasma is 55% of blood and the portion of blood cells is
45%.

Blood cells or formed elements of blood are mainly of three types:

They are:
1. Red Blood Corpuscles (RBCs) or Erythrocytes
2. White Blood Corpuscles (WBCs) or Leukocytes
3. Platelets or Thrombocytes

WBC are broadly classified into two types:

1. Granulocytes 2. Agranulocytes
Granulocytes are of three types:
1. Neutrophils 2. Eosinophils and 3. Basophils
Agranulocytes are of two types:
1. Lymphocytes and 2. Monocytes

Plasma
Difference between plasma and serum
Serum = Plasma without some clotting factors like

fibrinogen, prothrombin, V, VIII and XIII. Serum is the fluid oozing out of a
blood clot.

Plasma = Blood without blood cells

Composition of plasma
Plasma is made of water, solids and gases. Water = 90 – 92%, Solids = 8 – 10%.
The solids are classified into two:
1. Organic constituents and
2. Inorganic constituents
1. Plasma proteins

(a) Albumin

Alpha
(b) Globulins Beta
Gama
(c) Fibrinogen
(d) Prothrombin
(e) Enzymes — Biological catalysts

2. Carbohydrates are mostly present in the form of glucose.

3. Amino acids
4. The fats and lipids present in the blood are free fatty acids, monoglycerides,
diglycerides, triglycerides, phospholipids and cholesterol.

5. Hormones—They are organic chemical substances secreted by the duct-less

glands.
6. Nitrogenous waste products like, urea, uric acid, creatinine, xanthine, bilirubin
etc.
7. Vitamins.

Inorganic constituents
This comprises of various salts. This includes:
1. Sodium salts 3. Calcium salts 5. Manganese salts 2. Potassium salts 4.
Magnesium salts

These salts get ionised as cations like Na+, K+, Mg++, Ca++, Mn
++ and anions like Cl–, SO4– –, PO4– –, HCO–
3

Functions of blood
One of the important function of blood is transportation.
Blood acts as the transporting agent of the body. 1. Transportation of
respiratory gases i.e., O2 and CO2. Oxygen is needed to produce energy by
metabolism.
O2 is transported from the lungs to the tissues by blood.
CO2 is transported from the tissues to the lungs by the blood.
CO2 is formed by oxidation, as the end product of metabolism. Example if
glucose is oxidised we get CO2
C6H12O6 + 6O2 → 6CO2 + 6H2O 2. Transportation of nutrients (food like
vitamins, minerals, water, fats and lipids, carbohydrates) from the gastro
intestinal tract (G.I.T) to various parts of the body.
3. Transportation of waste products—Excretory function. Blood picks up the
waste products from the site of production and carries them to the site of
excretion, excretory organs like kidneys, lungs, G.I.T. and skin.
4. Transportation of hormones
Hormones are organic chemical substances secreted by ductless glands or
endocrine glands and manifest their functions away from the site of secretion.
Blood carries the hormones from the site of secretion to the site of action.

5. Defence
Blood helps in the defence of the body. Blood takes part in three types of
defence.
(a) Phagocytosis

WBC or leucocytes engulf foreign organisms, bacteria, fungus etc. and kill the
microorganisms. So the microorganisms thereby do not get the chance of
multiplication. The body is protected from the harmful effects of
microorganisms.

(b) Producing antibodies (formed from gama globulin).

When a group of micro organisms enter the body for the first time they act as
antigens. Against these antigens, antibodies are developed from gama globulins.
When same group of microorganisms enter the body at a later date, they will be
destroyed or killed by the antibody molecules already present in the body. This
gives a long term protection to the body. This mechanism is known as immunity.

(c) Blood shows the property of coagulation or clotting.

This mechanism converts liquid blood into semisolid. This minimises the loss of
blood from a cut
blood vessel.
6. Regulative functions

(a) Regulation of pH or regulation of acid-base balance i.e., maintaining a

constant pH. pH of blood is maintained by the action of chemical buffers of the
blood. There are three important groups of buffers in the blood. They are:
1. NaHCO3 and carbonic acid buffer (H2CO3). 2. Phosphate buffer, NaH2PO4,
Na2HPO4. 3. Protein buffers.

Buffer: Prevents wide fluctuation in pH. (b) Blood takes part in the regulation of
body
temperature.
Blood takes part in the distribution of thermal
energy between different parts of the body.
When the body temperature increases, blood
vessels of the skin undergo dilatation. Because
of this more blood may flow to the skin. Along

with the blood more thermal energy flows to the skin and higher thermal energy
is lost from the skin. This helps in the cooling of the body. When the body
temperature is low, vasoconstriction of pheripheral blood vessels takes place.
Because of this, less blood and less thermal energy will reach the skin. Less
thermal energy is lost from the skin. This helps in the conservation of thermal
energy.

(c) Blood takes part in the regulation of water balance.

Blood acts as a buffer for water. It takes part in the distribution of water among
the different compartments of the body (intra cellular, extra cellular etc.).

PLASMA PROTEINS

Plasma proteins are a group of proteins present in the plasma. Plasma protein
concentration is about 7.3 gms/ 100 ml (deci litre) of blood. The important
plasma proteins are serum albumin, serum globulin, fibrinogen and prothrombin.

Albumin is about 4.8 gm/100 ml of blood. Globulin is about 2.3 g/100 ml

Fibrinogen – 0.3 gm/100 ml of blood. Prothrombin is only in ‘trace’. 40 mg/100
ml.
Molecular weight

Albumin – 69,000
Globulin – 9000–150000
Fibrinogen – 340000
Normal albumin globulin ratio is 2 : 1.
Site of synthesis: All the proteins of plasma are synthesised in the liver except
gama globulins. They are produced by lymphocytes. The plasma proteins are
separated using a technique called as electrophoresis.

Functions of Plasma Proteins

1. When a blood vessel is injured, it produces prothrombin activator. This

converts prothrombin to “thrombin”. Thrombin is a proteolytic enzyme. It
converts fibrinogen to fibrin. Fibrin gets polymerised and give rise to fibrin
threads. The fibrin threads give rise to a net work or mesh work. This net work
of fibrin thread traps various type of blood cells. This will prevent excess loss of
blood from a cut blood vessel.

ProthrombinProthrombin activator Thrombin

Fibrinogen Fibrin
Fibrin threads clot

2. Plasma proteins contribute to the colloidal osmotic pressure of blood. About

80% of osmotic pressure is exerted by albumin because its concentration is
highest.
It controls the distribution of water among the different compartments of the
body. This force also controls glomerular filtration rate (G.F.R).

3. Plasma proteins, albumin and fibrinogen contribute to about 50% the viscosity
of blood. When the viscosity increase the resistance for the flow of blood will
increase. It is one of the factor controlling blood pressure. The viscosity depends
on the molecular shape of plasma protein. Fibrinogen contributes maximum
viscosity because of its elongated and fibrillar shape.

4. Transportation function
(a) Transportation of small amounts of CO2 as carbamino proteins.

(b) Transportation of hormones. Hormones usually get attached to plasma

proteins and carried from place to place.

(c) Transportation of minerals and vitamins. 5. Defensive function

Help in the protection of the body. The
gamaglobulins develop as antibodies. This helps in
the long term defence of the body against microorganisms.
6. Plasma proteins help in the regulation of acid base
balance or pH by acting as chemical buffers. 7. Plasma proteins act as a nutrient
reserve.
During nutritional crisis, plasma proteins may be
broken down for energy production. The nutritional
crisis includes malabsorption, malnutrition, fasting,
dieting and starvation.

Variations in Plasma Proteins

Decreases in
Decrease in Albumin: (a) Physiological

1. Infancy
2. Pregnancy
(b) Pathological–Impaired protein synthesis
1. Hepatitis
2. Cirrhosis of liver
3. Severe malnutrition 4. Malabsorption
5. Burns

Decreases in
1. Emphysema
2. Acute hemolytic anemia
3. Glomerulo nephritis

Decreases in
1. Carcinoma prostrate
2. Intravascular
coagulation
3. Use of anabolic steroids

II. Albumin
Increases in
1. Dehydration

2. Exess
glucocorticoids
3. Congestive
cardiac failure
III. Globulin
Increases in
1. Multiple myeloma 2. Tuberculosis
3. Lymphatic leukemia 4. Cirrhosis of liver 5. Nephritis
6. Rheuatic arthritis

IV. Fibrinogen
Increases in
1. Pregnancy
2. Malaria

3. Tissue injury
4. Acute or
chronic infections
5. Myocardial infarction
6. Stroke

I. Total Plasma Protein

Increases in
Hyperproteinemia
1. Dehydration

2. Hemolysis

3. Acute infections like hepatitis

4. Pheumatid Arthritis

5. Exess
glucocorticoides

V. Albumin Globulin Ratio A : G ratio

Decreases in
Hypoproteinemia
1. Haemorrahage

2. Nutritional deficiency and malabsorption

3. Malabsorption
4. Pregnancy due to hemodilution
5. Chronic liver disease

6. Renal disease like nephrotic syndrome

Increases in
1. Hypothyroidism
2. Exess
glucocorticoides

Decreases in
1. Liver dysfunction
2. Nephrosis

ERYTHROCYTE OR RED BLOOD CORPUSCLE (RBC)

These are non nucleated type of cells present in plenty in blood.

Shape: Biconcave disc or dumbbell shape. Below the erythrocyte cell membrane
there are two contractile proteins actin and spectrin. The positioning of spectrin
gives bicon cave shape to the RBC.

Advantages of shape:
1. It provides more surface area for gaseous exchange.
2. It helps to easily squeeze through narrow blood vessels.
2m
1 m7.2 m
2 m 7.2 m
Surface view Sideview
Fig. 2.2
Red blood corpuscles

A matered RBC has no nucleus, no mitochondria, no ribosome and no

endoplasmic reticulum. Advantage of having no nucleus. It gets more space for
the accommodation of more haemoglobin.

Size: Diameter 7.2 µ. Thickness at sides 2 µ, at centre 1 µ. Surface area 120 sq

micron, volume: mean corpuscular volume—90 cubic micron. Variations in the
size of the RBC is known as anisocytosis. e.g., In pernicious anemia RBC size
will be large and it is called as macrocyte, in iron depicient anemia size of RBC
is small known as microcyte. Variation in the shape of RBC is known as
poikilocytosis. e.g., Sickle cell anemia—RBC shape in sickle shape.

RBC count: 5 million/c.mm of blood.

Physiological variation in RBC count

1. Age: RBC count is more in infants and children, less in adult, still decreases
in old age. RBC count in a new born infant may be as high as 7–8 million/c.mm.

2. Sex: RBC count is more in male than female. In adult male RBC count is 4.5–
5.5 milliion/c.mm, average is 5 million/c.mm of blood, in adult female RBC
count is 4–5 million/c.mm, average is 4.5 million/c.mm of blood.

3. Altitude: Altitude is the height of place of living. RBC count is more in

people living at high altitude than those living at sea level. At high altitude
places oxygen content in atmospheric air is less (hypoxia). To take up whatever
oxygen is available, the number of RBC increases. This type of physiological
adjustments with environmental factors is known as acclimatisation.

4. Pregnancy: Total number of RBC in the blood increases during pregnancy,

but RBC count per c.mm of blood decreases. This is because more increase in
blood volume rather than increase in RBC count. This is known as
haemodilution 5. Exercise: RBC count increases during exercise. 6. Athlete:
RBC count is more in athletes. 7. Emotion: RBC count increases during
emotional

states.
Pathological variation
Pathological increase — Polycythemia
Pathological decrease — Anemia

Production of RBC — Erythropoiesis

Erythropoiesis or haemopoiesis is the physiological process of production of
RBC. Erythropoiesis mostly takes place in the bone marrow, but it depends upon
the stage of life.

TABLE 2.1
Stages, sites and phases of erythropoiesis Sl. Stage of Life No.
1. Embryo 1–3 months
2. Foetus 3–6 months
3. After Birth

4. After 20 years Bone marrow of all the bones

Bone marrow of small and flat bones.

Proerythroblast Basophilic cytoplasm
Basophilic erythroblast Early normoblast

Polychromatophilic erythroblast Intermediate normoblast

Orthochromatic erythroblast Late normoblst Cart wheel appearance

Reticulocyte Pyknosis
Erythrocytes

Site of
Erythropoiesis Yolk sac
Liver and spleen
Phase
Mesoblastic phase
Hepatic phase
Myeloid phase
Myeloid phase

Fig. 2.3 Stages of erythropoiesis

Stages of Erythropoiesis

RBC production starts from large nucleated type of cells known as pluripotent
stem cells. These cells undergo repeated mitotic cell division and gives rise to
committed stem cell or Progenitor cells. Committed stem cells of myeloid series
ultimately can produce RBC, neutrophil, monocyte, eosinophil or platelet. Again
mitotic cell division takes place and lead to colony forming cell unit—
erythrocyte. This colony forming cells give rise to proerythroblast or
pronormoblast. This is a nucleated type of cell with a diameter more than 22 µ.
Pronormoblast gives rise to the next stage of cells—early normoblast. The next
stage is intermediate normoblast or polychromatophilic normoblast. Intermediate
normoblast further gives rise to late normoblast. Late normoblast further give
rise to reticulocyte. Reticulocytes mature into erythrocytes or RBC. 1 million
RBCs are produced per second. Blood may contain about 1% of RBC in
reticulocyte stage. Increase in the percentage of reticulocyte in blood is known
as reticulocytosis.
Normal reticulocyte count
(a) Foetus — 30–50%
(b) At birth — 2–6%
(c) Adult — 0.5–1%
Important changes taking place during erythropoiesis. 1. Change in the size of
the cells. There is a gradual

reduction of size of the cells

2. Disappearance of nucleus: This is also a gradual
process. It starts from intermediate normoblast stage.
At this stage nucleus shows shrinkage. In the next
stage nucleus disintegrates or breaks down into
fragments. By reticulocyte stage, DNA strands/
nucleus disappears. Only RNA strands may be seen. 3. Synthesis of haemoglobin
starts from intermediate
normoblast stage. This process continues during
subsequent stages. Matured RBC is saturated with
haemoglobin upto 33%.

TABLE 2.2
Stages of erythropoiesis
S. No. Name of the cell Diameter

(in microns) Nucleus

Characteristics Cytoplasm Appearance

Characteristics
1. Haemocytoblast 18–23 Large Small amount, thin rim of deep basophilic
cytoplasm
2. Proerythroblast 14–19

Large with distinct nucleoli and reticulum of fine chromatin

threads
Basophilic and less in quantity No haemoglobin

3. Early normoblast Basophilic and less in quantity No haemoglobin 11–17

Nucleus and chromatin

becomes more dence, nucleoli are absent or rudimentary

4. Intermediate
normoblast
(polychromatophil)

10-14 More condensed often eccentric.

No nucleoli
Becomes
polychromatic because of
appearance of haemoglobin

5. Late Normoblast (orthochromatic erythroblast)

7-10 Nucleus is very dense

and takes a deep stain (pyknotic)

Polychromatic
Quantity cytoplasm increases

6. Reticulocyte 7-7.5 Round Disappears

Net like structure

(reticulum) in cytoplasm Some RNA is still present

7. Erythrocyte Mature RBC 7.2

Biconcave disc
No nucleus Plenty of
haemoglobin

4. Changes in the shape. Upto reticulocyte stage, all the cells are spherical in
shape. When reticulocyte matures the shape change into a biconcave disc.

5. Changes in the staining property of cells.

Haemoglobin synthesis starts at the intermediate normoblast stage and mitotic

cell division stops at late normoblast stage. It takes about 8 days from
pronormoblast to reticulocyte.

Factors Essential for Erythropoiesis or Factors Influencing Erythropoiesis

1. Proteins
Proteins are essential for supplying amino acids required in the synthesis of
haemoglobin. Deficiency of protein in the diet (food) will lead to nutritional
deficiency anaemia.

2. Iron

Iron is essential for the synthesis of haemoglobin. Green leafy vegetables are
good sources of iron. Deficiency of iron in the diet leads to improper
haemoglobin synthesis. This results in a type of anaemia iron deficient anaemia.
Which is characterised by Microcytic Hypochromic.

3. Vitamins: Maturation factors

Vitamin B12 or cyanocobalamine and folic acid. These two

vitamins are the members of vitamin B-complex. These two vitamins together
are called as extrinsic factors. These vitamins are essential for DNA synthesis.
Therefore they are required for cell multiplication and also for the maturation of
RBC. The deficiency of these vitamins will lead to maturation failure. This will
result in megaloblastic anaemia or maturation failure anaemia.

4. Intrinsic factor of Castle

It is a glyco protein secreted from the wall of the stomach or gastric mucosa. So,
it is one of the component of gastric

juice. This intrinsic factor gives a protective covering to the extrinsic factor—
vitamin B12 and folic acid. Because of this it prevents the destruction of the
vitamins by the actions of enzymes and acids of gastro intestinal tract (G.I.T.).
Deficiency of intrinsic factors will expose the extrinsic factors to the actions of
enzymes and acids. This will destroy the vitamins, ultimately leading to
pernicious anaemia. Deficiency of intrinsic factor is seen during severe peptic
or gastric ulcers.

5. Other vitamins
B1 Thiamine, B2 Riboflavine, B6 Pyridoxine and vitamin C are also essential for
erythropoiesis.
6. Other minerals
Like Copper, Cobalt, Nickel, Bismuth etc. are trace elements that are also
essential for RBC production.
7. Burst Promoting Action (BPA)
It is a group of proteins secreted by agranulocytes like monocytes and
lymphocytes. B.P.A. stimulates the bone marrow and increases the proliferation
of cells.

8. Hypoxia

It means low oxygen content in the blood. Hypoxia increases R.B.C. production
by stimulating the kidneys to produce erythropoietin. This stimulates committed
stem cells to multiply.

9. Hormones
Like androgens, thyroxine, corticoids, oestrogen, growth

hormone and prolactin. Androgens, corticoids, thyroxine, growth hormone and

prolactin increases the formation of erythropoietin, thereby stimulate bone
marrow and increases the rate of cryotherapies. Oestrogen decreases
erythropoiesis.

Regulation of Erythropoiesis

Regulation of erythropiesis means controlling the rate of R.B.C. production or

the rate of erythropoiesis. Body has to maintain a constant R.B.C. count of
around 5 million per cubic mm of blood. This provides an optimum cardio
vascular efficiency to the body. If the R.B.C. count increases, that condition is
known as polycythemia. This condition is harmful for the body. Decrease in
R.B.C. count is known as anaemia. This is also harmful to the body as R.B.Cs
once produced are not permanent. They are subjected to the process of aging.
The R.B.Cs have a life span of 120 days. The older R.B.C. cell wall becomes
less and less elastic and more and more (brittle) fragile. This senile (old) R.B.Cs
are easily destroyed by the Reticulo Endothelial system. This process is known
as haemolysis. At one hand there is erythropoiesis on the other hand there is
haemolysis. A constant R.B.C. count can be maintained by establishing an
equilibrium between the rate of erythropoiesis and haemolysis. But, body cannot
adjust the rate of haemolysis. Therefore the only way to maintain a constant
RBC count is by regulating erythropoiesis.

Mechanism
Suppose, if the O2 content in the blood decreases that condition is called as
hypoxia. Hypoxia stimulates kidneys. In response to hypoxia kidneys secrete
renal erythropoietin. Liver secrtes about 10% of erythropoietin. The
erythropoietin acts as a hormone. This hormone acts on the bone marrow,
Kidneys
Liver 2O /Hypoxia
–ve
Erythropoietin or HaemopoietinRBC
count
Rate of
erythropoiesis Bone marrow Fig. 2.4
Regulation of erythropoiesis

i.e., it stimulates the bone marrows, to increase the rate of erythropoiesis. So the
RBC count increases. This will increase the O2 content in the blood. So hypoxia
is removed. It is an example for negative feed back mechanism.

Polycythemia
It is a clinical condition in which there is a significant increase in erythrocyte
count and haemoglobin concentration.

HAEMOGLOBIN

It is a metallo protein present inside the RBC. It is an iron containing protein, a

red colored pigment present inside the RBC. It is a conjugated protein. It has got
two parts.

1. Protein part — Globin

2. Non-protein part prosthetic group — Haem. Globin is made up of 4
polypeptide chains, 2 α chains, 2 β chains, α chains contain 141 amino acids and
β chain contains 146 amino acids. Haemoglobin is a protein with 574 amino
acids and a molecular weight of 68,000. Haem consists of protoporphyrin ring
with iron in the ferrous state. Protoporphyrin is made up of 4 pyrole rings. Haem
contributes to 4% of weight of Hb, remaining 96% is by the globin part.

Functions of Haemoglobin
1. Transportation of oxygen.
2. Transportation of small quantity of CO2 .

3. It acts as a chemical buffer, helps in the regulation of pH or acid base balance.

4. Oxygenated haemoglobin gives red color to blood.
Haemoglobin concentration
15 gm/dl or 100 ml 15 gm %
Physiological variations

1. Age: Haemoglobin concentration is more in new born and infants than adults.
In new born infants Hb concentration is about 17 gm %.

2. Sex: Haemoglobin concentration is more in male than female

Adult male 14–17 gm %
Adult female 12–15 gm %
3. Altitude: Hb concentration is more in people living at high altitudes.

4. Emotion: Hb concentration increases during emotional states.

5. Exercise: Hb concentration increases.
6. Pregnancy: Total quantity of haemoglobin increases during pregnancy but
haemoglobin concentration decreases due to haemodilution.
1. Succinyl CoA + 2 Glycine abamino keto adipic acid
2.
-amino
ab-Keto adipic acid d -amino levulinic acid
d3. 2 -amino levulinic acidCondensation Porphobilinogen IIIALA dehydratase
4. 4 molecules of porphobilinogen Porphobilinogen IX
5. Protoporphyrin IX
Fe ++ Haem
6. Haem + Globin Haemoglobin

Fig. 2.5 Biosynthesis of haemoglobin

TABLE 2.3
Fate of RBC and haemoglobin
Bone marrow
R.B.C. Production
R.B.C. in blood life span 120 days
R.E. system (Liver, spleen lymph nodes and bone marrow
Haemolysis of R.B.C.
Haemoglobin
Haem Globin
IronProtoporphyrin Amino acid pool
Transferritin in blood Microsomal
oxygenase Reused in the synthesis of proteins including Hb Bileverdin (green)
Bileverdin reductase
Ferritin
stored in liver Bilirubin conjugated with a-albumin of plasma
LIVER
Conjugated with glucuronic acid
Bilirubin glucuronic acid
Bile
Intestine
bacterial degradation
(Brown) Stercobilinogen Urobilinogen (Yellow)
Stercobilin Reabsorbed to blood

Excreted through faeces Kidneys

Urobilin
Filtered and excreted through urine

Fate of Hemoglobin

RBC has a life span of about 120 days. The cell membrane of senile RBCs
become fragile and brittle such old RBCs are destroyed by the reticulo
endothelial cells of bone marrow, liver, spleen and lymple node. Hemoglobin is
liberated from ruptured RBC. The tetrapyrrole ring of home is opened up and
four pyrrole rings lie side by side. Globin and iron are removed. Iron is stored in
the liver as ferittin. Globin will be metabolised like any other proteins. The
tetrapyrrole straight chain compound is called as biliverdin. Biliverdin oxidised
to bilirubin. All these reactions take place with in the phagocytic cells. Bilirubin
come out of phagocytic cells. Bilirubin come out of phagocytic cells. It
combines with albumin—albumin complex. This portion of bilirubin is called as
free bilirubin or unconjugated bilirubin. Through the circulation free bilirubin
reaches the liver. Here bilirubin get conjugated with glucaronyl transferage. The
conjugated bilirubin is water soluble and released into bile and reaches small
intestine. Conjugated billirubin gives color to bile. Along with bile bilirubin
glucuronide reaches the lower part of small intestine. Here bacterial enzymes
split the conjugated bilirubin. Bilirubin immediately get oxidised. Two types of
compounds are formed brown colored stereobilinogen. Yellow colored
urobilinogen. Stercobilinogen is excereted through stool as stercobilin.
Urobilinogen is absorbed by the blood from the intestine, carried to kidney, get
filtered as lost through urine as urobilin.

TABLE 2.4
Types of haemoglobin

Hb A – Hb α2 β2
Hb A2 – Hb α2 δ2
Hb F – Hb α2 γ2
Hb S – Hb α2 β2

TABLE 2.5
Haemoglobin variants causing haemoglobinopathy
Haemoglobin Point mutation Amino Acid position substitution

Hb S
Hb C
Hb E
Hb D (Punjab) Hb O (Arab) Hb sM
Beta 6 Glu - Val Beta 6 Glu - Lys Beta 26 Glu - Lys Beta 121 Glu - Gln Beta 121
Gu - Lys

Proximal or His - Tyr distal Histidine

in α or β chain

TABLE 2.6
Compounds of haemoglobin
HAEMOGLOBIN
I. Addition Compounds Haemoglobin ligands II. Derived or Decomposition Compounds

1. Oxyhaemoglobin
2. Methaemoglobin
3. Carboxyhaemoglobin or
Co-haemoglobin
24. CO -haemoglobin or
Carbohaemoglobin or
Carbamino compound
5. NO-haemoglobin
or
Nitric oxide haemoglobin
6. Sulphahaemoglobin or
H S-haemoglobin

A. Iron containing compounds B. Iron free compounds

1. Haematin
2. Haemin
3. Haemochromogen
4. Cathaemoglobin
5. Haem
6. Cytochromogen
7. Methemoglobin—Iron is oxidised from ferrous to ferric state 8. Glycosylated or glycated hemoglobin.
Glucose attached to hemoglobin. 1. Haematoporphyrin 2. Haemopyrrole
3. Haematodin
4. Bilirubin
5. Biliverdin

6. Stercobilin
7. Urobilin

Haemoglobinopathies
Haemoglobinopathies (Hereditary disorders of haemoglobin; disorders of
haemoglobin structure and synthesis).

Haemoglobinopathies are disorders that affect the structure, function or

production of haemoglobin due to abnormalities in the formation of globin two
types.

1. Qualitative abnormality of haemoglobin results from alterations in the amino

acid sequence of the polypeptide chains which produces structurally defective
haemoglobins.

2. Quantitative abnormality of haemoglobin results from impaired or absent

polypeptide chain formation but amino acid sequence is normal.

TABLE 2.7
Types of haemoglobinopathies
Qualitative
haemoglobinopathies Quantitative
haemoglobinopathies Haemoglobin S
thalassaemia) Thalassaemias (α, β-
Haemoglobin C Combined qualitative and

quantitative haemoglobinopathies
Heaemoglobin E
Sickle cell β-thalassaemia

Haemoglobin D Punjab

Altered oxygen affinity High affinity

haemoglobin
Low affinity
haemoglobin
Haemoglobin that oxidise easily
Unstable haemoglobin
M haemoglobin
Defect in the synthesis of
heme-prophyrias. It may
be inherited or acquired.
Over production of
prophyrins due to over
activity of enzyme delta
amino levunic acid.
Symptoms-Photosensitivity and Psychosis.

Acquired
haemoglobinopathies Methaemoglobinaemia
Carboxyhaemo
globinaemia

WHITE BLOOD CORPUSCLES (WBCs) OR LEUKOCYTES

These are the nucleated type of blood cells. Total leucocyte count is 4000–
11000/c.mm of blood.
1. Leukocytopenia or Leukopenia
It is a clinical condition in which W.B.C. count is significantly below normal,
i.e., 2000 or 3000/c.mm

Cause
(a) Bone marrow aplasia
(b) Anaphylactic shock
(c) Typhoid
(d) Cirrosis of liver
(e) Excess of ACTH
(f) Drug induced bone marrow aplasia.
If the W.B.C. count is less, the power of defence will

be very weak, i.e., the body cannot defend against the microorganisms. As a
result the body gets infected easily.
2. Leukocytosis
It is a clinical condition in which there is a significant increase in W.B.C. count
It is seen in pathological conditions like allergy, tuberculosis, cold etc.
3. Leukemia
It is a clinical condition in which there is a significant increase in immature
nonfunctional W.B.C. due to carcinogenic reasons. The body is easily infected,
more prone for infection, pains in joints.

Differential Leukocyte count, DLC or DC

Classification of W.B.C.
Granulocytes Agranulocytes

The criteria for the classification is the presence or absence of granules in the
cytoplasm. If granules are present they are called as granulocytes. If the granules
are absent they are called as agranulocytes.

TABLE 2.8 Differential leukocyte count and absolute count

Sl. Types of No. leukocytes Granulocytes Percentage Absolute count
1. Neutrophils 40–70% 3000–6000/ cmm
methylene blue colour. The number of lobes of nucleus ranges from 1 to 5.
D.L.C. of neutrophils is 40–70%.
Classification of neutrophils

Neutrophils are further classified based upon number of lobes present in the
nucleus. They are classified into five types.

2. Eosinophils 1–5% 150–300/cmm 3. Basophils

Agranulocytes
1. Lymphocytes
2. Monocytes

0–1% 10–100/cmm
25–40% 1500–2700/cmm 2–8% 300–600/cmm
Type I Type II Type III Type IV Type V Number of lobes indicate the age of the
cells. As the age advances number of lobes increase.

Arneth count
The percentage of different types of neutrophils is
known as Arneth count.
Granulocytes
Neutrophils Basophils
Eosinophils Type I 5% Type II 30% Type III 45% Type IV 18% Type V 2% Fig. 2.8 Normal arneth
count
Neutrophil 40-70% Eosinophil 1-5%
Basophil 0-1% Fig. 2.6 Granulocytes Agranulocytes
LymphocyteMonocyte
LymphocyteMonocyte25-40% 2-8%
Fig. 2.7 Agranulocytes

Criteria of classification
Size of the cells, shape of the nucleus and mainly the staining behaviour or
staining property.

Neutrophil
It is a type of granulocyte. Cell is round in shape. Size is 10–12 micron in
diameter.

Nucleus: Nucleus is multilobed. The nucleus is blue in colour.

The cytoplasm is granulated. It consists of numerous fine granules. The granule
will take up both eosin and

Functions of Neutrophils
1. It acts as a mobile defence unit of the body.

When micro organisms enter the body, neutrophils are attracted to the site of
infection. This process is known as chemotaxis. At the site of infection the
neutrophils squeeze out of the pores of the blood capillary. This process is
known as diapedesis. The neutrophils engulf the micro organisms. This process
is known as phagocytosis. By this way it kills the micro organisms and protects
the body.

Basophils
It is a type of granulocyte. Shape is round or spherical. Size: It is smaller than
the neutrophil. It is about 8–10 micron in diameter.
Nucleus: Nucleus is usually bilobed, ‘S’ shaped, blue in colour.
Granules: Granules are big in size and appear in dull blue colour. Basophils take
methylene blue.
D.L.C. of Basophils: Percentage of basophil is 0–1%. Functions of Basophils

1. It secretes a natural anticoagulant heparin. It prevents intra vascular blood

clotting.
2. It shows mild phagocytic action.
Eosinophils: It is a type of granulocyte.
Shape–Spherical
Size: Size is same as neutrophil i.e., 10–12 micron in diameter. Nucleus is
bilobed and telephone receiver like.

Granules: Granules are plenty in number and coarse. Granules appear in shining
pink or eosin colour. Sometimes the density of the granules cover the nucleus.
i.e., nucleus is submerged. The cell wall of the eosinophil is weak and during
staining procedure it may be broken.

D.L.C: The percentage of eosinophils is 1–5%.

Function: It helps in fighting against allergic responses. Allergic responses are

mediated through a local hormone histamine. Eosinophil contains an enzyme
histaminase. This enzyme destroys histamine.

2. Shows mild phagocytosis.

Eosinophilia: It is a clinical condition in which the percentage of eosinophils

increases i.e., the percentage increases to 10 to 15%.

AGRANULOCYTES

Lymphocytes Monocytes
Lymphocytes: It is a type of agranulocyte.

Size: There are two types of lymphocytes, small and large lymphocytes.

Small lymphocytes: 7-9 µ diameters, Large lymphocytes – 14-16 µ diameters

Shape of the cell is round.
Nucleus: Nucleus is large, round and filling almost entire size of the cell,
leaving behind a thin rim of clear cytoplasm. Size of the lymphocytes indicates
the age. Small lymphocytes are older. Large lymphocytes are younger.

Function
(a) Lymphocytes are functionally of two types: 1. T-Lymphocytes 2. B-
Lymphocytes.
They take part in the production of antibodies and it gives a long term protection
to the body. The lymphocytes take part in the development of immunity.

TABLE 2.9
Comparison between B-lymphocytes and T-lymphocytes
B-lymphocytes T-lymphocytes 1. Form 20 % of the total lymphocytes. Form 80
% of the total lymphocytes. 2. Produce antibodies. Produce chemicals called
cytokines. 3. Processed by bone marrow. Processed by the thymus.

4. Responsible for humoral mediated immunity i.e.,act through antibodies.

Responsible for cell mediated immunity i.e.,they either directly attack or act
through cytokines.

5. Protect the body from bacterial infections.

6. Shorter life span.

7. Class 2 MHC present on the membrane.

8. These have membrane bound immunoglobulins on their surface.

Protect the body from viral infections tumors and auto immune diseases.

Longer life span.

Absent.
Immunoglobulins are absent on the cell surface.

MONOCYTES
Monocytes are the largest of blood cells. Size is 18 micron in diameter.
Nucleus is big, usually kidney shaped and placed at one side of the cell. i.e.,
excentrically placed.
D.L.C. is about 2 – 6%.
Functions
They show phagocytic action. Because of this, they help in the defence of the
body by killing the microorganisms.
Summary of functions of Leucocytes – WBC
Neutrophils

Properties and functions of leukocytes Leukocytes are the mobile defence

units of the body. The primary function of leukocytes is phagocytosis.
Neutrophils and monocytes are spceiatist type of leukocytes in phagocytosis. It
is the ultimate process by which a living cell engulf and destroys a microbe. The
major changes in the appearance of neutrophiles when they are active against
bacterial infection include toxic granulation, vacuolisation of cytoplasm. Arneth
count shifts to the left i.e., percentage of young neutrophils increases in
circulation.
Steps of Phagocytosis

(a) Margination
(c) Ameboid movement (e) Opsonisation
(b) Diapedesis (d) Chemotaxis (f) Phagocytosis.

Margination: Leukocytes are attracted to the endothelial surface by membrane

bound proteins like selectins. Leukocytes roll along the wall of blood vessel and
it is called as margination.

Diapedesis: It is the process by which the neutrophils squeeze out through the
narrow pores of blood capillaries and reach the interstitial space.

Ameboid movement: Leukocytes move through the tissues, in between the cell
space by ameboid movement by extending out pseudopodia.

Chemotaxis: The infected microorganism interacts with plasma proteins and

produces certain chemicals called chemokines. For example, leukotrienes and
cytotokines. These chemicals attract neutrophils to the site of infection. This
process is called as chemotaxis.

Opsonisation: (Greek-prepare for dining). Neutrophils cannot efficiently

recognise and attach to most microbes. By opsonisation some plasma factors like
opsonones coat the bacteria and there by mark the microbes for ingestion and
make them tasty for leukocytes. Opsorins include antibodies and compliment
systems.
Foreign Pseudopodium
particles Phagosome

Fig. 2.9 Steps of phagocytosis Phagocytosis

Neutrophil membrane pseudopods envelop the microbe forming a vacuole called
a phagosome within the cytoplasm.

The phagosome fuses with lysosomal granules from the neutrophils cytoplasm.
The granules release lytic enzymes into the phagosome.
The lytic enzymes lead to eventual killing and digestion of the foreign agent. All
these processes require energy that is derived by anaerobic glycolysis (glucose
breakdown).

One of the products formed in the digestion of the foreign particle is hydrogen
peroxide, which is capable of killing microorganisms. Myeloperoxidase one of
the enzymes in the primary granules, catalyses a reaction involving H2O2
resulting in a more toxic product. Myeloperoxidase deficiency is reported to be
the most common congenital neutrophil disorders.

One neutrophil can engulf 15–20 microbes at a time. Neutrophils form the first
line of defence against invading microorganisms.

Basophils

1. Mild phagocytosis –
2. Secrete histamine – responsible for immediate hypersensitivity and acute
allergic reactions.
3. Secrete heparin – an anticoagulant – prevent intravascular blood coagulation.
Basophils play a role in acute allergic reactions. Their granules contain
histamine, heparin and other substances that are released in response to the
presence of allergens. These substances cause increased vascular permeability,
smooth muscle spasm, vasodilation, and the clinical symptoms of an allergic
reaction: watery eyes, runny nose, and difficult breathing.
Histamine is a vasodilator that makes blood vessels more permeable. This effect
is usually seen at inflammatory sites and allows increased cellular movement
through the vessel walls.
Heparin prevents blood clotting. Both histamine and heparin enhance the
migration of leukocytes to the inflamed site.

Eosinophils
1. Mild phagocytosis

2. Produce Major Basic Protein – Kill larvae of parasites – protection against

parasitic infection.
3. It secretes Aryl Sulphate B, which inactivates slow reacting substance (SRB)
released from mast cells
– so prevents anaphylaxis (Exaggerated response to an antigen to which body
was sensitised previously). Eosinophil glanular contents react with products
from basophil, lymphocytes and mast cells.
4. It secretes enzyme – histaminase – destroys local hormone histamine, which is
the chemical mediator of allergy, thereby shows anti allergic response.
5. The factors released from eosinophils decrease the inflamatory response and
reduce granulocyte migration into the site of invasion.

Monocytes

Monocytes are found in peripheral blood; macrophages are found in tissue.

There is not a large reserve pool of monocytes in the bone marrow. Monocytes
are found both in the circulating and the marginal peripheral blood pools.
Stimulated by growth factors, monocytes migrate into tissues and are generally
called macrophages; some fixed in connective tissue fibres and other sites and
some wandering freely through the connective tissue.

Macrophages are most numerous in “filter” organs like the spleen, liver, lungs,
lymph nodes collectively known as the mononuclear phagocyte system,
(formerly the reticuloendothelial system) a system that serves as an important
body defence mechanism composed of phagocytic cells.

1. Phagocytic action – Macrophage, protection against micro organisms.

2. Secretion of colony stimulating factors, thereby regulate leucopoiesis.
3. Secrete Interleukin I or monokinin which stimulate T-Lymphocyte-cell
mediated immunity.

4. Take part in inflammation.

5. Phagocytosis of dead cells and abnormal erythrocytes.
6. Secrete BPA—which stimulate bone marrow and increases the rate of
erythropoiesis.
7. Secrete Trephones—helps in the repair of damaged tissue or wound.

8. Monocytes act as antigen presentors in that they process ingested material and
present the antigen on its surface to a T-helper lymphocyte.

Lymphocytes
1. Produce antibodies and thereby give long term protection to the body against
same group of micro organisms.

2. Concerned with development of immunity or resistance:

T-Lymphocyte—cell mediated immunity B-Lymphocyte—humoral immunity.
Leukopoiesis
It is the process of production of leukocytes. All the types of leukocytes are
produced in the bone marrow except lymphocytes. Lymphocytes are produced in
the lymphnode.
Pluripotent stem cell or Primitive stem cell
Committed stem cell
Myeloid stem cells Lymphoid stem cells
Erythroid series Megakaryoid Colony forming cells series Unit-G.M. Lymphoblast
Prolymphocyte
Erythrocyte Thrombocytes Colony forming Colony forming cells granulocytes cells monocyte Large
lymphocyte

Neutrophil Myeloblast Eosinophil myeloblast

Basophil myeloblast

Monoblast Intermediate lymphocyte

Neutrophil promylocyte

Small lymphocyte Eosinophil promyelocyte Basophil Promyelocyte

Monocyte

Neutrophil myelocyte Eosinophil myelocyte

Basophil myelocyte Macrophage Histiocyte Plasma cell

Mast cell
Neutrophil metamyelocyte Basophil metamyelocyte Basophil metamyelocyte
Neutrophil Eosinophil Basophil

Fig. 2.10
Leukopoiesis

The pluripotent stem cells give rise to committed stem cells. The committed
stem cells of leukopoiesis are of two types:

1. Myeloid stem cells.

2. Lymphoid stem cells. The myeloid stem cells can give rise to three series:
(a) Erythroid series ultimately forming RBCs. (b) Megakaryoid series—forming
platelets. (c) Stem cells for granulocyte-monocyte series. The stem cells of
granulocyte -monocyte series

further produce colony forming units or progenitor cells for neutrophil,

eosinophil, basophil and monocyte. These colony forming cells ultimately end
up with respective cells. Leukopoiesis takes about 10 days, about 5 days for cell
division and 5 days for maturation from metamyclocyte stage.

Changes in counts of various types of leukocytes Neutrophilia—increase in

neutrophils more than 10,000/ c.mm of blood
Causes: (a) Physiologic

1. Exercise
2. After injection of adrenaline
3. Pregnancy, lactation
4. Strong emotional stimuli
(b) Pathologic
1. Acute pyogenic infections.
2. Poisoning by heavy metals like lead, mercury.
3. Insect venom.
4. Tissue destructions like
(i) Burns
(ii) Acute Haemorrhage
(iii) Myocardial infarction.
5. Appendicitis
6. Emphysema
7. Cushing syndrome
8. Steroid drugs
Neutropenia: Decrease in neutrophils Causes:
1. Infancy
2. Typhoid/Para typhoid fever

3. Viral infection like measles, Parasitic infection malaria.

4. Bone marrow depression, aplastic anemia

5. Drug toxicity like chloromphenicol.
6. Hypor splunism.
Eosinophilia: Increase in eosinophils, increase in absolute eosinophil above 500
/c.mm of blood.
Causes:
1. Allergy – like asthma, hayfever
2. Parasitic infections of blood like malaria, filaria 3. Skin diseases.
4. Intestinal parasitic infection like worms. 5. Rheumatoid arthritis.
Eosinopenia: Decrease in eosinophil.
Causes:
1. After injection of ACTH or corticosteroids. 2. Cushing’s syndrome.
3. Aplastic anemia.
Agranulocytosis—Decreased or absence of granulocytes. This is mainly due
to bone marrow depression. Due to bone marrow depression the production of
granulocytes is reduced, but not much reduction in the production of
lymphocytes because they are produced in the lymph node. So
Granulocytopenia or agranulocytosis.

Basophilia – Increase in basophils

Causes:
1. Chickenpox
2. Small pox
3. Tuberculosis
4. Influenza
5. Polycythemia vera
6. Chronic sinusitis.
7. Allergic and inflammatory condition
8. Hypothyroidism, Diabetes mellitus
Basopenia: Decrease in basophils
Causes:
1. After administration of glucocorticoids
2. Drug induced reactions.
3. Hyper thyroidism
4. Cushings syndrome
Lymphocytosis: Increase in lymphocytes
Causes:
1. Infancy – Relative lymphocytosis
L-60 %, N-40 %
2. Chronic infections – Tuberculosis, Syphilis, Diphtheria
3. Lymphatic leukemia
4. Viral infections like mumps.
5. Infective hepatitis.
Lymphocytopenia: Decrease in lymphocytes
Causes:
1. Hypoplastic bone marrow
2. AIDS
3. Corticosteroid therapy
Monocytosis: Increase in monocytes.
Causes:
1. Tuberculosis
2. Malaria
3. Syphillis
4. Kalaazar
5. Polythenia vera
6. Hodykin’s disease
7. Gluco corticoid therapy
Monocytopenia: Decrease in monocytes.
Causes: Hypoplastic bone marrow Septicemia.
Life and fate of leukocyte
Compared to erythrocytes the life span of leukocytes is very
short. Average life span of neutrophil is 2-4 days, eosinophil
8-12 days basophil 12-15 days, lymphocyte and monocyte
2-3 days. The senile leukocytes get fragmented either in the
blood stream or in the reticulo endothilial cells of liver, spleen
and lymphnode.
Regulation of leukopoiesis
It is interesting to note that the count of different types of
leukocytes are maintained at a constant rate. This is possible
by establishing an equillibrium between rate of their
production and rate of their destruction. The nuclic acids
formed by dead leukocytes inturn stimulate the formation of
fresh leukocytes. Certain proteins likegranulopoietic
stimulating factor stimulate the proliferation of cells. Dead
WBCs are replaced by new formation and a balance is kept
up between production and loss.

LEUKEMIA

It is a clinical condition in which there is an abnormal increase in nonfunctional

immature leukocytes due to a carcinogenic reason. It is not a common disease
but it is a popular disease because of Indian cinema.

Classification

There are two major types of classification. First one is based on the basis of cell
types which are predominantly involvedMyeloid leukemia and Lymphoid
leukemia. Second classification is on the basis of history of the disease—acute
leukemia and chronic leukemia. Usually two classfications are clubed together
as acute myeloblastic leukemia, acute lymphoblastic leukemia, chronic myeloid
leukemia and chronic lymphocytic leukemia. Leukemia is about 4% of total
cancer.

Major causes:
1. Some unknown genetic factors.
2. Environmental factors like,
(a) Exposure to ionising radiations.
(b) Exposure to chemical carcinogens like benzene. (c) Drug induced leukemias.
3. Infection by RNA viruses (Retroviruses). Clinical signs and symptoms:
1. As the leukemic cells accumulate in the bone

marrow, they suppress normal haemopoietic stem cells.

2. Anaemia is commonly seen.

3. This produces pallor, lethargy and dyspnoea.
4. Bleeding manifestations due to thrombocytopenia.
5. Infections of mouth, throat, skin and respiratory tracts.
6. Pain and tenderness of bones.
7. Splenomegaly or enlargement of spleen.
8. Hepatomegaly due to infiltration of liver by leukocytes.
9. Gum hypertrophy.

Treatment:
1. Bone marrow transplant.
2. Periodic blood transfusion.
3. Use of anticancer drugs.

PLATELETS OR THROMBOCYTE
Platelets: These are the smallest non nucleated type of blood cells.

Shape: Round or oval. Lifespan 8–10 days

Size of the cell is 2–5 µ diameter.
Volume 6–8 cu.micron.
Platelets count: 2-4 lakhs/cu.mm of blood.

Variation in platelet count: Increase in platelet count is known as

thrombocytosis. Physiological increase in platelet is seen in
(a) violent exercise

(b) high attitude. Pathologic increase is seen in – trauma and hamorrage.

Pathologic decrease in the count rombocytopenia where platelet count
thrombocytopenia is less than 1 lac / c.mm. (a) purpura, (b) aplastic anemia (c)
viral infection like dengue fever, rat fever and chicken pox. Platelet count below
50,000/ c.mm is called critical count.
Mithochondrion Cell membrane Microtubule

Thrombopoiesis is controlled by two major factors:

1. Colony stimulating factors
2. Thrombopoietin.
(Hemocytoblast)
Megakaryoblast
Promegakaryocyte
Dense granule Glycogen Light
granules Canalicular
system Megakaryocyte
Fig. 2.11
Platelet

Structure of platelet: Platelet cell membrane gives rise to invaginations and this
forms a network called Canaliculor system. The membrane contains
glycoprotein receptors. These receptors are specific for binding with collagen,
ADP, fibrinogen, von Willebrard factor. These membrane reacptors help the
platelets to adhere on to injured blood vessel.

Cytoplasm of platelets contain microtubules, microfilaments, endoplasmic

reticulum, mitochondria and granules. Granules are of two types – light granules
and dense granules. Light granules or α granules contain platelet derived growth
factor, von Willebrand factor, thrombospondin. Dense granules or Σ granules
contain nonprotein substances like ATP, ADP, serotonin. Phospholipids from
platelet cell membranes forms factors like thromboxane A2. Calcium is stored
inside microtubules and endoplasmic reticulum. Microfilaments are made up of
protein called actomyocin and thrombosthenin. This gives integrity to cell and
helps in the movements.

Production of Platelets - Thrmbopoiesis

Platelets are produced in the bone marrow. Platelets are produced in a precursor
cell known as megakaryocyte. The megakaryocytes are large nucleated cells and
have a diameter of 22 micron. The megakaryocyte undergoes fragmentation and
the broken bits of cell wall develop as platelets. These cell have cellular
inclusions like mitochondria, ribosomes, cytoplasm. Platelets can also be formed
by budding off from megakaryocytes. Around “1×10” platlets are produced per
day. Each megakaryocyte produce 5000-10,000 platelets. Production of platelet
is controlled by a hormone thrombopoietin produced by liver and kidneys. Old
platelets are destroyed by phagocytosis mostly in the liver and spleen.
Metamegakaryocyte

Thrombocytes Peripheral blood

Fig. 2.12 Production of platelets

Properties and functions of platelets

1. Platelet plug formation: Platelets aggregate, or clump together, using
fibrinogen and vWF as a

connecting agent. The most abundant platelet aggregation receptor is

glycoprotein (GP) IIb/IIIa; this is a calcium-dependent receptor for fibrinogen,
fibronectin, vitronectin, thrombospondin, and von Willebrand factor (vWF).
Activated platelets will adhere, via glycoprotein (GP) Ia, to the collagen that is
exposed by endothelial damage. Aggregation and adhesion act together to form
the platelet plug. Myosin and actin filaments in platelets are stimulated to
contract during aggregation, further reinforcing the plug. Platelet aggregation is
stimulated by ADP, thromboxane, and α2 receptoractivator, but inhibited by
other inflammatory products like PGI2 and PGD2, platelet aggregation at the site
of injury act as a plug and block the flow of blood out of cut blood vessel.
Platelet aggregation is enhanced by exogenous administration of anabolic
steroids.

2. The aggregation of platelets release vasoactive substances which assist in the

vasospasm. Serotonin and thromboxane A2 are released at the site of the inury
by the damaged platelets. These two local hormones produce vasoconstriction of
damaged blood vessel. The narrowing down the flow of blood to the site of the
injury and there by minimising the loss of blood out of blood vessel. The
vasospasm lasts for about 30 minutes and is an important factor in the initial
process in the arrest of hemorrhage. Vasoconstriction and plug formation are
very important in rapid arrest of bleeding and together they form temporary or
primary haemostasis.

3. The platelets, release platelet factor III and help in blood coagulation. Due to
their thrombosthenin content, the platelets can retract and cause clot retraction,
which is necessary for making the clot firm.

4. Platelets help in the coagulation of exudate which follows an acute invasion

by bacteria. This coagulation helps to cordon off the bacteria and thus localise
the infection.

5. Platelets also responsible in maintaining the integrity and health of vascular

endothelium.
6. Platelets help in the repair of damaged endothelium by being deposited on the
damaged site and thus making a smooth layer on the intima.
7. In addition to being the chief cellular effector of hemostasis, platelets are
rapidly deployed to sites of injury or infection, and potentially modulate
inflammatory processes by interacting with leukocytes and by secreting
cytokines, chemokines, and other inflammatory mediators.
8. Platelet also secrete platelet-derived growth factor (PDGF).This causes
proliferation of endothelium and vascular smooth muscles. This helps in wound
healing.

TABLE 2.10:
The substances produced by the platelets and their functions
Substance Function Serotonin(5-HT) Vasoconstriction

Adenosine diphosphate (ADP)

Promotes platelet aggregation

Thromboxane
platelet aggregation Vasoconstriction and
Clotting factors Promotes coagulation Platelet derived growth factor
Stimulates wound healing

Thrombocytopenia: It is a clinical condition in which there is a significant

reduction in the platelet count.
Thrombocytopenic purpura: It is a clinical condition resulting from low
platelet count.
Cause:
1. Aplasia (Non functioning) of the bone marrow. It is due to
(a) repeated x-ray exposure
(b) exposure to nuclear radiations
(c) drug induced bone marrow depression (d) Bone marrow fibrosis
(e) Deficiency of Vit B12 and folic acid.

2. Increased destruction of platelets due to (a) drugs

(b) Infection like dengue
(c) hypersplenism
(d) Cytotoxic chemotherapy
(e) HIV infection

Signs and symptoms or clinical features:

1. The efficiency of platelet plug formation decreases. This leads to prolongation
of bleeding time.

Bleeding time is the time elapsed from the onset of bleeding till the stoppage of
bleeding.
Normal bleeding time is 2–5 minutes. Clotting time may be normal.
Clotting time is defined as the time elapsed from the onset of bleeding till the
formation of clot or fibrin threads. Normal clotting time is 5–8 minutes.
Subdermal blood patches is known as purpura. These patches initially appear in
red colour but later change into brown and black.
Treatment: Platelet transfusion.
Thrombosthenic purpura: Qualitative platelet defectsplatelet count may be
normal but function is impaired. It is mostly due to (a) drug actions like aspirin,
antibiotics, heparin, (b) uremia (c) congenital disorders - defects in membrane
glycoproteinsn defect in secretion of ADP/ thromboxene A2.

Idiiopathic thromobocytopenic purpura

It is an auto immune disorder seen more commonly in children and rarely seen in
adults. A self antibody is formed against platelets there by destroy the platelets
and bring down

their number. The common clinical features include spontaneous bleeding

mostly from skin, nose and gums. It can be managed by steroid administration
and spheenectomy.
Injury to blood vessel
Vesoconstriction Exposure of collagen Surrounding tissue injury

1. Stimulation of pain receptors and nerve plexus leads to neurogenic reflex, results in smooth muscle
contraction of bloodvessels

Blood comes in contact with wettable surface

Liberation of tissue thromboplastin or tissue factor Factor III Activation of platelets adhesion

2. Chemically thromboxane A2 and serotonin released

by damaged platelet produce contraction of smooth muscles of blood vessels.

Liberation of thromboplastin factor III

Platelet plug formation Intrinsic Extrinsic

Temporary haemostasis Initiation of blood coagulation by cascade mechanism

Arrest of bleeding Fibrin thread formation network of fibrin threads with trapped blood cells = clot

Permanent haemostasis
Permanent stoppage of bleeding

Haemostasis

Haemostasis is defined as stagnation for the flow of blood out of a cut blood
vessel by natural mechanism. There are four major mechanisms. They are

1. Vasoconstriction
2. Platelet plug formation
3. Blood coagulation or clotting and
4. Clot retraction.
Vasoconstriction
When a blood vessel is injured, the injured blood vessel become narrowed. This
process is known as vasospasm or vasoconstriction. There are two mechanisms
producing vasoconstriction.
1. Nervous reflex mechanism
When a blood vessels is injured it will stimulate pain receptors. This will in turn
stimulate local nerve fibres. This produces contraction of smooth muscles of
blood vessels leading to vasoconstriction. 2. Chemical mechanism
When a blood vessel is injured the damaged platelets secrete a local hormone
called serotonin. Serotonin produces vasoconstriction. Vasoconstriction takes
place immediately after injury. This helps to minimise the loss of blood from a
cut blood vessel.
Platelet plug formation
When a blood vessel is injured the properties of platelets change. The cell
membrane become more permeable to water. The cell becomes swollen and
sticky. Numerous platelets adhere to each other. This forms a cluster of platelets
at the site of injury. This is known as platelet plug. This will physically block the
free flow of blood out of a cut blood vessel.
Blood Coagulation or Clotting
Blood coagulation is defined as a complex physiological process by which blood
looses its fluidity and become jelly like or semi solid, there by minimising the
loss of blood from a cut blood vessel.
A number of chemical substances take part in blood coagulation or clotting.
These substances are known as blood coagulation factors or clotting factors.
They are: Factor I
Factor II
Factor III Factor IV Factor V
Factor VII Factor VIII Factor IX Factor X Factor XI

Factor XII Factor XIII

– Fibrinogen
– Prothrombin
– Thromboplastin
– Calcium ion
– Labile factor
– Stable factor
– Anti haemophilic factor
– Christmas factor
– Prower – Stuart factor
– PTA

(Plasma thromboplastin anticedent)

– Hageman’s factor
– Fibrin stabilising factor

Some new substances are added to the list of clotting factors. This include—high
molecular weight kininogen HMW-K or Fitzgeral factor, Prekallikrinin—Prek.
Fletecher factor, kallikrinin- ka, PL—platelet phospholipid. All the substances
required for blood coagulation are present in the blood itself. In spite of this,
blood does not clot as long as blood is inside the blood vessel. Blood will not
clot unless and until it is exposed to outside. It is because of the following
reasons:

1. Most of the clotting factors are in the inactive form, they require activation.
2. Presence of natural anticoagulants like heparin,

Antithrombin I, II, III, alpha 2 macroglobulin. Presence of these anticoagulants

oppose blood coagulation.

3. Inner surface of blood vessel is very smooth, which does not allow the factors
to stick.
4. The velocity of blood will not allow the factors to react with each other.

Mechanism of blood clotting

There are two major mechanisms:
1. Intrinsic mechanism and
2. Extrinsic mechanism.
Intrinsic mechanism

In this mechanism everything required for blood coagulation comes from blood
itself. When a blood vessel is injured blood is exposed to wettable surface. This
triggers blood coagulation process. This takes place in three major steps.

Step I

Blood vessel is injured and blood is exposed to outside. Inactive factor XII is
converted into active factor XII by the action of substance Kallikrein.

Active factor XII convert inactive factor XI into active factor XI. Active factor
XI convert inactive factor IX into active factor IX. Thrombin convert inactive
factor VIII into active factor VIII. Active factor IX, active factor VIII and Ca++
together convert inactive factor X into active factor X. All these reactions upto
the formation of active factor X is known as step I of blood coagulation.

Thrombin converts inactive factor V into active factor V.

Step II

Conversion of prothrombin into thrombin. The active factor X, V,

thromboplastin (Phospholipid) and calcium ions together act as a prothrombin
activator. This will convert plasma protein-prothrombin into thrombin.
Step III

Thrombin is a powerful proteolytic enzyme. Thrombin acts on fibrinogen and

converts it into fibrin. Fibrin is insoluble in water. Thrombin also converts
inactive factor XIII into active factor XIII. Fibrin get polymerised to give rise to
fibrin threads. These fibrin threads are stabilised by active factor XIII. The fibrin
threads give rise to a network or meshwork. This network of threads trap all the
types of blood cells. This complex is known as clot. Blood has become jelly like
and stops flowing out. Blood coagulation involves multiple chain of enzymatic
reactions. Therefore it takes time for coagulation. Therefore this mechanism is
known as cascade mechanism or water fall mechanism.
Kallikrein Factor XII Factor XII* b XII*
a XII* Preakallikrein HMW kininogen
Factor XI Factor XI*
Factor IX Ca
++
Factor XI*
Step I Factor VIII
Thrombin Factor VIII*
Ca++ Factor X Factor X*

Step II Prothrombin activator

Factor V Thrombin
Factor V*
Prothrombin Ca++
Phospholipids
Factor XIII
Step III Fibrinogen Fibrin
Factor XIII*
Fibrin thread clot
Fig. 2.13 Intrinsic mechanism of blood coagulation Extrinsic mechanism

In this mechanism one of the factor comes from the surrounding damaged tissue
– outside the blood. This factor is known as tissue factor or tissue
thromboplastin. When a blood vessel is injured the surrounding tissues get
damaged. This damaged tissue produce tissue factor. The produced tissue factors
diffuse into the blood at the site of injury. The tissue factor acts upon inactive
factor VII and convert it into active factor VII. Active factor VII convert inactive
factor X into active factor X. The reactions upto the formation of active factor X
is known as step I of blood coagulation. Active factor X converts inactive factor
V into active factor V.
Step II: Conversion of prothrombin into thrombin.

Active factor X, active factor V, calcium ions and thromboplastin (Phospholipid)

together act as prothrombin activator.

Step III: Thrombin is a proteolytic enzyme. It acts upon fibrinogen and converts
it into fibrin. Thrombin also converts inactive factor XIII into active factor XIII.
Fibrin gets polymerised into fibrin thread. These threads give rise to a network
or meshwork. This network of fibrin threads will trap all the type of blood cells
This complex is known as clot. The clot will physically block the free flow of
blood out of the cut blood vessel.
Tissue trauma
Tissue factor
Factor VII Factor VIII*

Ca++ Prothrombin activator

Factor X Factor X*
Step I Factor V* Factor V
++ Phospho lipids
Ca
XIII Step II Prothrombin Thrombin
Step III Fibrinogen Fibrin XIII*
Fibrin threads cloth
Fig. 2.14 Extrinsic mechanism of blood coagulation
Fibrinogen
Fibrinapoptides
Fibrin monomers Fibrinapoptides
Fibrin thread
Fig. 2.15 Scheme of formation of fibrin thread Fig. 2.16 Blood clot, RBCs
entangled in fibrin meshwork
TABLE 2.11
Comparison between intrinsic and extrinsic mechanism of blood clotting
Sl. No. Features Intrinsic mechanism Extrinsic mechanism 1. Source of
thromboplastin

2. Role of factor VII

3. Number of reactions
4. Speed
5. Starts from

Damaged platelets, comes from within the blood. Intrinsic source

Factor VII is not required
More
Slow, takes few minutes
Activation of factor XII

Damaged surrounding tissue, comes from outside the blood. Extrinsic source

Factor VII is required

Less
Fast, takes few seconds
Activation of factor VII
Common causes of bleeding disorders
Defective blood clotting
Defective capillary contractibility Combined defects
Purpura

Primary (Idiopathic) Secondary (Idiopathic)

Deficiency of clotting factors I, II, V, VIII, IX,

X, XI
Vitamin K deficiency dueAnticoagulant to overdose

Obstructive jaundice Chronic diarrhoea

Liver disease
Haemorrhagic states in infants

Fig. 2.17 Common causes of bleeding disorders

TABLE 2.12
Haemorrhagic (Bleeding) disorders deficiency of clotting factors
Deficiency of Factor Clinical syndrome Cause I Afibrinogenemia or
fibrinogenopenia Congenital, use of anticoagulant like Arvin II
Hypoprothrombinemia Decreased Hepatic synthesis of factor II V
Parahaemophilia Congenital VIII Haemophilia A (Classical Haemophilia)
Congenital IX Haemophilia B (Christmas disease) Genetic disorder X Staurt-
Prower factor deficiency Congenital XI Plasma thromboplastin antecedent
Congenital vWF Von Willebrands disease, Decreased platelet Acquired, Liver
disorder Congenital adherence, Decreased factor VIII

Clotting disorders: The common clotting disorders are:

1. Von Willebrand’s disease
2. Haemophilia
3. Thrombocytopenic purpura
4. Vitamin K deficiency bleeding
Von Willebrand’s disease. Von Willebrand factor is a protein secreted by platelet.
Factor VIII is transported in combination with vWF. During the activation of
factor VIII

it get separated from vWF. Inherited deficiency of vWF leads to inhibition of

platelet adhesion. This leads to severe bleeding.

Haemophilia

Haemophilia is a clotting disorder. It is a sex linked genetic disorder. It is more

common in male than in female. Haemophilia is common among British
population.

– Males 8% – Females 0.5%

This disease is inherited through a recessive gene ‘h’. This gene is situated in X
chromosome. Because of this males are suffers of haemophilia, while females
are carriers. Females can be hemophilic if her father is hemophilic and mother is
a carrier.
Normal male Carrier female
(Father) (Mother)
Carrier Normaldaughter
daughter HaemophilicNormalson son

Fig. 2.18 Inheritance of haemophilia Types of Haemophilia

There are three common types of haemophilia. Haemophilia A or classical

haemophilia. Factor VIII is deficient.

Haemophilia B — Christmas disease Factor IX is deficient.

Haemophilia C — Deficiency of factor XI — Autosomal recessive trait.

Signs and symptoms

1. Prolongation of clotting time to several hours with normal bleeding time.

2. Excessive bleeding even from minor injuries.
3. Excessive bleeding from internal injuries.
4. Soft tissue hematomas and bleeding into joints.
Complications
1. Haemophilic patients cannot face any surgery.
2. Cannot face tooth extraction.
3. Cannot face menstrual bleeding.

4. There will be excessive bleeding even from minor injuries which may be fatal.
Test for haemophilia – Determination of clotting time. Bleeding time time
and Prothrombin time may be normal. Management or Treatment
1. Find out which factor is deficient and inject that factor periodically.

2. Periodic, regular blood transfusion of fresh blood. Thrombocytopenic

purpura—Due to the decrease in platelet count.
Vitamin K deficiency
Vitamin K is a fat soluble vitamin. It is required for the synthesis of clotting
factors in the liver. Vit. K is needed for the post translational Carboxylation of
some coagulation factors, like prothrombin. Synthesis of following clotting
factors like prothrombin, VII, IX and X requires vitamin K. If vitamin K is
deficient clotting factors like prothrombin cannot be synthesised. Without
sufficient prothrombin, blood cannot clot. This leads to prolongation of clotting
time, excessive bleeding from minor injuries. Dietany deficiency of Vit. K is rare
because it can be synthesised by colonic bacteria. Vit. K deficiency mostly
occurs due to (a) diseases which disturb fat absorption like obstructive jaundice
(b) long term antibiotic therapy which dislodge colon bacteria. (c) long term
usage of drugs like warfarin which is a competitor of Vit. K.

Anticoagulants

Anticoagulants are chemical substances which prevent blood clotting.

Anticoagulants are broadly divided into two groups, natural anticoagulants and
lab. anticoagulants.

Natural anticoagulants: e.g., Heparin, Hirudin Laboratory anticoagulants:

Sodium or potassium citrate, ammonium/sodium/potassium oxalate, EDTA
(ethylene diamino tetra acetate) Dicoumarol and Warfarin. Double oxalate—
mixture of ammonium oxalate and potassium oxalate – 3 : 2, Aspirin.

Mechanism of action of anticoagulants

Heparin inhibit the conversion of prothrombin into thrombin. It also inhibits the
action of thrombin.
Hirudin also inhibits the action of thrombin. Heparin activates antithrombin III
and prevents coagulation by inhibiting factors IX, X, XI and XII.

Citrates act as chelating agents. When citrates are added to blood the calcium
ions of the blood will adhere to citrate molecules, so free calcium ions are not
available. So the blood fails to clot.

Ethylene Diamino Tetra Acetate (EDTA)

It also acts as a chelating agent. It removes free calcium ions from the blood and
thereby prevents blood coagulation.

Oxalates
When oxalate is added to blood, it will react with calcium

ions and forms calcium oxalate, which gets precipitated. Free calcium ions are
not available so the blood fails to clot. Dicoumarol and Warfarin

It is an organic chemical. It acts as antagonistic of vitamin K. This prevents the

synthesis of prothrombin and other clotting factors in the liver. Without
prothrombin, blood fails to clot. Dicoumarol can be used as an anticoagulant
only inside the body i.e., in vivo. It cannot act as anticoagulant outside the body
i.e., in vitro.

Aspirin: It inhibits the formation of thromboxane A2 and prevents platelet

activation.

Uses of Anticoagulants
1. To preserve blood in the blood bank.

2. To preserve blood samples required for the determination of ESR, PCV

(erythrocyte sedimentation rate and packed cell volume).

3. To prevent intra vascular blood clotting.

4. Used during dialysis.

5. In the treatment of pulmonary embolism and cerebral thrombosis.

Fibrinolytic system
A fibrin clot is not designed to last forever. It is a transitory device until
permanent repair of the vessel occurs. The fibrinolytic (or thrombolytic) system
is the principal effector of clot removal. This system is very much important and
keeps the lumen of the blood vessels patent by dissolving the clot.

Fibrinolytic system constitutes a plasma proenzyme, plasminogen, which can be

activated to the active enzyme plasmin by protein plasminogen activators. Once
formed, plasmin digests fibrin, thereby dissolving the clot. This is achieved as
follows:
Thrombin-thronmbodulin complex
on endothelium

Endogenous mechanism
The principal fibrinolytic factor is plasmin which is formed

from a circulating glycoprotein called plasminogen. Plasmin is formed from its

inactive precursor, plasminogen through intrinsic and extrinsic pathways.

The intrinsic activator system: Plasminogen is converted to plasmin by both

kallekrein and factor XIIa. This pathway contributes only about 15% of the total
fibrinolytic activity.

The extrinsic activator system: There are two extrinsic activator systems in the
body i.e., t-PA and u-PA. Tissue plasminogen activator
Plasminogen Plasmin
Urokinase plasminogen activator

Tissue plasminogen activator ( t-PA), which is secreted by endothelial cells.

During clotting, both plasminogen and t-PA bind to fibrin and become
incorporated throughout the clot. The binding of t-PA to fibrin is crucial because
t-PA is a very weak enzyme in the absence of fibrin. The presence of fibrin
profoundly increases the ability of t-PA to catalyse the generation of plasmin
from plasminogen. Thus, fibrin is an important initiator of the fibrinolytic
process that leads to its own dissolution.

Significance in clinical practice: The naturally occurring fibrinolytic system

can be activated in certain clinical conditions like:

1. Coronary thrombosis
2. Massive pulmonary embolism
3. Cerebral stroke
4. Acute myocardial infraction.
Tissue plasminogen activator, streptokinase, urokinase can be injected. These
drugs dissolve the intravascular clot and help to repurfuse the affected vital
organs.
Plasminogen activators
Plasminogen Plasmin
Fibrin Soluble
fibrin fragments
Fig. 2.19 Fibrinolytic system
INTRA VASCULAR BLOOD COAGULATION— THROMBOTIC
DISORDERS
Normally blood may not clot inside the blood vessels. It is because of the
following reasons.
1. Most of the coagulation factors are in the inactive form. They require
activation.

2. Presence of anticoagulants—like heparin, antithrombin, I, II, III, α2

macroglobulin etc. These chemicals prevent blood clotting.

3. Inner surface of blood vessel wall is very smooth so the clotting factors may
not stick.
4. Blood is under circulation.
5. Even if fibrin is formed inside the blood vessel it

will be immediately distroyed by fibrinolytic system by the enzyme plasmin.

However, sometimes blood may clot inside the blood vessels.

There are two common types of intravascular blood clotting
1. Thrombosis—Thrombus
Formation of intra vascular stationary blood clot, e.g., Cerebral thrombosis.
2. Embolism—emboli
Formation of intra vascular freely moving blood clot, e.g., Pulmonory embolism.

Problems and complications

Intra vascular blood clot may block narrow blood vessels. It will block the
supply of nutrients and oxygen to the tissues. If it happens in vital tissues like
heart and brain, it may cause a permanent irrepairable damage to these vital
tissues. This may even lead to death.
Causes of intra vascular blood clotting
1. Inner surface of blood vessel becomes rough due to deposition of minerals or
fat.
2. Inner surface of blood vessel becomes rough due to infection.
3. Sluggish flow of blood especially after a surgical operation.
4. Increased activity of procoagulants such as fibrinogen, prothrombin.

Prevention and management

Periodic injections of anticoagulants.
Disseminated intravascular coagulation (Defibrination
syndrome)
Disseminated intravascular coagulation (DIC) is a
complex systemic thrombohemorrhagic disorder involving
the generation of intravascular fibrin and the consumption
of procoagulants and platelets. The resultant clinical condition
is characterised by intravascular coagulation and
hemorrhage.
Disseminated intravascular coagulation is caused by
widespread and ongoing activation of coagulation, leading
to vascular or microvascular fibrin deposition, thereby
compromising an adequate blood supply to various
organs. Four different mechanisms are primarily responsible
for the hematologic derangements seen in disseminated
intravascular coagulation:
1. Increased thrombin generation,
2. A suppression of anticoagulant pathways, 3. Impaired fibrinolysis, and
4. Inflammatory activation.
Activation of intravascular coagulation is mediated
almost entirely by the intrinsic clotting pathway. This is
characterised by systemic activation of coagulation with the
formation of fibrin–platelet thrombin throughout the vascular
tree. This is triggered by increased tissue factor activity in
the circulation, which can be produced by a variety of stimuli
including bacterial endotoxin and lipopolysaccharide. Thrombotic occlusion of
small to medium sized vessels

by fibrin clot can lead to multiple organ failure. Continual depletion of platelets
and coagulation factors creates a consumption coagulopathy. Secondary
activation of the fibrinolytic system ensues. The clinical manifestations represent
a combination of those due to thrombosis and those due to bleeding, either of
which may predominate.

Cause of disseminated intravascular coagulation is septicemia, bacteremia

including both gram-positive and gram-negative organisms, fungal infections,
malaria, chronic malignancies, abortions, snake bite, heat stroke pathogenesesis
may cause disseminated intravascular coagulation.

Features of disseminated intravascular coagulation:

1. Low erythrocyte sedimentation rate (ESR)
2. Thrombocytopenia
3. Prolongation of prothrombin time and activated partial thromboplastin time
(aPTT).
4. Reduced plasma fibrinogen level which correlates most closely with bleeding
5. Elevated levels of fibrin degradation products (FDPs)
6. Schistocytes on peripheral smear.
Tests for coagulation
1. Bleeding time — 2–5 minutes
2. Clotting time — 5–8 minutes
3. Prothrombin time — 11–16 seconds
4. Platelet count — 2–4 lack/c.mm of blood
5. Clot retraction time — 30–60 minutes
6. Partial thromboplastin time — 60–80 sec. Bleeding time

It is defined as the time elapsed from the onset of bleeding till the stoppage of
bleeding. It is the time by which bleeding stops from an injury caused by the
puncture of a sharp needle. It measures the time between the injury and the
temporary haemostasis. It indicates the efficiency of vasoconstriction and
platelet plug formation. Normal value: 2-5 minutes.

Significance: Bleeding time is prolonged in thrombocytopenic purpura but it

remains normal in haemophilia.

Clotting time or Coagulation time

It is defined as the time elapsed from the onset of bleeding till the formation of
fibrin threads or clot. It is the time taken by the blood to coagulate outside the
body. Capillary tube method is commonly used for the determination of clotting
time. Normal value is 5 to 8 minutes.

Significance: Clotting time is prolonged in haemophilia and vitamin K

deficiency, but it is normal in purpura. Bleeding time and clotting time tests are
routinely performed before any surgery and tooth extraction.

Prothrombin time (PT)

It is the time required for the activation of prothrombin to thrombin. It is defined

as the time taken for coagulation of a sample of recalcified plasma mixed with
tissue thromboplastin.

Normal time: 11-16 seconds.

Procedure: Blood is collected from the veins without tissue injury, mixed with
sodium citrate. Plasma is taken from this blood. The citrated plasma is mixed
with tissue thromboplastin (Brain extract) at 370C. Time is noted when gel
develops in plasma.
Significance
1. This test measures the concentration of prothrombin, factor V, VII, and X and
reflects the efficiency of extrinsic mechanism of blood coagulation.
2. In haemophilia and Christmas disease PT will be normal because tissue factor
does not require factor VIII and IX for activation of prothrombin.
3. PT increases in vitamin K deficiency which produces deficiency of
prothrombin, V, VII and X.
4. Anticoagulant therapy with vitamin K antagonist is controlled by
measurement of PT, which should be prolonged to about 25-30 seconds, to help
prevent intravascular thrombosis.
Clot retraction time: 30-60 mins.

BLOOD GROUP

Human beings can be classified into different groups based upon the nature of
the blood. Classification of human blood into different types is known as blood
grouping. There are thirty different systems of blood grouping. Blood group was
first discovered by Landsteiner in 1901. The basis of blood grouping is the
presence or absence of antigens and antibodies. Two types of blood grouping are
clinically important. They are ABO system of grouping and Rh blood grouping.

Blood Group Systems recognised by the International Society for Blood

Transfusion

ABO
MNS
P
Rh
Lutheran
Kell
Lewis
Duffy
Kid
Diego
Yt
Xg

ABO system of classification

DOMBrod Colton
LW
Chi do
H
Kx
Gerbich
Cromer
Knops
Indian
Ok
MER2

According to this classification human blood is classified into four types. A, B,

AB and O.

The criteria for the classification is presence or absence of antigens and

antibodies or agglutinogen and agglutinins.
The antigens are mucopolysaccharides present in the cell wall of the R.B.C.
Antibodies are gammaglobulins present in the plasma. In the blood group A,
antigen A is present in the cell wall of the R.B.C. and beta antibody in the
plasma. In the blood group B, antigen B is present in the cell wall of the R.B.C.
and alpha antibody is present in the plasma. In AB blood group both antigen A
and antigen B are present in the cell wall of the R.B.C. and no antibody in the
plasma. In the blood group O, no antigen is present in the cell wall of R.B.C. but
both alpha and beta antibodies are present in the plasma. The α β antibodies
belong to IgM category.

Subgroups of A
A1 & A2
Difference between A1 & A2 appears to be quantitative. A2 reacts less strongly
with anti A.
Distinction between A1 & A2 made using Dolichos biflorus which only reacts
with A1.

TABLE 2.13
Classification of ABO blood grouping
Genotype Phenotype or blood group Antigen or agglutinogen Antibody or
agglutinins Percentage AA, AO A Antigen A β 22 BB, BO B Antigen B α 33
AB AB

OO O Antigen A — 5 Antigen B —

— β and α 40
Parents AO AO AB AB Parents AO BO OO OO
Children AOAA OO,AA BB AB Children AO AB OO OB, OO
Parents AO OO BO OO AB OO
Children AO OO BO OO AOBO

Fig. 2.20 Inheritance of ABO blood group Landsteiner’s Law

The first part of the law states that when a particular antigen is present on the
cell wall of the R.B.C. the corresponding antibody will be absent in the plasma.

Example: In blood group A, antigen A is present on the cell wall of the R.B.C.
The corresponding antibody alpha is absent in the plasma.

Second part of the law states that when a particular antigen is absent on the cell
wall of the R.B.C. corresponding antibody will be present in the plasma.

Example: In the blood group B, Antigen A is absent in the R.B.C. so a antibody

is present in the plasma.
Genetics of ABO blood group

There are three genes for the inheritance of ABO blood group. These 3 genes are
“Gene A, Gene B and Gene O”. When there are more genes for the inheritance
of a particular character such an inheritance is known as allelomorphic
inheritance. Gene A is responsible for the production of antigen A. Gene B
produces antigen B, but gene O does not produce any antigens. Genes have to be
present in pairs. Here no gene is dominant or recessive to each other. The 3
genes can exist in 6 different forms. They are AA, AO, BB, BO, AB, OO.
Therefore there are 6 genetic groups or genotypes. But only 4 phenotypes.

Bombay blood group

Red blood cells of type O and A2 have large amounts of

another antigen called H substance. It is genetically different from ABO. H

substance is a precursor of A and B antigens.

An O group individual who inherits A or B antigen but fails to inherit H gene

from either parent is called Oh phenotype or Bombay Blood Group. All three
antibodies – Anti A, Anti B and Anti H are present. R.B.C.’s are not agglutinated
by antisera.

Rh Blood Group
Blood from Rhesus monkey is injected into the rabbit’s body. Rabbit’s
circulatory system will develop antibodies against monkey’s blood. When
different samples of human blood is mixed with rabbit’s serum there may be
agglutination or no agglutination. If agglutination is present the group is Rh +ve
if agglutination is absent the group is Rh-ve.

The criteria for this classification is presence or absence of Rh antigen and Rh

antibodies. In the Rh+ve blood, Rh antigen is present in the cell wall of the
R.B.C. and no Rh antibody will be present in the plasma. In the Rh-ve blood
there is no Rh antigen present in R.B.C. and no antibody in the plasma. Rh
antibody may not be produced spontaneously. Circulating system of Rh-ve
person may develop Rh antibody only if it is exposed with Rh+ve blood. Rh
antibody belongs to IgG type which is small in size and can cross through
placental barrier.

Genetics:
This system has three allelic pairs Dd, Cc and Ee. This produce five antigens—
D, C, c, E and e which are present only on the surface of R.B.C. membrane. No
d antigen. C, D and E are strong antigens and c and e are weak antigens.
Individuals with antigen D are Rh + ve because this antigen is highly
immunogenic. If no antigen D, they will be Rh-ve Rh positive individual may be
homozygous with DD group.
Genotypes

Rh +ve Rh −ve
DCE dce
DCe dCe
DcE dcE
Dce dCE

TABLE 2.14
Rh blood grouping
Genotype Phenotype group
DD, Dd Rh +ve
dd Rh –ve

or hetrogygous with Dd. The risk of sensitisation to C and E antigens are less
when compared to strong antigen D. Antigen D is strong immunogenic.
Therefore antigen D should be matched in blood transfusion.

Only 1st part of Landsteiner’s law is applicable to the Rh blood grouping, IInd
part of the law does not hold good. The percentage is Rh +ve is 95% and Rh –ve
is 5%.

Antigen Antibody Percentage Rh antigen — 95% — — 5%

+ve –ve ParentsDd dd +ve +ve –ve –ve Dd Dd dd dd

Children Dddd +ve –ve Dd DD dddd +ve +ve –ve –ve

Fig. 2.21
Inheritance of Rh blood group

Genetics: There are two genes for the inheritance of Rh blood grouping, gene D
and gene d. Gene D is dominant, gene d is recessive. Gene D is responsible for
the production of Rh antigen. This two genes can exist in 3 different forms i.e.,
DD, Dd, dd. There are 3 genotypes and 2 phenotypes. If both the parents are +ve
the children’s blood group can be either +ve or –ve.

If the parents blood group is +ve and –ve then the children’s blood group can be
either +ve or –ve. If both the parents blood groups are –ve then the children’s
blood group will be −ve.

Agglutination: Antigen, antibody reactions are known as agglutination.

Agglutination reaction is specific. Antigen A can react only with a antibody.
Similarly antigen B can react only with beta antibody. Antibody molecule have
multiple reaction sites or binding sites. When two different samples of blood
groups are mixed it will produce agglutination reaction. Several R.B.Cs will bind
with a single molecule of antibody. This leads to the clumping of R.B.Cs.
Clumped R.B.Cs settle down. These reactions are known as agglutination
reactions.

BLOOD TRANSFUSION
Blood transfusion means collecting blood from one person and donating to
another person.
Indications of Blood Transfusion
1. To compensate blood volume after a serious accident, stabbing and bullet
injuries.

2. Before or after a major surgical operation.

3. Before or after delivery.
4. As a treatment for severe anaemia.
5. In the treatment of severe jaundice i.e., exchange transfusion.

6. In the treatment of erythroblastosis foetalis— exchange transfusion.

7. In the treatment of blood cancer (leukemia)— exchange transfusion.

8. In the treatment of hemophilia.

General considerations of a donor

1. Donor should be healthy and should be free from all types of communicable
diseases like AIDS, malaria, hepatitis etc.

2. The donor should have adequate resource of blood in terms of volume, and
haemoglobin concentration.
3. Age: Donor should be above 18 years and should not be very old.

Group considerations
The group of the donor’s blood should match with the recipient. It is always
preferred blood transfusion between the same group.
AABBA
AB AB B O
O
AOO
B
AB
Fig. 2.22 Donation of blood
When the same blood group is not available, blood group ‘O’ can be considered
as an alternative. TABLE 2.15 Compatibility between donor and recipient
Donor
Type O −ve O +ve B −ve B +ve A −ve A+ve AB−ve AB +ve

AB +ve ✓ ✓✓✓ ✓✓✓ ✓ AB −ve✓✓✓ ✓ A+ve ✓✓ ✓ ✓

A −ve✓✓
B+ve ✓ ✓✓✓
B −ve✓✓ O+ve ✓✓ O −ve ✓

During blood transfusion we are biased towards the well being of donors
R.B.Cs. We may not allow any blood transfusion where there is a risk for
donor’s R.B.Cs When blood group “O” is given to other groups, the antibodies
of donor’s plasma will get diluted in the huge volume of recipient’s plasma.
Therefore extent of destruction of recipients R.B.Cs will be minimum. Similarly,
when AB blood receives blood from other groups, the donors R.B.Cs are not
destroyed, because AB blood group does not have any antibodies. Therefore “O”
is considered as the universal donor and AB group as universal recipient.
Consideration of Rh-factor in blood transfusion

Rh +ve → Rh +ve
Rh –ve → Rh –ve
Rh –ve → Rh +ve
Rh +ve should not be given to Rh −ve

Incompatible blood transfusion or Mismatched blood transfusion

Mismatched blood transfusion means blood group of donor is not matching with
recipients blood. For example, Blood group A is donated to a person of blood
group B.

Possible reasons for Mis-matched blood transfusion 1. Mistake in the

determination of the blood group of the donor or recipient.
2. Mistake in the labelling of the blood bottle. 3. Carelessness and negligence at
the time of blood transfusion.

Complications
1. Antigen, antibody reactions or agglutination.
2. Several R.B.Cs will bind around a single molecule of antibody. This will
result in clumping of R.B.Cs. 3. Clumped R.B.Cs get precipitated.
4. This may block the free flow of blood. Circulatory shutdown.
5. The precipitated R.B.Cs may get destroyed. This is known as haemolysis.
6. Excess haemolysis will lead to jaundice. Jaundice causes renal problems and
nervous complications. Other symptoms include fever and rigors or convulsions.
7. If it goes unnoticed, it may result in the death of the patient due to renal
shutdown and circulatory shutdown.
Prevention
1. Adequate care should be taken at every step of blood transfusion.
2. Cross matching should be done before blood transfusion. Cross matching
means physical verification of compatibility between donor’s blood and
recipient’s blood.
Cross matching: It is of two types:
(1) Major cross matching and
(2) Minor cross matching.
1. Major cross matching: Donor’s RBC is mixed with recipient’s serum. Look
for agglutination. 2. Minor cross matching: Donor’s serum is mixed with
recipient’s RBC. Look for agglutination. If agglutination is seen, do not proceed
with blood transfusion.

Rh Incompatibility
There are two common complications resulting from Rh incompatibility.

1. Transfusion incompatibility and

2. Erythroblastosis foetalis.
Transfusion incompatibility
Suppose Rh +ve blood is donated to Rh –ve individual. There may not be any
agglutination reactions and problems during the first transfusion. But C.V.S. of
the recipient is exposed to Rh +ve blood. Because of this C.V.S. of recipient will
produce Rh antibody. If Rh +ve blood is given second time it will lead to
agglutination reactions and produce complications of mismatched blood
transfusion. Erythroblastosis foetalis. Haemolytic Disease of Newborn.
Father Mother Rh + ve Rh +ve ✓ Rh –ve Rh –ve ✓ Rh –ve
Rh +ve ✓
Rh +ve Rh –ve ✗
Suppose father’s blood is Rh +ve, mothers blood is Rh –ve, the child’s blood
group may be Rh +ve. Even if child’s blood group is Rh +ve there may not be
any serious problem to the first child. During parturition small quantity of Rh
+ve blood of the child may enter the mother’s circulation. This exposes the
C.V.S. of the Rh –ve mother to Rh +ve blood. Mother’s blood produce Rh
antibody. During subsequent pregnancy if the foetal blood is Rh +ve it may lead
to complications.
This clinical complication is known as Erythroblastosis foetalis.
1. Mother’s blood with Rh antibody may enter into foetal circulation.
2. This antibodies will produce agglutination and haemolysis of foetal RBC.
3. Excess haemolysis may lead to the death of the foetus.
4. Hydrops foetalis—severe oedema.
5. Excess haemolysis leads to severe jaundice. The bile pigment’s concentration
in the blood will increase.
6. Bile pigments get deposited in the neurons of brain. This produces a
neurological problem known as kernicterus.
7. If the child is born alive it will be suffering from severe jaundice and anemia.
Icterus gravis neonatorum.
8. Such a child shows high mortality rate. 9. Due to increased distruction of RBC
there will be increased rate of erythropoiesis. Adequate time is not available for
maturation. This leads to the release of large number of blast cells into the
circulation. The blood will have large nucleated RBCs known as Erythroblasts.
10. Liver may be damaged.
11. Severe anemia.
Erythroblastosis foetalis may not be a serious problem because:
1. The first child may be Rh –ve. So, no problem for the second child also.
2. There is no risk for the first child even if it is Rh +ve.
3. If the first child is Rh +ve, mother should be injected with Rh antibody within
48 hours of delivery. These antibodies may destroy the Rh +ve R.B.Cs entered
from the child. Because of this mother’s body is no longer exposed to Rh
antigen.

So there is no question of production of Rh antibody in the mother’s blood.

4. If the child is suffering from severe jaundice and anemia it can be treated with
exchange blood transfusion. Rh −ve blood is transfused to the child.

Blood Bank
Blood bank is a specialised medical centre where blood of different groups are
collected for transfusion during emergency. Blood is collected from voluntary
donors and is mixed with anti-coagulant EDTA or acid citrate. Blood is stored in
a smooth glass or plastic containers. Blood is mixed with dextrose or (D-
Glucose). Blood is preserved at a temperature of 4oC. The container should have
a label giving following details.

Name: Age: Sex: Address:

Blood Group:
Date:

Blood can be preserved for 3 weeks or 21 days. At the time of donation, allow
the temperature of the blood to reach the room temperature.

Preservation injury: Hazards of stored blood When blood is preserved in the

blood bank certain adverse

changes occur in the blood. These changes are collectively called as preservation
injury.

The major defects are:

1. Loss of ATP
2. Hyperkalemia due to leaking out of K+ from stored RBC.

3. Increase in intracellular concentration of Na+ upto 40 mEq/L.

4. Increased intracellular Na+ leads to swelling of RBC and increased fragility.

5. Concentration of blood clotting factors decreases particularly factor VIII.
6. Anticoagulant citrate toxicity produce hypocalcemia.
Autologous transfusion or predonation: Patients blood is collected a few days
earlier to surgery. It is preserved in the blood bank and given during elective
surgery.

Complication of blood transfusion

Because of blood transfusion certain problems may arise in the patient. They are
broadly divided into two types.

(a) Non-hemolytic reactions

(b) Haemolytic reactions.
Non-homolytic reactions

1. Use of non-sterile transfusion set. This will lead to infections and entry of
pyrogens developing fever.
2. If the donors blood is not screened for communicable diseases, the patient
may get malaria, syphilis, hepatitis, filaria and AIDS.
3. Patient may develop allergic anaphylactic shock.
4. Circulating over load leading to heart failure.
5. Disturbances in sodium potassium balance in the blood.

Haemolytic reactions
If the donor’s blood is not matching with recepients blood it will lead to
complications of mismatched blood transfusion causing hemolysis of donor’s
blood. Both ABO incompatibility and Rh incompatibility may develop.
Significance of blood group

1. Knowledge of blood group is important in blood transfusion. Blood of the

donor and recipient should be compatible.

2. Blood group is taken as a mark of identity.

3. Knowledge of blood group is useful in solving medicolegal problems.
4. It is useful in solving disputes of parenthood– maternity & paternity.

Medicolegal importance of blood group

Blood samples or saliva is collected from the site of crime. It is used to find out
the blood group of people involved. This is helpful to identify or rule of
criminals and victims.

Knowledge of blood group is useful in solving paternity dispute cases.

Sometimes paternity of a child is disputed. Knowledge of blood group is useful
to solve such disputes. Blood group of people concerned—child, mother and
disputed father are determined. Careful study of blood group of these three
people can be used to rule out a man from the dispute of being the father of the
child. Example, if the baby is O group the father cannot be AB group. If the
baby is AB group, father cannot be O group. If the mother is B or O group and
baby is A group, father cannot be B or O group. Same way if the mother is A or
O group a man with blood group A or O cannot be the father of the baby. Thus if
the blood group of mother and child is known the suspicion on the paternity of
the child can be resolved. It is always for exclusion of a person but cannot prove
a man as the father of the child.

5. The study of blood group is useful in the study of genetics.

6. Knowledge of blood group is useful in anthropological studies.
7. Knowledge of blood group is also useful in avoiding erythroblastosis foetalis.

Coombs’ test
This test is done to detect the presence of incomplete antibodies on the surface of
RBC. These antibodies are

incomplete in that they do not by themselves bring about agglutination takes

place. In order to procure antibodies to human globulins are injected into a
rabbit.

In the direct test, the patient’s RBCs are washed and to this washed RBCs anti
human globulin serum, prepared from rabbit, is mixed. If agglutination occurs, it
is a direct Coombs’ test. In this test, the RBCs on the surface contained
incomplete antibodies, which could not be washed away. patient’s RBCs
containing incomplete antibodies. If rabbit serum containing anti human globulin
is added, agglutination of RBCs occurs. This is indirect Coombs’ test.

ANAEMIA

Anaemia is defined as the significant reduction in oxygen carrying capacity of

blood when compared to normal individual of same age and sex group.

Anemia is also defined as the significant reduction in R.B.C. count and/or

haemoglobin concentration, when compared to normal of same sex and age
group. In Indian population among male haemoglobin concentration below
13.2% and hematocrit below 40% and among the female hemoglobin
concentration below 11.8 gm% and hematocrit below 35% is considered as
anemia.

Causes of Anaemia
The major causes are:

1. Decreased production of RBC due to (a) Deficiency of nutrients.

This will adversely affect either rate of erythropoiesis or formation of
haemoglobin.
(b) Bone marrow depression.
2. Excess haemolysis
3. Excess loss of blood or haemorrhage Example: Accidents, internal and
external bleeding, major surgeries.
Rabbit serum
anti
human globulin

++ Rabbit serum anti human globulin

EXCESS RBC DESTRUCTION HAEMOLYSIS

ANAEMIA Defective RBC's Abnormalities in synthesis of

Hbinfections like malaria chemicals physical trauma Drugs

Patient's
RBC +incomplete
antibodies
Normal RBC Patient's

serum
incomplete antibodies BLOOD LOSS DECREASED PRODUCTION

OF RBC OR Hb
Heavy and persistent menstrual loss persistent bleeding,
piles worm infestations
Acute loss—Accidents
Defficiency of iron, proteins, vitamin C, vitamin B12 and folic acid bone marrow depression Osteoporosis,
Hypothyroidism

Fig. 2.24 Major causes of anaemia

AgglutinationAgglutinationdirect indirect
Fig. 2.23 Coomb’s test In the indirect test, the surface incomplete antibodies are
removed while washing the RBCs are mixed with the

Aetiological Classification of Anaemia Classification based upon causes:

I. Decreased production of RBC

1. Deficient supply of essential nutrients. (a) Iron deficiency anaemia.

(b) Folic acid deficiency anaemia.
(c) Vitamin B12 deficiency anaemia (pernicious

anaemia).
2. Inactivity of the bone marrow: Hypoplastic anaemia (a) Irradiation, X-rays,
nuclear radiations. (b) Anticancer drugs
(c) Cause unknown

3. Chronic renal disease

4. Chronic inflammatory disease
5. Hypothyroidism
6. Infiltration of bone marrow
II. Increased destruction of RBC — Haemolytic anemia
1. Corpuscular defect
(a) Sickle cell anemia
(b) Thalassemias
(c) Hereditary Spherocytosis
(d) Glucose 6-Phosphate dehydrogenase deficiency
2. Extra corpuscular defect
(a) Immunological damage of RBCs due to antibodies
(b) Drugs like chlorophenicol
(c) Haemolysins in snake venoms
(d) Ether, chloroform
(e) Hypersplenism
(f) Infections like malaria
III. Abnormal loss of blood
1. Acute loss — accidents, stabbing, bullet injuries. 2. Chronic loss — internal
bleeding
(a) Heavy menstrual loss
(b) Piles
(c) Hookworm infection
Classification of anemia based on MCV and MCH/ MCHC: Morphological
classification
MCV is mean corpuscular volume: 90 cubic micron MCH is mean corpuscular
haemoglobin: 30 picogram.

Depending upon MCV there are three types of anemia. They are:

1. Normocytic, MCV is equal to 90 C µ

2. Macrocytic, MCV is above 90 C µ
3. Microcytic, MCV is below 90 C µ According to MCH, and MCHC anemia is
classified into three types:
1. Normochromic MCH is equal to 30 picogram MCHC is about 33%
2. Hypochromic MCH is below 28 picogram MCHC is less than 33%
3. Hyper chromic MCH is above 37 picogram MCHC is above 37% Normally
not seen.

TABLE 2.16
Morphological or Wintrobe’s classification of anaemia
Normochromic Hypochromic Normocytic
Macrocytic
Microcytic

After acute hemorrhage

All haemolytic anaemias except Thalassaemia Aplastic anaemia

All megaloblastic anaemia due to deficiency of Vitamin B12, folic acid or

intrinsic factor Chronic infections
After chronic hemorrhage
Secondary to liver disease

Iron deficiency anaemia Thalassaemia

Protein deficiency

Depending upon severity or haemoglobin concentration, anemia is classified

into three types. (a) Mild anemia—Hb content—10–11 gm%
(b) Moderate anemia—Hb content—7–8 gm%
(c) Severe anemia—Hb content is less than 6 gm%

TABLE 2.17
Laboratory characteristics in different types of anemia

Types of Anemia Colour Index

MCV MCH MCHC Appearance

Size of RBC Reticulocyte percentage Other features

Iron
deficiency Decreases Decreases Decreases Decreases Microcytic hypochromic
Increases Decrease in total iron binding capacity
Haemolytic* No

change No No No change change change Normocytic normochromic

Significantly increases Increase in serum bilirubin level
Pernicious or Megaloblastic Increases Increases No No

change change Macrocytic normochromic

Decreases Bone marrow shows

megaloblastic Blood loss No

change No No No change change change Normocytic normochromic Increases

Aplastic No

change No No No change change change Normocytic normochromic

Decreases Decrease in platelet, Increase in lymphocytes

* Features depend upon relative iron deficiency.

Common Types of Anemia Iron deficient anemia 1. Aplastic anemia Causes

of iron deficiency Aplastic anemia is due to non functioning of bone marrow. 1.
Deficiency of iron in the diet Aplasia of the bone marrow may be due to the
following Decreased intake—only milk fed infants reasons: The rich source of iron
is green leafy vegetables.

(a) Repeated x-ray exposure Inadequate intake of green leafy vegetables may (b)
Nuclear radiation result due to lack of availability, ignorance and (c) Natural
radiations, example: rocks, sands ofpoverty.
beaches emits natural radiation. 2. Increased requirements of iron during (d) Infections
like viral hepatitis.(a) Infancy

(e) Drugs. Certain drugs like sulphanamide depress(b) Pregnancy

the bone marrow. This will result in reduction in 3. Decreased absorption due to
deficiency of HCl and the rate of erythropoiesis. So, number of R.B.Cs vitamin
C, phytate.
will be less and it will manifest as normocytic 4. Excess loss of iron due to
normochromic anemia. Other symptoms—decrease(a) Acute hemorrhagein platelet and
leukocyte count. Bonemarrow— (b) Chronic hemorrhagehypocellular. (c) Excess menstrual
bleedingTreatment—Removal of causative factors. Salient features

2. Nutritional anemia
(a) Blood pictures—RBC-microcytic hypochromic.This type of anemias are due to deficiency
of one or more Anisocytosis and poikilocytosis are observed.
than one nutrients. This include protein deficient anemia. (b) Blood Indices—decrease in MCV, MCH,
MCHCInadequate intake of proteins may be due to poverty,
ignorance, and food habits. This type of anemia is(c)characterised by microcytic, and
hypochromic. Size of the (d)R.B.C. is less and less volume. MCV decreases and MCH

and MCHC are also decreased. (e)

and CI.
Lifespan of RBC—normal Bone marrow—normoblastic hyperplasia. WBC and
platelet count—normal.

Other symptoms:
Nail—Dry, soft, spoon shaped, striated.
Tongue—Red
Hair—Brittle
CVS—Palpitation
Dysphagia
Nervous system—Irritability, lack of concentration

Treatment:
(a) Iron supplementation through food.
(b) Oral administration of ferrous sulphate (c) Intramuscular injections of iron—
dextran complex.

Vitamin B12 deficiency Anemia—Megaloblastic, Macrocytic anemia

Vit B12 is essential for DNA synthesis and maturation of RBC. In case of Vit B12
deficiency, defective and slow chromosomal synthesis occurs. This slows down
maturation. Instead of normoblasts, megaloblasts are formed in the red bone
marrow. These megaloblasts from large RBC macrocytes. This type of anemia is
megaloblastic or macrocytic anemia.

Causes for Vit B12 deficiency

1. Nutritional causes for Vit B12 deficiency are very rare.

2. For the absorption of Vit B12 in the intestine, intrinsic factor of castle—a
glycoprotein secreted by stomach is very important. It gives a protective
converging to Vit B12 and there by helps in its absorption. If IF is not secreted
B12 cannot be absorbed even if it is present in adequate quantity in the diet.

The major reasons for non secretion of intrinsic factor are:

(a) Atrophy of gastric mucosa due to autoimmune destruction of parietal cells of
stomach.
(b) Gastrectomy.
(c) Severe gastric ulcer.
(d) Malabsorption syndrome, sprue where the fault lies with malfunctioning of
the enterocyte and no absorption of Vit B12 IF complex occurs. The anemia
resulting of from deficiency of Vit B12 due to the absence of intrinsic factor is
known as pernicious anemia or addisonion anemia. It is anemia causes due to
the deficiency of intrinsic factor with a consequent failure in the absorption of
extrinsic factor – Vit B12.

Characteristic features:
1. Bone marrow: Hyper plastic bone marrow.

Megaloblastic precursor cells.

2. Blood: RBC—macrocytic and normochromic.
RBC count decreases significantly
Haemoglobin—Decreases
Diameter of RBC—large 8.2 µ
MCV — >100 µ
MCH—increases up to 50 picogram
MCHC—almost normal, normochromic
Smear—nucleated RBC megaloblasts
Reticulocyte count – increases above 5%
RBC life span decreases
Haemolysis – increases
Serum bilirubin – increases above 1 mg% low grade
haemolytic jaundice, skin—lemon yellow.
WBC and platelet count decreases
Other symptoms include soreness and inflammation
of tongue
Diarrhea.

Nervous system
Neurological defects—demylination.
Subacute combined degeneration of spinal cord. Sensory and motor
disturbances.
Parasthesia, numbness, ataxia.
Treatment: Administration of Vit B12 through parenteral route (by injection).

Folic acid deficiency anemia: Megaloblastic, Macrocytic anemia

Folic acid deficiency produces anemia which is clinically identical to B12
deficiency anemia.

Causes for folic acid deficiency:

(a) Dietary deficiency.
(b) Poor absorption—steatorrhoea.
(c) Actions of anti-folate drugs—anticancer drugs.

Symptoms:
Failure for the maturation of RBC.
RBCs are large with immature nucleus
Macrocytic & hypochromic
No neurological disorders

3. Haemolytic anemia
It is due to excess destruction of R.B.C.
1. Actions of chemical haemolytic agents like ether and chloroform.

2. Complications of mismatched blood transfusion.

3. Erythroblastosis foetalis.
4. Infection like malaria.
5. Haemolytic actions of drugs like sulphanamides. This type of anaemia results
from excess destruction of RBCs. Bone marrow can compensate by increasing
the rate of production of RBC to some extent. Broadly there are two major
causes.

TABLE 2.18
Causes for haemolysis
S.No. Intra erythrocytic defects Extra erythrocytic defects

Congenital-membrane defects like hereditary spherocytosis

Haemoglobin defectssickle cell anaemia, thalassemias.

Enzyme defects- G6 PD deficiency.
Abnormal hemoglobins like Hb-C, Hb-E
Autoimmune antibodies

Exposure to haemolytic agents like ether , chloroform, snake venom Drugs —

sulphanamides Infections — malaria
Mismatched blood transfusion

1. Sickle cell anemia

passing through narrow capillaries. Hypoxia makes the haemoglobin further less
soluble and it complicates the situation. The excess destruction of R.B.C. result
in lowering of R.B.Cs count and anemia.
Clinical features: Server hemolysis, jaundice, fatigue, frequent infections,
cardiomegaly, systolic murmurs. The blood picture is normochromic and
normocytic.

2. Hereditary Spherocytosis
This is a genetic disorder. Autosomal dominant inheritance. Here R.B.Cs are
spherical in shape. Spectrin is absent in RBC cell membrane. This type of
R.B.Cs are more prone for destruction while passing through narrow capillaries.
This results in excess haemolysis and anemia.
3. Thalassaemia or Mediterranean anemia or Cooley’s

anemia
It is a genetic disorder. Synthesis of either a chain or β chain of haemoglobin
becomes depressed. Accordingly there are two types of thalassaemia—α
thalassaemia and β- thalassaemia. β-thalassaemia is more common. It is of two
types major—total absence of β-chain. Cooley’s anemia or mediterranean
anemia. Minor-partial absence of β- chain more common. In this type R.B.Cs
cell wall is less elastic and more fragile. This type of R.B.Cs are easily destroyed

while passing through narrow capillaries of reticulo endothelial system.

Thalassaemia

It is a genetic disorder. Homozygous disorder, inherited from both the parents.

Here the haemoglobin synthesised is of different type – HbS. In the HbS, 6th
position of β chain glutamic acid is replaced by valine. HbS is less soluble in
water. It gets easily precipitated and settles at one side of the R.B.Cs. This gives
a sickle shape to R.B.Cs. This type of R.B.Cs are more fragile, they get easily
destroyed while

TABLE 2.19
Types of thalassaemias
b-(More common) a( -rare)
Major Minor (More common)
Sl.No. Major β-thalassaemia Minor β-thalassaemia

1. It is also called Colley’s anaemia or Mediterranean anaemia

2. Prevalence
3. Inheritance

4. Anaemia
5. Basic defect
6. HbF levels
7. Life span Less common

‘Homozygous’ transmission ( i.e.,when identical abnormal genes are inherited

from both parents and all of the haemoglobin is abnormal)

Moderate to severe
Total absence of β-chain synthesis Markedly increased
Shorter average age of death 17th year. More common

‘Heterozygous’ transmission ( i.e.,when an abnormal gene are inherited from one

parent directs the formation of abnormal haemoglobin)

Mild
Partial synthesis of β-chain synthesis
Normal or slightly increased

Longer; the patient survives upto adult life and can transmit the gene to the
offsprings.

Effect of anemia on the body

1. Significant reduction in the O2 carrying capacity of the blood.

2. It will produce anemic hypoxia.
3. This will reduce the physical fitness and the ability to work.
4. The anemic person easily gets fatigue and giddiness.
5. It increases the work load of the heart.
6. Anemia increases heart rate, cardiac output and velocity of blood flow.
7. The individual will be pale, weak, and easily prone for diseases.
8. Haemolytic anemia is usually associated with jaundice.
9. Anemia increases rate and depth of respiration. Severe anemia produces
breathlessness. 10. Anemia produces symptoms like nausea, vomiting and
constipation.
11. Effect of anemia on nervous system includes lack of concentration,
restlessness and hyper irritability.

TABLE 2.20
Clinical features of anemia
Sl. Symptoms No.
Signs
1. Fatigue Palor – skin, mucus
membrane and conjuctiva 2. Breathlessness Tachycardia 3. Palpitation Oedema
4. Thrombing in head,

Dizziness, Headache Nail cracking Brittle nails

Test for anemia

1. Determination of R.B.C. count.

2. Determination of haemoglobin concentration. Calculation of MCH, MCHC

Treatment

1. Nutritional supplementation with proteins, vitamins, minerals etc.

2. Blood transfusion for treating severe anemia.
3. Bone marrow transplant.

Polycythemia
It is a condition where there is a significant rise in RBC count and increase in
haemoglobin concentration. WBC and platelet count may or may not increase.

There are two types of polycythemia.

1. True polycythemia — or polycythemia vera
2. Secondary polycythemia.

Polycythemia Vera—Erythremia
In this condition stem cells in red bone marrow start to produce new cells
without any inhibition. If this uncontrolled production of cells happens at
pluripotent stem cell stage counts of all the types of cells—RBC, WBC and
platelet increases. If the uncontrolled cell division starts from committed stem
cell stage, only RBC count may rise with

simultaneous increase in hemoglobin concentration. RBC count increase above

10 million/c. mm. Erythropoietin level will be normal.

Cause: Malignancy of red bone marrow.

Secondary Polycythemia—Erythrocytosis
In this condition there is a chronic hypoxia leading to rise in erythropoietin
production. Erythropoietin stimulates the bone marrow and increases the rate of
RBC production. This leads to a rise in RBC count. The persistant hypoxia may
be due to—

5. Dimness of vision Spleenomegaly 6. Insomnia Increase in respiratory rate and

depth
7. Hypoxia Decrease in the viscosity of blood

8. Increased cardiac output

Increased systolic blood pressure Systolic murmur

(a) High altitude

(b) Respiratory disorders like emphysema (c) Chronic hemorrhage
(d) Congenital heart disease
(e) Chronic carbon monoxide poisoning
(f) Inappropriate increase in erythropoetin secretion

due to renal tumors, liver tumors, brain tumors.

In this type of polycythemia there will be rise in RBC count and Hb

concentration but WBC count and platelet count will be mostly normal.

Relative polycythemia: the concentration of RBC becomes more than normal,

but total red cell mass is normal. This occurs as a result of loss of blood plasma.
Reduced plasma volume but normal red cell mass is seen.

Cause—dehydration, low fluid intake, vomiting, diarrhoeas and acidosis.

Clinical features:
1. Significant increase in RBC count above 7 million/c. mm.

2. Increase haematocrit value above 0.60

3. Increase in blood volume
4. Increase in the viscosity of blood
5. Increase in the total peripheral resistance

6. Entire vascular system becomes intensely engorged.

7. Plugging of many capillaries leading to blocking of blood flow.

8. Poor oxygen circulation. This leads to headache, dizziness, vertigo, ringing in
the ears (tinnitus) and chest pain.
9. Abnormal bleeding from nose and gums 10. Enlargement of liver and spleen

Erythrocyte Sedimentation Rate (E.S.R.)

It is defined as rate at which R.B.Cs settle down when a sample of blood is

mixed with an anticoagulant and allowed to stand in a graduated vertical tube. It
is expressed in terms of millimeters (mm) of clear supernatant plasma formed at
the end of one hour.

Methods of determination
There are two methods for the determination:
1. Wintrobe’s method and
2. Westergren’s method.
Westergrens method

A sample of blood is collected and mixed with an anticoagulant (Sodium citrate).

This sample of blood is pipetted into Westergren’s pipette. The pipette is placed
in the vertical stand. Time is noted. After one hour mm of clear plasma formed at
the top is noted.

Normal value
In adult male—1–4 mm at the end of one hour. In adult female—4–9 mm at the
end of one hour. In infants—0.5 mm at the end of one hour.

Physiological variations
Age: ESR is less in infants and more in adults. Sex: ESR value is more in
females than in males.
Altitude: In high altitude ESR decrease because R.B.C. count increases.
Pregnancy: ESR increases during pregnancy.

Pathological variations : Pathology increase

(a) Acute and chronic infections.
(b) Collagen disorder where there is an increase in

globulin.
(c) Malignancy.
(d) Anemia especially iron deficiency anemia.

Pathological decrease
(a) Allergy
(b) Polycythemia
(c) Sickle cell anemia
(d) Hereditary spherocytosis
(e) Hypofibrinogenemia.

Factors effecting ESR

1. R.B.C. count: When R.B.C. count increases ESR decreases.

2. Rouleaux formation is piling up of R.B.Cs, any factor which favours rouleaux
formation will increases ESR value.
05
20
40 ESR

60 0 10 1 9 PCV
80 2 8

37
100 4 6
55
120 6 4
73
140 8 2
91
180 10 0B

A Wintrobe's tubeWestergren's pipette

Fig. 2.25 Methods of determination of ESR and PCV

Concentration of plasma proteins

Gobulin and fibrinogen. Increase in these plasma protein concentration favours,

rouleaux formation and increases ESR. Increase in plasma protein albumin
opposes the rouleaux formation and decreases ESR.

3. Increase in oxygen level in the blood will increase ESR.

4. Increase in CO2 in the blood will decrease ESR.
5. Plasma lipids: Increase in cholesterol increases ESR. Increase in lecithin
decreases ESR.
6. Viscosity of blood: Increase in viscosity of blood decreases ESR.

Significance of ESR

ESR is of very little diagnostic importance – ESR increases during a wide

variety of infective diseases ranging from viral cold, typhoid, tuberculosis,
leprosy etc.

The increase in ESR does not point at any specific disorder or disease. But ESR
is of much prognostic importance. It is useful for the prognosis of disease and
treatment. ESR indicate severity of disease ESR helps in the differential
diagnosis of tumors as benign and malignant. In malignancy ESR increases very
much.

Packed cell volume (PCV) or Haematocrit

PCV means the percentage of volume of RBC in the blood. Haematocrit is the
ratio of volume of RBC to volume of blood.
Normal value PCV
Male 45% + 3% Female 42% + 3% Newborn 52% + 3%

Determination
Haematocrit 0.45 + 0.03 0.42 + 0.03 0.52 + 0.03

PCV is estimated using Wintrobe’s tube. A sample of blood is collected and

mixed with an anticoagulant mixture of ammonium oxalate and potassium
oxalate. The sample of blood is filled inside the Wintrobe’s tube using a Pasteur
pipette. This tube is centrifuged at a speed of 3000 (rpm) rotation per minute for
a duration of minimum 30 minutes. The R.B.Cs gets packed in the bottom.
Above the R.B.Cs there will be a thin layer of W.B.C. & platelets—Buffy coat.
Above that, plasma is seen.

Significance of PCV
1. PCV value gives a rough idea about R.B.C. count
2. PCV is required for the calculation of blood indices like MCV and MCH.

MCV = PCV × 10, MCHC =Hb × 100RBC PCV

3. The colour and nature of supernatant plasma may suggest certain disorders.
Suppose plasma is reddish it indicates that R.B.C’s are haemolysed. If it is
yellowish it indicates jaundice. If it is turbid it indicates the increase in lipid
concentration in blood.

4. Increase in PCV is seen in

(a) Polycythemia
(b) Hemoconcentration due to diarrhoea, dehydration. (c) Chronic heart disease.

5. Decrease in PCV is seen in

(a) Anemia
(b) Hemodilution as in pregnancy.

Blood Indices
I. Colour Index =

Percentage of Hb Percentage of RBC 15 gm as 100%

5 million/c.mm as 100%
Normal range: 0.85 to 1.15 and is not a dependable parameter.

II. Mean Corpuscular Volume (MCV): Normal value 80 to 94 c.µ

MCV = Volume of PCV in ml × 10Red
count in million/c.mm Normal value 80 to 94 c.µ.
This indicates the average volume of an RBC. MCV ↑ — Macrocytosis —
Megaloblastic anaemia
MCV ↓ — Microcytosis — iron deficiency anaemia

III. Mean Corpuscular Haemoglobiln (MCH): Normal value: 29.5 + 2.5

picogram
Hb in gms % ×10MCH = RBC in millions/c.mm.
This indicates the average Hb content in one RBC.
MCH ↓ — Iron deficiency anaemia MCH ↑ — Megaloblastic anaemia

IV. Mean Corpuscular Haemoglobin

Concentration (MCHC):
Normal MCHC is 33%
MCHC = Hb in grams per %× 100PCV

MCH = MCH ×100PVC

This can also be expressed as 33 gms/100 ml of PCV.

This also indicates that 33% of each RBC is Hb MCHC ↓ — Iron deficiency
anaemia. MCHC is normal in megaloblastic anaemia as MCV and MCH are
affected equally.

Osmotic fragility is a test to detect whether red blood cells are more likely to
break down. This test is performed to detect hereditary spherocytosis and
thalassemia. Hereditary spherocytosis makes red blood cells more fragile than
normal. Some red blood cells in patients with thalassemia are more fragile than
normal, but a larger number are less fragile than normal. Osmotic fragility is
usually expressed as concentration of saline at which hemolysis srarts and
completes.

BLOOD VOLUME
Quantity of blood present in the body. Normal volume— 5–6 litres.
70–90 ml/kg body weight 3 Lt/m2 of body surface area. Physiological Variation
1. Age
2. Sex
3. Altitude 4. Exercise
5. Emotion 6. Body size

7. Prolonged standing
8. Pregnancy
: More in adults
70 ml/kg in adults
85 ml/kg. in children

: More in male than female 10–15%

: More in high altitude
: Increase blood volume because of contraction of spleen

: Increase blood volume

: Larger body size—more blood volume

: Decrease in blood volume
: Increase in blood
volume 20–30%

Pathological variations in blood volume

Increase in blood volume
1. Congestive cardiac failure
2. Hyperthyroidism
3. Hyper aldosteroidism
4. Renal failure
5. Polycythemia
Decrease in blood volume
1. Haemorhage 2. Prolonged internal bleeding 3. Burns
5. Vomiting 4. Dehydration 6. Diarrhoea Determination of blood volume
There are two methods for the determination of blood
volume.
1. Direct method and 2. Indirect method.
Direct method cannot be practiced in human beings.
Indirect method
Dye dilution technique
The dye used should fulfill the following criteria: 1. Should be non-toxic.
2. It should be physiologically and biochemically inert. 3. It should stain only the
plasma and not cells. 4. It should not easily escape out of the blood vessels. The
commonly used dye are Evans blue and Congo
red.
Technique
About 10 ml of blood is collected and used for finding
out packed cell volume (PCV) 5 ml of 10% of Evan’s blue
is injected intravenously. After sometimes blood is collected
from the opposite side of the body. This sample of blood is
centrifuged and plasma is prepared.
A standard solution is prepared by diluting 0.01 ml of
dye to 5 ml using plasma of 1st sample of blood. 500 times dilution, optical
density of standard and
unknown sample (the plasma of 2nd sample of blood) are
estimated using a colorimeter. The plasma volume is
calculated using the formula.
PV = Amount of dye injected × Dilution factor

OS of std. OD of unknown Blood Volume = Plasma Volume ×100(100− PCV)

OD = Optical density
PCV = Packed cell volume

Regulations of blood volume

Blood volume is maintained within the normal range.

There are several mechanisms for the regulation of blood volume.

1. Regulation of blood volume by blood pressure.

2. Regulation of blood volume by thirst mechanism.
3. Regulation of blood volume by hormones like ADH.
4. Regulation of blood volume by
Renin-Angiotensin-Aldosterone axis.
5. The extra cellular fluid acting as a buffer.

1. Regulation of blood volume by B.P. Suppose blood volume increases it will

increase blood pressure. Increase in BP will increase GFR (Glomerular filtration
rate). This will increase urine output. This will increase water loss from the
body. It will inturn decrease blood volume and thereby

3. Regulation of blood volume by ADH (antidiuretic hormone): Suppose

osmotic concentration of blood increases. That will stimulate the hypothalamus.
This will inturn stimulates posterior pituitary. Posterior

decrease B.P.
+ Hypothalamus
+ Kidneys +
Post. pituitary
GFR Osmotic concentration of blood ADH
Blood pressure Urine output Starting blood volume (dehydration)+
– Kidney
Water loss Water loss Blood volume
– Water
reabsorption

Fig. 2.26
Regulation of blood volume by blood pressure

2. Regulation of blood volume by thirst mechanism:Suppose osmotic pressure

of blood increases that will stimulate certain neurons of the hypothalamus. These
neurons are known as osmo receptors. This will generate a sensation of thirst.
Thirst will lead to drinking. Drinking is a behavioural act. It is controlled and co-
ordinated by cerebral cortex. Drinking increases water intake and it will increase
blood volume. This will decrease osmotic concentration of blood to the normal
level.

Fig. 2.28
Regulation of blood volume by ADH

pituitary secrete more ADH. ADH acts at the kidneys, reabsorption of water
increases, this decreases water loss, increases blood volume. This in turn
decreases osmotic concentration of blood to normal.

4. Regulation of blood volume by ReninAngiotensin-Aldosterone

axis:Regulation of blood volume by Renin-Angiotensin-Aldosterone
mechanism. Suppose blood volume decreases, it will decrease the blood
pressure. Decrease in blood
+ Osmoreceptors hypothalamus + Kidneys

Osmotic
concentration of blood
Cerebral cortex

Thirst BP
BV– Renin
Angiotensin substrate

Angiotensin I converting enzyme

Angiotensin II Drinking
Blood volume (dehydration)
–
Water loss +
Adrenal cortex
Water intake Water
reabsorption

Sodium reabsorption Aldosterone

Kidneys+
Absorption
Fig. 2.27 Regulation of blood volume by thirst mechanism Fig. 2.29
Regulation of blood volume by Renin-AngiotensinAldosterone mechanism

volume and blood pressure will stimulate the kidneys to secrete renin. Renin will
act upon a plasma protein—angiotensin substrate. It forms angiotensin I.
Angiotensin I is converted into angiotensin II by the action of converting
enzyme. Angiotensin II stimulate adernal cortex and increases the secretion of
aldosterone. Aldosterone acts at the kidney. It increases sodium reabsorption
which inturn increases the reabsorption of water. This will decrease the loss of
water through urine. So water is retained in the body. This inturn increases the
blood volume to normal.

3L as plasma - 4%

Blood volume 5L
BODY FLUIDS
Major Components of Body
Plasma
2L as inside the cells
Extracellular fluid compartment
37%
Interstitial fluid

In young adult male Proteins

Fats
Carbohydrates Minerals
Water
Lymph

— 17% of body weight — 14.5% of body weight — 1.5% of body weight — 7%

of body weight — 60% of body weight.

Body fluid content or total body water

In a young adult of 70 kg body weight — 40 litres. Percentage of water content
in body — 45%–75%
Extracellular - 30% Infant 75%
63%
Intracellular fluid compartment

Fig. 2.30
Body fluid compartments
Intracellular - 45%

19% Extracellular Adult Male 57%

38% Intracellular

14% Extracellular Adult Female 47%

33% Intracellular Compartment of body fluid
Intracellular
25L (625.5%)

Total body water Plasma 4% 40L

Extracellular
15L = (37.5%)Interstitial

16%

Extracellular Fluid 15 L 37.5%

Divided into 5 sub units
1. Plasma — 7.5% of TBW 2. Interstitial fluid and lymph — 20% of TBW 3.
Fluids in bones — 7.5% of TBW

4. Fluid in dense connecting

tissues like cartilage — 7.5% of TBW 5. Transcellular fluid — 2.5% of TBW

Transcellular fluid includes

(a) Cerebro spinal fluid
(b) Intraoccular fluid
(c) Digestive juices
(d) Serous fluid—intrapleural fluid, pericardial fluid

and peritonial fluid.

(e) Synovial fluid in joints
(f) Fluid in urinary tract.
TABLE 2.21
Water Balance: Intake versus output of water
Intake Output

Water in foods 700 ml Lungs – expired air 350 ml Ingested liquids 1500 ml Skin
– By diffusion 350 ml Water formed by catabolism 200 ml By sweat 100 ml

Kidneys – urine 1400 ml In faeces 200 ml

Total 2400 ml 2400 ml

TABLE 2.22 Concentration of major substances in the different

compartments of body fluids Substance

Cations
Sodium Na+
Plasma extra cellular fluid Interestitial fluid Extracellular fluid
Intracellular fluid
135–145 mEq/L 145 mEq/L 14 mEq/L
Potassium K+ 3.5 to 5 mEq/L 5 mEq/L 155 mEq/L
Magnesium Mg+ 1.9 mEq/L 2 mEq/L 15 mEq/L
Calcium Ca++ 9–11 mg% 5 mEq/L 1 mEq/L
Other cations 2.7 mEq/L 2.0 mEq/L 2.0 mEq/L
Total Cations 163 mEq/L 154 mEq/L 184 mEq/L Anions Chloride 100–110 m
Eq/L 110 mEq/L 08 mEq/L
Bicarbonate 55–77 mg% 28 mEq/L 10 mEq/L
Phosphate 2.5–4.5 mEq/L 4 mEq/L 10 mEq/L
Sulphate 1 mEq/L 1 mEq/L 4 m Eq/L
Total Anions 163 mEq/L 154 mEq/L 184 mEq/L
Proteins 7.3 gm % 2 gm % 16 gm %
Amino acids 30 mg % 200 mg %
Glucose 80–120 mg % 90 mg % 0-20 mg % Urea 15–40 mg %
Lipids 0.5 g% 2–95 gm %
Creatinine 0.6–1.8 mg %
Uric Acid 3–7 mg %
Bilirubin 0.2–0.8 mg %
Cholesterol 150–250 mg %
Determination of body fluid
Principle of dye dilution method
The volume of any compartment of the body can be measured by placing a
substance in the compartment, allowing it to disperse evenly throughout the
fluid, and then measuring the extent to which the substance has become diluted.

Volume in milliliter
Quantity of test substance instilled= Concentration per ml of dispersed fluid

Fortunately certain substance remain in specific fluid compartments without

diffusing into the other compartments. Therefore by choosing the appropriate
‘marker substance’ the fluid volume of almost any compartment of the body can
be measured using dilution principle.

Characteristics of Marker substance

1. It must be nontoxic.
2. It must mix with the fluid compartment within a reasonable time.
3. It should not be excreted easily.
4. It should be excreted from the body completely within a reasonable time.
5. It should not change the color of body fluid.
6. It should not alter the volume of body fluid. Marker substance used to
measure
A. Total Body water

B. Extracellular Fluid

C. Plasma Volume
- Deuterium oxide (D2O), Antipyrine - Tritium oxide (H3O)

- Radioactive sodium, chloride, bromide, sulphate, Non metabolisable

saccharides like inulin, mannitol, sucrose.
- Radioactive iodine, Evan’s Blue (T-1824)

Measurement of Total Body Water

The volume of total body water (fluid) is measured by using the marker
substance deuterium oxide or tritium oxide (Radioactive water or heavy water)
which get distributed throughout all the compartments of body fluid. This
substance mix with fluids of the compartments within a few hours after
injection. Since plasma is the part of total body fluid, the concentration of
marker substance can be obtained from the sample of plasma. Total body water
is calculated using the principle and formula of dye dilution method. V =

M
C
where V = Volume of fluid
M = Quantity of substance injected

C = Concentration
Measurement of extracellular fluid volume

The substances which pass through the capillary membranes easily but not into
the cell are used to measure extracellular fluid volume. For example,
Radioactive sodium, chloride, inulin, sucrose etc. These substance remain in the
extracellular fluid only and do not enter the cell. When any one of these
substances are injected into the blood, it mixes with all the sub-compartments of
body fluid within ½ to 1 hr. Since plasma is a part of extracellular fluid,
concentration of dye in a sample of plasma is taken. Dye dilution method
formula is used. Some of the marker substance like sodium, chloride, inulin,
sucrose etc. diffuse more widely throughout all the subcompartments of
extracellular fluid. So the measured volume of extracellular fluid by using these
substance is called as sodium space, chloride space, inulin space etc.

Measurement of ECF volume using sucrose

Quantity of sucrose injected - 150 mg Urinary excretion of sucrose - 10 mg
Concentration of sucrose in plasma - 0.01 mg/ml. The sucrose space
Mass injected − amount lost in urine= Concentration in plasma

150 10 mg− ==140 14 000 ml.= 0.01 mg / ml 001

ECF volume = 14 litres
Measurement of intracellular fluid volume

The volume of intra cellular fluid cannot be measured directly. It is calculated by

finding both total body fluid volume and extra cellular fluid volume.

Intracellular fluid volume

= Total Body Water – Extracellular fluid volume.
RETICULO ENDOTHELIAL SYSTEM OR MONONUCLEAR
PHAGOCYTE SYSTEM
It is a specialised body defence mechanism. It is also known as macrophage
system. It involves cells, which destroy foreign organisms and particles.
Macrophages are broadly divided into two groups.
1. Fixed macrophages – also known as tissue

histiocytes.
2. Wandering macrophages.

Special names of macrophages are:

Histiocytes in loose connective tissue.
Kupffer cells in the liver
Osteoclasts in bone (they absorb and remove bone) Microglial cells in nervous
tissue like the brain Langerhans’ cells in the epidermis—they recognise antigens,
ingest them and present them to lymphocytes for eventual destruction
Glomerular mesangial cells in the kidney Pulmonary alveolar macrophages in
the lungs Macrophages in the spleen and lymph nodes Monocytes in the blood.

Tissue histiocytes are predominantly seen at spleen, bone marrow, lymph node,
liver (Kupfer cells), alveoli, skin and connective tissue. Wandering macrophage
includes monocytes and neutrophils.

Functions of Reticuloendothelial Cells

The cells of the reticuloendothelial system play an important role in the defense
mechanism of the body. The various functions of these cells are the following:

1. Macrophages take important role in defense of the body by means of

phagocytosis. The invading organisms like bacteria or other foreign bodies are
phagocytosed by the macrophages.

2. When any foreign body invades, macrophages ingest them by phagocytosis

and liberate the antigenic products of the organisms. These antigens activate the
B-Lymphocytes and helper Tlymphocytes.

3. Macrophages also secrete the hormonal substance interleukin-1. The

interleukin activates the maturation and proliferation of specific Blymphocytes.

4. These ingest the inorganic particles like carbon dust particles, silicon etc.
when injected into the body.
5. The reticuloendothelial cells particularly those in spleen destroy the senile red
blood cells and release hemoglobin.
6. The reticuloendothelial cells convert hemoglobin into the bile pigment-
bilirubin and biliverdin.
7. These cells play an important role in the production of blood cells.

OEDEMA

Oedema means presence of exess fluid in the tissues of the body mainly in the
extracellular fluid compartments. It is mainly due to:

1. Abnormal leakage of fluid from capillaries to outside. It is due to:

(a) Increased capillary pressure.
(b) Decreased plasma protein concentration. (c) Increased capillary permeability.

2. Failure of lymphatic system to return the fluid from extra cellular

compartments back to circulation.
3. Retention of salt and water by kidneys.

Aetiology
1. Cardiac oedema-seen in right heart failure.

2. Mechanical obstruction of veins-thrombosis of veins causes venous

obstruction leading to back pressure. This results in increased capillary
hydrostatic pressure and pushes the fluid out of blood capillary.

3. Renal disease – Nephrosis.

4. Inflammation – This produce increased capillary permeability at the site and
leaking of fluid.

5. Malnutrition – Plasma protein concentration decreases, colloidal osmotic

pressure of blood falls, more fluid will be leaked out.

6. Toxic substances produce increased permeability of capillaries leading to

leaking out of fluid.
7. Liver cirrhosis – Less synthesis of plasma proteins
– hypoprotenemia, decreases the colloidal osmotic pressure.
8. Lymphedema – Obstruction in the lymphatic drainage as in filariasis.

Types of Oedema—Pitting and Non pitting Oedema Pitting Oedema: If the

skin over an odematous area is pressed by a finger for some time, a small
depression is formed at the site. The pit disappears with in 30 seconds. The
pitting is due to displacement of fluid from the area of pressure. For example,
Inflammation, renal oedema. Non pitting Oedema: Pit is not formed in the
oedematous area when pressure is applied on the skin. This type is seen in late
filariasis, and myxoedema etc. Here swelling is not only due to collection of
fluid. Some other materials also get accumulated at the site.

IMMUNITY

The term immunity refers to the resistance exhibited by the host towards injury
caused by micro organisms and their products.

I. Innate immunity
(a) Non specific

(b) Specific Species Racial Individual

II. Acquired immunity Natural Natural

(a) Active (b) Passive
Artificial I. Innate immunity
Artificial

Innate or native immunity is the resistance to infections, which an individual

possesses by virtue of his genetic and consitutional make up. It does not depend
on prior contact with microorganisms or immunisation. It may be nonspecific,
when it indicates a degree of resistance to infections in general or specific when
resistance to a particular pathogen is concerned.

Innate immunity may be considered at the level of the species, race or

individual. Species immunity refers to the total or relative refractories to a
pathogen, shown by all members of a species. The mechanism of species
immunity may be due to physiological and biochemical differences between the
tissues at the different host species which determine whether or not a pathogen
can multiply in them.

Racial immunity: Within a species different races may show differences in

susceptibility to infections. This is known as racial immunity.

For example Algerian sheep to anthrax. Such racial differences are known to be
genetic in origin, and by selection and in breeding it is possible to develop at will
races that posses high degree of resistance or susceptibility to various pathogens.

Individual immunity
The differences in innate immunity exhibited by different individual in a race is
known as individual immunity.

Factors influencing the level of innate immunity in an individual are:

Age
Hormonal influences
Nutrition

Age: The two extremes of the life like infancy and old age carry a higher
susceptibility to infections and diseases as compared to young adults.

The foetus in uterus is normally protected from maternal infection by the

placental barrier. Old people are highly susceptible to infection due to gradual
waning in their immune response.

Hormonal response

Endocrine disorders such as diabetes mellitus, hypothyroidism and adrenal

disfunction are associated with an enhanced susceptibility to infections.

Nutrition

The interaction between malnutrition and immunity is complex. But in general

both hormonal and cell mediated immune process are reduced in malnutrition.

II. Acquired immunity

The resistance that an individual acquires during life is known as acquired

immunity as distinct from the inborn or innate immunity.

Active immunity

Active immunity is the resistance developed by an individual as a result of an

antigenic stimulus. This involves the active function of the passive immune
apparatus leading to the synthesis of antibodies and the production of
immunologically active cells. Once developed the active immunity is long
lasting and it is more effective and confers better protection than passive
immunisation

Passive immunity

The resistance that is transmitted to a recipient in a “ready made” form is known

as passive immunity. This immunity is transient, lasting usually for days or
weeks. Easily metabolised and eliminated. Passive immunity is less effective and
provide an immunity inferior to that produced by active immunisation.

TABLE 2.23
Comparison of active and passive immunity
S.No. Active immunity Passive immunity 1. Produced actively by the host’s
immune system.

2. Induced by infection (or) by contact with immunogens (allergens ) etc.

Received passively by host. No participation by the host’s immune system.

Conferred by introduction of ready made antibodies.

3. Affords durable and effective protection. Protection is transient and less
effective. 4. Immunity is effective only after a long period of time required for
the generation of antibodies.
Immunity is effective immediately.
5. Immunological memory present subsequent challenge.

More effective (Booster effect). No immunological memory. Subsequent

administration of antibody is less effective due to “Immune eliminate”.

6. Negative phase may occur. No negative phase. 7. Not applicable in immune-

deficient host. Applicable in immune deficient host.

Active immunity may be natural or artificial

Natural active immunity: Results from either a clinical (or) in apparent
infection with a parasite.

Example: A person who has recovered from an attack of small pox develops
natural immunity.
Artificial active immunity: It is the resistance induced by vaccines. Vaccines are
preparation of live or killed micro organism or their products used for
immunisation.
Example of vaccines are:
I. Bacterial vaccines:
(a) Live – BCG for tuberculosis.
(b) Killed – 7 AB for enteric fever.

II. Viral vaccines

(a) Live – small pox vaccine.
(b) Killed – Salk’s vaccine for polio myelitis

III. Bacterial products:

Ioxeids for diptheria and tetanus.
Stem cells Stem cells
Lymphocytes Lymphocytes
Encounter and recognisation Bursa processing Thymus processing
B-lymphocytes+ Antigen+ Cytotoxic T cell
B cell Helper T cell Cytotoxic T cell
Cytokines Cytokines + + Activation Cytotoxic cell or killer cell
Antibody Attack Directly attack antigen bearing cells, membrane rupture destruction of microbesGuide
phagocytes complement and N.K. cells to attack
antigen-bearing cells or to neutralise free antigen

Fig. 2.31
Mechanism of immunity

Live vaccines: Initiate an infection without causing any injury or disease. The
immunity following live vaccine administration, lasts for several years but
booster doses may be necessary. Live vaccines may be administered orally.

Killed vaccines: These are generally less immunogenic than live vaccines and
protection lasts only for a short period. Therefore they have to be administered
repeatedly. They may be given orally and parenterally.

Natural passive immunity: The resistance passively transferred from the

mother to the baby through placenta and colostrum.

Example: IgA, IgM.

Artificial passive immunity: If the power of resistance is passively transferred

to a recipient by administration of antibodies of one person to another. The
agents meant for this purpose are hyper immune serum of animal or human
origin.
Herd immunity: This refers to the overall level of immunity in a community
and is relevant in the control of epidemic disease. When herd immunity is lower
epidemics are likely to occur. Eradication of communicable diseases depends on
the development of a high level of herd immunity rather than in the development
of high level of immunity in individual.

TABLE 2.24
Comparison between cell mediated and antibody mediated immunity
S.No. Cell mediated immunity Antibody mediated immunity (Humoral)

1. Cell mediated immunity is based on proliferation of antigen—specific T Cells.

Antibody mediated immune response is initiated by B-Cells.

2. T Cells form when immature lymphocytes leave the bone marrow and are
transported by the blood to the thymus gland.
B - Cells mature in bone marrow and are then transported by the blood to
secondary lymphoid organs i.e., lymph nodes, spleen or tonsils.

3. During maturation, the presence of either CD4 or CD8 proteins results in the
production of two different kinds of T Cells with different functions, i.e.,
Cytotoxic T Cells from CD-8. Helper T Cells from CD-4.
During activation B-Cells are transformed into plasma cells, which secrete
antibodies.

4. Cytotoxic T Cells binds to antigens on plasma membrane of target cells and

directly destroy the cells. On the plasma membrane, B cells carry specific
antigen receptors which can bind to corresponding specific antigen.

5. Helper T Cells secrete cytokines that help to activate B

Cells.
B Cells present antigen on either membrane surface to helper T Cells.

6. NK Cells binds directly and nonspecifically to virus— infected cells and

cancer cells and kill them. When specific antibodies encounter the corresponding
specific antigen they bind together, forming an antigen antibody complex.

7. NK cells functions as killer cells in antibody-dependent cellular cytotoxicity

(ADCC).
Antigen-antibody complex will inactivate the antigen or make it more
susceptible to phagocytosis by neutrophils or macrophages.

Anaphylactic Shock
the administration of a vaccine. Vaccines stimulate the body’s Mostly allergic
symptoms localised at the site of entry ofown immune system to protect the person against
subsequent
antigen. But rarely large amount of chemicals released by infection or disease.
Immunisation is a proven tool for

mast cells enter circulation resulting into systemic symptomscontrolling and

eliminating life-threatening infectious diseases which cause severe hypotension and

bronchiolar constriction.and is estimated to avert over 2 million deaths each year. It This
sequence of events is called anaphylactic shock. It canis one of the most cost-effective
health investments, with cause death due to circulatory and respiratory failure.
proven strategies that make it accessible to even the most hard-to-reach and
vulnerable populations. It has clearly

Immunisation defined target groups; it can be delivered effectively through

Immunisation is the process whereby a person is made outreach activities; and
vaccination does not require any immune or resistant to an infectious disease,
typically by major lifestyle change.

Autoimmune disorders

Autoimmune disorders are diseases caused by the body producing an

inappropriate immune response against its own tissues. Sometimes the immune
system will stop to recognise one or more of the body’s normal constituents as
self and will create autoantibodies – antibodies that attack its own cells, tissues,
and/or organs. This causes inflammation and damage and it leads to autoimmune
disorders.

The cause of autoimmune diseases is unknown, but it appears that there is an

inherited predisposition to develop autoimmune disease in many cases. In a few
types of autoimmune disease (such as rheumatic fever), a bacteria or virus
triggers an immune response, and the antibodies or Tcells attack normal cells
because they have some part of their structure that resembles a part of the
structure of the infecting microorganism.

Autoimmune disorders fall into two general types: those that damage many
organs (systemic autoimmune diseases) such as rheumatoid arthritis (affects
joints, skin and somewhat lungs) and in another case type 1 diabetes mellitus
(affects islets of pancreas) where only a single organ or tissue is directly
damaged by the autoimmune process (localised). However, the distinctions
become blurred as the effect of localised autoimmune disorders frequently
extends beyond the targeted tissues, indirectly affecting other body organs and
systems.

Acquired immune deficiency syndrome-AIDS.

AIDS is the disease in which patient looses the basic resistance mechanism.

Cause: It is caused by human immunodeficiency virusHIV. HIV belongs to

retrovirus family. Its nucleic acid core is RNA rather than DNA. The virus
contains an enzyme called reverse transcriptase that once inside host cell
transcribes viral RNA into DNA. This DNA gets integrated into host cells
chromosomes. The association is permanent. Every time the host cell
reproduces, it also reproduces the retroviral RNA.

Virus may remain dormant inside the cell for years without any outside
symptoms. The individual shows antibodies against HIV in their blood. When
the virus becomes active and undergoes rapid replication inside the cell resulting
in cell death, person suffers from actual disease.

Complications: HIV preferentially enters and resides in helper T cells. This

leads to depletion of helper T cells. Without adequate number of helper T cells,
B cells cannot produce antibodies and cytotoxic T cells also cannot function. So
AIDS patients die of infection or cancer which ordinarily are handled readily by
the immune system.

Mode of transmission of HIV

1. Transfer of contaminated blood or blood products.
2. Through contaminated needles, blades.
3. Sexual intercourse with an infected partner.
4. From mother to foetus.
Graft rejection
When donated bone marrow infused during a bone marrow transplant is rejected
by the patient’s body. The immune system defends the body against disease.
Lymphocytes are one type of white blood cell that helps the body resist infection
by recognising harmful foreign substances, such as bacteria, and eliminating
them. The ability of the vertebrate immune system to distinguish self from
nonself depends largely on a group of protein makers (antigens) known as the
major histocompatibility complex (MHC). These markers are present on the
surface of every cell are slightly different in different individuals. The genes that
code for these proteins are found linked together on one chromosome
(chromosome 6 in humans).
In humans, the MHC is called the HLA (human leukocyte antigen) group. HLA
is determined by five different linked genes. These genes are all polymorphic -
that is, within the population there are multiple alleles at each locus. Tissues
from the same individual or from identical twins have the same HLA alleles and
thus the same HLA antigens. Because of the polymorphism (multiple alleles) of
the HLA genes, it is difficult to find identical matches among strangers. If a
tissue or organ is taken from a donor and transplanted to the body of an unrelated
host, several of the HLA antigens are likely to be different.
Cardio Vascular System
Otto Frank
20-06-1865–12-11-1944 German Physiologist Known for Frank
Starling’s law
Windkessel theory

Ernest Starling
17-4-1866–2-5-1927
English Physiologist
Known for Frank-Starling’s law of heart, Starling’s equation
Discovery of First hormone secretin
Willem Einthovan
21-05-1860–29-9-1927 Netherland’s Physiologist Discovered Electrocardiogram
in 1906
Nobel Prize (1924)
Rene-Laennec
17-2-1781–3-8-1826 French Physician
Invented stethoscope

Roderick Mackinnon 19-02-1956

American Professor of Neurobiology and
Biophysicist
Famous for discovery of structure of ion channels Nobel Prize (2003)

Scipioni Riva-Rocei 7-8-1863–15-3-1937 Italian Pediastrician Discovered easy

to use version of
sphygmomanometer

Carl J. Wiggers
28-05-1883–28-04-1963 American Physiology
Famous for Wiggers Diagram of Cardiovascular
Physiology

(72)
Chapter
3
CARDIO VASCULAR SYSTEM
Physiological anatomy of heart
Greater and lesser circulation.
Structure and properties of cardiac muscle. Junctional tissues of Heart—Origin
and spread of cardiac impulses,
Heart block.
Cardiac cycle—Definition, Mechanical events during different phases of systole
and diastole. Pressure volume changes inside heart chambers and aorta.
Innervation of heart

Heart Rate- Normal value, physiological variation. Regulation of heart rate,

Cardiac arrhythmias.

Cardiac output—Definition, normal values, Physiological variation, factors

affecting, cardiac index, cardiac reserve,
Regulation of cardiac output.
Measurement of cardiac output, Echocardiography. Electrocardiogram- Normal
ECG.
Characteristics of waves, Einthoven’s triangle and law.
Significance of ECG.
Heart sounds- Causes, characteristics, significance, phonocardiogram, Murmurs.
Arterial blood pressure-Definition, normal values, Physiological variations,
Factors affecting. Regulation of BP, Measurement of BP.
Hypertension and Hypotension.
Arterial pulse, venous pulse, circulation time, apex beat. Central venous
pressure.
Haemodynamics—Peripheral resistance, blood viscosity, laminar blood flow,
turbulent blood flow, velocity of blood flow.
Poiseuille’s Law.
Microcirculation—Capillary circulation, Starling forces and edema, Triple
response.
Local and humoral control of blood flow— Autoregulation of blood flow and
hyperemia. Regional Circulation—Coronary circulation and coronary artery
disease, pulmonary, splanchnic, cutaneous, cerebral and foetal circulation.
Circulatory shock and Syncope.
Cardiac failure, Cardiopulmonary resuscitation (CPR).
Cardio vascular changes during exercise and effect of gravity on CVS.
Lymphatic system: Lymph, formation,composition, circulation and functions,
lymphatic organs, Disorders of lymphatic obstruction.
CARDIO VASCULAR SYSTEM
Introduction

Cardio vascular system comprises of heart, blood and blood vessels. Heart is a
muscular pump located at the centre of circulation. Pumping action of the heart
keeps the blood in circulation. Types of blood vessels- arteries or arterial system,
capillaries and venous system.

Arterial system carries blood away from the heart. Capillary network links the
arterial system with venous system. Exchange of materials between the blood
and tissues takes place at the capillaries. Venous system carries blood back to the
heart. Heart is situated inside the thoracic cavity inbetween two lungs - this
space is known as mediastinum. Size of the heart is about a closed
fist.mediastinum. Size of the heart is about a closed fist.

Physiological Anatomy of the Heart

Human heart is covered by double walled covering called pericardium. It is a

fibroserous covering.The heart comprises of four chambers. Heart is divided into
upper atria and lower ventricles due to the presence of atrio- ventricular septum.
The atria is further divided into right and left artia. The ventricles are divided
into right and left ventricles. Muscles of the heart are collectively called as
Myocardium. The three layers are:
1. Outer-Epicardium
2. Middle-Myocardium Proper
3. Inner-Endocardium.
Pulmonary Aortic semilunar valve
semilunar
valve Cups
Cusp Cusp

Tricuspid opening Cusp

Mitral opening Cusp

Cordae tendinae
Papillary muscle

Systemic Circulation or Greater Circulation

Greater circulation begins from left ventricle. When heart contracts the
oxygenated blood (pure blood) from the left ventricle enters the aorta. It is
divided into numerous branches. These branches reach almost all the tissues
except lungs. Arteries give rise to arterioles. Arterioles end in capillaries.
Oxygen is given out of the capillaries to the tissues and CO2 is picked up by the
blood. The capillaries give rise to venules, venules join and give rise to large
veins. The two large veins are superior and inferior venacava. Superior venacava
carries blood from the upper part of the body. Inferior venacava carries blood
from the lower part of the body. The deoxygenated blood reaches the right
atrium. This part of the circulation is called as systemic circulation because it
supplies to most of the systems. It is called as greater circulation because it
travels a longer distance, covers a wider area and maintains a higher pressure.
Cordae tendinaeEpicardium Endocardium
Papillary muscle Head

Fig. 3.1 Heart–Structure Neck

Valves of Heart

There are four valves in the heart. Two atrio- ventricular valves (A.V.V) and two
semi lunar valves (S.L.V). The two A.V. valves are mitral valve or bicuspid
valve which is present between left atrium and left ventricle. Tricuspid valve is
present in between the right atrium and right ventricle. Semi lunar valves are
situated at the beginning of aorta and pulmonary artery. Aorta arises from the left
ventricle and pulmonary artery arises from the right ventricle.

Circulation: Circulation is divided into two parts:

1. Systemic circulation or greater circulation.
2. Pulmonary circulation or lesser circulation.
Common
Brachiocephaliccarotid artery
trunk Aorta
Pulmonary veins Superior
vena cava

Pulmonary
trunk
Right atrium

Right ventricle Vein Artery

Upper limb
Aorta
Pulmonary vein
Heart left
ventricle

Right ventricle

Artery Superior venacave

Pulmonory artery
Inferior
venacava

Vein Liver Subclavian artery

Pulmonary artery
Pulmonary
veins
Left atrium

Left ventricle Intestine

Kidneys
Vein Trunkartery

Inferior vena cava Left AV valve

Right ventricle Interventricular

septum
Papillary muscle

L. Limb

Fig. 3.2 Heart–Circulation Fig. 3.3 Organisation of circulatory system

Pulmonary Circulation or Lesser Circulation

It starts from right ventricle. During the ventricular contraction, the

deoxygenated blood (impure blood) from the right ventricle enters the
pulmonary artery. Pulmonary arteries reach the lungs and give rise to pulmonary
capillaries. At the pulmonary capillaries oxygen is taken up by the blood and
CO2 is given out. So the blood gets oxygenated. Oxygenated blood is carried
back through the pulmonary veins and it reaches the left atrium. This part of the
circulation is called as pulmonary circulation. This is called lesser circulation
because distance travelled is short, area covered is less and pressure maintained
is low.

All the arteries carry oxygenated blood except pulmonary arteries. All the veins
carry deoxygenated blood except pulmonary veins.
TABLE 3.1 Distribution of blood in percentage in different vascular
compartments at rest
Sl. No. Compartment Approximate percentage
1. Systemic veins and venules. 60
2. Systemic capillaries 5
3. Systemic arteries and arterioles 12–25
4. Heart 5–10
5. Pulmonary vessels arteries and veins.
TABLE 3.1A
Comparison between systemic circulation and pulmonary circulation
10-12

S.No. Features Systemic circulation or

Greater circulation Pulmonary circulation or
Lesser circulation

1. Starts from Left ventricle Right ventricle 2. Ends at Right atrium Left atrium
3. Thickness of vessels Thick Very thin

4. Pressure
Systolic pressure
Diastolic pressure Pulse pressure
Mean pressure

5. Small vessels
Resistance
Blood flow
Capillaries

6. Travels
Covers

7. Arteries carry
8. Veins carry
9. Velocity of blood flow

10. Resting sympathetic time High

120–140 mm of Hg
70–90 mm of Hg
40 mm of Hg
93 mm of Hg

Arterioles thick wall, small lumen High peripheral resistance Pulsatile

Long and narrow

A longer distance
A wider area

Oxygenated blood
Deoxygenated blood

High
50 cm/sec at the root of aorta

High
Very low
20–25 mm of Hg
6–12 mm of Hg
12 mm of Hg
15 mm of Hg

Venules, Thin wall, Large lumen Low peripheral resistance

Continuous
Short and wide

A shorter distance
A smaller area

Deoxygenated blood
Oxygenated blood

Low
40 cm/sec at the pulmonary trunk Absent

Histology of Blood Vessels

The blood vessels have three layers:

Outer coat or tunica externa or tunica adventitial consist of elastic fibres and
collagen fibres. Middle coat tunica media or the muscle layer consist of smooth
muscles and elastic fibres. Smooth muscles are arranged circularly.
Inner coat -tunica interna or tunica intima- consist of endothelial lining.

The blood vessel wall is basically made up of four types of components.

Endothelial cells, Elastic tissues, smooth muscles and fibrous tissues. These
materials are present in different proportions in the different types of blood
vessels.

Type of blood Average vessel diameter Thickness of wall Endothelial cells

Elastic material Smooth muscle Fibrous material

Trunk of aorta 18–20 mm Present More Present 2 mm Present Arteries 2 mm

Present Present More 10 mm Less Arterioles 15–17 mm Present Less Present 20
mm Present Capillary 7–8 mm Present Absent Absent 1 mm Absent Venules 15
mm Present Absent Absent 2 mm Less Small veins 5–6 mm Present Present
Present 0.5 mm Present Large vein venacava 15–17 mm Present Present Present
1.5 mm Present

Functional classification of blood vessels. Physiologically the vascular system

can be devided into several segments like:

1. The Windkessel vessels,

2. Resistance vessels,
3. Exchange vessels, and
4. Capacitance vessels.
1. Windkessel vessels include the aorta and large arteries. These vessel wall
have more elastic material so can act as elastic reservoir. They can stretch and
accommodate more blood easily. During systole these vessel wall stretches and
during diastole the vessel wall recoils back. This ability to recoil to original size
is called as Windkessel effect. This effect is the physiological basis of continuity
of blood flow during systole and diastolic phase of cardiac cycle.
2. Resistance vessels: Windkessel vessels open into resistance open into
resistance vessel conduit vessel. These vessels have smaller diameter, have more
musea fibres and have less elastic materials in their wall. This includes small
arteries, arteriles and metaarterioles. This segment of blood vessel exhibit
maximum peripheral resistance for the flow of blood.
3. Exchange vessels: The arterioles open into capillaries. The total cross
sectional areas of capillaries is enormous. The wall of capillary is very thin made
up of only endothelial cell. Blood flow through capillaries is very slow.
Exchange of materials, nutrients, gases, ions, water etc. takes place between
blood and tissue at this segment.
4. Capacitance vessels: capillaries open into venules. Venules join to form small
veins, later large veins - superior and inferior venacava. Small and large veins
together 3. accommodate about 60% of the total blood. So they are called as
capacitance vessels. Veins area easily distensible, their wall have high
compliance. So they can accommodate more

blood without developing compliance. So they can accommodate more blood

without developing higher venous blood pressure of capillaries: commonly three
varieties of capillaries are seen in different organs based upon their specific
requirements.

1. Continuous capillary or non fenestrated capillary.

2. Fenestrated capillary: This type of capillaries are seen in heart, skeletal

muscle, lungs and brain. These capillaries have small pores and allow the
exchange of particles less than 10 nm diameter. Penestrated capillary. This type
of capillaries are seen in glomerulus, peritubular capillaries and in endocrine
glands. These capillary wall have wider pores and allow exchange of particles
20–100 nm diameter.

Sinusoids-discontinuous: This type of capillaries are seen in bone marrow and

liver. The wall have pores of size 600-3000 nm. These allow the exchange of big
molecules.

Properties of Cardiac Muscle

1.
2.
3. Excitability or Excitation. Conduction
Contraction.
4. Refractory period
5.
6. Functional syncytium Autorhythmicity
7. All or none law
8. Staircase phenomenon.

Excitability
It means the ability to respond to a stimulus by way of
generating an action potential. Stimulus means a change in the energy level.

Resting membrane potential: The potential difference between inside and

outside of a muscle membrane, when it is not stimulated or when it is at rest. The
resting membrane potential is usually negative. It is about—70 – 90 millivolts.

The negativity inside the membrane is due to the unequal distribution of ions
across the membrane. Na+ Cl– K+ outside
Na+ K+ Cl– Pr– inside
Distribution of various ions inside and outside of a membrane

The unequal distribution of ions is due to three reasons. 1. Operation of Na+-

K+ pump: It is an active transport mechanism. It is a carrier mediated transport
by which sodium ions are pushed out of the membrane and potassium ions are
pushed in. It takes place against the concentration gradient and at the
expenditure of metabolic energy.

2. Muscle membrane is more permeable to potassium ions than sodium ions.

3. Presence of non-difusable net negatively charged protein molecules inside the
membrane.charged protein molecules inside the membrane. Action potential

It’s a sequential potential change across the membrane with a phase of

depolarisation followed with repolarisation.
Conduction

The action potential generated at any part of the muscle membrane is not
confined to that site. The action potential is propagated all along the length of
the muscle fibre. This phenomenon is known as conduction or transmission of
impulses.

Contraction

It means shortening of muscle fibres. It is a mechanical event. It usually follows

excitation. Excitation is an electrical event. The calcium ions link the excitation
with contraction. This process is known as excitation-contraction coupling.

Contraction of cardiac muscles develop a propulsive force which keeps the

blood in circulation. Contraction is followed by relaxation.
Refractory Period

It is defined as a period during which 2nd stimulus cannot generate a fresh action
potential. Refractory period is divided into two parts:

1. Absolute refractory period and

2. Relative refractory period.

Absolute refractory period

It is the first part of the refractory period during which the

2nd stimulus of whatever higher intensity cannot generate a fresh action

potential. Absolute refractory period normal value is 0.25 sec.

Relative refractory period

It is the later part of the refractory period in which 2nd stimulus of higher
intensity can generate an action potential. The normal value is 0.05 sec.

Cardiac muscles have long refractory period compared to skeletal muscles.

Because of this cardiac muscles may not get tetanised.

Functional Syncytium

Anatomically heart is made up of numerous individual muscle fibres. These

muscle fibres are connected to one another by a tight junction. Because of this,
impulse can pass from one muscle to another muscle very easily and it faces
very little resistance. Because of this, functionally cardiac muscles act as if a
single unit. This phenomenon is known as functional syncytium.

Autorhythmicity

The cardiac muscles can generate their own impulses. They are self excitable
muscles. The excitation is followed by contraction. Because of this, the heart
rate or the rhythmicity of the heart is basically decided by the heart itself. This
property is known as autorhythmicity. But the rhythmicity of the heart can be
influenced by endocrine and nervous system.

All or None Law

The minimum strength of stimulus required to excite the muscle is known as

threshold stimulus. Any strength of stimulus below the threshold level is known
as sub threshold. Muscle will not respond to sub threshold stimulus and the
magnitude of response is maximum when strength of stimulus is at the threshold
level. When the strength of stimulus is above the threshold(supra threshold) the
muscle will respond by generating an action potential but the magnitude is same.
There is no corresponding increase in the magnitude of response when the
strength of stimulus is above the threshold. If the muscle responds, it will
respond maximally otherwise not at all. This phenomenon is known as all or
none law.

Staircase phenomenon

When a series of stimuli are applied with intervals of 1 to 2 seconds there is an

incremental contractile responses for the first few stimuli and then the responses
becomes constant. This type of responses for the first few stimuli is called
staircase phenomenon or Bowditch phenomenon. This is due to the beneficial
effect of first contraction to the second one but up to 4th one only. The beneficial
effect is due to:

(i) ↑ Ca++ ion availability

(ii) ↑ Temperature
(iii) ↑ Change in visco-elastic property of the cardiac muscle

Summation of subliminal stimuli

When a single subliminal stimulus is applied no contractile response is elicited.
But when a series of successive stimuli are applied at a rapid rate, a contractile
response is elicited. When a subliminal stimulus is applied, it produces a local
response which exponentially dies off. But with a series of such stimuli local
responses get added up and produce a propagated A.P., which in turn leads to a
contractile response. Junctional tissues of the heart or special excitatory and
conducting system of the heart:

All the cardiac muscles are capable of excitation and conduction, but some parts
of the heart are specialised in these two properties. These parts of the heart is
known as junctional tissues of the heart. This includes

1. Sino Atrial Node (S.A. Node)

2. Atrio Ventricular Node (A.V. Node)
3. Bundle of His
4. Purkinje fibres.

Sino Atrial Node (S.A. Node)

It is a part of the wall of right artrium close to the opening of superior venacava.
S.A. Node generates impulses approximately at a rate of 72 times/miniute. It acts
as a pacemaker of the heart. If any other part of the heart act as a pace maker, it
is called as ectopic pace-maker. S.A. node is innervated by right vagus.
Internodal atrial pathways. From the S.A. node impulses spread easily to all the
muscles of both atria. But conduction is more rapid in some bands of atrial
fibres. These bonds conduct impulses at a faster rate to A.V. node. They are
called as internoded pathways. They are:
1. Anterior internodal pathway of Bachman. 2. Middle internodal pathway of
Wenckebach. 3. Posterior internodal pathway of Thorel.

Atrio Ventricular Node (A-V Node)

It is a part of the wall of the right atrium close to the atrioventicular septum. It is
nearer to the triscuspid valve. It generates impulses at a rate of 60/minute. It is
innervated by left vagus.

Bundle of His

It is a thick band of muscle fibres starting from A.V. Node. It runs along with
intra ventricular septum. It divides into right branch and left branch. It generates
impulses at a rate of 40/minute.

Purkinje fibres
These fibres arise from the branches of bundle of His. Purkinje fibres pierce into
the ventricular myocardium.
S.A Node Internodal
pathways

Right atrium A.V. Node

Tricuspid valve

Right ventricle Right bundle branch

Left atrium

Bicuspid valve
Bundle of His
Left bundle
branch
Left ventricle Purkinje fibres

Fig. 3.4 Junctional tissues of heart

Transmission of impulses
Impulses are generated at the S.A. node. From the S.A. node impulses are
transmitted through the muscles of the atria and impulses reach both right and
left atria. The impulses are preferentially transmitted to the A.V. node. Across
the

A.V. node the velocity of impulse transmission is very slow. Therefore it takes
time to cross the impulse from the atria to ventricle, from the A.V. node to the
bundle of His. This delay is known as A.V. nodal delay (0.1 second). This delay
ensures that ventricles start contraction only after atrial contraction. Impulses are
transmitted through the branches of bundle of His to the purkinje fibres.

Cardiac block
It is the block for the transmission of impulses in the junctional tissues. There
are different types of blocks.

1. 3rd degree block-complete bloc: block of transmission of impulses from S.A.

node to A.V. node.

2. 2nd degree block-incomplete block: block from A.V. node to bundle of His.
Some impulses are not transmitted from atria to ventricles.

3. 1st degree block-incomplete block slow conduction of impulses: bundle block,

i.e., block in the right or left branch.
Cardiac block can be detected and located by using E.C.G.

Origin and Spread of Cardiac Impulses

All the cardiac muscles are self excitable tissues, they can generate their own
action potentials. There are two types of action potentials seen in conducting
tissues.

1. Pace-maker potential—S.A. node

2. Plateau type action potential—ventricular myocardium.
Pace-maker potential
S.A. node generates impulses at the highest rate. Therefore it act as a pacemaker.
It generates impulses at a rate of about 72/min.
+20
03 2
M.V
–45 4
–60 0.8 sec 1.6 sec Fig. 3.5 Pace-maker potential from S.A. nodal cells
+30 1 2
0
M.V.0 3
4
–90
Fig. 3.6
Duration 300 msec
Action potencial from ventricular myocardium

The tissue with an unstable R.M.P. produces a pace maker potential. The slow
depolarisation between two action potentials is called pace maker potential (pre
potential). This is due to slow decline in membrane permeability to K+ ions and
an increase in Ca++ influx. When the permeability of K+ declines and Ca++
influx increase R.M.P. gradually declines and when it reaches the firing level, it
gives off an A.P. Thus, the production of impulses is automatic. Hence heart beat
is spontaneous.
Parts of pace-maker potential and their ionic basis

1. Rapid depolarisation due to Ca++ influx

2. Repolarisation due to K+ efflux
3. Diastolic depolarisation or pre potential due to (a) decrease K+ efflux
(b) Na+ influx
(c) Ca++ influx

Action potential from ventricular myocardium (Plateau type)

Ventricular myocardium has a plateau type of A.P. The ventricular myocardial
A.P. duration is less than the duration of the purkinje cell A.P. So also the
refractory period. The atrial muscle cells lack a distinct phase two.

Parts of a plateau type of action potential from the ventricular myocardium and
ionic basis.
O-phase rapid depolarisation due to Na+ influx through rapid channels.
1. Phase Na+ inactivation and K+ efflux.
2. Phase (plateau phase) sustained depolarisation due to Na+ and Ca++ influx
through slow channels.
3. Phase repolarisation due to rapid K+ efflux.
4. Phase restoration of membrane potential to resting level (R.M.P.) due to K+
efflux.

Spread of cardiac impulses

From S.A. node impulses are transmitted to entire atrial

muscles through fused ends of SAN. Velocity of conduction in atrial muscle is

1.0 m/sec.

Impulses are transmitted to A.V. node through anterior, middle and posterior
inter nodal pathways. Velocity of conduction 1m/sec.

Impulses are conducted through A.V. node very slowly. Velocity = 0.05 m/sec.
This causes a significant delay in reaching impulses into the ventricles. This
delay is known as A.V. nodal delay, about 0.1 sec. This delay ensures that the
ventricles get excited after atrial excitation and atrial contraction. From the A.V.
node impulses are transmitted to right and left branch of His bundle.

A.V. bundle has the property of “One Way Conduction”. Velocity of conduction
in purkinje fibres = 4 m/sec (highest).

Once the cardiac impulses enter the purkinje system, it spreads immediately to
the entire endocardial surface of the ventricular muscle.

Conduction velocity
(a) S.A. node –0.05 m/sec
(b) A.V. node 0.05 m/sec
(c) Purkinje fibres 4.0 m/sec
(d) Atrium 1.0 m/sec
(e) Ventricle 1.0 m/sec
(f) Bundle of His 1.0 m/sec.

CARDIAC CYCLE
Cardiac cycle is defined as sequence of cyclical changes taking place in the heart
from one beat to the next beat.
Cardiac cycle time: Time required for the completion of one cardiac cycle.
Normal duration is 0.8 second. Cardiac cycle time is inversely proportional to
heart rate.

The important changes that are taking place during cardiac cycle.

1. Mechanical changes: The contraction and relaxation of various chambers of

the heart.
2. Electrical changes in the form of generation and transmission of impulses. It is
represented by ECG.

3. Volume changes inside the heart.

4. Pressure changes inside various chambers of the heart.
5. Opening and closing of valves.
6. Heart sounds: Cardiac cycle is broadly divided into atrial events and
ventricular events.

Cardiac cycles 0.8 sec

Atrial events Ventricular events 0.8 sec 0.8 sec

Atrial events: Duration—0.8 sec. It is divided into two phases. Atrial systole
and atrial diastole. Duration of atrial systole is 0.1 sec. During atrial systole, the
right and left atria contract. Pressure inside the atria increases and volume
decreases.

Atrial diastole: Duration is 0.7 sec. During this period the two atria relax.
Pressure decreases in the atria and volume increases.

Ventricular events: Duration is 0.8 sec. It is divided into two parts. Ventricular
systole and ventricular diastole.

Ventricular systole: During ventricular systole the ventricles contract. Duration

is 0.3 sec. It follows atrial contraction. Ventricular systole is again divided into
two parts.

1. Isometric contraction period.

2. Ejection period.
Isometric contraction period duration is 0.05 sec. Ejection period duration is 0.25
sec.
Cardiac cycle 0.8 sec
Atrial events 0.8 sec
Ventricular events 0.8 sec
Atrial systole 0.1 sec
Atrial diastole Ventricular systole Ventricular diastole 0.7 sec 0.3 sec 0.5 sec

Dynamic Adynamic phase phase 0.05 0.05 Isometric or contraction 0.05

Ejection period 0.25
Proto
diastolic period 0.04 Isometric or Isovolumetric relaxation period 0.08 Filling phase 0.38

Max. ejection
0.11
Reduced ejection
0.14
Ist rapid
filling
0.1
Slow
filling or diastasis
0.18

Fig. 3.7 Cardiac Cycle—Events and duration

Last
rapid filling 0.1

4
LastRapidF
h a s e TO L EillinP S g
E ATRIALSYS
T O L E IC s
P
PDP = Proto diastolic period ICP = Isometric contraction period Fig. 3.8
Cardiac cycle

At the beginning of ventricular systole, pressure inside the ventricles increases.

This makes the closure of A.V. valves. This produces the first heart sound.

A.V. valves have just closed and semi lunar valves are not yet opened.
The ventricles contract as a closed chamber. No change in the volume and length
of the muscle fibre. So they are called isometric contraction period or isovolumic
contraction period. Only pressure increases.

Ejection period: Duration is 0.25 sec. Now pressure inside the ventricles
increases. This opens the semilunar valves. Blood from left ventricle is ejected
into the aorta. And blood from the right ventricle is ejected into the pulmonary
arteries. Ejection period is again divided into two parts:

1. Maximum ejection period.

2. Reduced ejection period.
Maximum ejection period duration is 0.11 sec. Reduced ejection period duration
is 0.14 sec.
Ventricular diastole: Duration is 0.5 secs. During this period the ventricles
relax. Ventricular diastole is divided into three parts.
1. Proto diastolic period (duration 0.04 sec). 2. Isometric or isovolumetric
relaxation period (duration 0.08 sec).
3. Filling phase (duration 0.38 sec).
Proto diastolic period: During this phase ventricular pressure falls very rapidly.
At the end of this phase semi lunar valves close. This causes the second heart
sound. Isometric relaxation period or isovolumetric relaxation period:
Semilunar valves have just closed. The A.V. valves are

not yet opened. The ventricle relax as a closed chamber. So no much change in
the length of the muscle fibre and blood volume. Therefore it is called as
isometric or isovolumetric relaxation period. Pressure continues to decrease.
Isovolumetric relaxation ends when pressure inside the ventricle falls below the
atrial pressure and A.V. valves open. Filling phase: A.V. valves open. Blood
starts flowing

from atria to ventricles.

Filling phase is again divided into three.
1. First rapid filling phase 0.1 sec 2. Slow filling phase or diastasis 0.18 sec 3.
Last rapid filling phase. 0.1 sec

During the Ist rapid filling phase blood rushes from atria through the A.V.
valves. This causes the vibration of A.V. valves. This produces the 3rd heart
sound. After that flow of blood becomes slow. This phase is called as slow
filling phase or diastasis.

Last rapid filling phase

During this time atria contract. Once again the flow of blood becomes turbulent.
This causes vibration of the A.V. valves. This produces the 4th heart sound.
Fundamental rules of the heart

1. 1st rule states that atrial systole and ventricular systole will never overlap.
2. 2nd rule states that trial diastole and ventricular diastole are partly overlaping.
Ejection Isovolumetric relaxation
Rapid inflow Isovolumic Diastasis
Contraction Atrial systole

120 Aortic valve

100 opens Aortic valve closes

Aortic pressure 80
60
40
A-V valve 20 closes A-V valve opens ac v

0
130
Atrial pressure
ventricular pressure

ventricular volume 90 R
50 P T QS
Electrocardiogram
1st 2nd 3rd Phonocardiogram
Systole Diastole Systole

Fig. 3.9
Various changes taking place during cardiac cycle
120
Left 100
ventricle Clossure of SLV
80 Opening of SLV
60 Opening of AV valves
40 Right ventricle
20
Closing of AV valves 0
Rightventricle
0 Atrial systole
0.2 0.4 0.6
Isovolumetric contraction
Ejection period First Slow fillingrapid filling
0.8

Atrial systole last rapid filling

Proto diastole Isometric relaxation or isovolumetric relaxation

Fig. 3.10 Cardiac cycle—pressure changes inside ventricles

Time in seconds
Pressure changes inside the left ventricle

At the begining of ventricular systole, pressure inside the left ventricle is 0

millimeters of Hg. This pressure gradually increases. This increasing pressure
causes the closure of A.V. valve. It produces Ist heart sound. When the pressure
reaches about 80 mm of Hg it opens the semi lunar valve. At the peak of systole
the pressure reaches to 120 mm of Hg. This maximum pressure during the
systole is end systolic pressure. During the ventricular diastole pressure inside
the left ventricle gradually falls and it reaches to a minimum of 0 mm of Hg. The
minimum pressure during the ventricular diastole is known as end diastolic
pressure.

Volume changes inside the left ventricle

During systole blood is pumped out of the left ventricle into the aorta. The
amount of blood remaining inside the left ventricle at the end of ventricular
systole is known as end systolic volume. Normal value is about 50 ml. During
ventricular diastole the left ventricle receives blood. The maximum amount of
blood collected inside the left ventricle at the end of diastole is called end
diastolic volume. Normal value is 120 ml. During each contraction 70 ml. of
blood is pumped out of the left ventricle. It is known as stroke volume. Fraction
of end diastolic volume that is ejected is called as ejection fraction.

Normal value is 60–70%

Innervation of heart
Nerve supply of the heart

Heart is supplied or innervated by the autonomic nervous system. Both

sympathetic and parasympathetic nerves innervate the heart. Sympathetic fibres
supply to the junctional tissues of the heart like SA node, bundle of His and
Purkinge fibre. It also innervate the muscles of the ventricles. There is no much
innervation of ventricular muscles by the parasympathic nerves. The actions of
sympathetic and parasympathetic nervous system are opposite to each other.
Sympathetic fibres that innervate the heart arise from intermediolateral horn
cells of T1 and T5 segments of spinal cord. post ganglionic sympathetic fibres
form— superior middle and inferior cardiac nerves. The post ganglionic fibres
secrete norepinephrine as neurotransmitter.
Cerebral cortex
Thalamus

The action of sympathetic and parasympathetic nervous system on the heart are
opposite to each other. The balancing action between the sympathetic and
parasympathetic maintains the normal heart rate.
Hypothalamus Medulla

Cardio vascular
center Pons
Baroreceptor in carotid sinus

Baroreceptor IX nerve
in arch of aorta Vagus

Medulla SA node AV node Right

sympathetic chain
Right Left vagus
vagus

S-A Sympathetic
node nerves
Ventricular myocardium Cardiac accelerator nerve Spinal cord Sympathetic trunk ganglion
Fig. 3.11 Innervation of heart

Effect of sympathetic stimulation on heart

Increase in sympathetic activities produces the following changes in the heart.

1. Increases heart rate—positive Chronotropic effect.

2. Increases velocity of conduction—positive Dromotropic effect.
3. Increases force of contraction of heart—positive Ionotropic effect.
4. Increases excitability of muscles—positive Bathmotropic effect.

Parasympathetic Innervation of Heart

Parasympathetic nerve Fibres supplying the heart originate in the dorsal nucleus
of vagus in the medulla oblongata. This is called as Cardio Inhibitory Centre
(CIC). Preganglionic parasympathetic fibres proceed as left and right vagusthey
are long and myelinated. The parasympathetic ganglia is very close to the heart.
Post ganglionic unmyelinated parasympathetic fibres innervate S.A. node, A.V.
node and muscles of atria. Right vagus supply S.A. node and left vagus supply
A.V. node. Post ganglionic parasympathetic nerves secrete acetylcholine as the
neuro transmitter. The continuous inhibitory action of vagus on heart keeping
heart rate low is called as vagal tone. Ventricular myocardium is not innervated
by parasympathetic.
Left
sympathetic chain

AV
node

Fig. 3.12 Innervation of heart

HEART RATE
Rate at which heart beats per minute. Normal rate is 72/minute. Normal range
70-90/min.

Intrinsie heart rate: When the tonic effects of parasympathetic and sympathetic
nervous system are abolished by the administration of drugs heart rate increases
to 100/minute. This is called as intrinsic heart rate.

Physiological Variations 1. Age:

Foetus
New born infants Children (1–7 years) Children (7–14 years) Adults
— 140–150 beats/min — 130–140 beats/min — 90–100 beats/min — 80–90
beats/min — 70–80 beats/min

In old age heart rate decreases.

2. Sex:
Heart rate is slightly higher in female than males
because
(a) B.P. is less in female.
(b) Sympathetic tone is more in female. 3. Sleep: During sleep heart rate
decreases. 4. Exercise: Exercise increases heart rate.
5. Emotions: During emotions heart rate increases. 6. After a meal, heart rate
increases.
7. Pregnancy: During late stages of pregnancy heart
rate increases.
8. Athletes: In athletes at rest heart rate is lower than
normal. This conditions is known as “Athletic
Bradycardia”.
Bradycardia—Decrease in heart rate around
60/min.
Tachycardia—Increase in heart rate around
100/min.
9. Phase of respiration: During inspiration heart rate
increases, during expiration it decreases.

Regulation of Heart Rate

Heart rate is maintained with narrow marginal fluctuation. Regulation of heart

rate is important in regulation of cardiac output.

Heart rate is regulated by the following mechanisms.

1. Nervous regulation.
2. Hormonal regulation.
3. Thermal regulation.
Nervous regulation

Heart rate is controlled by the autonomic nervous system. The pace maker of the
heart, S.A. node is supplied by sympathetic as well as parasympathetic nerves.
Sympathetic nervous system shows a stimulatory action on the S.A. node.
Therefore any increase in sympathetic activities will increase heart rate. The
parasympathetic innervations is through nerve ‘vagus’ (10th cranial nerve).
Vagus shows a continuous inhibitory action on the S. A. node. Increase in vagal
activity will decrease the heart rate. A constant heart rate is maintained by a
balance of action between sympathetic and parasympathetic nervous system. The
continuous inhibitory action of the vagus on the heart is known as vagal tone.
The basal heart rate depends on the vagal tone.

Role of central nervous system in the regulation of heart rate

(a) Spinal cord : The lateral horn cells in the thoracic segments of spinal cord
T1–T5 act as spinal cardio accelerating centre.

(b) Medulla oblongata: A group of neurons in the medulla controlling heart rate
is known as Cardiac centre. It is devided into two group.

(i) Cardio inhibitory centre or parasympathetic centre situated at dorsal motor

nucleus of vagus—nucleus tractus solitarius and nucleus ambigues.
(ii) Mudullary sympathetic centre or vasomotor

centre situated bilaterally in the reticular formation of the medulla oblongata.

The cell bodies are located in the rostal ventrolateral medulla.

Hypothalamus: It is the head ganglion of autonomic nervous system. Rostral

hypothalamus produce parasympathetic effect and caudal hypothalamus controls
sympathetic effect. Through the manipulation of ANS, hypothalamus exert an
influence of heart rate.

Cerebral cortex: It exterts its influence through limbic system and

hypothalamus. The cardiac centres get their afferent inputs mainly from -
baroreceptors and chemoreceptors.

Reflex mechanism
There are two important reflex mechanisms controlling
the heart rate.
1. Marey’s reflex or (Cardiac inhibitory reflex). 2. Bain Bridge reflex or (Cardiac
acceleratory reflex).
Marey’s reflex
Baroreceptors: These are the receptors which respond
to stretch. Baroreceptors are mainly located at the aortic arch
and carotid sinus. When blood pressure increases it will
stimulate the baroreceptors. From the baroreceptors impulses
are transmitted towards the CNS. From carotid sinus sensory
impulses are carried through carotid nerve or Herring’s nerve
which later joins IX cranial nerve or glossopharengeal nerve
to reach nucleus tractus soliltarius of medulla (NTS). From
the aortic arch baroreceptors the afferent fibres pass through
vagus nerve and reach medulla nucleus tractus solitarius.
These afferent fibres arising from carotid sinus and aortic
arch are also known as buffer nerves or sinoaortic nerves.
NTS sends excitatory impulses directly to cardiac inhibitory
area and suppresses it. Impulses from NTS are passed through
inhibitory interneurons and reach cardiac acceleratory area
or medullary sympathetic centre or vasomotor centre. The net result is
stimulation of parasympathetic nervous
system-vagus and decrease in the vagal tone. This produces
sudden decrease in heart rate and decrease in BP. Opposite happens when BP
falls. This reflex regulation
of heart rate in known as Marey’s reflex.
Marey’s law
States that heart rate is inversely proportional to B.P.

i.e., HR ∝
1.
B.P.
There is an exception for Marey’s law, during exercise both heart rate and BP
increase.
Medulla oblongata NTS
Cardiac inhibitory centre
Increase in Intra cranial pressure
+ Blood flow to brain decreases
+ Impulses through buffer nerves

Inhibitory interneuron Vagal tone increases Ischemia of vasomotor centre

Hypoxia, Hypercapnia at VMC

Baroreceptors carotid sinus Aortic arch Vasomotor centre or

sympathetic centre Stimulation of VMC

+ Increase in sympathetic tone

Increase in BP Decreased sympathatic

tone
–
S.A. node of heart Blood vessels
Blood vessels Increased vaso constriction Decrease in heart rate
Vasodilatation Increased TPR
Decrease in peripheral resistance
Increase in BP
Stimulation of baroreceptors
Decrease in B.P Sino aortic reflex
Fig. 3.13
Pathway of Marey’s reflex Cushing’s reflex or Cushing’s reaction

Cushing reflex is important to protect the vital centres of brain from ischemia.
Arteral blood pressure is increased above intracranial pressure. This enables
more blood flow to the brain and releives the effects of ischemia. Here a reflex
hypertension and bradycardia are observed.

Cardiac acceleratory reflex (or) Bain Bridge reflex When the venous return
increases it will increase the
load of blood on the right atrium. This will stretch the wall of the atrium. This
will stimulate the stretch receptors. From these receptors impulses are
transmitted to cardiac centre situated in the medulla oblangata. These impulses
will stimulate cardiac acceleratory centre, inhibit cardiac inhibitory centre. This
will increase sympathetic tone, stimulate S.A. node, increases the heart rate.
Therefore, whenever venous return increases, there will be a sudden increase in
heart rate. This is known as Bain Bridge Reflex.
Stimulation of cardio inhibitory centre
Increase in vagal tone
SANode
Heart rate decreases

Fig. 3.14 Cushing’s reflex or Cushing’s reaction

Hormonal regulation of heart rate

There are two hormones involved in the regulation of heart rate. They are:

1. Thyroxine 2. Adrenaline (Epinephrine)

These two hormones will stimulate the S.A. Node and increases the heart rate.
These two hormones increase the rate of metabolism. This requires more oxygen
supply and it is met with increasing the heart rate.

Thermal regulations
Increase in temperature increases the heart rate. Whenever

metabolic rate increases, body temperature increases, heart rate increases, so

cardiac output increases. So more O2 is supplied.

For every 1°F rise in temperature the hart rate increases by 10 beats.

CARDIAC OUTPUT

Cardiac output is defined as amount of blood pumped out of each ventricle per
minute. Cardiac output is expressed in two forms.

1. Stroke volume and 2. Minute volume

Stroke volume: It is defined as amount of blood pumped out of each ventricle

per beat or contraction. Normal value is 70 ml.
Minute volume: It is defined as the amount of blood pumped out of each
ventricle per minute. Normal value of cardiac output is 5000 ml/mt.

Minute volume = SV × HR
(Stroke volume × heart rate), 70 × 72
Cardiac Index: It is defined as amount of blood pumped out of each ventricle
per minute per one square metre of body surface area.
Cardiac Output = 5000 ml.Cardiac index = Body surface area 1.7 sq. metre = 3000
ml/mt/m2

Cardiac reserve: It is the difference between maximum cardiac output and

normal cardiac output.

30 L – 5 L = 25 L/min. Cardiac reserve can be expressed as the maximum

increase in Cardiac output above the normal and it is expressed as percentage. In
healthy adults it is 300-400% and in athletes it is 500–600%.

TABLE 3.2
Distribution of cardiac output at rest
Sl. No. Organ

1. Brain
2. Kidneys
3. Liver
4. Skeletal Muscle
5. Skin
6. Heart
7. Other organs GIT Total:
Distribution
in ml/min % 750 15 1200 24 1500 30 750 15 200 4 250 5 350 7 5000 100

Physiological variations of cardiac output

1. Age: Cardiac output is more in adults than in children because blood volume
is more.
2. Sex: Cardiac output is more in male than female.
3. Altitude: Cardiac output increases at high altitude places.
4. Pregnancy: Cardiac output increases during pregnancy.
5. Exercise: Cardiac output increases during exercise.
6. Emotion: Cardiac output increases during emotional expressions.
7. Sleep: Cardiac output decreases during sleep.
8. Posture: Cardiac put is maximum in lying down position minimum in
standing posture.
Pathological variation of cardiac output. Pathological increase—
Hyperthyroidism, fever pathological decrease— Hypothyroidism, hypovolumia,
hemorrhage, myocardial infarction.

Factors Effecting Cardiac Output

Cardiac output is the product of heart rate and stroke volume. Any change in
heart rate or stroke volume or both of them will alter cardiac output.

1. Heart rate: When heart rate increases cardiac output also increases. Cardiac
output is proportional to heart rate upto a physiological limit (about 140
beats/mt). Any factor which changes heart rate will also change cardiac output.
(a) Sympathetic tone—Increase in sympathetic tone

will increase heart rate and inturn increase cardiac output.

(b) Adrenaline level–Increase in adrenaline level will increase heart rate and
cardiac output.
(c) Thyroxine level.
(d) Temperature.
2. Force of contraction of the heart:
When the force of contraction of the heart increases,
stroke volume will increase. Therefore cardiac
output will increase.
Force of contraction of heart is influenced by
1. Size of the heart: The enlargement of the heart
will increase stroke volume and thereby increase
cardiac output.
2. Sympathetic stimulation and adrenaline
stimulation: Both will increase the force of
contraction of the heart, it will increase stroke
volume and cardiac output.
3. Blood volume: When blood volume increases cardiac output will increase.
4. Venous return: It is defined as the amount of blood returned to the heart by
the venacava per minute. Normal value is 5000 ml/mt.
Any factor influencing venous return will change the cardiac output. e.g.,
(a) Muscular exercise—Muscle pump: During muscular exercise venous return
increases due to the squeezing of the veins so more blood come to the heart. This
increases cardiac output.
(b) Thoracic pump or respiratory pump: During inspiration intrapleural
pressure and intrathoracic pressure becomes more negative. The intra abdominal
pressure rises due to the descent of the diaphragm. Pressure inside large veins
nearer to heart decreases. This creates a more pressure gradient. This suction
action of respiration is called as respiratory pump.
(c) Cardiac pump:
1. Vis A Tergo—force from behind which drives the blood forward. This
propelling force is due to
(i) contraction of heart
(ii) elastic recoil of arterial wall.
2. Vis a. fronte—the force acting from the front to attract blood in the veins
towards heart. It is exerted by the suction action of atrium.
(d) Total blood volume: Increase in blood volume will increase venous return.
(e) Venomotor tone: When sympathetic activity is increased veins undergo
constriction and the blood within it is driven towards the heart more speedily.
(f) Body position and gravity: In standing position peripheral pooling of blood
occurs and this decreases venous return.

Determination of cardiac output

There are two common methods:
1. Dye dilution technique and
2. Fick’s principle.
Dye dilution method–The dye used should fullfill the

following criteria:
(a) It should be non toxic.

(b) It should be physiologically and biochemically inert.

(c) It should easily mix.The commonly used dye is Evans blue, T1824.

Five ml of 5% dye is injected intravenously.Arterial blood samples are taken at

regular intervals.The concentration of dye in different samples are estimated
using colorimeter.The concentration of dye is plotted against time in a semi
logarithmic graph paper.The concentration of dye gradually increases, reaches to
a peak and then it decreases. Once again concentration of dye increases
indicating the recirculation of dye. From the graph the mean concentration of
dye is determined.The cardiac output is estimated using

the formula CO =
D , where D is the amount of dye injected,
ct
c is the mean concentration of dye, t is time in seconds.
Time
Fig. 3.15 Graph plotted for the determination of mean concentration of dye

Fick’s Method: Fick’s principle states

That the amount of any substance taken up or given out by any organ or whole
body per minute is equal to arterio venous difference in the concentration of the
substance into blood flow. So blood flow per minute throughout the body or
cardiac output is equal to amount of substance taken up by whole body divided
by arterio venous difference in the concentration of the substance.

Amount of O2 consumed by the person per minute is estimated using Douglas’s

bag. A sample of arterial blood and a sample of venous blood are collected. The
O2 content in these samples of blood are estimated using Gas analyser. Cardiac
output is calculated using the formula.
ml of O2 consumed in ml / mt ×100CO = Ocontent in 100 ml O
content in 100 ml22
of arterial blood− of venous blood Normal values are CO
250 ml ×100= 19.4 ml − 14.4 ml

= 250 ×100 = 5000 ml/mt5

Regulation of Cardiac output

It means maintaining a constant cardiac output around 5 l/ mt under normal

conditions and adjusting the cardiac output as per the physiological demand.

It has to be regulated to have an optimum cardio vascular efficiency.

Mechanisms of regulation
1. By venous return

Force of contraction of a muscle fibre is proportional to its initial length. It is

known as Starling’s law of muscle contraction.

Suppose more blood enters the left ventricle. This will increase the load of
blood, it will increase the stretching of the muscle fibres and increase the initial
length of the muscle fibres. So force of contraction and stroke volume will
increase. This will increase cardiac output. Therefore whenever venous return
increases cardiac output increases.

Frank Starling’s law

It is defined as cardiac output is equal to venous return within the physiological

limits or heart pumps out whatever blood received by it within the physiological
limit. This type of regulation is known as intrinsic regulation.

2. Regulation of cardiac output by nervous system

Autonomic nervous system takes a major role in the regulation of cardiac output.
Whenever sympathetic nervous system activity increases, e.g., during emotions,
exercise etc, it will stimulate both S.A. node as well as ventricular myocardium.
This will increase both heart rate as well as force of contraction of muscles or
stroke volume. This will inturn increase cardiac output. If parasympathetic
activity increases as during sleep, it will inhibit S.A. node, it will decrease heart
rate, this will inturn decrease cardiac output.
Parasympathetic Adrenaline Sympathetic
tone Adrenaline Venus return
++
– SA node + + Ventricular+ myocardium
Heart rate Force of contraction
Stroke volume
Cardiac out put
Fig. 3.16
Regulation of cardiac output

Hormonal regulation of cardiac output (adrenaline): Whenever adrenaline

level in the blood increases it will stimulate S.A. node and ventricular
myocardium. This will increase both heart rate and stroke volume. This will
inturn increase cardiac output.

Electrocardiogram (ECG)
Recording of electrical activities of heart is known as electrocardiography. The
technique was first devised by Sir Willem Einthovan in 1903. He was awarded
Noble Prize in the year 1924. Cardiac muscles generate and conduct impulses.
These electrical activities of the heart are cyclically repeated during each cardiac
cycle. The electrical activities of the heart will spread to the surface of the body.

ECG is defined as the graphical record of electrical changes taking place in the
heart during each cardiac cycle. ECG can be recorded by keeping the electrodes
either on the limbs or on the chest. The electrodes and the wires connecting them
to the instrument are known as ‘lead’. There are two common types of leads,
limb leads and chest leads. Limb leads are of two types (1) Bipolar limb leads or
standard limb leads (2) Unipolar limb leads. Unipolar limb leads are of three
types:

Leads Position of exploring electrode

aVL – Left arm
aVF – Left foot
aVR – Right arm
Chest leads are of six types V1, V2, V3, V4, V5 and V6 Leads Position of
exploring electrode. V1 – 4th intercostal space, right border of sternum. V2 –
4th intercostal space, left boarder of sternum. V3 – midway between V2 and V4.
V4 – 5th intercostal space, where it is cut by mid

clavicular line.
V5 – 5th intercostal space at anterior axillary line. V6 – 5th intercostal space at
mid axillary line.

Standard bipolar limb leads.

There are 3 types of bipolar limb leads. Lead I, Lead II and Lead III

TABLE 3.3
Bipolar limb leads
Lead Lead I Lead II Lead III Negative Terminal Positive Terminal Right arm
Right arm Left arm
Left arm Left leg Left leg

Intervals: P-P or R-R interval between two successive P waves or two—R

waves. Duration is 0.8 sec.
P Q interval or P–R interval: Interval between the beginning of P wave to
beginning of Q wave. Duration is 0.12 to 0.16 sec.
Normal Duration
P — Wave 0.1 sec
QRS complex — 0.08 sec
QRST — 0.26 – 0.45 sec
T — Wave – 0.2 sec

ECG
1.5
1.0R LEAD I
–+
– 0.5
+TP
0

–+ – LEAD II+ LEAD III Q

0.5S
0 0.2 0.4 0.6 0.8 Time-second

Fig. 3.18
Normal ECG
Normal intervals
R – R interval 0.8 sec
P – Q interval 0.12 – 0.16 sec
Q – T interval 0.40 – 0.43 sec
P – P interval 0.8 sec P – R interval 0.12 – 0.16 sec S – T interval 0.32 sec

+–

Fig. 3.17
Recording of ECG 2

The hypothetical triangle obtained by joining left arm, right arm and left leg is
known as Einthovan’s triangle. A normal ECG recorded from a standard limb
lead shows 5 waves, PQRST. Of this, P wave, R wave and T wave are positive
waves, Q and S are negative waves. There are two isoelectric (neutral) segments.
They are PQ segment and ST segment.

Einthovan’s law : This law states that sum of voltages in Lead I and Lead III
equals the voltage in Lead II. In ECG X-axis denotes time and Y axis denotes
amplitude.
P wave: P wave represents the depolarisation of atria. It’s a dome shaped wave.
Duration of P wave is 0.1 sec.
QRS is a complex. It represents the depolarisation of ventricles.
T-wave: T wave represents the repolarisation of ventricles.
1.5
1
0.5
0 0.2 0.4 0.6 0.8 1 Time (s)

Fig. 3.19 ECG paper: Five large divisions correspond to one second in the X
axis. One second is divided into 5 smaller
divisions so that each division corresponds to 0.2 sec. This is
again divided into 5 so that smallest division is 0.04 sec. In
the Y axis 10 divisions correspond to 1 mV so that one small division is 0.1 mV.

TABLE 3.4
Normal ECG showing durations and significance
S.No. Wave/Interval/Segment Duration Significance 1. P wave Up to 0.10
second wide and 3.0 mm tall
2. PR interval 0.12 to 0.16 second wide
3. PR segment or P-Q segment
4. QRS complex 0.08 to 0.1 second
5. QT interval 0.40 to 0.43 second

6. ST segment and T wave

7. U wave

Atrial depolarisation
It is normally positive in all ECG leads except aVR.

From the beginning of the P wave to the beginning of the QRS complex
represents conduction of the electrical impulse from the S.A. node to A.V. node.
A prolonged PR interval indicates a first degree heart block.

The PR or PQ segment is the isoelectrical portion between the P wave and QRS
complex. Represents ventricular depolarisation. Small initial down ward
deflection after PQ segment. Beginning of the Q wave to the end of the T wave
represents the refractory period of the heart. Represents ventricular
repolarisation.
Rarely seen as positive small round wave of 0.08 sec. duration. It is due to slow
repolarisation of papillary muscles.

Significance of ECG

1. ECG is used to find out the exact heart rate. To detect conditions like
bradycardia tachycardia.
2. It is used to assess the rhythmicity of heart.
3. ECG can be used to detect and locate cardiac block.
4. It is used to detect the hyperplasia or enlargement of the heart.
5. Prolongation of PQ interval beyond 0.2 sec. may indicate enlargement of the
atria or slow conduction in the atria. Increased amplitude of P wave indicates
enlargement of atria.
6. An inverted P wave indicates Ectopic pacemaker i.e.,Any other part of the
heart acting as pacemaker other than S.A. Node.
7. ECG is used to detect disorders of the heart like myocardial infarction. During
myocardial infarction the ST segment may either depleted below the 0 line or
elevated above the 0 line.
8. Inverted T wave indicates hypokalemia and post myocardial infarction.

HEART SOUNDS

The sounds produced by the heart are known as heart sounds. Heart sounds are
produced due to the vibration of the leaflets of valves. The vibration of the
valves may be due to three reasons.

1. Sudden closure of the valves.

2. Due to the turbulent flow of blood.
3. Contraction of chambers of heart.
There are four heart sounds.
Heart sound I
Heart sound II
Heart sound III
Heart sound IV
Of this I and II heart sounds can be heard using a stethoscope, III and IV are not
commonly heard but they can be recorded in a phonocardiogram.
I Heart sound
1. Cause: Vibration of the A.V. valves due to the sudden closure.
2. Occurrence: It takes place at the beginning of ventricular systole. i.e.,
Isovolumetric contraction period.
3. It coincides with R wave of ECG.
4. Nature of the sound: It is heard in the form of the word ‘LUBB’.
5. Duration — long, about 0.14 sec.
6. Frequency—25–45 cycles/sec.
7. Best heard at — the mitral area.
II Heart sound
1. Cause: Vibration of semilunar valves due to their sudden closure.
2. Occurrence: It happens at the end of protodiastole. 3. Coincides with T wave
of ECG.
4. Nature of the sound: It is heard in the form of the word ‘DUP’.
5. Duration: Shorter than the I heart sound. It is 0.11 sec

6. Frequency is higher than I heart sound. 50 cycles/ sec.

7. Best heard at pulmonary area and tricuspid area.
III Heart sound
1. Cause: Vibration of A.V. valves due to the turbulent flow of blood.

TABLE 3.5
Comparison between I and II heart sound

2. Occurrence: Happens during Ist rapid filling phase. Usually 3rd heart sound
is not heard but sometimes this sound can be heard in healthy young adults.

IV Heart sound
1. Cause: Vibration of the A.V. valves due to the turbulent flow of blood.

2. Occurrence: It happens during the last rapid filling phase or during the atrial
systole.
Therefore this sound is known as atrial sound.

Areas of auscultation of heart sounds

Aortic area — Second right intercostal space close to the sternal boarder.
Pulmonary area — Second left intercoastal space close to sternal boarder.
Mitral area — First left intercostal space 1 cm. medial to midclavicular line.
Tricuspid area — Fifth left intercoastal space close to the sternal boarder.

S.No. I heart sound II heart sound 1. Cause Vibration of A.V. valves due to
closure. Vibration of semilunar valves due to closure. 2. Occurrence Beginning
of ventricular systole. During early ventricular diastole, end of protodiastole.
3. Coincides with ‘R’ wave of ECG. ‘T’ wave of ECG 4. Nature LUBB DUP 5.
Duration 0.11–0.17 sec, longer. 0.10–0.14 sec, shorter 6. Frequancy 25–45
cycles/sec. 50 cycles/sec. 7. Significance 1. Loudness indicates force of
contraction of heart.
1. Loudness indicates blood pressure.
2. Clear sound indicates proper closing of A.V. valves. 2. Clear sound indicates
the proper closing of SLV.
8. Best heard at Mitral area, left 5th intercostal area. Pulmonory area, 2nd left
intercostal area close to sternum.

Significance of Heart Sounds

1. Auscultation of heart sound is done to find out the heart rate.

2. It helps to asses the rhythmicity of heart.
3. The time gap between I heart sound and II heart sound is considered as
clinical systole. Time gap between II heart sound and the I heart sound is
considered as clinical diastole.

4. The loudness of I heart sound suggests the force of

contraction of heart.
5. The loudness of II heart sound indicate BP.
6. First heart sound becomes very loud in left ventricular hypertrophy—booming
first heart sound.
7. In systemic hypertension the intensity of second heart sound at aortic area
increases and acquires a character called metallic.
8. Auscultation of heart sounds helps to detect abnormal heart sounds like
murmurs. These are due

to improper closing of valves e.g., mitral stenosis or regurgitation of blood.

Narrowing of valves is known as stenosis. If valves are not able to close

properly, leads to regurgitation of blood. This is called as incompetency of
valves. Murmur is due to turbulance created at or near the valve.
Types of murmur

1. Systolic murmur
2. Diastolic murmur
3. Continuous murmur.

TABLE 3.6
Murmur types and their causes
S.No. Type
LUBBDUP LUBPLUP
IHS II HS I HS II HS
Ventricular Ventricular Ventricular systole diastole systole
IHS II HS III HS IV HS
Causes 1. Systolic murmur Aortic stenosis,

Mitral stenosis,
Mitral and tricuspid Incompetency, Anemia
Electrocardiogram
Fig. 3.21
Phonocardiogram
2. Diastolic murmurs Mitral stenosis,

Tricuspid stenosis,
Aortic incompetency, Pulmonary incompetency

BLOOD PRESSURE

Blood pressure is defined as lateral pressure exerted by the blood on the walls of
the blood vessels while flowing through them.

3. Continuous murmur Patent ductus arteriosus

Stemum Clavicle
Right Mid Leftclavicular
lines

Pulmonary area Aortic area

Tricuspid area

Mitral area

Fig. 3.20 Location of auscultatory areas over the chest Phonocardiography

The graphic record of the heart sounds is called Phonogram. Because the sound
is from the heart, it is called phonocardiogram. The instrument used to measure
the heart sounds is called phonocardiograph. This instrument uses a
phonocatheter, a device similar to a conventional catheter, with a microphone at
the tip. The basic aim of phonocardiograph is to pick up the different heart
sounds, filter out the heart sounds and to display them (or) record them. Heart
sounds are acoustic phenomena resulting from the vibrations of the cardiac
chambers.

Blood pressure in a blood vessel depends upon two things.

1. Distance from the heart and
2. Nature of the blood vessel.
Blood pressure is more in blood vessels close to the heart. Blood pressure is
more in arterial system than in the venous system. This is because walls of
arteries are more thick and less elastic, the walls of the veins are more thin and
more elastic.
Normal blood pressure is 120/80 mm of Hg, i.e., Systolic BP is the maximum
BP during the ventricular systole —120 mm of Hg. Range: 110–130 mm of Hg.

Diastolic BP
The minimum pressure during the ventricular diastole.
It is 80 mm of Hg Range: 70–90 mm of Hg.
Pulse pressure
Pulse pressure means the difference between systolic
BP and diastolic BP i.e., 40 mm of Hg.
SBP : DBP : PP = 3 : 2 : 1
Mean arterial blood pressure
It is not the arithmetic mean but it is less than that. It
is because most of the time BP is more closer to diastolic
value than systolic value. It is because duration of ventricular
diastole is longer than duration of systole.

Mean arterial blood pressure = Diastolic blood pressure + 1/3 of pulse pressure
i.e., 80 + 13 = 93 mm of Hg.

Physiological variations
Age : BP is more in adults than in children. In children: SBP = 90–120 mm of
Hg.

DBP = 50–80 mm of Hg.

Sex : BP is more in males than females. This difference disappears after

menopause.
Pregnancy : During the later stages of pregnancy usually SBP increases DBP
decreases due to the vasodilator produced by progesterone.
Altitude : BP is higher in people living at higher altitude.
Editing
Exercise
Emotion
Sleep

: BP increases after a meal.

: Systolic BP increases during exercise. : BP rises during emotional expressions.
: BP falls during sleep.

Diurnal variation: BP is maximal in the morning and minimum in the late

evening

Factors Effecting Blood Pressure

Blood pressure is the product of cardiac output into total peripheral resistance.
Any factor which can change either cardiac output or peripheral resistance can
influence BP.

Determinants of BP
1. Volume of blood: When volume of blood increases

BP will increase.
2. Force of contraction of the heart: When the force
of contraction of the heart increases BP increases.
Force of contraction of the heart is influenced by
size of the heart. When the size of heart increases
force of contraction of heart increase so BP
increases. Sympathetic stimulation and adrenaline
stimulation will increase force of contraction of the
heart, it will inturn increase BP.
BP = CO × TPR (Total peripheral resistance).
Force of contraction of heart and stroke volume
are effected by preload, after load and myocardial
contractility. When venous return increase proload
will increase this will increase force of contraction
of the heart and stroke volume.
3. Peripheral resistance: It mostly depends upon the
caliber of asterioles and small arteries. The smooth
muscle of orterioles on in a state of constriction
and this exerts resistance for the flow of blood. Any
alteration in the total peripheral resistance influence
BP.
4. Heart rate and BP are inversely proportional. 5. Viscosity of blood: When the
viscosity of blood
increases the resistance for the flow of blood will
increase. This will increase the total peripheral
resistance. This will inturn increase BP.
For example, polycythemia and hyperproteinemia
will increase TPR and BP. Anemia and
hypoproteinemia will decrease viscosity, decrease
TPR and decrease B.P.
6. Nature of the blood vessels: Diameter of lumen
of blood vessel: Narrowing of the lumen of blood
vessel will increase the resistance for the flow of
blood and it will increase BP. The diameter of blood
vessels mostly depend on the sympathetic
vasoconstrictor time.
The cause for narrowing of blood vessel is
deposition of fats on the walls of the blood vessels
(atherosclerosis) This will decrease the diameter of
the blood vessel. This will increase BP.
7. Elasticity of the blood vessel: The deposition of
fats and minerals on the walls of the blood vessels
will reduce its elasticity. The deposition of minerals
mainly, calcium is called arteriosclerosis. This will
decrease the elasticity of blood vessel, this will
increase the BP.

Poiseuille’s law: Resistance =

8η 1××r4π
Blood flow between two points =
∆
P
πr4 1 8 ××1η

where, η = viscosity of blood, r = radius of blood vessel, l = length, ∆P =

difference of pressure between two points. Any factor which decreases the
compliance or distensibility of the arteries will increase BP.

Regulation of blood pressure

It means maintaining a constant blood pressure within a narrow variation. Both

increase in blood pressure (Hypertension) and decrease in blood pressure
(Hypotension) are harmful for the body. Chronic hypertension may produce
conditions like chronic renal failure, congestive heart failure, breakage of weak
blood vessels leading to hemorrhage. A cute sharp fell in BP may mean shock.
When perfusion pressure to vital organs decreases it may lead to death.

The mechanisms of regulation of BP is divided into two groups:

1. Rapidly acting mechanisms—Short-term regulation.
2. Slow acting mechanism—Long-term regulation.

Rapidly acting mechanism — Short term regulation This includes both

nervous regulation as well as
endocrine or hormonal regulation.

Short term regulation of blood pressure

Short term regulation of blood pressure means the correction in blood pressure is
achieved within seconds or minutes to hours. The short term control of BP is
mainly achieved through neural mechanisms, peripheral reflexes, vascular
mechanisms and hormonal mechanisms.

The neural mechanisms include the following: Control by autonomic nervous

system, role of medulla oblongata and hypothalamus. The major reflex
regulations are baroreceptor reflex, chemoreceptor reflex and Cushing's reflex.
The vascular mechanisms include capillary fluid shift and stress relaxation. The
major hormonal systems taking part in the control of BP are Renin—
angiotension- aodosterone axis, vasopressin catecholamines and ANP.

Control of BP by autonomic nervous system: Sympathetic nervous system

plays a major role. The wall of blood vessels lack parasympathetic innervations.
So there is no significant role for parasympathetic nervous system in the
regulation of BP. The degree of vasoconstriction of arterial system depends upon
the sympathetic tone. There are two groups of sympathetic discharge.

1. Sympathetic vasoconstrictor and

2. Sympathetic vasodilators.
Sympathetic vasoconstrictor fibres originate from the intermediolateral horm of
the spinal cord. They innervate heart, adrenal medulla, wall of arteries and
arterioles. Nor adrenaline is the neurotransmitter. It produces contraction of
smooth muscles of blood vessel. This in-turn produce vasoconstriction increase
peripheral resistance thereby elevate BP. The continuous discharge of
sympathetic vasoconstrictor fibres maintain basal vascular tone, and basal degree
of vasoconstriction.
In addition to manipulation of arterial vasoconstriction, sympathetic discharge
produce venoconstriction. This will increase venous return, cardiac output which
will inturn elevate BP. The actions of increased sympathetic tone can be
prolonged through catecholamines secreted from adrenal medulla.
Whenever the vasoconstrictor sympathetic tone decreases, it will lead to
vasodilatation, fall in peripheral resistance and decrease in BP. Sympathetic
vasodilator fibres innervate blood vessels of skeletal muscle. Here
neurotransmitter is acetylcholine. Stimulation of these fibres originate from
frontal cortex and relay in hypothalamus and midbrain. Role of medulla in the
regulation of BP. Groups of neurons controlling cardiovascular functions

are called as cardiovascular centres. They are situated at the medulla. The cardio
vascular centers are two types: vasomotor centre and cardio inhibitory centre.
These centers manipulate the sympathetic discharge there by exert an influence
on blood pressure. Vasomotor centre is mostly located in the rostral ventro
lateral medulla (RVLM). This group of neurons continuously fire impulses,
which reach the spinal cord through bulbo spinal tract. Whenever vasomotor
centre is stimulated it will increase sympathetic tone, the net result will be
increase in heart rate, force of contraction of heart , increase in cardiac output,
increase in BP. When this centre is inhibited opposite responses will be seen.

Medullary cardio inhibitory centre

This made up of nucleus tractus solitarios nucleus ambiguous and dorsal motor
nucleus of vagus. Stimulation of this area produce decrease in sympathetic tone
and increase in parasympathetic discharge. The manifestation of this can be seen
as decrease in heart rate, decrease in cardiac output, vasodilation and fall in
blood pressure.

The medullary centers integrate various inputs from cortex, hypothalamus,

limbic system, respiratory centers, ascending pain pathways. This finally control
the sympathovagal output.

Role of hypothalamus
Hypothalamus and limbic system exert their influence on blood pressure by their
influence on vasomotor centre. Hypothalamus control the secretion of ADH.
This hormone controls the water loss through urine. This will in-turn regulate the
BP by regulating blood volume.

Baroreceptor reflex
Pons Vasomotor centre
Medulla

Glossopharyngeal nerve
Hering's nerve Carotid body & sinus
Vagus nerve Common carotid artery
Aortic baroreceptors

Fig. 3.22
Sino aortic reflex or Baroreceptor mechanism
Cardio vascular centre
Medulla
Sympathetic tone
Vascomotor centre Cardiac inhibitory centre
Pressure area
Depressure area
Blood vessel SA node – +
Vasodilatation Heart rate Vagus nullius

TPR Parasympathetic tone

–+

BP Baroreceptors aortic arch carotid sinus S.A. node

Decreasin heart rate

Fig. 3.23
Baroreceptor mechanism or sino aortic mechanism for the regulation of BP

Suppose the BP increases that will be detected by the baro receptors situated at
the aortic arch and carotid sinus. This baroreceptors will send impulses to the
medulla oblongata. Impulses from carotid sinus is carried by glossopharyngeal
nerve and from aortic arch impulses are carried by vagus. They are sinus nerve
and aortic nerves respectively. In the medulla oblongata there is a group of
neurons concerned with control of BP. It is known as vasomotor centre. There
are two different areas, Pressure area and Depressure area. The impulses coming
from the baroreceptors will inhibit the pressor area, this will decrease the
sympathetic tone. This will increase vasodilatation. TPR decreases so BP
decreases to the normal level. This mechanism operates very fast. It corrects the
BP within few second. Baroreceptors responds to pressure change between 50 to
200 mm of Hg. Beyond this range there is no baroreceptor activation.

Limitation: This mechanism will try to correct the BP. But if the increased BP
remains persistent it stops operating. This is because of the adaptation of
baroreceptors. Baroreceptor resetting takes place in chronic hypertension.

Chemoreceptor reflex
This mechanism operates between 40-100mm of Hg mean blood pressure.
Mechanism: Fall in BP specially below 80mm of Hg decreases blood flow to tissues.

This increases PCO2 and decreases PO2 in blood. ↓

This stimulates chemoreceptors at the carotid body and aortic bodies.

↓
Impulses are transmitted from receptors to vasomotor centre, cardiac centre and respiratory centres.
↓
This increases heart rate, alveolar ventilation, ↑ vasoconstriction so ↑ BP

Fig. 3.24 Chemoreceptor mechanism CNS Ischaemic response

It operates between 15–50 mm of Hg range of mean blood pressure. Mechanism:

Fall in arterial BP below 50 mm of Hg.
BP
CNS Ischaemia
Accumulation of CO in vasomotor centre 2
Stimulate pressure area of VMC
Increase in sympathetic discharge
Increase in BP and heart rate
Helps to maintain normal blood supply to brain
Fig. 3.25
CNS ischaemic response

Cushing’s reflex: Decrease in O2 content and increase in H+ concentration (or

decrease in pH) in the artery feeding vasomotor centre may directly stimulate
VMC and thereby increase sympathetic activity. This will inturn increase BP.

Role of vascular system in controlling BP. There are two mechanisms which
operate within seconds to minutes for the control of BP. They are 1. Fluid shift
mechanism. 2. Stress relaxation. Fluid shift mechanism. Suppose blood pressure
falls significantly. Hydrostatic pressure in blood capillaries decrease. So fluid
from interstitial space move into the blood vessels. Fluid shift takes place which
will increase blood volume. Increase in blood volume will increase blood
pressure. This mostly happens during hemorrhage shock where fall in blood
pressure due to blood loss is prevented by compensatory mechanism. When
blood pressure increases significantly opposite response—shifting of fluid from
blood to interstitial space happens. This will decrease blood volume and blood
pressure.

Stress relaxation
When blood pressure increases suddenly to compensate that the wall of blood
vessels distend. This produces acute stretching of wall of the blood vessels. This
stretch produce relaxation of smooth muslces of blood vessels. This produce
vasodilatation, decrease vascular tone and total peripheral resistance. This will
inturn decrease blood pressure. This

mechanism is known as stress relaxation. When blood pressure falls suddenly

reverse stretch reflex occur. Sharp fall in blood pressure reduces the stretch of
the wall of the blood vessel. This inturn produce the contraction of smooth
muscles of blood vessel, this increases vasular tone, total peripheral resistance.
This inturn increases blood pressure.

Hormonal Regulation of BP—Long Term Regulation

There are three important hormones taking part in the regulation BP.
1. Renin-Angiotensin-Aldosterone axis or mechanism.
2. Vasopressin or ADH
3. Adrenaline or Epinephrine.
4. Atrial Natriuretic Peptide (ANP)
Renin-Angiotensin-Aldosterone axis or mechanism Suppose the BP falls, it
will stimulate the kidneys. The juxta glomerular apparatus of the kidney will
secrete renin. Renin acts as an enzyme. It acts on a plasma protein, angiotensin
substrate and converts it into angiotensin I. The angiotensin I is converted into
angiotensin II by the action of the converting enzyme. Angiotensin II is a
vasoconstrictor in action. It acts on the walls of the blood vessels and increase
the degree of vaso constriction. TPR will increase, this will inturn increase the
BP to normal. In addition to that angiotensin II stimulates adrenal cortex.

This will increase the secretion of the hormone aldosterone. Aldosterone act at
the kidneys. It increases the reabsorption of sodium and water. This will increase
blood volume. When blood volume increases that will inturn increase BP.
Decreased blood volume, decreased blood pressure
Liver Increases blood pressure Increases blood volume Decrease water loss Increase water
reabsorption

Renin Angiotensinogen Kidney

Angiotensin I

Angiotensin converting enzyme

Lung Aldosterone Blood vessel

Vasoconstriction

Angiotensin II Adrenal cortex

Fig. 3.26
Renin-Angiotensin mechanism for the regulation of BP
Decreased blood volume increased osmotic pressure Decreased blood pressure baroreceptors
Osmoreceptors of hypothalamus Posterior
pituitary
Increased water reabsorption

and natriuresis. This has the incidence of increasing water loss through urine,
decreasing blood volume. Inturn, decreases BP. ANP also produce vasodilation,
decrease peripheral resistance thereby decreases BP.

Long term regulation of BP by the kidneys

Suppose the BP increases. This will increase G.F.R, this will increase urine
output and water loss from the body. This will decrease the blood volume, this
will in turn decrease the BP.
ADH Kidneys
Vasopressin GFR
BP – ve Urine out put

Decreased water loss Blood

vessels

BV– Water loss

Increased peripheral resistance Increased blood volume

Increased blood pressure

Fig. 3.27 Regulation of BP by ADH

Regulation of blood pressure by Vasopressin or ADH Suppose BP falls that

will stimulate the hypothalamus. Hypothalamus in turn stimulate posterior
pituitary. Posterior pituitary secretes vasopressin. It acts on the walls of the blood
vessels. It increases vasoconstriction. TPR increases and BP will increases to the
normal level.

In addition to this, ADH acts at the kidneys. It increases the reabsorption of

water. That will increase blood volume, so BP increases to the normal.

Adrenaline (Epinephrine)
Suppose the BP falls that will stimulate hypothalamus. Hypothalamus in turn
stimulates sympathetic nervous system. This will in turn stimulate adrenal
medulla. It secretes more adrenaline. Adrenaline acts at the wall of the blood
vessel. It increases vasoconstriction. This will increase TPR, this will in turn
increase BP to the normal.

Role of atrial natriuretic peptide (ANP)

This hormone is secreated by atrial myocytes in response to stretching of atria.
When venous return increases, atrial filling increases. This will produce
stretching of wall of atria. This

will lead to the secretion of ANP. ANP acts on kidney and will decrease water as
well as sodium reabsorption-diuresis
Fig. 3.28 Regulation of BP by kidneys
HYPERTENSION
Definition

Persistent increase in systemic arterial blood pressure is known as hypertension.

Usually a mean arterial pressure greater than 110 mm of Hg. under resting
conditions is considered to be hypertensive; this level normally occurs when the
diastolic blood pressure is greater than 90 mmHg. and the systolic pressure is
greater than about 135 to 140 mm of Hg.

Hypertension

Hypertension is defined as sustained elevation of systemic arterial blood

pressure. Hypertension can be systolic or diastolic or both.

Systolic BP Diastolic BP mm of Hg mm of Hg. 110-120 60–79

Remarks
Normal 120-139 80–89 Pre hypertension 140-159 90–99 Mild hypertension 160-
169 100 Moderate hypertension Above 170 Above 115 Severe hypertension

Types of Hypertension
It is divided into two types:
1. Primary hypertension (essential hypertension) 90% 2. Secondary hypertension
10%.
1. Primary hypertension

It results when the arterial blood pressure is increased due to increased

peripheral resistance. It is further divided into two types namely: benign and
malignant hypertension.

Benign hypertension: Here, there is a moderate increase in blood pressure with

systolic pressure of 200 mm of Hg. and the diastolic pressure of above 100 mm
of Hg. However, in resting condition and sleep, the blood pressure returns to
normal level. Later, if there is increase in blood pressure it will not come back to
normal level in resting conditions.

Malignant hypertension: Here, the blood pressure is elevated to a great extent

of about 250 mm of Hg. of systolic pressure and 150 mm of Hg. of diastolic
pressure. It produces severe symptoms like renal diseases, retinal disease, and
being a fatal disease, it causes death within few years.

Some of the characteristics of primary/essential hypertension are:

1. The mean arterial pressure is increased 40 to 60 per cent.
2. The renal blood flow in the later stages, is decreased about one half of normal.
3. The resistance to blood flow through the kidney is increased two to four fold.
4. The kidneys will not excrete adequate amounts of salt and water unless the
arterial pressure is high. The exact cause for essential hypertension is not known.
But possible causes are:
(a) Hyperactivity of sympathetic nervous system. (b) Increased secretion of renin
from kidneys. (c) Exces salt.
(d) Hypersecretion of salt and water retaining hormones like aldosterone,
cortisol, growth hormone.

2. Secondary hypertension
The different forms of secondary hypertension are: Cardiovascular
hypertension: It is produced due to

(a) Atherosclerosis—hardening and narrowing of blood vessels.

(b) Coarctation of aorta—narrowing of aorta. (c) Hyper volumea.

Renal Hypertension: It is produced due to

(a) Stenosis of renal arteries—narrowing of one or both renal arteries, so that the
renal function is impaired.

(b) Glomerulonephritis—nephritis with inflammation of the capillary loops in

the renal glomeruli.

Endocrine hypertension: It occurs due to

(a) Pheochromocytoma—tumor in adrenal medulla. (b) Hyperaldosteronism—
excess secretion of

aldosterone from adrenal cortex Conn’s syndrome. (c) Cushing’s syndrome—

exess secretion of cortisol. (d) Gigantism orAcromegaly—excess secretion of

growth hormone.

Neurogenic Hypertension
Acute hypertension can be caused by strong stimulation of the sympathetic
nervous system.

(a) Sectioning of the baroreceptor nerves. (b) Lesions in tractus solitarius.

(c) Increased intracranial pressure.

Hypertension in toxemia of pregnancy

It occurs due to thickening of the glomerular membranes which reduces the rate
of fluid filtration from the glomeruli into the renal tubules so, the pressure level
of the renal output curve is elevated and the long – term level of the arterial
pressure becomes correspondingly elevated. These patients are especially prone
to hypertension when they eat large quantities of salt. Blood vessels become
hypersensitive to vasoconstictors.

TABLE 3.7
Causes of secondary hypertension
Sl.No. Cause Pathophysiology 1. Renal–produring tumors
2. Renal failure

3. Renal artery stenosis Exess renin production leading to increase in the level of
angistension II blood—which is a potent vasconstrictor.

Decreased GFR, decreased urine output. Water retentorn increase in blood

volume, increase in blood pressure.
Narrowing of one or both renal arteries.

4. Endocrine Disordess
Hypersecretion of Adrenal Cortex (a) Conn’s Syndome

(b) Cushing’s syndrome

Hyper function of Adrenal medulla Adrenal medullary tumour —
Pheochromocytoma
Hyper funtion of pituitary, growth hormone Gigantism and Acromegaly 5.
Polycythemia

Increase in RBC count

Excess aldosterone, increased reabsorption of Na+ and water Salt and water
retention increases blood volume, increase in blood pressure.

Increase in cortisol level, increased water and salt retention, increase in blood
volume, increase in blood pressure.
Excess secretion of adrenaline, Increase in
Vasoconstriction, Increase in BP
Increased water and salt retention, increase in blood volume, increase in blood
pressure.
Increase in viscosity of blood, increase in peripheral resistance, increase in blood
pressure.
Manifestation of Hypertension

Every moderate elevation of the arterial pressure leads to shortened life

expectancy. It means that if arterial pressure is 50 per cent or more above normal
a person can expect to live no more than a few years at most.

The lethal effects of hypertension are caused. 1. Excess workload on the heart
leads to early development of congestive heart disease, coronary heart disease or
both, often causing a death as a result of heart attack. Increased work load of the
heart produce left ventricular lypertrophy. Increase in ventricular mass demands
more oxygen. This leads to angina pectoris and ischemic heart disease.
Hypertensin produces loss of elasticity of blood vessel and decreases the
vascular compliance.
2. The high pressure frequently ruptures a major blood vessel in the brain: this is
a cerebral infarct, and depending upon what part of the brain is involved, a
stroke can cause cerebral hemorrhage, dementia, blindness, paralysis and other
serious brain disorders.
3. Renal failure—arteriosclerosis of renal arteries.
4. Retinal hemorrhage.
5. Myocardial infarction.
6. Left ventricular failure.

Management of Hypertension

The secondary hypertension is cured by treating the disease causing

hypertension. Primary hypertension is treated by using hypotensive drugs.

Several pressure control mechanisms exhibit significant responses only after a

few minutes following an acute arterial pressure change.

1. Stress-relaxation of the vasculature: When the blood pressure in the blood

vessels becomes too high, they become stretched, and they keep on stretching for
more and more minutes or hours, as a result the pressure in the vessels falls
towards normal.

2. The capillary fluid shift mechanism: When the blood pressure rises too
high, fluid is lost out of the circulation into the tissues thus reducing the blood
volume and also all the pressure throughout the circulations.
3. The renin angiotensin vasoconstrictor mechanism: It is an important factor
in the daily control of arterial pressure by the interaction of the renin-angiotensin
system with the aldosterone and renal fluid mechanism.

Steps to reduce blood pressure and prevent further complications of

hypertension.

1. Weight reduction.
2. Diet control. Restriction of salt and fat and encouraging fibre content in the
food.
3. Mental relaxation through meditation, yoga, music, travel etc. will reduce BP.
4. Stoppage of smoking and alcohol consumption. Pharmacological basis of
controlling hypertension The different types of drugs like beta blockers,
calcium channel blockers, vasodilators, diuretics, inhibitors of

angiotensin converting enzyme, etc. are used in the treatment of hypertension.

TABLE 3.8
Drug groups Physiological basis Vasodilators Produce vasodilation reduce
peripheral resistance, decrease BP
Angiotension converting enzyme inhibitors
Diuretics
Anti-adrenergic drugs
Calcium channel blocker
Vasomotor area inhibitors
Hypotension

Inhibits the action of angiotensin converting enzyme, so angiotensin II is not

formed. No vasoconstriction, vasodilatation decrease in resistance and BP.

Increases urine output, increases water loss, decreases blood volume and BP

Alpha 1 receptor blockers mainly block the actions of noradrenalin, there by

decreasing vasoconstriction. B-receptor blockers block the action of adrenaline
and sympathetic action on heart.

Decreases tone of blood vessel, thereby decrease resistance and BP.

Inhibition of VMC decreases vasoconstrictor tone, decreases resistance BP.

Hypotension is defined as a clinical condition in which blood pressure decreases

significantly.
Systolic BP mm of Hg Diastolic BP mm of Hg Remarks
110–130 70–90 Normal 90–99 60–70 Border line hypotension Less than 90 Less
than 60 Hypotension

Clinical classification of hypotension.

1. Chronic hypotension.
2. Acute hypotension
3. Postural hypotension.
Chronic hypotension means persistent decrease in blood pressure. Common
causes are
(a) Chronic diarrhea and vomiting.
(b) Chronic dehydration.
(c) Adrenocortical insufficiency.
(d) Malnutrition.
(e) Hypopituitarism.
Acute hypotension is characterised by sudden fall in BP and associated with
fainting major causes are: (a) Accidental acute hemorrhage.
(b) Acute myocardial infarction.
(c) Severe vomiting and diarrhea.
(d) Excess use of diuretics.

Postural hypotension or orthostatic hypotension Causes

Prolonged standing erect—Loss of fluid from blood vessel to interstitial space.
Blood volume decreases and BP falls.
Sympathetic dysfunction—Autonomic neuropathy polyneuropathy.
Surgical—sympathectomy.
Withdrawal of sympathetic drugs.
Usage of sympatholytic drugs.
Pathophysiology
Drop in blood pressure in carotid sinus and aortic arch.
Compensatory increase in heart rate. Mareys reflex. Increase in secretion of
rennin and aldosterone. Decreased blood supply and oxygen supply to brain.
Clinical features:
Giddines
Fainting
Dimness of vision. unconsciousness.

Management
1. Fluid supplementation.
2. Blood transfusion.
3. Administration of catecholamine.
When a person changes posture from supine to standing systolic BP falls more
than 20 mm of Hg is called as postural.

Determination of Arterial Blood Pressure Principle

It consists of method of balancing air pressure against the pressure of the blood
in the brachial artery and estimating the former by means of mercury or aneroid
manometer.

Material and Equipment

1. Sphygmomanometer
2. Stethoscope (binaural), Aneroid manometer. Sphygmomanometer
The instrument, used for estimating the arterial blood pressure by indirect or
clinical method, is called Sphygmomanometer (Sphygmos = pulse) of which
there are many different models.
Essentially the instrument consists of an inflatable cloth covered with flat rubber
bag 12 cm. wide which fits snugly around the upper arm and is held in position
by wrapping an extension of the cloth covering over the bag like a bandage. It is
usually referred to as cuff or the armlet.
The cavity of the rubber bag is connected by the length of tubing with the
manometer and by another tube with a pressure bulb or pump.

By using the pressure bulb the rubber bag can be inflated to any desired
pressure. On the tube leading from the bulb to the bag, there is a needle valve
which can be opened gradually to allow air to escape, there by reducing the
pressure in the bag as required.

The top panel of the portable instrument box is fitted with a U-shaped mercury
manometer. A steel reservoir containing mercury form the wide limb of the
manometer and calibrated glass cartridge tube form its narrow limb. The top
panel of the instrument is suitably marked in figures to read pressures from 0 to
300 mm. of Hg.
 Fig.
3.29 Recording of BP
Indirect or Clinical Method
Procedure

Wrap the uninflated armlet snugly around the upper arm (which should be bare
and thoroughly relaxed), leaving the cubital fossa exposed. Rest the subject’s
arm at about the level of the heart.
Place the manometer so as to be at the same level as your (observer’s) eye.
The estimation may now be made by one of the following methods, by one and
then other.

(a) The Palpatory method

Steadily inflate the armlet until the pulse is no longer felt at the wrist i.e., air
pressure within it overcomes the arterial pressure and obliterates the arterial

lumen. Increase the pressure by about 30 mm of Hg. beyond this point.

By means of the valve, allow the air to escape very gradually so that the pressure
falls. Watch the manometer while concentrating attention upon the pulse at the
wrist.
Immediately the pulse returns, read the scale, this reading is the systolic blood
pressure in mm. of Hg. The diastolic pressure cannot be measured by this
method.

(b) The Auscultatory method

This method is the one generally employed clinically. It was introduced in 1905
by the Russian physician Korotkoff.
Feel the brachial pulse in the cubital fossa and mark the position of the artery.
Raise the pressure by pumping to 30 mm, or so above the systolic blood pressure
as determined by the palpatory method.

Place the chest—piece of binaural stethoscope over the position of the brachial
artery and auscultate.

Open the valve and reduce the compression gradually (2 or 3 mm of Hg. per
second) until the faint tapping sounds produced by successive pulse— waves are
first heard, and immediately take a reading. This is the systolic blood pressure.
Continue to listen until the sound become loud and distinct suddenly become
soft and muffled. Take a reading at this point also. It is the diastolic pressure.
Difference between the systolic and diastolic pressures gives the pulse pressure.

Four phases of sound each having its distinctive characters may be heard in
succession in a normal individual as the pressure is gradually reduced form
about 120 to 80 mm. of mercury, or less. These sounds are referred to as
“Sounds of Korotkoff”.

Sounds of Korotkoff

Phase I: Sudden appearance of a clear, sharp tapping sound which becomes

louder during 10 mm. fall in pressure. The reading on the scale at the time of its
first appearance corresponds with the systolic pressure.

Phase II: The sound becomes softer, and takes on a murmurish quality during
the next 15 mm. fall in pressure.

Phase III: The sound becomes clear and louder, with little or no change in
quality during the next 15 mm. fall in pressure.

Phase IV: The sound suddenly becomes reduced in intensity and develops a
muffled quality. This sound lasts through the next 5 to 6 mm. Hg. fall after
which all sounds disappear.

(c) The Oscillatory method

In this method a tambour or capsule covered with a very delicate membrane or a
second bag connected with a cuff, is used to pick up and magnify the pulsations
transmitted from the artery.
The pulsations are made to appear as oscillations of the indicator needle on the
clock face of an aneroid manometer.
Pressures are marked by figures on the dial, as the cuff is inflated or deflated the
needle moves to indicate applied pressure at the moment.
At the pressure exceeding systolic the oscillations are minimal, but as the
pressure is gradually lowered and the pulsation pass beneath the cuff, sudden
increase in their amplitude and duration occurs. This is the criterion of systolic
pressure.
The oscillations show little change in magnitude as the cuff is deflated further,
until the pressure has fallen to the diastolic level at which they suddenly become
smaller. At this instant the figure on the dial to which the needle points is noted.
This is the diastolic pressure.

PULSE

Pulse is the expansion and elongation of the arterial walls passively produced by
pressure changes during systole and diastole.

Recording of radial pulse: For clinical purposes, the commonest instrument

used is Dudgeon’s Sphygmograph. The upstroke is abrupt and without any
secondary wave on it. Near the middle of the down stroke there is a sharp
depression called the dicrotic notch. This is immediately followed by a small
wave, the dicrotic wave. These two features are constantly present in a normal
pulse tracing. The wave from the beginning of the tracing up to the dicrotic
notch is called the primary wave or percussion wave. This whole wave
corresponds to ventricular systole. The rise and fall of pressure in this wave
follow the similar pressure changes in the aorta and ventricles. The dicrotic
notch is due to the sharp fall of pressure caused by the return of the same blood
column being reflected back by the sclosed semilunar valves. Some times
secondary oscillations are found on the down stroke both above and below the
dicrotic wave respectively, being known as the predicrotic wave and postdicrotic
wave respectively. These are due to elastic oscillations of the aorta. The normal
pulse is called Catacrotic pulse. When a secondary wave is found on the
upstroke the wave is called anacrotic wave and the pulse is called anacrotic
pulse. When the dicrotic wave becomes so prominent that it can be easily felt
with the fingers the pulse is known as dicrotic pulse.
Pre dicrotic wave

Dicrotic notchDicrotic or catacrctic limb

Anacrotic Post dicrotic limb wave

Fig. 3.30
Radial pulse

Significance: A large primary wave is generally due to:

1. a large stroke volume.
2. slow heart rate
3. low peripheral resistance.
A small primary wave is due to:
1. small output
2. rapid heart rate
3. high resistance of walls.
The down stroke becomes more abrupt in subjects with low diastolic pressure. It
becomes more sloping in cases with high blood pressure.

Clinical features of radial pulse: While examining pulse the following features
are to be noted:
1. Rate means the frequency of pulse per minute. Normally it corresponds to
heart rate. Increased pulse rate is called tachycardia, and diminished pulse rate is
called bradycardia.
2. Rhythm indicates whether the beats are equidistant or not.
3. Volume means the rise of the pulse wave above the diastolic level. Other
factors remaining constant it varies as the stroke volume.
4. Tension is the approximate measure of the systolic pressure. It is determined
by noting the amount of pressure required to obliterate the pulse wave. It is
examined with three fingers placed side by side on the radial artery. The
proximal finger adjusts the pressure, the middle finger remains stationary and
only feels the appearance and disappearance of the pulse wave, while the distal
finger applies a constant maximum pressure to stop retrograde pulsation.
Special varieties of pulse: Depending on the variations of the above features,
various types of pulse waves are clinically described. The following types are of
special interest:
1. Sinus arrhythmia: The frequency of the pulse increases during inspiration
and falls during expiration. Sometimes it is found in children. It is due to
alteration of the vagal tone during respiration. 2. Water—hammer pulse: The
rise and fall are steep and abrupt without any dicrotic notch or wave. This is
typically found in aortic incompetence. 3. Pulsus alternans: Here, the pulse is
alternately large and small. It is found in serious myocardial damage.
4. Pulses paradoxes: The volume and frequency is more during expiration than
during inspiration, i.e., reverse of sinus arrhythmia.
5. Weak pulse: A weak pulse at the radial artery generally indicates that the
quantity of the blood ejected by the left ventricle to the arteries with each beat is
less than normal.
The examination of pulse is of great clinical importance. From it, the condition
of the heart, of the arteries, the extent of blood pressure, etc, may be known.

VENOUS PULSE

Definition: Venous pulse is the positive and negative pressure changes occurring
in the right atrium during each cardiac cycle transmitted in the form of a wave to
the veins near the heart. Venous pulse is observed only in larger veins near the
heart like jugular vein. Significance: Venous pulse recording is used to
determine the rate of arterial contraction, just as the record of arterial pulse is
used to determine the rate of ventricular contraction.
In addition, more phases of cardiac cycle can be recognised by means of venous
pulse tracing. It is a simple and accurate method to measure duration of different
phases in diastole. It also represents the atrial pressure changes taking place
during cardiac cycle.
Methods to record venous pulse: A small funnel covered by thin rubber
membrane is placed over the skin at the level of the external jugular vein in the
supra clavicular fossa. Slight pressure is exerted to provide perfect contact
between edge of the funnel and skin.

The pressure changes in the vein cause some oscillations in rubber membrane
through the skin. These oscillations are transmitted through rubber tube to a
recording device like the Marey’s tambour. The electronic transducer may also
be used for this purpose.

The subject should be in such a position so as to avoid the effect of gravity,

which tends to empty veins and reduce the amplitude of the venous pulse.

Record of Venous Pulse (Jugular Venous Pulse Tracing) The recording of jugular
venous pulse is also called phlebogram. It is similar to intra atrial pressure curve.

Like intra atrial pressure curve, phlebogram also has 3 positive waves – a, c, v
and 3 negative waves
– x, x1, y.

a
cv
x
x1 y
Fig. 3.31
Phlebogram

“ a” Wave: This is the first wave and is a positive wave. The pressure rise is due
to atrial systole. It precedes ventricular contraction.

“ x” Wave: It denotes the fall of pressure in atrium and coincides with atrial
diastole and beginning of ventricular contraction.

“ c” Wave: Previously, it was thought to be due to the transmission of pulse

from neighboring carotid artery. Hence, it was called a ‘c’ wave. Now, it is
known that this wave occurs due to rise in atrial pressure during isometric
contraction period. During this period the atrio ventricular valves bulge into the
atria and increase the pressure in the atria slightly.

“ x1” Wave: This occurs due to fall in pressure during ejection period. During
ejection period, the atrio ventricular ring is pulled towards ventricles causing
distension of atria. So, the atrial pressure falls.

“ v” Wave: It shows rise in pressure in atria. The pressure increases because of

filling of atria (venous return). This is obtained during isometric relaxation
period or during atrial diastole.

“ y” Wave: It denotes the fall of pressure in atria. It is due to the opening of atrio
ventricular valve and emptying of blood into the ventricle. This appears during
rapid and slow filling periods, and the cycle is repeated.

Triple response or vascular response of skin

If the skin is stroked lightly by the smooth end of the scalpel

or glass rod, along the line described, develops a white line, in few second due to
the contraction of sub papillary venous plexus. This reaction does not involve
any chemical/nervous system. If the stroke is made very firmly the characteristic
triple response develops in a sensitive skin. The features of triple response are:

1. a red line
2. flush or flare
3. wheal
Red line: It develops within 10 seconds to 1 min. after

the stroke. This is due to capillary enlargement which is in turn due to the
relaxation of pre capillary sphincter. The relaxation of sphincter takes place due
to the release of histamine from the injured tissues.

Flush or flare: If the stroke is still firm, flare develops i.e., reddening of the
zone/area described by injury. At the region of flare the temperature increases.
The flare is due to arteriolar dilatation mediated by axon reflex.

Axon reflex: The afferent impulse from the receptor before reaching spinal cord
converts into efferent impulse. Efferent impulse to the arteriole causes dilatation.
This is the only reflex in the body that does not involve the CNS, Asynaptic
reflex.

Wheal: If the stroke is very hard, wheal develops. Here the skin at the injured
area is elevated due to collection of edematous fluid from capillaries.

Dermatophagia is the condition when the triple response is answered by skin

even by light stroke.
Skin
(scratch stimulus)

Spinal cord Axon reflex

Blood Axon reflexvessel
Fig. 3.32 Triple resonse
Circulation Time
Definition: It is the time taken by a particle of blood to flow from one point in
circulation to another point.

Methods of determination
Principle is to inject some substance intravenously and then to note the arrival of
the substance at a definite point.

Commonly used substances

Histamine, fluoresein, ether, decholin. The substance is injected commonly into
cubital vein. The time is measured

TABLE 3.9
Normal values of circulation time

from the time of injection to the signal of arrival of the substance at the site.
Each substance produces a characteristic effect by which the arrival can be
detected.

S.No. Where to where Substance used Character Time 1. Arm to tongue

Decholin bitter taste 13 sec 2. Arm to lungs Ether smell 6 sec 3. Arm to face
Histamine Flushing of face 24 sec 4. Arm to heart Radioactive method Isotope
counter 6.6 sec 5. Total circulation time – 25 sec.

Factors effecting circulation time

1. Increased cardiac output
2. Exercise
3. Excitement
4. Adrenaline
5. Increased BMR will increase the velocity of blood circulation. So it will
decrease circulation time. Significance

I. Circulation time is reduced in the following conditions.

1. Increased BMR
(a) Hyperthyroidism (b) Fever
2. Anemia—due to increased cardiac output and decreased viscosity of blood.
II. Circulation time is increased in—
1. Heart failure
2. Hypertension
3. Myxoedema
4. Polycythemia
5. Shock.

APEX BEAT

Definition: It is defined as outer most and lower most point of cardiac impulse.
It is the impulse or throb which is felt and seen on the chest wall.

Location: It is normally felt and seen on the chest wall in the left fifth
intercostal space just medial to left nipple – corresponds with mitral area.

Cause: It is caused due to impact of ventricle on the chest wall.

Inspection: Apex beat can be seen as a throb.
Palpation: Apex beat can be felt.

Central Venous Pressure

All the venous blood (from the veins) of the body drains into the right atrium.
The pressure in the large vein (vena cava) just outside the right atrium is called
the central venous pressure (CVP). Normal CVP can be measured from two
points of reference:

Sternum: 0–5 cm H2O

Midaxillary line: 5–10 cm H2O

This pressure is of special interest because it provides an indication of the

volume of blood that is flowing through the veins and into the right atrium. If the
heart is beating weakly, blood tends to “back up” in the veins. The CVP, as a
measure of this back-up, will increase.

Also, if the blood begins to back up (measured by increased CVP), the heart can
respond in two ways: 1. It can beat faster, and 2. It can pump more blood with
each beat. When the heart responds in this way, then the back-up is relieved. As
the back-up is relieved, the CVP decreases back to normal. Besides a weakly
beating heart, another factor that increases the flow of blood into the right
atrium, and thus causes the CVP to become elevated, is an increase in blood
volume.

TABLE 3.10 Characteristics of different types of blood vessels

S.No. Characteristics Aorta Arterioles Capillaries Venules Venaecavae 1.
Number 1 109 10 x 109 0.3 x 109 2 2. Cross-sectional area (cm2) 4.5 300 5,000
4,000 18 3. Wall thickness (µm) 2 0.02 0.001 0.002 1.5 4. Individual radius(mm)
12 0.01 0.004 0.02 17 5. Smooth muscle in the wall ++ +++ Absent + ++ 6.
Elastic tissue in the wall +++ + Absent + ++ 7. Collagen in the wall +++ ++
Absent + + 8. Velocity of flow (cm/sec) 50 0.3 0.017 0.02 4.6 +, low; ++,
moderate; +++, high.
Hemodynamics

The blood pressure, in a blood vessel, is defined as the force exerted by the
blood against the vessel wall. It is this pressure caused by the pumping of the
heart that keeps your blood circulating. Every blood vessel in the circulatory
system has its own blood pressure, which changes continually. Even so, the term
blood pressure is most commonly used to refer to arterial pressure.

Hemodynamics is an important part of cardiovascular physiology dealing with

the forces of the heart which helps to circulate blood through the cardiovascular
system. Adequate blood circulation is a necessary condition for adequate supply
of oxygen to all tissues, which, in return, is synonymous with cardiovascular
health, survival of surgical patients, longevity and quality of life. Hypertension
and congestive heart failure are two best known hemodynamic disorders.
According the physical factors governs the blood flow, it has been classified into
two types:

Laminar flow: The streamlined and steady blood flow, where outermost layer
moving slowest and center moving fastest.

Turbulent flow: The interrupted and turbulent blood flow with maximum
velocity results into formation of whorls in the blood called as eddy currents.

Relationship between Flow, Resistance and Pressure: Flow is a measure of

volume per unit time. Amount of blood moving through a vessel in a given time
period. Blood flow is directly proportional to pressure differences, inversely
proportional to resistance.
Velocity is a measure of distance per second along the axis of movement.
Velocity = Flow/Cross sectional area.

Viscosity of blood—It is the measurement of resistance of liquid to flow. As

viscosity increases, pressure required to flow increases.
Resistance is nothing but the opposition or impediment to normal blood flow.
Resistance varies inversely to the fourth power of the radius of the vessel. Thus,
if the radius is halved, resistance increases 16-fold enabling substantial blood
flow changes to be effected by relatively small adjustments to the radius of the
vessels. Peripheral resistance is an important indicator of cardiovascular fitness.
Physical training can favorably and significantly lower total peripheral
resistance, reducing the load on the heart.

Change in Pressure = Flow × Resistance ∆P= QR

According to Ohm’s Law I
=∆
V/R
Change in pressureFlow = Resistance
∆PQ=
R

Poiseulle’s law states that the flow rate Q is also dependant upon fluid viscosity
η, pipe length L and the pressure difference between the ends P, but all these
factors are kept constant for this demo so that the effect of radius is clear.
R=

8ηl πr4 Q=
∆ πr4
R
P = 8ηl ×()

Relationship between cross-sectional area of blood vessels and blood flow:

As diameter of vessels decreases, the total cross-sectional area increases and
velocity of blood flow decreases. Much like a stream that flows rapidly through
a narrow gorge but flows slowly through a broad plane.

Laplace’s Law—Force acting on blood vessel wall is proportional to diameter of

the vessel times blood pressure.
Microcirculation: The microcirculation is the blood flow through blood
vessels smaller than 100 µm (i.e., arterioles, capillaries, and venules). The main
functions of the microcirculation are transporting blood cells and substances
to/from the tissues, and as body coolant in thermoregulation processes. It also
contributes to tissues color and stiffness.
The microcirculation of some tissues (e.g., skin) contains direct A.V. connections
which act as shunts. The flow in these shunts does not participate in transfer of
gases, nutrients or wastes. These A.V. shunts are under the control of the nervous
system. In the skin, opening or closing of these shunts is important in heat
regulation. The smooth muscle of the metarterioles and the precapillary
sphincters contracts and relaxes regularly causing intermittent flow in the
capillaries: this is known as vasomotor. A local drop in pO2 is the most important
factor causing relaxation of the precapillary sphincters. The intermittent flow is
not due to the cyclical rise and fall of the blood pressure as these fluctuations are
almost completely damped out by the arterioles.
The principal function of the microcirculation is to permit the transfer of
substances between the tissues and the circulation. This transfer occurs
predominantly across the walls of the capillaries but some exchange occurs in
the small venules also. Substances involved include water, electrolytes, gases
(O2, CO2), nitrogenous wastes, glucose, lipids and drugs. Electrolytes and other
small molecules cross the membrane through pores. Lipid soluble substances
(including oxygen and carbon dioxide) can also easily cross the thin (1 mm)
capillary walls. Proteins are large and do not cross easily via pores but some
transfer does occur via pinocytosis (endocytosis/exocytosis).
Water molecules are smaller than the size of the pores in the capillary and can
cross the capillary wall very easily. The capillary endothelial cells in some
tissues (e.g., glomerulus, intestinal mucosa) have gaps (called fenestrations) in
their cytoplasm which are quite large. The water conductivity across these
capillaries is much higher then in non-fenestrated capillaries in other tissues of
the body. The transfer of water across the capillary membrane occurs by two
processes: diffusion and filtration.
Arterial circulation: Arterial circulation is that part of overall blood circulatory
system that involves arteries, like the aorta and pulmonary arteries. Arteries are
blood vessels that carry blood away from your heart. Healthy arteries are strong
and elastic. They become narrow between beats of the heart, and they help keep
blood pressure consistent. This helps blood circulate efficiently through the
body. Arteries branch into smaller blood vessels called arterioles. Arteries and
arterioles have strong, flexible walls that allow them to adjust the amount and
rate of blood flowing to different parts of the body.
Venous circulation: Venous circulation is the part of overall blood circulatory
system that involves veins, like the vena cavae and pulmonary veins. Veins are
blood vessels that carry blood to your heart. Veins have thinner walls than
arteries. Veins can increase in width as the amount of blood passing through
them increases.
Capillary circulation: Capillary circulation is the part of circulatory system
where oxygen, nutrients, and waste exchanged between blood and parts of body.
Capillaries connect the arterial and venous circulatory subsystems. Capillaries
are very small blood vessels. The importance of capillaries lies in their very thin
walls. Unlike arteries and veins, capillary walls are thin enough that oxygen and
nutrients in blood can pass through the walls to the parts of body that need them
to function normally. Capillaries’ thin walls also allow waste products like
carbon dioxide to pass from organs and tissues into the blood where it’s taken
away to the lungs.
The Starling equation is an equation that illustrates the role of hydrostatic and
oncotic forces (the so-called Starling forces) in the movement of fluid across
capillary membranes.
The four Starling’s forces are:
Hydrostatic pressure in the capillary (Pc) Hydrostatic pressure in the interstitium
(Pi) Oncotic pressure in the capillary (pc)
Oncotic pressure in the interstitium (pi).
The balance of these forces allows calculation of the net driving pressure for
filtration.
Net Driving Pressure = [(Pc – Pi) – (pc – pi)]
Net fluid flux is proportional to this net driving pressure. In order to derive an
equation to measure this fluid flux several additional factors need to be
considered: The reflection coefficient

The filtration coefficient (Kf ).

Local regulation of blood flow: Several mechanisms are responsible for local
blood flow regulation. Some mechanisms originate from within blood vessels
e.g., myogenic and endothelial factors, whereas others originate from the
surrounding tissue. The tissue mechanisms are linked to tissue metabolism or
other biochemical pathways e.g., arachidonic acid metabolites, histamine and
bradykinin.

Local blood flow increase with increase in rate of tissue metabolism and vice
versa. Local control system mainly regulates the peripheral blood flow to various
organs. The blood flow is directly proportional to the diameter and size of the
respective artery and arterioles. In acute control of local blood flow the rapid
constriction of arterioles and metarterioles takes place. However, many organs
regulate their blood flow according to their need via autoregulatory mechanism.
Autoregulation of blood flow: Autoregulation is the intrinsic capacity of tissues
to regulate their own blood flow. This autoregulation is particularly important in
organs such as the brain and heart in which partial occlusion of large arteries can
lead to significant reductions in oxygen delivery, thereby leading to tissue
hypoxia and organ dysfunction. Autoregulation, therefore, ensures that these
critical organs have an adequate blood flow and oxygen delivery. It is explained
by following two theories:

Metabolic theory: Blood flow to an organ or tissue is controlled by the

metabolic activity of the tissue. This helps in excess flow of blood so as to
provide nutrients to the tissues and it also helps in flush out the vasodilator
substances. These two effects cause blood vessels to constrict and flow returns to
almost normal despite of the increased pressure.

Myogenic theory: It is due to vascular compliance; vascular smooth muscles

contract in response to increased transmural pressure and relax in response to
decreased transmural pressure. Vasoconstriction increases the blood pressure so
it results into returns of the normal blood flow. Degree of vasoconstriction is
directly proportional to the change in the pressure.

Hyperemia: It is defines as the increase of blood flow to different tissues in the

body. It can have medical implications, but is also a regulatory response,
allowing change in blood supply to different tissues through vasodilation. The
mechanism for vasodilation is unclear, but it may have something to do with the
opening of precapillary sphincters. It is divided into active hyperemia and
reactive hyperemia.

Active hyperemia is a term used to describe dilation of arteriolar smooth muscle

to increase blood flow in response to an increase in metabolism. This is due to
lack of nutrients and oxygen leading to local vasodilation.
Reactive hyperemia is a profound increase in blood flow to an organ after being
occluded due to a shortage of oxygen and a build-up of metabolic waste. This is
due to metabolic control of local blood flow and shows the close relationship
between local blood flow regulation and supply of required amount of nutrients
to the tissues.

Regional Circulation
Coronary circulation
Functional anatomy: Blood supply to the heart is mainly carried out by the
coronary vessels i.e., right and the left coronary arteries arising from
VALSALVA sinus at the root of aorta. Right coronary arteries supply mainly the
ventricles. The left coronary arteries gives off the anterior descending and left
circumflex branch.

The left circumflex branch will supply the atrio – ventricular groove and left side
of the heart and ends up as posterior descending branch.

The anterior descending branch supply the apex of the heart.

The predominance of coronary artery supply is seen in about 50% of human
heart by right coronary artery, in about 20% of human heart by left coronary
artery and in about 30% of the cases by both coronary arteries.
According to Schlesinger the coronary supply where both arteries are dominant
are less prone to cardio vascular disorders.

Venous drainage: The blood from myocardium is chiefly returned through two
systems.
1. Superficial venous system
2. Deep venous system
Arota
Pulmonary artery
Extracoronary

arteries
Coronary arteries

Left coronary artery

Right
coronary artery

Marginal branch
Circumflex artery
Arterioles Arterioles

Anterior descending
branch
Capillaries Arterioluminal vessels
Arteriosinusoidal vessels
Veins Marginal

branch Coronary sinus or anterior cardiac veins

Heart chambers Thebesian veins

Fig. 3.33 Coronary circulation Determination of coronary blood flow Nitrous
oxide method

The subject inhales the mixture of 15% of nitrous oxide and air for 10 min. The
amount of nitrous oxide taken up per minute is determined. Several samples of
blood are taken from the arteries and catheter introduced into the mouth of
coronary sinus at intervals during inhalation of nitrous oxide. Nitrous oxide
content in arterial sample of blood and coronary sinus venous blood samples are
determined. The arterio venous difference of nitrous oxide is then calculated.
The coronary inflow is then determined with the help of Fick’s principle.

Coronary Inflow
=

Quantities of nitrous oxide inhaled / min Arterio venous difference of nitrous

oxide The value is about 60 – 80 ml/100 gm/ minute. The person of average size
have about 200 ml – 250

ml/min of total coronary blood flow. During very severe exercise value may rise
up to 250 ml/100 gm/min. The arterio venous difference is very high about 10 –
15 ml/100 ml. So extraction of oxygen by cardiac muscle is very high.

Factors influencing coronary circulation

1. Mean aortic pressure: Any alteration in aortic pressure will cause parallel
changes in coronary circulation.

2. Oxygen lack and CO2 excess: If oxygen supplied to the heart decreases,
there is accumulation of vasodilator substances like adenosine, potassium ion,
H+ , CO2 which will cause vaso dilatation. So, coronary blood flow is increased.

3. Increase in body temperature: Increase in body temperature increases

vasodilatation so coronary circulation increases.

4. During muscular contraction: There is an accumulation of H+ , CO2 , lactic

acid, increased body temperature and formation of adenosine. These vasodilators
bring about vasodilatation and coronary blood flow increases.

5. Nerve supply to heart: Nerve supply is by autonomic nervous system. The

sympathetic stimulation will increase the heart rate and contractility and also
increase coronary blood flow due to release of adrenaline.
The parasympathetic stimulation release acetylcholine, which increases coronary
inflow due to dilatation of coronary vessels.

6. Cardiac output: Increased cardiac output increases coronary blood flow.

7. Hormonal regulation: Thyroxine and adrenaline hormone increase coronary
blood flow. Vasopressin decrease coronary blood flow.

Peculiarities of the coronary circulation

1. It supplies the heart itself.
2. In majority of people, one artery is dominant over the other.
3. The vessels are subjected to the force of myocardial contraction and are
compressed during systole.
4. Unlike other vascular beds, it mainly perfuse during diastole.
5. Part of the blood from the microcirculation drains directly into the ventricles.

6. O2 extraction is highest in this bed (about 9 to 11 ml/100 ml of blood) at rest

and increases slightly in exercise. Hence, increased O2 demand is met with
increased blood flow.

7. Collateral circulation normally is not very important but may develop in

chronic coronary artery disease (CAD). Since less collateral circulation more
prone for ischemic attack.

8. The nervous regulation of coronary blood flow is much less important than the
metabolic regulation unlike circulation at other organs.

9. Number of capillaries is very high (about one capillary for each Fibre); hence,
intercapillary distance is very small. High apillary density.

10. Coronary circulation show reactive hyperemia, which means increased blood
flow to a part following a temporary obstruction of flow. This is probably due to
accumulation of metabolites during obstruction.

11. Myocordium does not receive significant nutrional blood from cardiac
chambers directly.
12. Myocardium is an aerobic tissue. i.e., it cannot with stand anarobic
conditions.
13. Coronary circulation exhibits excellent autoregulation.

Coronary artery disease: A decrease of coronary blood flow due to disease of

the coronary arteries is called coronary artery disease (CAD). This may be due to
atheroscelerosis, intravascular clot or rupture of the coronary vessels.

When there is a decrease in the CBF (ischaemia) the condition leads to angina
pectoris, i.e., severe chest pain. This can be treated by rest and by drugs which
cause vasodilatation. If the blood flow is stopped to some part of the heart due to
complete obstruction of an artery, there is death of the myocardium in that area,
the condition is then called myocardial infarction. It is treated by removing the
obstruction by angioplasty or plasmin activator injection. Now-a-days
intravenous streptokinase or urokinase is used in this situation in selected cases.
Later on a coronary bypass operation may be done, in which a venous or arterial
graft is used to bypass the obstructed part of the coronary artery.

The pulmonary circulation carries the blood to and from the lungs. In the heart,
the blood flows from the right atrium into the right ventricle; the tricuspid valve
prevents backflow from ventricles to atria. The right ventricle contracts to force
blood into the lungs through the pulmonary arteries. In the lungs oxygen is
picked up and carbon dioxide eliminated, and the oxygenated blood returns to
the heart via the pulmonary veins, thus completing the circuit. In pulmonary
circulation, the arteries carry oxygen-poor blood, and the veins bear oxygen-rich
blood.

Splanchnic circulation: It is the circulation of blood to the gastrointestinal tract.

The anatomy of the circulation of the gut is unusual in that the venous blood
does not return directly to the heart, but instead it flows in the portal vein to the
liver, and only after this does it reach the hepatic vein and the inferior vena cava.

Since the splanchnic circulation is concerned with the digestion and absorption
of food, this means that the blood carrying products of digestion passes through
the liver before reaching any other part of the body. Splanchnic vessels also
serve a reservoir function. Constriction of splanchnic arerioles —the resistance
vessels—is under the control of the sympathetic nervous system and makes a
major contribution to blood pressure control.

The splanchnic veins also constrict in response to stimulation of the sympathetic

nerves; this reduces their capacity and increases the flow of blood returning to
the heart.

Cerebral circulation: About 15% of the resting cardiac output supplies the
brain. This flow is vital as the brain cannot withstand more than a few seconds of
interruption of flow without loss of consciousness, and longer interruptions
cause irreversible damage. Overall brain blood flow remains relatively constant,
although regional changes occur in response to changes in neuronal activity.

For example, shining a light in the eye results in an increase in blood flow to the
region of the brain concerned with vision. In the upright position, because of the
effects of gravity, the blood pressure in the brain is lower than elsewhere,
making it susceptible to low blood pressure. However the brain does show the
phenomenon of autoregulation, whereby its blood flow is kept relatively stable
over a quite wide range of blood pressure.

Although the brain blood flow is determined to some extent by nervous control
of the diameter of blood vessels, it is more importantly controlled by chemical
factors, particularly the level of carbon dioxide which, when it increases, dilates
the cerebral vessels and increases flow. Overbreathing lowers the level of carbon
dioxide in the body and can cause dizziness due to decreasing brain blood flow.

Skeletal muscles: A contracting muscle produces several chemicals which are

the end products of its metabolic activity. These metabolites act directly on the
resistance vessels (arterioles), dilating them and thus regulating blood flow so
that it is appropriate for the level of activity. Although sympathetic nerves do
supply muscle blood vessels, they control only the resting blood flow and play
no part in the response to exercise. At rest, flow in all muscles comprises only
about 1 litre/min out of the cardiac output of 5 litres/ min. During exercise, if
cardiac output increases to 25 litres/ min, 20 litres of this goes to the working
muscles.

Cutaneous: Blood flow to the skin is controlled by the mechanisms of

temperature regulation. If local skin temperature or general body temperature
rises, skin vessels, including special arterio-venous shunt vessels, dilate to
increase skin blood flow and thereby increase skin temperature and facilitate
cooling. Skin flow is controlled partly by nerves and partly by direct local
temperature effects (warm hands are red). During very cold conditions blood
flow to the entire skin is almost completely cut off. During extreme heat, flow
may increase to the extent that most of the output of the heart flows through the
skin.

Renal: The kidneys are relatively small organs they receive about 24% of
cardiac output. Most of this blood flow is concerned with the filtration of the
plasma and the subsequent concentration of the filtrate to form urine. The blood
flow is normally autoregulated and is therefore relatively independent of blood
pressure unless this falls to abnormally low levels.

CARDIO VASCULAR CHANGES DURING EXERCISE

Introduction: Exercise is the performance of physical exertion for improvement

of health or for the correction of physical deformity.

Voluntary muscular movement or exercise is a cortical phenomenon and is under

the “feed back” control of cerebellum. During muscular exercise, the energy
needs of the muscle are increased tremendously and these energies are met with
increased metabolism, and these requirements are met with by causing oxygen
rich RBC more available to the active sites. This happens by increasing heart
rate, cardiac output, increasing venous return, increasing vascular resistance in
the inactive muscle, redistribution of blood and increasing pulmonary
ventilation.

Details of cardiovascular adjustment during exercise is given in the chapter

10, Physiology of Exercise.
Cardio Vascular Shock

Cardio vascular shock or circulatory shock is a clinical condition in which there

is a sudden significant reduction in cardiac output resulting in inadequate tissue
perfusion and tissue oxygen supply. Based on the causes for reduction of cardiac
output, shock can be classified into four major types.

Type—Pathophysiology and major causes

Cardiogenic Shock
Pumping action of heart decreases decrease in stroke volume, decrease in cardiac
output. Blood volume may be normal.

Causes
(a) Acute myocardial infarction, Heart failure, Cardiac arrhythmias.
Special features
Pulmonary edema
Hypervolumea
Dyspnea
Fall in BP

Cold, pale skin due to reflex vaso constriction of cutaneous blood vessels.

Obstructive Shock
The flow of blood from the ventricles into the arterial system is obstructed. Total
blood volume maybe normal.

Causes
Cardiac tumor, tension pheumothorax, aortic stenosis and distributive shock.

Total blood volume may be normal. Most of the blood remain back in the blood
vessels. Less blood is returned to the heart so less blood pumped out of heart.
Decrease in venous return leading to decrease in cardiac output. Vasodilation of
eutaneous blood vessels, skin blood flow is normal.

Warm Shock
Causes: Anaphylactic shock

Severe allergic response to drugs like penicillin. Large quantity of histamine is

released. Histamine produce wide spread relaxation of smooth muscles of blood
vessels. Severe vasodilatation, venous return falls, cardiac output falls- severe
bronchospasm leading to asthma is also seen. Severe increased capillary
permeability takes place. Loss of water from blood—it may lead to
hypovolumea.

Septicemic Shock

Due to severe bacterial infection most commonly gram negative bacteria.

Bacterial toxins produce the release of chemicals like cytokines and interleukins.
These substances produce severe vasodilatation decrease in venous return,
decrease in cardiac output and hypotension. These toxins can produce decrease
in myocardial contractility, cardiac insufficiency, and increasing capillary
permeability. This may decrease force of contraction of heart and loss of fluid
from blood, decrease in blood volume. So characteristics of cardiogenic shock,
hypovolumic shock and distributive shock all are seen. Ultimately this leads to
multiple organ failure.
Neurogenic Shock

During severe emotional out bursts like over excietement, fear, and anger
autonomic nervous system dysfunction can happen. This produce sudden marked
vasodilatation, fall in venous return decrease in cardiac out and hypo tension.
Fainting or syncope is commonly seen.

Hypovolumic Shock

Cold shock severe decrease in blood volume results in sharp fall in cardiac
output. Decrease in blood volume may be due to actual blood loss or fluid loss.
This type of shock is commonest among all the types of shock. Major causes are

(a) Acute hemorrhage to road accidents, industrial accidents, stabbing, bullet

injuries.

(b) Severe blood loss during surgery or parturition. (c) Severe fluid loss due to
diarrhea and vomiting. (d) Burn.

Major features include

(a) Pallor and clammy skin due to peripheral vaso constriction.

(b) Dyspnea due to hypoxemia and hypereapnea. (c) Oliguria due to renal
vasoconstriction. (d) Hypotension due to low blood volume. (e) Tachycardia due
to compensatory adjustment. (f) Usually patient is conscious.

Stages of shock—Wigger’s classification

1. Initial stage
2. Compensatory stage
3. Progressive stage
4. Irreversible stage

1. Initial stage
In this stage the amount of blood lost from the body is not much. Therefore there
is no significant fall in the BP.
2. Compensatory stage

By this stage the amount of blood lost from the body becomes more and this
may lead to the fall of BP. But the fall of BP is prevented by compensatory
mechanisms. This includes
A. Immediate compensatory mechanisms.
B. Delayed compensatory mechanisms.
A. Immediate compensatory mechanisms

1. Barorceptor reflex—Arterial bororeceptor stimulation is removed. This leads

to increase in sympathetic tone there by reflex increase in vasoconstriction and
tachycardia.

2. Increased venous constriction increases venous return—Sympathetic nervous

system response.

3. Vasoconstriction—mainly in the skin and viscera diverting the blood to vital

organs skin become cold and pale.

4. Increased sympathetic tone increases the release of catecholamines from

adrenal medulla. Catecholamines increases heart rate and force of contraction of
heart there by try to lift up cardiac output.

B. Delayed compensatory mechanisms

1. Secretion of rennin from kidney produces angiotensin I and later angiotensin
II. Angiotensin II produce vasoconstriction there by increase BP.

2. Interased secretion of ADH and aldosterone increase the reabsorption of water

and salt from renal tubule, decreases water loss through urine, there by try to
restore blood valume.

3. Shift of fluid from interstitial space into the blood vessel. This improves the
blood volume, there by prevents fall in blood pressure.

4. When ECF volume decrease, osmotic concentration of blood will increase,

this will stimulate hypothalamus. This will produce thirst leading to drinking
there by restores blood volume.

5. Increased secretion of erythropoietin stimulate the bone morrow there by

increases rate of RBC production and RBC count.

3. Progressive stage

By this stage the amount of blood lost from the body becomes too much, the
compensatory mechanism cannot maintain BP, so BP falls.
In progressive stage positive feed back mechanism operate and worsen the situation
+ Cardiac output Coronary blood flow Blood volume
2O supply to myocardium
Stroke volume Force of contraction of heart

Fig. 3.34 Positive feedback mechanism in progressive stage 4. Irreversible

stage

In this stage the amount of blood lost becomes very high and it will ultimately
lead to death.

Treatment
1. Blood transfusion
2. Plasma transfusion
3. Injections of ADH
4. Injections of noradrenaline, dopamine

Distributive shock or Vasogenic shock or Low resistance shock

It is also called ‘Warm Shock’ because skin is not cold and moist as it is in
hypovolumic shock. It includes:
(a) Fainting or syncope
(b) Anaphylactic shock
(c) Septic shock

(a) Syncope

It refers to a condition in which there is sudden and temporary unconsciousness

due to temporary stoppage of blood flow to the brain.

The brain cannot withstand stoppage of blood supply (which results in stoppage
of oxygen supply) for more than 10 seconds. This leads to unconsciousness.

Within a short period of time the defect is corrected, blood flow to brain is
restored and the person gains consciousness.

The different causes for syncope are:

1. Sudden decrease in BP
2. Vasodilation
3. Cardiac causes like arrhythmia, Stokes—Adam’s syndrome. When there is a
complete heart block, no impulses will come from atria to ventricle. Later the
ventricles start beating at their own rhythm. During this gap period systolic
blood pressure falls to a very low level and blood supply to brain becomes
inadequate. If lack of oxygen supply to brain lasts for longer seconds it leads to
dizziness and fainting. This is called as Stokes-Adams syndrome. If the delay of
starting of ventricular

pumping is prolonged beyond 1 minute it leads to unconsciousness, convulsions

and death.

4. Emotional reasons affecting CVS and CNS. Form 1. Vasovagal syncope

Fainting of a otherwise healthy person due to sudden exposure to unknown

environment like hearing an unexpected bad news, sudden excitement etc. It is
fainting due to emotional disturbance.

Cause for syncope

(a) Exposure to unknown environment. This leads to severe vasodilation of

blood vessels of skeletal muscles causing pooling of blood at tissue level which
decreases venous return by decreasing pheripheral resistance.
Vasodilation is due to:
1. Withdrawal of sympathetic activity 2. Hyperactivity of postganglionic
cholinergic

vasodilator nerves supplying blood vessels of muscles.

(b) Another reason for fainting is stimulation of cardiac inhibitory centre in

medulla by the impulses from hypothalamus which decreases heart rate and
force of contraction of heart.
Combined effect of (1) and (2) together decrease cardiac output and hence
results in syncope.

Other forms of syncope are:

2. Micturition syncope: It is syncope during micturition. It is due to decrease in
blood pressure and heart rate which decreases cerebral blood flow.

3. Postural syncope: Standing for long time results in pooling of blood in lower
extremities which decreases venous return and hence decreases cerebral blood
flow causing syncope.
4. Cardiogenic syncope: Decrease in cerebral blood flow due to cardiac causes
like heart-block, ischaemia of cardiac musculature etc.

(b) Anaphylactic shock

Some hypersensitivity reactions can lead to release of histamine or other

substances which produce vasodilation as well as increase in capillary
permeability. Decreases blood volume. Decreases cardiac output.

Cardiac failure or heart failure

Cardiac failure is defined as inadequate pumping ability of heart leading to

inadequate perfusion of tissues.
Types: Forward failure backward failure.
Definition: Failure of heart to maintain an adequate cardiac output (‘CO’) for
normal tissue perfusion throughout the body due to its poor contractility. It is of
two types: ‘forward’ failure and ‘backward’ failure.

A. Forward failure
It is due to “fall in cardiac output”, therefore, tissue
perfusion throughout the body is grossly inadequate.
Signs and Symptoms
1. Generalised weakness.
2. Exercise intolerance.
3. Fall in systemic B.P. produces cerebral ischaemia which is associated with:
confusion, drowsiness, disorientation, excessive talking, fixed ideas, giddiness,
headache and impaired judgement and eventually leads to loss of self control. 4.
Increase in ventricular end diastolic volume (EDV) leads to ‘cardiomegaly’.
B. Backward failure
It is due to failure of either ‘RV’ or ‘LV’ or both to put
out all the blood returned to them via the veins. This results
in congestion in venous system with rise of venous pressure.
Therfore, backward failure is also called as “congestive
cardiac (or heart) failure” (CCF/CHF). It presents in two
forms:

(a) Right ventricular failure (RVF)

Failure of ‘RV’ causes rise in systemic venous

pressure. This produces signs and symptoms due to backward pressure which
includes:

(i) Transudation of fluid from blood vessels causing oedema of dependent parts
(oedema over feet and sacral region).

(ii) Distension of neck veins.

(iii) Increase resistance to portal blood flow produces hepato-spleenomegaly
(enlargement of liver and spleen).

(b) Left ventricular failure (LVF)

Failure of ‘LV’ increases pulmonary venous pressure, which results in

pulmonary venous distension and transudation of fluid into air spaces, called
“pulmonary oedema”. Pulmonary oedema is characterised by:

(i) dyspnoea (difficulty in breathing) on exertion;

(ii) paroxysmal nocturnal dyspnoea (PND), i.e., dyspnoeic attacks at night;

(iii) orthopnoea i.e., dyspnoea in lying down position;

(iv) Forthy sputum due to irritation of diaphragm.
Biventricular cardiac failure: Cardiac failure, which starts as left or right
ventricular failure, ultimately becomes failure of both the ventricles. Since the
major features of biventricular failure are due to congestion in systemic veins
and congestion in the pulmonary vasculature, it is also called blood congestive
cardiac failure.
Left ventricular failure
Increase in left atrial pressure
Increase in pulmonary capillary pressure
Increase in pulmonary arterial pressure
Right ventricular hypertrophy
Right ventricular failure
Fig. 3.35 Sequence of events which leads to congestive cordiac failure

High output cardiac failure

This paradoxical situation in which the cardiac output is high

and yet the heart is failing can arise in the following situations:

(a) Left-to-Right shunts, as in tetralogy of Fallot. Blood flows from the left side
to the right side so that the output of the right ventricle is high, and yet the right
ventricle eventually fails.

(b) Hyperthyroidism: Tissue metabolic activity is high, and the blood flow
increases to meet the enhanced requirements. That necessitates a high cardiac
output on a continuing basis. The heart may not be able to cope with the high
workload, and eventually fail in spite of pumping more than the normal volume
of blood.

CPR stands for cardiopulmonary resuscitation, a combination of rescue

breathing (mouth-to-mouth resuscitation) and chest compressions. If a child isn’t
breathing or circulating blood adequately, CPR can restore circulation of
oxygen-rich blood to the brain. Without oxygen, permanent brain damage or
death can occur in less than 8 minutes. CPR is most successful when
administered as quickly as possible, but you must first determine if it’s
necessary. It should only be performed when a person isn’t breathing or
circulating blood adequately.

Three parts of CPR: The three basic parts of CPR are easily remembered as
“ABC”—A for airway, B for breathing, and C for circulation.

A is for airway: The victim’s airway must be open for breathing to be restored.
The airway may be blocked when a person loses consciousness or may be
obstructed by food or some other foreign object. The step will include what to do
to clear the airway if you believe a person has choked and the airway is blocked.

B is for breathing: Rescue breathing is begun when a person isn’t breathing.

Tilt the head back and listen for breathing. If not breathing normally, pinch nose
and cover the mouth with yours and blow until you see the chest rise. Give 2
breaths. Each breath should take 1 second.

C is for circulation: Chest compressions can sometimes restore circulation. If

the victim is still not breathing normally, coughing or moving, begin chest
compressions. Push down on the chest 11/2 to 2 inches 30 times right between
the nipples. Pump at the rate of 100/minute, faster than once per second.

Gravity is the weakest of the four fundamental forces, yet it is the dominant
force in the universe for shaping the large scale structure of galaxies, stars, etc.

Effect of gravity on circulatory system: Gravity is very important to blood

circulation, since the vascular system must work against gravity in order for
blood to reach the parts of the body that are higher than the pump (the heart).
Humans that walk upright provide a particular challenge for the blood
circulation system. On way to minimize these problems for humans is to lie
down prone. This is why patients recovering from injury or disease are
encouraged to stay in bed, since there is less strain on the vascular system when
we are horizontal. The situation is different, of course, when an organism is in
free fall in space, with no local effects of gravity microgravity). In the case of
human astronauts, microgravity decreases the head-to-foot arterial blood
pressure gradient. More blood than usual is pumped toward the head, resulting in
slightly bloated faces, while there is less blood in the legs, making some
astronauts looks skinny when they wear shorts.

Effect of gravity on different body parts

Positive G— Positive G is the force of acceleration experienced in the

downward (head-to-feet) direction, expressed in units of gravity. Also known as
eyeballs down. Positive G mostly affects the normal blood circulation, when the
positive G is increased it results into peripheral pulling of blood towards lower
extremities so as it decreases the cardiac output. This condition leads to
decreased oxygenated blood supply to the upper parts of the human body, due to
hypoxia the upper parts of body may show following changes.

1. Grey-out: Retina is more sensitive to hypoxia than brain. Loss of peripheral

vision (tunnel vision) with loss of colour perception, and no loss of
consciousness. The pilot can still hear, feel, and think. Recovery time two to
three seconds after release of positive G force.

2. Blackout: Complete loss of eyesight, no loss of consciousness. Pilot can hear,

feel, and think. Recovery time two to three seconds after release of positive G
force.

3. L.O.C.: Loss of consciousness. The subject cannot hear, feel, think, or

function. Frequently accompanied by seizure activity and/or loss of bladder and
bowel control. Recovery does not occur on the average for 15 to 20 seconds after
the G force is terminated. The time required to return to consciousness may vary
from nine to 20 seconds, and the subject does not return to normal function for
several minutes.

Negative G: Negative G is the force of acceleration that a subject experiences as

acting from below (feet-tohead direction). Also known as eyeballs up. Anything
below one G is considered a negative G. At zero G’s it is weightlessness.
1. This occurs because on the uphill, you are still going

up, while the train is trying to go down. Resistance to negative g’s, which drive
blood to the head, is much lower. This limit is typically in the –2 to –3 g (–20
m/s² to –30 m/s²) range.

2. The subject’s vision turns red, referred to as a red out. This is probably
because capillaries in the eyes swell or burst under the increased blood pressure.

Echocardiography

Echocardiography is a painless test that uses sound waves to create images of

your heart. It provides your doctor with information about the size and shape of
the heart and how well the heart’s chambers and valves are working.

Echocardiography is the application of ultrasound for imaging of the heart.

Standard ultrasound techniques are used imaging of the heart. Standard
ultrasound techniques are used D, conventional echocardiography also employs
M-mode and Doppler. Color Doppler is used to image flowing blood.
Continuous wave Doppler and Pulsed wave Doppler are used to measure the
velocity of flowing blood.

Echocardiography is used to assess the information of: 1. The size of the heart:
An enlarged heart can be the result of high blood pressure, leaky heart valves, or
heart failure.

2. Heart muscles that are weak and aren’t moving (pumping) properly.
Weakened areas of heart muscle can be due to damage from a heart attack. Or
weakening could mean that the area isn’t getting enough blood supply, which
can be due to coronary artery disease.

3. Problems with the heart’s valves. Echocardiography can show whether any of
the valves of the heart don’t open normally or don’t form a complete seal when
closed.

Cardiac arrhythmia is a term for any of a large and heterogeneous group of

conditions in which there is abnormal electrical activity in the heart. The heart
beat may be too fast or too slow, and may be regular or irregular.
Some arrhythmias are life-threatening medical emergencies that can result in
cardiac arrest and sudden death. Others cause symptoms such as an abnormal
awareness of heart beat (palpitations), and may be merely annoying. Still others
may not be associated with any symptoms at all, but predispose toward
potentially life-threatening stroke or embolus.

Some arrhythmias are very minor and can be regarded as normal variants. In
fact, most people will sometimes feel their heart skip a beat, or give an
occasional extra strong beat neither of these is usually a cause for alarm.

The term sinus arrhythmia refers to a normal phenomenon of mild acceleration

and slowing of the heart rate that occurs with breathing in and out. It is usually
quite pronounced in children, and steadily decreases with age. This can also be
present during meditation and breathing exercises that involve deep inhaling and
breath holding patterns.

The most common symptom of arrhythmia is an abnormal awareness of

heartbeat, termed palpitations. These may be infrequent, frequent, or continuous.
Some of these arrhythmias are harmless but many of them predispose to adverse
outcomes.

LYMPHATIC SYSTEM

Lymphatic system is a closed system of channels called lymph channels or

lymph vessels. It is the one way system and the lymph flows through this from
tissue spaces towards the blood.

Origin of Lymphatic System

The lymphatic system arises from tissue spaces as a mesh work of delicate
vessels. These vessels are called lymph capillaries.

The lymph capillaries start as enlarged terminals called capillary bulbs situated
in tissue spaces. These bulbs contain valves which allow flow of lymph in one
direction i.e., towards blood. There are some muscle fibres around these bulbs.
These muscle Fibres cause contraction of bulbs so that lymph can move through
the vessels.

The lymph capillaries are lined by endothelial cells. These capillaries form large
lymphatic vessels. These become still larger due to joining of many tributaries
with them along their course.

Drainage of Lymphatic System

The larger lymph vessels ultimately form right lymphatic duct and thoracic duct.
The right lymphatic duct opens into right subclavian vein and the thoracic duct
opens into left subclavian vein.

The lymph vessels are present in all parts of the body except the following
structures:
1. Superficial layers of skin
2. Central nervous system
3. Cornea
4. Bones and
5. Alveoli of lungs.

Lymphoid Organs

Lymphoid tissues: Lymphoid (or lymphatic) tissues, which mainly consist of

dense accumulations of lymphocytes, are widely distributed in the body.
Lymphoid tissues are typically located at sites that provide a possible route of
entry of pathogens and/or sites that are liable to infections. Epithelia delimit all
other tissues from the outside world and it is not surprising that lymphoid tissues
are often found near them. Such lymphoid tissues are grouped together as
epithelium-associated lymphoid tissues. Depending on their precise location
these lymphoid tissues may be referred to as e.g., mucosa-associated lymphoid
tissue (MALT) or bronchus-associated lymphoid tissue (BALT). The tonsils or
Peyer’s patches are examples of mucosa-associated lymphoid tissues. Lymphoid
tissues represent the sites of proliferation and differentiation of lymphocytes.

Lymphoid organs may be defined as anatomical entities which consist chiefly of

lymphoid tissues. The thymus is a primary lymphoid organ in that it supplies
other lymphoid organs and tissues with T-lymphocytes. Inserted into the blood
and lymph vascular system, the spleen and lymph nodes (secondary lymphoid
organs) monitor the internal environment of the body.

Thymus: The thymus is situated in the upper parts of the thorax, behind the
sternum and the upper four costal cartilages, in the anterior and superior
mediastina. The size of the thymus changes in the course of life. The thymus is
necessary for the development of the recirculating pool of small, long-lived (in
humans many years) lymphocytes, the T-lymphocytes. These cells are mainly
responsible for the cell-mediated part of an immune response. Stem cells invade
the cortical regions of the thymus, where they divide to form lymphocytes. Only
a small fraction (estimates range from 10-30%) of the cells generated in the
cortex leave the thymus. They migrate via the medulla into the blood stream to
populate the T-lymphocyte areas of other lymphoid tissues and organs. Cells
which do not express the necessary receptors to recognize antigens presented to
them or which react incorrectly towards “self-antigens” die and are removed by
cortical macrophages. Since the function of the thymus is to produce
lymphocytes for the other lymphoid tissues it is a primary lymphoid organ.

Lymph nodes: Lymph nodes are small, flattened, and oval or bean shaped
organs, which are situated in the course of the collecting lymph vessels. Their
size is variable (from a few mm to more than 2 cm). The capsule and trabeculae
of lymph nodes are formed by connective tissue. Afferent lymph vessels
penetrate the capsule and empty into the subcapsular space. The lymph continues
thereafter through cortical and medullary sinuses towards the efferent lymph
vessels, which emerge from the hilus of the lymph node. The walls of the sinuses
can be traversed freely by all components of the lymph, which allows
lymphocytes to enter/ leave the lymphoid tissue (as part of their constant
circulation) or to get in contact with antigens/antigenpresenting cells that may
arrive with the lymph.
CapsuleCortex

Efferent lymphatic vessel

Afferent lymphatic vessel

Artery

Vein Primary lymphoid follicle

Medulla Secondary lymphoid follicle

Fig. 3.36
Structure of a lymph node

Locations of lymph nodes: Most of the lymph nodes occur in groups, or

clusters in certain areas of the body, these locations has got great clinical
importance.

1. Submental and submaxillary groups in the floor of the mouth—lymph from

the nose, lips, and teeth drains through these nodes.

2. Superficial cervical lymph nodes in the neck along the sternocleidomastoid

muscle—these nodes drain lymph from the head and neck.

3. Superficial cubital or supratrochlear lymph nodes located just above the bend
of the elbow—lymph from the forearm passes through these nodes.

4. Axillary lymph nodes which drains the lymph from the arm and upper part of
the thoracic wall, including breast, drains through these nodes.

5. Inguinal lymph nodes in the groin—lymph from the leg and external genitals
drains through these nodes.
Lymphatic endothelial cell
Lymphatic capillary

Fig. 3.37 Lymph capillary

Formation of Lymph

Lymph is formed from interstitial fluid, due to the permeability of lymph

capillaries. When blood passes via blood capillaries through tissues, 9/10 of fluid
passes into venous end of capillaries from arterial end, and the remaining 1/10 of
the fluid passes into lymph capillaries, which have more permeability than blood
capillaries.

So, when lymph passes through lymph capillaries the composition of lymph is
more or less similar to that of interstitial fluid including protein content. Proteins
do not enter the blood capillaries because of their larger diameter than the
diameter of the pores in the capillary membrane. So, these enter lymph vessels
which are permeable to large particles also.

Addition of proteins and fats: The tissue fluid in liver and gastrointestinal tract
contain more protein and lipid substances. Thus, lymph in larger vessels have
more proteins and lipids.

Concentration of lymph flow: When the lymph passes through the lymph
nodes, the water and the electrolytes are absorbed. But, the proteins and lipids
remain in lymph itself and are not absorbed. So, the lymph becomes
concentrated. Many bacteria are removed from lymph and phagocytosed by the
macrophages of lymph node.

Rate of lymph flow: About 120 ml of lymph flows into blood per hour. Out of
this amount, about 100 ml/hour flows through thoracic duct and 20 ml/hour
flows through the right lymphatic duct. Rate of flow of lymph is 0.5–1 ml / min
is the thorasic duct. Drainage of lymph into general circulation is 2-4 liters per
24 hours.

Factors increasing formation of lymph: The amount of lymph formed is

increased by the following factors:
1. Increases in interstitial fluid pressure.
2. Increases in blood capillary pressure.
3. Increases in surface area of lymph capillary by means of dilatation.
4. Increases in the permeability of lymph capillaries and
5. Increases in functional activities of tissues.

Functions of Lymph

1. The important function of lymph is the return of proteins from tissue space
into blood 200 gm/day.
2. Lymph flow plays an important role in redistribution of fluid in the body.
3. Through the lymph, the bacteria, toxins and other foreign bodies are removed
from tissues.
4. It helps in the regulation of volume and pressure of extracellular fluid.
LYMPH
Water Cells 96% Lymphocytes Solids 4%
Organic substances Inorganic substances

(1) Proteins
Albumin
Globulin
Fibrinogen
Prothrombin
Clotting factors
Antibodies
Enzymes

(2) Lipids 5-15g%

Chylomicrons
Lipoproteins

(3) Carbohydrates Glucose - 120 mg % Cations Anions

Na++ HCO–K 3 Ca++ Mg++ Cl– ++ ––Mn SO4

PO
–– 4

(4) Non protein nitrogenous compounds

Amino acids
Urea
Creatinine

Fig. 3.38 Composition of Lymph

5. Take part in the absorption of fat from intestine.

6. Lymph flow is responsible for the maintenance of structural and functional

integrity of tissue. Obstruction to lymph flow affects various tissue particularly
myocardium, nephrons and hepatic cells. Functions of Lymph Nodes

1. When lymph passes through the lymph nodes, it is filtered i.e., , the water and
electrolytes are removed. But the proteins and lipids are retained in the lymph.

2. The bacteria and other toxic substances are destroyed by macrophages of

lymph nodes. Because of this, lymph nodes are called defense barriers.

Swelling of Lymph Nodes

During infection in a particular region of the body, the lymph nodes draining that
region become swollen due to excessive activities inside. Sometimes, the
swollen lymph nodes cause pain.
Respiratory System
Adolf Eugen Fick
1-4-1829–1901
German Physiologist and Biophysicist
Known for Fick’s law of diffusion Fick principle

C.H. L.O.E. Bohr

14-02-1855–3-2-1911 Danish Physician
Known for Bohr’s effect in Respiratory physiology

Ewald Weibel
Swiss biologist
Famous for Weibels model of respiratory tract

John Cheyne
3-2-1777–31-1-1836
England
Known for Cheyne-Stokes breathing
John Scott Haldane
3-5-1860–15-3-1936
Scottish Physiologist
Famous for self experimentation in respiratory physiology-Haldane effect

Robert Boyle
25-1-1627–30-12-1691. Ireland , London
Known for Study of physical properties of gases

Jacques Alexandre
César Charles
12-11-1746–7-4-1823 French Inventor, Scientist, Mathematician, and
Balloonist.
Known for Charles law

Adolph Kussmaul
(22-2-1822–28-5-1902) German physician
Known for Kussmaul’s breathing

William Stokes
1-10-1804–10-1-1878
Irish physician,
Known for Cheyne-Stokes breathing and Stokes-Adams disease

(122)
Chapter
4
RESPIRATORY SYSTEM

Functional anatomy. Functions of respiratory systemRespiratory and non

respiratory functions. Respiratory membrane.
Mechanism of breathing.
Intrapleural and intrapulmonary pressure. Forces acting on respiratory
membrane.
Pressure—Volume relationships.
Compliance—chest and lungs, values, total compliance.
Surfactant, Hyaline membrane disease
Airway resistance.
Spirometry—Lung volumes and Lung capacities, Normal values, significance.
Vital capacity and timed vital capacity—factors affecting and significance.
Minute respiratory volume. Maximum Voluntary Ventilation. Breathing Reserve.
Respiratory dead space. Defintion and normal value, Principle of measurement.
Pulmonory ventilation and alveolar ventilation. Ventilation purfusion ratio.
Pulmonary gas exchange.
Factors affecting gas exchange across the respiratory membrane.
Transportation of Oxygen in the blood.
Oxygen—Hb dissociation curve.
Transportation of carbondioxide in the blood. Chloride shift, Haldane effect.
Respiratory Quotient.
Regulation of Respiration- Neural Regulation— Respiratory centres.
Hering-Bruer’s inflation and deflation reflexes. Chemical regulation of
respiration. Peripheral and central Chemoreceptors.
Effect of H+ conc, PCO2 and PO2 on respiration. Hypoxia—Types and effects.

Cyanosis, Asphyxia, Dyspnoea, Periodic breathing. Acclimitisation to high

altitude, mountain sickness. Dysbarism. Asthma, Emphysema, Apnoea.
Artificial respiration—Manual methods.

Holger-Neilson method and mouth to mouth breathing.

Respiratory changes during exercise.

RESPIRATORY SYSTEM

Respiration is a complex physiological process by which a living organism

meets its oxygen requirement and expels out carbon dioxide.

Functions of Respiratory System: Respiratory Functions

1. Supply of O2 to the tissues.
2. Removal of CO2 from the body.

Non-Respiratory Functions of Lungs/Respiratory System

1. Protective functions or lung defence functions

(a) Filtration of inspired air. Particles present in the inspired air are filtered by
the hairs and mucus present in the respiratory tract.

(b) Large particles are trapped by mucus and forcibly thrown out by sneezing
reflex or coughing reflex.
(c) Pulmonary alveolar macrophage system engulf and distroy microorganisms
and particles.
(d) Air conditioning of inspired air. If inspired air is cooler than body
temperature it is warmed up to body temperature when it reaches the alveoli. If
inspired air is warmer than body temperature it is cooled down to body
temperature when it reaches the lungs.
(e) Secretion of immunoglobulins provides immunity against microorganisms
entering along with inspired air.
(f) Fibrinolytic system of lungs removes clot from the blood.
(g) Sense of olfaction

Metabolic functions of lungs

(a) Synthesis of surfactant for local use, to reduce surface tension and thereby to
prevent the total collapse of lungs.

(b) Synthesis of collagen and elastic fibres. (c) Conversion of angiotensin I to

angiotensin II by angiotensin converting enzyme. This helps in the regulation of
BP Endocrine function.
(d) Synthesise and release of substances like histamine, bradykinin,
prostaglandins in conditions like anaphylaxis.
(e) Removal and inactivation of substances from blood like bradykinin,
serotonin, prostaglandins, histamine etc.
(f) Pulmonary blood vessels trap and remove small emboli.

Other functions

1. Vocal chords help in the production of sound which is made into words used
in speech.
2. Plays a minor role in water balance.
3. Plays a minor role in body temperature regulation.

Stages or steps of respiration

1. Exchange of air between atmosphere and lungs. This is also called as external
respiration or ventilation.

2. Exchange of gases between alveoli and blood.

3. Transportation of respiratory gases by the blood.
4. Exchange of gases between the blood and the tissue.
5. Cellular utilisation of O2. This is also called as cell respiration or internal
respiration.
6. Regulation of respiration.

PHYSIOLOGICAL ANATOMY OF
RESPIRATORY SYSTEM
Respiratory system comprises of respiratory tract, respiratory organ or lungs and
respiratory muscles.

It is the passage for air. Respiratory tract it starts with external nostril and
ultimately ends in alveolus. Respiratory tract is divided into two parts:

1. Upper respiratory tract—consisting of external nostril, nasal cavity

oropharynx and larynx.

2. Lower respiratory tract starts from trachea or wind pipe, continue as airways
and end in alveoli Trachea is the main air way.

Trachea divides in two primary bronchi. Each bronchus enters into lungs. Right
bronchus is short, straight and broad than left bronchus. Infections of right lung
is more common than left lung. The bronchus divide into smaller and smaller
branches. Trachea divides into 23 generation of branches up to the tenth
generation they are called bronchus later generations are called as bronchioles.
The wall of trachea and bronchus are lined the wall of trachea and bronchus are
lined by hyaline cartilages and they have minimum smooth muscle content. The
wall of bronchioles do not contain cartilage but there smooth muscle content is
large. The cartilages prevent the collapse of airways. The tone of smooth
muscles of bronchi is called as bronchial tone. Sympathetic stimulation produce
bronchodilation where as parasympathetic stimulation produce broncho
constriction. The cross section area of trachea is about 2.5 sq.cm. whereas total
cross sectional area of the alveoli is 12.000 sq.cm.
Sinus Nasal cavity
Nostrill
Oral cavity
Larynx
Bronchus Hard plate
Soft plate
Pharynx
Epiglottis
Trachea
Bronchioles
Diaphragm
Right lung Left lung
Fig. 4.1
Anatomy of respiratory system

Weibel’s model: Between the trachea and alveoli, the air passage divides 23
times, each generation is numbered. Trachea is zero generation, primary bronchi
is first generation and so on. The respiratory tract is divided into 2 zones or
areas. First zone

1. Conducting zone—from trachea to tip of 16th generation or terminal bronchi.

Here there is no gaseous exchange, only passage of air takes place.

2. Respiratory zone—17th generation of respiratory tract to alveoli. Here passage

of air and exchange of gases both takes place. Amount of air in the upper
respiratory tract from external nostril to tip of terminal bronchi is called as
Anatomical dead space. Air of this region is not available for gaseous exchange
because there is no respiratory membrane. Its volume is 150 ml.
Epithelial basement membrane

Alveolar
Interstitial

fluid
Capillary
basement
membrane
Capillary
endothelium Plasma

Functions of Respiratory Tract

1. Passage of air from the atmosphere to the lungs and in the reverse direction.
2. Purification of inspired air. The inspired air gets filtered by the hair and
mucous of the respiratory tract.
3. Humidification. The inspired air is mixed up with water vapour while passing
through the respiratory tract.
4. Inspired air gets warmed up while passing through the respiratory tract or
cooled down.
5. Nose helps in olfactory sensation. Nasal secretion contain immunoglobulins.
So provide protection against micro organisms.
6. Tonsil is situated in the pharynx and it takes part in immunity.
7. Pharynx provide resonating chamber for speech and helps in phonation.
Respiratory Organ, Lungs

There are two lungs covered by pleura. Pleura is a two walled covering. The two
layers are outer parietal layer and inner visceral layer. In between two layers of
pleura there is a space known as intra pleural space filled with intra pleural fluid.

Function
1. This fluid keeps two pleural layers together
2. It acts as a lubricant and helps in the sliding movement between the two
layers.
Pneumothorax: Presence of air in the pleural space is known as pneumothorax.
This leads to collapse of lungs on the affected side because of recoil of lung
wall. The structural and functional units of the lungs are ‘alveoli’. There are
about 300 million alveoli.
Respiratory membrane: It is a membrane made up of wall of pulmonory
capillary and the wall of alveolar epithelium. Its thickness is about 0.5 microns,
and the total surface area is about 70 square metres.

Outermost layer is a layer of chemical substance known as surfactant. 2nd layer

is alveolar epithelial cells. 3rd layer is a thin membrane known as alveolar
basement membrane. 4th layer is interstitial space. 5th layer is capillary
basement membrane. 6th layer is capillary endothelium.
Surfactant O2
Red blood cell
CO2
Alveolus Capillary

Fig. 4.2 Respiratory membrane

Innervation of Lungs

Lungs are innervated by autonomic nervous system. The walls of the bronchi
and bronchioles are innervated by sympathetic nervous system. Post ganglionic
sympathetic fibres secrete norepinephrine as neurotransmitter. Stimulation of
sympathetic nervous systems produce bronchodilatation and decreased bronchial
secretion and vasoconstriction. Parasympathetic innervation of lungs is by vagus
and neurotransmitter is acetylcholine. Parasympathetic stimulation produces
broncho constriction, vasodilatation and increased secretion of mucus. Blood
supply to the lungs— Lungs receive blood from the pulmonary vessels and
bronchial vessels.
Respiratory muscles: They are divided into two groups.
1. Inspiratory muscles 2. Expiratory muscles

Inspiratory muscles
(a) Primary muscles:

Diaphram, External intercostal muscles. (b) Accessory muscles:

Scalane, Sternomastoid, Trapezium.

Expiratory muscles
Internal intercostal muscles
Muscles of abdomen

Mechanism of Respiration
Breathing means intake of air into the lungs and giving out of air from the lungs.
Breathing consists of two phases.

1. Inspiration and 2. Expiration. These two phases are alternatively repeated.

Normal rate of breathing is 12–18 times/minute. During normal breathing or
quiet breathing inspiration and expiration are mostly achieved by diaphragm.
Diaphragm is a dome shaped muscle. The dome of the muscle remain projected
into the thoracic cavity when the muscle is at rest. Inspiratory impulses originate
at the inspiratory centre situated at the medulla oblongata. The inspiratory
impulses come down through phrenic nerve and reach the diaphragm.
Diaphragm gets excited, this is followed by contraction. When diaphragm
contracts, it becomes flat, it descends by a few centimeters. This will increase
the vertical diameter of thoracic cage. In addition to diaphragm external
intercostal muscles also contract. Contraction of these muscles lift the thoracic
cage outward and upward – Bucket handle movement. This will increase
transverse diameter. Forward and upward movements of sternum increases
anterio-posterior diameter of thoracic cavity—Pump handle movement. This
will increase volume of thoracic cavity. As per Boyle’s law: When volume
increases pressure decreases, pressure inside the thoracic cavity decreases. This
will allow the lungs to expand, volume of lungs increase and pressure inside the
lungs decrease. This creates a pressure gradient between atmosphere and lungs.
760–757 mm of Hg. As per the pressure gradient air flows from atmosphere into
the lungs. This process is known as inspiration.

Sequence of events of quiet breathing inspiration and expiration Medulla

inspiratory centre
Inspiratory impulses
Phrenic nerve & intercostal nerve
Inspiratory muscles diaphragm and external intercostals
Contraction
Lifting of thoracic cage, volume of thorosic cage increases, pressure decreases
Intrapleural pressure becomes more negative
Increase in transpulmonory pressure
Expansion of lungs, increase in volume,
Decrease in intrapulmonary pressure below atmosphere
Airflows as per pressure gradient from atmosphere to lungs. Inspiration
Contraction of inspiratory muscle stops
Thoracic cage move downward and inward
Volume of thoracic cage decreases, pressure increases
Intrapleural pressure become less negative
Decrease in transpulmonary pressure
Deflection of lungs volume of lungs decrease
Intrapulmonory pressure becomes greater than atmosphere pressure
Air flows as per pressure gradient from lungs to atmosphere. Expiration.
Atmospheric pressure (760 mm of Hg)

Alveolar
pressure
(760 mm of Hg)

Intrapleural
pressure
(758 mm of Hg)

1. Before inspiration
Atmospheric pressure (760 mm of Hg)

than atmospheric pressure. As per the pressure gradient 763 mm of Hg (Lungs)

760 mm of Hg (atm) air flows from lungs to atmosphere. This process is known
as expiration.

During normal breathing inspiration is considered as an active process, because

it involves muscular contraction and it requires energy expenditure. Expiration is
considered as a passive process because it does not involve muscular contraction
and does not require energy.

During rigorous (vigorous) respiration both inspiration and expiration becomes

an active process. Expiration is not achieved by mere relaxation of inspiratory
muscles but it involves contraction of expiratory muscles. Internal intercostal
muscles and muscles of abdomen also contract.
500

Intrapulmonary pressure
(757 mm of Hg) 250

Volume in ml 0
2. During inspiration (diaphragm contracting)

Diaphram descends
754 mm of Hg-6 mm of Hg
Intrapleural
pressure
–2 Intrapleural pressure
–3

–4
–5
–6

Atmospheric pressure (760 mm of Hg) +3 Alveolar pressure

0
–3 763mmofHgor+3mmofHg500 Flow (ml/sec) 758 mm of Hg or –2 mm of Hg 0
500 3. During expiration (diaphragm relaxing)–diaphragm moves up Inspiration Expiration
Fig. 4.3 Mechanism of Breathing Time in sec
Expiration

During normal breathing expiration is achieved by relaxation of inspiratory

muscles. When diaphragm relaxs it once again become dome shaped and it will
decrease the vertical diameter of thoracic cavity. The relaxation of external
intercostal muscles make the downward and inward movement of thoracic cage.
This decreases transverse diameter and anterio- posterior diameter. This
decreases volume of thoracic cavity and increases pressure inside the thoracic
cavity. This will compress the lungs. Pressure inside the lungs increases.
Intrapulmonary pressure becomes greater
Intrapleural fluid
Thoracic wall Intrapleural fluid

Lung Heart
Fig. 4.4 Intrapulmonary, intrapleural and volume changes during respiration
When internal intercostal muscles contract the thoracic cage is pulled inward and
down ward this further decreases transverse diameter and anterio-posterior
diameter of thoracic cage. In addition to this muscles of abdomen contracts. This
will make the contents of abdominal cavity to fall on diaphragm. This pushes the
diaphragm further into thoracic cavity. This decrease vertical diameter of
thoroaic cavity. All these processes decrease the volume of thoracic cavity to a
greater extent. This will increase pressure inside the lungs. It will create a wider
pressure gradient. This leads to expulsion of greater quantity of air. Expiration
involves muscular contraction which requires energy expenditure therefore
becomes an active process.

Forces acting on the wall of the lungs

There are three forces acting on the wall of the lungs. 1. Negative intrapleural
pressure.
2. Surface tension.
3. Recoil tendency of the wall of the lungs. Of these three forces, negative
intrapleural pressure

favours the expansion of the lungs, the other two forces oppose, the expansion of
the lungs.
Negative intrapleural pressure

The lungs are covered with pleura. Pleura has got two layers, visceral layer and
parietal layer. The space between these two layers is known as intrapleural
space. It is filled with a fluid- intrapleural fluid. The pressure in the intra pleural
space is always –ve. At the beginning of inspiration it is about –2 mm of Hg.
During inspiration the intrapleural pressure becomes more –ve, it reaches up to
-6 mm of Hg. During inspiration the intrapleural pressure act as a sucking force
on the wall of the alveoli. This keeps the wall of the alveoli expanded.

Surface tension

It is a physical force operated when a solvent faces air or gas. This force is
developed at the interface of water and air. The surfactant on the wall of the
alveoli is exposed to air inside the alveoli. This will decrease the force of surface
tension. This prevents direct water-air exposure. Surfactant act as a detergent.
This decreases the force of surface tension. Suface tension is the force which
oppose the expansion of the wall of the alveoli.
Recoil tendency of the wall of the lungs

The wall of the lungs is made up of numerous small elastic fibers. During
inspiration the wall of the lungs expand. This will stretch the clastic fibers. The
stretched elastic fibers will show a tendency to come back to their original size
and shape. This force will oppose the expansion of the lungs. Usually the force
favouring the expansion of the lungs is greater than the sum of forces opposing
the expansion of the lungs. Because of this the lungs will always remain in a
state of expansion.

Transpulmonary pressure

Transpulmonary pressure is the pressure inside the lung (intra-alveolar pressure)

minus the pressure just outside the lung(intrapleural pressure).

Compliance of the lungs

Compliance is change in volume of the lung per unit change in transpulmonary

pressure. Normally it is 0.13 L/cm of H2O for lungs and thorax together. It is
0.22 L/cm of H2O for lungs alone.

50
25 Expiration
Inspiration
0
–4–5 –6
Pleural pressure (cm H O)
2
Fig. 4.5
Compliance diagram in a normal person Measurement

Intra-oesophageal balloon is passed in a person for recording intrapleural

pressure. Person is asked to inspire in steps (taking in about 50–100 ml of air
with each step). At the end of each step intra-oesophageal pressure is recorded.
These points are plotted on the graph of pressure against volume, and inspiratory
compliance curve is obtained. Similarly expiration is also done in steps and
expiratory compliance curve is obtained.

The slope (steepness) of this pressure

– volume curve denotes compliance.
∆VCompliance = ∆P

Where, ∆V = change in volume of the lung ∆P = change in transpulmonary

pressure.
The inspiratory and expiratory compliance curves do

not coincide. This type of curve is called hysteresis curve. Difference in

stretchability of lung in expiratory and inspiratory phase accounts for this type of
curve. Volume of lung is less in inspiratory phase than expiratory phase. This is
static compliance.
Specific compliance =

Compliance Functional residual capacity

Normal value is about 0.08 L/cm of water. It is clinically more significant.

Clinical conditions reducing compliance:
1. Tuberculosis
2. Abscesses
3. Respiratory distress syndrome.
4. Pulmonory fibrosis
All these are restrictive lung diseases.
Conditions in which compliance is increased: Chronic obstructive lung diseases,
In this, surface area is also decreased. So, this is not advantageous. E.g.,
Emphysema.
800
700

Emphysema total lung capacity

600
Normal lung
500 total lung capacity

400
300

200 Total lung capacity restrictive lung

100 disorder fibrosis

0
Fig. 4.6 Change in pressure-transpulmonary pressure in cm of water
Surfactant
Definition

Any surface acting material or agents that is responsible for lowering the surface
tension of the fluid is called as surfactant. Surfactant present on the alveoli is
called pulmonary surfactant.

Fig. 4.7
Surfactant

By type II alveolar epithelial cells of the lungs also called as pneumocytes.

They also called as surfactant secreting alveolar cells.
They contain micro villi on their surface Chemistry. Chemically surfactant is a
lipo-protein, a complex of lipid and protein, the lipid part is dipalmitoyl lecithin.
Phospholipids; e.g., Dipalmitoyl phosphotidyl choline. Other lipids; neutral fats,
phosphotidyl glycine,
Proteins; protein A, B C and D (collectin family). Ions; mainly calcium ions.

Mechanism of Action
This chemical acts as a detergent.

It reduces the force of surface tension to the extent of 7–14 times.

Functions
Reduces the muscular efforts required for breathing. Decreases the surface
tension of the lungs their by prevents the collapsing tendency of the lungs. Also
responsible for the stabilisation of the alveoli which have tendency to deflate.
This by decresing surface tention proportionatelly more in smaller alveoli.
Helps in inflation of the lungs during birth. Prevents pulmonary edema.
Keep the wall of the alveoli dry.
This helps in easy gaseous exchange.
Immunity. Ig A of surfactant provides innate immunity.

TABLE 4.1
Factors influencing surfactant production
S.No. Factors increasing Factors decreasing

1. Nervous factor
parasympathetic stimulation of type II cells.
Smoking Hypoxia
2. Hormonal factors: Thyroid hormone Gluococorticoids, Insulin.
Hypothyroidism

Deficiency of surfactant
In infants; Respiratory distress syndrome or hyaline membrane disease.
In adults; Adult respiratory distress syndrome.

Respiratory Distress Syndrome

Due to the deficiency of surfactant the force of surface tension increase upto 7–
14 times.

Now the forces opposing the expansion of the lungs becomes greater than the
force favouring the expansion of lungs.

The alveoli fail to expand.

This leads to respiratory failure and result in death. This clinical condition is
known as Respiratory Distress Syndrome or Hyaline Membrane disease.

Treatment
1. Administration of phospholipid by inhalation.
2. Glucocorticoid administration.
3. Inhalation of synthetic surfactant.
Adult respiratory distress syndrome
Cause: Injury of respiratory membrane caused by chemicals like —sulphur
dioxide, anticancer drugs, aspiration of gastric contents.
This damages capillary endothelium.Damage of alveolar epithelium leads to
accumulation of haemorrhagic fluid. This hampers gaseous exchange.
Accumulation of neutrophils and monocytes in the alveoli takes place.
Neutrophils undergoes lysis and release proteolytic enzymes which digest
proteins of capillary and alveolar membrane. This release of prostaglandins,
leukotrines. This destroys surfactant. Lack of surfactant increases surface
tension. This leads to decrease in compliance, alveoli collapse refuse to inflate.
Symptoms:
Severe hypoxia
Inability to inflate lungs
Athelectasis or Collapse of part of lungss.

SPIROMETRY: SPIROGRAM

Spirometer: It contains two chambers, outer chamber and the inner chamber.
The outer chamber is also called the water chamber. It is filled with water. A
floating drum is immersed in the water in an inverted manner. The drum is
counter balanced by a weight. The weight is attached to the top of the inverted
drum by means of string or chain.
Recording drum Counter balance with pen
Pulley
Inverted drum
Inner
container
Mouth piece
Water
Outer
container Lungs during expiration
Fig. 4.8
Recordings of spirogram. Arrangement of spirometer

The inner chamber is inverted and has a small hole at the top. A long metal tube
passes through the inner chamber from bottom toward the top. The upper end of
this tube reaches the top portion of the inner chamber. The tube passes through
the hole at the top of the inner chamber and penetrates into the outer water
chamber above the level of water. A rubber tube is connected to the outer end of
the metal tube. At the other end of this rubber tube, a mouth piece is attached.
The subject respires through this mouth piece.

When the subject breathes with the spirometer, during expiration the drum
moves up and the counter weight comes down. Reverse of this occurs when the
subject breaths the air from the spirometer i.e., during inspiration. The upward
and downward movements of the counter weight denotes inspiration and
expiration. The pen is made to write on calibrated paper, which is fixed to a
recording device. The upward curve of the graph shows inspiration and the
downward deflection denotes expiration.

There are several lung volumes and lung capacities. The technique of recording
of these lung volumes and lung capacities is known as Spirometry. The
instrument used is known as Spirometer. The graph obtained is Spirogram.

Lung volumes or pulmonary volumes

1. Tidal volume: It is defined as amount of air inspired or expired during normal
respiration. Normal value is 500 ml. in adults and 15-20 ml. in newborn infants.
2. Inspiratory Reserve volume (IRV): It is defined as maximum amount of air
that is inspired over and above the tidal volume by a deep inspiration. Normal
value is 3000 ml.
6000 Inspiration
5000 Inspiratory reserve 4000 volume
Tidal volume

3000
Inspiratory capacity Vital

capacity Total lung capacity

2000 Expiratory reserve volume
1000 Residual volume 0
Expiration

Functional residual
capacity

Time
Fig. 4.9
Spirogram: record of lung volumes and capacities

3. Expiratory Reserve Volume (ERV): It is defined as maximum amount of air

expired out over and above the tidal volume by a forceful expiration after a
normal inspiration. Normal value is 1100 ml.

4. Residual Volume (RV): It is defined as amount of air remaining inside the

lungs even after a forceful expiration. Normal value is 1200 ml.

Significance of residual volume

1. This prevents the total collapsing of the lungs.

2. This maintains continuity of gaseous exchange between the alveoli and blood.
This helps to maintain a constant oxygen and CO2 level in the blood.

3. Medicolegal importance—To detect whether the baby was born dead (still
born) or born alive. If the baby is born alive, minimum volume of our will be
there inside the lungs and thus lungs will float in water. If it was still born lungs
will be solid because it contain no air and it will sink down.

Residual volume cannot be recorded by spirometer. But it can be estimated using

‘Nitrogen washing technique’.
Tidal Volume : TV = 500 ml Inspiratory Reserve Volume : IRV = 3000 ml
Expiratory Reserve Volume : ERV = 1100 ml Residual Volume : RV = 1200 ml
Inspiratory capacity : IC = 3500 ml Functional Residual Capacity : FRC = 2300
ml Vital Capacity : VC = 4600 ml Total Lung Capacity : TLC = 5800 ml

Lung Capacities or Pulmonary Capacities

1. Inspiratory Capacity: It is defined as maximum amount of air that can be

inspired by a deep inspiration.
IC = inspiratory capacity = IRV + TV,
IC = 3000 + 500 = 3500 ml.

Functional residual capacity

It is defined as amount of air remaining inside the lungs
at the end of a normal expiration.
FRC = RV + ERV = 1200 + 1100 = 2300 ml.
Vital capacity
It is defined as maximum amount of air that can be
expired out by a forceful expiration after a deep inspiration. VC = IRV + TV +
ERV
i.e., VC = 3000 + 500 + 1100 = 4600 ml.
Physiological variation
1. Age: Vital capacity is more in adults than in children. But vital capacity per
kg. body weight is greater in children.
2. Sex: Vital capacity is more in male than female. 3. Built of the body or size
of the Body: Vital capacity increases with increase in size of the body.
Approximately vital capacity is proportional to height of the individual. In
Indian population the expected vital capacity of males
= height in cm × 20 ml.
In Indian females. VC = height in cm × 16 ml.6 4. Position of the body: Vital
capacity is more when5 the person is seated in a slightly reclined posture.4 It will
be less in lying down position. 3 5. Athletes: Vital capacity is more in athletes
than2

others. VC = Hcm × 29 ml. 16. Pregnancy: During later stages of pregnancy

vital0capacity decreases because movement of the
diaphragm becomes restricted. 67. Exercise: Regular exercise increases vital capacity.
5
Pathological decrease in vital capacity
4 (a) Neurological diseases affecting respiratory muscles3like neuritis, poliomyelitis. 2(b)
Myasthenia gravis—an auto immune disorder.

(c) Deformities of thoracic cage like kyphosis,1 0scoliosis.

(d) Diseases of lungs like asthma, emphysema,6pulmonary oedema, and pulmonary fibrosis.

5
Significance of vital capacity 41. It is taken as one of the lung function test. 32.
Determination of
vital capacity can be used to assess the prognosis of respiratory diseases.2
Time (Second)
0 12 3 4 5 6 78

Normal Maximum inspiratory level

Time (Second)

Restrictive disease Maximum Expiratory level

Maximum inspiratory level

Maximum Expiratory level

Obstructive disease Maximum inspiratory level

3. Vital capacity can be used to assess the physical1

fitness of athletes. 0

Timed Vital Capacity: Dynamic Lung Capacity

01 2 3 4 5 6 78 Fig. 4.10
Timed vital capacity in normal, restrictive and It is the vital capacity related to
the time. obstructive lung diseases It is expressed in terms of forced expiratory
volume I
FEV1 Dead space

Forced expiratory volume II, FEV2 , Forced expiratory

volume III, FEV3
FEV1 is defined as % of vital capacity expired at the
end of first second.
FEV1 normal value is 80–87%
FEV2 is 90–97%, FEV3 is 100%RV

Maximum Expiratory level

Significance

1. Timed vital capacity is useful to assess the prognosis

of respiratory diseases. ERV
2. It is used to differentiate between obstructiveTV(asthma) type of lung diseases and
restrictive type

of lung diseases, (kyphosis).1RV

Vital capacity decreases in both obstructive as well as

restrictive type of lung diseases. But the timed vital capacity Fig. 4.11 Lung
volumes. IRV-Inspiratory Reserve volume, will decrease in obstructive type of
lung diseases like asthma TV-Tidal Volume, ERV-Expiratory Reserve Volume,
RVit may be normal in restrictive type of lung diseases. Residual Volume

TABLE 4.2 Different types of restrictive lung disorders

S.No. Diseases Causes Category PFT 1. Paralysis
• Decreased VC 2. Spinal cord diseases
• Decreased EFV1 3. Pleural effusion Abnormal functions of Restrictive lung
disorders
• Normal FEV1/FVC 4. Myasthenia gravis thoracic cavity
TABLE 4.3 Different types of obstructive lung disorders
S.No. Diseases Causes Category PFT 1. Emphysema
• Bronchospasm
• Normal or slightly 2. Chronic bronchitis
• Infections of lower decreased VC 3. Cystic fibrosis respiratory tract
• Decreased FEV1 4. Asthma
• Loss of elasticity of lungs Obstructive lung disorders
• Decreased FEV1/FVC 5. Severe cough and cold Obstruction or infections 6.
Bronchitis of upper respiratory tract.

Total lung capacity It is defined as maximum amount of air that can be filled
inside the lungs.

TLC = VC + RV = 4600 + 1200 = 5800 ml. Total lung capacity is decreased in

pulmonary oedema and pneumothorax.

Minute respiratory volume: It is defined as the amount of air exchanged

between respiratory system and atmosphere per minute during normal
respiration.

MRV = TV × RR (Respiratory rate)

= 500 × 12 – 18
= 6000 – 9000 ml/min.

Alveolar ventilation: It is defined as the amount of air exchanged between

alveoli and atmosphere per minute.

Alveolar Ventilation = (TV – ADS) × RR

= [500 – 150] × 12
= 350 × 12 = 4200 ml.

ADS = Anatomical dead space.

RR = Respiratory rate.
TV = Tidal volume.

Anatomical dead space is the volume of air remaining in the upper respiratory
tract from the external nostril to the tip of terminal bronchi. Normal volume is
150 ml. This air is called as dead space because there is no gaseous exchange in
this space, because there is no respiratory membrane.
80
60

40 Area
without nitrogen

20
0 0 100 200 300 400 500 Air expired (ml)

Fig. 4.12
Determination of dead space Measurement of Anatomical Dead Space Single
breath Nitrogen Washout method Procedure :
Area
with
nitrogen

Step 1: Subject must ventilate normally for few minutes.

Step 2: Subject is made to inhale pure oxygen.
Step 3: Subject is made to exhale through a nitrogen meter.
Concentration of nitrogen in expired air can be measured. Plot the observation
on a graph.
Calculation: Dead space can be calculated by using following formula:

Volume of dead space

Volume of expired air
Area without Nitrogen= Area with Nitrogen + Area without Nitrogen
Physiological dead space

It is anatomical dead space together with dead space that results from wasted
ventilation. Under normal conditions in a healthy individual physiological and
anatomical dead space are equal. But under certain conditions,

1. Some of the alveoli may become non functional due to membrane disorder.
2. Some of the alveoli receive inadequate blood supply.
3. Some of the alveoli are hyperventilated. The air in these alveoli constitute
wasted ventilation.

Measurement of physiological dead space

Physiological dead space air is calculated from Bohr’s equation.
The equation is
Volume of dead space

PCOin alveolar air − PCO in expired air= 22

Tidal volume × PCO2 in alveolar air

The principle behind this equation is that inspired air contains only negligible
quantity of CO2 and all CO2 present in expired air comes from functional alveoli.

Maximum Breathing Capacity (MBC): Dynamic lung capacity

It is defined as maximum amount of air exchanged between respiratory system
and atmosphere per minute. It is also called as maximum ventilatory volume
(MVV) or maximum voluntary ventilation (MVV).

Normal value is 120 – 140 litres/min. MRV = minute respiratory volume.

Breathing reserve
It is the difference between the maximum breathing capacity and minute
respiratory volume.
Normal value is MBC – MRV
= 120 – 6 = 114 litres/min.
Ventilation Perfusion Ratio: V/P ratio. It is the ratio of alveolar ventilation to
pulmonary blood flow. Normal alveolar ventilation is 4 lit/mt, pulmonory blood
flow 5 Lt/min, so ventilation perfusion ratio is 4/5 = 0.8. Ventilation perfusion
ratio

Gaseous exchange takes place at the alveoli across the respiratory membrane
oxygen diffuses from alveoli to pulmonary capillary blood and carbon dioxide
diffuses out from pulmonary capillary blood to alveoli. This is possible only if
proper alveolar ventilation and perfusion are maintained. Approximately 5000
ml of blood flows through the lungs per minute and about 4000 ml of air flows
in and out of alveoli per minute. So at rest normal ventilation perfusion ratio will
be 4000/5000 – 0.8.
Pulmonory blood flow-perfusion
Ventilation
V
Average — = 0.8P
V V — = 0.6 — = 3.6P P

Fig. 4.13
Base apex ventilation perfusion ratio at different parts of lungs

But both ventilation as well as perfusion are not uniform in all the parts of the
lungs. Gravity is a major cause for creating a difference in perfusion in the
different parts of the lungs. Upper zone of lungs is poorly perfused where as
lower zone of lung is well perfused. In standing position ventilation per unit
volume is more at the base if the lungs than at apex. Blood flow is greater at base
than apex. So base of the lung is better ventilated and better perfused than apex.

At apex of lungs ventilation perfusion is high about 3–6 because more

ventilation and less blood flow. At the base V/P ratio is very less because
perfusion is relatively very high compared to ventilation. V/P will be 0.6.

Significance of V/P ratio

Mismatching in V/P ratio may occur either due to change in alveolar ventilation
or lung blood flow. This mismatching ultimately lead to poor gaseous exchange
across the respiratory membrane.

TABLE 4.4 Comparison of composition of atmospheric air, alveolar air and

expired air
Atmospheric air or inspired air Alveolar air Expired air
Gas % Partial pressure mm of Hg % Partial pressure % Partial pressure
mm of Hg mm of Hg N2 78.6 597 74.9 569 74.5 566 O2 20.8 159 13.6 104 15.7
120 CO2 0.04 0.3 5.3 40 3.6 27 H2O 0.5 3.7 6.2 47 6.2 47

Airflow through the airways

Air flows from outside to inside – Inspiration. Inside to outside – Expiration. Air
flows as per pressure gradient.

Types of Airflow–Two types:

1. Laminar flow: Stream lined flow takes place in small peripheral airways –
character – silent.
2. Turbulent flow: Occurs in large airways.
– Disorganised flow producing sound.

Airways resistance
Defined as the ratio of pressure gradient P to Airflow (V).
Pmounth Palveoli−Total Airway Resistance =
V

Normal value: 1–3 cm of H2O/L per second. Major sites of resistance:

Medium bronchi, bronchi up to 17th generation. Resistance by small airways–10
to 15%

Factors affecting airway resistance

R α11. Diameter of airway = r4

2. Lung volume: Airway diameter increases with lung expansion. Thus airway
resistance decreases during inspiration increases – during expiration.

3. Bronchial smooth muscle tone. This controls the degree of broncho

constriction – controls airway diameter, so controls airway resistance. Smooth
muscle tone is influenced by:
(a) ↑ Parasympathetic tone – ↑ Brochoconstriction. (b) Sympathetic tone – ↑
Bronchodilatation. (c) Hormones – Epinephrine, Norepinephrine – β2

adrenergic receptors – ↑ Airway dilatation. Histamine – ↑ Bronchoconstriction.

(d) Drugs – Isoproterenol – β2 adrenergic Bronchodilatation.

(e) Environmental factors – Dust, smoke produce reflex bronchoconstriction →

↑ airway resistance.

4. Viscosity and density of inspired air – High barometric pressure.

Assessment of airway resistance

Timed vital capacity. FEV1, FEV2, FEV3.
Ratio of FEV1 to FVC
Differentiate obstructive and restrictive lung diseases. Peak expiratory flow rate
(PEFR): It is defined as

maximum velocity of flow in litres per minute with which air is forced out of
lungs.
Normal value: 400–600 L/mit 6–10 L/sec.

Work of Breathing
Definition

The energy generated by respiratory muscles to overcome the resistance in

thorax and respiratory tract is known as work of breathing.

Respiratory muscles work only during the inspiration, during normal breathing.
Work of breathing is required to
A. To expand the lungs,Elastic resistance = 65%
B. To overcome air way resistance
– Non-elastic resistance = 35%.
Work done = Change in lung volume multiplied by the change in Tran
pulmonary pressure. W = P × ∆V.
About 5% of total body energy expenditure 0.3 to 0.8% kg/min.
Work done increases during
1. Exercise
2. Emphysema
3. Bronchial asthma
4. Congestive cardiac failure

Factors affecting diffusion of gases

Partial pressure gradient
More is the difference in partial pressure of a gas on either side of the membrane
more will be the diffusion.
Surface area of membranes.
Decrease in surface area – Decrease in diffusion. e.g., emphysema.
Increase surface area – Exercise - increase diffusion.

Thickness of the membrane: Diffusion

1 ∝ Thickness Increase thickness – decrease diffusion

E.g., Pulmonory oedema
Solubility of the gas

Diffusion ∝ solubility.
CO2 is 20 times more soluble in water than O2. Molecular weight
Diffusion
∝
1

Molecular weight
Diffusivity or diffusion coefficient Graham’s law: Diffusibility = S
Molecular Wt.
Diffusion coefficient

∝
Pressure gradientSolubility Area×× Molecular weight × Thickness

Diffusivity depends on membrane character: Fibrosis of membrane as in

asbestosis, silicosis decrease solubility of gas, decrease diffusion.

Ventilation perfusion ratio Va/Q

Normal perfusion, decreased ventilation – Decrease
gas transfer.
Decrease perfusion – Normal ventilation – Decrease
gas transfer.
Reaction time:
Time taken for the biochemical reactions to occur and
time required for the movement of gases.
Time taken for gas transfer.
RBC stays in pulmonary for 0.75 Sec. Transit time Both O2 CO2 transfer takes
within 0.25 sec. Diffusion reserve: 2/3rd – Safety margin.
Summary: Fick law:
Volume of gas diffusing per minute α
Area Diffusion coefficient P×× Thickness
Diffusion capacity of lungs
Defined as amount of gas that crosses the alveolar
capillary membrane per minute per partial pressure difference
of 1 mm of Hg on either side of the membrane. Diffusion capacity for O2 at rest
= 20–30 ml/min/mm of Hg.
Surface AreaDC = Thickness

Reduction in DC is seen in:

Block in pulmonary capillary
Block in airway
Pulmonary Oedema
Increase in DC
Exercise – due to opening of closed capillaries. Vasodilation.

Measurement
DO2 = O2
Consumption/mt: Alveolar PO2 – pulmonary PO2 Determination of pulmonary
PO2 is difficult. So DO2 is measured by finding DCO.
CO is poisonous – but not harmful in very low

concentrations.
Steps: Subject takes single breath of CO mixture. Holds for 7 seconds – Exhales
CO concentration in inspired air with expired air is

measured by infrared CO analysis.

Lung volumes are measured simuttaneouslly by helium dilution technique.

CO uptakeDCO = Alveolar PCO − Pulmonary PCO (zero)

= 25 ml/mt/mm of Hg.
Comparision of atmospheric air (Inspired air), Alveolar air and Expired air:

Atmospheric air is a mixture of gases—N2, O2, CO2 and water vapour. Normal
atmospheric pressure is 760 mm of Hg. This pressure is contributed by all the
gases present in the air. The pressure exerted by a individual gas in a mixture of
gases is called as partial pressure. Partial pressure of a gas is proportional to its
concentration.

The comparison of atmospheric air with alveolar air shows that alveolar air has
less O2 and more CO2 compared to atmospheric air. The expired air has less O2
and more CO2 compared to the atmospheric air. The comparison of alveolar air
with expired air shows that expired air has more O2 and less CO2 than alveolar
air.

The expired air is not entirely coming from alveoli. Actually it is a mixture of
alveolar air (350 ml) and anatomical dead space air (150 ml). The composition
of anatomical dead space is almost same as inspired air as far as O2 and CO2 are
concerned. Therefore the composition of expired air is in between the
composition of inspired air and alveolar air.
Lungs
Alveolus PO 104 mm
2
of Hg
AV
2PO 40 mm of Hg O2 2PO 95 mm of Hg
Tissue

Cell
2PO 23 mm of Hg

O2AV

Transportation of Respiratory Gases

2PO 95 mm of Hg2PO 40 mm of Hg
Fig. 4.15 Pressure gradient for the transportation of O2
159
104
pa 95
46
40
Portial p ressure 40carbondioxide
Atmospheric Alveolar Blood air air
28
Tissue
Fig. 4.14 Pressure gradient of respiratory gases
Transportation of Oxygen
O2 is transported from the lungs to the tissues by the blood. This flow of O2 is as
per the pressure gradient. Partial pressure of O2 in the alveoli is 104 mm of Hg.
The partial pressure of O2 at the arterial end of pulmonary capillary is 40 mm of
Hg. As per the pressure gradient O2 diffuses from the alveoli into the blood.
Partial pressure of O2 at the venous end of pulmonary capillary reaches to 95
mm of Hg. The partial pressure at the arterial end of tissue capillary is 95 mm of
Hg. Partial pressure of O2 in the interstitial fluid is 40 mm of Hg. As per the
pressure gradient O2 will diffuse from the blood into the interstitial fluid. PO2
inside the cell is approximately 23 mm of Hg. O2 will diffuse from the interstitial
fluid into the cell. Partial pressure of O2 at the venous end of tissue capillary is
40 mm of Hg.

Forms of O2 transportation
O2 is transported in two forms:

1. In the dissolved form:

About 3% of O2 dissolves in water of the blood and transported as physical
solution. This is about

0.3 ml of O2 is carried by 100 ml of blood. This dissolved state of oxygen is very

small quantity. Still it is important because it is the readily available oxygen to
the tissues.

2. As Oxy hemoglobin.
97% of O2 is transported by the hemoglobin. O2

combines with hemoglobin giving rise to oxy hemoglobin. One molecule of

hemoglobin can combine with 4 molecules of oxygen. It is known as
oxygenation. Oxygenation takes place step by step.

Haemoglobin is made up of four subunits. Each sub unit has one heme and one
polypeptide molecules.
Iron is present in ferrous form in the heme. Oxygen binds to iron in an easily
reversible reaction.
Forms of hemoglobin—hemoglobin exists in two different forms. T form or
tense form and R form or relaxed form. The forms of heme are interchangeable.
In T form of hemoglobin, the four sub units are tightly bound to each other. It
shows less affinity to oxygen. When first oxygen binds with hemoglobin, the
subunits get separated, exposing more oxygen binding sites. Now hemoglobin
becomes R state, and enhances its affinity towards oxygen to several fold. The
changing of state of hemoglobin depends on PO2. At alveoli, when PO2. is high,
T form becomes R form, increases affinity towards oxygen. This favors grated
uploading of oxygen or favours the formation of more oxy hemoglobin. At
tissues, PO2 is less, R form becomes T form of Hb. Affinity of HB towards
oxygen decreases more oxygen get unloaded, this favors the formation of more
deoxy hemoglobin.

TABLE 4.5
Comparison of arterial blood with venous blood
S.No. Features Arterial Venous blood blood 1. O2 content/100 ml 19.4 ml 14.4
ml of blood
O2 O2 4Hb + O2 Hb O4 2
O2 Hb
4
O2
2. % of saturation of Hb 97 70 3. P O2 95 mm 40 mm of Hg of Hg
O2 O2
Hb
4
O
2
Hb (O ) 42 4
O2 HbO2
4O
2
O2 O2

One gram of hemoglobin when fully saturated can carry 1.34 ml of O2. 100 ml
of arterial blood with 15 gm of Hb may have about 20.1 ml of O2. This is called
as oxygen carring capacity of blood. But Hb may not get saturated beyond 97 %.
Therefore, 100 ml of arterial blood with 15 gm of Hb may have 19.4 ml of
oxygen. Percentage saturation of hemoglobin with oxygen is equal to quantity of
actual quantity of oxygen bound with hemoglobin devided by the quantity of
oxygen potentially bound with hemoglobin multiplied by 100. 100 ml of venous
blood will have 14.4 ml of O2. That means every 100 ml of blood releases 5ml
of O2 to the tissues. Blood releases about 250 ml of O2 per minute.
Coefficient of utilisation of oxygen

This depends upon the ability of tissues to extract oxygen from blood. Oxygen
extraction is the amount of oxygen taken up by the tissues from the blood. It
reflects the oxygen extraction is the amount of oxygen taken up by the tissues
from the blood. It reflects the oxygen consumption of the tissues and their
metabolic state. This can be calculated using the formula:

Coefficient of oxygen O2 extracted by the tissue/Utilisation

100 ml of blood × 100= Oxygen

content in 100 ml of blood
For whole body at rest = 5 ml
×100 = 25%19.4 ml

This ratio varies from tissues to tissues. In metabolically active cardiac muscles
it can be 60–85% at rest coefficient of utilisation of oxygen is very low, but
during vigorous exercise it may go up-to n 90%.

Oxygen hemoglobin dissociation curve

There is a relationship between partial pressure of O2 and % saturation of
hemoglobin. The graphical representation of the relationship between partial
pressure of O2 and %

saturation of hemoglobin is called oxygen hemoglobin dissociation curve. This

curve is obtained by plotting partial pressure of O2 against % saturation of
hemoglobin. The shape of the curve is sigmoid shape or ‘S’ shape.
100
97
90
80

70
60
50
40
30

20
10 plateau Plateau phase

teep phase
10 20 30 40 50 60 70 80 90 95 100 110 120 Partial pressure of O mm of Hg2

Fig. 4.16
Oxygen-Hemoglobin dissociation curve

Initially for a slight increase in partial pressure of O2 there is a sharp increase in

% saturation of Hb. When the partial pressure of O2 is 40 mm of Hg the %
saturation reaches to 70%. Afterward when the partial pressure increases, the %
saturation increases very slowly. When the partial pressure of O2 is 95 mm of Hg
it reaches to 97% saturation of Hb. Afterward even if the partial pressure of O2
increases there is no corresponding increase in % saturation. The curve reaches a
plateau.

The oxygen Hb dissociation curve is not linear. It is sigmoid shape. Lower part
of the curve is steep and upper part of the curve is flat or plateau. Steep phase of
the curve is seen at the PO2 between 0mm of Hg to 60 mm of Hg. Initially slight
increase in PO2 there is a sharp increase in % saturation of Hb-steep phase.
When PO2 is 60mm of Hg percentage saturation will reach to 90% In this phase
slight increase in PO2 leads to greater loading of Hb with O2. Where lower PO2
prevails more O2 will be released. Flat phase or plateu phase of curve is
observed from PO2 60 mm of Hg, further increase in PO2 may increase %
satuvation of Hb to a very small extent. When PO2 is 95mm of Hg, percentage
saturation will reach 97% Beyond that percentage saturation may not increase
even if PO2 increases.

Significance: The plateau phase enable the respiratory system to cope up the
normal percentage saturation of Hb even with compromised lung functions. It
can be considered as a safety factor. This also ensure that even with
hyperventilation percentage saturation of Hb cannot be increased beyond 97%.

P 50: It means the partial pressure of oxygen at which the haemoglobin is half
(50%) saturated with oxygen. Its normal value is 26 mm of Hg. Haemoglobin
affinity for O2 is inversely proportional to P50 value. When P50 increases
affinity of Hb towards oxygen decreased, so more oxygen can be unloaded,
curue will shift to right. When P50 is lowored, affinity of Hb towords oxygen
increases. Graph will shift to left, more oxygen get 1oaded.
Factors effecting Oxygen—Hb dissociation curve There are four factors:
1. Concentration of CO2.
2. Concentration of hydrogen ion or pH.

3. Concentration of 2, 3 DPG i.e., (2, 3 Diphospho glycerate)

4. Temperature.

1. Concentration of CO2

When the CO2 concentration increase that will shift the O2 hemoglobin
dissociation curve to the right. That means affinity of Hb towards O2 decreases.
So more and more O2 is dissociated from Hb whenever CO2 concentration
increases. This effect of CO2 concentration on the O2, Hb dissociation curve is
known as Bohr’s effect.

Significance:
(a) CO2 concentration in the blood at the lungs is relatively lower than tissue. So
more and more

oxygen get attached to haemoglobin when blood is at the lungs. But CO2 in the
blood at tissue is more. So more and more oxygen is liberated from haemoglobin
to the tissues.

(b) This effect controls the O2 released to the tissues as per the metabolic
demand of O2.
100
97 plateau
90
80 CO2 CO2
70

60%
saturation 50 Normal CO
2of Hb
40 30 20 10

10 20 30 40 50 60 70 80 90 95100110 120 Partial pressure of O mm of Hg2

Fig. 4.17
Effect of CO2 concentration on Oxygen-Hemoglobin dissociation curve
2. Concentration of hydrogen ion or pH
Increase in H+ concentration or decrease in pH will shift the O2-Hb dissociation
curve to the right.

Significance: Whenever CO2 concentration increases the H+ ion concentration

will also increase CO2 + H2O → H+ + HCO− and pH will fall.3

So pH of blood at the lungs is higher than pH of blood at the tissue. So in the

lungs more and more O2 associates with Hb and when blood reaches tissues
more O2 dissociates from Hb. Therefore this effect helps in the transportation of
O2 by the Hb. This also controls the O2 release to the tissues as per the O2
demand.

3. Concentration of 2, 3 DPG (2, 3 Diphospho glycerate)

It is an intermediate compound formed during the break down of glucose. The

increase in the concentration of 2, 3 DPG will shift the O2-Hb dissociation curve
to the right.

Significance: Whenever metabolic rate increases, the break down of glucose

increases. This will increase the concentration of 2, 3 DPG. This will in turn
shift the O2-Hb dissociation curve to the right. So whenever metabolic rate
increases body requires more O2, due to this effect more O2 is supplied. At high
altitude, 2, 3 DPG concentration increases in RBC. This increases the unloading
of oxygen to the tissues.

4. Temperature

Increase in temperature will shift the O2-Hb dissociation curve to the right.
Whenever metabolic rate increases temperature also increases. Increase in
metabolic rate require more O2 supply and more O2 is released because of this
effect.

TABLE 4.6
Comparison of arterial blood and venous Tissue

blood S.No. Features

1. PO2 mm of Hg.
2. % Saturation of Hb

3. Amount of O2 in ml 100 ml of blood

4. PCO2 mm of Hg

5. Amount of PCO2 in ml/ 100 ml of blood

Arterial blood Venous blood 95 40

97 70
Cell
2PCO 46 mm of Hg

Dissolved form 0.43 ml 0.58 ml. = 3%

Oxyhaemoglobin
18.8 ml = 97% 14.0 ml Total = 19.4 ml. 14.4 ml

40 45
AV
PCO 40 mm of Hg CO PCO 45 mm of Hg 222
Lungs

Dissolved form 3.64 ml 3.36 ml = 7%

Carbomino 11.96 ml compound
11.04 ml. = 23% 36.4 ml Bicarbonate = 70%
33.60 ml. 52 ml Total 48 ml. 52 ml
Alveolus
2PCO 40 mm of Hg
CO2
AV

CARBON DIOXIDE TRANSPORTATION

CO2 is transported from the tissues to the lungs. CO2 flows as per the pressure
gradient. Partial pressure of CO2 at the arterial end of tissue capillary is 40 mm
of Hg. Partial pressure of CO2 inside the cell is 46 mm of Hg. CO2 diffuses from
the cells into the blood. Partial pressure of CO2 at the venous end of tissue
capillary reaches to 45 mm of Hg. Partial pressure of CO2 inside the alveoli is 40
mm of Hg. Partial pressure of CO2 at the arterial end of the pulmonary capillary
is 45 mm of Hg. As per the pressure gradient CO2 diffuses from the blood into
the alveoli.

Forms of CO2 Transportation

CO2 is transported in three different forms.

1. In the dissolved state: About 7 % of CO2 dissolves in the H2O of the blood
and transported as physical solution.

2. Binding with proteins: About 23% of CO2 binds with proteins of the blood.
e.g., Hb, albumin etc. CO2 combines with hemoglobin gives rise to carbamino
hemoglobin, when it binds with other proteins it is called as carbamino proteins.

3. Transportation of CO2 as bicarbonate ions: 70% of CO2 is transported in the

form of bicarbonate ions. CO2 from the plasma diffuses into the R.B.C. Inside
the R.B.C. it reacts with H2O

PCO 45 mm of Hg2PCO 40 mm of Hg2

Fig. 4.18 Pressure gradient for the transportation of CO2

RBC Tissue Plasma
CO2 CO2 CO2
+
HO
2 Carbonic anhydrase
HCO 23
HCO
–3
H
+– HCO3
Cl–
Fig. 4.19
Chloride shift

and give rise to carbonic acid. This reaction is catalysed by the enzyme, carbonic
anhydrase. Carbonic acid dissociates into hydrogen and bicarbonate ions. The
bicarbonate ions formed inside the R.B.C. diffuses out to the plasma. To
compensate the electrical disturbances, the –vely charged chloride ions from the
plasma move into the R.B.C. This movement of chloride ions is called as
chloride shift. When the blood reaches the lungs all these reactions get reversed.
CO2 gas is once again formed. This gas is expelled out from the blood into the
alveoli and later into the atmosphere. 100 ml of venous blood contain 52 ml of
CO2. 100ml of arterial blood contain 48 ml of CO2 100 ml of blood releases 4 ml
of CO2 to the alveoli. So, blood releases 200 ml of CO2 to the alveoli per minute.

Haldane effect

CO2 combines more easily with deoxy haemoglobin than oxy haemoglobin.
Therefore wherever oxygen concentration in the blood increases more and more
CO2 is released from hemoglobin. This is known as Haldane’s effect. So
because of this effect CO2 dissociation curve shifts to the left when the blood
flows through the tissues and it shifts to the right when blood flows through the
pulmonary capillary. Due to the combination with oxygen haemoglobin becomes
more acidic. This unloads more coarbondioxide from heamoglobin because of
higher acidity of haemoglobin has less affinity towards carbondioxide.

Benefits of Haldane effect: This effect almost doubles the quantity of CO2
transported by the blood from tissue to the lungs and helps to unload more CO2
from blood to alveoli where more oxygen is available.

Respiratory Quotient (R.Q)

It is the ratio of CO2 produced to O2 consumed. Normal value is 0.8. When only
carbohydrate is taken as the food R.Q will be one.
REGULATION OF RESPIRATION

It means controlling the rate and depth of respiration as per the physiologic
demand.
It serves three important purposes. They are
1. To maintain a constant O2 and CO2 level in the blood.
2. It adjusts the O2 supply as per the metabolic demand of the body.
3. It helps to regulate acid base balance or pH.
Mechanism of regulation of respiration
There are two major mechanisms:
1. Nervous regulation of respiration
2. Chemical regulation of respiration
RESPIRATORY CENTRES
Medulla
Dorsal respiratory Ventral Group DRG group
Pons

80 Decreased PO2 Appeustic Pneumotaxic centre centre

70
60 50 Increased PO2
40
30
20
10 0 10 20 30 40 50 60 70 80 2PCO in mm of Hg

Fig. 4.20 CO2 dissociation curve—Haldane effect

Central pattern generator in and around medullary respiratory neurons.

Fig. 4.21 Nervous regulation of respiration Dorsal Respiratory Group –

Primarily Inspiratory Neurons. Location – Bilaterally – Nucleus Tractus
Solitarius Impulses

↓
Phrenic nerve C3 – C5
↓
Inspiratory muscles

Ventral Respiratory Group—Ventrolateral Medulla. Location—Nucleus

ambiguous and Retrofacialis This group contains the following neurous:
Expiratory neuron Rostral
Botzinger complex Inspiratory Neurons
Middle
Expiratory Neurons
Caudal

Central pattern generator—within and surrounding DRG-VRG-Pre Botzinger

complex
This acts as a pace maker of respiration.
It generates normal respiratory rhythm.
The main basis of rhythm—is oscillation of impulses.
Interaction of inspiratory—expiratory centres, shows a mutual inhibition.

Higher Centres of Brain

Reticular activating system
Limbic system—Influence actions of respiratory centres.
Pneumotaxic centre +
–
–
Apneustic centre
+
Expiratory centre Mutual–

– inhibition

+ Oscillatory Inspiratorycircuit centre

Expiratory impulses Stretch Inspiratory receptor impulses

Intercostal nerveSpinal motor neuron

Expiratory muscles Phrenic nerve
Diaphragm
Fig. 4.22 Nervous regulation of respiration

Inspiratory centre
It is a group of neurons situated in the medulla oblongata. It consists of several
neurons arranged in a closed circuit. Because of this inspiratory impulse once
generated is transmitted again and again and it is sustained for a long duration of
time. This is known as a oscilation of impulses.
4th ventricle +

– Pneumotaxic centre

Apneustic centre
Glossopharyngeal Ventral respiratory group
Vagus Dorsal respiratory group
Respiratory impulses to the respiratory muscles
Fig. 4.23
Organisation of respiratory centres

During this period inspiratory impluses are transmitted down to the inspiratory
muscles. These muscles contract. This leads to inspiration.

Expiratory centre

It is a group of neurons arranged in the medulla oblongata. The neurons are

arranged in a closed circuit. Because of this expiratory impulse once generated is
sustained for long duration. During this period expiratory impulses are
transmitted to expiratory muscles. These muscles contract leading to expiration.

Inspiratory centre and expiratory centre show mutual inhibition. When

inspiratory centre is active it will send impulses to the expiratory centre. These
impulses will inhibit the expiratory centre. Similarly when expiratory centre is
active it will send impulses to the inspiratory centre and inhibit it. Because of
this inspiratory centre and expiratory centre are not activated simultaneously,
they are activated one after the other.

Apneustic centre
It is a group of neurons situated in the pons. Inspiratory impulses are actually
originated at the apneustic centre. These impulses will stimulate the inspiratory
centre. This initiate the inspiratory process. Apneustic centre also sends impulses
to pneumotaxic centre. Once pneumotaxic centre is activated

it will send impulses back to apneustic centre. These impulses will inhibit the
apneustic centre. This will stop inspiratory process.

Reflexes
1. Hering-Bruer’s inflation reflex
2. Hering-Bruer’s deflation reflex

Hering-Bruer’s inflation reflex

During inspiration the wall of the lungs expand. When it

reaches an optimum level of expansion it will stimulate stretch receptors. From

these stretch receptors sensory impulses are transmitted to medulla oblongata.
These impulses will inhibit the inspiratory centre. This stops the activities of
inspiratory centre. No more inspiratory impulses are transmitted to the
inspiratory muscles, contraction of inspiratory muscles stop. There is no more
inspiratory effort. This prevents over expansion of wall of the lungs and thereby
preventing the rupture of the lungs. This protective reflex mechanism is known
as Hering–Bruer’s inflation reflex.

Hering-Bruer’s deflation reflex

During expiration, the wall of the lungs collapse. When it reaches an optimum
level it will stimulate decompression receptors present in the wall of the lungs.
From these receptors impulses are transmitted to medulla oblongata. These
impulses will inhibit the expiratory centre.
This stops the activities of expiratory centre. No more expiratory impulses are
transmitted to the expiratory muscles, contraction of expiratory muscles stop.
This prevents total collapsing of wall of the lungs. Some amount of air will be
always available inside the lungs (residual volume) so that the continuity of
gaseous exchange between blood and alveoli can be maintained.
TABLE 4.7 Integration of neural mechanism of

respiration

Chemical regulation of respiration

There are three important chemical factors controlling
respiration.
1. Concentration of CO2 in blood.
2. Concentration of Hydrogen ion or pH
3. Concentration of Oxygen in the blood.
Regulation of respiration by CO2 concentration of blood

Medulla

Glossopharyngeal nerve (IXth

cranial nerve) Respiratory centre

Right
aortic
nerve
(branch of vagus)

Right
subclavian artery

Carotid sinus Carotid body

Common carotid artery Left aortic

nerve (branch of vagus)

S.No. Experiment

1. Transaction of brain stem below medulla

2. Transaction above medulla below pons.

3. Transaction in upper pons— Above

Apneustic
centre
Observation Abolishes
respiration

Respiration
continues with irregularity

Amplitude of respiration
increases.

4. Transaction in upper Pons + Bilateral

Vagotomy
Prolonged
inspiratory effort + Apneusis.

5. Transaction above pons No affect on respiration.

Inference

Basic rhythm generator is in medulla

Pons control regularity of

respiration

Pneumotaxic centre at upper pons normally controls

Apneustic
centre.

Vagus inhibit output of

Apneustic
centre.

Medulla and Pons are major parts of the

brain which
controls
respiration.
Aortic bodies

Aortic arch Left

subclavian artery
Fig. 4.24
Location of peripheral chemoreceptors

Suppose CO2 concentration in the blood increases. It will stimulate

chemoreceptors. There are two groups of chemo receptors:

1. Peripheral chemoreceptors—situated at the carotid body and aortic body.

2. Central chemoreceptors—situated at the medulla oblongata.
From these chemo receptors sensory impulses are transmitted to respiratory
centres. These impulses stimulate the respiratory centres. This increases the
activities of respiratory centres. This will produce increase in the rate of
respiration and depth of respiration. This will increase alveolar ventilation. This
will increase CO2 expulsion from the body. This will inturn decrease CO2 level
in the blood to the normal.
Central
chemoreceptors

Medulla
oblongata
respiratory centres

+ Peripheral
chemoreceptors

+
carotid body

aortic body
Rate Depth of respiration

Alveolar ventilation
CO2 – 2CO expulsion

Fig. 4.25 Regulation of respiration by CO2 of blood

Regulation of respiration by H+ ion or pH

Suppose CO2 concentration increases, this will increase H+ ion concentration or

decrease pH. Increase in H+ ion concentration will stimulate the peripheral
chemoreceptors. The H+ ion of the blood cannot pass through the blood brain
barrier. So hydrogen ion of the blood cannot enter the brain, cannot stimulate the
central chemo receptors. CO2 diffuses into the brain, reacts with water forming
carbonic acid. This acid dissociates in to hydrogen and bicarbonate ions. This
hydrogen ion formed inside the brain will stimulate the central chemo receptors.
From the chemo receptors impulses are transmitted to respiratory centers. These
impulse stimulate the respiratory centers. Their activity will increase. This will
increase the rate and depth of respiration, increases alveolar ventilation. This
will increase CO2 expulsion from the body. This will decrease CO2 level in the
blood. This will inturn decrease hydrogen ion concentration in the blood or
increase the pH to the normal.

CO + H O HCOH+ + 22 22Central HCO3 Chemoreceptors + Medulla oblongata respiratory centres

+
Rate Depth of Respiration

Peripheral chemoreceptors carotid body

+ aortic body Alveolar ventilation

2CO expulsion
+
H/ pH
CO2 –

Fig. 4.26 Regulation of respiration by pH of blood

Regulation of respiration by O2 concentration of blood Suppose O2 content in

the blood decreases, it will stimulate peripheral chemoreceptors. From these
chemoreceptors impulses will be transmitted to the respiratory centres.These
impulses will stimulate the respiratory centers and increase their activities. This
will increase the rate and depth of respiration. It will increase alveolar
ventilation. It will increase O2 uptake by blood. This will increase the oxygen
content in the blood back to normal.
+
Medulla oblongata respiratory centres

Peripheral chemoreceptors carotid body aortic body

+
Rate Depth of respiration
Alveolar ventilation
O2 –
2O uptake
Fig. 4.27 Regulation of respiration by O2 Concentration Summary of chemical
regulation of respiration
Hypercapnea arterial Pco2
2CO in brain interstitial fluid
+
CO +H O–H CO –H +HCO 22 2 3 3 +

Increased H brain interstitial fluid

+ Medullary
respiratory centres
+

Central chemoreceptors Depth of Rate of respiration respiration

Peripheral chemoreceptors ++ Increased ventilation

Hypoxia Increased H+ arterial PO +
2 in blood 22PCO , PO and blood H level come to normal

Increased production of metabolic acids (Acidosis)

Fig. 4.28 Chemical regulation of respiration

HYPOXIA
It is a clinical condition in which there is a low O2 content in the blood or
inadequate supply of O2 to the tissues.

Depending upon the causes ‘hypoxia’ is classified into four types.

1. Hypoxic hypoxia
2. Anaemic hypoxia
3. Stagnant hypoxia or Hypo kinetic hypoxia
4. Histotoxic hypoxia or Cytotoxic hypoxia

Hypoxic Hypoxia
Causes:

1. Low O2 content in the atmospheric air This may be due to:

1. High altitude 2. Pollution
3. Depth of mines 4. Over crowding

2. Hypo ventilation
This may be due to:
1. Paralysis of respiratory muscles.
2. Block in the respiratory tract
3. Respiratory diseases like asthma, emphysema 4. Depression of respiratory
centers due to brain

tumors.
3. Reduction in the surface area of respiratory membrane
This may be due to: 1. Smoking
3. Injuries
2. Pollution 4. Infection

5. Presence of non-functional alveoli.

4. Increase in the thickness of the respiratory
membrane
This may be due to:
1. Infection
2. Inflamation
3. Oedema.
5. Cardiac disorders
1. Venous Arterial shunt
2. Congestive heart failure.
Hypoxic hypoxia
Special features:
Low arterial PO2
Low arterial O2 content
Low % saturation of Hb
Low arterio-venous PO2 difference
Utility of O2 therapy – 100%

Anaemic hypoxia
It is due to significant reduction in the H.b
concentration.
Or poisoning of Hb with carbon monoxide. Affinity of Hb towards carbon
monoxide is 250 times greater than its affinity towards O2.
Therefore even a small quantity of carbon monoxide can easily combine with
Hb.
So Hb is not available for the transportation of O2. Methemoglobinemia is
another cause where ferrous iron is oxidised to ferric form.

Special features of anemic hypoxia:

Arterial PO2 is normal
Percentage of saturation of Hb decreases. Arterial O2 content decreases.
Venous O2 content decreases.
Arterial-Venous PO2 difference almost normal. Utility of O2 therapy – 70%.

Stagnant hypoxia or hypokinetic hypoxia:

1. It is due to sluggish flow of blood.
2. It may be due to weakening of force of contraction

of the heart or due to increased resistance for the flow of blood.

3. Surgical shock, thrombosis, vasospasm.

4. Congestive cardiac failure.
Special features:
5. Arterial PO2 is normal.
6. Arterial O2 content is normal.
7. Percentage saturation of Hb is normal.
8. Blood stays longer in tissues.
9. So resting O2 uptake by tissues increases. 10. Accumulation of CO2.
11. Shifting of O2-Hb dissociation curve to the right. 12. Venous PO2 decreases
25 mm Hg.
13. Venous % satuartion of Hb decreases. 14. Venous O2 content decreases.
15. Arterio-Venous PO2 difference increases 95 – 25 = 70 mm Hg.

Histotoxic hypoxia or cytotoxic hypoxia

In this type of hypoxia the amount of O2 in the blood may be normal. But the
tissues cannot take any O2.
It is due to toxins like cyanide and sulphides.

These toxins block the uptake of O2 by the cells. Special features:

Arterial PO2 is normal.

No difference in O2 content in arterial and venous blood.

% of O2 saturation is normal.
Arterial-Venous PO2 difference decreases 95 – 90 = 5 mm Hg.
Effects of hypoxia on the body: (Summary)
1. It will reduce the O2 carrying capacity of the blood.
2. The hypoxic person easily get fatigued.
3. It leads to giddiness and fainting.
4. It decreases the muscular ability.
5. It increases the work load of the heart.
6. Severe brain hypoxia may lead to death. Effects of hypoxia on the body:
Immediate effect:
On Blood
Hypoxia stimulate kidneys – Produce REF – Forms

erythropoietin – stimulates bone marrow – increases rate of erythropoiesis-

increases RBC count.
On CVS

Stimulate peripheral chemoreceptors- vasomotor centre

– increases heart rate – increases force of contraction – increases cardiac output
and BP.

On prolonged period hypoxia decreases cardiac functions.

On Respiratory system
All types of hypoxia except anemic hypoxia

stimulate peripheral chemoreceptors – increases rate and depth of respiration –

increases CO2 washoutthis leads to alkalemia.

Later respiration becomes shallow and periodic. Finally rate and depth of
respiration decreases due to failure of respiratory centres.

On Digestive system
Symptoms like loss of appetite, nausea and vomitting.
Dryness of mouth leading to thirst.

On Renal system
Hypoxia stimulate juxtaglomerular apparatus to produce REF.
Kidney excretes alkaline urine.

On Nervous system
Drowsiness
Impaired judgment and confusions.
Depression or excitement.
Disorientation.
Change in mood and personality Delayed effects
Talkativeness and emotional outbursts. 1. Person becomes highly irritable.
Memory disturbances. 2. Depression, Loss of co-ordinations. 3. Weakness
If severe leads to comma and death. 4. Fatigue

TABLE 4.8
Comparison of different types of hypoxia
Sl. Type
No.
1. Hypoxic Hypoxia
Cause and Examples

At high altitude Mountain

sickness

Dissolved O2
Decrease
Arterial Blood Venous Blood
PO2
Decrease
O2 PO2 Content Decrease Decrease
O2
Content Decrease

Arterio venous Difference of O2

Normal
No change
2. Anemic Hypoxia Severe Anemia Normal Normal Decrease Decrease
Decrease Normal
No change
3. Stagnant

Hypoxia Left shock ventricular failure

Normal Normal Normal Decrease Decrease Increases Very high
4. Histotoxic

Hypoxia Cyanide poisoning

Normal Normal Normal Increase Increase Very very low decrease

Treatment of hypoxia
1. It depends upon the cause.
2. Try to remove the causative factors.
3. O2 therap.
(a) O2 therapy with normal atmospheric pressure useful only in hypoxic hypoxia
(b) Inhalation of Pure O2 at high barometric

pressure – hyperbaric O2 therapy useful in anemic and stagnant hypoxia.

Efficacy of O2 therapy in hypoxia

Hypoxic hypoxia – 100%
Anemic hypoxia – 70%
Stagnant hypoxia – 50%
Histotoxic hypoxia – 0%

CYANOSIS

It is a clinical condition manifested by bluish discoloration of skin and mucus

membrane. It is due to increase in the concentration of deoxy hemoglobin.
Cyanosis is manifested when the concentration of deoxy Hb in the blood reaches
to 5 gm/100 ml and above.

Types of Cyanosis There are two types of cyanosis: 1. General cyanosis and 2.
Local cyanosis.

Factors Effecting the Severity of Cyanosis

1. Amount of deoxy Hb present.

2. The speed of blood flow. Sluggish blood flow increases the severity of
cyanosis.
3. Colour and thickness of the skin. Cyanosis will be more evident in people
with fair and thin skin.
Causes of Cyanosis
Hypoxic hypoxia and stagnant hypoxia are the causes for cyanosis.

Asphyxia
It is a clinical condition in which hypoxia is coupled with hyper capnea (increase
in CO2). It is a condition in which there is low O2 level in the blood and
increased CO2 content in the blood.

Causes
1. Drowning 2. Hanging
3. Strangulation 4. Choking
Stages of asphyxia
There are 3 stages of asphyxia. Stage I, Stage II, Stage III
Stage I: It is characterised by exaggerated breathing attempt. Duration of this
stage is 1 minute. The cause is increase in CO2 level in the blood stimulating the
respiratory centers.
Stage II: It is characterised by convulsions, increase in blood pressure,
micturition. Duration is about 1 minute. Cause: This is due to the further
increase in CO2 concentration which stimulate the vaso motor centre, micturition
centre and the neurons controlling the skeletal muscles.
Stage III: It is characterised by gasping type of respiration (slow opening and
closing of mouth). It leads to respiratory failure and death. Duration is about 3
minutes. Cause
Severe acidosis or fall in pH and hypoxia of the brain. Treatment
If the patient is at the earlier stages of asphyxia it can be treated with artificial
respiration.

DYSBARISM/CAISSON’S DISEASE/DECOMPRESSION SICKNESS

It is a condition seen in divers. When the divers go into the depth of sea water,
the pressure surrounding the body increases tremendously. Under this high
pressure the nitrogen of the sea water will diffuse into the blood. Nitrogen will
get dissolved in the water of the blood and fats and lipids of the brain. Suppose
the diver comes out of the sea water all of a sudden the pressure surrounding the
body will fall drastically. Because of this the dissolved nitrogen start to appear in
gaseous form. Nitrogen bubbles will appear. This condition is known as air
thrombosis. It will block the free flow of blood in the minor blood vessels. This
will cause severe muscular pains—joint pains, chest pains. In addition to this it
may cause permanent irrepairable damage to the heart and brain. This may even
lead to death. This clinical complication is known as dysbarism. Caisson’s
disease or decompression sickness.

Depending upon the sites of bubble formation and size of bubbles, symptoms
vary.
(a) N2 bubbles in and around joints lead to severe pain called bends.
(b) Bubbles in pulmonary blood capillaries lead to
pulmonary oedema and dyspnea called as chokes. (c) Bubbles in coronary
arteries lead to myocardial
damage and result in myocardial infarction. (d) Bubbles in cerebral arteries lead
to ischemia and
stroke.

Prevention

1. The diver should be advised to come out of the sea water slowly and steadily.
2. Use of pressure tight jackets known as Caisson’s bag.

Treatment

1. Prompt recompression in a pressure chamber, followed by slow

decompression.
2. Hyperbaric oxygen therapy.
3. O2 helium mixture can be provided.

SCUBA
Self Contained Under water Breathing Apparatus. Used by deep water divers.

Contains: Tank with compressed air

Mixture of O2 and Helium.
Breathing is through a tube and mask with valve. Valve enables availability of
approximate amount of compressed air.

Expired air is released into water.

Effects of high barometric pressure

Groups
1. Deep sea divers
For every 10 mt. Pressure increases by 1 Atmosphere.
2. Caisson’s workers – Under water tunnel workers working inside high pressure
chambers.

Hazards of deep sea diving

1. Nitrogen Narcosis
2. High pressure nervous syndrome
3. Dysbarism/Caisson’s Disease Decompression Sickness.
4. Air Embolism.
Nitrogen narcosis

When exposed to high atmospheric pressure 4 atmospheric.

P N2 in the blood increases.
Produces Nitrogen Narcosis.

Symptoms :
Euphoria
Mental disturbances

Symptoms similar to alcoholic intoxication.

High pressure nervous syndrome

To avoid N2 narcosis O2+ Helium mixture is used because: 1. Narcotic effect of
helium is very less.
2. Resistance for the flow of helium is less. 3. Work of breathing is less.
4. Helium is less soluble in body flow.

But inhalation of helium at very deep diving produce— High pressure nervous
syndrome Anaesthic effect of helium produce tremors, drowsiness, in
coordination.

HIGH ALTITUDE PHYSIOLOGY—MOUNTAIN SICKNESS

As we ascend to high altitude the composition of air does not change, but
because a decrease in total barometric pressure PO2 of environmental air
decreases significantly. The consequent risk of developing hypoxia is seen in:

(a) Permanent residents of mountains.

(b) Mountaineers.
(c) Armed forces stationed at high altitude places. (d) Aviators.

TABLE 4.9
Barometric pressure, atmospheric air PO2and alveolar air PO2 at various altitudes

Altitude in Barometric Atmospheric Alveolar feet pressure air PO2 air PO2
mm of Hg mm of Hg mm of Hg

O 760 159 104

10,000 523 110 67
20,000 349 73 40
30,000 226 47 21
40,000 141 29 12

Critical altitude
At 10,000 feet some degree of hypoxia may develop, but body can acclimatize to
the oxygen lack. 18,000 feet is the highest altitude at which permanent
inhabitation is possible.

Above 20,000 feet hypoxia can endanger life unless O2 is supplied.

Mountain sickness
When a person is brought quickly or slowly to a high altitude (10,000 feet)
various symptoms develop. These symptoms are together called as high altitude
sickness or mountain sickness.
Two types:
1. Acute mountain sickness and
2. Chronic mountain sickness

1. Acute mountain sickness

If the person ascends quickly – the symptoms are quick and severe.

Symptoms: Headache, dizziness, loss of apetite, dyspnea, palpitation, nausea,

insomnia, periodic breathing, sweating, loss of memory.

2. Chronic mountain sickness (Monge’s disease) It develops in long term

residents of high altitude. Symptoms: Easy fatigability, polycythemia,

hypervolumia, pulmonary hypertension, right ventricular hypertrophy, exercise

intolerance, pulmonary oedema.

Acclimatisation to high altitude

When a person ascends to a high altitude and stays there for longer periods, he
slowly gets adapted to the new environment. The body mechanisms which
undergo changes to bring an adjustment with new environment are together
called as acclimatisation.

1. Changes in respiratory system: Low PO2 stimulates peripheral

chemoreceptors and in turn stimulate respiratory centers. This increases rate and
depth of respiration and alveolar ventilation. Hyperventilation leads to washing
off CO2, and alkalosis develops. This opposes the effect of hypoxia on rate and
depth of respiration. Kidney corrects the pH which once again makes the
respiratory centre to respond to PO2. Vital capacity, lung volumes and MVV
increases.

2. Kidney changes: Excretes HCO– ions. Excretes3

more alkaline urine. This brings back the pH of blood to lower level.

3. Changes in blood: Hypoxia stimulate kidney to secrete renal erythropoietic

factor. This factor produces erythropoietin. Erythropoietin stimulate bone
marrow and increases the rate of erythropoiesis. RBC count increases up to 8
million/cu.mm leading to polycythemia. Hb concentraction increases—20 g%.
PCV increases upto 60% O2 carrying capacity of blood increases. Blood volume
increases—20–30 %.

4. Changes in CVS
(a) Initially every thing increase like heart rate, cardiac output and blood
pressure. Hyper dynamic circulation results due to stimulation of VMC by
hypoxia.
(b) Tissue blood flow increases.
(c) Coronary blood flow increases.
(d) Cutaneous vasoconstriction.
(e) Increase in number of blood capillaries so that

intercapillary distance is decreased so that even with low PO2 adequate O2 can
be supplied to tissues.
After a long time cardio vascular changes become normal.
5. Change in O2– Hb dissociation curve:
Concentration of 2, 3 DPG inside RBC increases. This will shift the oxygen –
Hb dissociation curve to the right. So more oxygen is released from blood.

6. Tissue changes:
(a) Increase in capillary density.
(b) Increase in oxidative enzyme activity. (c) Increase in number of
mitochondria. (d) Increase in the amount of myoglobin. (e) Increase in
cytochrome oxidase.

Eupnoea: It means normal respiration with normal rate and depth of respiration.
Tachypnoea: It is a condition in which rate of respiration increases.
Bradypnoea: It is a condition in which rate of respiration decreases.
Polypnoea: Increase in rate of respiration, rapid shallow breathing.
Apneoa: It is a condition in which there is a temporary stopage of breathing. It
can be voluntary or otherwise.
Hyperventilation: It is a condition in which both rate and depth of respiration
increase leading to increased pulmonary ventilation.
Hypoventilation: It is a condition in which rate and depth of respiration
decreases leading to decreased air exchange between lungs and atmosphere.
Dyspnoea: It is a clinical condition in which patient becomes aware of his
breathing. It is a state of breathlessness and patient experiences difficulty in
breathing. Dyspnoea is of two types 1. Physiological dysponea 2. Pathological
dysponea.
1. Physiological dyspnoea usually results from very severe muscular exercise.
2. Pathological dyspnoea—cause include asthma, emphysema, paralysis of
respiratory muscles, block in the respiratory tract, metabolic acidosis, cardiac
dyspnoea due to heart failure.
Dyspnoeic point: It is the level of hyperventilation at which patient becomes
aware of breathing. Increase in pulmonary ventilation by 4 – 5 times.
Dyspnoeic index or pulmonary reserve: It is the percentage of breathing
reserve to maximum breathing capacity. Normal DI = 60 – 90%.
When DI is less than 60% dyspnoea is felt.
Dyspnoea in lying down position is known as orthopnoea.

ASTHMA

Asthma is a chronic, inflammatory disorder that produce sporadic narrowing of

air ways. Attacks are brought on by spasms of smooth muscles in the wall of the
small bronchi and bronchioles causing these airways to close partially or
completely, causing dyspnoea.

Cause
Two forms of bronchial asthma are recognised.

1. Extrinsic asthma developing in the childhood. It is the development of allergy

against air borne particles, pollen, dust, cigarette smoke, food etc., allergens.

2. Intrinsic asthma: Usually develops after 40 years. Cause is something more

than allergy.

Signs and Symptoms

1. Periods of coughing.
2. Difficulty in breathing especially expiration.
3. Wheezing.

4. During severe attacks it leads to asphyxia and acidosis.

5. Increased mucus secretions, which block the bronchi.

Treatment
1. Use of bronchodilators – B2 stimulants.
2. Anti inflammatory drugs – corticosteroids – commonly inhaled.

Pneumothorax

If air is present in the pleural cavity, the condition is called pneumothorax. This
causes loss of intrapleural negativity and collapse of the lungs. This affects
respiration very much. Tension pneumothorax develops when the hole through
which air enters behaves like a flap valve and the air which enters, cannot leave.
Tension of air inside increases with each breath as if air is pumped into the chest.

Hydrothorax

When fluid is present in excess in pleural cavity the condition is called

hydrothorax. It also leads to collapse of the lungs. 3. Morphine poisoning 4. Left
ventricular failure.

EMPHYSEMA
It is a disease where there is an increase in the size of air spaces distal to
terminal bronchi and destruction of their wall. The word meaning is “blown up”
or “full of air”.

Cause
1. Cigarette smoking
2. Industrial smoke and dust.

Patho physiology: Damage of the wall of alveoli. Loss of elasticity of lungs

therefore the alveoli do no deflate properly and remain distended. Air inside the
distended alveoli is not available for mixing, This leads to decrease in O2 and
increase in CO2.

Loss of elasticity also increases intrapleural pressure, it loses negativity and

reaches zero. This leads to narrowing of smaller bronchioles and then collapse—
chronic obstructive lung disease.

Signs and Symptoms

1. Hypoxia
2. Decrease in surface area for gaseous exchange.
3. Increases the size of chest cage “barrel chest”.

Periodic Breathing

Normally breathing is regular and uniform. But sometimes breathing becomes

irregular, and arrhythmic. It is known as periodic breathing. There are two
common types of periodic breathing:

1. Cheyne-Stoke’s breathing
2. Biot’s respiration
1. Cheyne-Stoke’s breathing: It is a type of periodic

breathing in which hyperventilation and apnoea are alternatively repeated.

Respiration shows alternate waxing and waning of tidal volume.

Causes: Physiological
1. Seen in prematurely born infants.
2. Seen at high altitude places before getting acclimatisation.
3. Deep sleep.
Pathological
1. Increased blood urea level: uremia
2. Increased intra-cranial pressure.
Apnea

Fig. 4.29 Cheyne-Stoke's breathing Biot’s respiration: It is a type

Hyperventilation
of periodic breathing in which

alternate eupnoea and apnoea are repeated.

Causes:
1. Case of meningitis.
2. Severe brain damage
3. Brain stem injuries.
Apnoea normal breathing
Fig. 4.30 Biot’s respiration
ARTIFICIAL RESPIRATION

Artificial respiration means adequate pulmonary ventilation is maintained in one

whose respiratory mechanism has failed but heart continuous to beat.

1. By maintaining the gaseous exchange the vitality of nerve centers as well as

that of heart is maintained. Also it helps to maintain circulation. After sometime
respiratory centre functions spontaneously.

2. During artificial respiration the alternate inflation and deflation of lung

reflexly stimulate the respiratory centre and helps them to take up spontaneous
rhythm.

Artificial respiration is done under two situations:

1. In surgical theatres where operation is usually pre arranged and various

mechanical devices are at the disposal of the anesthetist.

2. In emergency conditions when the physician or any person trained in “first

aid” finds that victim is unable to carry out voluntary ventilation. (a) Drowning
(b) Electrical shock

(c) Choking
(d) Gas poisoning
(e) Accidents
(f) Damage to brain stem
(g) Snake bite.

General instructions
1. Avoid delay.
2. Clean the mouth of the subject.
3. Continue artificial respiration till natural one starts.
4. When natural ones appear, adjust your passive movements to synchronise with
natural ones.
5. An inclination of body with head downwards is always desirable.
6. Care should be taken while turning the victim.
7. Do not insist on any particular procedure. Types of artificial respiration
1. Manual methods and
2. Mechanical methods.
Manual methods
1. Holger Neilson method or Arm Lift Back Pressure (ALBP) method.
2. Schafer’s method
3. Sylvester’s method
4. Mouth to mouth method
5. Eve’s rocking method.
Favours
inspiration
Favours expiration
Fig. 4.31 Holger-Nielson method for artificial respiration or ALBP method

Holger-Nielson method or Arm Lift Back Pressure (ALBP) method

It is a very popular method of artificial respiration rendered mainly to the
victims of drawning.
Principle: It is a manual manipulation of thorax and intrathoracic pressure
which will cause alternate expansion and compression of lungs.

Steps:
1. Lay down the patient in prone position.
2. Abduct the arms at the shoulders and flex the elbows.
3. Allow the forehead to rest on his hands which are placed one over the other.
4. Turn the head of the victim to one side, this prevents the obstruction of air
flow.
5. Kneel down on both the knees at the victims head.

6. Keep the head of the victim inbetween your two knees.

7. Place the spread out palms of both hands on the back below the scapula on
each side. See that your two thumbs touch each other at the midline.

8. Keep the arms straight and bend forward until both arms carry the weight of
your body vertically down along the arms. During this process thorax get
compressed, lungs also get compressed. This favours expulsion of air or
expiration.

9. This procedure takes about 3 seconds. 10. Relax the pressure on the back.
11. Lift your hands off the thorax.
12. Hold the patient’s elbows.
13. Turn and lift the elbows inwards horizontal to

vertical. During this procedure thoracic cavity gets expanded leading to decrease
in intrathoracic pressure. This result in inspiration.

14. This cycle is repeated at a rate of about 12 times per minute.

15. It may be continued till the victim regains spontaneous breathing.

Advantages of this method

1. In this method both inspiration and expiration are actively assisted.

2. Relatively good tidal volume can be obtained.
3. Easy to perform.
4. Because it is done in prone position, mucus, saliva, vomits comes out of the
mouth. They do not obstruct the air passage.

Disadvantages

In case of fractures of rib cage, dislocation of shoulder and other fractures of

upper limb this procedure is contra indicated.

Mouth to mouth respiration: Kiss of life:

1. Using thumb and index finger of (r) hand clamp his nostrils.
2. Take a deep breath.
3. Place your mouth over victims and exhale forcefully about 2 times the tidal
volume.
4. Repeat this at a rate of 12 per minute.

The artificial respiration by Schafer’s method Schafer’s method – Subject is

placed in prone position with a small pillow underneath the epigastrium and
upper abdomen. His head is turned to one side. Operator kneels by the side of
the subject and places his two hands on the two sides of lower part of the chest.
Operator leans forward and

puts his body weight forwards pressing on the loins of the subject. The intra-
abdominal pressure rises. The diaphragm is pushed up and the air is pushed out
of the lungs. Then the pressure is released (by coming back to the original
position). This causes lungs to come to the original position (as abdominal
pressure falls and diaphragm descends) and air is drawn in. This manoeuvre is
repeated 12 times per minute.
A
Pressing with the
B
Coming back to kneeling position
C

Fig. 4.32
Schafer’s method

Advantage of Schafer’s method

1. Subject is in prone position therefore mucus, saliva, vomits come out and do
not obstruct the respiratory passage.

Disadvantages of Schafer’s method

In this method first the air is pushed out of the lung to cause expiration so
expiration is active whereas inspiration is passively occurring when pressure on
the loins of the subject is relieved. Therefore respiration of the subject occurs in
expiratory reserve volume phase which is much less as compared to inspiratory
capacity. Moreover expiratory reserve volume is lesser in prone position. Also it
is less if the subject has long standing obstructive disease of the lung. Due to
these reasons, tidal volume obtained is much less.

Sylvester’s method of artificial respiration

Sylvester’s method: The subject is placed in supine position and the operator
kneels at the head of the subject. Arms of the subject are raised above his head
(this causes inspiration) and then folded over the chest compressing the chest
wall at the same time (this causes expiration). Such movements alternately
increase and decrease the size of the thoracic cage. The procedure is repeated at
a rate of 12/minute. Disadvantages of Sylvester’s method

1. The subject is in supine position and therefore tongue is likely to fall back and
obstruct the respiratory passage. To avoid this one assistant is asked to hold the
subject’s tongue.

2. Because of supine position mucus, saliva, vomits are likely to enter into the
respiratory passage.

Advantages of Sylvester’s method

1. In this method because inspiration and expiration both are active, tidal volume
attained is much more than that attained in Schafer’s method.

Mechanical Methods
Advantages
1. Can be continued indefinitely.

2. Can be used in conditions like morphine poisoning and respiratory muscle

paralysis.
3. More efficient.

Types:
1. Negative pressure method
2. Positive pressure method

Negative pressure method: By alternate compressing and relaxing of chest

wall.
Drinker’s method
Here patient is placed in air tight chamber with head outside. Pressure is exerted
and released through a side tube.

Bragg Paul’s method

A rubber bag is wrapped round the chest and air is
pumped in and out of the rubber bag.
Positive pressure methods

A. Continuous inflation method: Used in operation theatres.

B. Intermittent inflation method: Used in animals.

Resuscitation of newborns
1. Holding baby upside down and patting on back.
2. Alternatively patting child in cold and hot water.
3. Pumping CO2 through nostrils

Oxygen Therapy
Administration O2 to treat acute severe hypoxia. O2 therapy is ................
Hypoxic hypoxia ................ useful
Anemic hypoxia ................ useful
CO Poisoning ................ useful
Stagnant hypoxia ................ not much useful Histotoxic hypoxia ................ not
useful
Methods of treatment
1. Using oxygen tent
2. Using oxygen mask
3. Mechanical ventilator
4. Intranasal tube.
Hyperbaric oxygen therapy
100% pure oxygen inhalation at high barometric pressure.
Indication:
Anemic hypoxia – CO poisoning
Stagnant hypoxia
Histotoxic hypoxia.
Acute Oxygen toxicity
High PO2 effects the CNS.
Symptoms: Nausea, vomiting, dizziness, irritability
disorientation, disturbed vision convulsions.
Oxygen toxicity

100% pure oxygen treatment for more than 8 hours – produce.

Soar throat, sneezing, coughing, bronchoconstriction. More than 24 hours –

produce nausea, irritability, dizziness, disorientation, muscle twitching
convulsions, coma, death.
Mechanism of toxicity
1. Cerebral vasoconstriction—cerebral blood flow.
2. Accumulation of free radicals like super oxide anion, hydrogen peroxide.
They destroy enzymes.
Respiratory acidosis
Decrease in the pH of blood due to respiratory defect. Acute type
Bronchopnemonia Status asthmaticus Overdose of sedatives Overdose of
narcotics Compensation – Renal

Chronic type
Obstructive
Lung diseases
Pulmonary oedema Pulmonary fibrosis

Activation of carbonic anhydrase

Generation of more bicarbonate
Bicarbonate recovery by kidney
Return of HCO3/CO2 ratio to normal
pH raises to normal

Respiratory Alkalosis
Increase in pH of blood due to respiratory defect. Hyper ventilation, excess
washing out of CO2 e.g.,

high attitude.
Ratio of HCO3/CO2 increases
pH increases
Compensation by kidney
Increased excretion of bicarbonate
Ratio HCO3/CO2 returns to normal
pH comes down to normal.

Respiratory changes during exercise

During exercise oxygen consumption and CO2 production increases by about 25

times. The rspiratory system meets this challenge by various mechanisms.

For details refer chapter Physiology of Exercise.

Excretory System
Pierre-Simon Laplace 23-3-1749–5-3-1827 French Austronomer and
Mathematician
Known for Laplace
distribution, Laplace principle, Laplace law

Peter Agre
30-01-1949
American Medical Doctor and Molecular Biologist Famous for Aquaporins
Nobel Prize (2003)

Marcello Malpighi
10-03-1628–29-11-1694 Italian Doctor
Famous for Malphigian Capsules
Microscopic Anatomist
(156)

James D Hardy.
14.05-1918–19-02-2003 American Surgeon
Famous for First Lung Transplant
And First Heart Transplant

Joseph E Murray
1-04-1919
American Surgeon
Famous for First Human Kidney transplant
Nobel Prize (1990)

Bowman, Sir William 20-07-1816–29-03-1892 English Surgeon and Histologist

Famous for Bowman’s capsule of Nephron

Chapter
5
EXCRETORY SYSTEM

Kidney: Functional anatomy. Functions of kidney, types of nephrons.

Renal blood flow and its peculiarities.
Juxtaglomerular apparatus.
Mechanism of urine formation, Glomerular Filtration
– GFR.
Mechanism, factors affecting and measurement. Tubular reabsorption – Sodium,
water and glucose
– Tmg and renal threshold.
Tubular secretion of H+.
Mechanism of concentration of urine—Counter current mechanism.
Role of urea, action of ADH.
Micturition—Innervation of bladder, Cystometrogram.
Micturition reflex, abnormalities of micturition. Properties and composition of
normal urine. Abnormal constituents of urine.
Non excretory functions of kidney

Acid base balance.

Regulation of plasma osmalality, ECF volume.

Endocrine Functions. Hormones acting on kidney.

Renal Function Tests – Clearance tests.

Diuresis.
Applied Aspects – Renal failure, Artificial kidney, Nephrotic syndrome.
Skin and its Appendages – Structure and function.

EXCRETORY SYSTEM

Excretion: It is the process of elimination of three types of substances from the

body i.e.,
1. Waste products.

2. Toxic substances produced by microbial infection, food etc.

3. Substances which are in excess.

Excretory Organs
1. Kidneys
2. Lungs
3. Skin
4. Gastro intestinal tract (GIT)

Kidneys or Renal System

Kidneys are major excretory organs of the body. Functions of kidneys

1. Formation of urine which helps in removal of three groups of substances from

the body
(a) Toxic substances

(b) Waste products and

(c) Substances which are in excess.

2. Maintenance of Homeostasis: Kidneys play major role in maintenance of

constant internal environment.

Regulatory functions of kidneys: Non-excretory functions of kidneys

(a) Plays major role in water balance by controlling loss of water through urine.
(b) Regulation of blood volume.

(c) Regulation of extra cellular fluid volume (ECF). (d) Regulation of electrolyte
balance.
(e) Regulation of concentration of various substances
in blood
Blood urea level = 15–40 mg %.

(f) Regulation of erythropoiesis: In response to hypoxia kidneys secrete

erythropoietin and this stimulate bone marrow, this inturn increases RBC
production.

(g) Regulation of Blood pressure: When blood pressure comes down kidneys
produce renin, this produces – Angiotensin I and Angiotensin II – Renin –
Angiotensin – Aldosterone mechanism or axis helps in the regulation of blood
pressure by adjusting blood volume and total peripheral resistance.
“Composition of body fluids like blood is not decided by what we take through
the mouth but it is decided by what the kidneys retain”.
Renal hilus Cortex
Renal pyramid Kidney
Calyx minor
Ureter Calyx major
Renal pelvis

Body
urinary bladder trigone

Urethra Splincters Renal capsule

Fig. 5.1 Organisation of renal system Nephrons

Structural and functional unit of the kidneys. Approximately 2.2 million

nephrons are present in both kidneys (i.e., 1.1 million in each kidney).

Parts of nephron
1. Glomerulus — Renal corpuscles
2. Bowman’s capsule — Malphigian corpuscles.

Glomerulus is a cluster of capillaries made up of 50 parallel running capillaries

which fits into a cup like structure called as Bowman’s capsule. This portion of
nephron is concerned with filtration. Filtrating membrane is made up of
glomerulus and Bowman’s capsule which is highly porous.

3. Renal tubule
(a) Proximal convoluted tubule (b) Loop of Henle
Descending limb
Ascending limb
(c) Distal convoluted tubule (DCT) (d) Collecting duct.
Proximal convoluted tubule Collecting duct
Efferent arteriole Glomerulus
Peritubular

capillaries
Proximal convoluted tubule
Distal tubule

Prorimal tubule Cortex

Afferent arteriote Distal Bowman'stubule capsule
Renal corpuscle Renal

corpulse Collecting

duct
Peritubular capillary Outer
medulla
Loop of henle
Loop of henle

Nephron Vasa recta Inner

medulla

Loop of henle
Fig. 5.2 Cortical and juxtamedullary nephrons
Function of renal tubule is reabsorption, active secretion and formation of new
substances. TABLE 5.1
Functions of the components
Sl.No. Part Function 1. Glomerulus Water and dissolved substances are filtered
from the plasma. 2. Bowman’s capsule PCT
3. Descending limb of loop of Henle Ascending limb of loop of Henle 4. DCT
5. Collecting duct Glomerular filtrate is received.

1. Glucose, amino acids, lactic acid, uric acid, ascorbic acid, phosphate,
sulphate, potassium, calcium, sodium ions are reabsorbed by active transport.

2. 70% water is reabsorbed by osmosis.

3. Chloride ions are reabsorbed by electrochemical attraction.
4. Penicillin, histamine, hydrogen ions are actively secreted.

Water is reabsorbed by obligatory mechanism sodium, potassium and chloride

ions are reabsorbed by active transport.

1. Sodium ions are reabsorbed by active transport.

2. Water is reabsorbed in presence of ADH.
3. Hydrogen ions are actively secreted.

1. Potassium ion is secreted actively and by active electrochemical action.

2. Water is reabsorbed by the influence of ADH.

TABLE 5.2
Comparison of superficial and juxtamedullary nephrons
S.No. Features Superficial nephrons or
Cortical nephrons Juxtamedullary nephrons
1. Position Mostly situated in the cortex, a small portion of loop of henle dips
into outer medulla
2. Size of glomeruli Small 3. Length of loop of Henle Short 4. Efferent arteriole
give rise to Peritubular capillaries 5. Size of afferent and efferent arterioles
6. Nature of loop of Henle
7. Rate of filtration 8. Functions

9. Number Afferent arteriole is broader than efferent arteriole

Descending limb of loop of Henle contains a thin segment and ascending limb
contains a thick segment

Low
Mostly concerned with formation of urine

More, 85%
Mostly situated in the medulla, a small portion occupies in the cortex at the
border of medulla.

Large
Long
Vasa recta

Both afferent and efferent arterioles are of same size

Both ascending and descending limbs of loop of Henle contains thin segments.
High
Mostly concerned with concentration of urine.
Less, 15%

RENAL CIRCULATION
Renal artery
Segmental arteries
Interlobar arteries
Arcuate arteries
Interlobular arteries
Afferent arteries
Glomerular capillaries
Efferent arterioles
Peritubular capillaries or vasa recta
Interlobular veins
Arcuate veins
Interlobular veins
Segmental veins
Renal veins
Fig. 5.3 Blood supply to kidneys
Peculiarities of Renal Circulation

1. Renal blood flow is very high. Renal blood flow means amount of blood
flowing through the kidneys per minute. It is approximately 1200 – 1300
ml./min. This accounts for about 1/4th of cardiac output or 24% of cardiac
output. 420 ml of blood / 100 gm of tissue, much higher than other tissues for
example brain blood flow is only 50 ml / 100 gm. The mass of kidneys is less
than 1% of body weight. The renal blood flow is not proportionate to its weight
or mass. This high renal blood flow is meant for the removal of waste products
from blood.

2. There are two sets of capillary beds or networks in a single circulation.

Afferent arterioles give rise to the first set of capillaries in the form of
glomerular capillaries. This glomerulus give rise to efferent arterioles. These
efferent arterioles give rise to a second set of capillaries in the form of
peritubular capillaries or vasa recta. This type of circulation is called portal
circulation.

3. Blood pressure at the glomerular capillaries is high i.e., –60 mm of Hg. Blood
pressure in capillaries any where in the body is 15–30 mm of Hg (Normal). But
here it is 60 mm of Hg. This high capillary blood pressure of glomerulus is a
favouring force for filtration of fluid.
4. Blood flow to kidneys is not homogenous or uniform. There is no uniform
blood flow to different parts of the kidneys. Cortex is perfused more than the
medulla. Blood flow to the cortex is 90% and to medulla only 10%. Blood flow
to renal cortex 4.5 ml/g/min. outer medulla— 1.5 ml/g/min. Inner medulla — 0.2
ml/g/min.

5. Auto regulation of renal blood flow is very efficient.

6. Difference in oxygen content in arterial blood and venous blood in kidneys is
very small. Venous blood have high oxy haemoglobin content. Therefore it is
bright red in colour.
Auto regulation of renal blood flow
The kidney itself continuously regulates distribution of flow within the renal
tissue. This process is called autoregulation and is responsible for maintaining
intra-renal blood flow over a wide range of systemic perfusion pressures. All
tissues demonstrate this to some degree, but the kidney does it intrinsically with
great precision and even when denervated. The response of maintaining a
constant blood flow over a wide range of arterial pressure is one

manifestation of the phenomenon of autoregulation. Constant

manifestation of the phenomenon of autoregulation. Constant 220 mm Hg

(systolic blood pressure).

The mechanism behind autoregulation is felt to be via myogenic receptors that

regulate vasoconstriction. These sense blood pressure changes through stretch
receptors and respond accordingly through relaxation or constriction. The
autoregulatory system accomplishes this by maintaining renal tubular pressure.
The purpose of the autoregulation of renal blood flow is to maintain normal
glomerular filtration rate.

Juxtaglomerular Apparatus/Complex

It is a combination of specialised tubular and vascular cells located at the

vascular pole where the afferent and efferent arteriole enter and leave the
glomerulus. It is formed where each ascending limb of loop of Henle meets its
own glomerulus.
Thick ascending Afferent limb
arterioleMacula
Juxta densa glomerular
cells

Laci’s cells
Efferent arteriole

Mesengial cells
Bowman’s space
Proximal tubule

Fig. 5.4
Juxtaglomerular apparatus

It is composed of three types of cells

1. Juxtaglomerular cells
2. Macula Densa
3. Laci’s cells or Mesangial cells.

1. Juxtaglomerular cells or granular cells

These are modified smooth muscle cells situated at the afferent arteriole where it
enters into the Bowman’s capsule. These cells have well developed golgi
apparatus and endoplasmic reticulum, abundant mitochondria and ribosomes.
They synthesize, store and release the enzyme ‘renin’. The juxtaglomerular cells
are baroreceptors and respond to changes in the transmural pressure gradient
between afferent arteriole and the interstitium. They are innervated by
sympathetic nerves.

The vascular volume receptor monitor renal perfusion pressure and are
stimulated by hypovolumia or decreased renal perfusion pressure.

2. Macula Densa
These are specialised renal tubular epithelial cells located at the thick ascending
limb close to DCT in contact with glomerulus. These cells have prominent
nuclie and act as chemoreceptors. They are stimulated by decreased NaCl load
and thereby cause the release of renin.

3. Laci’s cells: Mesangial cells

They are contractile and play a role in regulation of GFR. Functions of
Juxtaglomerular Apparatus

(a) Autoregulation of renal blood flow and autoregulation of GFR. Decreased

renal blood flow will decrease GFR. Decreased GFR may slow down the flow
rate in loop of Henle, causing an increase in reabsorption of NaCl in ascending
limb of loop.

This reduces the concentration of NaCl at macula densa. Macula densa initiates
signals with two effects.
1. It decreases the resistance of afferent arteriole which increases glomerular
blood pressure and thereby increases GFR towards normal.
2. It increases renin release from juxtaglomerular cells. Renin produces
angiotensin I in blood which later get converted into angiotensin II. Angiotensin
II produces constriction of efferent arteriole, thereby increases the hydrostatic
pressure at glomerulus. This increases GFR.
The volume and the composition of the tubular fluid bathing the macula densa
have role in regulation of blood flow through the glomerulus and thus in
regulation of the GFR. It is called tubulo glomerular feed back.
Renal arteriolar pressure
Glomerular capillary pressure

GFR Tubuloglomerular feedback

Glomarulotubular balance

Solute reabsorption in proximal tubule

Fluid delivery to loop of henle
Solute reabsorption in thick ascending limb

Fig. 5.5
Tubulo-glomerular feedback

(b) Regulation of blood pressure by Renin – Angiotensin Aldolsterone

Mechanism: Whenever blood pressure decreases, Juxtaglomerular Apparatus
secrete renin. Renin produces angiotensin I and later it get converted into
angiotensin II. Angiotensin II is a vasoconstricter. It increases vasoconstriction,
total peripheral resistance and inturn increases BP. In addition to this,
angiotensin II stimulates adrenal cortex, increases the secretion of aldosterone.
Aldosterone increases sodium and water reabsorption at the kidneys. This
increases blood volume. This inturn increases BP.

(c) Regulation of erythropoiesis: In response to hypoxia Juxtaglomerular

Apparatus secrete renal erythropoietin in Blood. Erythropoietin stimulate bone
marrow and increases the rate of erythropoiesis.
(d) Controls water and salt retention in the body.
Mechanism of Urine Formation or Physiology of Urine Formation
Urine is formed by the kidneys.
Capillary endothelial cell Basement membrane Epithlial cell
Plasma Filtrate
Fenestra Slitpore
Fig. 5.6 Filtrating membrane Urine is formed by nephrons of kidneys. Urine is
formed from blood.

Stages of Urine Formation

1. Ultrafiltration or Glomerular filtration
2. Selective reabsorption
3. Tubular secretion
4. Formation of new substances.

Ultrafiltration: Two parts of nephrous are involved —Glomerular capillary and

the Bowman’s capsule. It is a cluster of capillaries. Filtrating membrane is made
up of wall of glomerular capillary and wall of Bowman’s Capsule. Filtrating
membrane is porous . Total surface area is 2 Sq.M. From the blood plasma is
filtered and not the cells.

Criteria for filtration: Both essential and non essential substances are filtered.
It depends on molecular size of the substance e.g., Glucose, urea, sodium,
potassium are also filtered.

Everything except plasma proteins are filtered. The filtrate is plasma minus
plasma proteins. Plasma proteins are not filtered because of the larger molecular
size. The fluid collected down is called as ultrafiltrate. The composition of ultra
filterate is everything except plasma proteins.

Quantitative aspect
Glomerular filtration rate (GFR): It is defined as total amount of ultra filtrate
formed by all the nephrons of both kidneys per minute.

Normal – approximately 125 ml/min. 180 litres/day, 2 ml/sec.

Factors affecting glomerular filtration rate (GFR)
Three forces acting at filtrating membrane are:
1. Blood pressure in glomerular capillaries to the extent of 60 mm of Hg.

2. Colloidal osmotic pressure 32 mm of Hg.

3. Hydrostatic pressure in Bowmann’s capsule 18 mm of Hg.
Only the first force favours filtration. Other two forces, second and third oppose
filtration. Effective or net filtration pressure
= BP – (Colloidal Osmotic pressure + Hydrostatic pressure) = 60 – (32 + 18)
= 10 mm of Hg
Filtration co-efficient (Kf): Kf is defined as total amount of ultrafiltrate formed
by all the nephrons of both kidneys per minute per 1 mm of Hg effective
filtration pressure.

Kf =
125 = 12.5 ml/min/mm of Hg
10
Plasma fraction: It is defined as percentage of plasma which is filtered as
ultrafiltrate per min.
Plasma Fraction = 125 × 100 = 19%650
Renal plasma flow = 1200 ×55 = 650 ml/min100

Any change in any of the 3 forces affect Glomerular Filtration Rate.

1. When BP rise high, GFR rise high.
2. When COP rise high, GFR decreases down provided other two factors are
constant.
(COP decreases down in starvation, under nutrition).
3. When hydrostatic pressure in Bowman’s Capusule increases GFR will
decrease.
4. Increase in blood volume increases GFR. 5. Increase in cardiac output
increases GFR. 6. Number of functional nephrons present. Decrease in the
number of functional nephrons will decrease GFR. Some nephrons loose
functions due to old age syndrome.
7. Sympathetic discharge will produce constriction of afferent arteriole and
lower GFR.

Significance of glomerular filteration rate

Glomerular filteration rate is taken as one of the kidney function test.
Determination of glomerular filteration rate

It is by inulin clearance test. Inulin is easily filtered. Not reabsorbed nor

secreted. Therefore, inulin clearance is equal to GFR.

TABLE 5.3 Amount of substances filtered and lost

Sl. No. Daily Glomerular filtrate Urine
1. Water 180,000 ml 1,800 ml 2. Sodium 500 ml 4 gm 3. Protein 20 gm 0.02 gm
4. Urea 60 gm 30 gm 5. Phosphate 5 gm 1 gm
Selective reabsorption
Three groups depending on reabsorption:

1. Substances which are completely or totally reabsorbed → 100%. e.g.,

Glucose, Amino acid.
2. Partially reabsorbed or partly reabsorbed. Anything absorbed above 0% and
below 99%.
e.g., Water 99% Sodium 99% K+ 90% Urea 50%.
3. Not at all reabsorbed. i.e., substance once filtered lost forever, e.g., Creatinine,
Creatinine phosphate, Insulin.

Mechanism of reabsorption
1. Active transport mechanism
It takes place against concentration or electro chemical gradient, e.g., Sodium.

2. Secondary active transport mechanism, e.g., Glucose.

3. Passive transport – Involves osmosis and diffusion. Energy is not required
e.g., Water.
Reabsorption of glucose and sodium
Glucose is a small molecule which is easily filtered from glomerulus. Body is
not affordable to loose glucose. Whatever glucose is filtered it is completely
reabsorbed by secondary active transport mechanism.
Most of reabsorption takes place in PCT. Mechanism is a secondary active
transport i.e., no energy is spent for transport but glucose and sodium ions are
reabsorbed by a common carrier protein. It has two binding sites. This type of
transport is called cotransport or symport. It carries glucose from lumen to
cell.
SGLT Luminal side Mass filtered
Na+ Glucose Brush border Mass excreted
Tubular cellSplay Mass reabsorbed Na+ K
+ Glucose Glut
Na+ Glucose Basolateral space
TmG
Theoretical threshold
Peritubular capillary Basement membrane
Basal side Plasma glucose concentration
Fig. 5.7
Glucose reabsorption

No glucose is lost in urine. Tubular load for glucose is defined as total amount
of glucose filtered by all the nephrons of both the kidneys per minute.
Tubular load for glucose = 125 mg/min.
Filtered l oad for glucose = 180 gm/day.
Transport maximum for glucose or Tubular

Maximum for glucose is defined as maximum amount of glucose that can be

reabsorbed by all the nephrons of both the kidneys per minute.

It is written as TMG/TMg/TmG Normal

= 320 mg/min in females, 375 mg/min in males. Average = 360 mg/min.
If tubular load for glucose becomes 400 mg, then it

will be excreted in urine i.e., 40 mg/min of glucose is lost. When tubular load is
less than Transport Maximum for Glucose no glucose will be lost in urine.

Glucose lost in urine = Tubular load of glucose

– Transport maximum for glucose.
Theoretically when tubular load of glucose reaches upto 350 mg/min., glucose is
not excreted in urine. Practically, when tubular load exceeds 225 mg/min. then
glucose is excreted in urine. This difference between theoretical and practical
values is explained by a phenomenon called splay. Reason is
1. Heterogenecity of nephrons i.e., all nephrons do not have same capacity of
reabsorption.

2. The kinetics of transport: When tubular load is high energy may not be
available and hence it is practically low.

Renal threshold for glucose

Concentration of glucose in blood above which it starts appearing in urine. It is
about 180 mg %.

Sodium reabsorption
Sodium is present in a large amount in blood. It is easily filtered off electrolyte.
About 99% of sodium is reabsorbed. There are three mechanisms:

1. Unidirection sodium transport → passive transport. Sodium moves because of

concentration gradient.
2. Sodium–Potassium exchange—takes place due to expenditure of metabolic
energy.
3. Chloride driven sodium transport: Chloride moves due to scarcity of negative
charged ions. 2/3rd of sodium reabsorbed in PCT.
+ CA CO + H O Na+ HCO + H3 22 Cl–
Lumen H+ Na+ Na+ Na+
– K+ K+2Cl Lumen
H
+ Na+ Na+
2Cl
– Na+ K+
+K +Na

Na+ + K+ Cl– K

Cl–Cl–K+K+ +Na + Na+ K

Peritubular capillary Peritubular capillary

Fig. 5.8 Reabsorption of sodium Urea reabsorption

Urea is an end product of protein metabolism. About 50 % of urea is reabsorbed

and 50 % is eliminated. Reabsorption takes place in PCT (small amount) In loop
of Henle urea goes to lumen. Most is reabsorbed in collecting duct where lot of
water is reabsorbed. Ammonia is more toxic which is converted to urea which is
less toxic.

Water reabsorption
About 180 litres of water is filtered per day, of that 99 % is reabsorbed
approximately 178.5 L/day. Only 1.5 Ltrs./day is lost i.e. 1500 ml/day. It can be
ajusted for water balance.

Two types of water reabsorption.

1. Obligatory
2. Facultative water reabsorption.

TABLE 5.4 Comparison between obligatory and facultative water

reabsorption
Sl.No. Features Obligatory Facultative 1. Occurrence 2/3rd at PCT and loop of
Henle DCT and collecting duct. 2. Depends upon Sodium reabsorption
Independent of sodium reabsorption. 3. ADH influence No influence Influenced
by ADH 4. Quantitatively 80% of total reabsorption 20% of total reabsorption.
5. Aldosterone influence Influenced by aldosterone No influence of aldosterone
Tubular secretion

Para amino hippuric acid, K+, Na+, urate are secreted into the lumen. Mostly
carrier mediated and active transport mechanism and takes place against
concentration gradient. This requires energy expenditure.
and electrogenic passive absorption of Cl− along with Na+.

3. Passive diffusion of large amounts of urea from the collecting duct into the
interstitium.

MECHANISM OF URINE CONCENTRATION

It is very important to concentrate the urine as much as possible, so that excess

solutes can be eliminated with as little loss of water from the body as possible.
The complex mechanism developed by the kidneys for concentrating the urine is
called Counter Current Mechanism.

The Counter Current Mechanism depends on a peculiar anatomical arrangement

of the loops of Henle and vasa recta in the renal medulla. The counter current
system is a system in which the inflow runs parallel to, counter to, and in close
proximity to the outflow for some distance. This occurs for both the loops of
Henle and the vasa recta in the renal medulla.

The first step in the concentration of urine or excretion of excess solutes with
minimum water is to create a very high osmotic pressure or hyper osmolarity of
medullary interstitial fluid. The osmolarity of interstitial fluid at the top of
medulla is about 300 milli osm. This osmalarity becomes progressively greater
at the deeper parts of medulla—it increases from 300 mosm/L at the cortex to
1200 milli osm/L. It is established by three different solute concentrating/
mechanisms.

1. Active transport of Na+ (K+.Cr) out of the thick portion of ascending limb or
loop of Henle into the interstitium. The sodium and the associated ions become
concentrated in this fluid and they are carried downward inner medulla by the
downward flow of blood in the vasa recta.
2. Smaller amounts of ions are also transported into the medullary interstitial
fluid from the collecting duct, mainly resulting from active transport of Na+

Counter Current Multiplier

The sodium and its associated ions are transported from thick ascending limb of
loop of Henle into the medullary interstitium. These ions immediately diffuse
into both the thin descending limb of loop of Henle and also into the descending
limb of vasa recta. NaCl is carried down by the fluid to the tip of the loop. As it
goes down much of sodium diffuses into the medullary interstitium, further
increasing its osmolality. This repetitive reabsorption of NaCl by the thick
ascending segment of loop of Henle along with the continual inflow of new
sodium chloride from PCT into the loop of Henle, is called Counter Current
Multiplier. Obviously, the reabsorbed sodium chloride keep adding to the newly
arriving sodium chloride. Thus “Multiplying” its concentration in the medullary
interstitium.

Counter current exchange mechanism in vasa recta The inner medullary

blood flow is very slight in quantity, amounting to only 1–2% of the total blood
flow of the kidney. Because of this very sluggish blood flow, removal of solutes
is minimised.

Vasa recta function as Counter Current Exchanger that also minimises the
washout of solutes from the medulla. This can be explained as follows. A
counter current fluid exchange mechanism is one in which fluid flow through a
long U- tube with the two arms of the U-lying in close proximity to each other,
so that fluid and solutes can exchange readily between the two arms. This
obviously also requires that each of the two arms of the U tube highly permeable
which is true for vasa recta. When the fluids and solutes in the two parallel
streams of flow can exchange rapidly, tremendous concentrations of solute can
be maintained at the tip of the loop with negligible washout of solutes.
HO
2
300 200
HO 2
HO 2
Cortex
320 300 300 300 300 300 400 400 320 400320 400 400 320NaCl 400 400 NaCl HO
2
Outer
medulla600 600 600 400
400 HONaClHO
22
600 600600 600
HO800 800 800 800800 2
800 800NaCl 800 NaCl HO
2& 800 HO
& UreaInner 2
1000 Urea Urea 1000HOmedulla
1000 1000 2 10001000 1000 1000 1000
1200 12001200 1200
Vasa Int. Loop of Int. Collecting recta fluid henle fluid duct
Fig. 5.9
Counter current mechanism

As blood flows down the descending limbs of the vasa recta, sodium chloride
and urea diffuse into the blood from the interstial fluid, while water diffuses
outward into the interstitium. These two effects cause the osmolal concentration
in the capillary blood rise progressively higher to a maximum concentration of
1200 mosm/L at the tips of the vasa recta.

Then as the blood flows up the ascending limb, the extreme diffusability of all
molecules through the capillary membrane allows almost all the extra sodium
chloride and urea to diffuse back out of the blood into the interstitial fluid, while
water diffuses back into the blood. Therefore by the time the blood finally leaves
the medulla, its osmolal concentration is only slightly greater than that of the
blood initially entered into vasa recta.

Role of ADH in concentration of urine

ADH acts at the collecting duct and increases its permeability. This increases the
reabsorption of water and increases the concentration of urine to 1200 mosm./L.
Hence urine becomes four times more concentrated than the ultra filtrate.

MICTURITION
Micturition is the physiological process of passing urine or emptying of urinary
bladder or voiding of urine.

Formation of urine is a continuous process. Micturition is a periodic process,

because storage facility is provided i.e., urinary bladder. Urinary bladder is one
in number. It is a muscular bag divided into two regions → body and trigone
(triangular region). A tapering portion is called as urethra or bladder neck which
is 3 cm long. Bladder is made up of smooth muscles called detrusor muscles
(involuntary). Ureters open into urinary bladder in oblique fashion to prevent
backflow through trigone region.

Bladder neck can be kept closed by sphincters (which is a circular band of

muscle fibres).

2 types = 1. Internal sphincter → thick band of smooth muscle fibres –

involuntary.
2. External sphincter → skeletal or striated muscles voluntary.

Parasympathetics S2 Inferior L1mesentericL2ganglion L3

S3 Sympathetic
S4 Hypogastric nerves
Pelvic nerves BladderS2
S3
Internal sphincter S4Somatic
pudendal nerves
External sphincter
Fig. 5.10 Innervation of the bladder. Dashed lines indicate sensory nerves
Innervation of Bladder (Nerve Supply)

Bladder is a visceral organ and hence innervated by autonomic and somatic

nervous system.
Autonomic Sympathetic nervous system Nervous System Parasympathetic
nervous system

Sympathetic: Preganglionic sympathetic fibres arise from lumbar segments of

spinal cord. They will end in ganglion on either side of spinal cord. Post
ganglionic fibres innervate the bladder, both blood vessels and muscles of
bladder

Parasympathetic: The preganglionic parasympathetic fibres arise from sacral

segments of spinal cord S2, S3, S4. The preganglionic fibres end in ganglion,
which is close to the organ. Post ganglionic fibres innervate muscles of bladder
and muscles of internal sphincter.

Somatic: Comes from sacral segments of spinal cord in the form of pudendal
nerve. It innervates only muscles of external sphincter.
TABLE 5.5
The nerve supply of urinary bladder
Sl.No. Function Nerve roots Peripheral nerves Structures Action innervated

1. Efferent fibres (a) Sympathatic T11 and T12 L1 and L2

(b) Parasympathetic
2. Afferent fibres (a) Sympathetic

(b) Parasympathetic Dorsal roots of L1 and L2 and lower thoracic segments

Sacral roots Hypogastric nerve Detrusor muscles

Pelvic nerve Detrusor muscles Sensation of pain

Sensation of, strectching Hypogastric nerve Detrusor muscles of Relaxation

constriction Fiiling of bladder

Contraction Emptying

Initiates Micturion reflex

3. Somatic afferent fibres

S2, S3 and S4 Pudendal nerve Urethra Sensation of

presence of
urine in urethra Relaxation of External
sphincter

4. Somatic efferent fibre

S3 and S4 Pudendal nerve External sphincter and distal urethra. Constriction
Voluntary control of micturition
Cystometrogram
S2, S3, S4 Nervi erigentes

(pelvic nerves) the bladder

internal sphincter Detrusor muscle of bladder
internal sphincter

There is a relationship between volume of urine collected inside the bladder and
the pressure developed.
Relaxation
-do

Cystometrogram is the graphical representation of relationship between the

volume of urine collected inside the bladder and the pressure developed.
40
30 ontraction
20 Micturition
contractionMicturition
10 Ib
Ia Basal cystometrogram
0
II
0 100 200 300 400 Sensation of fullness
Filling phase volume in ml
Fig. 5.11 Cystometrogram

Urodynamic studies These studies are done to obtain graphic recordings of

activity of bladder and urethral sphincters. The urodynamic studies relating to
the bladder function are

(a) Cystometry, (b) Radiographic-cine fluoroscopy.

Cystometry: It is a common urodynamic study. Cystometrogram is defined as

graphical representation of relationship between the volume of urine inside the
bladder and the pressure developed.

Objectives: Performed to assertain.

1. Accomodation: The ability of the bladder of accommodating large volumes
of urine without significant rise in the pressure.
2. Total bladder capacity: The bladder volume at which voiding cannot be
prevented.
3. Bladder contractions
(a) The ability of the bladder to contract when full.
(b) The ability of bladder to sustain a contraction till the bladder is empty. It is
indicated by the residual urine left in the bladder at the end of voiding.
(c) The ability of the bladder to respond to parasympatheric drugs.
4. Voluntary bladder control
The ability to initiate voiding even before filling is complete.
The ability to inhibit voiding in midstream.
5. Bladder sensations: i.e., The ability to perceive fullness of the bladder.

Types of Cystometry
(a) Voiding Cystometry (b) Static Cystometry. Voiding cystometry

It allows physiologic filling of the bladder with urine. Recording of the

intravesical pressure is started when the patient’s bladder is empty and continued
until the bladder is full. The patient is then asked to urinate. The disadvantage
with this method is that the bladder volume is inferred from the amount of urine
voided, with the assumption that there is not residual urine.

Static cystometry
In this, the bladder is progressively filled with water and the intravesical
pressure is recorded. This method permits accurate determination of the bladder
volume and pressure at each level of filling. The disadvantage with this method
is that the fluid is introduced at a more rapid rate than occurs naturally through
urine. That might affect the bladder function.
Normal cystometrogram
A normal cystometrogram shows three phases of filling:

Phase Ia: The initial phase of filling up to 50 to 100 ml is associated with a

slight increase in pressure to about 10 mm of H2O.

Phase Ib: The next phase of filling last till the bladder volume is about 300 to
400 ml. There is almost no change in pressure in this phase.This is because the
increase in the bladder volume keeps the pressure unchanged, which is in
accordance with the Laplace law.

Law status that distending pressure (P) in a spherical viscus is equal to twice the
wall tension (T) divided by the radius (R) i.e., P = 2T/R. Thus the tension
increases as the organ fills but so does the radius. So no apparent increase in
pressure.

Phase II: This phase denotes voiding contractions. Normally,the voiding

contractions raises the intravesical pressure by about 20–40 cm of water.

Micturition Reflex

Reflex is a sudden involuntary response to a sensory stimulus. When the volume

of urine inside the bladder reaches above 100–150 ml it produces mild urge for
micturition. When the volume of urine collected inside the bladder is about 350
ml. it produces significant distention of wall of bladder. This will stimulate the
stretch receptors present in the wall of bladder. Sensory impulses from stretch
receptors are transmitted to the spinal cord. The sacral segments of spinal cord
acts as lower center of micturition.

Higher center for micturition is in medulla oblongata, lower center is in S2, S3,
S4 segments of spinal cord. It sends efferent impulses through parasympathetic
fibres to the muscles of bladder. Detrusor muscles contract.

Internal sphincter muscle relaxes which opens the sphincter. Urine passes only if
simultaneously the external sphincter also opens. External sphincter is always
under inhibitory control of higher centers. Due to the voluntary involvement the
external sphincter is made to open. This leads to voiding of urine.

Pathology of Micturition
Abnormality in micturition

1. Continence, holding urine in bladder: Ability to exercise voluntary control.

2. Incontinence: When micturition occurs involuntarily i.e., It cannot be
controlled voluntarily.
3. Residual urine: It is the small amount of urine left inside the bladder even
after micturition. It is a type of urinary bladder dysfunction, contraction of
bladder is insufficient to empty the bladder completely.
4. Deafferentation: Atonic bladder
Causes: Injury to the afferent fibres due to (a) Tabes dorsal is – neurosyphilis.
(b) Crushing injuries of dorsal root of spinal nerve.
Inhibitory impulses
from higher centres
Afferent nerves Urinary bladder
Cut
ferent nerves

Somatic nerve Sacral segment of

spinal cord
Internal sphincter

External sphincter
5. Decentrallised bladder—or Autonomous bladder Denervation or Isolated
bladder.
Cause: Effect of injury to both afferent and efferent nerves-damage to cauda
equine Characteristics: Initially flassid neuropathic bladder with over flow
incontinence. Later detrusor develops denervation hypersensitivity. Due to
decreased bladder distensibility there is a steep rise in pressure. Overflow
incontinence.

6. Spastic neuropathic bladder: Isolation of the sacral micturition center from

the brain may occur with a suprasacral spinal cord injury. Immediately following
the injury, There is abolition of the micturition reflex resulting in a flaccid
neuropathic bladder with all its attendant features, e.g., overflow incontinence
etc.

In the absence of supraspinal inhibition, the micturition reflex is exaggerated,

resulting in the spastic neuropathic bladder. The micturition reflex is triggered
whenever the bladder gets distended, resulting in incontinence.

On return of reflex activity, depending on the level of the lesion following

features reseen:
(i) If below S2, S3, S4 are damaged, micturition is normal.

(ii) S2, S3, S4 are damaged autonomous bladder results. Here urine goes on
collecting upto a large volume, them some amount goes out and the rest is left
inside. This is also called overflow incontinence.

If above S2, S3, S4 automatic bladder develops and there is no control from
higher centre. There is reflex evacuation when some urine collects. This occurs
frequently and is also called hypersensitive bladder. The bladder gradually
becomes small and contracted.
Inhibitory impulses from higher centre
Cut Urinary bladder Afferent nerves
Fig. 5.12
Atonic bladder

Characteristics
Patient is unaware of filling of bladder. Bladder gets overfilled.
Dribling of urine-overflow in continence. Bladder wall is thin and distended-
flassid. Voluntary micturition is possible.
Sacral segment of spinal

cord
ferent nerves
Somatic nerve

Fig. 5.13 Automatic Bladder

Internal sphincter External sphincter

Urine
Water 1500 ml 96 %
Solids 60 gms 4%
Organic 60% 36 g
Inorganic 40% 24 g

Nitrogenous
Urea = 30 gm/day
Uric acid = 0.4–1.0 mg Creatinine = 1.0 mg Hippuric acid = 0.7 mg Indican = 0.01
Non nitrogenous
Citrate
Lactate
Ketone bodies (trace) Cations Anions

Na
+
–
Cl 15 g/day K
+ PO–– 4

Ca++ Cl–
Mg–++ HCO3 NH+ ––4 SO4

Fig. 5.14 Composition of normal urine Properties and Composition of Normal

Urine Properties → Physical

1. Volume = 1500 ml/day

Factors affecting volume are
(a) Water intake
(b) Water present in solid food
(c) Changes in weather – water is lost more in

urine during rainy season and winter season. In summer there is water loss as
sweat.
2. Colour = Pale yellow due to a pigment urochrome and urobilinogen.
3. pH = Slightly acidic, 6.5. When allowed to stand the urea present in urine
decomposes, forming ammonia, pH becomes alkaline.
4. Specific Gravity is 1001–1040 or 1010–1025.
5. Turbidity is clear and transparent, when allowed to stand becomes turbid.
6. Smell is aromatic, when allowed to stand becomes ammonia like.

Abnormal Constituents of Urine

These are substances which are not present in urine of a healthy person but may
be found in urine due to pathological reasons. Example glucose, proteins, blood,
pus, ketone bodies, micro organisms, bile pigment, bile salts.

I. Glucose: Glucose appears in urine in a clinical condition called glycosuria

Causes are diabetes mellitus due to insulin deficiency. Here blood glucose level
goes above 180 mg.% Amount of glucose filtered is above 225 mg./min. So
glucose appears in urine.
Another condition where glucose is seen in urine is renal glycosuria. Blood
glucose level is normal. Due to lack of kidney functioning glucose is not
reabsorbed completely. Nephrons do not reabsorb glucose completely due to lack
of carrier proteins.

II. Proteins: Proteins are reabsorbed by pinocytosis. Usually proteins are not
filtered because of macro molecular size. Due to infection or injury the filtrating
membrane becomes more porous. The infection may be renal nephritis. Hence
the proteins may be filtered. Albumin is more likely available for filtration
because it is a linear protein. Albumin can also be filtered because of its
cylindrical shape, charge etc.

The condition is called proteinurea. If albumin is in urine = Albuminuria

Hb in urine = Haematuria.

III. Blood: In urine is called haematuria. Bleeding in any part of kidneys due to
injury, infection, internal injury due to renal stones or due to trauma.

IV. Appearance of ketone bodies in significant quantity is called Ketosuria.

For example, Acetone and acetoacetic acid appear in urine. In diabetes mellitus
and starvation there is excess breakdown of fats and lipids, producing more
ketone bodies. When there is poor intake of carbohydrates, there will be excess
production of ketone bodies.
V. Appearance of bile pigments in urine is called bilirubinuria. Bilirubin is a
breakdown product of haemoglob in This causes Jaundice.

VI. Microorganism—Urinary tract infection leads to appearance of micro

organisms in urine. VIII. Pus—It is a result of some infection. Pus is a

collection of dead leukocytes.

TABLE 5.6
Bedside tests for detecting the abnormal constituents in urine
S.No. Substance Test Observations 1. Glucose Benedict’s

test
Green yellow, red or orange precipitate

2. Albumin/

Protein Heat and acetic acid test

Coagulation at top

3. Blood Bensedine

test
Bluish green colour

4. Ketone bodies Rothera’s test

Violet colour ring at the junction of two

5. Bile salts Hay’s test Sinking of sulphur powder.

6. Bile
pigments Fouchet’s test
Blue or brown colour.

ACID BASE REGULATION OR REGULATION OF pH

For convenience the hydrogen ion concentration of body fluid is expressed in pH

scale. pH is the negative logarithm of [H+] to the base 10 or pH = − log10 [H+].

For water [H+] is 10−7 mol/L, so pH of water = −Log 10 [10−7] = 7

A fluid having pH more than 7 is alkaline, less than 7 is acidic.
Normal pH of blood → 7.35 − 7.45.
Normal hydrogen ion concentration is 45 nanomoles/L to 35 nanomols/L or [H+]
= 10−7.4 meq/L.
Intracellular fluid pH is usually 0.5 less than plasma pH. When blood pH falls
below 7.35 it is called as acidosis when the pH rises above 7.45 it is called as
alkalosis.

1. Importance of Regulation of Blood pH

pH is very much important for life. Any change in pH leads to problems. Most
of the body proteins can function normally only at a particular pH range. So, the
enzymes, receptors, channels etc., all are affected by pH change. Serum [Ca2+] is
also dependent on pH and hence the various physiological functions of Ca2+. So,
various body functions including the metabolic reactions are very much affected
by a change in pH. That is why the body tries to maintain the pH rigidly though
the pH is continuously threatened by various processes.

It is estimated that the blood pH compatible to life is between 6.8–7.8.

The pH of plasma can be changed due to addition or removal of acids or alkalies.

Addition of acids
1. Volatile acids: The CO2 behaves as an acid— H2CO3 which is volatile.
Increased CO2 level in blood decreases the pH of blood.

2. Fixed acids: These are produced out of normal metabolism of protiens and
phospholipids. e.g., H2SO4, H2PO4.

3. Weak organic acids: These acids are added to the body in exercise—lactic
acid, oxaloacetic acid. Addition of alkalies: Alkalies are added to the body due
to consumption of alkalies in the form of medicine, fruits and vegetables.

Major mechanisms for the regulation of pH of blood.

1. Blood buffers
2. Respiratory mechanism
3. Renal mechanism.

Blood buffers
A buffer may be defined as a solution of a weak acid (HA) and its salt (BA) with
a strong base. The buffer resists the change in pH by the addition of acid or
alkali and the buffering capacity is dependent on the absolute concentration

of salt and acid. It should be borne in mind that the buffer cannot remove H+
ions from the body. It temporarily acts as a shock absorbant to reduce the free H+
ions. The H+ ions have to be ultimately eliminated by the renal mechanism.

The blood contain 3 buffer systems.

1. Bicarbonate buffer
2. Phosphate buffer
3. Protein buffer.

1. Bicarbonate buffer system

Sodium bicarbonate and carbonic acid (NaHCO3 – H2CO3)

is the most predominant buffer system of the extracellular fluid, particularly the
plasma. Carbonic acid dissociates into hydrogen and bicarbonate ions.

H
2
CO
3
H
+ + HCO−
3

When H+ ions are added (e.g., when H2SO4 produces free H+ ion and appears in
the blood), these H+ ions (from H2SO4) combine with the HCO-3 ions to produce
H2CO3 (the equation shifts to left). Now, H2CO3 being a very weak acid, it (=
the H2CO3) dissociates (into H+ and HCO−3) very poorly, so that, in the ultimate
analysis, only few H+ ions are added and the fall of pH of the solution (in which
the buffer is present) is either nil or marginal. Had there been no buffer, the fall
of pH would have been great.

Note, as H+ ions are being added, although the pH does not alter (or alters only
marginally), the HCO− ions begin to disappear. Thus, addition of H
+
3
causes loss of HCO− (= bicarbonate ions). The blood HCO-3 is alkali reserve3
or bicarbonate reserve. In short, as H+ are added to the blood, although the pH
does not fall, the concentration of blood bicarbonate, that is “bicarbonate
reserve”, falls. When the blood bicarbonate reserve becomes nil, then the buffer
loses its efficiency and now slight addition of H+ ions will cause a sharp fall of
blood pH.

The H2CO3 thus produced, breaks down to H2O and CO2, the CO2 is breathed
out.
On the other hand, in alkalosis, i.e.,where H+ ions are withdrawn from the blood,
the dissociation of H2CO3 of equation is accelerated, more H+ ions are generated
by the buffer system so that rise of pH is prevented. However, there is rise of
HCO− ions.3
Viewed in one way, carbonic acid-bicarbonate buffer system is the most
important buffer system in blood because the system is tied up with respiratory
system and renal system. The basic component HCO− is regulated by kidneys3
(metabolic component) and the acid component (H2CO3) is under respiratory
regulation. It is quickly adjustable.
When there is addition of excess H+ (acidosis), more H2CO3 is formed →
respiration is stimulated → CO2 of H2CO3 is exhaled and H2O excreted via
urine. Thus, the H+ are quickly removed.
The bicarbonate-carbonic acid buffer system accounts for 40–50% of total
buffering capacity.

2. Phosphate buffer system

Sodium dihydrogen phosphate and disodium hydrogen phosphate (NaH2PO4 –

Na2HPO4) constitute the phosphate buffer. It is mostly an intracellular buffer and
is of less importance in plasma due to its low concentration. With a pK of 6.8
(close to blood pH 7.4), the phosphate buffer would have been more effective,
had it been present in high concentration. It is estimated that the ratio of base to
acid for phosphate buffer is 4 compared to 20 for bicarbonate buffer.

3. Protein buffer system

The plasma proteins and haemoglobin together constitute the protein buffer
system of the blood. The buffering capacity of proteins is dependent on the pK
of ionisable groups of amino acids. The imidazole group of histidine (pK = 6.7)
is the most effective contributor of protein buffers. The plasma proteins account
for about 2% of the total buffering capacity of the plasma.

Haemoglobin of RBC is also an important buffer. It mainly buffers the fixed

acids, besides being involved in the transport of gases (O2 and CO2).

2. Respiratory Mechanism for pH Regulation

Respiratory system provides a rapid mechanism for the maintenance of acid-base

balance. This is achieved by regulating the concentration of carbonic acid
(H2CO3) in the blood i.e., the denominator in the bicarbonate buffer system.

The large volumes of CO2 produced by the cellular metabolic activity endanger
the acid-base equilibrium of the body. But in normal circumstances, all of this
CO2 is eliminated from the body in the expired air via the lungs, as summarised
below.

HCarbonic anhydrase CO2 + H2O2CO3 →

The rate of respiration (or the rate of removal of CO2) is controlled by a

respiratory centre, located in the medulla. This centre is highly sensitive to the
changes in the pH of blood. Any decrease in the blood pH causes
hyperventilation to expell out more carbondioxide, there by reduce H2CO3
concentration. Respiratory control of blood pH is rapid but only a short term
regulatory process.

3. Renal Mechanism for pH Regulation

The role of kidneys in the maintenance of acid-base balance of the body (blood
pH) is highly significant. The renal mechanism tries to provide a permanent
solution to the acidbase disturbances. This is in contrast to the temporary
buffering system and a short term respiratory mechanism, described above.

The kidneys regulate the blood pH by maintaining the alkali reserve, besides
excreting or reabsorbing the acidic or basic subtances, as the situation demands.

The renal regulation of pH occurs by the following mechanisms.

1. Excretion of H+ ions
2. Reabsorption of bicarbonate
3. Excretion of titratable acid
4. Excretion of ammonium ions.

1. Excretion of H+ ions
Kidney is the only route through which the H+ can be eliminated from the body.
H+ excretion occurs in the proximal convoluted tubules (renal tubular cells) and
is coupled with the regeneration of HCO−.3

Blood Renal tubular cell Tubular lumen

Na+ Na+ Na+

HCO
–HCO–+ 3 3+H

+–
H+B
HCO
23
HB
CA
CO + H O 22 Excreted

Fig. 5.15
Renal regulation of blood pH-Excretion of H+ ions. CA-Carbonic anhydrase. B-
base.

Carbonic anhydrase catalyses the production of carbonic acid (H2CO3) from

CO2 and H2O in the renal tubular cell. H2CO3 then dissociates to H+ and HCO−.
The H+ ions are3
secreted into the tubular lumen in exchange for Na+. The Na+ in association with
HCO-3 is reabsorbed into the blood. This is an effective mechanism to eliminate
acids (H+) from the body with a simultaneous generation of HCO−. The3 latter
adds up to the alkali reserve of the body. The H+ combines with a non-carbonate
base and is excreted in urine.

2. Reabsorption of bicarbonate
This mechanism is primarily responsible to conserve the blood HCO−, with a
simultaneous excretion of H+ ions. The3
normal urine is almost free from HCO−. This is explained3
as follows.
Plasma Tubular cell Tubular lumen

3. Excretion of titratable acid

Titratable acidity is a measure of acid excreted into urine

by the kidney. This can be estimated by titrating urine back to the normal pH of
blood (7.4). In quantitative terms, titratable acidity refers to the number of
milliliters of N/10 NaOH required to titrate 1 liter of urine to pH 7.4. Titratable
acidity reflects the H+ ions excreted into urine which resulted in a fall of pH
from 7.4 (that of blood). The excreted H+ ions are actually buffered in the urine
by phosphate buffer as depicted in the figure.

4. Excretion of ammonium ions

This is another mechanism to buffer H+ ions secreted into the tubular fluid. The
H+ ion combines with NH3 to form

ammonium ion (NH 4+). The renal tubular cells deamidate glutamine to
glutamate and NH3. This reaction is catalysed by the enzyme glutaminase. The
NH3, liberated in this reaction, diffuses into the tubular lumen where it combines
with H+ to form NH4+. Ammonium ions cannot diffuse back into tubular cells
and, therefore, are excreted into urine.

NH+ is a major urine acid. It is estimated that about4

half to two-thirds of body acid load is eliminated in the form of NH+ ions. This
mechanism becomes predominant4
particularly in acidosis.
Blood Renal tubular cell Tubular lumen Glutamine
Glutaminase NH3 Glutamate
NH3
Na+ Na+ Na+
HCO
– 3 HCO
–+ 3+ H
H+
HCO
23
CA
CO + H O 22 Excreted
Na+ Na+ Na HCO– (filtered)3
– HCO–+ H+
HCO 3 3+H

Fig. 5.17 Renal regulation of blood pH - Excretion of ammonium ions (CA -

Carbonic anhydrase).
HCO HCO23
23 CA CA
H O+CO CO + H O 22 22
Fig. 5.16 Reabsorption of bicarbonate from the tubular fluid — CA = Carbonic
anhydrase
Disturbances in Acid Base Balance
The acid base disorders are mainly classified into 4 types.

Acidosis Alkalosis (a) Metabolic acidosis (a) Metabolic alkalosis (b)

Respiratory acidosis (b) Respiratory alkalosis

Acidosis can develop due to accumulation of

(i) Either fixed acids leading to metabolic acidosis or

(ii) Volatile acids leading to respiratory acidosis.

Metabolic acidosis
Causes:
1. Accumulation of hydroxy butyric acid as in diabetic

ketoacidosis.
2. Renal acidosis—failure of kidneys to excrete H+.
3. Accumulation of lactic acid in severe muscular exercise.
4. Severe diarrhea—excess loss of bicarbonate ions through faeces.
Compensatory mechanisms
1. The blood buffers absorb the H+ and pH is not allowed to fall shortly but
bicarbonate concentration falls.
2. Pulmonary compensation—Acidosis causes stimulation of respiratory centres,
increases pulmonary ventilation, increases the expulsion of carbondioxide,
decreases the CO2 content in blood.
3. Kidneys secrete exess H+ ions.
4. Reabsorbs all bicarbonate ions.

Respiratory acidosis
It occurs due to retention of CO2 owing to decreased pulmonary ventilation seen
during severe asthma, emphysema.

Renal compensation: Kidneys reabsorb more bicarbonate ions so that

bicarbonate/Carbondioxide ratio returns to normal value; pH returns to normal.

Alkalosis: Metabolic alkalosis—causes

1. Severe vomiting—leading to exessive loss of HCl
2. Consumption of alkaline drugs, foods. Compensatory mechanisms
1. Buffers try to resist the change in pH.
2. Decrease in pulmonary ventilation rise of PCO2. This increases the
concentration of carbonic acid in blood → lowers the pH.
3. Renal secretion of H+ is severely curtailed.
4. Bicarbonate secretion by kidney is increased. Respiratory alkalosis
Cause: Removal of too much CO2 from blood due to hyperventilation as occurs
in high altitude. HCO−/CO2 ratio increases, so pH increases.3 Compensatory
mechanism
Kidney secretes more bicarbonate ions and less H+, so HCO−3/CO2 ratio returns
to normal, pH comes near to normal. TABLE 5.7 Laboratory findings of
disturbances in acid-base equillibrium

Sl.No. Bicarbonate

concentration in plasma Partial pressure of CO2

pH of Plasma

1. Acidosis
Metabolic acidosis (compensated) e.g., diabetic acidosis
Decreases due to loss of alkali reserve from blood. Decreases due to
hyperventilation. Decreases Marginal decreases since loss of more alkali reserve.

2. Respiratory acidosis (compensated)

e.g.,Advanced stage of emphysema
Increases since excess CO
2

is accumulated.
Increases since CO2 is accumulated.
Decreases since
accumulation of CO2.

3. Alkalosis
Metabolic alkalosis (compensated)
e.g.,severe vomiting Increases since increase in bicarbonate level in blood.
Increases since respiration becomes depressed,
hypoventilation.
Slight increase due to the accumulation of
bicarbonate.

4. Respiratory alkalosis (compensated)

e.g.,severe
hyperventilation

Normal values: Plasma pH

Decreases since excess washing of bicarbonates. Decreases since excess washing

of CO2.
Slight increase due to decrease in CO2.

= 7.35 – 7.43 Plasma bicarbonate = 22 – 26 m moles/L Arterial blood plasma

PCO2 = 40 mm of Hg Venous blood plasma PCO2 = 45 mm of Hg

Regulation of water balance

Balance of water between input and output is done by regulating the volume
ingested as drinks and by controlling the water loss as urine output. The volume
ingested is determined by thirst and urinary output via ADH from posterior
pituitary. In both these regulating mechanisms, plasma osmolality and plasma
volume are the prime mediators.

Role of Osmolality
The normal plasma osmolality is approximately 280

mosmol/L. Whenever there is increase in osmolality due to loss of watery part

(e.g., sweating in summer) the osmoreceptors of anterior hypothalamus stimulate
thirst. Appropriate amount of water is taken so that the osmolality reaches down
to the normal value.

Role of Plasma Volume

Whereever there is fall in blood volume there originates signal from volume
receptors (low pressure baroreceptors in atria, pulmonary vessels and high
pressure baroreceptors in aorta, carotid sinus) to increase ADH secretion.
Diminished volume also increases angiotensin II formation. Angiotensin II
stimulates thirst and increases Na+ reabsorption by kidneys via increased
aldosterone secretion and, at the same time, prevents loss of water by increased
ADH secretion.

Water balance is controlled by regulating water loss through urine and sweating
and controlling water in take by thirst mechanism. In all these mechanisms
hypothalamus plays a major role.
Acute dehydration
Plasma volume Plasma osmolality

Inhibition of baroreceptors Stimulation of osmoreceptors

ADH secretion Thirst

Plasma ADH Drinking
Water reabsorption by renal tubules
Water loss Water intake
Correction of dehydration

Fig. 5.18 Summary of mechanism of water balance

TABLE 5.8
Disturbances in salt and water balance
Sl.No. Disorders Plasma

volume Plasma osmolality Interstial fluid volume

ICF volume Kidney Clinical symptoms 1. Water exess overhydration Increases

Decreases

Hypoosmolar Increases Increases Increases Increases GFR

increases
2. Water depletion

Dehydration Headache water,

intoxication

Thirst
Decreases Increases
hyperosmolor Decreases Decreases

Cellular
dehydration GFR
decreases

3. Sodium exess Hypernatraemia Increases Increases

hyperosmolor from cells
Increases Decreases

Exosmosis GFR
increases Oedema

4. Sodium depletion Hyponatraemia Decreases Decreases

hypoosmolor Decreases

Increases
Endosmosis GFR
decreases Postural
Hypertension

TABLE 5.9
Hormones acting on the kidneys
Sl.No. Stimulus for secretion Action on kidneys 1. Vasopressin (ADH)

2. Aldosterone Decrease blood volume

Increase in plasma osmolarity

Decrease blood volume

Increase plasma K+
3. Angiotensin II Decrease blood volume

4. Atrial
Natriuretic Peptide (ANP)

5. PTH
Increased arterial B.P. Increase H2O permeability of cells in collecting ducts and
DCT. Increase in reabsorption of water

Increase Na+ reabsortion

Increase K+ secretion
Increase H+ secretion

Contraction of mesangial cells

Decrease GFR
Increase Na+ and HCO– reabsorption in PCT3

Decrease Na+ reabsorpiton

Increase GFR
Decrease plasma Ca2+ Increase Ca++ reabsorption Decrease PO-- - reabsorption4
Increase calcitriol production.

Endocrine functions of kidneys or hormones secreted by the kidneys

Kidneys show endocrine functions either by secreting hormones or by secreting
some chemicals which later produce hormones in the blood.

1. Calcitriol or 1, 25 Dihydroxycholecalciferol is formed by the conversion of

vitamin D under the influence of parathyroid hormone. Calcitriol secreted from
kidneys increases the calcium absorption from intestine.

2. Renin: Renin is a proteolytic enzyme secreted by the juxtaglomerular

apparatus of kidneys. Renin acts on alpha 2 globulin known as angiotensiogen
and forms angiotensin I. Angiotensin I later get converted to angiotensin II at the
lungs by the action of converting enzyme. Angiotensin II helps in the
regularation of blood pressure and for the regulation of secretion of aldosterone.

3. Erythropoietin: In response to hypoxia, kidneys release renal Enythropoietin.

Erythropoietin stimulates bone marrow and increases the rate of erythropoiesis.

KIDNEY FUNCTION TESTS OR RENAL FUNCTION TESTS

It is a series of tests conducted to assess the functioning of kidney. These tests
are based upon following:
1. Analysis of urine.
2. Analysis of blood.
3. Accessing the concentrating and diluting power of kidney.
4. Plasma clearance technique.
5. Radiological investigations.

1. Analysis of Urine
Physical analysis of urine

Volume: By estimation of volume of urine passed per day, we can detect

following condition like polyurea, oligurea, anuria.

Colour: Suppose the colour is red it indicates haematuria. If colour is yellow it

indicates jaundice.
pH: A significant reduction in the pH indicates acidurea or ketosurea or acidosis.
Specific gravity: This reflect the ability of kidneys for concentrating or diluting
the urine.
Microscopic analysis of urine: By this we can detect the presence of abnormal
constituents of urine like micro organisms, pus etc.
Chemical analysis of urine: Specific biochemical tests are conducted for
detecting the abnormal constituents of urine like blood, glucose, ketone bodies.

2. Analysis of Blood

The waste products from the blood are removed by the kidneys. The
concentration of waste products like urea, creatinine etc. in the blood will be
normal if the kidneys are functioning properly.

Example: Normal blood urea level is 15–40 mg/ 100 ml of blood.

A sample of blood is collected for estimation of urea level. Suppose blood urea
level is more than normal that indicates that kidneys are not functioning
properly.

3. Assessing the Diluting Power and

Concentrating Power of Kidneys
1. To access the diluting power of the kidneys Make the subject to drink two
litres of water. Collect the samples of urine. Usually within 5 hours of time about
70% of water should be lost through urine. Find out the specific gravity of urine
collected. If the specific gravity of urine is below 1.011 it indicates that the
kidneys have the power of dilution. If the specific gravity is above this value that
indicate that kidneys have lost the power of diluting.

2. To assess the concentrating power

Withhold water from the subject for 12 hours. After that collect samples of urine
and find out the specific gravity. If the specific gravity is above 1.022 it indicates
that kidneys have the ability for concentrating.

4. Plasma Clearance Technique

Plasma clearance means volume of plasma from which a particular substance is

completely cleared or cleaned per minute. The clearance of following substance
are usually done.

1. Inulin clearance.
2. Para amino hippuric acid clearance.
3. Urea clearance.
4. Mannitol clearance.

1. Inulin clearance
Inulin is a polysaccharide of fructose with a molecular weight

of 5200. Inulin is inert and non toxic. It is easily filtered from the glomerulus but
not reabsorbed and not secreted. About 5 ml of 5% inulin is injected intra
venously. Sample of urine is collected using a catheter or canula. The volume of
urine collected is measured. The concentration of inulin in the sample of urine
and plasma are estimated. Inulin clearance is calculated using the formula.

C in =
Uin × V
Pin
Where

C in = Clearance of inulin ml/min.

V = Volume of urine formed ml/min.
U in = Concentration inulin in urine
P in = Concentration of inulin in plasma Significance. Inulin clearance is used to
find out G.F.R. Normal inulin clearance is 125 ml/minute.

2. Para amino hippuric acid clearance—PAH clearance PAH is easily filtered

but not reabsorbed. It is also secreted. Normal PAH clearance is 585 ml/min.
PAH clearance is used to find out renal blood flow. PAH is not completely
cleared off from the plasma, only 90 % of PAH is cleared.

90% = 585 ml.

100% = ?
=585 × 100 = 650 ml90
This is equal to renal plasma flow per minute. Therefore renal blood flow
55% = 650 ml
Blood flow 100% = ?
=650×100 = 1200 ml/min55
5. Radiographic Investigations

This includes x-ray diagnosis and ultra sound scanning. The x-rays of kidney
may reveal gross damages, larger stones etc. Ultra sound scanning is a better
investigating tool.

DIURETICS
Diuretics are substances which increase urine output.
Types of Diuretics

1. Water diuretics
Drinking of lot of water or fluids will increase urine output.

2. Osmotic diuretics
Example: Urea, glucose, sucrose, mannitol etc. These substance are filtered from
the glomerulus and there is a limit for their reabsorption. Most of them are
excreted. Along with them, they carry a lot of water.

3. Loop diuretics
Example: Furesimide and ethacrynic acid. These drugs inhibit the reabsorption
of Na+ from the loop of Henle. So it indirectly decrease water reabsorption.
Therefore more water is lost through urine.

4. Drugs acting at DCT

Example: Chlorothiozide

This drug inhibits the reabsorption of Na+ at the DCT, so indirectly it inhibits the
reabsorption of water and more water is lost through urine.
5. Spiranolactone

This drug acts as an antogonist to aldosterone. Thereby it decreases the

reabsorption of Na+ and water. So more water is lost through urine.

Uses of Diuretics

1. It is used in the treatment of kidney stones. To increase urine output to flush

out renal stones.
2. It is used in the treatment of oedema.
3. It is used in the treatment of hypervolumic hypertension.

RENAL FAILURE AND ARTIFICIAL KIDNEY

The kidneys are not only essential excretory organs, but also play an important
role in circulatory dynamics. Renal failure is caused due to the improper
functioning of the kidneys. Renal failure is a type of renal disease. Almost any
condition that seriously interferes with kidney function can cause renal failure.
Two of the most common causes are:

1. Acute glomerulonephritis and

2. Acute damage and obstruction of the tubules.

Acute glomerulonephritis is caused by an abnormal immune reaction. This

include infection like streptococcal, sore throat, streptococcal tonsilitis etc. It is
not the infection that causes damage to the kidneys, instead, as antibodies
developed during the succeeding few weeks against streptococcal antigen,
antigen and antibody react with each other to form an insoluble immune
complex that becomes entrapped in the glomerulus, especially in the basement
membrane portion of the glomerulus. Once the immune complex has deposited
in the glomeruli all the cells of the glomerulus and large number of W.B.C. also
become entrapped in the glomeruli. Many of glomeruli become blocked entirely
by this inflammatory reaction, and those that are not blocked usually become
excessively permeable allowing both protein and R.B.C. to leak into the
glomerular filtrate.

In a few of the severest cases, either total or almost total renal shutdown occurs.
Another cause of renal shut down is tubular necrosis which means destruction of
epithelial cells in the tubules.
Damage to the distal tubule as a result of shock
Common causes of tubular necrosis are:

1. Various poisons that destroy the tubular epithelial cells and

2. Severe acute ischemia of the kidneys
– Mismatched, blood transfusion reaction also causes failure of renal system.
– A severe transfusion reaction normally results in haemolysis of large amount
of R.B.C. with release of haemoglobin into the plasma. The size of the
haemoglobin molecule is slightly less than that of the pores in the glomerular
membrane, so that much of the haemoglobin passes through the membrane into
the glomerular filtrate.
– The excess haemoglobin becomes so concentrated that it is likely to precipitate
in the nephron and in this way causes blockage.

Physiological effects of renal failure

Retention of salt and water.
Tissue become oedematous.
Hypertension.
Uremic retention of waste products ensues and acidosis develops.

The patient may die in complete renal shutdown within a week.

Large number of nephrons get destroyed. Urinary tract obstruction takes place
resulting from renal stones.

Effects of renal failure on the body fluids

The effect of renal failure on the body fluids depends on to a great extent on
water and food intake.

The most important effects are:

1. Generalised oedema.

2. Acidosis resulting from the failure of the kidneys to get rid the normal acidic
products from the body.

3. High concentration of nitrogenous compounds especially urea, creatinine and

uric acid, resulting from failure of body to excrete the metabolic end products of
proteins.

Effect of kidney shutdown on extracellular fluid constituents

High concentration of other urinary products including phenol, sulphates,
phosphates etc.

This condition is called uremia because of the high concentration of urea in the
body fluids. During renal failure the concentration of end products of protein
metabolism get accumulated. This leads to coma.

The acidosis is believed to be the principal factor responsible for the coma
because acidosis caused by other conditions such as severe diabetes mellitus also
causes coma. The patient may die if the pH falls to 6.8.

ARTIFICIAL KIDNEY

Kidney is the most important organ of the body required in the formation of
urine and excreting the other toxic and unnecessary substances from the body.
Radial artery
Bubble trap

Blood pump Diffusion waste

such as urea

Saphenous vein Dialysis membrane

Compressed 2CO and air

Fresh dialysis fluid Constant

temperature bath

Used dialysis
fluid

Fig. 5.19
Principle of dialysis

If a person looses his both kidneys due to any renal diseases, then the survival of
that person becomes a great challenge for the medical profession. To overcome
from this situation they performed many experiments for that in the form of
artificial kidney. However, it cannot perform the whole functions of a natural
kidney. So the patient has to be dependent upon several kinds of drugs.

Artificial kidney is being used for almost 40 years to treat patients with severe
renal failure. In certain types of renal failure such as mercury poisoning or
following circulatory shock, the artificial kidney is used simply to tide the
patient over for a few weeks until the renal damage heals so that kidneys can
resume function. The artificial kidneys has now being developed to the point that
thousand of persons with permanent renal failure or even total kidney removal
are being maintained in health for years at a time.

The basic principle of artificial kidney is to pass blood through very minute
blood channels bounded by a thin membrane. On the other side of the membrane
is a dialyzing fluid into which unwanted substances in blood pass by diffusing.

The above figure illustrates the components of one type of artificial kidney in
which blood flows continuously between two thin membranes of cellophane, on
the outside of the membrane i.e., the dialysing fluid. The cellophane is porous
enough to allow all constituents of the plasma except plasma proteins and from
dialysing fluid back to plasma.

The amount of the substance of the membrane that is transferred depends upon:
1. The permeability characteristics of the membrane.
2. The difference characteristics between the concentration on the two sides of
the membrane.
3. Molecular size.
4. The length of time that the blood and the fluid remain in contact with the
membrane. In the normal operation of the artificial kidney, blood flows
continuosly or intermittently back into vein.
The total amount of blood in the artificial kidney at any one time is usually less
than 500 milliliters. The rate of flow may be several hundred milliliters per
minute. The total diffusing surface is usually between 0.6 and 2.5 square meters.

To prevent coagulation of blood in the artificial kidney, a small amount of

heparin is infused into the blood as it enters the “Kidney”.

Effectiveness of the artificial kidney

The effectiveness of an artificial kidney is expressed in turn on the amount of
plasma that can be cleared of different substances each minute. Artificial kidney
can clear 100 to 225 milliliters of plasma/minute. The artificial kidney can
function about twice as rapidly as the two normal kidneys together.

Nephrotic syndrome is a condition that is often caused by any of a group of

diseases that damage the kidneys’ filtering system, the glomeruli. The structure
of the glomeruli prevents most protein from getting filtered through into the
urine. Normally, a person loses less than 150 mg of protein in the urine in a 24-
hour period. Nephrotic-range proteinuria, the urination of more than 3.5 grams
of protein during a 24-hour period, or 25 times the normal amount, is the
primary indicator of nephrotic syndrome.

Causes: There are a number of different disorders that can cause nephrotic
syndrome. Diabetes and, to a lesser extent, hypertension can cause diffuse
damage to the glomeruli and can ultimately lead to nephrotic syndrome.

Symptoms
1. Swelling of the ankles and legs.
2. Hypoalbuminemia (low level of albumin in the blood)
3. Extra fluid may also accumulate in the abdomen and around the face,
especially overnight. In children and young adults the ankles may be less
affected and the abdomen and face more affected.
4. Urine tests and blood samples are required to prove that nephrotic syndrome is
the cause.
The protein leakage can sometimes make the urine frothy. Some people feel
tired.

THE SKIN
Skin is the outermost protective covering of the body. With all its appendages it
is called integument.
Structure

The skin though not uniformly thick all over the body is divided into two main
layers to be present uniformly every where. These are: epidermis and dermis

Epidermis, the outer epidermal layer is composed of: (i) Stratum corneum
(ii) Stratum lucidum
(iii) Stratum granulosum
(iv) Stratum spinosum
(v) Stratum germinativum
Dermis, the inner dermal layer is composed of: (i) Papillary layer (ii) Reticular
layer.

The epidermis
It is formed of stratified squamous epithelium. Its layers, from superficial to
deep, are as follows:

Stratum corneum: It is composed of dead cells containing keratin but no

nuclei. The superficial cells are continuously shed off. This is thick particularly
in palm and sole, where the skin is thicker than any other part of the body.

Stratum lucidum: It looks homogenous and is composed of flattened cells

containing eleidin, the precursor of keratin. These cells degenerate to form the
stratum corneum. It is also present in thick skin.

Stratum granulosum: Cells of this layer contain granules (keratohyaline),

hence the name, formed of multiple layers of rhomboidal cells.

Stratum spinosum: It is formed of multiple layers of polyhedral cells. These are

also called prickle cells due to presence of spine like processes on their surface.
These cells move towards the surface forming the above layers one after another.
Langerhans cells are present in this layer.

Stratum germinativum: This is formed by the last layer of cells of the

epidermis. Cells are situated on a basement membrane in a single layer. Mitosis
is seen in this layer and the cells gradually move through the above layers
towards the surface. Melanocytes are seen in this layer of skin.
Sweat gland Stratum corneum

Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum germinativum
Dermal papilla
Neural receptor
Reticular tissue
Fat cells Sebaceous gland Errector pilorum Hair bulb Blood vessel

Fig. 5.20
Structure of skin

All these layers are not present everywhere, but in the skin of palm and sole.
There is no blood vessels in the epidermis.

The dermis
It is the true skin and can be divided into a superficial papillary layer and a
deeper reticular layer.

The papillary layer is compact and form papillae which project into the
epidermis. This papillae contain the blood vessels, nerve endings and
lymphatics.

The reticular layer is composed of reticular and elastic fibres impregnated with
fat and loose areolar tissue. It merges with the subcutaneous fatty layer and binds
the skin with deeper structures.

Different glands, hair follicles, some smooth muscles along with fibroblasts and
histiocytes are present in the dermis.

Colour of the Skin

It depends on many factors. Firstly, the amount of melanin formed in stratum

germinativum in the skin determines its black colour. Next is the amount of
blood flow, more flow means the skin is pink, less flow means pale. Thickness
of skin also determines its colour.

In abnormal cases carotene, reduced Hb, bilirubin etc. also change the colour of
the skin accordingly.
The Glands

Sweat glands are present all over the skin except in ear drum, lips, glans penis,
etc. There are two types. Merocrine and apocrine.

The merocrine glands are also called eccrine glands. These are simple tubular
glands but the tubes are very long and coiled. These glands are present in huge
number and produce the usual sweat. Cells from these glands may contribute to
regeneration of the skin in case of loss of epidermis.

The apocrine glands are present on mons pubis, axilla, areola of breasts etc.
(The ceruminous glands also belong to this variety, so also the mammary
glands). The secretion of these glands start after puberty and is responsible for
the characteristic body odour).

Sebaceous Glands

These are small pear shaped alveolar glands and open at the hair follicles or
directly to the skin surface. The sebum is formed in these glands. These glands
are responsible for acne, which is seen at puberty due to increased activity of
dehydroepiandrosterone (DHEA).
TABLE 5.10
Comparison between eccrine and apocrine sweat glands.

S.No.
1. Characteristic of secretion
2. Process of secretion
3. Begins to function
4. Localisation

Eccrine or Merocrine Thin, watery and clear Rapid, large quantity

Soon after birth
Generalised distribution

5. Innervation
6. Stimulus for secretion
7. Physiological importance Parasympathetic (Cholinergic) Heat as well as
emotion Major thermoregulatory role

Apocrine
Thick and turbid
Slow, minute quantity
Onset of puberty

Restricted localisation, axilla, pubic region and around the nipple.

Sympathetic (Adrenergic)
Emotion only

Minor thermoregulatory role., related to reproductive physiology

Functions of Skin Skin is a vital organ which is essential for life. A. Protective
function

(i) By covering the whole body, skin as a mechanical barrier which prevents the
internal organs from mechanical, thermal and chemical injuries.

(ii) The keratin present in the epidermis contains pre amino acid which actually
resists the action of dilute alkali and acid. (Amino acid acts as buffer).

(iii) Melanin pigment acts as a safe guard against the harmful effects of U.V.
rays.

B. Thermal regulation
(i) The skin is one of the major regulatory factor in body temperature regulation.
It regulates body temperature in association with vasomotor centre. Evaporation
of sweat helps in cooling the body.

Mechanism

During hot environment heat is eliminated from the body by secretion of sweat
and cutaneous vaso-dialatation (not throughout the body). In cold environment
the receptors are stimulated which sends impulses to the vasomotor centre. It
increases sympathetic discharge or stimulates the sympathetic system, results in
constriction of cutaneous blood vessels. So less blood flows to skin, less heat
reaches the skin, less heat is lost from the skin.

(ii) In case of animals, during cold climate horripillation (erection of hair) takes
place and heat elimination is reduced.

(iii) In cold environment: Fat contained in subcutaneous layer insulates the body
from heat loss. About 80 % of heat loss is by skin. The skin looses heat by
conduction, convection, radiation and evoporation.

C. Synthetic function
In the skin vitamin D3 is synthesised from 7-dehydrocholesterol using energy of
U.V. rays.

D. Sensory function (Acts as a sense organ) Skin contains a variety of sensory

receptors like touch receptor, pressure receptor, cold receptor, warm receptor etc.
Through these sensory receptors skin can perceive touch, pressure, cold, pain
sensations. It acts as an organ for general sensation.

E. Excretory functions
Skin excretes small amount of NaCl, urea and other waste products. In case of
renal failure skin excretes more urea.

F. Absorptive functions
Through the skin the fat soluble substances, several drugs (in form of ointments)
can be absorbed.
G. Storage functions
Skin stores water, glucose, amino acid and small amount of blood.
H. Secretory functions

(i) Secretion of sebaceous gland i.e., sebum helps in the water conservation, thus
prevents the dryness of skin.

(ii) Sweat plays important role in thermoregulation. (iii) Milk is secreted from
modified sweat glands called as the mammary glands.

I. Maintenance of water balance

According to need the amount of sweat secretion varies, this helps in water
balance.

J. Muscle attachment to the skin is known as erector pilli. Contraction of this

muscle helps in erection of hair (Horipillation) and helps in the regulation of
body temperature.
Digestive System

Ivan Petrovich Pavlov 14-09-1849–27-02-1936 Soviet Physiologist

Psychologist, Physician. Demonstrated Classical Conditioning
Nobel Prize (1904)

William Bayliss
2-5-1860–27-08-1924
British Physician
Famous for discovery of first Hormone Secretin and Peristalsis along with
Starling

Robert Milton Zollinger 4-9-1903–1992

American Surgeon
Known for Zollinger Ellison Syndrome
John Robin Warren
11-06-1937
Australian Pathologist Known for rediscovery of Helicobacter pylori—cause for
Gastric Ulcer
Nobel Prize (2005)
Barry Marshall
30-09-1951
Australian Microbiologist Known for
Helicobactor pylori
Nobel Prize (2005)

Rudolf Peter Heinrich Heidenhain

29-1-1834–13-10-1897 German Physiologist and Histologist
Famous for
Heidenhain’POUCH

A.V. Hill
1886-1997
British Physiologist Nobel Prize (1922)

(184)
Chapter
6DIGESTIVE SYSTEM
Introduction, functional anatomy of gastro intestinal tract and its innervations.

Secretory functions of GIT

Saliva—properties, composition.
Functions and regulation of secretion and applied aspects.
Stomach—functional anatomy.
Gastric juice—properties, composition, functions, mechanisms and regulation of
secretion.

Experimental evidences of gastric secretion (Sham feeding and Pavlov’s pouch).

Applied aspects—Gastritis, Peptic ulcer, ZollingerEllison Syndrome,

appendicitis.
Exocrine Pancreas-Pancreatic juice—properties, composition, functions and
regulation of secretion. Applied aspects- Pancreatitis.
Liver—Functions of liver.
Bile—composition, functions and regulation of secretion.
Functions of Gall bladder.
Enterohepatic circulation—Gall stones, Jaundice. Small intestine—Functional
anatomy—Succus entericus—properties, composition, functions and regulation
of secretion.
Functions of large intestine.
Applied aspects—Irritable bowel syndrome (IBS). Inflammatory bowel disease
(IBD).

Motor functions of GIT

Mastication, Deglutition—stages–Gastro Esophageal Reflux Disorder (GERD),
Achalasia.
Gastric emptying, Movements of stomach, Vomiting. Small intestine—
movements.
Large intestine—functions and movements, Defecation.
Applied aspects—Hirschpurng’s disease, Diarrhea, Constipation.
Digestion and absorption of Carbohydrates, Proteins and Lipids.
Applied aspects—Malabsoption syndrome, Steatorrhea.
Dietary fibres.

DIGESTIVE SYSTEM

The digestive system includes the alimentary canal or gastro intestinal tract
(GIT) and other related structures. The Gastro Intestinal Tract physiology deals
with transport, digestion, absorption of various nutrients and elimination of
various wastes. Food is essential for providing energy to the body,
Mouth Parotid gland
Pharynx
Oesophagus
Liver Stomach
Gall bladder
Duodenum Pancreas
Small intestine Large intestine
Vermiform appendix Rectum
Anus

Fig. 6.1
Digestive system

the body, as building block of body, for the repair of body tissues and for several
regulatory activities of life. The six major food groups are:

1. Carbohydrates
3. Fats and lipids
5. Minerals and 2. Proteins 4. Vitamins 6. Water.
Digestion is a process by which complex food materials

are broken down into simpler and smaller molecules so that it can be easily
absorbed and used up by the body. Digestion takes place in different parts of
digestive system by the process of physical breakdown and chemical breakdown
by the help of hydrolytic enzymes.

Primary mechanisms of the digestive system. Mechanism Ingestion

Digestion
Motility
Secretion
Absorption
Elimination or
Regretion
Assimilation
Description

Process of taking food into the mouth, starting on its journey through the
digestive tract.

A group of processes that break complex nutrients into simpler ones, Thus
facilitating their absorption; mechanical digestion, examples includes
mastication.
Movement by the muscular components of the digestive tube, examples include
peristalsis and segmentation.

Release of digestive juices (containing enzymes, acids, bases, mucus, Bile, or

other products that facilitate digestion); some digestive organs also secrete
endocrine hormones that regulate digestion or metabolism of nutrients.
Movement of digested nutrients through the gastro intestinal mucosa and into the
blood, internal environment.
Excretion of the residues of the digestive process (faeces) from the rectum.
through the anus; defecation. Utilisation of absorbed materials by the cells of the
body.

Functions of Digestive System

1. Receiving of food—Ingestion.

2. Digestion of food, digestion means making bigger and complex molecules

into smaller and simpler molecules.
3. Absorption of digested food stuff.
4. Elimination of undigested food materials. 5. Secretion of a group of juices like
saliva, gastric

juice, pancreatic juice, bile, and intestinal juice.

6. Take part in the regulation of water balance.
7. Take part in the regulation of electrolyte balance.
8. Excretion of microbial toxins, food toxins and heavy metal ions.
Digestive system comprises of mouth, pharynx, oesophages, stomach, small
intestine, large intestine and anus. These parts are collectively called as Gastro-
intestinal tract (GIT).
Accessory glands: Includes pancreas, liver and gall bladder.

Organisation and Structure of Gut

The Gastrointestinal tract or alimentary canal which extends from upper end of
oesophagus upto lower end of the anal canal forms a fibromuscular tube.

The wall shows following layers from inside to outside.

Lymph node
Serosa
Submucosal
plexus
Myenteric
plexus Gland in submucosa Villus
Lamina
propria

Muscularis mucosae Submu

cosa

Circular
muscle
Longtudinal muscle
Muscularis externa

Fig. 6.2 Cross section of the gastrointestinal system (a) Mucosa

(b) Sub Mucosa (loose areolar tissue layer) (c) Muscularis externa
(d) Serosa

The mucosa is further made up of, from inside to outside

(a) Epithelial lining
(b) Lamina propria (Connective tissue layer)
(c) Muscularris Mucosa (Smooth muscle layer) Muscularis externa—is made up
of
(a) inner circular muscle layer.
(b) outer longitudinal muscle layer.

Innervation of GIT
1. Intrinsic plexus 2. Extrinsic plexus.
Extrinsic innervation
1. Sympathetic and 2. Parasympathetic.
Intrinsic innervation
1. Myenteric plexus (Auerbach’s plexus).
2. Meissner’s plexus (Submucus plexus).
Sympathetic Fibres

Preganglionic fibres arise from lateral horn of spinal cord between T5 – L2

segments.
Postganglionic fibres arise from coeliac and mesenteric ganglia.

Effects of stimulation
1. Decreases gastric motility.
2. Decreases secretions of Gut.

Parasympathetic Fibres
Mouth and salivary glands—innervated by VII and IXth cranial nerves.

From oesophagus to upper part of large intestine— innervated by vagus.

Lower part of large intestine—innervated by parasympathetic fibres arising from
S2 – S4 segments of spinal cord and pass through pelvic nerve.

Effects of stimulation
1. Increases gastric motility.
2. Increases the secretions of gastro intestinal tract.

Myenteric Plexus
Located between the two muscle layers (circular and longitudinal) of muscularis
externa. It is mainly motor in function.
Function
It controls motility of gastro-intestinal tract.

Meissner’s Plexus
It is located in the submucus layer of GIT.
Functions

1. It controls contractions of blood vessels supplying GIT.

2. It controls secretion of gastro intestinal tract.

SALIVA

It is a digestive secretion of the mouth. It is secreted by the salivary glands.

There are numerous salivary glands. They are arranged in 3 group.

1. Sub mandibular/sub maxillary

2. Sub lingual
3. Parotid glands.

Salivary Glands

The salivary glands in humans are exocrine glands, glands with ducts that
produce saliva. They also secrete amylase, an enzyme that breaks down starch
into glucose. In human body there are mainly three types of salivary glands:

1. The parotid glands are a pair of glands located in the subcutaneous tissues of
the face overlying the mandibular ramus and anterior and inferior to the external
ear. The secretion produced by the parotid glands is serous in nature, and enters
the oral cavity through the Stensen’s duct after passing through the intercalated
ducts which are prominent in the gland. Despite being the largest pair of glands,
only approximately 25% of saliva is produced by the glands. Saliva contains a
mixture of enzymes like salivary amylase (ptyalin), lysozyme which disinfect
and kills bacteria and germs which enter the mouth.

2. The submandibular glands are a pair of glands located beneath the floor of the
mouth, superior to the digastric muscles. The secretion produced is a mixture of
both serous and mucous and enters the oral cavity via Wharton’s ducts.
Approximately 70% of saliva in the oral cavity is produced by the
submandibular glands, even though they are much smaller than the parotid
glands.
3. The sublingual glands are a pair of glands located beneath the floor of the
mouth anterior to the submandibular glands. The secretion produced is mainly
mucous in nature; however it is categorised as a mixed gland. Unlike the other
two major glands, the ductal system of the sublingual glands do not have striated
ducts, and exit from 8-20 excretory ducts. Approximately 5% of saliva entering
the oral cavity comes from these glands.

Properties
Volume: 1 – 1.5 litres per day or daily secretion. pH: Slightly acidic i.e., 6.5.
Specific gravity: 1.002 – 1.020.
Appearance: It is a colourless, odourless, tasteless watery fluid.
Stensen’s duct
Parotid gland
Wharton’s duct Subimaxillary gland
Sublingual gland Fig. 6.3 Location of salivary glands
Main duct
Inter lobar duct
Inter labular duct
Inter calated duct
Acinies
Fig. 6.4 Salivary glands—ducts and acini Composition:
Saliva
Water 99.5 % Solids 0.5 %
Organic constituents Inorganic constituents
Cations Anions + +– –– Na , K Cl , SO4 Mn
++, Ca++, Mg++ PO–– – , HCO
4 3
Fig. 6.5 Composition of saliva

Organic Constituents
1. Enzymes:
(a) Salivary amylase (Ptyalin)
(b) Lysozyme
(c) Lingual lipase.

2. Mucin
3. Blood group antigens
4. Traces of urea, uric acid etc.
5. IgA antibodies
6. Nerve growth factor.
Functions of Saliva
1. Digestive function

It takes part in the digestion of carbohydrate. The salivary amylase acts on boiled
starch and convert it into dextrin and maltose. Digestion of starch by the salivary
amylase in the mouth is negligible because food usually remains for a very short
duration in the mouth. But salivary amylase get mixed with food and enters the
stomach. Here it continues to act for some more time.

Boiled starch salivary amylase Dextrin and Maltose. Non digestive functions

2. Protective function
1. The enzyme lysozyme kills micro organisms. 2. The acidity of saliva also
destroys micro organisms. 3. The saliva flushes down micro organisms to the

stomach where micro organisms are destroyed by the hydrochloric acid of the
stomach.
Function of mucin
1. Mucin acts as a lubricating agent and helps in the easy passage of food.

Other functions
1. Saliva acts as a solvent for solid foods.
2. The solid food dissolves in saliva and stimulate the taste buds. It is responsible
for the sensation of taste.
3. Saliva keeps the mouth moist and helps in speech.
4. It plays a minor role in the regulation of water balance and body temperature
regulation.
5. It plays a minor role in the regulation of electrolyte balance.
6. It plays a major role in oral hygiene – cleansing action keeping mouth and
teeth clean.
7. Cools hot substances and dilutes irritant food substances.
Superior and inferior
salivatory nuclei

Parotid gland Glossopharyngeal

Otic ganglion
Medulla oblangata

Nucleus tractus
solitaries
Tongue Corda tympani [Branch of facial nerve)
Sublingual Submandibular
gland ganglion Submandibular
gland

Fig. 6.6 Nervous regulation of salivary secretion

Regulation of Secretion of Saliva

There are two types of salivary secretion:
1. Spontaneous secretion

About 5 % of saliva is continuously secreted. This helps to keep the mouth

moist.

2. Periodic secretion
This is controlled by salivary reflex. There are two types of salivary reflex.

(i) unconditioned reflex (ii) conditioned reflex

The presence of food in the mouth will stimulate the touch receptors and taste
receptors. From these receptors sensory impulses are transmitted to the medulla
oblongata. There are 2 groups of neurons controlling salivation.

1. Superior salivary nucleus

2. Inferior salivary nucleus.
This acts as centre for salivation. Efferent impulses from the center are
transmitted through the facial and glossopharyngeal nerves to the salivary
glands. Salivary glands get stimulated. This increases the secretion of saliva.
Conditioned reflex
Various factors like thought of food, time of food, sight of food etc initiates a
conditioned reflex for salivation. From the higher centers impulses are
transmitted to the salivary nucleus. This in turn increases salivation.
Xerostomia is also known as dry mouth is the feeling that there is not enough
saliva in the mouth. Everyone has a dry mouth once in a while—if they are
nervous, upset or under stress. But if you have a dry mouth all or most of the
time, it can be uncomfortable and can lead to serious health problems. It can also
be a sign of certain diseases and conditions.

There are several reasons why these salivary glands might not work right.

1. Side effects of some medicines: More than 400 medicines can cause the
salivary glands to make less saliva. Medicines for high blood pressure and
depression often cause dry mouth.

2. Disease: Some diseases affect the salivary glands. Sjögren’s Syndrome,

HIV/AIDS, diabetes, and Parkinson’s disease can all cause dry mouth.

3. Radiation therapy: The salivary glands can be damaged if they are exposed
to radiation during cancer treatment.

4. Chemotherapy: Drugs used to treat cancer can make saliva thicker, causing
the mouth to feel dry.
5. Nerve damage: Injury to the head or neck can damage the nerves that tell
salivary glands to make saliva.
Mumps or epidemic parotitis is a viral disease of the human species, caused by
the mumps virus. Prior to the development of vaccination and the introduction of
a vaccine, it was a common childhood disease worldwide. Painful swelling of
the salivary glands (mainly parotid gland), it is in 60–70% of infections and 95%
of patients with symptoms. Parotitis causes swelling and local pain, particularly
when chewing. This condition decreases the production mainly serous type of
saliva, which may lead to temporary loss of taste sensations.
Drooling is generally caused by excess production of saliva, inability to retain
saliva within the mouth, or problems with swallowing. In infants and toddlers it
may be normal. Sudden onset of drooling indicates poisoning, reaction to snake
or insect venom.

Gustatory salivary reflex: When food is ingested, large quantitave saliva are
poured into the mouth due to activation of afferent salivary centres. Receptors
are present in the taste buds and there are also tactile receptors in oral and
pharyngeal mucosa. Mere movement of tongue on palate and cheek produces
salivation due to stimulation of receptors.

Masticatory salivary reflex: This condition results due to increase in salivary

secretion. The contraction of teeth upper jaw muscles stimulate further salivary
gland releases extra quantity saliva to help you in digestion.

STOMACH
Stomach is the widest part of GIT intervening between oesophagus and
duodenum.

It is the J shaped muscular organ which serves as reservoir of food and also helps
in digestion of food.
The stomach is an organ of digestion. It has a saclike shape and is located
between the esophagus and the intestines. The human stomach is a muscular,
elastic, pearshaped bag, lying crosswise in the abdominal cavity beneath the
diaphragm. It changes size and shape according to its position of the body and
the amount of food inside. The stomach is about 12 inches (30.5 cm) long and is
6 inches (15.2 cm) wide at its widest point. The stomach’s capacity is about 1 qt
liters in an adult.
1. The stomach is a muscular organ of the digestive tract. It temporarily stores
and mixes food; it also secretes gastric juice into the lumen (the hollow inside
the stomach) and a hormone called gastrin.
2. The wall of the stomach is made up of four layers: the mucous, submucous,
muscular, and peritoneal layers.
Oesophagus Fundus
Pyloric sphincter

Body Angularis incisura Lower

oesophageal

sphincter
(Cardiac
sphincter)

Duodenum (Ist part) Pyloric antrum

Pyloric canal
Fig. 6.7
Functional anatomy of stomach

3. The mucous and submucous layers are made up of ridges called rugae. Within
the ridges are gastric glands made up of mucous cells, parietal cells, chief cells,
and G-cells.

4. Each of these cells secretes a chemical that aids in the process of digestion.
Position: It lies obliquely in the abdomen (upper and left part).
Shape: Empty - J shaped and vertical,
Distended - piriform,
Obese - horizontal.

External features: The stomach has two curvatures.

1. Greater curvature: It is convex and is separated from oesophagus by a notch

called cardiac notch. It is also called left border of stomach.

2. Lesser curvature: It is concave. It presents a notch at its lower end called

Angularis incisura. It is also called right border of stomach.

Two orifices
1. Cardiac orifice: Near the oesophageal end of stomach. It presents a
physiological sphincter called cardiac sphincter.

2. Pyloric orifice: Near the duodenal end of stomach. It presents an anatomical

sphincter called pyloric sphincter.

Two surfaces
1. Anterior surface: facing infront and upwards.
2. Posterior surface: facing backwards and down. Sub-division: It is sub divided
into three divisions:
1. Fundus: This part is filled with air even when the stomach is empty.
It lies above the horizontal line passing through cardiac notch.

2. Body: It lies between the horizontal line passing through cardiac orifice above
and a line extending from angularis incisura to greater curvature below.

3. Pyloric part: Part distal to the body . It is further sub divided into pyloric
antrum and pyloric canal.

Functions of Stomach
1. It acts as a reservoir of food.
2. Digestion of food.
3. Absorption of digested food.
4. Timely release of partly digested food.
5. Secretion of gastric juice.
6. Haemopoietic function - secretion of intrinsic factor.

GASTRIC JUICE

It is an important digestive secretion of the stomach. It is secreted by numerous

gastric glands present in the wall of the stomach.

Properties
1. Daily secretion — About 2 litres per day.
2. pH 1.2—highly acidic.
3. Specific gravity — 1.003 – 1.020.
4. Appearance — It is a colouress, odourless watery fluid.

Composition

out of the cell into extracellular fluid in exchange for chloride ions that enter cell
and later into the canaliculi.

7. The key player in acid secretion is a H+/K+ ATPase or proton pump located in
the canalicular membrane. This ATPase is magnesium-dependent, and not
inhibitable.

8. Parietal cells bear receptors for three stimulators of acid secretion, reflecting a
triumverate of neural, paracrine and endocrine control: Acetylcholine, Gastrin,
Histamine.
CO2
Gastric juice
Water 99.45% Solids 0.55% NaHCO3
Carbonic HCOCO + H O anhydrase
2322
+
HCO
– 3 Photon pumpH HCO3
HO
2
Organic Inorganic constituents constituents H
+ H+ +OH– HO 2 Na+ +

Hydrochloric acid
K
K+

Enzymes
1. Pepsinogen
2. Rennin Cations Anions

3. Gelatinase++ ––
4. Gastric lipaseH,K Cl , HCO 3 +++ ––, PO ––Na , Ca SO44Mucin Mg++, Mn++

Intrinsic factor (IF)

Fig. 6.8
Composition of gastric juice
Cl Cl– Cl– Cl–

Parietal cells or
Oxyntic cell

Mechanism of HCl Secretion

1. Parietal cells secrete HCl at a concentration of roughly 160 mM (equivalent to

a pH of 0.8).
2. The acid is secreted into large canaliculi, deep invaginations of the plasma
membrane which are continuous with the lumen of the stomach.
3. The hydrogen ion concentration in parietal cell secretions is roughly 3 million
fold higher than in blood, and chloride is secreted against both a concentration
and electric gradient. Thus, the ability of the partietal cell to secrete acid is
dependent on active transport.
4. There is active transport of chloride ions from cytoplasm of the cell into the
canaliculi.
5. Water is dissociated into H+ and OH- ions in the cell cytoplasm. H+ ions are
actively secreted into the canaliculi in exchange for potassium ions by H+/K+
ATPase.
6. The HCO3– formed after reactions of CO2 with hydroxyl ions of water. These
HCO– ions diffuse3

Nael

Fig. 6.9 Mechanism of secretion of hydrochloric acid

Functions of the Gastric Juice

1. Digestive functions
Digestion of proteins

Pepsinogen is activated by HCl to pepsin. Pepsin is an endo peptidase. It breaks

the proteins and gives peptones and polypeptides.

Pepsinogen
HCl Pepsin
→
Protein
Pepsin
→ Peptones + Polypeptides Rennin: It is a milk curdling enzyme. It converts
caseinogen to casein
CaseinogenRennin Casein →
This enzyme is important in infants whose major food is milk.
Gastric lipase: It is a weak enzyme. There is no significant digestion of fats in
stomach.

Functions of HCl
1. Activation of pepsinogen to pepsin.

2. It provides an optimum acidic pH for the action of pepsin.

3. Antimicrobial action: It destroys the micro organisms entering the stomach.

4. It helps in the absorption of iron.
5. It hydrolyses sucrose into glucose and fructose.

Sucrose
HCl Glucose + Fructose
→

Functions of mucin
1. It acts as a lubricating agent for food.

2. It gives a protective inner covering to the wall of the stomach. So it prevents

the digestion of the walls by the acids and enzymes.

Functions of intrinsic factor

1. It helps in the proper absorption of Vitamin B12 and folic acid. Therefore it is
indirectly essential for RBC maturation.

Other functions

1. Gastric juice helps in the excretion of heavy metal ions like Hg, Pb, Bi, Ar etc.
and bacterial toxins.
2. It takes part in the regulation of water balance.
3. It takes part in the regulation of electrolyte balance.

Regulation of Secretion of Gastric Juice Secretion of gastric juice take place in

three phases. 1. Cephalic phase
2. Gastric phase
3. Intestinal phase
Cephalic phase of gastric juice secretion is controlled by conditioned reflexes.
The sight of food, time of food, thought of food etc stimulate the higher centers
of the brain. This will increase the parasympathetic activities of vagus. Vagus
stimulates the gastric glands and increases the secretion of gastric juice. This
helps to keep the stomach prepared for future action.

Gastric phase of gastric juice secretion: It is the most important phase of

gastric juice secretion. It is controlled by a local hormone gastrin. When the food
enters the stomach it will stimulate the pyloric glands. These glands secrete the
hormone gastrin. Gastrin is absorbed by the blood and carried to the body of the
stomach. Gastrin stimulates the secretion of gastric juice.

Experimental evidences for gastric acid secretion: Heiden Hain’s Pouch

This experiment is a modified version of Pavlov’s pouch. In Pavlov’s pouch the

pouch portion of the stomach retained both sympathetic and Sham
parasympathetic innervations as well as blood flow. Only entry of food is
prevented. In Heidenhain’s pouch blood flow and sympathetic innervations is
retained. But by cutting the isthmus selectively parasympathetic innervations is
cut. This experiment is useful to demonstrate the influence of sympathetic
nervous system and hormones on the control of secretion of gastric juice.
Vagus nerve
Pavlov’s pouch
Gastric juice

Fig. 6.10 Pavlov’s pouch with intact nerve supply

Vagus nerve
Heiden hain pouch
Gastric juice
Fig. 6.11 Heiden-Hain’s pouch without parasympathetic innervation
Sham Feeding

In this experiment the oesophagus of the dog is cut transverly. The two ends of
oesophagus were brought and sutured. When the dog ate the food came out, but
not entered the stomachsham feeding or false feeding. A fistula was inserted to
stomach to collect the gastric juice. It was observed that whenever the dog ate, it
increased the secretion of gastric juice, even if the food never entered the
stomach. This demonstrated the cephalic phase of gastric juice secretion which
was stimulated by the psychological factors and the act of eating. The secretion
of gastric juice stopped after vagotomy. This proved the role of vagus in
controlling gastric juice secretion.
Food
Gastric juice

Fig. 6.12 Pavlov’s experiment. Sham feeding. As the dog ate, gastric juice
flowed from the stomach, even though the food did not enter the stomach.

Pavlov’s Pouch

In this experiment a small portion of stomach of dog separated out surgically

from the bulk of stomach. The mucus membrane was completely divided. A
small canula was fitted to the pouch to collect gastric juice. The nerve supply
both sympathetic and parasympathetic and blood flow to the pouch was intact.
Pavlov’s pouch was used to demonstrate the cephalic phase of gastric juice
secretion. This technique was also used to collect the pure sample of gastric juice
without contamination with food.

Intestinal phase of gastric juice secretion

When a small amount of food enters the small intestine it will stimulate the wall
of the intestine to secrete a hormone enterogastrin. Enterogastrin is absorbed by
the blood and carried to the stomach. It stimulates the secretion of gastric juice.
Cerebral cortex Sight of food trigers cephalic phase
Vagal antre in medulla
Medulla Vagus +

+ Sympathetic
Parasympathetic Sympahetic

Autonomic nerve
– Local nerve plexus
Blood vesels Gastrin
Spinal cord

Small intestine Gastric phase

1. Nervous mechanism by

local nerve
stimulation
2. Hormonal mainly
by gastrin

Intestinal phase
1. Local nervous secretary reflexes
2. Stimulation by enterogastrin

Fig. 6.13
Regulation of secretion of gastric juice

Gastritis: Gastritis is an inflammation of the stomach. Inflammation of the

stomach means that white blood cells move into the wall of the stomach as a
response to an injury to the stomach. Gastritis does not mean that there is
stomach ulcer or stomach cancer.
1. Gastritis can be caused by infection, irritation,

autoimmune disorders, or backflow of bile into the stomach.

2. Infections can be bacterial or viral.

3. Irritation can also be caused by medications. Some of the common
medications that may irritate your stomach are: aspirin or anti-inflammatory
drugs.

4. Other stomach irritants are: alcohol, chronic vomiting, excess gastric acid
secretion, and eating poisons.

Zollinger-Ellison syndrome is a rare disorder that causes tumors in the pancreas

and duodenum and ulcers in the stomach and duodenum.

The tumors secrete a hormone called gastrin that causes the stomach to produce
too much acid, which in turn causes stomach and duodenal ulcers (peptic ulcers).
The ulcers caused by Zollinger-Ellison syndrome are less responsive to
treatment than ordinary peptic ulcers. What causes people with Zollinger-Ellison
syndrome to develop tumors is unknown, but approximately 25 per cent of
Zollinger-Ellison syndrome cases are associated with a genetic disorder called
multiple endocrine neoplasia type 1, which is associated with additional
disorders. The symptoms of Zollinger-Ellison syndrome include signs of peptic
ulcers: gnawing, burning pain in the abdomen; diarrhea; nausea; vomiting;
fatigue; weakness; weight loss; and bleeding.

PEPTIC ULCERS

Peptic ulcer is a break in the continuity of mucosa of oesophagus, stomach,

duodenum or any other part of GIT which come into contact with gastric juice.
Occurrence
Incidence is about 10 % of population, common in the age group of 40 to 60
years, more common in males than females.

Major Causes—Etiology
1. Infection with Helicobacter pyloibacteria.

2. Intake of aspirin, cortisones, ACTH, caffeine, alcohol—they stimulate acid

production leading to ulcer.

3. Cause of duodenal peptic ulcer is increased vagal activity during fasting.

4. Emotional stress like anxiety, anger and frustration.
5. Hepatic and biliary disease.
6. Irregularity in food intake timings.
7. Genetic predisposition—Individuals with ‘O’ blood group and non secretors
are more prone for duodenal ulcer.

Types of Peptic Ulcers

1. Gastric ulcers
2. Duodenal ulcers
3. Stress ulcer—Stress erosion gastritis.

Gastric ulcer: Caused due to the break in the mucosal barrier. Usually found at
the junction of fundus and pylorus. Most of them occur at the lesser curvature.

Duodenal ulcer: It is a chronic break in the deuodenal mucosa, close to pylorus.

Stress ulcer: Stress–erosion gastritis.They occur after acute medical trauma, like
head injury, burn, respiratory failure, shock, drug ingestion like alcohol, aspirin,
lesions are usually multiple.

Complications and Clinical Manifestations

1. Pain: Patient experiences aching , burning cramp like pain. In case of gastric
ulcer food causes pain and vomiting releaves pain. In duodenal ulcer patient
have pain in empty stomach, eating releaves it.

2. Nausea, vomiting: Patient vomits undigested food.

3. Hemorrhage: Bleeding is the most serious complication.
4. Perforation: In patients with perforation the gastro duodenal contents, acids,
enzymes empty through
the anterior wall of stomach into peritoneal cavity. It produces sudden sharp pain
in the mid epigastric region, spreads to entire abdomen. It is a surgical
emergency.

5. Pyloric obstruction: It is manifested by vomiting. 6. Develops stress, life

style changes and discomfort.

Principles of Management of Ulcer

1. Neutralisation of gastric secretion.
2. Inhibition of gastric secretion.
3. Enhancement of mucosal resistance.

4. Relieve pain and promote ulcer healing neutralisation of acids can be achieved
by administering antacids.

5. Inhibition of acid secretion – by

H2 receptor blockers – like cimetidine.
H+–K+ pump blockers – Omeprazole.

6. Mucosol resistance is enhanced by – coating agents like sucralfate. Pain

allevating drugs. Further complications can be prevented by avoiding smoking,
spicy food, coffee, alcohol and taking food at regular time. Surgical management
– partial gastrotomy or vagotomy.

PANCREATIC JUICE

Pancreas is a mixed gland because it has got both exocrine function and
endocrine function. The exocrine function is the secretion of pancreatic juice.
Pancreatic juice is carried through the pancreatic duct and later by the common
bile duct. Pancreatic juice enters into the small intestine.
Gal bladder Common hepatic duct Common bile duct
Pancreatic duct
Islets of
langerhans
Sphincter of oddi
Duodenum Pancreas

Fig. 6.14
Location of pancreas
- Chymotrypsinogen
- Procarboxy peptidase
- Collagenase
- Elastase
- Nuclease

(a) DNAase
(b) RNAase
(b) Pancreatic amylase

(c) Pancreatic lipase

(d) Phospho lipase
2. Mucin
3. Trypsin inhibitor

Functions of Pancreatic Juice: Digestive Functions

Protein digestion
The inactive enzyme trypsinogen is activated by enterokinase in intestine. This
gives rise to trypsin. This trypsin further converts all other inactive enzymes to
active form.

Properties
1. Volume/daily secretion—1–2 litres/day.
2. pH—8 to 8.5.
3. Specific gravity—1.003–1.030.
4. Appearance—Colourless, odourless watery fluid.

Composition
Pancreatic juice
Trypsinogen
Enterokinase → Trypsin
Trypsinogen
Trypsin
→ Trypsin
Chymotrypsinogen
Trypsin
→ Chymotrypsin Trypsin is a powerful endopeptidase. It acts on proteins and
converts them to polypeptides and oligopeptides.
Protein Trypsin Poly peptides, oligopeptides. →
Procarboxypeptidase Trypsin Carboxypeptidase. →
Water 97.5% Solids 2.5%
Organic constituents Inorganic contituents
Cations Anions + + –Cl , HCO–
Na , K3
Mn++, Ca++ SO––, PO4 Mn++ 4
––
Fig. 6.15 Composition of pancreatic juice 1. Enzymes
(a) Proteolytic enzymes
- Trypsinogen
Collagenase digest collagen. Elastase digest elastin. DNA is digested by
DNAase, RNA is digested by RNAase. Carbohydrate digestion
Pancreatic amylase is a powerful enzyme. It digests starch into maltose and
isomaltose.
Starch
→
Pancreatic amylase Maltose + Isomaltose Lipid digestion: Pancreatic lipase digest
trigylcerides to monoglycerides, free fatty acids and glycerol.

Triglyceride Pancreatic Lipase Monoglycerides, →

Free fatty acids Glycerol

Trypsin inhibitor prevents the activation of trypsinogen to trypsin till pancreatic

juice reaches the small intestine.

Functions of mucin:
1. It acts as a lubricating agent for food.

2. It gives a protective inner covering to the wall of the pancreatic duct.

Other functions:

1. Pancreatic juice take part in the excretion of heavy metal ions like Pb, Bi, Ar,
Hg etc.
2. It takes part in the regulation of water balance.
3. It takes part in the regulation of electrolyte balance.
4. The bicarbonate ions helps in neutralising the acidic chyme entering the
intestine.

Regulation of Secretion of Pancreatic Juice Secretion of pancreatic juice takes

place in three phases. 1. Cephalic phase
2. Gastric phase and
3. Intestinal phase
Cephalic phase

Cephalic phase of pancreatic juice secretion is initiated by conditioned reflexes.

The site of food, time of food, thought of food etc. stimulates the higher centers
of the brain. This will in turn increase the para sympathetic activities of vagus.
Vagus stimulate the pancreas and increase its secretion.

Gastric phase
When food enters the stomach it will stimulate the secretion

of gastrin. Gastrin is absorbed and carried by the blood to the pancreas. It

stimulates the secretion of pancreatic juice.

Intestinal phase
When the food enters the small intestine, it will stimulate

the wall of the small intestine. The wall of the small intestine secrete two
important local hormones secretin and pancreozymin—cholecystokinin (PZ -
CCK).

Secretin is absorbed by the blood from the small intestine and carried to the
pancreas. Secretin stimulates the pancreas to secrete pancreatic juice rich in
electrolytes.

Pancreozymin is absorbed by the blood and carried to the pancreas.

Pancreozymin stimulate the pancreas to secrete more pancreatic juice rich in
enzymes.

Pancreatic function tests: Pancreas is a mixed gland because it has got both
exocrine function and endocrine function. The exocrine function is the secretion
of pancreatic juice. Following tests are used to assess the normal functions of
pancreas:
1. Blood tests:Blood tests can detect digestive

enzymes that leak out of the pancreas into the bloodstream when the pancreas is
inflamed; the two most common tests are the serum amylase test and the serum
lipase test.
2. Stool tests: Stool tests can detect steatorrhea, abnormal levels of fat in a stool
sample.
3. Imaging tests: Imaging tests provide information about the structure of the
pancreas, the ducts that drain the pancreas and the tissues surrounding the
pancreas.
4. Using fiber optic duodenoscope: The pictures of pancreas are taken to find
out any structural abnormalities.
Pancreatitis is inflammation of the pancreas. The pancreas is a large gland
behind the stomach and close to the duodenum—the first part of the small
intestine. Pancreatitis can be acute or chronic. Either form is serious and can lead
to complications. In severe cases, bleeding, infection, and permanent tissue
damage may occur. Acute pancreatitis is inflammation of the pancreas that
occurs suddenly and usually resolves in a few days with treatment. Acute
pancreatitis can be a life-threatening illness with severe complications.
Normally, digestive enzymes secreted by the pancreas do not become active until
they reach the small intestine. But when the pancreas is inflamed, the enzymes
inside it attack and damage the tissues that produce them.

LIVER
Liver is the largest gland of the body. It is considered as the metabolic factory of
the body.
Right
hepatic duct

Cystic duct
Left hepatic duct

Common bile duct Gall

bladder
Duct of santorini
Ampulla of Vater
Duodenum Pancreas

Fig. 6.16 Liver, gall bladder and pancrease

Functions of pancreatic juice: Digestive functions
Protein digestion

The inactive enzyme trypsinogen is activated by enterokinase in intestine. This

gives rise to trypsin. This trypsin further converts all other inactive enzymes to
active form.

Functions
1. Synthetic function

The important substances like plasma proteins, blood clotting factors, glycogen
etc. are synthesised in the liver.

2. Storage function
1. Carbohydrate is stored as glycogen
2. Storage of minerals like iron as ferritin
3. Storage of vitamins.

3. Metabolic functions of liver

Carbohydrate metabolism
(a) Liver is the site of gluconeogenesis.
(b) Glucose is converted to glycogen and stored. (c) Liver acts as a buffer organ
in the regulation of

blood glucose level.

When the blood glucose level increases, a portion of glucose is converted to

glycogen and stored in the liver. When the blood glucose level decreases,
glycogen is broken down to glucose and released to the blood.
Role of liver in protein metabolism

(a) Important proteins like plasma proteins and blood clotting factors are
synthesised in the liver.
(b) Liver is the site of following reactions: (i) Decarboxylation reaction
(ii) Transamination reaction
(iii) Synthesis of urea
(iv) Synthesis of non essential amino acids (v) Inter conversion of amino acids
and carbohydrates.

Role of liver in fat and lipid metabolism

(a) Liver is the site of Beta oxidation.
(b) It is the site of synthesis of lipids and lipoproteins. (c) It is the site of inter
conversion of carbohydrates

and fats.

4. Detoxification function or action

Liver is concerned with making toxic substances less toxic

or non-toxic. This action is called detoxification. Liver is the site of degradation

of hormones.
5. Haemopoietic function
During foetal life R.B.Cs are produced in the liver. 6. The old R.B.C’s are
destroyed in the liver.

7. Secretion of bile
Liver secretes an important digestive and excretory juice known as bile.

BILE
Bile is a digestive and excretory secretion of liver. Properties

Daily secretion : 1 Litre/day

pH : Liber bile 7.8 – 8.3, gall bladder bile 7.1 – 7.5.

Specific gravity : 1.003 – 1.030.

Appearance : Greenish yellow, watery fluid of bitter taste.

Composition
There are two forms of bile. Bile from liver, and bile from gall bladder.
Bile
Water 97.5% 2.5% Solids
Organic
Mucin
Bile saltsBilirubin

Bile pigments
Biliverdin
Cholesterol
Fatty acids
Phospholipids like
lecithin Inorganic

Cations Anions ++ –––Na , K Cl , SO4 Ca

++, Mg++ PO–– 4, Mn++ –HCO
3

Fig. 6.17 Composition of bile

TABLE 6.1
Comparison between liver bile and gall bladder bile
S.No. Characteristics Liver bile Gall bladder bile 1 Volume 500 ml/day 500
ml/day 2 Colour Light golden Black yellow

3 pH 8 to 8.6 7 to 7.6
4 Water content 97.6% 89%
5 Specific gravity 1010 to 1011 1026 to 1032
6 Total solid 2.4% 11% Organic substances (gm %)

7 Bile pigments 0.5 6 8 Bile salts 0.05 0.3 9 Fatty acids 0.2 1.2 10 Lecithin
0.05 0.4 11 Cholesterol 0.1 0.5 12 Mucin Absent Present

Inorganic substances (mEq/L)

13 Bicarbonate 30 10
14 Potassium512

2. Activates pancreatic lipase.

3. Bile salts help in the absorption of fat soluble vitamins like Vit. A, D, E and
K.
4. It also helps in the absorption of digested fatty acids.
5. Bile salt stimulates the liver to secrete more bile. This action is known as
choleretic action.
6. Bile salt stimulates the gall bladder and produces its contraction. This
increases the flow of bile into the small intestine. This action is known as
cholagogue action.
About 500 mg. of bile salts are secreted per day. Out of this about 95% of bile
salts are reabsorbed from the

intestine and carried back to the liver. Only 5% of bile salts are excreted through
faeces. The bile salts reabsorbed are reused. This part of the circulation is known
as entero hepatic circulation. This helps in the conservation of bile salts and
decreases the work load of liver. It also helps to increase the secretion and
emptying of bile.

Mucin
1. Mucin acts as a lubricating agent.
2. It gives a protective covering to the wall of the intestine and prevents its
destruction.
Other functions
1. The bicarbonate ions helps in neutralising the acidic chyme entering the small
intestine.
2. Bile helps in the excretion of bile pigments and excess cholesterol.
3. Bile helps in the excretion of heavy metal ions and

15 Chloride 100 10
toxic substances.
16 Sodium 150 135 Synthesis Liver
17 Calcium 422 Bile salt
Functions

1. Bile salts: The important bile salts are sodium taurocholate or sodium
glycocholate, potassium taurocholate or potassium glycocholate. Bile salts are
derived from bile acids. The important bile acids are
(a) Cholic acid and (b) Chenodeoxy cholic acid.

These bile acids are in turn derived from cholesterol. Functions: Bile salts act as
a detergent and help in the emulsification of fats. i.e., large fat drops are
fragmented into numerous small fat droplets. This serves as a physical digestion
and it increases the surface area exposed to enzyme action.
Portal vein Gall bladder
Storage

Superior mesentric vein

Reabsorption Common bile duct

Ileum
Bile salt s 5% lost in faces
Duodenum
Intestine

Fig. 6.18 Entero-hepatic circulation

Regulation of Secretion of Bile

To a small extent bile secretion is increased by vagal stimulation. But secretion
of bile is controlled by the hormone Pancreozymin-cholecystokinin (PZ-CCK).

When the partly digested food reaches the small intestine it will stimulate the
wall of the small intestine. This will secrete a local hormone (PZ – CCK). This
hormone is absorbed by the blood and carried to the liver and gall bladder. This
hormone increases the production of bile in the liver and it also produces the
contraction of gall bladder. Bile flows from the gall bladder and it relaxes the
sphincter of oddi. Therefore bile enters the small intestine.
Bile salts stimulate paranchymal secretion (choleretic action)
Liver

Secretin (increases secretion) Vagus (weak contraction of

gallbladder)

Gall bladder stores and concentrates bile

Cholecystokinin

[1. Gall bladder Contraction 2. Relaxation of

Duodenum sphincter of oddi 3. Emptying of bile]

Fig. 6.19 Regulation of secretion of bile Gall Bladder

It is a small muscular bag like structure on the passage of bile from liver to small
intestine. Gall bladder capacity to hold bile is 50–60 ml.

Functions
1. Storage of bile.
2. Concentration of bile—mucosa of gall bladder absorbs water and electrolytes
and concentrates the bile upto 10 times.
3. Controls the flow of bile to the small intestine whenever it is required.
4. Reduces the alkalinity of stored bile by reabsorption of bicarbonates.
5. Regulates equalisation of pressure in the biliary system.
6. It secretes mucin and makes the bile more thick. Development of hard
particles inside the gall bladder is known as gall stones. Gall stones are of two
types: 1. Cholesterol stones
2. Pigment stones—containing more of calcium bilirubinate. Cholesterol usually
get precipitated, once it forms a nidus, it gathers more cholesterol and grows.

Treatment

1. Surgical removal of gall bladder— Cholecystectomy.

2. Drugs which reduce cholesterol secretion by hepatic cells.

Small Intestine

Small intestine is the part of the alimentary canal from the pyloric sphincter to
the ileocecal sphincter. It is divided into duodenum, jejunum and ileum and is
extensively adapted for digestion and absorption due to presence of microvilli,
villi and circular folds of its wall which provide a large surface area.

It is continuous with the stomach at pyloric sphincter and leads into large
intestine at the ileocecal valve. The length of the small intestine is a little over 5
meters.

Chemical digestion of carbohydrate, protein and lipids mostly get completed in

the small intestine. The digested products of food are absorbedmostly from small
intestine .

The small intestine is divided into three parts which are continuous with each
other. The duodenum is about 25 cm long and curves around the head of the
pancreas. At its mid-point there is an opening common to the pancreatic duct and
common bileduct, guarded by the hepatopancreatic sphincter. The jejunum is the
middle part of the small intestine and is about 2 meters long. The ileum, or
terminal part, is about 3 meters long and ends at ileocecal valve which controls
the flow of materials from the ileum to caecum.

The character of mucosa of small intestine

The surface area of the small intestinal mucosa is greatly increased by permanent
circular folds, villi and microvilli.

The permanent circular folds, unlike the rugae of the stomach, are not smoothed
out when the small intestine is distended. They promote mixing of chyme as it
passes along.

The villi are tiny finger-like projections of the mucosa layer of the intestinal
lumen (about 0.5-1mm long). Their walls consist of columnar epithelial cells or
enterocytes.

Because of their presence, the total surface of the small intestinal mucosa is
tremendously increased. Numerous microvilli are seen on the surface of each
enterocyte and these microvilli, in turn, increase the surface area of each
enterocyte.
Microvilli

Composition
Succus entericus
Globlet cell 98.5% Water 1.5% Solids
Central lacteal Organic Inorganic
Erepsin
Venule
Arteride Villus
Fig. 6.20 Intestinal gland and villi The functions of small intestine
(a) Onward movement of its contents by peristaltic and segmental movements.

(b) The movement of small intestine helps to mix the chy me with panercatic
juice, bile and suceus enterieos.

(c) Secretion of intestinal juice.

(d) Completion of chemical digestion of carbohydrate, protein and fat.

(e) Protection against microbes that have survived the antimicrobial action of
HCI in the stomach by the solitary lymph follicles and aggregated lymph
follicles (Peyer’s patches).
(f) Secretion of local hormones like CCK, secretin motilin etc. These hormones
control various gastrointertiral functions.
(g) Absorption of nutrient materials.

INTESTINAL JUICE OR SUCCUS

ENTERICUS
It is a digestive secretion of small intestine.

Properties
Daily secretion : 2–3 Litres
p H : 7.5–8
Specific gravity : 1.002–1.020

Appearance : Colourless, odourless, watery fluid.

1. Mucin
2. –Enzymes
Dipeptidase
Tripeptidase Oligopeptidase Aminopeptidase Carboxypeptidase Mn

3. Carbohydrate digesting enzymes, Intestinal amylases

-Sucrase - Maltase - Isomaltase - Lactase
4. Lipid digesting enzymes : Intestinal lipase, cholesterol esterase, lecithinase
5. Enterokinase

Fig. 6.21 Composition of succus entericus

Cations Anions Ca++ Cl––, SO4++ ––Na , K PO4
Mg++ – ++ HCO3
––
Functions
1. Digestive function
The intestinal juice contains enzymes meant for completing the digestion of
food.
Protein digestion:

The proteolytic enzymes like dipeptidase, tripeptidase, amino-peptidase, carboxy

peptidase etc. act upon dipeptide, tripeptide etc. and convert them into amino
acids.

Dipeptide

→
Dipeptidase
aminoacids.

Carbohydrate digestion
Disaccharides are acted upon by the disaccharidases
and give rise to monosaccharides.

Lactose Sucrose Maltose

Isomaltose Lipid digestion

Lactase
→ Sucrase
→ Maltase
→ Isomaltase →

Glucose + Galactose Glucose + Fructose Glucose + Glucose Glucose + Glucose

Intestinal lipase breaks triglycerides into monoglycerides, free fatty acids, and
glycerol. Cholesterol esterase converts cholesterol esters into free cholesterol.

2. It takes part in the regulation of electrolyte balance. 3. It takes part in water

balance.

4. Enterokinase is an activator. It converts trypsinogen into trypsin.

5. Mucin
(a) It acts as a lubricating agent for food. (b) It protects the wall of the intestine
from actions of enzymes.
6. Bicarbonate ions help in neutralising the acidic food entering the small
intestine.
Regulation of Secretion: Secretion of intestinal juice is controlled by autonomic
nervous system, by local nervous reflexes and by hormones. Increase in
parasympathetic activities will increase the secretion of intestinal juice.
Sympathetic stimulation will decrease the secretion of intestinal juice. When the
food is inside the intestine it will generate a local reflex mechanism which will
increase the production of intestinal juice.

Hormones: Enterocrinin

The presence of food inside the small intestine gives a physical as well as
chemical stimulus. Because of this the wall of intestine secrete a local hormone
enterocrinin. This hormone stimulates the glands of the intestine and increases
the production of intestinal juice.

Large Intestine
Transverse colon
Ascending
colon Descending colon ileum
Cecum
Sigmoid Appendix
colon Rectum
Fig. 6.22 Large intestine

Functions of large intestine

1. Absorption of water.
2. Absorption of Na+ K+ Ca++.
3. Mucus secreted by large intestine helps in the lubrication of intestinal
contents.
4. Mucus protects the inner surface of wall of intestine.
5. Bacterial flora of large intestine produces vitamin K, cyanocobalamin, folic
acid etc.

6. Storage of unabsorbed food materials as faeces and timely emptying of faeces

—defecation.

Movements of large intestine

Movements of large intestine are mixing and propulsive movements. The main
aim of the movements here is to prolong the stay of the contents, this is why the
movements are slower and antiperistalsis is more prominent.

Different movements in the large intestine are as follows:

(A) Stationary movements for agitation of colonic contents. These are:
1. Segmentation contractions: As in small intestine.
2. Haustral contractions: It is a sort of segmentation contraction with haustra
becoming prominent.
3. Peristalsis and antiperistalsis: This moves the colonic contents forward and
backward, and behaves in effect as stationary movement. It is also called
kneading movement.
(B) Propulsive movements: These movements carry the colonic contents
forward, i.e., towards the rectum. These are:
1. Peristalsis occurs as in small intestine but is more powerful.
2. Mass peristalsis: It is a modified and stronger peristalsis. In mass peristalsis a
large segment of the colon contracts at a time and thus pushes the contents
forcefully forward. The contents may reach the rectum to give rise to the desire
for defecation. It is also said that in mass peristalsis a ring of contraction travels
along the large gut.

Gastrocolic Reflex

After a meal, i.e., the presence of food in the stomach reflexly stimulates
contraction of large gut, this is called gastrocolic reflex. It may sometimes lead
to mass peristalsis in colon and may result in defecation. This reflex needs the
extrinsic nerves.

MASTICATION

Most of the food we take are raw materials or hard substances. They have to be
broken down or grinded to less harder, paste-like form. It is made possible by the
participation of jaws, teeth, lips and assisted by muscles.

Mastication is the process of breaking up of larger food molecules into smaller

ones and mechanically mixing it with saliva. It makes the food soft and converts
it into bolus.

The important purpose served by mastication are:

1. It favours the action of digestive enzymes present in saliva by increasing the
surface area of the food particles.

2. It breaks non digestable cellulose covering of raw food material. 3. It helps in

the flow of saliva. Salvia inturn act as a lubricant helping in mastication.

4. It helps in subsquent swallowing.

It is very important for breaking up of the undigestable portions of food like
cellulose.

Muscles of Mastication

The muscles which cause the movement of mandible during speech and
mastication are called the muscles of mastication. These are supplied by the
mandibular nerve. The major masticatory muscle are

TABLE 6.2
Muscles of mastication
Sl.No. Muscle Origin Insertion Functions 1. Temporalis Temporal fossa

Coronoid process and anterior border of ramus of mandible (a) Elevation of

mandible as in closing

of mouth
(b) Retraction of protruded mandible 2. Masseter Zygomatic arc Ramus of
mandible (a) Elevates the mandible and closes the mouth
(b) Clenching of teeth
3. Lateral Pterygoid 1. Lateral pterygoid plate

2. Greater wing of sphenoid (infrastemporal surface) Neck of mandible (to

pterygoid fovea) (a) Depresses mandible and opens the

mouth
(b) Along with medial pterygoid of both
side protrude the mandible
(c) Lateral and medial pterygoid muscle
of one side acting alternately with
that of other produce chewing
movement (side to side)
4. Medical Pterygoid (a) Tubercle of maxilla

(b) Lateral pteryzoid plate medial surface of ramus of mandible (a) Elevates the
mandible
(b) Along with lateral pterygoid of both

side protrude the mandible

(c) Lateral and medial pterygoid muscle
of one side acting alternately with
that of other produce chewing
movement (side to side)

Buccinator is a secondary muscle of mastication which prevents the food from

accumulating in the gap between cheek and jaw. It is supplied by facial nerve.

Deglutition (Swallowing ): Swallowing is a mechanism that moves the food

from the mouth to stomach. Swallowing is a complex neuromuscular event
which is party voluntary and party reflex in nature. The act of swallowing
follows mastication and may be described in three stages.

1. Oral or buccal phase.

2. Pharyngeal phase
3. Oesophageal phase.

1. Oral phase This stage is under voluntary control. This consists of passage of
material through the oral cavity into the pharynx. The

bolus is collected on the posteriodorsal surface of the tongue and is thrown back
into the pharynx. The movement of the tongue is principally caused by the
contraction of the mylohyoid, styloglossus and hyoglossus muscles. During this
stage, mastication ceases.

2. Pharyngeal phase
It is an involuntary phase. It consists of involuntary passage of bolus through
pharynx to oesophagus. This is a reflex
Oral cavity Food bolus

Epiglottis
Trachea
Oesophagus
AB

Hard palate Soft palate Tongue

Epiglottis
Food bolus
CD

Fig. 6.23
Stages of deglutition

process known as swallowing reflex. Swallowing is a complex neuromuscular

event which is party voluntary and party reflex in nature. The pharynx
communicates both with the trachea and oesophagus. So the swallowing have to
serve two functions.

1. To propel the food from pharynx to oesophagus.

2. To protect airway both above and below from possible entrance of food
particles. The protective and propulsive movements occur almost

simultaneously. During this phase, respiration is inhibited reflectively. The

temporary stoppage of respiration is known as Deglutition apnea. The major
events of this stage are
(a) By the movements of the tongue, the bolus is

pushed back against the epiglottis. (b) Almost simultaneously, epiglottis deflects
in
transverse direction.
(c) The laryngeal opening is closed by closure of
vocal cords. The larynx is elevated. (d) The upper oesophageal sphincter relaxes
and
the bolus enters the oesophageal tube.

3. Oesophageal phase
It is under involuntary control. It consists of involuntary passage of food through
the pharyngeos—oesophageal junction through the body of oesophagus.
Immediately after the food enters, the upper oesophageal, sphincter closes,
contraction process of pharyngeal muscle spreads into oesophagus and a
peristaltic wave propels the bolus from the upper oesophageal sphincter through
the body of the
oesophagus, then towards the lower oesophageal sphincter. The movement of
upper part of oesophagus is controlled by vagus nerve where as the lower
portion of oesophagus is controlled by myentric plexus.

Disorders of swallowing:
1. Abolism of deglution reflex: Cause: lesion of medulla or cranial nerves IX or
Effect: Regurgitation of food into nose or laxynx.

2. Aerophagia: It is the swallowing of air during drinking or eating. Cause: Loss

of tone of lower oesophageal sphincter.

Achalasia: Achalasia is a primary esophageal motility disorder characterised by

failure of a hypertensive lower esophageal sphincter (LES) to relax and the
absence of esophageal peristalsis. These abnormalities cause a functional
obstruction at the gastroesophageal junction.

1. In people with achalasia, the LES fails to relax, creating a barrier that prevents
food and liquids from passing into the stomach. One theory is that the nerve cells
responsible for relaxation are destroyed by an unknown cause.

2. Damage to the LES and esophagus causes large volumes of food and saliva to
accumulate in the esophagus. Most people can initially compensate for this.
Eventually, the barrier progresses to the point where food and saliva cannot
reliably enter the stomach. As a result, food and saliva build up in the esophagus.

3. The most common symptom of achalasia is difficulty swallowing (liquids or

solids). This problem begins slowly and progress gradually;

4. Other symptoms can include chest pain, regurgitation of swallowed food and
liquid, heartburn, difficulty burping, a sensation of fullness or a lump in the
throat, hiccups, and weight loss.

VOMITING
Vomiting is a visceral reflex integrated in the medulla oblongata.

Vomiting centre: It is in the reticular formation of the medulla which lies near
the tractus solitarius at approximately the level of the dorsal nucleus of the
vagus.

Vomiting reflex: Irritation of the mucosa of the upper GIT is the strong stimulus
for vomiting. Distension or irritation of the duodenum provide the strongest
stimulus.
Irritation of upper GIT

Vagal & sympathatic

afferents Vomiting centre

Spinal nerveV, VII XII Cranial nerves

because motion stimulates the labyrinthine organs → Impulses →

Vestibular nucleus → Cerebellum → Chemo receptor trigger zone →
vomiting centre → Vomiting.

Emetics are substances that cause vomiting.

Diaphragm muscles of

abdomen Upper GIT

Vomiting
Fig. 6.24 Vomiting reflex pathway
Cerebral Excitation of Vomiting

Other afferents reach the vomiting centre from the diencephalons and limbic
system because emotionaly charged stimuli also cause vomiting (e.g., nauseating
smell and sickening sights).

Vomiting Act

In the early stages antiperistalsis occurs and empties contents from upper part of
small intestine into stomach within 3 to 5 minutes at the rate of 2–3 cm/sec.

Once the vomiting center is stimulated the vomiting act is initiated which
consists of
1. deep breath
2. closure of mouth
3. lifting of the soft palate to close the posterior nares
4. raising of the hyoid bone and the larynx to pull the upper oesophageal
sphincter open then there is a strong downward contraction of diaphragm along
with simultaneous contraction of abdominal wall muscles. This increases the
intra abdominal pressure. Finally the lower oesophageal sphincter relaxes
completely, allowing the gastric contents upward through the oesophagus.
Chemo receptor trigger zone: It is a small area located bilaterally on the floor
of the IVth ventricle in or near the area postrena. A chemo receptor cell in this
area initiate vomiting when they are electrically stimulated or stimulated by
certain circulating chemical agents. Administration of certain drugs morphine,
apomorphine stimulate chemoreceptor trigger zone and initiate vomiting.
Destruction of this area inhibits vomiting but does not inhibit vomiting due to
irrigative stimulation of upper GIT.
Vomiting due to motion sickness: Rapidly changing direction of the motion of
the body causes vomiting. This is

Movements of Stomach
There are three different types of movements of stomach: 1. Weak constrictor
waves (Mixer wave)
2. Peristaltic wave
3. Hunger contractions.

The weak constrictor—waves and peristaltic waves are seen when stomach is
filled and hunger contractions are seen when stomach is empty for a long time.

1. Weak constrictor waves

These are weak mixing waves, which travel along with the stomach wall and
moves towards the pyloric antrum. These waves as they move down cause
secretion which mix the stored food and provides weak propulsion to move the
mixed food into the antrum.

This is about 3 waves/min normally once in 20 secs.

2. Peristaltic wave
This wave propels the content of the stomach to the duodenum through pylorus.

The contractor waves when reaches the pylorus becomes intense and converts
into peristaltic wave. These waves also help in mixing the contents of the
stomach.

3. Hunger contractions:
Besides the peristaltic contractions seen when food is present in stomach, there
are hunger contractions seen when stomach is empty for a long time. Hunger
contractions are most intense in young healthy persons (adult). When hunger
contractions occur, the person experiences pain in the stomach. It is called as
hunger pangs. These hunger pangs fulfills the intake of food.
Gastric emptying time: Mechanism of emptying of stomach

It is the duration at which the—given food remains in the stomach. It is the time
after a meal food leaves the stomach.

Gastric emptying time depends upon:

1. Type of food ingested.
2. Fluidity of chyme and volume of liquid food present in stomach.
3. Pressure gradient from stomach to duodenum. 4. Resistance of pylorus.
1. Type of food
Food rich in carbohydrate leaves the stomach in few hours. Protein rich food
leaves more slowly and it is slowest for fat rich food.
Gastric emptying time: Carbohydrates — 2 hrs Proteins — 2–3 hrs Lipids — 3–
4 hrs The normal mixed diet takes 2–3 hr to empty from stomach.
Stomach - Stimulation of gastric emptying

1. Distension of stomach
2. Partially digested proteins and alcohol in stomach

Stimulates G cells of stomach and increases Gastrin secretion

2. Fluidity of chyme
Greater the fluidity of chyme more rapidly it passes through the pylorus.
3. Pressure gradient from stomach to duodenum

When stomach is full, pressure is more in stomach, than in duodenum. The

emptying is rapid when stomach is full. As it empties progressively, the rate of
gastric emptying decreases. Hence gastric emptying time is less at first and
increases gradually.

4. Resistance of pylorus

Normally pylorus remains in contracted state. Only fluid is emptied from

stomach to duodenum. Semisolid chyme can enter duodenum, only if strong
peristaltic contraction occurs.

5. Other factors

Gastric inhibitory peptide and cholecystokinin inhibit the gastric motility.

Cutting the vagus nerves slows the gastric emptying. Excitement is said to
hasten gastric emptying and fear slows down gastric emptying. Products of
protein digestion and acid in dueodenum decreases gastric emptying—
Enterogastric reflex.
Increase motility of stomach
Gastric Emptying
Decrease motility of stomach
1. Reflex : Enterogastric
2. Hormones : Secretin, CCK, GIP

1. Partially digested proteins, lipids and carbohydrates in duodenum.

2. Distension of duodenal wall.
3. Hypertonic and hypotonic fluid in duodenum.
4. Irritation of duodenal mucosa

Small intestine – Inhibition of gastric emptying

Fig. 6.25 Factors stimulating and inhibiting gastric emptying
MOVEMENTS OF THE SMALL INTESTINE

There are three types of movements seen in the small intestine:

1. Peristalsis
2. Rhythmic segmental movements
3. Pendular movements.

1. Peristalsis

It is a wave of relaxation followed with contraction spreading along a muscular

tube. The relaxation is called as receptive relaxation and contraction is called as
propulsive contraction.

Direction: Direction is from oral to anal direction. The wall of the intestine in
front of the food shows a wave of relaxation. It is meant for receiving the food.
There is a wave of contraction behind the food. This contraction propels the food
forward.

The direction of peristalsis is from the oral to the anal direction. It is explained
by two theories.
1. Law of the Gut: The anatomical organisation of the myenteric plexus prefers
the transmission of impulses in the oral to anal direction. Excitation is usually
followed with contraction. Therefore the direction of peristalsis is also in the oral
to anal direction.
Contraction Bolus
A
B
C

Fig. 6.26
Peristalsis

2. Gradient theory: The parts of the intestine close to the mouth generate
impulses at a higher frequency. Therefore the contraction takes place as per the
gradient.

Functions of peristalsis
1. Propulsion of food forward.
2. Mixing of food with digestive secretions.
3. It increases the blood flow to the wall of the intestine because of the above
action it helps in absorption of food.

2. Rhythmic segmental movements

The circular muscles of the small intestine contract at regular intervals. This
divides the intestine into several segments.

The point of contraction is not permanent. It changes at regular intervals.

Contraction Bolus
A
B
C
Fig. 6.27 Segmental movements

Functions:
1. It helps in the mixing of food with digestive juices
2. It increases the blood supply to the wall of the intestine. This helps in the
absorption of food. Pendular movements

It is due to the alternate contraction and relaxation of longitudinal muscles of the

intestine. This produces alternate shortening and lengthening of intestine.

Functions:
1. It helps to reorganise the intestinal coil within the space available.
2. It helps in the mixing of food with digestive secretions.
3. It increases the blood supply to the wall of the intestine.
4. It helps in the absorption of food.

DEFECATION

Defecation is the process of expelling feces to the exterior. This is controlled by

reflex process and is influenced by appropriate stimulus. The continuous
dribbling of fecal matter through anus is prevented by

1. Internal anal sphincter (involuntary)

2. External anal sphincter (voluntary)
The process of defecation involves contraction of rectum and relaxation of the
two sphincters.
Defecation reflex: It is the sudden involuntary act of evacuating fecal matter.
Desire for defecation is initiated by
1. entry of feces into rectum by mass peristalsis.
2. rise in intrarectal pressure.
3. stretching of rectal wall by fecal matter. These stimulate the peristaltic
movement in distal colon including rectum and relaxes internal anal sphincter.
This is because the distention of rectal wall initiates afferent signals that spread
through myentric flexus and initiate peristaltic wave in the lower part of colon.
This forces feces towards anus. The relaxation of internal anal sphincter is by the
inhibitory impulses from the myentric plexus which inhibit the influence of
parasympathetic nerve fibres.
Defecation occurs if this is accompanied by voluntary relaxation of external anal
sphincter too.
This forms the intrinsic defecation reflex. This is a weak reflex.
The rectal distension also stimulates the pelvic splanchnic nerves (which are
para sympathetic nerves) which leads to another type of reflex called
parasympathetic defecation reflex. It involves the sacral segments of the spinal
cord. The parasympathetic stimulus intensifies the effect of intrinsic reflex.
Other efforts required for defecation include: 1. Pulling the anal canal up over
the stool mass, due to contraction of the levator ani muscle. 2. Taking a deep
breath.
3. Closure of glottis.
4. Contraction of abdominal wall.
5. Extension of pelvic floor downwards.
6. Pulling of anal ring outward.
Cerebral cortex
Conscious impulus

Parasympathetic nerve fibres (Pelvi nerves) Sensory nerve fibre

Sensory receptors Descending colon

Sigmoid colon
Skeletal motor nerve Rectum External anal sphincter
Internal anal sphincter
Fig. 6.28
Defecation reflex

Basically defecation is an involuntary reflex process, the voluntary control is

imposed over it by external sphincter.
If the desire for defecation is not attended then there will be strong voluntary
contraction of external anal sphincter. And after sometimes the desire for
defecation is lost automatically.
In infants and persons with spinal cord lesion voluntary control of external and
sphincter is lost and automatic emptying of bowel is seen.
1. Constipation: Constipation is the result of neglected calls to defecate. It is
due to adaptation of sensory mechanism and its reflex effects. The symptoms
caused by constipation include anorexia, abdominal discomfort, distension,
furred tongue and foul breath etc; other symptoms such as headache,
restlessness, irritability are due to anxiety. These symptoms are not due to
absorption of toxic substances because they are quickly relieved with evacuating
the rectum.
2. Diarrhoea: Increase in frequency of passage of stools is called diarrhoea or
loose motions. It has many cause e.g., due to infection, typhoid, gastro enteritis
(food poisoning), ulcerative colitis etc.
Severe diarrhoea is debilitating and can be fatal specially in infants. Loss of
large amount of electrolytes (N+ and K+) and water in the diarrhoeal stool causes
dehydration, hypovolemia, electrolyte imbalance, shock, cardio vascular
collapse and finally death.

JAUNDICE

The normal serum total bilirubin concentration is 0.2 mg – 0.8 mg / dl. Of this
about 0.2 – 0.6 mg/dl is unconjugated while 0-0.2 mg/dl is conjugated bilirubin.

Jaundice is a clinical condition characterised by yellow colour of eyes, skin and

mucus membrane caused by deposition of bilirubin due to its elevated level in
serum.
The term hyperbilirubinemia is often used to represent the increased
concentration of serum bilirubin.

Classification of Jaundice

Jaundice (also known as icterus) may be more appropriately considered as a

symptom rather than a disease. Jaundice is classified into three major types
—hemolytic, hepatic and obstructive.

1. Hemolytic jaundice
This condition is associated with increased hemolysis of

erythrocytes ( e.g., incompatible blood transfusion, malaria, sickle cell anemia).

This results in the over production of bilirubin beyond the ability of the liver to
conjugate and excrete the same. Without conjugation. It should, however be
noted that liver possesses a large capacity to conjugate about 3.0 g/day.

In hemolytic jaundice, more bilirubin is excreted into the bile leading to the
increased formation of urobilinogen and stercobilinogen. Hemolytic jaundice is
characterised by

(a) Elevation of unconjugated bilirubin in the serum. (b) Increased excretion of

urobilinogen in urine. (c) Dark brown colour of faeces due to high content

of stercobilinogen.

2. Hepatic (hepatocellular) jaundice

This type of jaundice is caused by dysfunction of the liver due to damage to the
parenchymal cells. This may be attributed to viral infection (viral hepatitits)
poisons and toxins (chloroform, carbon tetra chloride, phosphorus etc.) cirrhosis
of liver, Among these, viral hepatitis is the most common.

Damage to the liver adversely affects the bilirubin uptake and its conjugation by
liver cells. Hepatic jaundice is characterised by

(a) Increased levels of conjugated and unconjugated bilirubin in the serum.

(b) Dark coloured urine due to the excessive excretion of bilirubin and
urobilinogen.
(c) Increased activities of alanine transaminase (SGPT) and aspartate
transaminase (SCOT) released into circulation due to damage to hepatocytes.
(d) The patients pass pale, clay coloured stools due to the absence of
stercobilinogen.
(e) The affected individuals experience nausea and anorexia (loss of appetite).

3. Obstructive (regurgitation) jaundice

This is due to an obstruction in the bile duct that prevents the passage of bile into
the intestine. The obstruction may be caused by gall stones, tumors etc.

Due to the blockage in bile duct, the conjugated bilirubin from the liver enters
the circulation.
Obstructive jaundice is characterised by
(a) Increased concentration of conjugated bilirubin in

serum.
(b) Serum alkaline phosphatase is elevated as it is
released from the cells of the damaged bile duct. (c) Dark coloured urine due to
elevated excretion of
bilirubin and clay coloured faeces due to absence
of stercobilinogen.
(d) Faeces contain excess fat indicating impairment
in fat digestion and absorption in the absence of
bile (specifically bile salts).
(e) The patients experience nausea and gastro
intestinal pain.
Neonatal-physiologic Jaundice: It is caused by increased hemolysis coupled
with immature hepatic systems for the uptake, conjugation and secretion of
bilirubin. The activity of the enzyme UDP. Glucuronyltransferase is low in the
new born Further, there is a limitation in the availability of the substrate UDP –
glucuronic acid for conjugation. The net effect is the serum uncojugated
bilirubin is highly elevated (may go beyond 25 mg/dl), which can cross the
blood-brain barrier and cause damage to the brain leading to mental retardation.
Deposition of bilirubin in the neurons produces a condition known as
kernicterus.
Phototherapy: Exposure of child to sun light. Bile pigment bilirubin get
converted into more water soluble lumirubin. It is easily excreted through urine.

TABLE 6.3:
Differences between hemolytic, hepatocellular and obstructive jaundice
Sl.No. Hemolytic Hepatocellular Obstructive 1. Colour of urine Golden
yellow Dark (due to bilirubinuria) Dark (due to bilirubinuria) 2. Colour of stool
(more urobilinogen) 3. Urine for bile pigment

4. Liver function test

(a) Serum bilirubin
1. Total
2. Unconjugated 3. Conjugated

(b) Van den Bergh reaction (c) ALT (SGPT)

(d) Alkaline phosphatase (e) Prothrombin time Golden yellow (less
urobilinogen)

Absent
Clay coloured
(less urobilinogen)

Present
Clay coloured
Present

Increased
80%
20%
Indirect positive Normal
Normal
Normal

5. Ultrasonography of liver Normal

Increased
50%
50%
Biphasic
Markedly raised
Slightly raised
Prolonged, not corrected by vit. K injection.

Intrahepatic biliary radicles are not dilated

Increased
20%

80%
Direct positive
Slighlty raised
Markedly elevated
Prolonged, can be corrected by vit. K.

Intrahepatic biliary radicles are dilated.

Appendicitis
Inflammation of appendix is called as appendicitis. Appendix is a vestigial organ
situated close to rectal wall.

Cause: It is produced by obstruction of lumen of the appendix by faecal

materials or foreign body, carcinoma of caecum or stenosis. The opening
between the lumen of the appendix and caecum is large in children and young
adults. Therefore food or faecal material trapped in the appendix will irritate and
inflame its mucous lineup causing appendicitis. It is rare in old people because
the opening between the appendix and the caecum is completely obliterated.

Signs and symptoms:

1. Oedema
3. Gangrene 2. Ischaemia 4. Perforation
5. Referred pain in the umbilical region
6. Loss of appetite 7. Nausea and vomiting Complications:
Rupture of appendix and release of contents into the abdomical cavity leads to
peritonitis. This may result in death. Management: Early appendectomy

Functions of Spleen
Spleen is a lymphoid and highly vascular organ. Important functions are:

1. Haemopoietic function or production of RBC in embryo and foetus.

2. Destruction of old blood cells. The older erythrocytes, leukocytes and
thrombocytes are destroyed by the spleen.
3. Reservoir function: Large number of red blood cells are stored in spleen.
These RBCs are released into circulation in emergency conditions like hypoxia
and hemorrhage.
4. Defence of body: The macrophages in elemis pulp phagocytes the micro
organisms and other foreign bodies.
Hyperspleenism: It is the condition when the activities of spleen are increased.
It is always associated with enlargement of spleen which is called as
splenomegaly.

Symptoms of hyperspleenism:
1. Anemia
2. Leukopenia
3. Thrombocytopenia

STEATORRHEA
It means fatty diarrhea. The stool contains excess fat.

Causes:
A. Pancreatic cause:
1. Chronic pancreatitis.
2. Fibrocystic disease of pancreas, there is a

pancreatic insufficiency.

B. Intestinal causes: Like sprue, massive resection of the intestine. In sprue the
villi are lost and do not regenerate.

Villi are also stunted in severe protein malnutrition. In Crohn’s disease there is a
damage of mucosa of terminal part of ileum.

Irritable bowel syndrome is a disorder characterised most commonly by

cramping, abdominal pain, bloating, constipation, and diarrhea. IBS causes a
great deal of discomfort and distress, but it does not permanently harm the
intestines and does not lead to a serious disease, such as cancer. Most people can
control their symptoms with diet, stress management, and prescribed
medications. For some people, however, IBS can be disabling.

1. They may be unable to work, attend social events, or even travel short dist
abdominal pain, bloating, and discomfort is the main symptoms of IBS.
However, symptoms can vary from person to person.

2. Some people have constipation, which means hard, difficult-to-pass, or

infrequent bowel movements.
3. Often these people report straining and cramping when trying to have a bowel
movement but cannot eliminate any stool, or they are able to eliminate only a
small amount.
4. If they are able to have a bowel movement, there may be mucus in it, which is
a fluid that moistens and protect passages in the digestive system. Some people
with IBS experience diarrhea, which is frequent, loose, watery, stools. People
with diarrhea frequently feel an urgent and uncontrollable need to have a bowel
movement.
Inflammatory bowel disease (IBD): The term inflammatory bowel disease
(IBD) refers a group of disorders in which the intestines become inflamed (red
and swollen), probably as a result of an immune reaction of the body against its
own intestinal tissue. Two major types of IBD are described: ulcerative colitis
(UC) and Crohn disease (CD). Ulcerative colitis is limited to the colon (large
intestine).
1. Crohn’s disease can involve any part of the gastrointestinal tract from the
mouth to the anus; it most commonly affects the small intestine and/or the colon.
2. Both ulcerative colitis and Crohn’s disease usually run a waxing and waning
course in the intensity and severity of illness.
3. When there is severe inflammation, the disease is considered to be in an active
stage, and the person experiences a flare-up of the condition. 4. When the degree
of inflammation is less (or absent), the person usually is without symptoms, and
the disease is considered to be in remission. Gastroesophageal reflux disease
(GERD): Gastroesophageal reflux disease (GERD) is a digestive disorder that is
caused by gastric acid reflux, it happens when a muscle at the end of esophagus
does not close properly. This allows stomach contents to leak back, or reflux,
into the esophagus and irritate it. GERD is a chronic condition. Once it begins, it
usually is life-long. If there is injury to the lining of the esophagus.
Person may feel a burning in the chest or throat called heartburn. Sometimes,
you can taste stomach fluid in the back of the mouth. This is acid indigestion. If
you have these symptoms more than twice a week, you may have GERD.
Anyone, including infants and children, can have GERD. If not treated, it can
lead to more serious health problems. In some cases, you might need medicines
or surgery. However, many people can improve their symptoms by
Avoiding alcohol and spicy, fatty or acidic foods that trigger heartburn.
Eating smaller meals.
Not eating close to bedtime.
Losing weight if needed.
Wearing loose-fitting clothes.
Hirschsprung’s disease is a disease of the large intestine. The large intestine is
also called as the colon. The word bowel can refer to the large and small
intestines. Hirschsprung’s disease usually occurs in children. It causes
constipation, which means that bowel movements are difficult. Some children
with Hirschsprung’s disease can’t have bowel movements at all. The stool
creates a blockage in the intestine.
Normally, muscles in the intestine push stool to the anus, where stool leaves the
body. Special nerve cells in the intestine, called ganglion cells make the muscles
push. A person with Hirschsprung’s disease does not have these nerve cells in
the last part of the large intestine. Treatment of Hirschsprung’s disease consists
of surgical removal (resection) of the abnormal section of the colon. Intestinal
obstruction: Intestinal obstruction is a partial or complete blockage of the bowel
that results in the failure of the intestinal contents to pass through. Obstruction of
the bowel may due to:
1. A mechanical cause, which simply means muscle spasm, growths and worms.
2. It causes severe pain called intestinal colic. 3. The normal peristaltic wave
intensified into strong peristaltic rush.

Digestion of Carbohydrates

The main carbohydrates in human diet are sucrose, lactose (milk), starch,
amylose, amylopectin and cellulose. There is no enzyme in the human gastro
intestinal tract for digestion of cellulose. So it is excreted mostly unused.

Total carbohydrate intake is 200–800 g/day, i.e., about 50–60% of the diet.
Mouth-salivary glands-salive.
Salivary amylase – Acts on boiled starch– Converts them into Dextrin and maltose
Stomach – Gastric cells – Gastric juice
Gastric amylase (weak) – The action on carbohydrate is negligible.
Small Intestine

Pancreatic amylaseActs on all sorts

of carbohydrates– Digest them into
dextrin, maltose
and isomaltose

Sucrase – acts on sucrose – convert it into glucose and fructose

Maltase – acts on maltose and isomaltose–convert them into glucose

Lactase – acts on lactose – convert it into glucose and galactose

Fig. 6.29 Steps involved in digestion of carbohydrates

Digestion

1. Digestion begins in the mouth. Salivary alpha amylase acts on boiled starch
and converts it into maltose and dextrin.

2. Pancreatic alpha amylase is more powerful, so it acts on boiled as well as

unboiled starch and varieties of other oligosaccharides.

3. Oligosaccharides are converted to monosaccharides by brush border enzymes

of small intestine such as maltase, sucrase, lactase, isomaltase.

4. The end products of carbohydrate digestion are the monosaccharides, fructose,

glucose and galactose. The digestion is completed in small intestine.

Absorption of Carbohydrate
Carbohydrates are absorbed from gastrointestinal tract in the form of
monosaccharides.
Mechanism of absorption

1. Glucose and galactose are absorbed by secondary active transport or Na+ co

transport mechanism as follows:
(a) Carrier present in the membrane has two

binding sites.One for Na+ ion and other for glucose or galactose.

(b) Unless both the binding sites are occupied, no confirmation change occurs in
the carrier molecule.

(c) When both the sites are occupied (by Na+ ion and glucose) confirmational
change occurs in the carrier protein molecule.

(d) Because sodium ions are transported down the electrochemical gradient, a
large amount of energy is available for transport so that all the glucose or
galactose present in the intestine can be absorbed (against the gradient).

(e) Energy is required for Na+–K+ pump activity to maintain sodium gradient.

3. Fructose is absorbed by facilitated diffusion. Most of the fructose is also

converted to glucose and lactic acid within the intestinal cells. This maintains
high concentration gradient for fructose across the membrane. After absorption,
monosacharides are transported across the basolateral membrane by facilitated
diffusion into the intestinal interstitium. From here monosaccharides diffuse into
the capillaries of villus.
Digestion of proteins in gastrointestinal tract
Proteins include exogenous (dietary) proteins and endogenous proteins (from
desquamated cells). Quantity of dietary protein is about 75–100 g/day.

Proteins are digested to amino acids and small polypeptides before they are
absorbed. Digestion of proteins begins in the stomach. Pepsin of the stomach
digests about 10-15 % of ingested protein completely. Pepsin breaks apart the
metal particles and facilitates further digestion of proteins because of ability of
pepsin to digest collagen which is the main inter cellular substance (connective
tissue constituent).

After the chyme enters the small intestine, proteolytic enzymes of pancreas play
a major role in their digestion. All the pancreatic proteolytic enzymes are
secreted in inactive form. They are converted to active form after they enter
small intestine. Enterokinase from succus entericus activates tryspinogen to
trypsin. Once small quantity of trypsin is formed, it activates trypsinogen,
chymotrypsinogen as well as procarboxypeptidase. Trypsin and chymotrypsin
are endopeptidases and they break proteins and protein breakdown products into
small lower peptides, mainly into tripeptides and dipeptides.
Mouth-salivary glands-salive.
No proeolytic enzyme – no protein digestion
Stomach – Gastric cells – Gastric juice
Pepsin – Acts on proteins – converts them into peptones, large polypeptides
Small Intestine
Pancreatic juice Succus enterius

Trypsin and
Chymotrypsin– Acts on proteoses and
peptones – Digest them into dipetides, tripeptides and
polypeptides

Dipeptidases – acts on dipeptides – convert it into amino acids

Carboxypeptidases
– A and B – Acts on dipeptides,
tripeptides
and polypeptides– convert them into amino acids Tripeptidases – acts on tripeptides – convert them into
amino acids

Amino peptidases – acts on

large polypeptides –
convert it into amino acids

Fig. 6.30
Steps involved in digestion of proteins

Trypsin has a wider range of action as compared to that of pepsin.

Carboxypeptidase splits the amino acid possessing a free carboxyl group from
protein.

Peptidase (amino polypeptidases and dipeptidases) secreted by intestinal

epithelial cells eventually convert polypeptides into lower polypeptides and
amino acids.

Nucleoprotiens are digested by nucleosidase, nucleotidase and nuclease secreted

in pancreatic juice and succus entericus.

Absorption of proteins by gastrointestinal tract Proteins are mainly absorbed

in the form of amino acids and to lesser extent in the form of dipeptides and
tripeptides. Larger polypeptides are very rarely absorbed by pinocytosis
(responsible for allergic reaction to absorbed whole protein). Amino acids are
absorbed by secondary active transport or Na+ co-transport mechanism similar
to that for monosaccharides. But there are number of transport systems, example
separate transport systems are available for basic aminoacids, acidic amino acids
and neutral aminoacids. There are also tripeptide and dipeptide transporters.
Once amino acids and polypeptides are absorbed into the intestinal epithelial
cells, intra cellular peptidases break the remaining linkages of tripeptides and
dipeptides causing release of amino acids. Amino acids thus formed are
transported through basolateral surface of the intestinal cell by facilitated or
simple diffusion into the interstitium and then they enter the capillaries of villus
by simple diffusion. Almost all protein ingested is absorbed. Any protein that
appears in stools is derived from bacteria or cellular debris.

Digestion of fat in gastrointestinal tract

Daily dietary intake of fat varies from 25 to 150 g. For absorption, lipids must be
made water soluble. Bile salts are required for solubilisation of lipids.

Fat digestion is initiated in stomach but gastric lipase only acts on butter. The
major digestion of fats begin in the small intestine when bile salts cause the
emulsification of fat. The enzyme which plays major role in fat digestion is
pancreatic lipase. It digests almost all the triglycerides of food to free fatty acids,
glylcerol and monoglycerides.

Small intestinal epithelial cells contain small quantities of intestinal lipase which
can also digest triglycerides. Thus end products of triglyceride digestion are free
fatty acids, monoglycerides and very small quantity of diglycerides. Cholesterol
in the food is in the form of cholesterol esters (choleterol + one molecule of fatty
acid). Cholesterol esterase enzyme digests it to cholesterol and fatty acid.
Phospholipids are digested by phosphorylase A2 which separates fatty acids
from phospholipid.
Mouth-salivary glands-salive.
Lingual lipase – acts on small amount of tryglycerides – fatty acids and glycerol
Stomach – Gastric cells – Gastric juice
Gastric lipase (weak) – acts on tryglycerides converts them into fatty acids and glycerol
Small Intestine
Pancreatic juice Succus enterius

Pancreatic lipase
– acts on triglycerides digest them into monoglycerides and fatty acids
Phospholipase – A – acts on lysopholipids – convert it into free fatty acids

Phospholipase – A – acts on phospolipids – convert them into lysophospholipids

Intestinal lipase Tripeptidases – acts on triglycerides – convert them into amino acids

Amino peptidases – acts on

large polypeptides –
convert it into Small peptides
and amino acids

Fig. 6.31 Steps involved in digestion of lipids Absorption of fat by

gastrointestinal tract

About – 30 molecules of bile salts aggregate forming a micelle. In the formation

of micelle, polar ends of bile salts project outwards and the steroid groups
project inwards forming a central fat globule. Products of lipid digestion (fatty
acids, monoglycerides, cholesterol) get dissolved in the central fatty portion of
micelle.

Micelles move along the microvilli surfaces allowing their lipids to diffuse
through the membrane of microvilli into the cell. Lipid gets dissolved in the
membrane lipid or microvilli and then diffuses to the interior of the intestinal
cell. Lipids, cholesterol, lipid soluble vitamins are very rapidly removed from
micelles once they make contact with microvilli. So the rate limiting step in lipid
absorption is migration of micelles from intestinal chyme to microvilli surface.
Once the bile salts are freed, they again go back to intestinal chyme for ferrying
more fat digestion products. Normally all ingested fat is absorbed. Once the
digested fat enters the intestinal cell, it is reconstituted as follows:

(a) Monoglycerides are converted to triglycerides.

(b) Lysophosphatides combine with fatty acid to form phospholipid.

(c) Cholesterol is re-esterified.
These reformed lipids form chylomicrons which are small lipid droplets in the
smooth endoplasmic reticulum cell. The chylomicrons are covered by B-
apolipoprotein. It is because of covering of B-apolipoprotein that exocytosis of
chylomicrons is made possible. After coming out from the cell they diffuse into
lacteals and then into hepatic circulation.
Most of the absorption of fat occurs in duodenum and upper jejunum. Therefore
by the time food reaches mid jejunum, almost all the dietary fat is absorbed.
Small quantities of short chain fatty acids are absorbed directly into the portal
blood.
Lipid malabsorption occurs when there is inadequate supply of pancreatic lipase
or bile.
Water and sodium in the diet and in the salivary , gastric, intestinal, biliary and
pancreatic secretions are absorbed in small intestine.

1. Water absorption

Active reabsorption of electrolytes and nutrients create an osmotic gradient for

water. Water is absorbed passively and iso-osmotically. In duodenum, entry of
chyme increases osmotic pressure causing water to flow in the intestine. In
jejunum and ileum, active reabsorption of NaCl creates osmotic gradient which
favours water absorption.

2. Absorption of sodium and chloride

(a) Sodium is first transported from the lumen into the intestinal cell (enterocyte)
and then across the basolateral membrane into the intestinal innterstitium.

(b) Sodium enters the enterocytes in three ways: (i) About 30% is transported
into the cell by Na+ – Glucose, Na+ – amino acid cotransport system.
(ii) About 30% is transported into the cell by Na+ – Cl– co-transport system.
(iii) The remainder enters the cell passively down an electrochemical gradient.

(c) Once enter inside the enterocyte, Na+ is transported across the basolateral
membrane by a Na+ – K+ ATPase active transport system.
DIETARY FIBRES

This mainly includes cellulose, hemicellulose and lignin present in food. Human
enzymes cannot digest cellulose. However a small quantity of cellulose can be
digested by microorganisms of GIT.

Importance of Cellulose or Fibre in Food

1. This gives bulkness to food and satisfies hunger and thereby prevents excess
intake of pure digestable carbohydrate which is likely to add up calorie.

2. The bulk-ness of food due to fibre stimulates peristalsis and helps in easy
passage of food. 3. High fibre diet helps in prevention and treatment of
constipation.

4. It reduces the efficiency of absorption of digested food stuffs by forming a

mechanical barrier between digested food and wall of intestine. This helps in
avoiding sudden steep increase in blood glucose level after a meal.

5. High fibre diet is helpful in the treatment of diabetes mellitus.

6. It reduces blood cholesterol level by binding with bile salts.
7. So very much useful in controlling metabolic disorders related with over
nutrition like obesity, atherosclerosis etc.
8. Dietary fibre reduces the incidence of colon cancer. Malabsorption
syndrome is an alteration in the ability of the intestine to absorb nutrients
adequately into the bloodstream. Malabsorption may be due to an abnormality of
the gut wall, failure to produce enzymes or bile to aid digestion, or there may be
abnormalities of the flora of the gut. Malabsorption may occur for many
nutrients or for specific carbohydrates, fats or micronutrients. Protein, fats, and
carbohydrates normally are absorbed in the small intestine - the small bowel also
absorbs about 80 per cent of the eight to ten liters of fluid ingested daily.
Malabsorption means the failure of the GI tract, usually the small intestine, to
absorb one or more substances from the diet. This is generally the result of some
defect or damage to the mucosal lining of the small intestine where most of our
nutrient absorption takes place. The most common symptoms of malabsorption
syndrome are:
1. Diarrhea, bloating, flatulence, cramping and weight loss.
2. Over time, one may become deficient in iron, proteins, various vitamins and
minerals and this can lead to degrees of malnutrition and a variety of anemias.
3. The most common anemias that may occur are vitamin B12, folate, and iron
deficiency. 4. Vitamin K malabsorption causes the blood to thin out and could
result in excess bleeding.
5. Protein depletion can lead to impaired bone formation and osteoporosis.
6. Calcium deficiency leads to weakening and demineralisation of the bone,
causing a condition called osteomalacia.
7. Impaired absorption of vitamin A could result in poor vision and night
blindness as well as dermatitis.
8. Malabsorption of protein, fat and carbohydrate leads to loss of calories,
generalised malnutrition and diarrhea.

Dumping syndrome
This condition is seen in partial or total gastrectomy. It is characterised by
dizziness and sweating after meals. It results

due to rapid delivery of large amounts of osmotically active solids and liquids
into the duodenum. Common symptoms include abdominal cramps and nausea.
Endocrine System
Sir Frederick Grant Banting
14-11-1891–21-2-1941 Canadian Physiologist Discovery of Insulin Nobel Prize
(1923)

Harvey Williams
Cushings
8-4-1869–7-10-1939
American Neurosurgeon Famous as Father of
modern Neurosurgery and Cushing’s Syndrome

Johannes Peter Muller 14-07-1801–28-4-1858 German Physiologist Famous

for Muller’s law
Charles Herbert Best 27-2-1899–31-3-1978 Canadian
Isolated Insulin and
applied it to treat diabetes Nobel Prize (1923)

Robert James Graves 20-3-1796–1853

Irish Surgeon
Famous for Grave’s disease

Otto Loewi
3-6-1873–25-12-1961 German Pharmacologist Father of neuroscience Discovery
of acetylcholine Nobel Prize (1936)

Alfred Gilman
1-7-1941
American Physician Famous for G- proteins Nobel Prize (1994)

(216)
Chapter
7
ENDOCRINE SYSTEM

Types of chemical messengers. General properties. Classification of hormones

and mechanism of action. Major endocrine glands.
Anterior Pituitary.
Physiological functions and regulation of secretion of growth hormone.
Dwarfism, Gigantism, Acromegaly.
Prolactin, TSH, ACTH, Gonadotropins. Posterior Pituitary.
Antidiuretic hormone—Function and regulation of secretion.
Diabetes insipidus and SIADH.
Oxytocin—Functions and regulation of secretion. Thyroid gland—Synthesis,
secretion, functions and regulation of secretion.
Disorders of thyroid—Goitre, Cretinism, Myxoedema, Grave’s disease.
Thyroid function tests, Antithyroid substances.

Adrenal cortex
Synthesis and secretion of adrenocortical hormones, Functions and regulation of
secretion of aldosterone. Conn’s syndrome.
Functions and regulation of secretion of cortisol, disorders- Addison’s disease,
Cushing’s syndrome. Adrenal androgens. Adrenogential syndrome. Adrenal
medulla—Biosynthesis of catecholamines. Functions of adrenal medullary
hormones. Alarm reaction, Pheochromocytoma.
Endocrine Pancreas—Physiological functions and regulation of insulin secretion.
Mechanism of action—Insulin Receptors. Diabetes mellitus—types and
pathophysiology. Glucagon—Functions and regulation of secretion.
Somatostatin—Pancreatic polypeptide.
Hormonal regulation of blood glucose.
Parathyroid Gland—functions and regulation of secretion of PTH.
Tetany.
Calcitonin—Functions and regulation of secretion. Calcium metabolism—
Hormonal regulation of plasma calcium level.
Other endocrine glands—Pineal gland, thymus. Local hormones—Histamine,
Serotonin, Prostaglandins, Acetylcholine, Bradykinin.
GIT hormones.
Growth, development and ageing.

ENDOCRINE SYSTEM

Endocrine system comprises of a group of ductless glands which secrete

hormones. There are two important control systems of the body. They are

1. Nervous system and 2. Endocrine system

These two systems together control and co-ordinate various body functions. This
takes place at three important levels.

1. Biochemical level,
2. Physiological level and
3. Behavioural level
Secretions of most of the hormones are controlled by the nervous system. At the
same time hormones influence the functions of nervous system. There is a close
interaction between the nervous system and the endocrine system. These two
systems are together called as Neuroendocrine system.

Hormone

Hormones are defined as organochemical substances secreted by ductless glands

(endocrine glands) into the blood and manifest their physiological actions at a
place away from the site of their secretion.
ENDOCRINE
Endocrine cell Target cell
Hormone Blood Hormone
PARACRINE
Secretory cell Neighbouring cell
Secretion Interstitial fluid Secretion
AUTOCRINE
Secretory cell Secretion
Secretion Interstitial fluid
NEUROCRINE
Neuron Excitable or Secretory cell

Neuromodulator or
Neurotransmitter

Synaptic cleft Neuromodulator or

Neurotransmitter

Fig. 7.1 Chemical messengers

The basic stimilarity between endocrine, paracrine, autocrine and neurocrine
secretions.
Sensing and signalling
Biosynthesis Degradation
Storage Feedback
Hormone Release
Action
Secretory Extracellular cell fluid Target cell
Fig. 7.2 Sensing and signalling mechanism for hormone secretion

General properties of hormones

1. They are of low molecular weight.
2. They are easily soluble.
3. They can easily diffuse out of the blood vessels. 4. Hormones are not stored
anywhere in the body except in the gland from which they are secreted. 5. Each
hormone has a half life, e.g., Thyroxine-6 days. Cortisol 60–100 minutes.
6. Certain physiological functions are controlled by more than one hormone.
When more hormones are involved in the control of a particular physiological
function there are two types of interactions between these hormones.
(a) Synergestic action
(b) Antagonistic action
Synergestic action means complementary action, e.g., in the regulation of blood
glucose level, the action of cortisol and glucagon are complementary to each
other. Both of these hormones increase the blood sugar/glucose level.
Antagonistic means actions of two hormones are opposite to each other.
For example, Actions of insulin and glucagon. Insulin decreases blood glucose
level. Glucagon increases blood glucose level.
7. Target organ or target cell.
Certain hormones act at specific organ or cells. These organs or cells are known
as target organ or target cells. The cells having receptor of a particular hormone
become the target for that hormone. A cell may have receptors for many
hormones and thus can become the target of many hormones.
For example, Thyroid stimulating hormone acts only on thyroid gland.
8. Secretions of all the hormones are regulated. There are two types of regulatory
mechanisms. (a) Positive feedback mechanism.
(b) Negative feedback mechanism.
9. Hyposecretion or hypersecretion of hormone may lead to endocrine disorders,
e.g., diabetes mellitus. 10. Certain hormones are used for treatment or
therapeutic uses of hormones.
For example, Insulin for the management of diabetes mellitus.
11. Hormones undergo continuous degradation and replacement.
12. Hormones are not consumed or utilised in the process of function or action
produced by them.
Hormone
Gland Target tissue Inhibition
Product
Negative feedback mechanism
Hormone
Gland Target tissue
Classification of hormones
Hormones are broadly classified into two groups. (a) General hormones and (b)
Local hormones. General hormones
(a) These are hormones secreted by well defined endocrine glands.
(b) Site of action is for away from site of secretion.
(c) Example: Growth hormone, Insulin, Thyroxine.

Local hormones

(a) These are hormones secreted by cells or structures which are not developed
as a well defined endocrine glands.

(b) Site of action is very close to site of scretion. (c) For example,
Pancreozymin, Gastrin, Serotonine,
+
Histamine.
Product Positive feedback mechanism
Fig. 7.3 Feedback mechanism

TABLE 7.1 Comparison of nervous system and endocrine system regulation

of homeostasis

Sl.No. Characteristics

1. Mechanism of control Neurotransmitters Hormones released in

response to
nerve impulses. delivered to
tissues throughout the body by the blood.
CH OH
212 CH OH
18 CO O2

HO Dehydroepiandrosterone (DHEA)

Fig. 7.4
Steroid hormones

2. Cells
affected Muscelle cells, gland cells, other neurons.
Virtually all body cells.

3. Time to onset of action

Typically within millisecond
Seconds to hours or days.

4. Duration of action
Generally longer Generally briefer
5. Latency of response Short Long
6. Evolutionary level
Nervous system Endocrine system
New Primitive
HO
19CH
3
HC
20
3 CO OH CH 17 HO
CH3 C D
O
Cortisol AB O
AldosteroneO(Aldehyde
form)

Mechanism of action of hormone

There are two mechanisms of action.
1. Cyclic AMP (Adenosine mono phosphate) 2. Gene manipulation
Cyclic AMP
Most of the hormones of protein group manifest their
physiological functions through cyclic AMP mechanism. The
hormone is secreted by the gland into the blood. Blood carries
the hormone to the target cell. In the target cell it combines
with a receptor protein situated on the cell membrane. The
hormone-receptor protein complex activate the enzyme

Chemical Classification of Hormones

Hormones
Lipid group Nonsteroid
Steroids Eicosanoids fatty acid derivatives

Sex steroids testosterone oestrogen

progesterone Non sex
steroids
aldosterone cortisol
Prostaglandins Leukotrienes Proteins and

long peptides Glycoproteins

Growth hormone (GH)
Prolactin
Parathyroid hormone Calcitonin
Adrenocorticotropic hormone (ACTH) Insulin
Glucagon

Follicle-stimulating hormone (FSH)

Luteinising hormone (LH)
Thyroid-stimulating hormone (TSH)
Human chorionic gonadotropin (HCG)
Small peptides Hormones derived from single amino acids

Antidiuretic hormone (ADH) Oxytocin

Melanocyte-stimulating hormone (MSH) Somatostatin
Thyrotropin-releasing hormone (TRH) Gonadotropin-releasing hormone (GnRH) Amines

Norepinephrine Epinephrine
Melatonin
Iodinated amino acids

Thyroxine (T )4
Triodothyronine (T )

adenyl cyclase. The activated enzyme converts ATP into cyclic AMP and
inorganic phoshate. Cyclic AMP is called as second messenger. The further
changes in the cell is brought about by the cyclic AMP. It produces some of the
following changes like:

1. It may increase or decrease the permeability of the membrane.

2. It may activate enzyme or enzymes.
3. It may inhibit enzyme or enzymes.
4. It may increase or decrease the contraction.
Gland Target cell membrane
Hormone
Stimulating hormone ATP 5¢-ATP PhosphoReceptor
Adenyl diesterase cyclase
Cyclic 3 -5¢¢-AMP + PPi Physiological responses

1. Activates enzymes
2. Alters cell permeability
3. Cause muscle contraction or relaxation
4. Cause protein synthesis, cause secretion

Fig. 7.5
Cyclic AMP mechanism
Mechanism of hormone action by gene manipulation The steroid hormones
manifest their physiological

functions through manipulating the genes. The hormone is secreted by the gland
into the blood. Blood carries the hormone to the target cell. The hormone
diffuses into the cytoplasm of the cell. Here it combines with a receptor protein.
The hormone receptor protein complex diffuses into the nucleus. Inside the
nucleus it will activate certain specific genes. This produces messenger
RNA(mRNA). mRNA comes out of the nucleus and reaches the ribosome. At
the ribosome the information of mRNA is used for the synthesis of protein. The
protein so formed may be an enzyme, an inhibitor, may be a carrier protein. The
further functions of the hormone depends upon what protein is formed at the
target cell.
Gland Target cell membrane

Endocrine glands 1. Hypothalamus

Hormone
H+R
Nucleus
DNA H+R
2. Anterior Pituitary or Adenohypophysis
mRNA

Ribosome H-R = Hormone Receptor complex

= mRNA
Fig. 7.6
Mechanism of hormone action by gene manipulation Major endocrine glands
of the body
3. Pars Intermedia
4. Posterior Pituitary or Neurohypophysis
Pineal gland Hypothalamus Pituitary gland

5. Adrenal Cortex
Parathyroid gland
Thyroid gland
Thymus

Kidney Pancreas Adrenal gland

6. Adrenal Medulla
Testis
(in male) Ovary
(in female)

Fig. 7.7
Location of major endocrine glands
7. Islets of Langerhans
Hormones
1. Growth Hormone Releasing

Factor. (GHRF)
2. Growth Hormone
Inhibiting Factors (GHIF)
or Somatostatin
3. Thyrotrophin Releaing
Factor (TRF)
4. Corticotrophin Releasing
Factor (CRF)
5. Prolactin Inhibiting Factor
(PIF)
6. Prolaction Releasing Factor
(PRF)
7. Gonodotrophin Releasing
Factor (Gn TRF)

1. Growth Hormone (GH)

2. Prolactin
3. Thyroid Stimulating
Hormone (TSH)
4. Adrenocorticotrophic
Hormone (ACTH)
5. Follicular Stimulating Hormone (FSH)
6. Luteinising Hormone (LH)

1. Melanocyte Stimulating Hormone (MSH)

1. Vasopressin or Anti
Diuretic Hormone (ADH)
2. Oxytocin
: Zonaglomerulosa—
Minerelocorticoids—
Aldosterone
Zonafasciculata—
Glucocorticoids—Cortisol Zonareticularis—Androgen

: Epinephrine / Adrenaline Nor-Epinephrine /

Noradrenaline

: α Cells – Glucagon
: β Cells – Insulin
: δ Cells – Somatostatin. : PP cells – Pancreatic

Polypeptide
8. Gonads: Ovary
Testis
9. Placenta
10. Gastrointestinal tract
11. Heart
12. Kidneys

13. Lungs
14. Pineal Gland
15. Thymus
16. Liver and Muscles Pituitary Gland

: Oestrogen, Progesterone, Relaxin

: Androgens – Testosterone, Inhibin

1. Human Chorionic
Gonodotrophin (HCG)
2. Oestrogen.
3. Progesterone.
4. Somatotrophin.

1. Gastrin
2. Secretin
3. Pancreozymine –
Cholecystokinin
4. Villikinin, Motilin
: Atrial Natriuretic Peptide (ANP)
: Calcitriol or 1-25
Dihydroxychole calciferol.

: Angiotesin II
: Melatonin
: Thymosin
: Somatomedins
Optic chiasma HypothalamusMamillary body
Pars tuberalis Infundibulum
Pars Intermedia Neurohypophysis Pars anteria
Anterior Posterior
pituitary pituitary

Fig. 7.8
Pituitary gland

The pituitary gland or hypophysis lies in the hypophyseal fossa of the sella
tunica of the sphenoid bone and attached to the hypothalamus by a stalk, the
infundibulum. The pituitary gland is a pea shaped structure measuring 1–1.5 cm
in diameter.

Pituitary is called as “Master gland” because it regulates and coordinates the

secretion of most of the other endocrine glands. Pituitary is also called as “leader
of endocrine orchestra”. It is divided into anterior pituitary and posterior
pituitary. The zone separating this is called as pars intermedia.

Hormones of anterior pituitary

In the anterior pituitary there are 3 types of cells. They are: 1. Acidophilic cells
2. Basophilic cells and
3. Chromophobes
The acidophils secrete two hormones:
1. Growth Hormone
2. Prolactin
Basophilic cells secrete four hormones:
1. Thyroid stimulating hormone (TSH) or Thyrotrophin
2. Adreno cortico tropic hormone or Cortico trophin (ACTH)
3. Folicular stimulating hormone (FSH)
4. Luteinising hormone (LH).
FSH and LH are together known as gonado tropic
hormone (GnTH).
The intermediate zone or pars intermedia secretes one
hormone:
1. Melanocyte stimulating hormone (MSH) Posterior pituitary secrete two
hormones:
1. ADH or vasopressin and
2. Oxytocin

Growth hormone
Source: It is secreted from the acidophilic type of cells of anterior pituitary.

Chemistry: It is a protein made up of 191 amino acids and a molecular weight

of 22,000.

GH also brings about growth of visceral organs like liver, spleen, kidney, heart,
GIT, lungs etc. GH promotes prepubertal sexual maturation by sensitising the
gonads for actions of FSH and LH.

Plasma concentration of GH = 0–5 ng/ml in adults. Physiological functions and

actions—direct actions

Growth hormone promotes growth. It is brought about by increasing the number

of cells as well as increasing the size of the cells.

Role of growth hormone in the growth of the bones Direct action of growth
hormone in promoting overall
growth.
GH stimulate the cartilage forming cells known as
chrondrocytes. The number and size of these cells increases.
Synthesis of RNA, DNA and protein in the bones increases.
Organic materials of bone synthesis increases, this produce
a linear growth of bones. This results in overall growth of
skeletal frame work and height of an individual. This happens
before the closure of epiphyses of bones.
Metabolic functions of growth hormone
Action on carbohydrate metabolism
1. It will decrease the cellular uptake of glucose. 2. It decreases the cellular
break down of glucose for energy production.
3. It increases hepatic gluconeogenesis.
4. Because of the above actions, growth hormone increases blood glucose level.
This action is known as hyperglycemic action. So GH is a diabetogenic
hormone.
5. It also stimulates the conversion of glucose to glycogen.
Action on protein metabolism
1. It increases the permeability of cell membrane to amino acids.
2. It increases the concentration of amino acids inside the cells.
3. Growth hormone stimulates both transcription and translation stages of
protein synthesis. Therefore it promotes protein synthesis. It produces greater
protein synthesis than protein breakdown. This process is known as positive
nitrogen balance. This is very much essential for growth. 4. It decreases blood
urea level.
Action on fat and lipid metabolism
It increases the break down of fats and lipids for the energy
production. It also stimulates synthesis of lipids taking part
in the formation of cell wall. It increases FFA level in plasma,
promotes ketogenesis.

Indirect actions of growth hormone

GH actions are mediated through formation of certain polypeptides called as
insulin like growth factor or somatomedins. There are two prominent types of
IGFs- IGFI somatomodin C and IGFII.

IGF-II is prominent during fetal life—IGF-I is prominent in post natal life. IGFs
are mostly formed by liver in response to GH action. IGF plasma concentration
is about 20–700 ng/ml.IGFs act like insulin . It can bind with insulin receptor. It
promotes the growth.
Stress Dopamine High plasmaglucose
Sleep + High plasma FFA

–
+ +– Hypothalamus –

GHRF GHF
+ Somatostatin
Anterior pituitary– –
GH +
Liver
IGF
Fig. 7.10
Regulation of secretion of growth hormone

Secretion of growth hormone is regulated by the hypothalamus. Hypothalamus

secretes small peptides. There are two types of peptides. They are:

1. Growth hormone releasing factor—GHRF

2. Growth hormone inhibiting factor—GHIF. This is also known as somatostatin.

These factors are transported through the hypothalamohypophysial portal blood

vessels. Growth hormone releasing factor stimulates the anterior pituitary to
secrete growth hormone whereas growth hormone inhibiting factor inhibits the
anterior pituitary from secreting of growth hormone. Ultimately the secretion of
growth hormone depends upon the relative concentration of Growth hormone
releasing factor and Growth hormone inhibiting factor. Factors like sleep, stress,
dopamine etc. will stimulate the hypothalamus to secrete more of GHRF.
Increased plasma concentration of glucose, FFA and IGF will exert inhibitory
action on hypothalamus.

Disorders related to growth hormone

Dwarfism
It is an endocrine disorder resulting from hyposecretion of growth hormone
during the critical developmental period in children.
Causes

1. Lesion of the anterior pituitary due to infection or injury.

2. Lesion of hypothalamus resulting in hyposecretion of growth hormone
releasing factor.
Fig. 7.11 Dwarfism
Signs and symptoms:
1. Height will be abnormaly short.

2. Stunted skeletal growth. Decreased muscle mass and total body mass.

3. Low blood glucose level.

4. Development of gonads may be normal and the individual may have
reproductive ability. But delayd sexual maturation.
5. Mental growth may be normal and IQ may be normal.

Sheehan’s syndrome
It is a type of Panhypopituitorism (Hyposecretion of whole of anterior pituitary).
Cause: Obstetric shock (= severe fall of cardiac output following a hazardous
delivery) causes ischemic necrosis (death) of hypothalamus.

Laron Dwarf: Serum concentration of GH may be normal, but decreased

production of Insulin like Growth factor I (IGF-I) or somatomedin. Failure of
skeletal growth. Stunted growth.

Administration of GH is of no use, but administration of IGF is beneficial.

Gigantism or giantism
It is an endocrine disorder resulting from hyper secretion of growth hormone
during critical developmental period or in children.
Causes: Tumorous growth of acidophilic type of cells of anterior pituitary.

Tumorous growth of hypothalamus secreting excess growth hormone releasing

factor.

Symptoms:
1. Height of the individual will be abnormally tall.

2. Increase in blood glucose level or hyperglycemia. This may result in pituitary

diabetes mellitus.
3. Enlargement of soft tissues like liver, spleen, tongue etc.

Fig. 7.12 Gigantism

Acromegaly
It is an endocrine disorder resulting from hypersecretion of growth hormone in
adult.
Causes: Tumorous growth of the acidophilic type of cells of anterior pituitary.

Tumorous growth of hypothalamus secreting excess growth hormone releasing

factor.
Signs and symptoms: Acromegaly means enlargement of peripheral parts.

There is no abnormal increase in the height. The epiphysis of the bones closes at
the time of puberty. Therefore increased secretion of growth hormone cannot
increase the length of the bones. Deposition of organic matrix on the bones will
produce the thickening of the bones. This takes place especially in the small and
membraneous bones like vertebra, clavicle, cranial bones etc.

1. This produces protrusion of forehead, flatening of nose. Overgrowth of malar,

frontal and facial bones.
2. Increased hairs in the body.
3. The pituitary tumor enlarges the stella turcica. This

will compress the optic chiasma. This will change the visual field and can cause
bitemporal hemianopia.

4. Bending of vertebral column (hunch back— kyphosis).

5. Thickening of soft parts like tongue.
6. Increase in blood glucose levels—hyperglycemia. Pituitary diabetes.
7. Enlargement of liver—hepatomegaly, enlargement of spleen—spleenomegaly.
8. Enlargement of heart—cardiomegaly.
9. Enlargement of feet and hands, enlargement of peripheral parts.
10. Elongation and widening of mandibleprognathism-protrusion of jaw.
 Fig. 7.13 Acromegaly
Prolactin or Lactogenic hormone
It is secreted from the acidophilic type of cells of anterior pituitary.
Chemistry: It is a protein made up of 198 amino acids and with a molecular
weight of 25,000.

Physiological functions and actions

1. During pregnancy prolactin promotes the growth and development of breast or
mammary gland. It

prepares the mammary gland for the secretion of milk. It produces hyperplasia of
breast tissue. 2. It promotes the production of milk during lactation.

3. During lactation prolactin initiates the milk let down or milk ejection.
4. During pregnancy prolactin is responsible for the maintenance of corpus
luteum for months.

Influence of prolactin on reproductive functions

During lactation plasma concentration of prolactin will be high. This high
prolactin level a inhibits the secretion of gonadotropic hormone releasing factor
from the hypothalamus. This in-turn suppresses the secretion of FSH and LH.
Without gonadotropic hormones no ovulation. This is amenorrhea during
lactation. So no chance of fertilisation and pregnancy. Lactation prevents
pregnancy by maintaining a high plasma level of prolactin. It is the physiological
contraception during lactation. This natural process ensure adequate spacing
between two children. Prolactin promotes the maternal behaviour of mother and
increasing the love, affection and caring of the new born.

In males—Prolactin decreases spermatogenesis. Disorder: Hyper secretion of

prolactin
Cause: Tumorous growth of lactotrophs of anterior pituitary Signs and
symptoms

Abnormal increase in prolactin level in the blood. Inhibits FSH and LH

secretion, no ovulation amenorrhea, leads to infertility.
Milk secretion even without pregnancy. Amenorrhea- galactorrhea syndrome.
Regulation of secretion of prolactin
Hypothalamus
–
Breast PIF
Lactation Anterior pituitary
Prolactin

Fig. 7.14
Regulation of secretion of prolactin

Prolactin secretion is controlled by a neuro endocrine reflex. It is known as

suckling reflex. Hypothalamus secretes a small peptide known as prolactin
inhibiting factor(PIF). Prolactin inhibiting factor is carried through the
hypothalamo hypophysial portal vessels and reaches the anterior pituitary. It
inhibits the anterior pituitary from the secretion of prolactin.

During lactation the receptors of the breast get stimulated. The sensory impulses
from these receptors are transmitted to the hypothalamus. These impulses will
inhibit the hypothalamus from the secretion of PIF. Now anterior pituitary
becomes free to secrete prolactin. Prolactin level in blood increases, it promotes
production of milk.
Thyroid Stimulating Hormone (TSH)
Secreted from basophilic type of cells of anterior pituitary. Chemistry

It is a glycoprotein of molecular weight of 25,000. Physiological functions and

actions

1. It promotes and controls the growth and development of thyroid gland.

2. TSH stimulates the thyroid gland and controls the secretion of thyroid
hormones.

Adrenocorticotropic hormone/cortico trophin (ACTH) It is secreted from the

basophilic type of cells of anterior pituitary.
Chemistry

It is a polypeptide made up of 39 amino acids and a molecular weight of 4,500.

Physiological functions and actions

1. It promotes and controls the growth and development of adrenal cortex.

2. It controls the secretion of hormones from the adrenal cortex particularly it
controls the secretion of cortisol.
3. Helps in facing stress and strain.
4. It stimulates melanocytes in skin.

Gonadotropic hormone (GnTH)

FSH and LH are together called as gonadotropic hormone or gonadotrophins.
Gonodotropins are secreted from the basophilic type of cells of anterior pituitary.
Follicular stimulating hormone FSH

Source: It is secreted from the basophilic type of cells of anterior pituitary.

Chemistry: It is a glycoprotein of molecular weight of 25,000.

Physiological functions and actions

Females
1. It stimulates the proliferation and maturation of

graafian follicle or ovarian follicle.

2. It produces the maturation of one of the ovarian
follicle at a time during menstrual cycle. 3. Along with luteinising hormone,
FSH produces the
rupture of matured ovarian follicle leading to the
release of ovum. This process is known as ovulation. Males
1. It promotes spermatogenesis.
2. It maintains the health of seminiferous tubule.

Luteinising hormone - LH
Source: It is secreted from the basophilic type of cells of anterior pituitary.
Chemistry: It is a glycoprotein. Molecular weight is 25,000. Physiological
functions and actions

Females

1. Luteinising hormone stimulates the growing ovarian follicle to secrete the

hormone oestrogen.
2. Along with FSH it produces the rupture of matured ovarian follicle leading to
the release of ovum.
3. LH is responsible for the maintanence of cells of ruptured follicle as corpus
luteum and LH stimulates the corpus luteum to secrete progesterone. Males
LH is also called as interstitial cell stimulating hormone (ICSH). This hormone
stimulate the interstitial cells of testis or interstitial cells of Leydig to secrete
androgens or testosterone.

Melanocyte stimulating hormone (MSH)

It is secreted from the intermediate zone of pituitary. Chemistry: It is a
glycoprotein
Functions and actions

1. It promotes and controls the proliferation and dispersion of melanocytes in

skin.
2. It controls the secretion of melanin and controls skin colour.

Regulation of secretion of MSH

Secretion of MSH is controlled by the hypothalamus. Hypothalamus secretes a

small peptide known as MSH inhibiting factor. This factor is carried by the
hypothalamo hypophysial portal vessels. This inhibits the pituitary from the
secretion of MSH.

Posterior Pituitary
Secretes two hormone:
1. Vasopressin/ADH 2. Oxytocin
Anti Diuretic Hormone or vasopressin
It is secreted from the posterior pituitary. ADH is actually synthesised at the
supra optic nucleus of the hypothalamus. From the hypothalamus it is carried to
the posterior pituitary by hypothalamo-hypophysial nerve tract.
Chemistry: It is a polypeptide made up of nine amino acids and molecular
weight of 1100.
Physiological actions and functions of vasopressin/ADH Action at wall of
blood vessel: Action of vasopressin on wall of blood vessel is mediated through
the receptor V1. Vasopressin binds with V1 receptors present on the smooth
muscles of blood vessels. This binding of hormone with receptor activate
enzyme phospholipase C that hydrolysis of phosphatidylinositol. This increases
intracellular availability of calcium ions on the smooth muscles of blood vessel.
This will produce vasoconstriction of arterioles and venules. This increases total
peripheral resistance, cardiac output and thereby increases the blood pressure. So
vasopressin plays a role in regulation of BP.
Action at the renal tubule: This action of ADH is mediated through the
receptor V2 ADH binds with V2 receptors present mostly at collecting duct and
DCT. This binding of hormone with receptor makes the formation of cyclic
AMP. cAMP activates protein kinase. This enzyme causes phosphorylation of
membrane and cellular proteins. This enhances the transport of endosomes
containing water channels. More and more water channels are get incorporated
into membrane. These water channels are called aquaporins. Aquaporin 2 is
mostly responsible for increasing the permeability of DCT and collecting duct.
So more water is reabsorped. Urine is concentrated. Less water is lost through
urine—anti-diuretic action.

More water is retained in the body. So take part in: Regulation of extracellular
fluid volume. Regulation of blood volume.
Regulation of blood pressure.

Vasopressin shows its water conservation action at very low concentration and
shows it vasoconstrictor action at a relatively higher concentration.

Other actions of ADH

ADH acts as a neurohormone or neurotransmitter in
brain and help in storage of information as memory. ADH increases the
secreation of CRF and ACTH. This
action is mediated through receptor V3.
It increases the break down of glycogen in liver.
Functions and actions: Summary

1. Vasopressin is a vasoconstrictor in action. It produces vasoconstriction of the

blood vessels. This will help to increase TPR. So it is useful in the regulation of
BP.

2. ADH acts at the renal tubule, at the collecting duct of the nephron. ADH
increases the reabsorption of water at the collecting duct. Because of the above
action ADH takes part in the regulation of water balance.

3. It also controls the extra cellular fluid volume and blood volume.
4. By controlling blood volume it takes part in the regulation of B.P.

Regulation of secretion
+ Hypthalamus
Osmotic concentration of blood
+
Posterior pituitary
Blood volume
–

ADH + Kidneys

Water loss through

urine Water reabsorption

Fig. 7.15
Regulation of secretion of ADH

Secretion of ADH is controlled by the hypothalamus. It is influenced by the

osmotic concentration of the blood. Osmolality of blood. Suppose osmotic
concentration of blood increases that will stimulate the hypothalamus.
Hypothalamus will inturn stimulate posterior pituitary. This will increase the
secretion of ADH. ADH acts at the kidneys. It increases water reabsorption from
renal tubule, decreases water loss through urine. It increases blood volume and it
will decrease the osmotic concentration of blood to normal.

Other factors influencing ADH secretion

Decreased blood volume, ECF volume, decreased angiotensin II, hypoglycemia

etc. stimulate ADH secretion. A change in 1% of blood Osmolality significantly
influence ADH secretion. When blood volume changed by 10% it will influence
the secretion of ADH.

Diabetes insipidus
It is an endocrine disorder commonly resulting from
hyposecretion of ADH manifested with polyurea.
Cause: Injury of hypothalamus or posterior pituitary.

TABLE 7.2
Types of diabetes insipidus
Deficient production of ADH
Deficient action of ADH

Central Diabetics inspidus Primary deficiency

Causes: Destruction of hypothalamus and neurohypophysis due to (a) Severe
head injuries (b) Chronic meningitis (c) Viral encephalitis
(d) Vascular injury – block

in the feeding artery to posterior pituitary

Secondary deficiency:
Inhibition of ADH
secretion.
Nephrogenic diabetes
insipidus
Causes: Partial or complete failure of nephrons to respond to ADH. It may be
due to action of drugs like Rifampicin.
demeclocycline
– Obstructive uropathy
– Hypercalcaemia
– Hypokalaemia. Acute tubular necrosis

Clinical features of diabetes insipidus

1. Poly urea – Urine output increases to several litres per day

2. Tasteless urine
3. Polydipsia -excessive thirst due to dehydration.
4. Dilute pale urine with low specific gravity. Osmolality of urine is less than
300 mosm/L.

Treatment
1. Drugs to improve the renal response to ADH.
2. Injections of ADH.
3. Excess water intake.

Syndrome of inappropriate ADH secretion (SIADH)

Cause

1. Hypersecretion of ADH from tumorous posterior pituitary.

2. Excess secretion from an ectopic source—small celled cancer of lungs.
3. Neurogenic disease like multiple selerosis.
4. Head injury.

Clinical features
1. Excess levels of ADH in the blood.
2. Increased water reabsorption from renal tubule leading to water retention.
3. Increase in ECF and blood volume.
4. Decreases aldosterone secretion. This will lead to

increased excertion of sodium, resulting in hyponatremia. Blood osmolality

decreases in spite of excess ADH. Hypotonicity of the extracellular fluid
normally inhibits the secretion of ADH. But in SIADH, the secretion of ADH
may continue “in appropriately”, despite hypotonicity of the extracellular fluid.

5. The excess retained water in the blood decreases plasma osmolality. Later
water enters into intratracellular space. This will produce oedema. SIADH
produces water intoxication called as over hydration or a dilution syndrome.

Urine osmolality exceeds plasma osmolality. Hypovolumia is a more important

factor influencing increased secretion of ADH than hyperosmolarity. A 10-20 %
reduction in blood volume increases the secretion of ADH.

OXYTOCIN

It is secreted from the posterior pituitary. It is synthesised at the paraventricular

nucleus of the hypothalamus. From the hypothalamus oxytocin is carried to the
posterior pituitary through the hypothalamo hypophysial nerve tract.

Chemistry
It is a polypeptide made up of 9 amino acids and a
molecular weight of 1100.
Functions and actions
1. During last stage of pregnancy oxytocin level in the blood increases. Oxytocin
produces a strong contraction of muscles of the uterus. This develops a
propulsive force. This helps in parturition or child birth. Parturition reflex.
2. During sexual intercourse or coitus oxytocin produces the contraction of
uterine muscles. This uterine contraction increases the motility of sperms. This
increases the chance of fertilisation and increases chance of pregnancy.
3. During lactation oxytocin produces the contraction of myoepithelial cells of
breast. This produces a squeesing effect on the breast and it is responsible for the
maintenance of continuity of milk flow from

the breast to the mouth of the baby. Milk ejection reflex.

4. Functions of oxytocin in male: Concentration of oxytocin increases during

ejaculation. This melioration oxytocin level produce increased contraction of
smooth muscles of the vas deferens. This propels sperms toward the urethra.

Therapeutic uses of oxytocin: Synthetic oxytocin is used to induce labour on

full term of pregnancy and also to facilitate the progress of labour.

Injected after delivery to prevent exess post partrum bleeding.

Used as intranasal spray to induce lactation.

Regulation
There are two different mechanisms controlling the
secretion of oxytocin:
1. During pregnancy 2. During lactation.
Regulation of secretion of oxytocin during pregnancy It is controlled by a
positive feedback mechanism. The
presence of foetus inside the uterus produces distension of

the wall of the uterus. This will stimulate the stretch receptors present in the wall
of the uterus. From this stretch receptors impulses are transmitted to the
hypothalamus. It will stimulate the hypothalamus. The hypothalamus, will in
turn, stimulate posterior pituitary. This will increase the oxytocin release. This
will increase uterine contraction. This will increase the uterine distension further,
more stimulation of the receptors, further stimulation of hypothalamus and
posterior pituitary, further increase in concentration of oxytocin, further increase
in uterine contraction and uterine distention. The oxytocin level in the blood
gradually increases, reaches a peak and it falls abruptly after parturition.
+ Hypothalamus
Stretch receptors +
Posterior pituitary +

Uterine distention + Oxytocin

Contraction of uterine muscles Wall of+uterus

Fig. 7.16
Regulation of secretion of oxytocin during pregnancy. Positive feedback
mechanism

Regulation of secretion of oxytocin during lactation It is controlled by a

neuro-endocrine reflex- suckling
reflex. During lactation the suckling of the breast by the
child stimulates numerous receptors of the breast. From these
receptors sensory signals are transmitted to the hypothalamus.
It stimulates the hypothalamus. It will inturn stimulate
posterior pituitary. It increases the secretion of oxytocin.

Fig. 7.17 Suckling reflex

THYROID GLAND

The thyroid gland is butterfly—shaped and is located just inferior to the larynx.
It is composed of right and left lateral lobes, one on either side of the trachea,
that are connected by an isthmus anterior to the trachea. The normal mass of the
thyroid is about 30g. The thyroid gland has a rich blood supply. Microscopically,
the thyroid is composed of a large number of spherical sacs called thyroid
follicles. Cuboidal epithelial cells line each follicle. The lumen of the follicle is
filled with a colloid. The major constituent of the colloid is a glycoprotein called
thyroglobulin. When the gland is inactive, the colloid is abundant, follicles are
large, and cells lining them are flat. When the gland is active, cells lining them
are cuboidal or columnar, and the edge of the colloid is scalloped. Thyroid
secretes three hormones.

1. Triiodothyronine (T3) and reverse T3

2. Thyroxine (T4)
3. Thyrocalcitonin/calcitonin.

Bio synthesis of thyroid hormones

It takes place through a number of steps.

1 . Synthesis and secretion of thyroglobulin Thyroid cells secrete a

glycoprotein thyroglobulin.

It is a large protein with molecular weight 660000. This protein is rich in amino
acid tyrosine. 123 tyrosine residues.
Epiglottis
Hyoid bone
Larynx

Superior parathyroid glands

Thyroid glands

Inferior parathyroid
glands

Trachea Capillaries
Normal folicle
Basal
membrane Apical
membrane Stored hormone (colloid)

Stimulated hyperplastic follicle

Colloid undergoing resorption

Fig. 7.18
Thyroid gland and follicles
2. Iodine trapping, iodine pump or iodine uptake

The follicular cells of the thyroid gland takes up iodine from blood against the
concentration gradient. This takes place at the expenditure of metabolic energy.
The concentration of iodine inside the follicular cells of thyroid gland is about
30 times greater than the other cells of the body. Daily minimum requirement of
iodine is 150 microgram.

3. Activation of iodine
Iodine is activated by the action of oxidative

enzymes like peroxidase. Iodine is converted to iodine by oxidation. This

process is known as organification.
4. Iodination of tyrosine
Iodination of tyrosine give rise to monoiodotyrosine and diiodotyrosine.

5. Oxidative condensation reaction

One molecule of diiodotyrosine and one molecule of monoiodotyrosine

undergoes oxidative condensation and give rise to T3 or Triiodothyronine.
Diiodotyrosine + Monoiodotyrosine →

Triiodothyronine (T3). Monoiodotyrosine + Diiodotyrosine

Oxidative condensation T (Reverse T ) →
3 3

Two molecules of diiodotyrosine undergoes oxidative condensation and give rise

to thyroxine or T4.
Diiodotyrosine + Diiodotyrosine →
Oxidative condensation T4 or thyroxine →

About 90% of thyroid hormones are secreted in the form of thyroxine. About
10% is secreted in the form of T3 or triiodothyronine.

Concentration of thyroid hormones in plasma: In a euthyroid (normal)

individual plasma concentration of thyroid hormones are—T4 = 8 mg%, T3 =
0.15 mg %. Most of thyroid hormones (99%) bind with plasma proteins namely
thyroxine binding globulin, and thyroxine binding prealbumin. Only 1.% of
thyroid hormones will be in the free form in the plasma. This free form of
thyroid hormones are biologically active, bound form act as a reserve. The
concentration of free T4 and T3 on the plasma—2 mg% and 0.3 mg%
respectively.

Mechanism of action of thyroxine: Both T3, T4 enter into the cell crossing the
cell membrane. Inside the cell the T4 molecules are converted into T3 molecules.
T4 mostly acts as pro-hormone. The T3 combines with receptor situated on the
nucleus. This hormone receptor complex activates specific genes. This forms
mRNA. The mRNA goes out of nucleus to the ribosome. Here as per the coded
information of mRNA a new protein is synthesised. The protein so synthesised
may be an enzyme, a peptide hormone, or muscle protein like myosin. Further
actions will depend upon the biological nature of protein synthesised.
Follicle Blood
capillaries
Iodide Oxidation Iodide peroxidase Tyrosine Iodination
Iodine
Iodinase
Thyroglobulin
Monoiodo Diiodotyrosine (MIT)
Tyrosine (DIT) Plasma
T3

T4 Triiodothyronine

(T ) 3 Tetraiodo thyronine or
Thyroxine

T4

Fig. 7.19 Biosynthesis of thyroid hormones

–
2I + H O I
22 2
II
2I+HO2CH CHCOOH HO2CH CHCOOH or HO2CH CHCOOH
NH2 NH2 NH2
Tyrosine Monoiodotyrosine (MIT) Diiodotyrosine (DIT)
IIII
HO2CH CHCOOH +HO2CH CHCOOH NH2 HO
O
CH CHCOOH + CH —CHCOOH 23
I NH2 I
DIT
NH2
DIT NH2I I
¢¢3, 5, 3 5 -Tetraiodothyronine (thyroxine, or T )4 Alanine
IIII
HO CH CHCOOH +HO
2
CH CHCOOH
2
HO NH2 O
CH CHCOOH + CH —CHCOOH 23
NH2
I I DIT
Alanine NH2 I NH2I
MIT ¢3, 5, 3 -Triiodothyronine (reverse T )3 or
Thyroid hormone synthesis Follicular cell
DIT + MIT DIT + DIT
I I OXIDATIVE CONDENSATION HO
I NH2 O
CH CHCOOH + CH —CHCOOH 23
Alanine NH2I
¢¢3,3 5 -Triiodothyronine (reverse T )3 Fig. 7.20 Steps of biosynthesis of thyroid
hormones
Functions and actions of thyroid hormones

Actions of thyroxine and triiodothyronine are similar. T3. is more potent than T4.
Thyroid hormones are calorigenic hormones. Oxygen consumption and
thyroxine increase the rate of metabolism in almost all the tissues of the body
except, brain, spleen, retina.

Metabolic functions
Action on carbohydrate metabolism

1. It promotes the absorption of glucose from the intestine.

2. It promotes gluconeogenesis.
3. It promotes of glycogenolysis.
4. It will increase the blood glucose level. This action is known as
hyperglycemic action.

Action on protein metabolism: Thyroxine stimulates both transcription and

translation stages of protein synthesis. By this way it promotes the synthesis of
proteins. This produces greater protein synthesis than break down and results in
positive nitrogen balance. This action is very much essential for the promotion
of growth and development of child. A higher pharmacological doses of
thyroxine produce greater protein catabolism due to increases in BMR. The
catabolic effect in skeletal muscle may produce severe muscle weakness with
high fatiguability. Thyroxine myopathy. Mobilisation of bone protein produces
osteoporosis.

Action on lipid metabolism: It increases the break down of fats and lipids for
energy production.

It decreases the stores of triglycerides and phospholipids. It produces a net effect

of decrease in plasma cholesterol and total lipid.
Action on individual organs and systems
(a) Action on cell: Thyroxine increases the intracellular concentration of
enzymes. It increases the size and number of mitochondria.

(b) Action on cardio vascular system: Increases the rate of erythropoiesis by

increasing the synthesis of erythropoietin.
1. It increases blood glucose level.
2. It slightly increases blood volume. 3. It increases the heart rate by increasing
betal

adrenergic receptors of heart.

4. It increases the cardiac output.
5. It increases systolic blood pressure.
6. It decreases diastolic B.P.
7. Increases pulse pressure.
(c) Action on respiratory system: Thyroxine increases the rate and depth of
respiration or it increases alveolar ventilation. It increases of O2 utilisation.
(d) Action on digestive syste
1. It increases appetite.
2. It increases the secretion of digestive juices. 3. It increases the motility of GIT.
4. It increases glucose absorption.
(e) Action on excretory system
1. It increases renal blood flow and it increases GFR and urine output. It
increases reabsorption of salt and water.
(f) Action on other endocrine glands: Thryoxine stimulates the parathyroid
gland, adrenal cortex and pancreas.
(g) Action on neuro muscular system: It increases the excitability of neuro
muscular system. (h) Action on gonads: Thyroxine is essential for the proper
maturation of gonads. It is also important for the proper functioning of the
gonads. Required for sperimatogenesis in male ovulation in female. (i) Action of
thyroxin on CNS
1. T3 and T4 are essential for the proper development of brain during fetal life
and infancy.
2. T3 and T4 promote the growth of cerebellum and cerebrum by enhancing the
proliferation of neurons and by increasing the branching of nerve fibres. Thyroid
hormones enhance velocity of conduction of impulses in nerve fibre. The
hormones are essential for mental alertness, proper reflex responses, learning
and memory.
Thyroid hormones enhance the synthesis of neurotransmitter by increasing the
synthesis of enzymes needed for it. Thyroid hormones promote myelination.
Deficiency of thyroid hormones during early critical developmental period make
permanent damage to brain and irreversible retardation in CNS development.
Therefore the insult caused by hypothyroidism during infancy cannot be
corrected by administering thyroid drugs later in life.

Role of thyroid hormones on growth and development

Thyroid hormones promote the synthesis and secretion of growth hormone.

Thyroid hormones promote linear growth of bones, increasing the height of an

individual.
Thyroid hormones are responsible for timely eruption and development of teeth.

Regulation of Secretion of Thyroxine

Hypothalamus
–
TRF
+ Anterior pituitary
–
TSH
+ Thyroid gland
Thyroxine and T3

Fig. 7.21 Hypothalamo—hypophysial—thyroid axis Negative feedback

mechanism for the regulation of secretion of thyroid hormones. TRF—
Thyrotropin Releasing Factor. TSH— Thyroid Stimulating Hormone

Secretion of thyroid hormones is controlled by TSH (thyroxine stimulating

hormone) secreted from anterior pituitary. It is a negative feedback mechanism.
It operates along the hypothalamo hypophysial thyroid axis. This axis is an
example for 3 tier endocrine hierarchy. Hypothalamus is at the highest level,
anterior pituitary is at the middle level and thyroid gland is at the lowest level.
Hypothalamus secretes a small peptide thyrotropin releasing factor (TRF). TRF
reaches the anterior pituitary through the blood. It stimulates the anterior
pituitary and increases the secretion of TSH. TSH reaches the thyroid gland and
it stimulates the secretion of thyroid hormones. When the blood concentration of
T3 and T4 increases, it will exert a negative feedback effect at the level of
hypothalamus and anterior pituitary. This inhibits further secretion of TRF from
the hypothalamus and TSH from the anterior pituitary. This allows the
concentration of T3 and T4 to come down to the normal. This endocrine axis is
very sensitive and effective. At each level of endocrine hierarchy there is a
thousand time magnification.

Endocrine disorder related to the thyroid gland

1. Cretinism
2. Myxoedema
3. Goitre
4. Grave’s disease or hyperthyroidism.
Cretinism

It is an endocrine disorder resulting from the hypo secretion of thyroid hormones

in children.

Causes:
1. Lesion of thyroid gland due to infection or injury.
2. Lesion of anterior pituitary leading to hypo secretion of TSH.
3. Lesion of hypothalamus leading to hypo secretion of TRF.
4. Depression of thyroid gland function due to repeated x-ray exposures.
5. Action of anti thyroid drugs.
6. Autoimmune disease.
Signs and symptoms
1. All the milestones of growth and development are significantly delayed. This
includes the starting of crawling, standing, walking, running, talking etc. But the
clinical manifestations of cretinism may be seen only after sixth month of life.
Till that time the thyroxine received through the mother’s milk is sufficient.
2. Stunted skeletal growth, resulting in short height, club like fingers. Body is
not proportionate. 3. Retarded mental growth resulting in low IQ. 4. Improper
growth and development of gonads resulting in impotency.
5. Irregular deposition of fat in the body. Pot belly. 6. Low BMR (Basal
metabolic rate).
7. Low heart rate, low body temperature. 8. Mentally sluggish. Idiotic look with
thick parted lips.
9. Cold intolerance.
10. Rough, thick, dry wrinkled skin.
11. Tongue becomes big and hangout of mouth with dribling of saliva.
12. Thick and husky voice.
Cretinism arrest of growth
I. Physical growth II. Mental growth III. Sexual growth

A. Skeletal B. Muscular C. Visceral Mental retardation low I.Q.

DwarfWeak muscles Not so retarded; hence pot bellied bloated body

Sluggish
movements
(i) Infantile sex
(ii) Secondary sexual

characteristics may not appear

(iii) Infertility

Fig. 7.22 Cretinism or thyroid dwarf clinical features Myxoedema: Gull’s

disease

It is an endocrine disorder resulting from hyposecretion of thyroid hormones in

adults.
Causes

1. Lesion of the thyroid gland due to infection or injury.

2. Lesion of the anterior pituitary due to infection and injury and leading to hypo
secretion of TSH.
3. Lesion of hypothalamus due to infection or injury and leading hyposecretion
of TRF.
4. Depression of thyroid gland due to repeated x-ray exposures.
5. Action of anti thyroid drugs.
6. Autoimmune disease.
7. Thyroidectomy

Fig. 7.23
Myxoedema
Signs and symptoms
1. Fluid collection in the face. Oedematous face. Non pitting type of oedema. It
is due to the accumulation of proteins and hyalunonic acid. Face becomes
bloatted—Puffy face.
2. Irregular deposition of fat on the body. 3. Thickening of tongue and speech
becomes slurry.

Low pitched voice.

4. Falling of hair from the body. Alopecia.
5. Decrease in BMR.
6. Decrease in body temperature.
7. Degeneration of gonads leading to impotency or sterility.
8. Mental lethargy-psychosis-Myxoedema madness.
9. Atherosclerosis—It is due to increased content of cholesterol in plasma which
later get deposited in the walls of blood vessels.
10. Blood vessels become narrow, resistance increases this leads to hypertension.
11. Weight gain and obesity.
12. Decrease in heart rate, cardiac output and blood volume.
13. Skin—dry and rough.
14. Constipation and anorexia.
15. Increased sensitivity to cold—cold intollerance 16. Froglike husky voice.
17. Poor memory, inability to concentrate.

Goitre

It is a non-neoplastic, non-inflammatory enlargement of the thyroid gland

manifested in the form of mid line swelling of the neck. It is commonly due to
deficiency of iodine in the food.

Goitre is divided into two types:

1. Simple Goitre.
2. Toxic Goitre.

Fig. 7.24
Goitre
Simple goitre or endemic goitre: Non toxic goitre

It is due to deficiency of iodine. It is commonly seen in people living at interior

hilly regions, not common in coastal belt.

Toxic goitre: May be due to the actions of goitrogenic substances.

Simple goitre: Deficiency of iodine leads to inadequate synthesis of T3 and T4.
This leads to a total failure in the negative feedback mechanism. The anterior
pituitary becomes free to secrete TSH. TSH level in the blood increases
abnormally. This will stimulate the thyroid gland and produces its enlargement.

Types of simple goitre

There are four types of simple goitre.

1. Colloidal goitre: Here quantity of thyroglobulin increases producing the

enlargement of the thyroid gland.

2. Parenchymatous goitre: Here the number of follicular cells increases. This

produces the enlargement of the thyroid gland.

3. Nodular goitre: In this case the follicles branches and it increases the number
of follicles and it produces the enlargement of the gland.

4. Toxic goitre: It is due to the action of goitrogenic substances goitrin, found in

cabbage. Enlargement of thyroid gland with hyper secretion of hormones are
seen.

Treatment for goitre

1. At initial stages it can be treated with iodine supplementaion through iodised

salt.
2. At the later stages it can be treated with thyroxine and by the surgical removal
of the thyroid gland.

Hyperthyroidism/Grave’s Disease or Thyrotoxicosis

 Fig. 7.25
Exophthalmus—Grave’s disease It is a common endocrine disorder resulting
from hyper secretion of thyroid hormone.
Causes

1. Autoimmune disorder. Plasma cells derived from B-lymphocytes are activated

by antigens. They produce—Thyroid stimulating antibodies or long acting
thyroid stimulator (LATS). It acts like TSH on the thyroid gland and increases
the secretion of T3 and T4.

2. Tumorous growth of thyroid gland.

3. Tumorous growth of anterior pituitary secreting excess TSH.

4. Tumorous growth of hypothalamus secreting excess TRF.

Signs and symptoms

1. Increase in BMR.
2. Increase in body temperature.
3. Increase in heart rate—tachycardia-palpitation.
4. Increase in systolic blood pressure.
5. Increase in the excitability of neuro muscular junction.
6. Fine tremors of fingers.
7. Loss of body weight due to exess mobilisation of fat.
8. Protrusion of eyeball, exophthalmus due to oedematous swelling of
retroorbital tissue.
9. Hypersensitive to heat—heat intolerance. 10. Nervousness and mental
restlessness. Feels tired but cannot sleep.
11. Diarrhoea due to increased motility of GIT. 12. Hyperphagia and increased
appetite.
13. Inspite of hyperphagia, weight loss.
14. Increased sweating.
15. Menstrual disturbances.
16. Infertility, abortion.
Antithyroid substances

Drugs that are known to inhibit the secretion of thyroid hormones are generally
known as antithyroid substances. Three of the best known antithyroid substances
are propylthiouracil, thiocy anate and inorganic iodides. Each of this drugs
blocks thyroid secretion in a different way and the different mechanisms by
which they do so are further explained.

Thiocyanate: Thiocyanate ions decrease iodide trapping, the mechanism by

which the thyroid gland acquires iodine from the circulating blood. The same
pump that transports the iodide ions necessary for normal thyroid function can
also pump thiocyanate ions, perchlorate ions, and nitrate ions.So iodine is not
available preventing the synthesis of thyroid hormones.

Inorganic iodides: Inorganic iodides inhibit most of the activities only when in
very high concentrations, as in 100 times the normal plasma levels of iodides.
This effect, however, remains only for a few weeks. It prevents organic binding
of iodine. This inhibition is called Wolf-Chaikaff effect.

Propylthiouracil —and its relatives, methimazole and carbimazole—decrease

thyroid hormone formation by preventing its formation from iodides and
tyrosine. This drug acts by blocking the peroxidase enzyme that is necessary in
the first step of the formation of thyroid hormones.

Thyroid function tests (TFTs) is a collective term for blood tests used to check
the function of the thyroid. TFTs may be requested if a patient is thought to
suffer from hyperthyroidism (overactive thyroid) or hypothyroidism (underactive
thyroid), or to monitor the effectiveness of either thyroid-suppression or
hormone replacement therapy. It is also requested routinely in conditions linked
to thyroid disease, such as atrial fibrillation and anxiety disorder.

A TFT panel typically includes thyroid-stimulating hormone (TSH, thyrotropin)

and thyroxine (T4), and triiodothyronine (T3) depending on local laboratory
policy.

Thyroid function tests

This may include following tests:
Estimation of plasma free T3 and T4.
Estimation of plasma T3 and T4 bound form Estimation of plasma TSH level
Measurement of thyroxin binding protein TRH response test
Radioactive iodine uptake test
Determination of BMR
Estimation of plasma cholesterol.

Measurement of T3 and T4—concentration of T3 and T4 in plasma is estimated

by radio immune assay or ELISA test. Increase in T3 and T4 level with decrease
in TSH indicate primary hyperthyroidism. Increased TSH level with decreased
T3 and T4 level indicate hypothyroidism.

Thyroid storm
It is seen in hyperthyroid patients. It is a clinical condition

observed sometimes in hyper thyroid patient when they are exposed to severe
stress like surgery, tissue trauma or illness. The patient suddenly becomes
severely ill. The major features exhibited are high fever, tachycardia, palpitation,
restlessness and circulating collapse. It is a serious medical emergency. It can be
managed by immediate fluid replacement and steroid administration.

Adrenal Gland or Supra Renal Gland

Adrenal glands are situated above the kidneys. Therefore they are called as supra
renal glands. The two adrenal glands each of which weighs 3.5–5 g lie at the
superior poles of the two kidneys. Each gland has a flattened pyramidal shape
and measures 3–5 cm in height, 2–3 cm in width and a little less than 1 cm thick.

Physiologically adrenal gland is divided into two independent glands:

1. Outer—adrenal cortex and
2. Inner—adrenal medulla.

Adrenal Cortex
Histologically adrenal cortex is divided into three zones:

1. Outermost zone—Zona Glomerulosa.

Hormones—Minerelocorticoids, e.g., Aldosterone.
2. Middle zone—Zona Fasciculata.
Hormones—Glucocorticoids, e.g., Cortisol.
3. Innermost zone—Zona Reticularis.
Hormones—Sex Steroids, e.g., DHEA. The outermost zone or zona glomerulosa
secretes a group of steroid hormones collectively known as mineralocorticoids.
Zona fasciculata secretes another group of steroid hormones collectively called
as glucocorticoids. Zona reticularis secretes another group of steroid hormones
called sex steroids.
Minerelocorticoids aldosterone
Gluco corticoids cortisol
Androgens
Epinephrine and norepinephrine
Progesterone
Deoxycorticosterone
Corticosterone
18 oxidase
Aldosterone (Line A)

Fig. 7.26
Adrenal gland
Cholesterol (C 27)
Desmolase
Pregnenolone (C 21)
17 Hydroxypregnenolone
17 Hydroxy Progesterone
21 Hydroxylase
11 Deoxycortisol (compound S)
11 Hydroxylase
Cortisol (Compound F)
(Hydrocortisone)
(Line B)
Zona glomerulosa

Zona fasiculata
Zona reticularis
Dehydropiandrosterone
Androstenedione (Line C)

Fig. 7.27 Major steps of cortical hormonal biosynthesis

Aldosterone
The important mineralocorticoids are aldosterone and deoxycorticosterone.
Aldosterone is the most important mineralocorticoid.
Source: Aldosterone is secreted from the zona glomerulosa of the adrenal
cortex.
Chemistry: It is a steroid hormone.
Daily secretion: 100–200 microgram/24 hrs.
Plasma concentration: 0.6 ng %.
21
CH OH 2
CH OH 18 20COO 2 HO
HC
3 OH CO19
CH 17 CH 3 HO
CH3 CD
Renin angiotensin mechanism
+ Kidney
BP Renin
– ve
O
Cortisol AB
(compound F of kendal) OAldosterone O(Aldehyde form) BV
–
Angiotensin Angiotensin I substrate
ve
Converting enzyme
H O loss Angiotensin II+ Adrenal2
cortex H O reabsorption2
Aldosterone
HO
Dehydroepiandrosterone (DHEA) Fig. 7.28 Hormones of adrenal cortex
+ Na+ reabsorption Kidney
Fig. 7.29 Regulation of secretion of aldosterone by Renin– Angiotensin
Physiological functions and actions

1. It plays a major role in the control of concentration of potassium and sodium

ions in the blood.
2. Aldosterone acts at the renal tubule. It promotes the re-absorption of sodium
ions.
3. Indirectly increases water reabsorption.

4. It takes part in the regulation of extracellular fluid volume and blood volume.
5. It takes part in the regulation of B.P.
6. It decreases the potassium reabsorption at the renal tubule. So it increases the
excretion of potassium through the urine.
7. It stimulates urinary secretion and excretion of hydrogen ions. This helps in
the regulation of pH of blood.

Regulation of secretion of aldosterone

Secretion of aldosterone is regulated by three mechanisms. 1. Renin angiotensin
mechanism
2. Potassium ion concentration of the blood 3. Regulation by ACTH.
Suppose blood pressure falls. That will stimulate

kidneys. Kidneys respond by the secreting renin. Renin produces the conversion
of angiotensin substrate to angiotensin I. This angiotensin I is converted into
angiotensin II. Angiotensin II stimulates the adrenal cortex. That will increase
the secretion of aldosterone. Aldosterone acts at the kidneys. It increases the
reabsorption of Na+ and water. This will increase blood volume. This will in turn
increase the blood pressure to normal. It is known as renin angiotensin
aldosterone axis.

Potassium ion concentration in the blood

Suppose potassium ion concentration in the blood increases, it directly

stimulates the zona glomerulosa of the adrenal cortex. This will increase the
secretion of aldosterone. It acts on the kidneys. So the potassium reabsorption
decreases. So potassium excretion through the urine increases. So K+ level in the
blood comes down to normal.
+ Adrenal cortex
Potassium ionAldosteroneconcentration
– ve
+ Kidneys
+
K loss
+
K reabsorption

Fig. 7.30 Regulation of secretion of aldosterone by K+ concentration in blood

Regulation of secretion of aldosterone by ACTH Hypothalamus secretes a

small peptide known as corticotropin releasing factor (CRF). This CRF will
stimulate anterior-pituitary and increase the secretion of ACTH. ACTH
stimulates adrenal cortex and increases the secretion of aldosterone.
Hypothalamus
CRF
+
Anterior pituitary
ACTH
++
Adrenal cortex
7.31 Regulation of secretion of aldosterone by ACTH Disorder
Aldosterone Fig.
related to aldosterone
Primary hyper aldosteroidism/Conn’s syndrome Conn’s syndrome is an
endocrine disorder resulting from hyper secretion of aldosterone.
Cause
1. Tumorous growth of adrenal cortex secreting excess aldosterone.

Signs and symptoms

1. Disturbance in the electrolytic balance of the blood.
2. Na+ ion concentration increases K+ ion concentration decreases.
3. It increases extracellular fluid volume and blood volume increases.
4. B.P. increases or it develops hypertension.
5. Prolonged hypokalemia leads to
(a) muscular weakness
(b) kidney damage.

6. Metabolic alkalosis because aldosterone stimulates urinary secretion and

excretion of hydrogen and ammonium ions.

7. Muscle weakness and fatigue due to potassium depletion.

Aldosterone Escape
An increase in extracellular fluid volume increases arterial blood pressure.
Increase in BP increases GFR and causes greatly increased kidney excretion of
both salt and water— this phenomenon is known as Pressure diuresis.

When extracellular fluid volume increases to about 5–15 % above the normal in
response to excess of aldosterone, the arterial BP increases by about 15–25 mm
of Hg. This increased BP (hypertension) returns the salt and water loss to normal
inspite of high aldosterone level. This secondary increase in salt and water
excretion by the kidneys as a result of pressure diuresis is called aldosterone
escape.

Because of this the rate of gain of salt and water by the body is zero.
Zona Fasciculata—Middle zone

It secretes a group of steroid hormones collectively called as glucocorticoid. The

important Glucocorticoids are:
1. Cortisol and 2. Corticosterone.

Cortisol
It is an important glucocorticoid secreted from the zona fasciculata of adrenal
cortex.
Chemistry: It is a steroid hormone.
Daily secretion: 10–15 mg/24 hours.
Plama concentration: 14 micro......
CH OH 21 2
18 CO
20 HC
HO3 OH 19CH17
3
O Cortisol Fig. 7.32 Cortisol

Physiological Functions and Actions

1. Metabolic functions
1. Action on carbohydrate metabolism
(a) Cortisol stimulates gluconeogenesis in liver.

(b) It promotes the conversion of glucose to glycogen and favours the deposition
of glycogen.
(c) It opposes the action of glucose uptake by cells. (d) It stimulates the
absorption of glucose from the intestine into blood. Cortisol increases blood
glucose level and this will lead to hyperglycemia. This action is called as
hyperglycemic action.

2. Action on protein metabolism

(a) Cortisol increases the synthesis of proteins in the liver.

(b) Cortisol increases the breakdown of proteins in the peripheral tissues like
muscle.
(c) Body as a whole cortisol produces greater breakdown of proteins than
synthesis. Therefore this hormone leads to negative nitrogen balance.

3. Action on lipid metabolism

Cortisol facilitates the lipolytic actions of growth hormone, catecholamines,

glucagon and thyroxin. So it causes lipolysis and causes the mobilisation of fatty
acids from adipose tissue. Cortisol stimulates hypothalamus to secrete
neuropeptide Y. This increases appetite and food intake. It also activates
lipogenesis by activating tepo protein lipase and glucose 6-phosphate
hydrogenase activity of adiposites. This causes fat accumulation and
maldistibution of fat in the body resulting in obesity.

4. Action on cardio vascular system

(a) It increases blood glucose level. Hyperglycemic action.

(b) It increases R.B.C. count. It increases platelet count. It increases neutrophil
count.
(c) It decreases lymphocyte count, eosinophil count and basophil count.
(d) Slightly increases blood volume and blood pressure.

5. Action on mineral metabolism

(a) Action of cortisol is similar to aldosterone in mineral metabolism. But it is
not as potent as

aldosterone. Increases sodium reabsorption. Decreases potassium reabsorption

from renal tubules.

6. Action on nervous system

Cortisol increases the excitability of the nervous system. It may in fluence mood
changes, irritability and sleep.

7. Action on gonads
Cortisol is essential for the proper functioning of the gonads.

8. Anti inflammatory action and anti allergic action

Anti-inflammatory action: Inflammation is a local response of body to tissue

injury. These responses in general include the following—movement of
leukocytes to the site of injury and phagocytosis if microorganisms, dilation of
blood capillaries increasing vascularity thereby increasing the availability of
antibodies, greater production of lymphocytes and macrophages. Cortisol
opposes all the inflammatory responses by

(a) Inhibiting the synthesis of chemical mediators of inflammation like—

prostaglandins, leukotriene.
(b) Inhibiting the release of interleukins from macrophages.
(c) Suppress the proliferation of T lymphocytes.
(d) Inhibits the migration of leukocytes to the site of injury.
(e) Stabilises lysosomal membrane thereby reduce the release of proteolytic
enzymes.
(f) It decreases the sensitivity to tissue to microbial toxins.

Anti allergic action

Allergic responses are mediated through the local hormone histamine secreted
by mast cells. Cortisol opposes the allergic responses by

(a) Suppressing the proliferation and growth of mast cells.

(b) Inhibiting degranulation of mast cells thereby preventing the release of
histamine.
Immunosuppressive action of control is produced by

(a) By decreasing the number of lymphocytes in the blood by stimulating their

apoptosis.

(b) By inhibiting the release of interleukins. 9. Permissive action

Small amounts of cortisol must be present for a number of reactions to occur,

although they may not produce the reactions by themselves, this is called
permissive action. For example, cortisol must be present for

1. Glucagon and catecholamines to exert their calorigenic action.

2. For catecholamines to produce pressor response and bronchodilatation.
3. Development of mammary gland during puberty.
4. Surfactant synthesis in fetal lungs.

Regulation of Secretion of Cortisol

Circadium regulation Stress Emotion Pain
Hypothalamus
–
CRF
+ Anterior pituitary
–
ACTH
+ + Adrenal cortex
Cortisol Fig. 7.33
Regulation of secretion of cortisol

Secretion of cortisol is controlled by ACTH. This regulatory mechanism is a

negative feedback mechanism. It operates along the hypothalamo hypophysial
adrenal axis. Hypothalamus secretes a small peptide known as corticotropin
releasing factor (CRF). CRF stimulates the anterior pituitary and increases the
secretion of ACTH. ACTH stimulates the adrenal cortex and increases the
secretion of cortisol. It is an example for 3 tier endocrine organisation. At each
level of organisation there is a thousand time magnification. When the
concentration of cortisol in the blood increases that will exert a strong –ve
feedback effect at the level of hypothalamus and anterior pituitary. This stops
further secretion of CRF from hypothalamus and ACTH from anterior pituitary.
The secretion of CRF from hypothalamus is influenced by several factors. This
includes circadian effect, the mental stress, pain, anxiety stimulate hypothalamus
to secrete more of CRF.

Disorders related to cortisol

1. Hypo secretion of cortisol and aldosterone: Addison’s disease: Primary
adrenocortical insufficiency. It is an endocrine disorder commonly due to the
chronic hyposecretion of hormones of adrenal cortex, cortisol and aldosterone.

Causes

1. Lesion of the adrenal cortex due to infection like tuberculosis.

2. Lesion of the anterior pituitary secreting less ACTH.
3. Lesion of the hypothalamus secreting less CRF.
4. Withdrawal of steroid drugs.

Signs and Symptoms

1. Muscular weakness and muscle cramps. It is due to lack of glycogen storage
in the muscle and also due to disturbance in electrolytic balance.

2. Disturbance in functions of digestive system leading to nausea, vomiting and

diarrhea.
3. Pigmentation of the body.
4. Low blood volume.
5. Low blood pressure or hypotension.
6. Low blood glucose level - Hypoglycemia.
7. Depression of reproductive functions.
8. Decrease in the excitability of the nervous system.
9. Decrease ability to withstand stress.
10. Reduced cortisol secretion leads to hypochlorohydria and associated intrinsic
factor deficiency. This impairs the absorption of Vitamin B12 and leads to
megaloblastic anemia or Addison’s anemia.
Addisonian crisis or Adrenal crisis: This is an acute form of adrenal cortex
insufficiency which occurs due to (a) adrenalectomy (b) abrupt withdrawal of
therapeutically administered glucocorticoids. It abolishes all secretions and is
fatal, death occurs due to circulatory collapse.

2. Cushing’s syndrome
It is an endocrine disorder resulting from hyper secretion of cortisol. There are
two types of Cushing’s syndrome.

1. ACTH dependent—it is also known as Cushing’s disease.

2. ACTH independent.
Causes

1. Tumorous growth of the zona fasciculata of the adrenal cortex secreting

excess cortisol.
2. Tumorous growth of the anterior pituitary secreting excess ACTH.
3. Oat cell cancer of lungs which secretes a polypeptide which behaves like
ACTH.
4. Iatrogenic (produce by a doctor) excess cortisol administration for a long time.

Fig. 7.34
Signs and Symptoms

1. Muscular weakness and muscular wasting - steroid myopathy.

It is due to the excess breakdown of the muscular proteins due to the action of
cortisol and also disturbance in sodium, potassium level, in the blood.

2. Irregular deposition of fat in the body, centripetal distribution of fat. Central

obesity.
3. Moon’s face, narrow eye slit.
4. Obesity of trunk and pendular abdomen. Limbs are thin. Steroid myopathy.
5. Buffallo hump. Fat deposition at lower part and back of neck.
6. Blood glucose level increases—Hyperglycemia— steroid diabetes. Insulin
resistant diabetes. 7. Blood volume increases.
8. Blood pressure increases—Hypertension—due to salt and water retention.
9. Increase in facial hairs (Hirsutism)—due to increased secretion of adrenal
androgens. 10. Impotensy and hypogonadism.
11. Skin becomes thin due to collagen breakdown. 12. Purple striae—due to
thinning of skin from collagen breakdown.
13. Blood—Increase in blood freefatty acid, cholesterol level, eosinopenia,
lymphopenia, basopenia, neutrophilia, polycythemia. 14. Excess secretion of
HCl leading to peptic ulcer. 15. Osteoporosis.
16. Mental disturbances—mood changes, hyper irritability.

Zona Reticularis
It is the innermost zone of the adrenal cortex. It secretes a
group of sex steroids. The amount of sex steroids secreted by the zona reticularis
of the adrenal cortex is very little. Major sex steroids are
dehydroepiandrosterone and androstenedione.

Functions:
1. It contributes to increase in muscle mass.
2. Increases pubic hairs.
3. Exert very little masculinising effect.
4. Facilitates growth.
5. Stimulates the gonads to secreat more sex hormones. Secretion is controlled
by ACTH.
Disorder—Congenital adrenal hyperplasia or adrenogenital syndrome
It is a genetic disorder. Here one of the enzyme required for the synthesis of the
cortisol is missing. Deficiency of for the synthesis of the cortisol is missing.
Deficiency of β hydroxylase. Because of this negative feedback mechanism
operating at the level of hypothalamus and anterior pituitary fail, so secretion of
ACTH becomes

uncontrolled and it increases. Increased ACTH stimulates the adrenal cortex but
it cannot increase the production of cortisol, instead it results in the enlargement
of all the zones of the adrenal cortex. The enlarged zona reticularis secrete large
amount of androgens. This disorder is more common in the female.

Female starts showing the secondary sexual characteristic of male. This includes
the appearance of hair on the face and change in the muscular patterns etc.
Enlargement of clitoris, deepening of voice. Hirsutism, small breast, receding
hairline.

ADRENAL MEDULLA

Adrenal medulla is situated within the adrenal cortex. Constitute about 20–30%
of mass.It secretes three hormones. 1. Adrenaline/Epinephrine – 85% 2. Nor
Adrenaline/nor epinephrine – 12% 3. Dopamine – 03% Adrenaline,
noradrenaline and dopamine are together
called catecholamines.

Biosynthesis of Catecholamines

1. Phenyl alanine is converted to tyrosine by the action of enzyme phenylalanine

hydroxylase.
2. Tyrosine is converted to Dopa—dihydroxyphenyl alanine by the enzyme
Tyrosine hydroxylase.
3. Dopa is converted to Dopamine by the action of dopa decarboxylase.
4. Dopamine is converted to noradrenaline by the action of the enzyme
dopamine beta hydroxylase.
5. Noradrenaline is converted to adrenaline by the action of the enzyme phenyl
ethanolamine N-methyl transferase.

Biosynthesis of Catecholamines
Phenylalanine
Phenylalanine
hydroxylase
Tyrosine
Tyrosine
hydroxylase
Dopa
(Dihydroxyphenylanine)
Dopa decaroxylase Dopamine
Dihydroxyphenylethylamine
Dopamine
b-hydroxylase
Norepinephirine
Phenylethanolamine N-methyltransferase Epinephrine

Plasma concentration
Norepinephrine — 300 pg/ml Epinephrine Dopamine — 30 pg/ml — 3.5 pg/ml

Adrenaline and noradrenaline are secreted in the ratio of 80 : 20.

Functions and actions of Adrenaline

Actions of adrenaline on cardio vascular system

1. It stimulates the S.A node and increases the heart rate.

2. It stimulates the ventricular myocardium and increases the force of contraction
of the heart and stroke volume.

3. It increases cardiac output.

4. It increases systolic blood pressure.
5. It increases vasoconstriction of the blood vessels except coronary blood
vessels and blood vessels of the skeletal muscles.
6. Increases RBC count.
Action on renal system
1. It decreases renal blood flow.
2. It decreases urine output.
Action on nervous system
1. It increases the excitability of nervous system.
2. It delays the onset of fatigue.
3. It produce anxiety.
Action on respiratory system
1. It increases alveolar ventilation.
2. It increases oxygen consumption by about 20–30%.
3. It increases carbondioxide production by about 30–50%. So R.Q. increases.
4. It produces bronchodilatation, anti asthmatic action.

Metabolic functions
1. It increases BMR.
2. It promotes gluconeogenesis and glycogenolysis.

3. It promotes the conversion of pyruvate to glucose through Cori’s cycle.

4. It inhibits insulin mediated glucose uptake by cells.

5. It shows anticholinergic action.

6. It shows hyperglycemic action.
7. It shows lipolytic action and increases free fatty acid in blood.
NH2
HC—COOH CH2
Phenylalanina
Phenylalanine hydroxylase
NH2
HC—COOH CH2
Tyrosine
OH Tyrosine hydroxylase NH2
HC—COOH
DopaCH2 (Dihydroxyphenylalanine)
HO
OH Dopa
NH2 decarboxylase
CH2
CH2 Dopamine
(Dihydroxyphenylethylamine)

HO
OH
NH
2
Dopamine b-hydroxylase
CH2 HC—OH

Nor epinephrine
or
Nor adrenaline HO

OH
HN—CH3 Phenylethanolamine-N
CH2 methyltransferase
HC—OH
Epinephrine
or HOadrenaline
OH
Fig. 7.35
Biosynthesis of catecholamines
Action on smooth muscles

1. It inhibits the contraction of the muscles of the intestine. Produces

constipation.
2. It produces pupillary dilatation.
3. Produces contraction of radial muscle of eye leading to mydriasis.

Alarm reaction

The initial stage in the body’s response to stressful stimuli characterised by

adaptive physiological changes, such as increased hormonal activity and
increased heart rate.

1. The response of the sympathetic nervous system either to physical stress or to

a strong emotional state. Also called stress reaction and fight or flight reaction.

2. It is an automatic and instantaneous response that increases the body’s

capability to cope with a sudden emergency.

3. The physiological changes occurring during this reaction increase physical

strength and mental activity.
4. The heart rate increases and blood pressure is elevated. This helps in better
perfusion of vital organs. The blood glucose level is raised for additional energy,
the blood coagulates more readily, and the flow of blood to muscles needed for
activity is increased, while those organs not needed for fight or flight receive a
diminished blood supply.

5. Increases ventilation.
6. Dilatation of pupil letting more light to enter the eye.
7. One of the most striking manifestations of this reaction is the involution of
lymphoid tissues due to the action of adrenal hormones.
Summary of functions of adrenaline
1. It plays a major role in the regulation of basal metabolic rate.
2. It is important in the regulation of body temperature.
3. It is important in the regulation of heart rate, stroke volume, cardiac output
and blood pressure.
4. It takes part in the regulation of sweating.
5. It is important in the mediation of fight or flight response.

Therapeutic uses of catecholamine: Catecholamine action and sympathetic

nervous system actions are almost similar. Catecholamine mimic the sympathetic
action. Therefore agonists and antagonists of catecholamine are extensively used
in clinical practice.

Examples:
Hypertension—A α β receptor antagonists Bronchial asthma—Agonists
Nasal congestion—Agonists
Hyperthyroidism—Antagonists (β receptor blockers) Cardiovascular shock—
Catecholamines Cardioegenic shock—Dopamine

Disorder
Phaeochromocytoma

It is an endocrine disorder resulting from hyper secretion of hormones of adrenal

medulla.
Cause: Tumorous growth of the adrenal medulla. Signs and symptoms
1. Increase in blood pressure—sustained or paroxysmal hypertension.

2. Increase in B.M.R.
3. Severe headache, chest pain.
4. Increase in blood glucose level, hyperglycemia that may lead to diabetes
mellitus.
5. Increase in body temperature.
6. Excessive free fatty acid in the blood.
7. Increase in heart rate and palpitation.
8. Anxiety, weakness and dizziness.
9. Weight loss
10. Sweating and flushing
11. Gastrointestinal symptoms like abdominal pain, vomiting and constipation.
12. Glucose intolerance.
Treatment
1. Surgical removal of adrenal medulla.
2. Long term treatment with α and β adrenoreceptor blocking drugs.

TABLE 7.3
Comparative effects of epinephrine and nor-epinephrine
Sl. Part or Function affected Epinephrine or Adrenaline

1. Heart rate
2. Cardiac Output, minute volume
3. Force of contraction of heart
4. Systolic B.P.
5. Diastolic B.P.
6. Mean Arterial B.P.
7. Total peripheral resistance
8. Blood vessels

9. Air ways
10. Eosinophil count 11. Reticular formation 12. Liver

13. Blood glucose

14. Metabolic rate
15. Allergy
16. Action on α and β receptors Increases
Increases
Increases
Increases
Decreases
No change
Decreases

Vasodilatation of blood vessels of muscle and liver

Dilated
Decreases
Activated

Promotes conversion
of glycogen to glucose

Increases
Increases
Antiallergic

Nor-epinephrine or Nor
adrenaline affected

No effect on heart, or heart rate decreases Decreases

Increases
Increases
Increases
Increases
Increases
Overall vaso constriction

Less effect No effect Little effect Little effect

Little effect Increases No effect

Acts equally on α and β receptors Acts on α receptors

Epi Nor
100
150 50

PANCREAS

Pancreas is called a mixed gland because it has got both endocrine and exocrine
functions. The pancreas is a flattened organ, which measures 12.5–15 cm in
length. It is located in the curve of the duodenum, first part of small intestine.
100
50 8
6 Gall bladder Common hepatic duct Common bile duct
Pancreatic duct 30 4

20 Islets of
langerhans

10 15 20 35 40 Time (min)
Epi = Epinephrine Nor = Norepinephrine
Fig. 7.36 Comparison of actions of epinephrine and norepinephrine on CVS
Sphincter of oddi
Duodenum Pancreas
Fig. 7.37
Endocrine pancrease

It consists of a head, a body and a tail. 90% of the pancreatic cells are arranged
in clusters called acine, which produce pancreatic juice and enzymes, which
flows into gastrointestinal tract.

Scattered among the acine are ovoid collections of cells called pancreatic.
Islets of Langerhans: There are 1–2 millions Islets in humans.
The exocrine function of the pancreas is the secretion of pancreatic juice.
The endocrine function of the pancreas is by Islets of Langerhans. In the Islets of
Langerhans there are four types of cells.
1. Alpha cells
3. Delta cells 2. Beta cells
4. PP cells or F cell Alpha cells secrete a hormone known as glucagon— 15–
20%.
Beta cells secrete insulin 70–80% of cells. Delta cells secrete somatostatin 10%
of cells. F cells or PP cells—Pancreatic polypeptide 1–2% of cells.

INSULIN
Insulin was discovered by Banting and Best in 1921.

Source: Insulin is secreted from the Beta cells of islets of langerhans of

pancreas.

Chemistry: It is a peptide made up of 51 amino acids and molecular weight of

5,800. It has got two chains. A chain with 21 amino acids and B chain with 30
amino acids. A and B chains are linked by disulphide brides.
Peptide C
1S
2 S3
6 COOH 21S
1S 30 2
B

10 20 Fig. 7.38 Insulin structure

Physiological functions and actions: It is an important hormone concerned

with control of blood glucose level. It is a powerful hypoglycemic hormone.
Plasma level of Insulin: Fasting: 10 uu/ml.

Insulin receptor
The insulin receptor is a transmembrane receptor that is activated by
insulin.The insulin receptor is composed of two

alpha subunits and two beta subunits linked by disulfide bonds. The alpha chains
are entirely extracellular and house insulin binding domains, while the linked
beta chains penetrate through the plasma membrane.

The insulin receptor is a tyrosine kinase. In other words, it functions as an

enzyme that transfers phosphate groups from ATP to tyrosine residues on
intracellular target proteins. Binding of insulin to the alpha subunits causes the
beta subunits to phosphorylate themselves (autophosphorylation), thus activating
the catalytic activity of the receptor. The activated receptor then phosphorylates
a number of intracellular proteins, which in turn alters their activity, thereby
generating a biological response.

Several intracellular proteins have been identified as phosphorylation substrates

for the insulin receptor, the beststudied of which is insulin receptor substrate 1 or
IRS-1.

Metabolic functions of insulin

I. Action on carbohydrate metabolism:

1. It promotes the cellular uptake of glucose. Insulin induced cellular uplake

takes place in all the tissues except brain, RBC and renal tubule.

2. It increases the breakdown of glucose for the energy production.

3. It decreases gluconeogenesis.
4. It promotes the conversion of glucose into glycogen. Inhibits hepatic
glycogenolysis.
Because of all these actions insulin decreases the blood glucose level. It is
known as hypoglycemic action. Insulin suppresses the production of
neuropeptide. It increased leptin production. This reduces appetite. Increases the
entry of potassium, phosphate and magnesium into the cell.
Increases the reabsorption of sodium and potassium at the renal tubule.

Role of insulin on growth.

Insulin is very much essential for growth.
Insulin stimulates transcription of genes for growth factors like IGF-1, IGF -11.
Promotion of protein synthesis facilitates growth. Insulin produces leniar growth
of bones.
II. Action on protein metabolism
1. Insulin stimulates protein synthesis decreases protein breakdown. Insulin
produces positive nitrogen balance.

III. Action on fat and lipid metabolism

1. It stimulates lipogenesis or promotes the synthesis of fats and lipids. Denovo
synthesis.

2. Decreases the mobilisation of lipid from liver.

3. Insulin keeps the circulating free falty acid concentration under a constant
check.
4. It decreases the breakdown of fats and lipids for the energy production.
Decreases the formation of ketone bodies. This action is known as anti ketogenic
action.

Regulation of secretion of insulin

Secretion of insulin from the pancreas is mostly controlled by blood glucose
level.

Suppose blood glucose level increases that will stimulate beta cells of islets of
Langerhan’s of pancreas. This will increase the secretion of insulin. Insulin
increases the

1. breakdown of glucose.
2. conversion of glucose to glycogen increases.
3. it decreases gluconeogenesis.
4. increases cellular uptake of glucose.
These actions together will decrease the blood glucose level to the normal. This
is an example for negative feedback mechanism.
+

Blood glucose
level
Beta cells of islets of Langerhans of pancreas

Cellular uptake of
glucose Insulin

Cellular Gloconeogenesis breakdown

of glucose

– ve

Fig. 7.39 Regulation of secretion of insulin

Paracrine control of secretion of hormones of Pancrease. The hormones

secreted by different types of cells of pancrease control the secretion of
hormones from neighbouring cells. This type of control is important in
homeostasis of body nutrition. Somatostatin inhibits the secretion of insulin,
glucagon and pancreatic polypeptide. Glucagon stimulates the secretion of
insulin and somatostatin. Insulin inhibits the secretion of glucagon.
– Insulin
–

Somatostatin
Pacreatic polypeptide

+
Glucagon
–

Fig. 7.40 Paracrine regulation of secretion of pancreatic hormones

Disorder. Diabetes Mellitus
It is an endocrine disorder commonly resulting from hyposecretion of insulin.

The diabetes mellitus is broadly classified into two:

1. Primary diabetes mellitus.
2. Secondary diabetes mellitus.
Primary diabetes are those cases where no frank cause of diabetes can be shown.
There are two further sub groups in this group, viz.
(a) insulin dependent diabetes mellitus (IDDM), (b) non insulin dependent
diabetes mellitus (NIDDM).

IDDM is type 1 diabetes and NIDDM is type II diabetes. The terms IDDM and
NIDDM have only recently been introduced. IDDM may be equated with the
“juvenile diabetes” and NIDDM with “maturity onset diabetes”, of the older
days.

In IDDM, due to some immunologically mediated process, the β cells of the

islets are destroyed so that there is a deficiency of insulin. These cases become
fatal if not treated with insulin. Also, the disease usually starts early in life.

In NIDDM, the insulin secretion is normal in amount but usually the target cells
of insulin are, due to one reason or other, resistant to insulin. In some cases,
there is deficiency of insulin receptors, but in most cases, the site of resistance is
beyond the receptor, The diesease starts mostly in older ages.

Secondary diabetes
This may be due to damage of islets of langerhan’s of pancreas later in the life.
The lesion of the pancreas may be due to following reasons:

1. Excessive intake of carbohydrates for a prolonged period of time. This

increases the work load of beta cells and in the process they get destroyed
exhaustion of β cells.

2. Damage of the pancreas due to pancreatitis.

3. Damage of the pancreas due to action of activated pancreatic enzymes.
4. Hyper secretion of growth hormone in the case of acromegaly and gigantism.
5. Hyper secretion of cortisol in Cushing’s syndrome. 6. Hyper secretion of
adrenaline in pheochromocytoma.
Signs and symptoms
1. Hyperglycemia—Increase in blood glucose level.

2. Polyphagia—excess intake of food. As a result of insulin deficiency,

insufficient glucose uptake into hypothalamus. Less glucose within
glucoreceptors which causes hunger.

3. Polydipsia—increase in thirst. It is because of increased osmotic concentration

of blood due to increased glucose.
4. Polyuria—urine output increases to several litres because of osmotic diuresis
produced by glucose.
5. Glycosuria—presence of glucose in urine. It is because blood glucose level
exceeds renal threshold for glucose.
6. Specific gravity of urine increases.

7. Urine is sweet in taste.

8. Ketosis followed with ketosuria—Appearance of ketone bodies in urine.
9. pH of blood decreases because of ketone bodies. This condition is known as
acidosis.
10. Excess breakdown of proteins leading to muscular wasting and loss of body
weight.
11. Poor wound healing.
12. Diabetic coma due to severe acidosis of brain leading to death.

Treatment
Treatment includes:
1. Diet control with exercise.
2. Oral antidiabetic drugs/oral hypoglycemic drugs. 3. Insulin injections.

TABLE 7.4 Comparison between type I and type II diabetes mellitus

Sl.No. Characteristics Type I IDDM Type II NIDDM 1. Age of onset Usually
below 40 years After 40 years. 2. Duration of symptom Days or weeks Months
or years 3. Plasma insulin level Low to absent Normal to high 4. Autoantibodies
and destruction of Beta cells
Yes No
5. Family history of diabetes No Yes 6. Plasma glucogon High, Suppressible.
High, Resistant 7. Insulin resistance No Yes 8. Effectiveness of oral
hypoglycemic drugs
Not effective Effective
9. Major cause Deficiency of insulin Lack of insulin receptors 10. Appearance of
symptoms Rapid Slow 11. Acute complication Ketoacidosis Hyperosmolar
hyper glycemic state 12. Sulphonylurea therapy Responsive Responsive to
resistant 13. Body mass Normal to wasted Obese 14. Percentage of occurance
10% 90%
TABLE 7.5 Pathophysiology of diabetes mellitus
Insulin dependent diabetes mellitus Non-insulin dependent diabetes mellitus b - cells secrete less insulin
target cells have less receptors for insulin a - cells secrete more glocagon a - cells secret more glocagon
Blood concentration Insulin Glucogon
Glucose uptake by the cells glycogen storage
Thus accumulation of glucose in blood Hyperglycemia

Thus, cells shift from consumption of glucose and glycogen to the breakdown of proteins and fats for
energy

Micro organisms thrive

More glucose is filtered

at the glomerulus Excess breakdown of proteins

Increased
consumption of fat

Poor wound healing

There is a limit for glucose reabsorption
Excess glucose is lost through urine - Glycosuria
Atrophy of muscles Increases fatty acid &

keonebody concentration in blood ketosis and acidosis

Water is carried along with glucose osmotic diuresis

Ketone bodies appear in urine ketosuria
Polyurea

Loss of more water, presence of more glucos

in blood increases osmotic concentration of blood Decreased uptake of glucose into the brain Acids entering
to the brain disrupt their normal functions

Dehydration of cells, thirst polydipsia Hunger

Dehydration of brain cells disrupts their normal functions Polyphagia

If the dehydration and acidity extreme, they cause behavioural changes, coma and death,

TABLE 7.6
Difference between diabetes mellitus and diabetes insipidus
Features Diabetes Mellitus Diabetes Insipidus 1. Major cause Deficiency of
Insulin secretion from

pancreas
Deficiency of ADH secretion from posterior pituitary

Lesions of pancreas
2. Metabolic changes
3. Urine output 4. Cause of polyuria
5. Presence of glucose in urine

(a) Defective storage of glucose as glycogen in muscles

(b) Increased breakdown of liver glycogen
(c) Increased breakdown of fat
(d) Increased formation of Ketone bodies

Excertion of large volume of urine-polyuria

Osmotic pressure effect of glucose in the lumen of renal tubule prevents

reabsorption of water, so more water is lost through urine

Glucose is present in urine—glycosuria Lesion of supra optic nucleus of

hypothalamus

No such effect

No such effect
No such effect
No such effect

Excertion of large volume of urine-polyuria

Deficiency of ADH decreases reabsorption of water at DCT and collecting duct,

so more water is lost

Glucose is absent in urine

6. Taste of urine Sweet No sweet taste 7. Specific gravity of urine
High–due to the presence of glucose Low, dilute hypotonic urine sp.gr.l.002-
1.006
8. Blood glucose level High – Hyperglycemia No increase in blood glucose level

9. Ketone body concentration in blood

Increase – Ketosis No effect.

10. Symptoms

11. Treatment Polydipsia

Polyphagia
Ketosuria
Poor wound healing

1. Oral hypoglycemic agents Polydipsia

No effect
No ketone body in urine No such effect

Injection of ADH
2. Insulin injection

GLUCAGON
2. Metabolic functions It is secreted from the alpha cells of islets of Langerhan’s
ofAction on carbohydrate metabolism. pancreas. (a) It promotes gluconeogenesis.

Chemistry: It is a polypeptide made up of 29 amino acids (b) It decreases the

breakdown of glucose for and a molecular weight of 3200. energy production.
Functions and Actions (c) It stimulates glycogenolysis.

1. It is one of the important hormone controlling blood(d) It decreases the conversion of

glucose to glucose level. It is a hyper glycemic hormone.glycogen.

Action on protein metabolism.

It increases the breakdown of proteins. Action on lipid metabolism.
Glucagon increases the breakdown of fats and lipids. This will lead to more
production of ketone bodies. This action is called ketogenic action.

Regulation of secretion of glucagon

It is controlled mostly by blood glucose level.

Suppose blood glucose level decreases, that will stimulate the alpha cells of
islets of Langerhans of pancreas. This will increase the secretion of glucagon.
Glucagon increases gluconeogenesis, but it decreases the breakdown of glucose
and also decreases the conversion of glucose to glycogen. As a result of this it
increases the blood glucose level to the normal.
Alpha cells of islet of+ Langerhans of pancreas
Glucagon
Blood Cellularglucose uptake of
level glucose
– ve

BreakGloconeogenesis down of
glucose

Fig. 7.41 Regulation of secretion of glucagon

Somatostatin
It is also known as growth hormone inhibiting factor (GHIF). Source:

1. Delta cells of islets of pancrease.

2. Antrum of stomach.
3. Hypothalamus.
Functions and actions
1. It inhibits the synthesis and release of growth hormone.

2. It blocks the secretion of insulin, glucagon and gastrin and secretion.

3. It inhibits the intestinal absorption of glucose producing a state of

hypoglycemia.
4. It decreases the motility of stomach, duodenum and gall bladder.
5. It regulates feedback regulation of gastric emptying. When intestine is full, it
prevents gastric emptying thereby prevent intestinal overloading.

Factors increasing the secretion of somatostatin: (a) hyperglycemia

(b) Increase in amino acid concentration
(c) local hormone CCK.
(d) increase in free fatty acid.

Pancreatic polypeptide

It is a polypeptide secreted by F Cells of islets of Langerhans of pancreas.

Action: It slows down the absorption of food from GIT. 2. Decreases food
intake.

Regulation of Blood Glucose Level

Dietary carbohydrates
(starch, sucrose, glucose)
Hormonal regulation

Amino acids, glycerol, propionate Glycolysis and

TCA cycle
Glucose

CO , H O 22 Glycogenolysis in muscle
Lactate Digestion and absorption
Gluconeogenesis in liver

Blood glucose
fasting 70 - 100 mg/dl Random 70 - 110 mg/dl Post-prandial 120 - 140 mg/dl

Synthesis of other monosaccharides and amino sugars

HMP shunt for pentoses and NADPH
Glycogenolysis in liver
Sources of blood glucose
Synthesis of fat

Excreted into
urine (> 180 mg/dl blood glucose) Renal handling of glucose

Fig. 7.42 Glucose homeostasis

Glycogensis in liver and kidney
Utilisation of blood glucose
Normal blood glucose level

(a) Fasting venous blood glucose level: 70–90 mg % or 3.3 to 5 mmol/L.

(b) Fasting plasma glucose level: 80–120 mg % or 4.5–5 mmol/L.
After a meal, post prandial blood glucose level: 120–140 mg %.
Arterial blood glucose is about 20% higher than that in the venous blood.

Importance of regulation of blood glucose level When blood glucose level is

within the normal limits it is known as normoglycemia. Hyperglycemia is a
condition in which blood glucose level increases significantly above

150mg%. Hypoglycemia is a condition in which blood glucose level decreases

below 50 mg %. The regulation of blood glucose is important because it is
essential to have continuous supply of glucose to the brain. The brain mainly
depends on glucose for its energy needs and even though it can utilise ketone
bodies to some extent, it has an obligatory requirement for glucose. Certain other
tissues like RBC and renal medulla are also dependent on glucose for meeting
their fuel needs.

The plasma glucose level at an instant depends on the balance between glucose
entering and leaving the extra cellular fluid.

Sources of blood
glucose

1. Dietary sources:
The dietary carbohydrates are digested and absorbed as
monosaccharidesglucose.

2. Gluconeogenesis:
Conversion of lactate, glycerol, proprionate, aminoacids into glucose, mostly in
the liver.

3. Glucogenolysis:
Breakdown of glycogen into glucose in the liver.

Utilisation of blood glucose

1. Utilisation of glucose by tissue for energy production mainly by brain RBC,

renal
medulla.

2. Conversion of
glucose into glycogen.

(a) Glucagon
(b) Cortisol
(c) Adrenaline
(d) Thyroxine
(e) Growth hormone.

Role of insulin in the regulation of blood glucose

It is a major hypoglycemic hormone. Insulin decreases the blood glucose level
by:

Increasing cellular uptake of glucose.

Increasing cellular breakdown of glucose. ↑ glycolysis
Inhibits gluconeogenesis.
Decreases the release of amino acids from muscles and glycerol from
adipocytes. Increases glycogen synthesis.
+ Beta cells of islets of Langerhans of pancreas

Insulin
Blood
glucose level Cellular ve uptake of– glucose

Cellular breakdown of glucose Gluconeogenesis

3. Conversion glucose into fat.

Hormonal regulation of blood glucose level

The blood sugar level is mainly regulated by hormones. The hormones
regulating blood glucose level are broadly divided into two groups.

Hyperglycemic hormones — Hypoglycemic hormone — Insulin

Fig. 7.43 Regulation of blood glucose level by Insulin

Role of Glucagon
It is a powerful hyperglycemic hormone. Its action is achieved by

Promoting glycogenolysis-activates phosphorylase. Increasing gluconeogenesis.

Decreasing glycogen synthesis.
Inhibiting glycolysis.
+ Alpha cells of islet of Langerhans of pancreas Less than 80 mg% hypoglycemia 80–120 mg%
Euglycemia Above 120 mg% Hyperglycemia
Cortisol (and ACTH) Glucagon Glucagon
Blood Cellularglucose level
uptake of
– ve glucose

Breakdown of
glucose Gluconeogenesis

Insulin
Catecholamines Adrenaline Growth hormone Thyroxine
Hypoglycemia Euglycemia normal
Hyperglycemia

Fig. 7.45 Hormonal influence to maintain blood sugar homeostasis

Fig. 7.44 Regulation of blood glucose level by glucagon

Role of cortisol
Increasing gluconeogenesis by increasing release of amino acids and lactate by
muscles.
Inducing enzymes like Fructose-1,6 biphospatase, glucose-6 phosphatase and
hepatic amino transferases.
Inhibits insulin stimulated uptake of glucose by tissues.
Increases hepatic glycogen storage and decreases the breakdown of glycogen.

Role of catecholamines
Immediate hyperglycemic effects of adrenaline is mediated by

Promoting glycogenolysis—increasing phosphorylase activity.

Increasing gluconeogenesis.
Increasing uptake of amino acids.

Thyroxine: It elevates blood glucose level by stimulating Hepatic

gluconeogenesis
Hepatic glycogenolysis.

Growth hormone: It increases blood glucose level by Decreasing cellular

uptake of glucose

Role of liver
Liver acts as a glucostat and buffer organ in the regulation of blood glucose
level. When blood glucose level increases liver lowers it by

Increasing the conversion of glucose to glycogen. Decreasing gluconeogenesis.

Stopping glycogenolysis.

When blood glucose level falls, liver rises it to normal by:

Increasing glycogenolysis.
Increasing gluconeogenesis.
Stopping glycogen synthesis.

Role of kidney
When blood glucose level increases above 180 mg %, called renal threshold for
glucose, the extra glucose is not

reabsorbed, and it is lost through urine. This helps to prevent too much increase
in blood glucose level.

Role of sympathetic nervous system:

During hypoglycemia, sympathetic nervous system is stimulated, this increases
the secreation of catecholamines from adrenal medula, thereby hypoglycemia is
corrected.

Also,sympathetic system stimulation leads to inhibition of insulin secretion.

Role of skeletal muscle

At rest as well as during mild activity, fuel of muscle is fatty

acid but during severe exercise, muscle utilises only glucose and thus glucose is
catabolised. This helps to lower blood glucose level to normal.
Hypoglycemia

When the blood glucose concentration falls to less than 45–50 mg %, the
symptoms of hypoglycemia appear. The symptom includes headache, anxiety,
confusion, sweating, slurred speech, seisures and coma, and, if not corrected,
death. All these symptoms are directly or indirectly related to the deprivation of
glucose supply to the central nervous system (particularly the brain) due to fall
in blood glucose level.

The following three types of hypoglycemia are encountered by physicians.

1. Post-prandial hypoglycemia: This is also called reactive hypoglycemia and
it is obseved in subjects with an elevated insulin secreation following a meal.
This causes transient hypoglycemia and is associated with mild symptoms. The
patient is advised to eat frequently rather than the three usual meals.
2. Fasting hypoglycemia: Low glucose level in fasting is not very common.
However, fasting hypoglycemia is observed in patients with pancreatic β-cell
tumor and hepatocellular damage.
3. Hypoglycemia due to alcohol intake: In some individual who are starved or
engaged in prolonged exercise, alcohol consumption may cause hypoglycemia.
This is due to accumulation of NADH (during course of alcohol metabolism by
alcohol dehydrogenase) which diverts the pyruvate and oxaloacetate (substrate
of gluconeogenesis) to form, respectively, lactate and malate. The net effect is
that gluconeogenesis is reduced due to alcohol consumption.
4. Hypoglycemia due to insulin overdose: The most common complication of
insulin therapy in diabetic patients is hypoglycemia. This is particularly
observed in patients who are on intensive treatment regime.
Microscopically it contains two types of cells: 1. Chief (principal) cells which
are more numerous, and secrete PTH.
2. Oxyphil cell—less abundant and larger. Their function is not known.
It secretes one hormone called parathyroid hormone or parathormone, PTH.

Chemistry: It is a polypeptide made up of 84 amino acids and has molecular

weight of 9500.

Physiological Functions and Actions

It plays a major role in the regulation of blood calcium and phosphate levels.
Actions
Parathyroid hormone acts at three different sites in the body.
1. Bones 2. Kidney 3. Intestine.
Action on the bones

Parathyroid stimulates resorption of bones. It produces demineralisation of bones

i.e., it releases calcium ions from the bones—osteolytic effect.

Action on the kidneys

Parathyroid hormone promotes the re-absorption of calcium from the renal
tubule. Because of this action PTH decreases calcium loss through urine and
thereby increases blood calcium level. In the kidneys PTH brings about the
conversion of vitamin D into 1, 25-dihydroxy cholecalciferol or calcitriol. It
decreases the reabsorption of phosphate. So more phosphates is lost through
urine.

TABLE 7.7 Steps involved in activation of vitamin D

Factors Organsinfluencing
Biochemical changes
Sunlight Skin 7 Dehydrocholestrol
Cholecalciferol (Vitamin D )3 (Inactive form of vitamin D)
Liver Cholecalciferol (Vitamin D )
3
Inhibition
25-hydroxycholecalciferol Inhibition
PARATHYROID GLAND

In human, there are 4 parathyroid glands, embedded in the posterior surface of

lateral lobes of the thyroid gland, two in the superior poles and two in the
inferior poles.

Each parathyroid gland is richly vascularised disc, measuring 3 × 6 × 2 cm.

ParathyroidKidneyshormones
1-25-Dihydroxycholecalciferol calcitriol
(Active form of vitamin D )3

Intestine 1, 25 —
Dihydroxycholecalciferol

Calcium

Action of parathormone on the intestine +It is mediated through the formation of 1, 25

dihydroxy
cholecalciferol or calcitriol. Calcitriol acts as a hormone, it
promotes absorption of calcium from the intestine. PTH also
increases the absorption of phosphate from the intestine.

All these actions together will increase the blood

calcium level. It is known as hyper calcimic action.

Regulation of Secretion of Parathyroid Hormone

Blood calcium
level

Secretion of parathyroid hormone is controlled by blood–ve calcium level.

Parathyroid gland
PTH
Bone Intestine Kidneys
Calcium Calcium ralease absorption Calcium reabsorption

Suppose blood calcium level falls that will stimulate parathyroid gland. This will
increase the secretion of PTH. Parathyroid hormone will act at the bones,
kidneys and intestine. At the bones it increases the release of calcium, at kidneys
it increases reabsorption of calcium, and in theCausesintestine it increases the absorption of
calcium.

All these actions together will increase the blood calcium level to normal.

Disorder—Tetany
It is an endocrine disorder commonly resulting from hyposecretion of
parathyroid.

Lesion of the parathyroid gland due to injury or infection.

Accidental removal of parathyroid glands during thyroidectomy.
Deficiency of calcium in the diet. Deficiency of vitamin D in the food.
Tetany
Glandular cause Metabolic cause Nutritional cause
Hypoparathyroidism Alkalaemia
After Lesion of parathyroid Parathyroidectomy gland

Nutritional deficiency of
calcium or
decreased absorption of calcium as in sprue
Nutritional deficiency of
Vit.Dasin Nutritional deficiency or
rickets magnecium

Deficiency of PTH 1. In hyperventilation

Fig. 7.46
Regulation of secretion of PTH
2. In increased intake of alkaline salts
3. After excess loss gastric juice during vomiting
Loss of acids

Experimental Surgical or operative accidental removal of parathyroid during thyroidectomy

Fig. 7.47 Aetiological classification of tetany Signs and symptoms or clinical

features
The low blood calcium level.

Increase in the excitability and irritability of neuromuscular junction.

Convulsions—uncontrolled, unwanted painful contractions of the skeletal
muscles.
Profuse sweating.
Bronchospasm.
Accoucher’s hand: It is due to the contractions of metacarpophalyngeal
muscles. The fingers take a peculiar position, like obstretic hand.
Carpopedal spasm: Spasm of muscles at the ankle joints.
Chvostek’s sign: Tapping of face below the ears produces painful spasmodic
contraction of facial muscles.
Trousseau’s sign: When blood pressure cuff is tied around the hand it produces
bending of fingers similar to Accoucher’s hand.
Laryngeal stridor: Respiration temporarily stops. When the respiration restarts
it produces crowing sound.
Phosphate level increases.

Fig. 7.48 Position of the hand in hypocalcemic tetany Accoucher’s hand or

Trousseau’s sign

Treatment
1. Dietary supplementation of calcium through food.
2. Supplementation of vitamin D through food.
3. Injections of parathyroid hormone.
Hyper Parathyroidism—Hyper Secretion of Parathyroid Hormone
Cause

Physiological Functions and Actions

1. It plays an important role in the regulation of blood calcium level.

Hypocalcemic action.
2. It acts on the bones and it promotes the deposition of calcium on the bones. It
exerts calcium lowering effect by inhibiting osteoclastic activity. It inhibits the
active transport of calcium from bones to extracellular fluid.
3. Decreases the renal formation of calcitriol which inturn decreases serum
calcium level, by decreasing the absorption of calcium from intestine.
4. Increases Na+, Cl–, Ca++ and PO4−− excretion through urine.
5. Increases intestinal secretion of water and electrolytes.
6. Decreases gastric motility and acid secretion.
7. Calcitonin protects the bone during pregnancy and lactation.

Regulation of Secretion of Calcitonin

Calcitonin secretion is regulated by blood calcium level.

Suppose blood calcium level increases, that will stimulate the ‘C’ cells of thyroid
gland. This will increase the secretion of calcitonin. Calcitonin will increase the
deposition of calcium on the bones. It decreases calcium absorption at the
intestine. This will decrease blood calcium level to the normal.
+ Thyroid gland
Calcitonin

Blood calcium
level

Bones Intestine

Tumorous growth of parathyroid gland. Blood calcium level increases.

Excess demineralisation of bones. Bones become weak and brittle.
It leads to formation of kidney stones. It will further lead to renal failure.

CALCITONIN OR THYROCALCITONIN Source: It is secreted from the

‘C’ cells of thyroid gland.

Chemistry: It is a polypeptide made up of 32 amino acids and a molecular

weight of 3600.
– ve Calcium absorption Calcium
depostion
Fig. 7.49 Regulation of secretion of calcitonin

CALCIUM METABOLISM
Introduction

The human body contains more calcium than any of the other essential minerals
as much as 1100–1200 gm in a 70 kg adult. That is about 1.5 % of body weight
and about 27.5 mol. The body of the infant at birth contains about 27.5 gms of
calcium and calcium continuously get deposited in the bone during the growth of
the body. About 99 % of total calcium are present in bones and teeth and
remaining 1% in the soft tissues including blood. About 1188 gms of calcium is
present in bone and teeth. Intracellular fluid may have about 0.9% of total
calcium is about 11 gm. The calcium content in extracellulor fluid is about 0.1%
of total calcium and it is about 1 gm.

Source

The important dietary sources of calcium are milk and milk products, sesame
seeds and green leafy vegetables. Milk is the best natural source and skim milk
powder is very rich source (1.37%) of calcium. Ragi is the cheapest natural
source of calcium, containing about 0.3 to 0.36%.

Daily Requirements

The FAO\WHO expert group on calcium requirements suggested practical

allowances for calcium for different age groups.
Recommended allowances for calcium:

TABLE 7.8
Daily requirement of calcium
Sl.No. Subject Calcium mg/Day 1. Infants (0–12 months) 500–600 2. Children
(1–9 yrs) 400–500 3. Children (10–15 yrs) 600–700 4. Adolescents (16–19 yrs)
500–600 5. Adults 400–500 6. Pregnancy and Lactation 1000–1200
Calcium absorption and factors effecting calcium absorption

Calcium is absorbed at the intestine by two different mechanisms.

1. Active transport, where calcium absorption occurs against a concentration
gradient and is dependent on 1–25 dihydroxy cholecalciferol. Active transport
occurs in the duodenum.
2. Passive diffusion, occurs lower down in the small intestine and the amount
absorbed by this process is small.
The various factors affecting the absorption of calcium are: Vitamin D: It is
essential for the absorption of calcium and the deficiency of Vitamin D impairs
calcium absorption.
Phosphates: Excess of phosphates lowers calcium absorption.

Phytic acid: Phytic acid is seen in green leafy vegetables. It forms insoluble.
calcium salts and interferes with calcium absorption. In the past the ability of
phytic acid to reduce the calcium absorption in man has been overemphasised.
Many green vegetables also contain the enzyme phytase, which splits phytic acid
and hence nullifies the effect of phytic acid.
pH: Calcium is well absorbed at the normal pH of the intestine. If the intestinal
pH becomes alkaline, calcium absorption is lowered due to the formation of
insoluble tricalcium phosphate.

Fats and fatty acids: Faulty absorption of fats leading to the presence of large
amounts of fatty acids in the stools interfere with calcium absorption, as
insoluble calcium salts of fatty acids are formed and excreted in faeces.
Protein: Higher levels of proteins in diet help to increase the absorption of
calcium.
Fibre: Presence of excess of fibre in the diet interferes with the absorption of
calcium. Oxalic acid: Oxalic acid present in certain foods that forms insoluble
calcium salts which is excreted in the faeces, thus lowers the calcium absorption.

Distribution of calcium in the body

Ninety-nine per cent of calcium is in the bones and teeth. Most skeletal calcium
is deposited as a form of

hydroxyapatite, Ca 10 (Po) 46 (OH)2, but some amount of calcium is present as

monocrystalline calcium phosphates and carbonates. Calcium concentration of
the ECF and intracellular fluid (ICF) are different, the ECF having a higher
concentration than ICF. In the cell the cytosol concentration of calcium is very
poor but the mitochondria concentration is higher. The plasma concentration of
calcium is 9–11 mg/ 100 ml. Calcium is present in plasma in three forms:

1. lonised calcium—60% i.e.,–5.4 – 6 mg/100 ml.

2. Protein bound calcium –35% – 3.5 – 4.4 mg/100 ml.
3. Complexed calcium—5% as citrate, phosphate and bicarbonate 0.5to 1.0
mg/100 ml 1 and 3 are diffusable forms of calcium.
Calcium and phosphate product in serum
The plasma phosphate content in normal infants and children (5–6 mg) is higher
than that (2.6 to 4.0 mg) found in normal adults. The Ca and P product is over 50
in normal infants

and children and about 30–40 in normal adults. The Ca and P product is very
much low in children suffering from rickets (20–30) and in adults suffering from
osteomalacia. A high product is very important for normal ossification of bone.

If it is low, ossification does not take place. For normal ossification of bone the
Ca and P product should be over 50 in children and 30 to 40 in adults. Phosphate
depletion in man is non-existent under normal dietary regimens. Long term
antacid use however will render phosphate unabsorbent. Such a condition is
characterised by weakness, anorexia, malaise and bone pain.

Physiological functions of calcium

1. Calcium is chief mineral of the bone and teeth and it gives hardness to the
bone and teeth.
2. Calcium ions participate in many enzymatic actions including succinic
dehydrogenase, digestive enzyme like trypsin.
3. Calcium ions take part in muscular contractions.
4. Calcium ions are essential for the clotting of blood.
5. Calcium regulates the permeability of capillary walls.
6. Calcium regulates the excitability of nerve fibres, nerve centres, and neuro-
muscular system.
7. Calcium acts as the second messenger in some hormonal actions.
8. Some neurotransmitters (noradrenaline) are stored normally within the
vesicles of nerve terminals. Their discharge from these vesicles require the
presence of calcium ions.

Calcium homeostasis and regulation of calcium metabolism

Ultimately the food calcium is the source of calcium in our body. However the
bones act, as a reservoir of calcium supplying calcium to the serum when there is
deficiency and taking out calcium from blood when it is in excess. The serum
calcium, particularly the ionised calcium, is kept at a remarkable constant level
and this calcium homeostasis is achieved by three hormones namely,

Parathyroid hormone (PTH)

Dihydroxycholecalciferol-derived from Vit D. Calcitonin.

Calcium absorption undergoes adaptation i.e., it is high when the calcium intake
is low and decreased when the calcium intake is high. Thus the intestine
regulates the calcium metabolism by adjusting the absorption of calcium. This
adjustment of absorption is made possible by changing the availability of 1,25-
dihydroxy cholecalciferol—Vit. D derivative.

Parathyroid Hormone PTH: PTH is a single chain peptide with 86 amino acid
residues and a molecular weight of 9500. PTH is secreted from the parathyroid
gland. PTH is a hypercalcaemic hormone and it acts on bone and kidneys. PTH
acts on bones and inhibits the osteoblastic activity and as a result new bone
synthesis stops and causes increased resorption of bones. This leads to the rise in
blood calcium level and to osteoporosis. Actions on the kidneys: PTH converts
vit D into 1, 25 dihydroxy cholecalciferol, calcitriol at the kidney. Calcitriol is
the active form of the Vit D, and acts on the intestine wall, and increases the
absorption of calcium at the duodenum. Moreover calcitriol increases calcium
reabsorption at the distal renal tubule by active transport.
Calcitonin: This hormone is a 32-amino acid peptide secreted by the
parafollicular “C” cells of the human thyroid. Its action is mainly on the bone. It
inhibits resorption and mobilisation of calcium from bone. This leads to
lowering of serum calcium content. This is a hypocalcaemic hormone. The
serum calcium level is a major factor controlling

the secretion of PTH and Calcitonin. When serum calcium level is elevated it
stimulates the “C” cells of thyroid gland and stimulates the increased secretion
of calcitonin. Calcitonin action will bring the serum calcium level back to
normal level. In contrary the fall in serum calcium level stimilates the
parathyroid gland to secrete more of PTH. Once PTH level increases it brings
about a rise in serum calcium level by acting at bone, kidneys and intestine. The
interrelationship between the serum calcium level and secretion of calcitonin
with PTH can be summed in the following diagram.

Role of other hormones in calcium homeostasis Steroid hormones decrease

osteoclastic activity and decrease calcium absorption at the intestine, thereby
decreases plasma calcium level. GH increases calcium absorption at intentions.
Thyroid produce osteoclastic action.
4000
700 Calcitonin
3000 PTH 600
500
2000400
300
1000200
Undetectable Undetectable
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Serum calcium, mg/dL
Fig. 7.50 Relationship between blood calcium level and secretion of PTH and
calcitonin

Disorders of calcium metabolism

Effects of calcium deficiency: The dietary deficiency of calcium in children will
lead to

1. Decreased rate of growth.

2. Negative calcium balance.
3. Loss of calcium from bone leading to the development of osteoporosis.
4. Hyperplasia of parathyroid gland.
5. Hyperirritability and tetany leading to death. In adults calcium deficiency will
lead to osteoporosis, it is a condition in which decalcification of bones occur.
Fracture of bones may happen even due to minor accidents.

Hypoparathyroidism: Hypocalcaemia may result from hypofunction of

parathyroid gland. This may occur due to accidental damage or removal of the
parathyroid glands during surgery of the thyroid or in cancer larynx. When the
parathyroids are absent the serum calcium level with the ionised fraction falls
rapidly. The outstanding sign of Ca++deficiency is tetany. When serum Ca++
level falls,the irritability of nerves as well as neuromuscular junction rises and
the muscle contracts when subjected to subthreshold stimulus and even
spontaneously. Basic feature of tetany is uncontrolled, painful prolonged
contraction (spasm) of the voluntary muscles. The important clinical features
are:

1. Accoucher’s hand: There is muscular spasm leading to uncontrolled

prolonged flexion of the metacarp ophalangeal joints while fingers remain
extended.
2. Trousseau’s sign: Apply pressure on arm by inflation of the
sphygmomanometer cuff carpal spasm appears similar to Accoucher’s hand.

3. Laryngsmus stridulous (laryngeal stridor): There is spasm of the larynx,

the patient tries violently to inspire. After sometime the spasm disappears, the air
enters the larynx with a characteristic crowing sound, during inspiration, after a
temporary stoppage, is called laryngeal stridor.

4. Chvosteck’s sign: Taping the facial nerve at the ramus of the mandible in
front of the ear produces the painful spasm of the facial muscles.

5. Bronchospasm.
Treatment
1. Intravenous injections of soluble calcium salts.

2. Large dosage of vitamin D and increased amount of dietary calcium are long
term measures.
3. Injection of PTH.

Hyperparathyroidism leading to Hypercalcaemia High level of serum PTH

leads to excess bone resorption and brings about an increase in serum calcium
level. The important signs of hypercalcaemia are

1. Neural sedation as manifested by drowsiness.

2. Renal stone and osteoporosis leading to development of bony cysts and
pathological fractures.
The main uses of calcitonin so far are in the treatment of hypercalcaemia and
Paget’s disease.
Hypercalcaemia: The cause includes thiazide drug therapy, Addison’s disease,
immobilisation, sarcoidosis, multiple myeloma, malignancy of bone,
hyperparathyroidism, and Vitamin D intoxication. Calcitonin acts rapidly and
can reverse severe hypercalcaemia, which might otherwise be fatal due to renal
failure or cardiac arrhythmias.
Paget’s disease: In the early stages especially, osteoclastic activity predominates
and may cause hypercalcaemia and severe bone pain. These can both be
corrected by giving calcitonin but there is usually antibody production after a
time. Salmon calcitonin is less strongly antigenic than porcine but antibody
production is a limiting factor in the prolonged treatment necessary for Paget’s
disease. Disodium etidronate: Etidronate is adsorbed into hydroxyapatite
crystals and slows both their rate of growth and resorption. This reduces the rate
of bone turnover characteristic of Paget’s disease and etidronate is probably the
treatment of choice since it can be given in repeated courses without diminished
activity.

Summary
Some of the factors controlling blood calcium can be summarised as follows:

1. Dietary intake of vitamin D and calcium.

2. Parathormone secretion promotes removal of calcium from the bone raises the
blood calcium level. PTH also potentiates the conversion of vitamin D into 1–25
DHCC, which increases absorption of calcium at intestinal level and decreases
renal excretion of calcium.
3. Calcitonin opposes the action of parathormone and

lowers the blood calcium mainly by increasing deposition of calcium in the

bones.

4. Absorption of calcium may also be depressed in intestinal diseases

characterised by malabsorption, i.e., steatorrhoea.

5. Excretion of calcium is enhanced in some chronic renal diseases.

6. There is a greater demand for calcium during pregnancy and lactation, hence
requiring nutritional support, failing which removal of calcium may be excessive
from the bone by these mechanisms.
7. Ionisable calcium is depressed when there is alkalosis. This inturn may be due
to overbreathing (losing CO2) or vomiting (losing gastric acid) and can lead to
tetany.
8. Osteoporosis is evident increasingly in the menopausal females and males due
to long term negative calcium balance. Androgen and oestrogen replacement
therapies have been alternately used, instead of high calcium intake together
with strontium and NaF ingestion.

PINEAL GLAND

It is a tiny gland, situated on the dorsal side of the mid brain, in between the
superior colliculi. The pineal gland secretes melatonin. The gland is richly
supplied by sympathetic nerve fibres. The pineal gland is connected by nerve
fibres with the retina.
The hormone melatonin is derived from serotonin (melatonin is N acetyl 5
methoxy tryptamine).
In the lower animals, the pineal gland acts as eye but this function is lost in
higher animals.

Functions
1. Melatonin in the frogs reduces the dark colour of the skin.

2. In higher animals, melatonin inhibits the hypothalamus; when hypothalamus

is suppressed, there is a suppression of the anterior pituitary gonadotropins
leading to suppression of menstruation, gonadal activity—testis/ovary.
Melatonin can also directly suppress the anterior pitutitary so that gonadotropin
is inhibited.

3. Melatonin is also, in some way connected with the sleep. In midnight

melatonin secretion is very high.
4. Melatonin administration in healthy human volunteers may elevate their
moods.
5. Anti schizophrenic action.

Control of secretion

I. Light and darkness affect the pineal gland. When there is darkness, there is
more pineal gland secretion and reverse occurs when there is excess light.

II. During sleep there is high melatonin secretion.

Calcification of the pineal gland starts early in life and advances steadily.
Surprisingly however, calcification does not affect the functions of the pineal
gland.

THYMUS

Thymus gland is a partly endocrine and partly lymphoid structure. It is situated

in mediastinum behind the sternum and between lungs. At the time of birth it is
large in size, reaches the maximum size at 10–12 years of age. The size may be
between 30–40 gms by the time person attains puberty. After puberty the thymus
undergoes progressive atrophy and in old age it weighs 3–6 gm.

When it starts degenerating, most of the glandular tissue is replaced by

connective tissue.

Histological structure
The left lobe is smaller than right lobe. It is a bilobed structure. Section of it
shows that each lobe is further divided into a number of lobules and lobules
contain number of follicles. Lobes are covered by a connective tissue capsule.
This capsule gives off extensive branch into lobes called trabeculae which will
divide lobes into lobules. Each lobule consists of an outer cortex and an inner
medulla.

Functions
It is a lymphoid organ. It is the primary lymphatic organ formed in the body, it is
formed before any lymphoid tissue. Thymus produces T lymphocytes which are
important for providing immunity. The pre T cells migrate from bone marrow to
thymus and there they proliferate and develop into mature T lymphocytes.
These T lymphocytes are important for
1. Cellular immunity—which is responsible for

delayed allergic reaction in the body.

Responsible for rejection of transplant or foreign tissue. It constitutes a major
defense against virus, few bacteria (tubercle bacilli) and fungi. Also regulates
antibody production by lymphocytes.

2. Thymus gland produces a hormone known as thymosin responsible for

proliferation and development of T lymphocyte. Thymosin is a polypeptide.

3. It produces thymopoietin, it inhibits release of Acetyl choline at motor nerve

endings., leading to a condition called Myasthenia gravis.

4. In human beings if thymus is removed after birth it does not impair T

lymphocyte immune system much but if it is removed just after the birth of child
then the cellular immunity will be impaired. Most of proliferation of T
lymphocytes occur before birth of baby.
If transplantation is to be done, thymus should be removed.

Disorders
1. Myasthenia Gravis: Thymus is associated with autoimmune disease.
Thymus enlarges in thyroiditis and also to some extent in hemolytic anemia.
When there is a proliferation of thymus it interferes with the function of
oesophagus,trachea and veins of neck.
LOCAL HORMONES
Definition

Local hormones are substances which are released locally and have local effects
on the surrounding tissues. Local hormones are:
1. Histamine
2. Acetylcholine
3. 5-hydroxytryptamine (serotonin)
4. Bradykinin
5. Prostaglandins

Histamine
Source: In mammalian tissues, histamine occurs in highest concentration in
connective tissues of skin, intestine and lungs. It is also seen in basophils,
sinusoids of liver, platelets and endothelial cells of capillaries.

Biosynthesis
Histidine
Functions

decarboxylase
→
Histamine

1. It is a vasodilator- causes arteriolar as well as precapillary sphincter dilatation.

2. Causes fall in B.P. and heart rate.
3. Induces headache.
4. Produces pain and itching sensation.
5. It acts as stimulant for the release of acid in the gastric juice.
6. Responsible for the production of triple response.
7. Anaphylatic shock is mainly due to histamine release.
8. Bronchial asthma may be induced by histamine.

Acetylcholine
Location: Myoneural junction, Preganglionic autonomic endings,
postganglionic parasympathetic endings, postganglionic sympathetic fibres to
sweat glands. Biosynthesis

Acetyl CoA + Choline Functions

Choline acyl
 → Acetylcholinetransferase

1. Impulse transmission in the NMJ and at synapse.

2. Heart rate regulation.
Serotonin or 5-Hydroxytryptamine
Sources: Occurs in platelets, nervous tissue (brain stem, sympathetic ganglia,
hypothalamus) and secreted by enterochromaffin cells of small intestine.
Biosynthesis Tryptophan Tryptophan

hydroxylase →
5-hydroxytryptophan
Functions
1. Acts as a vasoconstrictor. Decarboxylase

5-Hydroxytryptamine or
Serotonin

2. Increases B.P. and produces tachycardia.

3. Reflexly stimulates peristalsis.
4. It is a potent stimulant of pain.
5. Induces sleep.
6. Has physiologic effects on mood and behaviour. 7. Raises body temperature.
8. Causes reflex apnoea and hyperapnoea in asthmatic subjects, it may induce
acute attack of asthma.

Prostaglandins
Source: The chief source of prostaglandins is semen.

The name prostaglandins is a misnomer since earlier it was thought that it was
secreted only from prostate gland. But it is synthesised in almost all organs.
Other important sources are uterus, heart, pancreas, G.I.T.

Biosynthesis: The precursor of prostaglandins in the body are linoleic and

arachidonic acids.
Membrane phospholipids
Phospolipase
Arachidonic acid
Cyclooxygenase

9. It has a purgative action on G.I.T. Motility of intestine increases.

10. Has antilipolytic effect, causes obesity. 11. Thromboxane A2 occurs in
platelet causes vaso

constriction, platelet aggregation.

But prostacyclin is a vasodilator and inhibits platelet aggregation.

Bradykinin
Bradykinin is a monopeptide found in plasma. It is formed from kininogens.
Synthesis:

Factor XII
Surface contact Active factor XII
Precursor
Permeability factor
Cyclic endoperoxide (unstable)
Permeability factors
PGG 2
Prekallikrein Kallikrein (Plasma)
Thromboxane A2 Prostacyclins PGH 2 (Vasoconstrictor) (unstable)

(Vasodilator unstable) PGE2 PGF2a (stable) (stable) Thromboxane

B2
(stable inactive compound)

Fig. 7.51
Biosynthesis of prostaglandins Functions:

1. In normal doses, prostaglandins promote fertilisation and implantation of

zygote.
2. Therapeutically used in causing abortion.
3. Normal doses—initiates the onset of labour (PGF2a).
4. Responsible for dysmenorrhea (Painful menstruation).
5. Produces heat by stimulating posterior hypothalamus. This is called pyrogenic
action. Leucotrienes cause fever.
6. PGA1, and PGA2 produce vasodilatation of splanchnic vascular bed.
7. PGE produces relaxation of bronchial muscles.
8. PGF2a produces contraction of bronchial muscles leading to bronchial
asthma.

Kiningen Kinin
Activation of factor XII initiates kinin formation. Kallikrein is a proteolytic
enzyme known as Kininogenase. Kininogen is a substrate globulin. It is
converted to kinin by the action of kininogenase (Kallekrein). Functions:
1. Acts as a vasodilator, it increases the blood flow to

the glands eg to salivary gland, lacrimal glands etc. increases salivation,

lacrimation etc.

2. Produces pain.
3. Causes systemic fall in B.P. during shock.
4. Increases vascular permeability and allows the escape of plasma proteins.
5. In high concentration promotes migration of leucocyte from blood to tissues.

Autacoids
Autacoids are substances with biologic activity that are

synthesised at the site of action and exert primarily localised effects. They are
not stored and relaesed from neither glands, nor do they need to circulate to the
site of action like “classical” hormones. Autacoids are primarily characterised by
the effect they have upon smooth muscle. With respect to vascular smooth
muscle, there are both vasoconstrictor and vasodilator autacoids. Vasodilator
autacoids can be released during periods of exercise. Their main effect is seen in
the skin, allowing for heat loss. These are local hormones, therefore have a
paracrine effect. Some notable autacoids are: eicosanoids, angiotensin,
neurotensin, NO (nitric oxide), kinins, histamine, serotonin, endothelins, etc.
Receptors for serotonin, histamine, prostaglandins, leukotrienes consist of seven
transmebrane domains, the typical structure of Gprotein coupled receptors.
Autacoids are considered to be the root-cause of many pathophysiological
conditions such as, fever, inflammation, and allergy.

TABLE 7.9 Autacoids

Amine autacoids Peptide autacoids Lipid
autacoids 5 HT Angiotensin Eicosanoids Histamine Kinins PAF
TABLE 7.10
Summary of the gastrointestinal hormones
Sl.No. GI hormones 1. Gastrin
G-cells in the gastric antrum.

2. Pancreozymin—Cholecystokinin—PZ-CCK I-cells lined in the duodenum

and jejunum

3. Secretin
S-cells of duodenum and jejunum

4. Vasoactive intestinal Peptide—VIP

Neurons in the enteric system and in the body (a) It stimulates the secretion of

pancreatic digestive enzymes; (b) Contraction of gall bladder; (c) It inhibits

gastric emptying; (d) Growth of exocrine pancreas.

(a) It stimulates H2O and HCO–3 secretion by pancreas and bile ducts;

(b) It potentiates the action of CCK; (c) Pepsin secretion;

(d) Growth of exocrine pancreas.

(a) It is responsible for secretion of ions, H2O and HCO3 from intestine and
pancreas;

(b) It increases intestinal blood flow; (c) Relaxes GI smooth muscle Protein
digestion Fat digestion
Acid in lumen G-protein
[Ca2+] via IP3

Acid in lumen Fat digestion G-Protein cAMP

Unknown G-protein cAMP

5. Gastric Inhibitory Peptide—GIP

K-cells in the small intestine
(a) It initiates insulin secretion; (b) It inhibits water and electrolyte

absorption in the small intestine; (c) Inhibits gastric acid secretion. Amino acid
Fats
Glucose
Not known

6. Somatostatin
– D-cells in intestine,
– Neurons in the enteric nervous system
(a) It inhibits HCI secretion in the

stomach and decreases release in gastrin;

(b) It inhibits enzyme secretion in the pancreas;

(c) Decreases release of insulin and glucagon.
Glucose, Fats and bile salts in the intestine G-protein

7. Enteroglucagon L-cells in distal ileum and colon

Motilin
Duodenum, Jejunum

Functions

(a) HCl secretion;

(b) Pepsinogen secreion; (c) IF secretion;
(d) Growth of gastric mucosa

Stimulus
Gastric and intestinal motility are decreased
Glucose and fats in lumen
–

(a) It stimulates gastric motility; (b) It stimulates intestinal motility; Distension

of stomach vagal stimulation

Nerves Fat
Acid

Cellular action G-protein

[Ca2+] via IP3
–

GROWTH, DEVELOPMENT AND AGING

The terms growth and development are very closely and mutually dependent.
Growth means increase in the physical size whereas development means the
maturation which is the improvement of capacity of an organ and body parts.
Growth usually refers to physical increase in size whereas development means
qualitative changes. Growth involves an increase in size and weight of the body
tissues and thus a measurable quantitative change. In contrast development
occurs through a series of coordinated changes which affect the complexity and
function of body tissues.

Growth patterns: Growth of all the organs and systems do not show an uniform
pattern. Growth patterns are different for neural, gonadal and lymphoid tissues,
so it shows different types of growth curve. General growth, curve shows two
growth spurts, two periods of rapid growth one in infancy and another around
puberty. It is the growth of the body as whole including increase in height and
weight.

Infantile growth spurts: Birth weight of the infact steadily increases and it
become double birth weight at the age of six months. It becomes three times of
birth weight at the age of 1 year. Height gain is maximum during first two years
of postnatal life which records about 25 cm per years. Then height gain
gradually falls an 5–10 cm per year for next 8–10 years.

Growth spurt in puberty: Body shows a rapid weight gain during pubertal age
12–18 years. It shows a gain of 3 to 4 kg per year. During this period both height
and weight increases because both muscles and bones show a growth. Height
gain during puberty is 10 cm/ year. Increase in height stops after puberty due to
the closure of epiphyses under the influence of sex steroids.
120
100 Lymphoid 80 Neuraltissue
60
Height General 40
20 Gonadal or reproductive 0
0 5 10 15 Age in years

Fig. 7.52
Growth pattern of different parts of the body

Neural growth curve: Neural growth is extremely rapid after birth recording a
80 per cent of adult brain size at the age of 2 years, where as body weight gain
by 2 years only 20% of adults. Remaining increase in brain size occurs in next 3
to 5 years.

Gonadal growth curve: Gonadal growth pattern is essentially opposite to neural

growth factor. The reproductive organs like gonads and accessory sex organs
remain in dormancy throughout childhood. Gonadal growth takes place at a
rapid rate around the age of puberty—12 to 18 years.

Lymphoid growth curve: Growth of lymphoid organs is very rapid in

childhood. Lymphoid organs like lymphnodes, spleen, tonsil, adenoids, thymus
grow fast till the age 6–10 years and attain their maximum size.

Factors influencing and regulating growth. Important factors affecting growth

are
1. Hormonal 2. Nutritional
3. Social 4. Environmental
5. Genetic factors.

Hormonal factors influencing growth

Major hormones influencing growth are growth hormone thyroid hormone
insulin, gonadal hormones and cortisol. Role of growth hormone:

Growth hormone increases the number of cells and size of the cells. It also
produces the elongation of bones increasing the height and frame work of body.
The positive nitrogen balance produced by the growth hormone is useful in
promoting growth and development.

Insulin: It is an anabolic hormone increasing protein synthesis. It increases

amino acid uptake by cells and thereby increase protein synthesis which leads to
positive nitrogen balance. It may stimulate the secretion of Insulin like growth
factor-1. (IGF-1) during childhood days.

Sex hormones or gonadal hormones: Testosterone. It controls growth and

maturation during pubertal and adolacent periods in male. It promotes protein
biosynthesis which leads to positive nitrogen balance. An increased secretion of
testosterone during puberty is required for the normal pubertal growth spurt
which reflects the growth of long bones and vertebrae. The dual effects of the
sex hormones explain the pattern seen in adolescence—rapid lengthening of the
bones culminating in complete cessation of growth for life. Testosterone causes
eventual closures of epiphysis leading to stoppage of further increase in height.

Oestrogen: It stimulates the secretion of growth hormone at puberty thereby

increases the growth of body. Later it leads to eventual epiphysial closure.

Thyroxine: Thyroxine stimulates the secretion of growth hormone and IGF-I,

thereby promotes the growth. Thyroxine also produces the greater protein
biosynthesis leading to positive nitrogen balance. This also leads to growth.
Thyroxine enhances myelination of nervous tissue.

Insulin like growth factor -1. Growth hormone stimulates the liver to secrete
IGF-1 or somatomedin C. Somatomedin C, in turn promotes protein
biosynthesis, visceral growth, epiphysial growth and new skeletal development.

Cortisol: It shows antigrowth effect. It inhibits DNA synthesis. It produces

protein catabolism so inhibits bone growth and muscular growth. Elevation of
cortisol in children due to stress or infection adversely effect the normal growth
and produce growth retardation.

TABLE 7.11
Summary of hormonal influences on growth
1. Growth hormone
2. Thyroid hormones
3. Parathyroid hormone, vitamin D and calcitonin 4. Glucocorticoids
(cortisol)
5. Insulin

6. Oestrogens
7. Oestradiol
8. Androgens

Stimulates growth in many tissues.

Stimulates protein synthesis. Positive nitrogen balance.
Mainly secreted during sleep.
Many effects mediated through somatomedins.

Permissive for action of growth hormone.

Deficiency in early childhood leads to irreversible small stature and mental
retardation.
Essential for normal development of the central nervous system.
Essential for normal bone
formation and growth.
Regulatory effect on tissue growth.
In excess inhibits growth in height.

Stimulates protein synthesis and inhibits protein breakdown.

Somatomedins, the insulin-like growth factors (IGF) have similar molecular
structure to proinsulin.

Growth of female organs at puberty

stimulates female pattern of fat distribution.

Widespread anabolic effects on reproductive organs and somatic tissues.

Stimulates protein synthesis via direct influence on cellular DNA and RNA.
Stimulates development of typical male physique and characteristics.

Nutritional factors: Growth of tissues depends upon adequate supply and

utilisation of all the major and minor nutrients. Balanced diet influences optional
growth. Nutritional deficiency many cause growth retardation.

Environmental factors: Temperature, humidity, light–dark cycle, altitudes may

influence growth and development.

Social factors: Social condition like proper love, affection, care and attention
during childhood days influence the psychological and behavioural growth of the
child.

Genetic factors: Genetic factors influence the growth and development

influencing height and weight of the individual. Behavioural development
depends mostly on genetic factors, environmental, nutritional, social and cultural
factors.

Aging

Aging or senescence is the process of growing older with an increase in the age
of an individual. The study of aging process is known as gerontology. Nobody
likes aging but nobody can avoid aging because it is a fundamental truth of
nature. Physiologically aging refers to the impaired ability to maintain
homeostasis in the face of external and internal challenges or stresses. This is
known as homeostenosis. As a result of this the individual becomes more
vulnerable to these challenges and succumbes to death. In human beings
maximum performance is achieved around 25 years of age and measurable
decline in various functions starts at the age of 30 years. The decline in
efficiency continued slowly and later it becomes considerable and functionally
significant. Every organ undergoes changes, they show their least performance at
early age and in old age.
Many factors influence the aging process. They are
1. Chromosomal abnormalities
2. Increased DNA cross linking
3. Decrease in DNA methylation
4. Loss of DNA telomeric sequences
5. Changes in protein structures
6. Deformation of mitochondria.
There are two important theories explaining aging process:
1. Genetic theory of aging
2. Random damage theories
Genetic theory of aging suggests that repair of DNA becomes less efficient with
age or that there is an increase in somatic mutations with aging with subsequent
alteration of the genetic sequences in DNA. This theory proposes a programmed
senescence by a biological time table. Each cell will have a predetermined life
span. Many errors may occur in the way proteins are synthesised as age
advances. These protein may be considered as foreign and antibodies may be
developed against them. All these leads to lesser performance of the organs and
body as a whole.
Random damage theory explains that aging is due to the loss of balance
between on going damage and repair. The tissue damage is a continuous process
mostly caused by the attack by the free radicals. These free radicals damage the
cells by oxidation. They damage DNA and proteins, destroy membrane lipids.
This is known as oxidation stress. The scavenging system to remove this free
radicals exist in the body. But as age advances their efficiency declines, oxidants
dominates.

TABLE 7.12
Age related physiological impairments on various organs
Sl. No. System or organ Age related physiological impairments
Manifestations

1. Bodyweight and composition Increase in body fat. Decrease in body water

content
Increase in body weight, atherosclerosis. Dehydration

2. Blood and immunity Bone marrow depression

Decrease in T-Lymphocyte count Decrease in RBC count, Anemia. Decrease in

immunity, more prone for infection.
3. Cardio vascular system Decreased arterial compliance.

Atherosclerosis
Decreased heart rate
Increase in systolic blood pressure hypertension. Heart attacks. Bradycardia

4. Respiratory system Decrease in lung elasticity

Decrease in thorasic and lung compliance Stiffness of chest.

Decreased ventilation, Decreased lung capacities

5. Digestive system Decrease in gastric acidity

Decrease in motility of gastrointestinal tract Poor digestion Constipation

6. Renal system Decrease in number of nephrons

Decrease in GFR
Decrease in clearance value Decrease in GFR. Accumulation of waste products.
Decreases in renal efficiency.

7. Muscular system Decrease in muscle mass. General weakness, Decreased

ability to work.
8. Bones—Skeletal system Osteoporosis

Degenerative joint disease Easy fracturability Osteoarthritis.

9. Skin Becomes dry, thin and less elastic Pigmentation, sagging and wrinkles
formation
Contd…
10. Endocrine system Decrease in insulin secretion

Decrease in thyroxine secretion Increased ADH and decreased aldosterone

secretion
Increase in blood glucose level likely to get diabetes mellitus
Decrease in basal metabolic rate Increased urine output, disturbance in
electrolyte balance

11. Reproductive system Decreased secretion of testosterone

Male: Prostate enlargement
Female: Atrophy of vaginal mucosa Low sperm count
Urinary incontinence. More prone for infection

12. Nervous system

13. Special senses
Eyes — Vision Ear — Hearing

Tongue — Taste Brain atrophy

Decreased in dopamine secretion degeneration of neurons in basal ganglia.
Disturbance in posture and equillibrium, defect in righting reflex
Decrease in sleep.

Lens becomes opaque

Lens becomes less elastic
Ciliary mussels become weak Incresed intra occular pressure Reduction of
number of hair cells in cochlea.
Loss of taste buds. Decrease in cognitive ability, amnesia, decrease ability to
learn.
Parkinsonism
Tendercy to fall, change in gait

Insomnia.

Cataract.
Presbyopia or long sightedness of old age Glaucoma, Blindness.

Hearing impairment, deafness.

Decreased sense of taste and appetite.

TABLE 7.13 Aproximate percentage of functions of organs remaining at the

age of 75 taking the value of 30 year old as 100 per cent

5. Avoiding bad habits of smoking, drinking and excess sex.

6. Avoiding mental stress and physical strain.

Sl.No. Tissue Percentage

1. Brain weight 65
2. Nerve condution velocity 90
3. Number of taste buds 36
4. Body water content 82
5. Basal metabolic rate 84
6. Resting cardiac output 70
7. Number of glomeruli in kidneys 56
8. Hand grip strength 55
9. Speed of regulation of blood acidity 17

Mechnisms to delay the onset of aging are:

1. Controlled food intake—Avoid over eating.
2. Balanced diet—intake of antioxidents like Vitamin C and Vitamin E.
3. Regular physical activity.
4. Regular physical and mental relaxation.

PHYSIOLOGY OF STRESS
Introduction

The term stress was first used by the endocrinologist Hans Selye in the 1930s to
identify physiological responses in laboratory animals. He later broadened and
popularised the concept to include the perceptions and responses of humans
trying to adapt to the challenges of everyday life. In Selye’s terminology, stress
refers to the reaction of the organism, and stressor to the perceived threat.

Stress can be defined as actual or potential destabiliser of homeostasis.

Psychological Stress

Physiological stress is defined as the state of the body. Psychological stress

might be defined as a state of the mind. It is caused by psychological stressors
and manifested by a syndrome. A psychological stressor is anything that an
individual perceives as a threat - a threat to survival or to self-image. Moreover,
the threat does not need to be real. Psychological stressors produce a syndrome
of subjective and objective responses.

Dominant among the subjective reactions is a feeling of anxiety. Other emotional

reactions such as anger, hate; depression, fear, and guilt are also common
subjective responses of psychological stressors. Some characteristic objective
responses are restlessness, fidgeting, criticising, quarreling, lying, and crying.
Another objective indicator of psychological stress is that the concentration of
lactate in the blood increases.
Three Stages of Stress

Alarm reaction: Mediates mainly by norepinephrine from the sympathetic

nervous system and epinephrine from the adrenal medulla.

They prepare the body to take action

Causes a consumption of glycogen
Aldosterone level rise to promote sodium and water
conservation, which helps to offset possible losses
by sweating and bleeding
Angiotensin levels rise to raise the blood pressure. Stage of resistance: Occurs
when the body’s glycogen

reserves are exhausted and the body begins to provide alternative fuels for
metabolism.

This stage is dominated by cortisol which promotes the breakdown of fat and
protein for gluconeogenesis.
It also inhibits protein synthesis, leaving the free amino acids available for
gluconeogenesis.

The immune system is depressed with long term cortisol exposure due to its
heavy dependency of protein synthesis of antibodies and other products.
Wounds heal poorly.
Gastric secretions increase leading to ulcers. Depresses the secretion of sex
hormones.

This stage leaves the body more susceptible to disease and cancer.

Stage of exhaustion: When the fat stores are depleted and the body turns to
protein for fuel.
Leads to a progressive weakening and wasting away
of muscle.
Eventually the adrenal cortex stops producing
glucocorticoids, making fuel homeostasis
impossible.
At last, the effects of aldosterone begins to be
detrimental to the body.
Increase retention of sodium and water creates hypertension.
Elimination of potassium and hydrogen causes hypokalemia and alkalosis
resulting in nervous and muscular system dysfunction.
Death usually results from heart failure, kidney failure, or overwhelming
infection.

Mechanism of Stress

Stressors produce a state of stress. A state of stress, in turn, inaugurates a series

of responses that termed as General Adaptation Syndrome (GAS). A state of
stress turns on the stress response mechanism. It activates the organs that
produce the responses that make up the general adaptation syndrome. Selye, a
renounced endocrinologist postulated that some unknown alarm signals which
act through the floor of the brain mainly the hypothalamus to stimulate the
sympathetic nervous system and the pituitary gland.

Physiological Basis of Stress

The neurophysiology of the stress response is now believed to be well

understood, although much remains to be discovered about how the components
of this system interact with one another, in the brain and throughout in the body.
In response to a stressor, corticotropin-releasing hormone (CRH) and arginine-
vasopressin (AVP) are secreted into the hypophyseal portal system and activate
neurons of the paraventricular nuclei (PVN) of the hypothalamus.

The locus ceruleus and other noradrenergic cell groups of the adrenal medulla
and pons, collectively known as the LC/NE (locus ceruleus / norepinephrine)
system, also become active and use brain epinephrine to execute autonomic and
neuroendocrine responses, serving as a global alarm system. The autonomic
nervous system provides the rapid response to stress commonly known as the
fight-or-flight response, engaging the sympathetic nervous system and
withdrawing the parasympathetic nervous system, thereby enacting
cardiovascular, respiratory, gastrointestinal, renal, and endocrine changes.

1. Role of sympathetic nervous system

Stimulation of brain stem during stress with increase sympathetic discharge.
Increased sympathetic action produces the following responses:

Cardiovascular—Tachycardia
Respiratory—Tachypnea
Metabolic—Lipolysis, hyperglycemia – increases the availability of fuels to the
tissues.
Increased sympathetic activity will stimulate the adrenal medulla. This will
increase the secretion of catecholamines. Because of this the actions initiated by
sympathetic nervous system is continued for longer duration.

The hypothalamic-pituitary-adrenal axis (HPA), a major part of the

neuroendocrine system involving the interactions of the hypothalamus, the
pituitary gland, and the adrenal glands, is also activated by release of CRH and
AVP. This results in release of adrenocorticotropic hormone (ACTH) from the
pituitary into the general bloodstream, which results in secretion of cortisol and
other glucocorticoids from the adrenal cortex. These corticoids involve the
whole body in the organism’s response to stress and ultimately contribute to the
termination of the response via inhibitory feedback.

2. Behavioral response

Stress makes the individual to become widely awakened. Becomes aggressive

and attain combative aggressive mood. It may decrease food intake and sex
drive.

Stress can significantly affect many of the body’s immune systems, as can an
individual’s perceptions of, and reactions to, stress. The term
psychoneuroimmunology is used to describe the interactions between the mental
state, nervous and immune systems, as well as research on the interconnections
of these systems. Chronic stress has also been shown to impair developmental
growth in children by lowering the pituitary gland’s production of growth
hormone, as in children associated with a home environment involving serious
marital discord, alcoholism, or child abuse.

Signs and symptoms: Stress can cause headaches, irritable bowel syndrome,
eating disorder, allergies, insomnia, backaches, frequent cold and fatigue to
diseases such as hypertension, asthma, diabetes, heart ailments and even cancer.
Signs of stress may be cognitive, emotional, physical or behavioral and include
symptoms such as: poor judgment, a general negative outlook, excessive
worrying, moodiness, irritability, agitation, inability to relax, feeling
overwhelmed, feeling lonely or isolated, depressed, nausea, dizziness, chest
pain, rapid heartbeat, eating too much or not enough, sleeping too much or not
enough, withdrawing from others, procrastinating or neglecting responsibilities,
using alcohol, cigarettes, or drugs to relax, and nervous habits (e.g., nail biting,
pacing).
Management: Methods of coping with stress are aplenty. The most significant
or sensible way out is a change in lifestyle. Relaxation techniques such as
meditation, physical exercises, listening to soothing music, deep breathing,
various natural and alternative methods, personal growth techniques,
visualisation and massage are some of the most effective of the known non-
invasive stress busters.

The ‘Fight or Flight’ response, the hormones and the part of adrenaline in
the stress response
What is the Fight of Flight response?

The major difference between organic and inorganic systems is the self-
perseverance instinct. The world is an ever changing environment, demanding
abilities of reacting, defending one, changing the inner or outer surrounding for
one single aim: survival. Hence, when an animal is confronted with a perceived
dangerous—it reacts. The animal will use as many resources as needed, as much
energy as possible—to deal with the threat.

In the animal kingdom the rules of survival are simple—only the stronger
survives. When faced with danger, the two main options are fighting (when you
perceive the enemy to be weaker than you, or when defending your cubs or
herd), and running away (when you encounter a huge hungry lion, for example).
In face of danger, the body changes its inner-balance and priorities into a high
physiological arousal, to enable these two functions.

The fight or flight response named by Cannon and Selye in the 1930s is a pattern
of physiological responses that prepare the organism (that’s us) to emergency.
When the external balance is disputed, our body changes its internal balance
accordingly. The fact that modern problems do not require such means is exactly
the setting of stress-related problems.

The manifestations of the F or F are mainly through two channels: the

sympathetic branch of the ANS and the Endocrine system—both are closely
interconnected. The ANS affects many bodily functions instantly and directly,
while hormones have slower yet wider effect on the body. Both hormones and
neurons communicate with cells and create the delicate dynamic balance
between the body and its surrounding, through paired systems and feedback
mechanisms.
Some of the events occurring in our body, preparing it for either an F or F
response:

Increased heart rate, blood pressure and respiration. Pumping more blood to the
muscles, supplying more oxygen to the muscles and heart-lung system.
Increased sugar level in the blood. Allowing rapid energy use, and accelerating
metabolism for emergency need.
Thickening of the blood—to increase oxygen supply (red cells), enabling better
defense from infections (white cells) and to stop bleeding quickly (platelets).
Sharpening of senses—the pupils dilate; hearing is better etc., allowing rapid
responses.
Prioritising—increased blood supply to peripheral muscles and heart, to motor
and basic-functions regions in the brain; decreased blood supply to digestive
system and irrelevant brain regions (such as speech areas), this also causes
secretion of body waists, leaving the body lighter.
Secretion of Adrenaline and other stress hormones —to further increase the
response, and to strengthen relevant systems.
Secretion of endorphins—natural painkillers, providing an instant defence
against pain.

There are further systems involved in the F or F response, and even more
consequences to it. It is clear that the F or F response is crucial to dealing with
some shortterm dangers but it is incapable of dealing with long-term stress. The
grave consequences of long-term stress on our body and mind, is a direct result
of this inadequacy.

Stress Hormones

Stress hormones such as cortisol, growth hormone and norepinephrine are

released at periods of high stress. The hormone regulating system is known as
the endocrine system. Cortisol is believed to affect the metabolic system and
norepinephrine is believed to play a role in ADHD (Attentiondeficit
hyperactivity disorder) as well as depression and hypertension. Stress hormones
rise in the body during any neuroendocrine reaction such as surgery and they
remain high to as long as 72 hours after which all these hormones return back to
their normal level, the last being cortisol.

Adrenaline
There is a good reason why the first discovered hormone (1894) was Adrenaline
(Epinephrine). Produced and secreted by the adrenal gland (that all its hormones
are known as stress hormones), adrenaline is secreted as a direct reaction to
stressful situations, and its powerful effects are similar to those of the
sympathetic branch of the ANS (such as increasing heartbeats, blood pressure,
sugar-levels, muscle activity etc.).

Besides its hormonal functions, adrenaline is also an excitatory neurotransmitter

in the CNS (indirectly controlling its own production). It is involved both in
neural and hormonal processes and its effects as a neurotransmitter is further
reinforced by its hormonal function (a positive feedback loop).

It is therefore by far the most important single hormone in regarding to stress—

taking a major role in the stress reaction (and staying longer in the body than
autonomic nervous system—[ANS] processes).

Noradrenalin also acts as a stress hormone; noradrenalin affects parts of the

brain where attention and responding actions are controlled. Along with
epinephrine, norepinephrine also underlies the fight-or-flight response, directly
increasing heart rate, triggering the release of glucose from energy stores, and
increasing blood flow to skeletal muscle.

Cortisol

It has been termed the stress hormone because it’s also secreted in higher levels
during the body’s fight or flight response to stress, and is responsible for several
stress-related changes in the body. Small increases of cortisol have some positive
effects: Stress stimulate hypothalamus to secrete more of CRF. CRF stimulates
anterior pituitary and increases the secretion of ACTH. ACTH stimulates the
adrenal cortex and increases the secretion of cortisol. Hypothalamohypophysial-
adrenal axis. Cortisol helps to overcome the stressful situation by following
ways:

1. It increases blood glucose and free fatty acids levels. Thus makes the
availability of fuel to tissues.

2. It suppresses immune response and allergic reactions.

3. By its permissive action cortisol increases the efficacy of catecholamines.
Because of this more lipolytic action and beneficial changes in cardiovascular
and respiratory system are produced.
4. Cortisol decreases the sensitivity for pain.

5. It will help to restore the lost homeostasis. ADH: During stress ADH
secretion increases. This leads to conservation of fluid and restores fluid
homeostasis.

While cortisol is an important and helpful part of the body’s response to stress,
it’s important that the body’s relaxation response to be activated so the body’s
functions can return to normal following a stressful event. Unfortunately, in our
current high-stress culture, the body’s stress response is activated so often that
the body doesn’t always have a chance to return to normal, resulting in a state of
chronic stress.

The words ‘positive’ and ‘stress’ may not often go together. But, there are
innumerable instances of athletes rising to the challenge of stress and achieving
the unachievable, scientists stressing themselves out over a point to bring into
light the most unthinkable secrets of the phenomenal world, and likewise a
painter, a composer or a writer producing the best paintings, the most lilting of
tunes or the most appealing piece of writing by pushing themselves to the limit.
Stress is, perhaps, necessary to occasionally clear cobwebs from our thinking. If
approached positively, stress can help us evolve as a person by letting go of
unwanted thoughts and principle in our life. Very often, at various crossroads of
life, stress may remind you of the transitory nature of your experiences, and may
prod you to look for the true happiness of life.
Nervous System
Patric David Wall
25-4-1925–8-8-2001
British Neuroscientist
World’s most leading expert on pain- Known for Gate control theory of pain
Sherrington medal (1988)

Bernard Kartz
26-03-1911–20-4-2003
British Neurophysiologist Known for Neurophysiology of synapse
Nobel Prize (1970)

Sir Charles Bell

10-11-1774–28-4-1842 Scottish Anatomist Known for New Idea of Anatomy of
Brain, BellMagendie law

Froncois Magendie
6-10-1783–7-10-1855
French Physiologist
Known fo-Foramen of
Magendie and Bell-Magenie law, Magendie sign
Predecessor of Claude Bernard
Korbinian Brodmann
17-11-1868–22-08-1918
German Neurologist
Known for his study of Cytoarchitecture of cerebral cortex and naming the
distinct
regions with numbers
Brodmann’s numbers

Carl Wernicke
15-5-1848–15-6-1905
German Physician, Anatomist Psychiatrist and Neurobiologist. Known for
sensory area for speech-Wernicke’s area
 (274)

James Parkinson
11-4-1775–21-12-1824
English Physician
Discovered Parkinson’s disease

Camillo Golgi
7-7-1843–21-1-1926
Italian Neuroscientist
Known for Golgi apparatus, Golgi cells, Golgi 1st and Golgi 2nd neurons
Nobel Prize (1906)

H.W.G.Von Waldiyer-Harty 6-10-1836–23-01-1921

German Anatomist
Famous for Neuron theory of nervous system, Waldeyer’s gland

Burrhus Frederic Skinner 20-3-1904–18-8-1990

American Physiologist
Known for Operant conditioning Radical Behaviour, Operant conditioning
chamber, Verbal behaviour

Paul Pierre Broca

28-06-1824–9-7-1880 French Anthropologist, Physician and Anatomist Known
for Motor area for speech Broca’s area

Alosius Alzeimer
German Psychiatrist and Neuropathologist
Famous for Identifying
presenile dementia later known as Alzeimer’s disease.

Chapter
8
NERVOUS SYSTEM

Organisation of Nervous system.

Neuron—Structure, classification and properties. Nerve fibre—Classification,
conduction of impulses. Degeneration and regeneration of nerve fibre,
Neurotrophins.
Neuroglia—Types and functions.
Sensory Receptors—Definition, Classification and properties.

Synapse—Structure, transmission, properties, synaptic inhibition,

Neurotransmitters.

Organisation of spinal cord

Reflex action, Reflex arc, Classification, properties Ascending Tracts—Sensory
pathways.
Pathway for fine touch, crude touch, pressure, pain, and temperature.

Physiology of Pain—Definition of pain, Pain receptors, Classification of pain,

Pain pathways— fast and slow.

Modulation of pain at spinal cord level.

Central pain analgesic mechanisms.

Referred pain, Phantom pain, Projected pain, Analgesia, Principles of pain

management.

Descending tracts—Pyramidal and extra pyramidal pathways: Origin, course,

termination and functions. Upper and lower motor neuron lesion.
Lesions of spinal cord.
Structure and functions of—Medula and Pons Cerebellum—Structure,
connections and functions. Cerebellar disorders
Posture and equilibrium, muscle spindle and postural reflexes.
Decerebrate rigidity
Hypothalamus—Structure, connections and functions.
Thalamus—Structure, connections and functions. Thalamic syndrome.
Basal ganglia—Connections, functions and disorders.
Reticular formation
Cerebral cortex, cytoarchitecture, lobes and functions. Dominant hemisphere,
Disorders. Limbic system, organisation, connections and functions.
Electroencephalogram.
Physiology of Sleep.
Speech and speech disorders.
Learning and Memory—Definition, types of memory.
Amnesia, Alzheimer’s disease.
Cerebrospinal fluid.
Hydrocephalus—lumbar puncture, Blood—Brain Barrier.
Autonomic Nervous System, Organisation and functions.
Cranial nerves.

Organisation of the nervous system

Central nervous system Peripheral nervous system
Brain Spinal cord Somatic nervous

system
Automatic nervous system (ANS)

Fore Mid brain (or Hind brain (or brain mesencephalon Rhombencephalon
Spinal nervous Cranial nerves (31 pairs) (12 pairs)
Pons Medulla Cerebellum oblongata
Sympathetic

nervous system Parasympathetic nervous system

Telencephalon (consists of cerebral

hemisphere)

Upper 2/3rd thalamus Dien

cephalon

Lower 1/3rd hypothalamus with pituitary complex Ventral part

'Cerbral peduncle' (consists of tegmentum, substantia nigra and basis peduncle)
Dorsal part
tectum (comprises superior and
inferior colliculi)

Fig. 8.1 Organisation of the nervous system

FUNCTIONS OF NERVOUS SYSTEM 1. Control and Co-ordination

Nervous system and endocrine systems are considered as control systems of the
body. Nervous system control and co-ordinates body functions at various levels,
at molecular level, cellular level, tissue level, organ level, system level and
whole body level.

2. Information Handling

Changes taking place inside the body and outside the body are detected by
sensory receptors and these informations are transmitted to the brain. If the brain
information is processed, a small fraction of information is stored. This stored
form of information is known as memory. It can be recalled at a later time and
date.

3. Motor Function

Motor impulses are generated at the motor cortex of cerebral cortex. These
motor impulses are transmitted down to the skeletal muscles. The muscles get
excited and followed by contraction. Contraction of voluntary muscles is
responsible for each and every movement i.e., work. The work is planned,
programmed and executed by the nervous system.

4. Higher Functions of Nervous System

This includes thinking, logic, reasoning, prediction, planning, judgement,
language etc.
Stimulus
Sensory organs

5. Functionally they are:

1. Sensory neurons 2. Motor neurons
6. Depending upon chemistry of neurotransmitter secreted:

1. Adrenergic 2. Cholinergic.
Sensory memory Forgotten
due to fading Dendrites

NonVerbalisation verbalised
Forgotten Nissl bodies
Solid
Inter
mediary
store Repetition

Primary
memory storage time seconds Maked by
new information Cell body Nucleolus Nucleus

Neurofibrils

Tertiary memory Secondary

memory very large capacity minutes to lifelongyears
very large capacity

Forgotten on account of
interference by previously or
Slow
subsequently acquired
knowledgeRapid
Fig. 8.2 Information storage in the brain (Memory)
NEURONS
Neurons are the structural and functional units of the nervous system. There are
about 100 to 140 billion neurons.
Nucleus of schwann cell Axonal hillock Axon
Myelin
Collateral

Nodes of ranvier Cell body Nucleus Nucleolus

Nissl
bodies Axon
Myelin Nucleus of schwann cell
Nodes of ranvier
Marshburn

Classification of Neurons 1. Based on shape: 1. Oval

3. Pyramidal

2. Based on polarity: 1. Apolar

3. Bipolar

3. Depending upon size: 1. Micro neurons

Dendrites
2. Spherical 4. Stellate
2. Unipolar 4. Multipolar

2. Macro neurons 4. Histologically they are divided into two depending upon
the presence or absence of myelin sheath: 1. Myelinated 2. Non-Myelinated

Motor neuron Sensory neuron Fig. 8.3 Neurons

Properties of Neurons
1. Excitation 2. Conduction
3. Refractory period 4. All or none law 1. Excitation or Excitability

It is a property shown by nerves and muscles. Excitability is defined as ability to

respond to a stimulus by way of generating an action potential. Stimulus means a
change in the energy level. Resting membrane potential (RMP) is defined as the
potential difference or voltage difference
+30 Spike potential
+20 Overshoot
+10

0
–10
–20
–30
–40

–50
Firing
level–55 Points of
–60 stimulus–70
After
depolarisation

Latent period After

hyperpolarsation

Time (ms)

Absolute refractory period

Relative
refractory period

Fig. 8.4
Action potential

existing between inside and outside of a nerve membrane when it is at rest.

Normal RMP is –70 mv to –90 mv. RMP is due to unequal distribution of ions
between inside and outside nerve membrane. There is more sodium ions and
chloride ions outside the nerve membrane where as K+ and negatively charged
protein ions are more inside the membrane. This unequal distribution of ions are
due to the following reasons:

1. Operation of sodium potassium pump: It is an active transport mechanism. It

involves carrier proteins and requires energy expenditure.

2. Permeability of membrane to potassium ions is greater than sodium ions.

3. Presence of net negatively charged non-diffusable protein ions inside the

membrane.
When the nerve is stimulated the permeability of membrane changes. It becomes
more permeable to sodium ions. Na+ rush from outside to inside of membrane.
This is known as sodium influx. Entry of positively charged ions make the inside
of the membrane more and more positive, less and less negative. The polarity is
lost. This phase is depolarisation. For a fraction of a second the inner side of the
membrane becomes positive (+30 mv.) But once again polarity is reestablished.
This phase is known as repolarisation. Action potential is defined as a changing
potential taking place across the membrane with depolarisation followed with
repolarisation spreading along the length of nerve membrane.

2. Conduction

Action potential or impulse generated at any part of nerve membrane is not

confined to that region, it is propagated throughout the length of nerve
membrane. This is known as propagation or transmission or conduction of
impulse or action potential.

3. Refractory period
It is defined as period after the first stimulus, the second

stimulus can not generate a fresh action potential. It is divided into two parts.

(a) Absolute refractory period

(b) Relative refractory period.
Absolute refractory period: This is the earlier part

of the refractory period during which second stimulus of whatever higher

intensity can not generate a fresh action potential.

Relative refractory period: This is the later part of the refractory period during
which second stimulus of higher intensity can generate a fresh action potential
but, second stimulus of same intensity cannot produce.

4. All or None law

The minimum strength of stimulus required for generating an action potential is

known as threshold stimulus. Any strength of stimulus below the threshold
stimulus is known as sub-threshold stimulus, above the threshold it is known as
supra-threshold stimulus. When the strength of stimulus is below the threshold
there is no response at all. When the strength of stimulus reaches threshold level
there will be a response. The magnitude of response is maximum. When the
strength of stimulus is increased above the threshold there will be a response, but
there is no proportional increase in the magnitude of response. That is, if the
nerve responds it will respond maximally otherwise not at all. This phenomenon
is known as all or none law.

Excitability curve or strength duration curve:

6R
5R
4R R - Rheobase C - Chronaxie 3R U - Utilisation time
2R C RU R
Duration of stimulus
Fig. 8.5
Excitability curve

There is a relationship between strength of stimulus and duration of its

application. When the strength of stimulus is high it has to be applied for a short
duration of time to generate an action potential. When the strength of stimulus is
low it has to be applied for a longer duration to excite the nerve. The graphical
representation of relationship between strength of stimulus and duration of its
application is known as excitability curve or strength duration curve.

1. Rheobase: It is the minimum strength of stimulus when applied for a long

time can generate an action potential.

2. Utilisation time: It is the duration of time a stimulus of strength equal to

rheobase has to be applied to excite the nerve.

3. Chronaxie: It is the duration of time, at which strength of stimulus equal to

double the rheobase has to be applied to generate an action potential. The time
taken to respond when a stimulus strength of double the rheobase is applied is
called chronaxie.

Chronaxie is the measure of excitability of the nerve. The nerves of low

chronaxie value are more excitable. Excitability α 1/chronaxie.

NERVE OR NERVE FIBRE

Nerve or nerve fibre is a bundle of axons.
Classification of Nerve Fibres

1. Based upon function:

1. Sensory
2. Motor
3. Mixed

2. Based on presence or absence of myelin sheath: 1. Myelinated

2. Non myelinated

3. Depending upon the chemistry of neurotransmitter secreted:

1. Adrenergic
2. Cholinergic

4. Depending upon the thickness or diameter of the nerve fibre or Gasser-

Erlanger classification: According to this classification nerves are broadly
classified into 3 types:
1. A-thickest fibres
2. B-medium sized fibres
3. C-thinnest fibres
A fibre are further classified into Aα, Aβ, Aϒ, Aδ,

TABLE 8.1
Numerical classification of nerve fibres
Number Type of fibre Example 1a Aα
1b Aα II Aβ
III Aδ
IV Dorsal root

C fibres of spinal nerve Annulospiral ending of muscle spindle

Glogitendon organ
Flower spray ending of muscle spindle carry touch and pressure sensations

Carry fast pain and cold sensation

Carry slow burning pain and temperature

TABLE 8.2
Gasser-Erlanger classification of nerve fibres
Type Nature Diameter in micron Function Velocity of impulse transmission.
m/sec A α Myelinated
Motor and sensory 12–22
A β Myelinated
Motor and sensory 6–12
A ϒ Myelinated
Motor and sensory

3–6 Sensory–proprioception Motor–Somatic

Sensory–touch, pressure Motor—somatic

Motor—to muscle spindle 70–120
30–70
15–30
A δ Myelinated
Motor or sensory 2–5 Sensory—pain, temperature 12–30
B Myelinated efferent Preganglionic
C Unmyelinated Less than 2 Preganglionic autonomic nerves 3–10
0.3–1.5 Sensory—slow pain, temp Post ganglionic sympathetic 0.5–2

5. Depending upon the length of axon: 1. Golgi type I—Short axons

2. Golgi type II—Long axons

6. Depending upon oxigin:

1. Cranial nerves 2. Spinal nerves Conduction of impulses in the nerve fibre
There are two types of conduction of impulses in the nerve fibre.

1. Continuous conduction 2. Saltatory conduction Continuous conduction

This type of conduction takes place in non myelinated nerve fibres, here influx
and efflux (movement of ions out side) of ions takes place continuously
throughout the length of nerve membrane This type of conduction requires more
energy expenditure. This type of conduction is slow conduction. It is a primitive
type of conduction.

Saltatory conduction
This type of conduction takes place in myelinated nerve fibres. Action potential
jumps from one node of Ranvier to the next node of Ranvier. Ionic influx and
efflux takes place

only at the nodes of Ranvier. Other parts of the axon are impermeable to ions.
Action potential RMP

–+
–++

–
+
–– +
–+

Depolarization during the action potential causes adjacent Na+ channels to open

Resting
membrane potential

+ +++++++–+ + + + + + +++ + +++++

––– – –– – – + –– –– – –– – – – – – –––
––– – –– – – + –– –– – –– – – – – – ––– + +++++++ –+ + + +++ +++ ++++++

Fig. 8.6
Conduction of impulses in a nerve fibre

Saltatory type of conduction is a more evolved type of conduction. It requires

less energy expenditure and is faster than continuous conduction.

TABLE 8.3
Comparison between saltatory and continuous conduction
S.No. Features Saltatory conduction Continous condution 1. Seen in
Myelinated nerve fibres Non myelinated nerve fibres 2. Characteristics Action
potential jumps from one node of

Ranvier to next nerve membrane

Action potential spreads throughout the segments of

3. Ionic movements Takes place only at the nodes of Ranvier Takes place
everywhere in the nerve membrane 4. Speed Fast Slow 5. Energy expenditure
Less More 6. Efficiency More efficient Less efficient 7. Evolutionary grade
More evolved type Less evolved type or primitive

Factors effecting velocity of impulse transmission 1. Presence or absence of

myelin sheath: Myelinated nerve fibres conduct impulses 50 to 100 times faster
than non-myelinated nerve fibres

2. Diameter or thickness of the nerve fibres: Thicker nerve fibres conduct

impulses faster than thinner fibres. In a myelinated nerve fibre velocity is
proportional to its diameter. In a myelinated nerve fibre the velocity of impulse
transmission is approximately equal to diameter in microns ×6. In a non-
myelinated nerve fibre velocity is directly proportional to the square root of the
diameter.

Vd
α

3. Temperature: Increase in temperature increases the velocity of impulse

transmission. Cold decreases the velocity.

4. Hypoxia: Decreases the velocity of impulse transmission.

5. Drugs: Narcotic drugs like morphine decreases the velocity of impulse
transmission.
6. pH: When pH increases velocity of impulse transmission increases upto a
limit.

Nerve degeneration or Wallerian degeneration When a nerve is severely

injured, certain changes take place at a part of the nerve in front of the injury as
well as behind the injury. These changes are known as degenerative changes or
Wallerian degeneration.
Changes taking place at the distal part or peripheral part

1. The peripheral part of the injured nerve may retain the ability of transmission
up to three days from the day of injury.
Cell body Chromatophilic substance (Nissl bodies)
Myelin sheath
(a) Normal neuronAxon Injury site Neurolemmocyte (schwann cell)
(b) Chromatolysis
(c) Wallerian degeneration Regeneration tube
 Fig. 8.7 Nerve degeneration or Wallerian degeneration 2. The axon
(d) Regeneration
rods get disintegrated, breakup into

numerous rodlets or fragments.

3. The myelin get hydrolysed, this starts from 8th day
of the injury and completes by 32nd day. Hydrolysis
of myelin produces the chemical components of
myelin like cerebroside, fatty acid, cholesterol,
sphingomyelin. These chemicals appear in droplets. 4. The Schwann cells
multiply.
Changes taking place in the proximal part
1. The changes taking place in the axon of the

proximal part is restricted upto the first node of Ranvier from the site of injury.
2. The cell body or soma swells.
3. The disintegrate and disappear. This process is known as chromatolysis.

Regeneration
Regeneration means repair of damaged nerve fibre: 1. Regeneration is seen only
in the peripheral nervous system but not in the central nervous system.

2. For regeneration neurilemma (tight covering of axon) is required. Neurilemma

is present only in the peripheral nervous system and not in the CNS.

3. The broken end of the axon of the proximal side starts growing. The growing
end of the axon fits into the empty tube or ghost tube.

4. The myelin sheath is secreted by the Schwann cells around the newly formed
axon. This establishes functional contact between the two broken ends of axon.

5. Regeneration is possible only if the gap is upto 3 mm. If the gap is more than
this, the growing end of axon bulges out and produces a surgical complication
known as neuroma.
– Microglia

– Ependymal cells

NEUROGLIA

Neuroglia are connective tissue of the central nervous system. Neuroglias are not
excitable and they can not conduct impulses.

Number of neuroglia is much more than neurons. Types of neuroglia

– Oligodendrocytes :

Functions
They secrete myelin sheath around axon in CNS.
: 1. They support neurons.

2. Helps in the nutrition of neurons and removal of waste products.

3. Take up neurotransmitters from extracellular fluid.
4. They produce trophic substance for neurons.

5. Absorb excess potassium ions from interstitial fluid.

6. Forms a part of blood-brain-barrier.
7. They act as electrical insulators.

: Shows phagocytic action and protect the brain from microorganisms.

: Get modified as choroid plexus and secrete CSF.

Protoplasmic astrocyte Fibrous astrocyte
Microglia
– Astrocytes
Oligodendrocytes
Fig. 8.8
Different types of neuroglia

Neurotrophins: This is a generic term to denote a number of neurotrophic

factors enhancing neuronal differentiation, inducing proliferation, influencing
synaptic functions, and promoting the survival of neurons that are normally
destined to die during different phases of the development of the central and
peripheral nervous system. Most of these factors are active at extremely low
concentrations.

Growth factors such as neurotrophins that promote the survival of neurons are
known as neurotrophic factors. Neurotrophic factors are secreted by target tissue
and act by preventing the associated neuron from initiating programmed cell
death—thus allowing the neurons to survive. Neurotrophins also induce
differentiation of progenitor cells, to form neurons.
Growth factors such as basic-FGF or LIF due to their trophic activities on a
number of neurons are frequently also counted among the neurotrophin group.

BDNF, NGF and NT-3 are referred to as the NGF protein family as NGF is the
founder member of this family of proteins. The multifunctional Pan-
Neurotrophin-1 (PNT-1) protein efficiently activates all trk receptors and
displays multiple neurotrophic specificities.

SENSORY RECEPTORS

Receptors are specialised nerve cells or nerve endings which detect a change in
energy level or stimulus and transmit this information to CNS as action potential.
Receptor acts as transducers, convert one form of energy to another form, e.g.,
mechanical to electrical.
(b) Enteroceptors—Receptors which receive stimuli

within the body, e.g.,chemoreceptors, baroreceptors.

(c) Teloreceptors—Receptors which receive stimulus coming from the distance,

e.g., visual receptors (rods and cones), cochlear receptors (hair cells).

(d) Proprioceptors—Receptors detecting changes in muscle length, tension and

movements of joints.
2. Classification based on type of stimulus energy
Stimulus energy (a) Mechanical
TOUCH
PRESSURE
STRETCH
SOUND
EQUILIBRIUM
Blood Pressure
(b) Photic (Light)
(c) Thermal
The different receptors: B A. Meissner s corpuscle¢ B. Ruffini's end organ C C. Pacinian corpuscle D. Free
nerve ending A E. Merkel s disc¢ F. Krause's end bulb
E
(d) Chemical

(e) Extremes of
mechanical, thermal and chemical energy or pain
Receptors
Mechanoreceptors
(i) Skin and deep tissue—

Merkel’s disc
(ii) Pacinian corpuscles. (iii) Muscle and tendon

stretch receptors— Muscle spindle.

(iv) Hair cells of cochlea.

(v) Hair cells of vestibular apparatus.

(vi) Baroreceptors of carotid sinus and aortic arch.

Photoreceptors of retina rods
and cones.
Cold and warm receptors
which detect environmental
temperatures.
(i) Chemoreceptor for taste and smell.
(ii) Aortic and carotid body receptors for detecting level of arterial PO2, PCO2
and H+ ions.
Nociceptors (detecting pain).
Free nerve endings.
D
F

Fig. 8.9 Types of sensory receptors

Classification of Receptors
1. Classification based on the source of stimulus

(a) Exteroceptors—Receptors which receive stimuli from immediate external

surrounding, e.g., cutaneous receptors for pain, touch, warm, cold etc.

Sensory modality or Receptor

1. Stimulus: Touch — Meisner’s corpuscles, Merkel’s Disc, Pacinian corpuscles
Touch, deep pressure, stretch—Ruffini end bulb, free nerve ending
Touch, low frequency vibration—Krause’s end bulb 2. Pressure—Pacinian
corpuscle
3. Thermo receptor
Cold—Cold receptors
Warm—Free nerve endings
4. Pain—Free nerve endings
5. Proprioceptors: Receptors for movement sense and
give information about the position of the body
in space.
6. Muscle receptors, joint receptors, hair cells of
vestibular apparatus for equilibrium.
Muscle tension
Muscle length : Golgi tendon receptors : Muscle spindle
7. Vision-light—Rods and cones
8. Hearing-sound—Hair cells of cochlea 9. Taste—Gustation—Taste buds
10. Smell—Olfaction—Olfactory cells
11. Receptors of visceral senses
Stretch—Baroreceptors
Chemical change—Carotid body, Aortic body Osmotic change—Osmo receptors
of hypothalamus

3. Classification based on rate of adaptation of receptors

(a) Slowly adapting receptors (tonic or static receptors).
These receptors fire action potentials continuously during stimulus application,
Muscle spindle.

(b) Rapidly adapting receptors (phasic or dynamic receptors). These receptors

fire action potentials at a decreasing rate during stimulus application. Touch
receptor, Olfactory receptor.

(c) Nonadapting receptors – pain, equilibrium.

4. Clinical classification of receptors

(a) Superficial receptors—Receptors present in skin and mucous membrane.

(b) Deep receptors—Receptors present in the muscles, tendons, joints and
subcutaneous tissue.

Properties of Receptors
1. Specificity

Every receptor is sensitive for only one form of energy or stimulus, e.g., touch
receptors are sensitive only for touch. They are not sensitive for temperature.

2. Doctrine of specific nerve energies or Modality of sensation or Muller’s

law
A receptor can be stimulated by stimulus for which it is
specialised. Other forms of stimulus of moderate intensity
cannot stimulate the receptor. Other forms of stimulus of
very high intensity can stimulate the receptor. When a
receptor is stimulated by a form of energy other than to which
it is specialised, the sensation will depend upon what receptor
is stimulated and sensation does not depend upon how it is
stimulated. From every receptor impulses are transmitted
through a definite route and reach definite and specific groups
of neurons in the brain. Ultimately sensation depends upon
the groups of neurons of the brain which receives impulses
from the receptors. This concept is known as Muller’s law,
modality of sensation or doctrine of specific nerve energies.

3. Receptor potential or generator potential

Normally inside the receptor membrane it is negative compared to outside.
When a receptor is stimulated,

permeability of the membrane changes. It becomes more permeable to Na+.

Sodium influx takes place at the site of stimulus. This leads to depolarisation of
membrane. It is known as receptor potential or generator potential.

TABLE 8.4
Differences between receptor potential and action potential
S.No. Receptor potential Action potential

1. Receptor potential is a graded response, i.e.,amplitude of receptor potential

increases with increasing velocity of stimulus application and increasing strength
of stimulus.

2. Can be added together, if second stimulus arrives before the receptor potential
developed due to first stimulus is over.

3. Has no refractory period.

4. Mostly it is local and cannot be propagated along the nerve fibre.
5. Duration is greater (approximately 5-10 ms).
6. Does not obey all or none law.

Action potential obeys all or none law. Once the stimulus strength is great
enough to bring the membrane potential to a threshold level, further increase in
stimulus strength does not cause any change in the amplitude.
Cannot be added together.

Has a refractory period of about 1 ms.

It can be propagated without loss in the amplitude.
Duration is small (approximately 1–2 ms). Obeys all or none law.

4. Labelled line hypothesis

Information of any particular sensation is carried to sensory cortex involving a
set of or series of neurons.

A labelled line is a set of series of neurons meant for carrying a particular

sensation. Modality of a particular sensation can be perceived if the receptor is
stimulated or any other neuron in the pathway is stimulated. So modality
depends upon the pathway. This is known as Labelled Line.

Example: Visual pathway Rods/cones, Optic nerve, Optic tract, Occipital cortex
receptors. If visual pathway is stimulated any where in the series by any other
stimulus like electrical ,sensation of light is felt.

5. Waber’s law
States that least perceptable increase in the intensity of

sensation is the constant fraction of the original strength of stimulus.

6. Weber-Fechner’s law
There is a relationship between the strength of stimulus and intensity of
sensation. The intensity of sensation is proportional to log strength of stimulus. It
is known as WeberFechner’s Law. The intensity of sensation α log strength of
stimulus.
7. Stevan’s law or Power law

Intensity of sensation = K × strength of stimulus A, where K and A are

constants.
8. Law of projection
If any part of a sensory pathway is stimulated any where from sensory receptor
to sensory cortex, the conscious sensation felt is at the site of the receptors. No
matter where specific sensory pathway is stimulated along its course to the
cerebral cortex, the sensation formed is referred to the location of the receptors.
This is law of projection. Projection continues even if receptors are removed.
Phenomenon of Phantom limb.

9. Sensory unit
Defined as a single sensory axon and all its peripheral branches.
Receptive field of a sensory unit is the area from which a stimulus produces a
response in that unit.

10. Adaptation
When a receptor is stimulated for the first time it will be highly sensitive. It will
send impulses to the CNS at a high frequency. If the stimulus is persisting for a
longer time, the sensitivity of the receptor gradually decreases and the frequency
of impulse transmission from the receptor declines and it may even stop. This
phenomenon is known as

adaptation of a receptor. There are three types of receptors depending upon their
ability to adapt.

1. Fast adapting receptors: e.g., Touch receptor, Pressure receptor, Olfactory

receptor.
2. Slow adapting receptor: e.g., Muscle spindle.
3. Non adapting receptor: e.g., Pain receptor and equillibrium receptor.

SYNAPSE
Synapse is the functional junction between two neurons.

Depending upon mode of transmission across the synapse there are two
types of synapses:
1. Electrical synapse: very rare.
2. Chemical synapse: most common.
Depending upon the parts of the two neurons contacting there are four types of
synapses:
1. Axo-axonal 2. Axo-dendritic
3. Axo-somatic 4. Dendro-dendritic
Dendro-dendritic Axo-axonic
Axo-somatic Axo-dendritic

Fig. 8.10 Types of synapses

Structure of a Synapse

There are two neurons taking part at a synapse. These two neurons are known as
pre-synaptic neuron and post synaptic neuron. These two membranes are known
as pre-synaptic membrane and post-synaptic membrane.

Inside the pre-synaptic membrane there are several vesicles (sacs). These
vesicles are filled with neurotransmitters. At the post synaptic membrane, there
are receptor proteins. The gap between pre and post synaptic membranes is
known as synaptic cleft, the gap is about 20–50 nm (nano meter).
Synaptic cleft

Presynaptic neuron Post synaptic neuron

Neurotransmitter Synaptic Vesicles

Receptor proteins
Fig. 8.11
Structure of synapse

An action potential or an impulse reach the tip of pre synaptic neuron. This
makes the vesicles to move towards pre-synaptic membrane. In the presence of
calcium ions the
Sequence of events of synaptic transmission
Initiation of action potential in the presynaptic neuron.
Passage of action potential to the terminals leading to depolarisation.

vesicle ruptures and release the neurotransmitter into the synaptic cleft. The
neurotransmitter travels across the synaptic cleft and reach the post synaptic
membrane. Here it binds with receptor protein. This binding changes the
permeability of post synaptic membrane.

The membrane becomes more permeable to sodium ions. Na+ influx takes place.
Post synaptic membrane gets depolarised. This leads to the generation of fresh
action potential in the post synaptic neuron. This action potential is propagated
further. Transmission of impulse across the synapse is chemical in nature.
Properties of Synapse

1. Uni directionality: Impulses can be transmitted in only one direction across

the synapse. Impulses can be transmitted from presynaptic neuron to post
synaptic neuron.

2. Synaptic delay: It is the minimum time required for the transmission of

impulse from one neuron to the next neuron across the synapse. 0.5 milli second.

3. Excitatory Post-synaptic potential EPSP and Inhibitory Post-synaptic

Potential IPSP.
Increase permeability of presynaptic membrane for calcium ions.
Entry of calcium from ECF of synaptic cleft into the axon terminal.
Rupture of synaptic vesicle
Release of neuro transmitter from synaptic vesicles into the synaptic cleft.
Binding of neuro transmitter to the receptor proteins of postsynaptic membrane.

EPSP

The action potential reaches the tip of pre-synaptic neuron. This makes the
synaptic vesicles to move towards the presynaptic membrane. With the help of
calcium ions the vesicles rupture and neurotransmitter is released into the
synaptic cleft. Neurotransmitter reaches the post synaptic membrane and binds
with receptor protein. This increases the permeability of post synaptic membrane
to Na+ ions. Sodium influx takes place. This leads to depolarisation of post
synaptic membrane and generation of a fresh action potential. This type of
potential change at the post synaptic membrane is known as Excitatory Post
Synaptic Potential. The neurotransmitters producing EPSP are called excitatory
neurotransmitters, e.g., adrenaline, acetylcholine etc.
Change in the permeability of postsynaptic membrane to specific ions.
Ion channels open-either depolarisation or hyperpolarisation
+–
(When K or Cl channels open) of the postsynaptic membrane.

IPSP

An action potential reaches the tip of pre-synaptic neuron. This makes the
vesicles to move towards the pre-synaptic membrane. The vesicles rupture in the
presence of calcium ions.
Conduction of depolarisation or hyperpolarisation electronically over the entire membrane of postsynaptic
neuron.
Initiation of action potential in the postsynaptic neuron.

Fig. 8.12
Transmission across a synapse

This releases the neurotransmitter into the cleft. Neurotransmitter reaches the
post synaptic membrane and binds with receptor protein. This binding increases
the permeability of membrane to potassium ions. Potassium efflux takes place.
Inside of the post synaptic membrane becomes more negative or it get
hyperpolarised. This type of potential changes in the post synaptic membrane is
known as Inhibitory Post Synaptic Potential. The neurotransmitters producing
IPSP are known as Inhibitory neurotransmitters. For example, Glycine and
GABA (Gamma Amino Butyric Acid).

4. Summation
Summation means adding up of the effects of multiple impulses at the synapse.
There are two types of summation. 1. Spatial summation and 2. Temporal
summation Spatial summation
Suppose multiple impulses make synaptic contact at different parts of a common
post synaptic membrane. The effects of multiple impulses coming and striking at
a common post

synaptic membrane simultaneously get added up. This phenomenon is know as

spatial summation.

Temporal summation
Suppose multiple impulses come and strike at a common post synaptic
membrane one after the other in quick succession. The effect of these multiple
impulses will get added up at the post synaptic membrane. This phenomenon is
known as temporal summation.

5. Convergence

Suppose many neurons synapse with a common post synaptic neuron. The
impulses coming from various directions through the multiple neurons get
converged at the synapse. All these impulses are further transmitted in a single
uniform direction. This phenomenon is known as convergence.

Fig. 8.14 Divergence

7. Fatigue
When impulses are transmitted across a synapse repeatedly, after some time it
stops transmitting impulses. This phenomenon is known as fatigue. Fatigue is
due to the depletion of neurotransmitters. It is a temporary phenomenon.

8. Fate of neurotransmitters
The neurotransmitters released at the synaptic cleft reach

the post synaptic membrane and produces the desired change in the post synaptic
potential. After that the neurotransmitters are inactivated by the following
means:

1. Most of the neurotransmitters are taken back by the pre-synaptic membrane

andreused.
2. The neurotransmitters are degraded enzymatically.
3. Small quantity of neurotransmitter escapes at the interstitial space.

10. Reverberation
It is the phenomenon of passage of impulses from pre

synaptic neuron to post synaptic neuron, again back to the presynaptic neuron, so
that a continuous transmission of impulses in the circuit is maintained.

Mechanism: Some collaterals of axons of post synaptic neuron make contact

with pre synaptic neuron or cell body of same post synaptic neuron.

This causes reverberation of impulses through same circuit again and again.
+ Output
+

Fig. 8.13 Convergence Output

6. Divergence

Suppose a neuron makes synaptic contact with many second order neurons. The
impulses coming through the first neuron in a single direction get diverted at the
level of synapse and transmitted further in different directions. This phenomenon
is known as divergence.
+
Fig. 8.15 Reverbaration at the synapse Fatigue may prevent this phenomenon.
11. Synaptic facilitation

It is the process by which transmission through a synapse is increased when

presynaptic axon is stimulated with several consecutive individual stimuli, each
may evoke a larger post synaptic potential than that evoked by the previous
stimulus.

It is caused by increasing the neurotransmitter release.

Here first stimulus is to facilitate the second. Mechanism
If the transmitter released by pre-synaptic synapse on a pre-synaptic ending can
prolong depolarisation ( by closing K channel).
Then more Ca can influx which in turn lead to more release of NT.
Persistence of depolarisation can be achieved by NT like serotonin which closes
K+ channels and then prevents depolarisation.

12. Post Tetanic Potentiation

It also means enhanced synaptic transmission but of prolonged duration.

Short term potential is due to increased Ca in the presynaptic knob due to series
of stimuli and increased NT release .

Long term potentiation is due to increased Ca in the post synaptic neuron due to
opening of N-Methyl-DAspartate (NMDA) channels by NT like glutamate.
Drugs that bind to a receptor and produce a response similar to normal
neurotransmitter is called agonists.

Antagonists
Drugs that bind to the receptor but are unable to activate
are called Antagonists.
By occupying the receptors, antagonists prevent binding
of the normal NT when it is released at the synapse.
Tetanus toxin
Decrease inhibiting synaptic input to motor neurons
Elimination of inhibitory input
Increase unchecked excitory input
Excessive motor neuron activity
Leads to involuntary contraction of skeletal muscles
Examples: Spasm of jaw muscles, Lock jaw
Fig. 8.16
Affect of disease on synaptic transmission Blocking

The chemical transmission can be blocked by various agents, called “synaptic

blockers”.
For example, drugs like Hexamethonium block autonomic ganglia.
Various sedatives and anesthetics block reticular activating system to produce
sleep and anesthesia.

Synaptic inhibition
Upper motor neuron Motor impulses
Inhibitory neuron renshaw cell
Collateral
Anterior horn cell Muscle

Fig. 8.17 Renshaw cell inhibition or Negative feedback inhibition

Dorsal root ganglion cell Inhibitory inter neuron
Anterior horn cell
+ Stimulation
– Inhibition
Fig. 8.18 Reciprocal inhibition at spinal cord
l
l
Renshaw cell inhibition
Inhibitory Golgibottle neuron
output
–
+
Excitatory input +
Excitatory input Fig. 8.19
Golgi bottle inhibition
+

–
–– +

Post synaptic inhibition Presynaptic Direct post inhibition synaptic inhibition

Fig. 8.20 Different types of synaptic inhibition

Significance of synaptic inhibition

Botulin toxin
Tetanus toxin
Low doses of these toxins are used clinically. Botulin produces relaxations of
sphincter in Achlasia
Cardia.
Reduces wrinkles on the face by reducing facial muscle contraction.

Factors affecting synaptic transmission

Hypoxia: Transmission of impulses across synapse requires energy expenditure.
It depends on O2 supply.

So hypoxia or non availability of O2 stops synaptic transmission.

Acidosis and alkalosis: Acidosis decreases synaptic transmission and alkalosis
increases.
Drugs: Caffeine, theophylin—increases excitability. Mode of action is decreased
in threshold of excitation.

Anesthetic agents— decrease the excitability by increasing the threshold of

excitation.
Hypocalcaemia: Facilitates synaptic transmission.

Hypercalcaemia: Retards synaptic transmission. Effect of Acidosis and

Alkalosis on Synaptic Transmission

Alkalosis greatly increases neuronal excitability. For example, a rise in arterial

blood pH from 7.4 to 8 causes cerebral epileptic seizures because of increased
excitability of neurons.
Asking a person who is predisposed to epileptic seizures to over breathe
demonstrates this. It elevates the pH of blood momentarily but even this can
precipitate epileptic attack.

Acidosis greatly depresses neuronal activity. Fall in pH from 7.4 to 7 causes

comatose state. For example, in very severe diabetic or uremic acidosis,

coma develops.

Effect of hypoxia on synaptic transmission

Cessation of oxygen for only a few seconds causes complete in excitability of
some neurons.

When the brains blood flow in temporarily interrupted, within 3 to 7 seconds the
person becomes unconscious.
Effect of drugs on synaptic transmission

Caffeine, theophylline, theobromine, which are found in coffee, tea and cocoa,
respectively, all increase neuronal excitability (by reducing threshold for
excitation of neurons).
Strychnine best known of all agents that increase the excitability of neurons
(inhibits the action of some of the normal inhibitory transmitters like glycine).

Most anesthetics decrease synaptic transmission by increasing neuronal

membrane threshold for excitation.
They are lipid soluble, may change the physical characteristics of the neuronal
membrane making them less responsive to excitatory agents.

Antidepressants—Physiological basis
Psychic depression occurs when deficit of norepinephrine, dopamine, serotonin
and other amines exists in certain brain synapses. Mode of action of
antidepressants
Inhibition of COMT—COMT (Catechol-O-methyl transferase) is the enzyme
which inactivates NA. Inhibition of MAO—MAO (monoamine oxidase) is the
enzyme that inactivates dopamine and serotonin. Examples: phenelzine. Prevents
the break down of amines. Relieves the symptom of depression.

Blocking uptake of amines into axon terminal, examples: imipramine,

amitriptyline increase amine level at synapses.

Blocking uptake of dopamine into axon terminal, example: cocaine.

Local Anesthetics (LAs)—physiological basis

Examples—procaine, lignocaine, bupivacaine etc. Mechanism of action
—block nerve conduction by decreasing the entry of Na ions during upstroke of
action potential (AP).

As the conc. of LA is increased—rate of rise of AP and maximum depolarisation

decreases causing slowing of conduction and finally depolarisation fails to reach
the threshold potential and conduction block ensues.

Co-transmitters
Chemicals that are secreted along with neurotransmitters.
Examples—release of VIP with acetylcholine neuropeptide gamma with
norepinephrine. Functions—co-transmitters facilitates the actions of
neurotransmitters.

NEUROTRANSMITTERS

These are the chemical substances liberated at the nerve endings and help to
transfer the message of the nerve impulses in the presynaptic neuron to an
adjacent cell, e.g., postsynaptic neuron, a muscle or a gland.

Chemicals secreted by neurons when enter the blood act as a hormone, the
chemicals are then called neurohormone. For example, ADH, GnRH.

Criteria for calling a chemical as neurotransmitter

1. The chemical must be synthesised in the neuron concerned.

2. Should be stored in the presynaptic endings.
3. Should be released at the synapse.
4. Should have its specific receptors on the post synaptic membrane.
5. On binding with receptor proteins on the surface of the post synaptic
membrane, it should produce either EPSP or IPSP.
6. Should be disposed quickly by a suitable system as soon as its action is over.
7. Exogenous application of the substance should mimic the effects of
stimulation of the neuron.

Different Types of Neurotransmitters

There are about 40 different neurotransmitters and they are classified as

1. Small molecule, rapidly acting transmitters- which cause acute response: (a)
Acetyl choline
(b) Different amines

(i) Norepinephrine (iii) Dopamine

(ii) Epinerphrine (iv) Serotonin

(c) Different amino acids like.

(i) Gamma-amino butyric acid (GABA) (ii) Glycine

(iii) Glutamate
(iv) Aspartate

2. Neuropeptides—slowly acting transmitters having prolonged affect

(a) neuroactive peptides- releasing hormones from

hypothalamus.
For example, TRH, LH releasing hormone, somotostatin.

(b) Pituitary peptides— e.g., ACTH, beta endorphins, vasopressin, oxytocin.

(c) Peptides acting on gut and brain, e.g., leucin, enkephalin, methionine,
substance P, cholecystokinin, VIP (Vasoactive intestinal polypeptide),
neurotensin, insulin, glucagon.
(d) Neuropeptides from other tissues, e.g., angiotensin II, bradykinin, carnosine,
bombesin. Neurons containing neurotransmitter are named accordingly, e.g.,
cholinerginc neurons, adrenergic neurons, dopaminergic neurons, etc. Duration
of action of the neuro transmitter, and removal of the transmitter from the
synapse. When either an excitatory or an inhibitory transmitter is released into
the synaptic cleft, it binds almost instantly with its specific chemically activated
ion channels and opens them either to the flow of sodium ions in the case of the
excitatory transmitter or the flow of potassium, chloride ions in the case of
inhibitory transmitter. However, after these channels have remained open for
only 1 to 2 milliseconds, in most instances they close quickly and rapidly
removed from the synaptic cleft. This is achived in three different ways: 1. By
diffusion of the transmitter out of the cleft into
the surrounding fluids.
2. By enzymatic destruction within the cleft itself. For
instance, in the case of acetylcholine, the enzyme
cholinesterase is present in the cleft, bound in the
proteoglycan matrix that fills the space. Similar
effects occur for other transmitters.
3. Many of the transmitters are actively transported
back into the presynaptic terminal itself and are then
reused again and again. This is called transmitter
re-uptake. It occurs especially prominently at the
presynaptic terminals of the sympathetic nervous
system for the re-uptake of norepinerphrine. The degree to which each of these
methods of removal are utilised is different for each type of transmitter.

SPINAL CORD
It is the caudal, tubular, elongated part of central nervous system.

The medulla oblongata continues as spinal cord at the level of first cervical
vertebra. The lower end of spinal cord lies at the level of lower border of L1
vertebra. Below this it continues as Cauda equina.

Spinal cord gives of 31 pairs of spinal nerves. Dimension: Length — about 50

cm. Breadth — about 1- 2 cms.
T.S. of Spinal Cord: It shows centre grey matter and surrounding white matter.
Grey matter: It is made up of neuronal cell bodies. It is in the form of H shaped
mass. The grey matter has two larger ventral masses called as ventral grey horns
and narrow dorsal masses called dorsal grey horns. In addition to this the lateral
masses called lateral grey horn may also be present. Grey commissure: It is the
connection between the right and left halves of grey matter. The grey
commissure is traversed by the central canal which contain CSF and is lined by
ependyma.
White matter: White matter surrounds the grey matter. Anterior median fissure
and posterior median septum divides it into two halves.

White matter is further divided into ventral, dorsal and lateral white columns or
funiculus with reference to their positions. Medial to dorsal grey horn—dorsal
funiculus. Medial to ventral grey horn—Ventral funiculus and lateral to both the
grey horns—Lateral funiculus.

Connection between the white matter of both the halves is called white
commissure. It lies anterior to grey commissure.

The spinal nerves arise from two roots, dorsal and ventral nerve roots.
Dorsal nerve root: Contains sensory fibre i.e., afferent fibres. The cell body of
these fibres lies in ganglion called dorsal root ganglion which produces a
swelling in dorsal root, and these are fibres of a pseudo unipolar neuron.
Ventral nerve root: It is made up of efferent fibres or motor fibres.

They arise from the nerve cells in anterior grey column. The two roots combine
to form mixed nerve which contain both sensory and motor components. This
further divides into dorsal and ventral rami of spinal nerve.

Major contents of grey matter

1. Doral horn: Contains I to VI Rexed lamina which contains fusiform cells and
cells of substantia gelatinosa of Rolando.

2. Lateral horn: Contains Rexed lamina VII it contains preganglionic

autonomic neurons.
Posterior median septum
Dorsal horn

Posterior
funiculus
Lateral horn
Central canel
White
commisure

Ventral horn Dorsal

nerve

root Dorsal nerve root ganglion Dorsal ramus of spinal nerve

Lateral corticospinal tract

Grey
commisure
Ventral
nerve root

Anterior median fissure

Ventral ramus of spinal nerve
Tract of goll

Rubrospinal tract
Lateral reticulospinal tract Vestibulospinal tract

Medial
reticulospinal tract
Anterior cortiospinal

Tectospinal tract
tract
Tract of burdach

Dorsal
spinocerebellar tract

Lateral
spinothalamic tract
Ventral
spinocerebellar tract

Anteror
spinothalamic
tract

Transverse section of spinal cord Organisation of tracts in the spinal cord Fig. 8.21
Organisation of spinal cord
3. Ventral horn: Contains Rexed lamina VIII and IX and contains cell bodies of
motor neurons, α, γ and Renshaw neurons.

Rexed Lamina
It is the division of spinal grey matter into ten layers based on their histological
character and types of cells.
Lamina
I

II
II
III
IV
V
VI

VI
VII
VIII
Fig. 8.22 Lexed lamina of spinal cord Contents of white matter
1. Dorsal white column contains mainly—Sensory tracts (ascending):
(a) Tract of Goll
(b) Tract of Burdach

2. Lateral white column contains mainly— Sensory tracts (ascending tracts):

(a) Dorsal and ventral spino cerebellar tracts (b) Lateral spinothalmic tract
(c) Spino Olivary tract d. Spino-reticular tract (e) Spino-pontine tract f. Spino-
Vestibular tract (g) Spino-tectal tract

Motor tracts (Descending tracts) (a) Lateral cortico spinal tract

(b) Rubro spinal tract
(c) Lateral reticulospinal tract
(d) Olivo spinal tract
(e) Lateral vestibulo spinal tract.

3. Ventral white column contains mainly—Sensory tracts—Ventral

spinothalamic tract.

Motor tracts:
(a) Anterior corticospinal tract.
(b) Medial vestibulo spinal tract.
(c) Medial reticulo spinal tract.
(d) Tecto spinal tract.
Body of the neurons provides the grey matter, a grey

(ash colour) appearance.

Bell-Megendie Law: Afferent fibres or sensory fibres enter the spinal cord
through the posterior or dorsal root and the efferent fibres or motor fibres come
out through the anterior root of spinal nerve.

Functions of spinal cord

1. It acts as an important part of central nervous system.

2. Sensory pathways are organised in the spinal cord.
3. Motor impulses from the brain comes down through the motor pathways
situated in the spinal cord and reaches the muscles.

4. It acts as centre for a number of reflexes—like withdrawal reflex, postural

reflexes.
5. 31 pairs of spinal nerves arise from the spinal cord which forms the bulk of
peripheral nervous system. 6. Visceral functions: It includes breathing, urination,
defecation and sexual functions in male. 7. Vasomotor function T11– L2
segments of spinal cord controls vasomotion, sweating and piloerection.

REFLEX ACTION

Reflex action is defined as a sudden stereo typed, involuntary motor or secretory

response to a sensory stimulus. For example, suppose the finger tip touches a hot
object there will be a sudden withdrawal of hand.

Functions of reflex action

1. It reduces the duration of exposure of the body to an unpleasant stimulus and

thereby minimises the extent of damage to the body.

2. It helps to keep the organ or system prepared for a future action.

Association neuron (centre)
Afferent pathway Receptor
Integrating centre Efferent pathway Effector organ
Fig. 8.23
Reflex Arc
Reflex Arc is the anatomical structure taking part in a reflex action. Reflex arc
consists of five important structural elements:
1. Sensory receptor
4. Efferent pathway 2. Afferent pathway 3. Centre 5. Effector organ (group of
muscles or glands).
Interneuron Axon of
sensory neuron Direction of impulse

Cell body of
sensory neuron
Dendrite of
sensory neuron

Spinal cord Cell body of motor neuron Axon of

motor neuron

Pain receptors in skin

Effector
muscle contracts and withdraws part being
stimulated

Pin

Fig. 8.24
A withdrawal reflex involves a sensory neuron, an interneuron, and a motor
neuron, bisynaptic reflex
Spinal cord Axon of
sensory neuron

Cell body of sensory neuron

Dendrite of motor neuron Axon of

motor neuron

Cell body of motor neuron Direction of impulse Dendrite of

sensory neuron

Effector
quadriceps femoris
muscle group Receptor ends of sensory neuron

Patella
Femur
Tibia
Fig. 8.25 The knee-jerk reflex involves two neurons—a sensory neuron and a
motor neuron, monosynaptic reflex Classification of reflexes
Reflexes are classified in different ways: TABLE 8.5
Classification of reflexes
(a) Clinical (b) Antomical (c) Number of synapse (d) Physiological (e)
Psychological 1. Superficial 1. Segmental 1. Mono-synaptic 1. Flexor 1.
Unconditioned 2. Deep 2. Inter segmental 2. Bisynaptic 2. Extensor 2.
Conditioned 3. Visceral 3. Supra segmental 3. Multi-synaptic 4. Pathological
1. Clinical classification:

(a) Superficial reflexes: These are the reflexes which are initiated by stimulating
appropriate receptors of skin or mucous membrane. They are usually
multisynaptic, usually involving moving e.g., plantar response, abdominal and
cremasteric reflexes, cornial and conjuctival reflexes.

(b) Deep reflexes: These are elicited on stroking the tendon. They are basically
stretch reflexes and are also called tendon reflexes, e.g., knee jerk, ankle jerk,
etc.

(c) Visceral reflexes: These are the reflexes where at least one part of the reflex
arc is formed by automatic nerves, e.g., pupillary reflex, carotid sinus reflex.

(d) Pathological reflexes: These are the reflexes which are not found normally
and their presence indicates pathological condition within the body, e.g.,
Babinski’s sign.

2. Anatomical classification of reflexes

(a) Segmental reflexes: In these, end of afferent neuron and the beginning of
efferent neuron are in the same segment of the spinal cord.

(b) Intersegmental reflexes: In these reflexes, end of afferent neuron and the
beginning of efferent neuron are in the spinal cord but in different segments.

(c) Suprasegmental reflexes: The center for such reflex lies above the spinal
cord.

3. Physiological classification of reflexes

(a) Flexor reflexes: They are produced when nociceptive (pain) stimulus is
applied. Such stimuli cause flexion of the joint, e.g., thorn prick to the sole,
cause flexion of knee, hip joints. These reflexes are protective in nature.

(b) Extensor reflexes: Stretch reflexes are extensor reflexes which are the basis
of tone and posture. 4. Depending upon inborn or acquired, reflexes are
classified into two types

(a) Unconditioned reflexes: They are inborn reflexes, i.e., they are present since
birth.
(b) Conditioned reflexes: These are the reflexes which develop after birth. Their
appearance depends on previous experience.

5. Depending upon number of synapses involved reflexes are classified into

three types

1. Monosynaptic reflexes
2. Bisynaptic reflexes
3. Multisynaptic reflexes
- e.g., knee jerk
- e.g., withdrawal reflex
- e.g., Postural reflexes

Properties of reflex action

1. Reflex delay: It is the time gap between the application of stimulus and onset
of reflex response. Reflex delay depends upon the number of synapses involved.

2. Summation: There are two types of summation: (i) Spatial summation (ii)
Temporal summation. The effects of multiple stimuli applied on different parts
of the body get added up and give a stronger reflex response. It is known as
spatial summation. Temporal summation: Effects of multiple stimuli applied one
after the other can get added up and give a stronger reflex response.

3. Fatigue: When a reflex action is elicited repeatedly, after some time it stops
responding. This phenomenon is called fatigue. It is a temporary phenomenon.

TABLE 8.6
Comparison between unconditioned and conditioned reflex
S.No. Unconditioned Reflex Conditioned Reflex 1. It is a sudden response to a
proper stimulus. It is a sudden response to some thing related to stimulus. 2.
Inherited, Iborn Acquired. 3. Commonly seen at the time of birth. Not seen at the
time of birth but appears later in the life. 4. Permanent and stable Not permanent
or temporary, unstable. 5. Cannot be erased. Can be erased. 6. It is uniform in all
the members of a species. It differs from individual to individual depending upon
personal past experience.
7. Limited in number Unlimited in number 8. Lower level of CNS like spinal
cord and brainstem. are involved.
Higher centres of CNS like cerebral cortex is involved.

4. Occlusion: Suppose a reflex action can be elicited by stimulating two

different afferent pathways A and B. When these afferent pathways are
stimulated separately the magnitude of reflex responses obtained are ‘t1 and t2’.
When both the afferent pathways are stimulated together magnitude of response
obtained is ‘T’

T < t1 + t2

This phenomenon is known as occlusion. It is because some of the structural

components are overlapping and common for both pathways.
T< t + t12
AB
Fig. 8.26
Occlusion

5. Subliminal fringe: Suppose a reflex action can be elicited by stimulating two

different pathways A and B by minimum strength of stimulus. The magnitudes
of reflex responses obtained when they are stimulated separately are t1 and t2.
The magnitude of reflex response obtained when both the pathways are
stimulated together is T.

T > t1 + t2
A

B
Fig. 8.27 Subliminal Fringe
This phenomenon is known as subliminal fringe. It is because when two stimuli
are applied together, their combined strength becomes strong and spreads to
some nearby structures, involves more muscles, produces a stronger response.

6. Adequate stimulus: The reflex activity is stereotyped (fixed) and specific in

terms of both the stimulus and the response. Therefore, a particular stimulus
produces a particular response. As the receptors respond maximally only when
an appropriate specific stimulus is applied, likewise, the stimulus that produces a
reflex is very precise and is called the adequate stimulus for the particular reflex.

7. Final common pathway: The α-motor neurons that supply the extrafusal
muscle fibres in the skeletal muscle are the final common pathway over which
the neural control system coordinates the activity of skeletal muscle fibres. All
neural influences (excitatory and inhibitory) affecting muscular contraction
ultimately funnel through them to the muscles.

8. Central excitatory and inhibitory states: The spinal cord shows prolonged
changes in excitability because of activity in reverberating circuits or prolonged
effects of synaptic mediators. The prolonged states in which excitatory
influences last is called central excitatory state; conversely, if inhibitory state
dominates, it is called central inhibitory state. For example: After complete
transection of the spinal cord, when reflex movements return, a mild noxious
stimulus on the lower limbs may cause withdrawal reflex and autonomic
changes like urination, defecation sweating and fluctuations in B.P. This is
referred to as Mass Reflex. It occurs when central excitatory state is marked.

9. Habituation and sensitisation of reflex responses: Though the reflex

responses are stereotyped, still they can be modified by experience. Therefore,
(a) if the stimulus begins and repeated at frequent

intervals, the response declines and disappears, a phenomenon called

‘habituation’. This usually happens to nonnoxious stimulus.

(b) opposite response i.e., prolonged facilitation of synaptic conduction in a

reflex can be produced by noxious stimulus, this phenomenon is called
sensitisation. This can last from hours to days.

Withdrawal reflex
Definition

It is a polysynaptic reflex that occurs in response to a noxious or painful

stimulus. Therefore when a noxious stimulus is applied to a limb it leads to

(i) contraction of flexor group of muscles and inhibition of extensor muscles,

therefore limb stimulated is flexed and withdrawn from the stimulus. This is
called flexor response or flexor reflex; and

(ii) with a stronger stimulus, in addition to flexor reflex there occurs extension of
the opposite limb also. This is called crossed extensor reflex/ response.

Significance

The withdrawal reflex is protective, therefore, while the stimulated limb is

withdrawn to get away from the source of the stimulus, the extension of the
other limb supports the body.

Withdrawal reflexes are prepotent more stronger than other, therefore they block
the spinal pathway from any other reflex activity taking place at that moment.

TABLE 8.7
Superficial reflexes of clinical importance
S.No. Reflexes 1. Anal
2. Plantar
Method of eliciting

Scratching perineal region. i.e., neighbouring skin of the anal sphincter.

Scratching the skin of the outer margin of the sole of the foot from the heel
towards the little toe.

3. Palmar
4. Gluteal
5. Cremastaric

6. Abdominal (a) lower

(b) Upper

(epigastric)
7. Scapular
8. Conjunctiva or cornea
9. Pupillary (Light) 10. Pupillary (Ciliospinal)

11. Bulbocavernous Scratching of the skin of palm Scratching the skin of

buttock
Stroking or scratching the inner side of the thigh.

Scratching of abdomen—above the inguinal ligament

Scratching in the line of nipple over the 6th and 5th interscostal spaces

Scratching of inter-scapular region

Touching conjunctiva or cornea
Fall of light on eye
Scratching the skin of neck
Result
Contraction of external anal sphincter.
Segmental level Sacral 4 and 5

Normal – Plantar flexion

Infant – Dorsi Flexion of great toes and fanning out of the other toes and
withdrawal of foot. Pyramidal lesions – Same as in infants.

Flexion of fingers (Infants)

Contraction of gluteal muscles Drawing up of the testicles. Lumbar 5 to sacral 2

Cervical 8 and thoracic 1. Lumbar 4 and 5

T12 to L2

Contraction of the lower abdominal muscles of the same side. Contraction of

epigastrium T10 – T12

T6 – T7
Contraction of scapular muscle C5–T1
Winking by contraction of orbicularis occuli
Contstriction of pupil Dilatation of the pupil 5th and 7th cranial nerves
3rd Cranial nerve. Cilio-spinal centre
Stimulation of glans penis Contraction of the
bulbocavernous muscle S3 – S4

Plantar reflex
The plantar reflex is of two types:

(a) The normal Reflex or Thrust Reflex – It is flexion of the toes and is best seen
by a gentle scratch of sole of the foot.
(b) Withdrawal Reflex – Involves dorsi – flexion (extension) of the toes.
A. Normal plantar reflex
B. Plantar reflex – Dorsi flexion (extension) or plantar flexion of great toe and
fanning out of other toes i.e., Babinski’s sign in infant and pyramidal lesion.
Babinski’s sign present in:
1. Morphine poisoning
2. Uraemia
3. Eclampsia
4. Epilepsy
5. Lateral sclerosis
6. Subacute combined degeneration of the spinal cord 7. Tabes dorsalis
8. Disseminated (Multiple) sclerosis.
Regardless of the nature or location of the central lesion the Babinski’s sign will
not be elicited if the:
(a) Great toe is ankylosed,
(b) Extensor tendon is severed,
(c) Extensor longus hallucis muscle is destroyed, (d) Muscular nerve to this
muscles interrupted, (e) Related anterior spinal root is seriously damaged, (f)
Anterior horn cells are seriously damaged. It is the sign only due to interruption
of the corticospinal fibres which innervate the muscles of the great toe but not a
sign of damage to any other cortico – spinal fibres.

Deep reflexes or Tendon reflexes

It is the sudden contraction of muscles brought about by a tap on the tendons
after putting them in a slightly stretched condition.

Nature of deep reflex

Tendon reflexes are deep proprioceptive or kinaesthetic reflexes and can be
considered as fractionated stretch reflexes. A sharp tap on the slightly stretched
tendon elicits an equally sharp contraction of the corresponding muscles;
variation occurs in many diseases.

TABLE 8.8
The deep or tendon reflexes

Importance:
1. To detect whether the lesion is in upper or lower motor neuron as these
reflexes are exaggerated in lesions of the upper motor neurons e.g., lateral
sclerosis, and are lost in lesions of the lower motor neurons e.g., infantile
paralysis.

2. To ascertain approximately the level of the spinal cord involved.

S.No. Reflex How to elicit? Response cord involved Level of spinal

1. Knee (or patellar) jerk or quadriceps femoris jerk

2. Ankle jerk
or gastrocnemius and soleus jerk

3. Triceps jerk
4. Biceps jerk
5. Supinator jerk or brachioradialis jerk

6. Jaw jerk (i) The subject either supine or sitting (ii) The examiner’s hand is
passed

under the knee to be tested and placed on the opposite knee. (iii) The test knee
rests on the dorsum

of the examiner’s wrist.

(iv) Strike the patellar tendon midway
between its origin and insertion,
alternatively it can also be more
easily elicited with the subject
sitting up, the leg hanging freely
over the other knee or the edge of
the bed.

(i) Place the lower limb in everted and slightly flexed position, then with one
hand, slightly dorsiflex the foot so as to stretch it.

(ii) With other hand, strike the tendon on its posterior surface.

(i) Flex the elbow and allow the forearm to rest across the subject’s chest.

(ii) Tap the triceps tendon with a patellar hammer (broad end).

(i) Elbow is flexed to right angle and forearm is placed in a semiprone position.
(ii) Examiner then places his thumb or index finger on the biceps tendon and
strike it with the patellar hammer (pointed out).

(i) Tap the brachiorodialis.

(ii) Tap the supinator tendon upon the styloid process of radius.

(i) Ask the subject to open his mouth but not too widely.
(ii) Place a finger and then tap it suddenly with other hand (as in percussion)
A brief contraction of the quadriceps femoris muscle results in extension of the
knee.
(If unable to elicit, apply reinforcement; Jendrassik’s manoeuvre.
L2, 3, 4
(femoral nerve)

A sharp contraction of calf muscle (gastrocnemius) is seen

S1, 2
(Tibial nerve)
Contraction of triceps muscle
C6, 7
(Radial nerve)
Contraction of biceps muscle
C5, 6
(Musculocutaneous nerve)

Contraction of supinator muscle with supination of elbow

C5, 6
(Radial nerve)

Contraction of messeter muscle resulting in closure of the jaw (this jerk is

sometimes absent in healthy people)
Fifth cranial nerve nuclei.

TABLE 8.9
Reflexes based on cranial nerves
1. Conjunctival reflex Touch the conjunctiva with a cotton wool swab
2. Corneal reflex Touch the cornea with cotton
Contraction of orbicularis oris resulting in rapid closure of eyelid.

Closing of eyes
3. (i) Pupillary reflexes

(ii) Accommodation reflex

Focus light on eyes
(i) light reflex direct and

indirect
Bring an object close to the eyes.
Constriction of pupil Convergence of eye balls Bulging of lens

NERVE TRACTS

Nerve tract is a bundle of nerve fibres carrying sensory or motor impulses from
one part of the C.N.S. to another part. The tracts are broadly classified into 3
types:

1. Ascending or sensory tracts

2. Descending or motor tracts
3. Inter segmental tracts

Ascending Tracts
These are organized in 3 different columns of spinal cord. 1. Posterior column 2.
Lateral column 3. Anterior column

Posterior column
Afferent: fifth nerve Efferent: seventh nerve
Afferent: fifth nerve Efferent: seventh nerve Afferent: second nerve Efferent:
third nerve

In the posterior column there are three important sensory tracts. They are
1. Tracts of Goll – Fasciculus Gracilis
2. Tract of Burdach – Fasciculus Cuneatus
3. Comma tract of Shultze.

Tract of Goll or Fasciculus Gracilis

Somatosensory cortex

3rd order neuron

thalamocortical radiations Thalamus
2nd order neuron

Nucleus gracilis Medulla oblangata Nucleus cuneatus Ist order neuron

Spinal cord
Touch receptor
Dorsal root ganglion cell

Touch recorder
pathway for finetouch and vibration

Fig. 8.28
Tract of goll

It carries sensation from lower half of the body. Origin:

The dorsal root ganglion cells acts as 1st order neuron. The sensory impulses
enter the spinal cord through the dorsal root of spinal nerve. These fibres climb
up in the posterior column of spinal cord. These fibres reach medulla oblongata.
At the medulla oblongata the 1st order neuron synapses with second order
neuron. This takes place at nucleus Gracilis. Because of this the tract is also
called as fasciculus gracilis. The fibres of 2nd order neuron divides into 2
groups.

1. External arcuate fibres and

2. Internal arcuate fibres
The external acruate fibres are further divided into 2

groups. The dorsal group of external arcuate fibres cross over and reach the
cerebellum of opposite side. The ventral group of external arcuate fibres reach
the cerebellum of same side. The internal arcuate fibres cross over to the
opposite side of the body and reach thalamus. From the thalamus 3rd order
neurons arise and these fibres are known as thalamo-cortical radiation. The 3rd
order neurons terminate at the sensory cortex. Sensory homunculus: It is the
representation of each and every part of the body in the sensory cortex. The area
of representation of a part of the body is not proportional to its size or mass, but
it is proportional to density of receptors present. In the sensory or cerebral
cortex, the sensory fibres coming from different parts of the body are projected
at a specific region. There is an upward down projection i.e., lower part of the
body is projected at higher part of the cerebral cortex and fibres from upper part
of the body is projected at lower part of the cerebral cortex.
Functions:
The tract of Goll carries the following sensations: 1. Fine touch
2. Touch discrimination, touch localisation. 3. Vibration
4. Stereognosy
5. Proprioceptive sensation
6. Texture discrimination
Unit
Central Postcentrai sulcus gyrus
T
6 7 4 Anterior
Central sulcus 3 2 5
S 312
T

r57
Posterio
Middle
Index
ThumbEyeNose
Upper lipFace Lower lip T eeth,gumandJaw ToungeRight cerebral
hemisphere
TT
40
S.11

Fig. 8.29
Sensory homunculus Brain areas concerned with somatic sensation pathway
termination of different parts of the body in the sagittal section (i.e. in
anteroposterior direction) of fronto-occipital region somatosensory cortex
Tract of Burdach or Fasciulus Cuneatus
Somatosensory cortex
3rd order neuron
thalamocortical radiations
Thalamus
2nd order neuron
Nucleus gracilis
Nucleus cuneatus Medulla Fasciculus cuneatus 1st order neuron
Spinal cord
Touch receptor
Dorsal root ganglion cell
Spinal cord

Touch receptor
pathway for finetouch vibration

Fig. 8.30 Tract of burdach It carries the sensation from upper parts of the body.
Origin: 1st order neuron. The dorsal root of ganglion

cells acts as 1st order neuron. The sensory impulses enter the spinal cord through
the dorsal root of spinal nerve. These fibres reach the medulla oblongata. The 1st
order neurons synapse with second order neurons. This takes place at nucleus
cuneatus. Because of this, this tract is known as fasciculus cuneatus. The fibres
of 2nd order neuron divide into 2 groups.

1. External arcuate fibres 2. Internal arcuate fibres

The fibres of external acruate fibres are further divided into 2 groups—A dorsal
group of external arcuate fibres cross

over and reach the cerebellum of opposite side. The ventral group of external
arcuate fibres reach the cerebellum of same side. The internal arcuate fibres
cross over to the opposite side of the body and reach the thalamus. From the
thalamus 3rd order neurons arise. The sensory fibres coming from different,
regions show an upward down projection i.e., lower part of the body is projected
at higher part of the cerebral cortex and upper part of the body is projected at
lower part of cerebral cortex.

Functions:
1. Fine touch
2. Sense of vibration
3. Sensation of two point discrimination
4. Stereognosy
5. Propriceptive sensation
6. Texture discrimination
Comma tract of Shultze

This is situated in between tract of Goll and tract of Burdach in the posterior
column of spinal cord. The fibres of the tract originate from the dorsal root
ganglion cells. The fibres of dorsal root ganglion cells after entering the spinal
cord may go up or down to an extent of a few segments. These fibres appear like
comma.

Functions:

1. The fibres of this tract establishes inter segmental communications.

2. These fibres may take part in multisynaptic reflex actions.
Lateral column of the spinal cord

There are many important sensory tracts organised in the lateral column of the
spinal cord. They are:
1. Lateral spinothalamic tract- pathway for pain and temperature
2. Dorsal spinocerebellar tract
3. Anterior spinocerebellar tract
4. Spino-olivary tract
5. Spino-tectal tract
6. Spino-reticular tract
7. Spino-pontine tract
8. Spino-vestibular tract
9. Spino-cortical tract.

Lateral Spinothalamic tract (S.T.T)

Dorsal column Gracile Cuneate(touch, pressure,
fasciculus fasciculusvibration,
joint position
SLTC

Lateral spinothalamic tract (pain, temperature) S L

TC

SL T C
Ventral spinothalamic tract (touch pressure)

Fig. 8.31 Cross section of spinal cord, showing location of ascending sensory
pathways.
Note that each is laminated.
S, sacral; L, lumbar; T, thoraclc; C, cervical.

Origin: The dorsal root ganglion cells acts as first order neurons. The fibre of
dorsal root ganglion cells enter the spinal cord through the dorsal root of spinal
nerve. In the spinal cord segment itself these fibres synapses with of 2nd order
neurons. The fibres of 2nd order neurons cross over to the opposite side of the
spinal cord. These fibres climb up and pass through medulla oblongata, pons and
midbrain to
Somatosensory cortex

3rd order
neuron
thalamocortical adition
Thalamus
Dorsal root ganglion cell
Medulla oblangata

Ist order neuron 2nd order

neuron

Lateral column
Receptors Ist order neuron

Pain/Temperature receptors pathway for pain and

temperature 2nd order neuron

Lateral column spinal cord

Fig. 8.32
Lateral spinothalamic tract

reach thalamus of opposite side. From the thalamus the 3rd order neurons arise
and the fibres of 3rd order neuron terminates at cerebral cortex. These fibres are
arranged as thalamocortical radiations. In the cerebral cortex there is an upward
down projection of sensory fibres.

Functions: 1. The Fibres of this tract carries the sensation of pain and
temperature.

Spino cerebellar tracts

The informations carried by these tracts will not reach the level of
consicousness. There are two important spino cerebellar tracts.

1. Anterior or ventral spino cerebellar tract or Gower’s tract.

2. Dorsal or posterior spino cerebellar tract or Flechsig’s tract.
Gower’s tract or ventral spino cerebellar tract

Origin: First order neurons are dorsal root ganglion cells. They arise from the
muscle spindle, joints and skin. These enter the spinal cord through dorsal root
of spinal nerve. First order neurons synapse with second order neurons at clarkes
columns of spinal cord. Most of the second order neuron fibres cross over to the
opposite side of the spinal cord climbs up via ventral spino cerebellar tract
passes through medulla enters the midbrain goes upto the level of red nucleus. In
the midbrain the fibres turn sharply, pass through superior cerebellar penduncle
and reach vermis of cerebellum. From here third order neurons arise and
terminate at cerebral cortex. Fibres of this tract already crossed at spinal cord
level, but some fibres recross and reach cerebellum of same side.

Functions:
1. It carries unconscious kinaesthetic sensation.
2. Helps in the maintenance of posture and equilibrium.
Dorsal spinocerebellar tract or Flechsig’s tract Origin and Course: First order
neurons of this tract arises from dorsal root ganglion cell. It brings sensations

from muscle spindle, joints and skin. It enters the spinal cord through dorsal root
of spinal cord. Climbs up a few segments through the dorsal column of same
side. Then synapse with second order neurons at Clarke’s column or nucleus
dorsalis. The second order neurons proceeds up through the lumbar, thoracic and
cervical regions of spinal cord of same side. On reaching medulla turns
posteriorly to enter cerebellum through inferior cerebral peduncle. These fibres
terminated at vermis. From here third order neurons arise and passes to the
cerebral cortex.

Functions:
1. Carries unconscious kinaesthetic sensations to the cerebellum.

2. It helps in the coordinated movements brought about by cerebellum for

maintaining posture and equilibrium.

Anterior Spinothalamic tract

Somatosensory cortex

3rd order
neuron
thalamocortical radiation

Dorsal root ganglion cell

Thalamus
Medulla oblangata
Ist order neuron 2nd order neuron Anterior collumn
Ist order neuron Anterior collumn

Pathway for crude touch and pressure

Cerebral cortex
Third order neuron Spinal cord

Fig. 8.34
Anterior spinothalamic tract
Red nucleus

Cerebellum Superior cerebellar peduncle

Inferior cerebellar peduncle Midline

Gower's tract
Flechsign's tract
Dorsal root ganglion cells

Clarke's columns
Dorsal root of spinal nerve

Fig. 8.33
Spinocerebellar tracts

Anterior column of the spinal cord: There is one important tract in this column
of the spinal cord i.e., anterior spinothalamic or ventral spinothalamic tract.

Origin : The dorsal root of ganglion cells act as first order neurons. The fibres of
dorsal root of spinal nerve, enters the spinal cord through the dorsal root of
spinal nerve. At the spinal cord segment itself these fibres synapse with second
order neurons. The fibres of 2nd order neuron crosses over to the opposite side
of the spinal cord. These fibres are organized in the anterior column of the spinal
cord. These fibres climb up , pass through medulla, pons and then the thalamus.
From the thalamus the 3rd order neurons arise as thalamo cortical radiations.
The fibres of 3rd order neuron are terminated at sensory cortex. In the sensory
cortex different parts of the body are represented in an upward down fashion.

Functions: It carries the sensation of crude touch, pressure, bladder sense and
itch.

TABLE 8.10
Comparison between dorsal spinothalamic pathway with anterolateral
pathways
S.No. Spinothalamic pathways/anterolateral pathways Dorsal column
pathways

1. The peripheral sensory neurons of the lateral spinothalamic pathway travel

within the spinal nerves joining the cord through their dorsal horn of the spinal
cord.
The dorsal column sensory neurons pass through spinal nerves from peripheral
receptors and enter the cord through their dorsal roots.

2. Theses fibres mainly carries the sensation of crude touch, pressure, pain and
temperature.
Theses fibres mainly carry the sensation of fine touch, vibration tactile
localisation, and tactile discrimination.

3. The spinothalamic pathway is somewhat less myelinated. The dorsal column

pathway are thickly myelinated.
4. Thinner fibres. Thicker fibres. 5. The spinothalamic pathway has more
synapses; there are greater opportunities for divergence.

6. The second order neurons cross the midline in the same spinal segment and
ascend up in the opposite side of the anterolateral funiculus to reach the
thalamus.

7. The sensation of one side of the body travels in the opposite side of the spinal
cord and reach opposite side of the thalamus and cerebral cortex.

8. Spinothalamic pathway transmits neural information slowly that’s why

spinothalamic sensations are those that The dorsal column pathways has less
synapses, there is very less opportunities for divergence.

The second order neurons are present in the nucleus gracilis and cuneatus in the
medulla then it transmits impulses to the contralateral thalamus.

The sensation of one side of the body travels in the same side of the spinal cord
upto medulla, only after medulla crosses over and reach opposite side of the
thalamus and cerebral cortex.

Dorsal column pathway transmits neural information quickly and precisely.

are less of an emergency in nature.

PHYSIOLOGY OF PAIN
Introduction

Pain is an unpleasant sensation caused due to tissue damage. Pain may be felt
everywhere in the body except brain. Pain has got two major components which
is experienced as hurting:
1. Sensory component. Reaction or response to pain.
2. Emotional component. Somatic and autonomic reflexes and voluntary effort to
remove pain.

Definition of Pain

According to Sherington pain is defined as “Physical adjunct of an imperative

protective reflex”. Pain can be defined as the feeling of distress or suffering or
aching caused by stimulation of receptors of pain. It is an unpleasant sensation
caused due to tissue damage or potential tissue damage.

Functions of Pain/Purpose of Pain

Pain is a protective mechanism. It gives a warning signal to the body; it informs

the nervous system that something is wrong at some parts of the body. It makes
us aware of actual or impending damage to the body. Pain helps to avoid the
noxious stimulus e.g., fire either by: (1) somatic reflex (2) autonomic reflex (3)
or by voluntary efforts to remove the pain stimulus. Pain, although unpleasant, is
a protective sensation with enormous survival value.

Pain Receptors
Fig. 8.35
Pain receptors free nerve endings

Free nerve endings present maximally in the skin, also present in the
periostenum, arterial walls, joint surfaces, falxcerebri, tentorium, visceral organs.
Pain receptors are absent in the brain.
Types of stimuli for pain: Tissue damaging agents Mechanical - Mechnosensitive
pain receptors Thermal - Thermosensitive pain receptors
Chemical - Chemosensitive pain receptors Electrical

Initiation of Pain

It is believed that noxious stimuli lead to the release of some chemicals from the
damaged tissues. These chemicals initiate the pain through stimulation of pain
receptors. The chemicals are

(a) Pain producing substance (PPS)—It is a polypeptide and is produced from a

plasma protein by the action of proteolytic enzymes released from damaged
tissues.
(b) Other chemicals—bradykinin, prostaglandins, AMP, hydrogen ions, K+
Histamine.

Types of Pain – Classification of Pain

(a) Depending upon speed of transmission of pain impulses.
TABLE 8.11
Classification of pain

Pathway for pain—Transmission of pain impulses There are two pathways—

fast and slow. Fast pain sensation from the receptor is conducted to the spinal
cord by A-delta type of nerve fibres.

They have a transmission velocity of 6–30 m/sec. The cell bodies of these
neurons are in DRG cells. The slow pain is carried by naked or non-myelinated
‘C’ fibres. They enter the spinal cord through dorsal root of spinal nerve. Before
terminating at the dorsal horn of spinal cord, these fibres ascend or descend one
or two segments in the spinal cord. This forms Lissauer’s tract. The fast fibre
axons terminate mainly in Rex lamina I but also in lamina II and V. Substantia
gelatinosa Rolando. Here neurotransmitter is glutamate. The type C fibre
terminate at posterior horn and laminae II and III. Neurotransmitter is substance
P. The second order neurons arise from Substantia Gelatinosa Rolando and also
from laminae IV and V. The second order neurons cross to the opposite side of
spinal cord in the anterior white commissure just in front of central canal. Then
they ascend through the segments of spinal cord. These fibres make lateral spino
thalamic tract.
C

1. Fast pain
Conducted by A fibres
Velocity–6-30 M/sec. Well localised
Character – sharp pricking

Slow pain
Conducted by “c” delta fibres
Velocity–0.5 – 2M/sec. Poorly localised
Burning or dull and aching.
Cerebral
5th Cranial nerve Trigeminal
Collaterals
3rd order neuron

Thalamus
Spinal tract of trigeminal

2. Epicritic
Low threshold but accurate localisation

Protopathic pain high threshold poor localisation

Dorsalroot ganglion cell Lateral
spinothalamic tract

3. Deep pain
Pain arising from deeper structures like Periostenum, muscle tendon etc.
– Poorly localised.

4. Somatic pain
Pain arises from somatic structures and may be
superficial or deep. Well—localised

Superficial pain
pain arising from superficial structures

like skin.
2nd order

neuron
Well localised.

Visceral pain
arise from viscera due to inflammation,
spasm, stretching.
– Poorly localised
– Diffuse in character
– May radiate or may

be referred.
1st order SGR
Tract cell
Central canal
Fig. 8.36 Pathway for pain, (Lateral spinothalamic tract)

Note: When the central canal is widended as is the disease syringomyelia the
fibres carrying pain and temperature are affected first as this crossing leading to
the loss of pain and temperature sensation below the level but other sensation
persist. This is called dissociated sensory loss.

As more and more fibres join the tract from the successive spinal segments, the
fibres from the lower segments are pushed towards the surface of the spinal cord.

Therefore, a damage of spino thalamic tract from inside (by intra spinal tumour)
destroys initially the pain fibres from the upper levels of the body. But a damage
from outside (e.g., by extra spinal tumours) will first destroy the fibres coming
from the lower levels of the body.

Pain pathway by A-delta fibre is called Neospino thalamic tract—pain pathway

by C fibres is known as Paleo spinothalamic tract—more primitive.

Collaterals:
On their way to thalamus pain pathway gives collaterals to

(a) Reticular Activating system—to alert the brain. (b) Tectum.

(c) Peri Aqueductal Gray (PAG)—to activate central

pain inhibiting mechanism.

(d) Hypothalamus.
(e) Limbic system—Amygdala and hypothalamus

which are responsible for the emotional responses caused by pain sensation.

Lateral spino thalamic tract continues as the spinal lemniscus in the brain stem
and ends in the ventral postereo lateral nucleus (VPLN) of the thalamus.

Neospinothalamic tract relay in the ventrobasal complex of thalamus.

Arrangement of neurons in the ventrobasal complex is topographic. So very
much localisation of pain sensation.

Paleo spinothalamic tract fibres relay in the non specific nucleic (i.e., midline
and intralaminal nuclei). Therefore, slow pain is poorly localised.
The third order neuron starts at the thalamus and via internal capsule reaches the
primary sensory cortex Area— 3, 1, 2, in S II and in cingulate gyrus of the
opposite side.

Trigeminal pain pathway

Pain sensation is also carried by spinoreticular and spinomesencephalic tract.

Pain sensation from the face, nasal and oral cavity, cranial dura mater etc is
carried by the trigeminal nerve. The neurons of trigeminal nerve are pseudo
bipolar neurons. The cell bodies are present in the semilunar ganglion or
trigeminal ganglion. The axons divide in to two groups of fibres—ascending and
descending branches and reach brain stem nuclei- spinal nuclei and main
Main
sensory nucleus

Semilunar ganglion

SI Somatosensory cortex I II

V1
V2
V3
Oral
Spinal Interpolar
nucleus

Caudal Fig. 8.37 Trigeminal pathways

sensory nuclei. The spinal nuclei have three subdivisions bringing pain sensation
from face, oral cavity and head. From the spinal nuclei the second order neurons
arise and reach the thalamus of opposite side. This forms the spinothalamic
pathway of trigeminal system. Main sensory nucleus carries mechano sensory
inputs.

Perception of Pain: Pain is perceived at two levels.

1. Sub cortical level—at thalamus-crude.
2. Cortical perception—sensory cortex.

Referred Pain

Referred pain is a type of pain felt at the part of the body away from the cause of
the pain. Usually visceral pains are referred to the somatic regions.

TABLE 8.12
Examples for referred pain
S.No. Visceral organ site of origin of pain

1. Cardiac pain
2. Appendix
3. Gall bladder
4. Ovary
5. Testis
6. Duodenum

7. Kidney
8. Diaphragm
9. Ureter

Somatic region site where pain is felt

Left arm, shoulder Umbilicus

Right shoulder
Umbilicus
Abdomen

Anterior abdominal wall above umbilicus

Loin
Right shoulder
Testicles

Explanation:

The visceral organ and the somatic region to where pain is referred might have
originated from a common embryological structure, dermatome. Because of this
the visceral organ and the somatic region may have a common nerve supply or
innervation.

The phenomenon of referred pain is explained by two theories.

1. Convergence theory: The pain fibres coming from the visceral organ and the
somatic region converge with a common 2nd order neuron. Because of this, the
pain sensation is carried to a common part of the brain. There is an error in the
localisation of the pain. The visceral pain is felt as somatic pain because brain is
more familiar with somatic regions.
Lateral spinothalamic tract Somatic region
Significance: Knowledge of referred pain is important in the early diagnosis and
treatment of visceral problems.
Projected pain
Lateral spinothalamic Painfultract stimulus
Ulnar nerve

Fig. 8.40
Projected pain

Projected pain : When a sensory nerve is get stimulated on its way to brain, the
pain is usually felt at the site from which nerve originates. For example, if ulnar
nerve is stimulated at elbow, pain is felt at hand.
Phantom pain Left shoulder

Stimulus Pain perceived in non-existent leg

Lateral column Visceral organ

Fig. 8.38
Convergence theory

2. Facilitation theory: The pain fibres coming from visceral organ and the
somatic region synapse with two different 2nd order neurons. But some of the
branches of visceral pain fibres also synapse with 2nd order neurons carrying
pain sensation from somatic regions. A portion of brain receiving pain sensation
from somatic region also receives pain impulses from visceral organ. This leads
to a misinterpretation in the location of the pain.
Lateral spinothalamic tract
Somatic region
Left shoulder

Fig. 8.39 Facilitation theory

Amputated leg lamic tract Lateral
spinotha
Fig. 8.41
Phantom pain Phantom pain—Habit Reference:

Following the amputation of limb, the cut ends of severed nerves innervate the
skin covering the stump. Stimuli exciting these nerve fibres at the stump are
interpreted as originating from limb which does not exist any more. This is
known as Phantom Pain.

Modulation of pain
At the spinal cord: Gating of pain
It is the process by which pain transmission is gated

i.e., modified at the posterior horn of spinal cord. It is achieved through

stimulation of touch pathway. It gives collaterals to inhibiting interneurons with
in the posterior horn. It blocks the transmission of pain. For example, pain is
relieved to some extent when a painful part of body is gently caressed or
touched.
Descending Painpain inhibitory Touch
fibre Lateral
Touch pathway spinothalamic tract
Touch fibre Inhibitory interneuron ++
–

+–
InhibitorPain p athway – interneuron +

Pain fibre
GATE Pain pathway
Fig. 8.42
Gating of pain at the posterior horn Central pain inhibiting mechanism

Gating of pain can also be effected by the descending inhibitory path. Different
individuals will react differently to same type of pain and same individual may
react differently in different situations. This is due to difference in their central
pain inhibiting mechanism or Endogenous analgesia system. The body has a in
built system for reducing the intensity of pain.

The important central structures are:

1. Periaqueductal Grey – PAG.
2. Nucleus Raphe Magnus—lower pons and upper medulla.
3. Reticular activating system.
4. Intralaminar thalamic nuclei.
Limbic system Cerebral cortex Cerebral cortex Thalamus
Hypothalamus
Periaqueductal
grey Lateral reticular formation Nucleus
Medial reticular formationraphe
magnus
Dorsal horn of spinal cord Inhibitory
interneuron Dorsal root
ganglion cell
e
PAG Periaqueductal grey

Collaterals from spinothalamic

dorsal columns and pyramidal tracts
Nucleus raphe
magnus Substantia nigra Enkepalins

Medulla
+ Serotonin
+
InternuncialSpinal cordneurons
Release of Presynaptic inhibition enkephalins

Fig. 8.43 Central pain suppressing mechanisms Fig. 8.44 Descending fibre tracts
which influence the transmission of pain in the central nervous system

Mechanism of action

As in other sensory systems, there are descending fibres, which parallel the
ascending fibres. Pain activates analgesic system via limbic system. The
descending fibres converge at PAG. Activation of PAG secretes encephalin.

It stimulates the raphemagnus nucleus in pons / medulla. These neurons secrete

serotonin. It in turn reach spinal cord – SGR and stimulate inter neurons which
secrete Enkephaline. This inhibits the transmission of pain. Thus pain helps to
cure itself.

Just as a drop of water gets lost in a river when pain crosses its limit it cures
itself.
“Dard Ka had se guzarna hal dava ho jana”.

Descending fibres fromCerebral cortex cerebral cortex thalamus

and hypothalamus
Reticular formation
Periaqueductal grey
Enkephalinergic neuron

Nucleus raphe magnus

Enkephalinergic
neuron in spinal cord

Serotonergic neuron
Enkephalinergic neuron inhibitory interneuron

Pain afferent
Inhibitory interneuron
Pain
– fibre
Touch
fibre
Dorsal horn of spinal cord

Fig. 8.45
Revaluation of the gate control theory

Hyperalgesia
Excessive sensitiveness to pain is called hyperalgesia
primary and Secondary.
Primary hyperalgesia: Immediately after an injury
certain chemicals are released. This decreases the threshold
for pain so sensitivity of pain increases.
Secondary hyperalgesia: It is felt over a wider area
around injury. The pain felt in this case is of high threshold
and prolonged. It may be due to subliminal fringe effect at
spinal cord and at higher level.
Management of pain
Transcutaneous Electrical Nerve Stimulation
(TENS): Applying or implanting small electrodes, this can
be activated to supply a low electrical current. This results
in stimulation of nerve fibres and reduction of pain impulses.
– Acupuncture—Inflicting mild pain.
It will act as a gate control mechanism, or it may release
endogenous opiads.
– Balm/Counter irritants—Gate control.
– Distraction—At cortical level—listening to music.
Pharmacological management of pain
(a) At receptor level (b) At higher level (a) Stimulation of pain receptors are
mediated through chemicals like bradykinin. Prostaglandins promote the actions
of Bradykinins. Drugs which will suppress the production of prostaglandins help
to relieve pain e.g., Aspirin.
(b) Opiod drugs: These drugs act at neurons and modulate the transmission of
pain. These drugs act both at spinal cord level and supra spinal level, e.g.,
Morphine.
Surgical methods
1. Nerve block: Peripheral nerves are temporarily interpreted by injection of a
local anesthetic or destroyed by neurolytic agent such as phenol. 2. Rhizotomy:
Divison of sensory nerve roots at the level of pain and neighbouring segments. 3.
Cordotomy: Cutting of sensory fibres in the lateral spinothalamic tract.
4. Thalamotomy: Stereotaxic—destruction of pain fibres in the thalamus.
5. Prefrontal lobotomy: Separation of prefrontal lobe from other parts.

Descending Tracts (Motor Tracts)

These are broadly classified into 2 types.
1. Pyramidal tracts 2. Extra pyramidal tracts.

Pyramidal tracts: These are important motor tracts. There are two groups of
pyramidal tracts:
1. Corticobulbar tract. 2.Corticospinal tract.
Corticobulbar tracts: The motor fibres arise from motor cortex situated in the
frontal lobe of cerebral cortex. Climbs down through cerebral peduncle, internal
capsule etc. and reach pons and medulla. Here these fibres synapse with the
nucleus of motor cranial nerves.
Functions: This tract carries motor impulses to the cranial nerves and thereby
responsible for the motor functions of cranial nerves. It mainly concerned with
movements of head and neck.
Motor cortex
Pyramidal tract

Nuclei of
cranial nerves Internal capsule

III
IV Midbrain Toes
Thumb
Neck Eye FaceLip s
Jaw
TongueRight cerebral
cortex Pharynx

V Pons
VI
VII
IX Medulla oblongata

X
XI

Fig. 8.46
Pyramidal tract—corticobulbar tract
Motor cortex

Internal capsule Medulla oblongata Motor decussation

Lateral column

Uncrossed or
anterior corticospinal tract
Uncrossed corticospinal tract or corticospinal tract

Anterior horncell

To muscle Crossed corticospinal tract or lateral corticospinal tract

Interneuron
To muscle
Anterior horncell

Fig. 8.47 Corticospinal tract Fig. 8.48 Motor homunculus Corticospinal tracts:
It is an important pyramidal tract.

Origin: It is made up of 1 million nerve fibres. Most of the fibres are large and
myelinated. These fibres originate from the large pyramidal cells known as Betz
cells. Betz cells are situated mainly at area no.4 which is situated at frontal lobe.
Apart from Betz cells the numerous small pyramidal cells of motor cortex also
contribute fibres to corticospinal tract. These fibres climb down and pass through
the structures like internal capsule and cerebral peduncle and these fibres reach
the medulla oblongata. At the medulla oblongata most of the fibres cross over
(80–85%). This crossing over of motor fibres at the medulla oblongata is known
as motor decussation. This gives rise to two types of corticospinal fibres.

1. Crossed corticospinal tract.

2. Uncrossed or direct corticospinal tract. In the medulla oblongata the fibres
of pyramidal tract are organised compactly and it appears like a pyramid. This is
one of the reason to call it as pyramidal tract. Another reason that is it originates
from pyramidal cells. The crossed corticospinal tracts are organised in the lateral
column of spinal cord and the uncrossed corticospinal tracts are located in the
anterior column of spinal cord.

Termination: The crossed corticospinal tract fibres synapses with the

interneuron situated at lateral horn of the spinal cord. These interneurons
synapse with anterior horn cells. The fibres of uncrossed corticospinal tract
directly synapse with anterior horn cells. From the anterior horn cells, the
efferent fibres come through the ventral root of spinal nerve and these fibres
reach various skeletal muscles. The pyramidal cells and their fibres are known as
upper motor neuron. The anterior horn cells and their fibres are known as lower
motor neuron. Motor tract comprises of either 2 or 3 neurons.

Functions:

Pyramidal tract carries motor impulses to all the skeletal muscles. They are
responsible for control and coordination of each and every voluntary activities.

(i) The size of the representation of the individual body parts is proportional to
the skill with which the parts are used in fine voluntary movements. Thus there
is large area for the hands and face.

(ii) The face, the pharynx, the vocal cords and the muscles for closing the jaws
are bilaterally represented.

Functions of pyramidal tracts

1. Carry motor impulses form motor cortex to spinal cord alpha motor neurons.
These impulses execute fine skilled movements.

2. Impulses carried by this tract influences stretch reflex.

3. These impulses control the gravity and anti gravity muscles and there by helps
in postural movements.
4. Impulses carried through cortico-spinal tract ultimately influences both alpha
and gamma motor neurons of spinal cord.

Motor homunculus: The body is represented upside down in the cortex; very
similar to as in the corresponding ‘sensory cortex’ in the postcentral gyrus.
Thalamus Motor cortex
Pyramidal neurons
Medulla oblongata Motor
decussation

Crossed corticospinal tract or lateral corticospinal tract Uncrossed corticospinal tract or anterior

corticospinal tract
Lateral column interneuron
To muscles

Anterior horncell Anterior column

Fig. 8.49
Pyramidal tracts (corticospinal pathway)

1. The size of the representation of the individual body parts is proportional to

the skill with which the parts are used in fine voluntary movements. Thus there
is large area for the hands and face.

2. The face, pharynx, vocal cords and the muscles for closing the jaws are
bilaterally represented.
Extrapyramidal Tracts

These are additional motor pathways other than pyramidal tracts. They originate
from different parts of cerebral cortex and brain stem. The major tracts are:

1. Rubro – Spinal tract

2. Vestibulo – Spinal tract – lateral and medial
3. Pontine – Reticulospinal tract
4. Tecto-spinal tract.
Extrapyramidal tracts: Special features
1. The uncrossed tracts of motor nerves from the brain to the anterior horns of
the spinal cord, except the crossed fibres of the pyramidal tracts.
2. Within the brain, extrapyramidal pathways comprise

various relays of motoneurons between motor areas of the cerebral cortex, the
basal nuclei, the thalamus, the cerebellum, and the brainstem.

3. The extrapyramidal pathways are functional rather than anatomic units,

comprising the nuclei and the fibres and excluding the pyramidal tracts.
4. They especially control and coordinate the postural, static, supporting, and
locomotor mechanisms and cause contractions of muscle groups sequentially or
simultaneously.

5. The extrapyramidal pathways include the corpus striatum, the subthalamic

nucleus, the substantia nigra, and the red nucleus, together with their
interconnections with the reticular formation, the cerebellum, and the cerebrum.

Components of the extrapyramidal tract include the basal ganglia, the red
nucleus, the substantia nigra, the reticular formation and the cerebellum. All
of these structures send information to the lower motor neurons. There are
different descending pathways that contribute to the extrapyramidal system.

1. The rubrospinal tract passes through the red nucleus. The cerebellum sends
messages to the spinal nerves along this tract. Information flows from the
superior cerebellar peduncle to the red nucleus and finally to the spinal nerves.
This information is very important for somatic motor, or skeletal muscle control
and the regulation of muscle tone for posture.

2. The reticulospinal tract runs from the reticular nuclei of the pons and medulla
to the spinal nerves. It is involved in somatic motor control like the rubrospinal
tract and also plays an important role in the control of autonomic functions.

3. The tectospinal tract has points of origin throughout the brain stem, but
especially in the midbrain area, and ends in the spinal nerves. It is involved in
the control of neck muscles.

4. The vestibulospinal tract runs from the vestibular nuclei located in the lower
pons and medulla to the spinal nerves. It is involved in balance.

Functions:

1. Rubro spinal tract is responsible for the control of tone and posture.
2. Tecto spinal tract controls visuo spinal reflex.
3. Vestibulo—spinal tract controls equilibrium.

4. These tracts control complex movements of body and limb such as

coordinated movements of arms and legs during walking.

5. They exert tonic inhibitory control over the lower centers—so their damage
increases rigidity of the muscles called release phenomenon.

6. In case of damage of pyramidal tracts, their functions are taken over to some
extent by extrapyramidal tracts.

2 4 13 5
4
5
12 3

1. Rubrospinal tract
2. Tectospinal tract
3. Vestibulospinal tract
(lateral) 1 3 2 4 5
4. Reticulospinal tract
(medial)
5. Reticulospinal tract (lateral)

Fig. 8.50 Extrapyramidal tracts

TABLE 8.13
Signs and symptoms of upper motor neuron paralysis and lower motor
neuron paralysis
S.No. Signs and symptom UMNP LMNP 1. Voluntary muscle power Lost for
skilled movements Lost 2. Tone of muscles

3. Superficial abdominal reflexes Hypertonic, clasp knife rigidity spastic type

paralysis

Lost
Lost—flaccidity Flaccid type of paralysis.
Lost only when the particular neuron supplying the muscle is damaged.
4. Plantar reflex Babinski’s Sign + ve

Normal flexor plantar response provided the segment S1 is not affected. When S1
is lost. Plantar reflex is absent or no response to scratch in the sole.

5. Tendon Jerks Exaggerated Lost 6. Clonus Present Absent 7. Muscle atrophy

Nil, if present that is due to disuse Marked wasting
8. Muscle power Is lost or greatly diminished Loss of muscle power

TABLE 8.14
Effects of lesion at various levels in pyramidal tract
1. Motor area of cerebral cortex Mono plegia-contra lateral side 2. Corona
radiata Monoplegia 3. Internal capsule Depends on severity of lesion hemiplegia
of contra lateral half. In severe lesions sensory and visual tracts are involved so
hemianaesthesia 4. Mid brain Hemiplegia of contra lateral half and 3rd nerve
palsy of ipsilateral side. 5. Pons Hemiplegia of contra lateral half and facial
paralysis and 5th nerve paralysis of ipsilateral side.
6. Medulla Hemiplegia of contra lateral side and hypoglossal nerve palsy on the
same side (12th cranial nerve)
7. Upper level of spinal cord Quadriplegia +Respiratory paralysis 8. Thoracic
and Lumbar Paraplegia-respiration remains normal.

Destruction of pyramidal tract should result in Hypotonia. But extra pyramidal

fibres also descend along with pyramidal tract. Usually there will be lesion of
both pyramidal and extra pyramidal tracts. Hence in upper motor lesion,
Hypertonia develops (spasticity) instead of Hypotonia.

TABLE 8.15
Comparison between pyramidal and extra pyramidal motor pathways
Sl.No. Features Pyramidal pathway Extra pyramidal pathway 1. Originates
from brain areas 6, 4, 3, 1, 2, 5 and 7 6, 4-S, 2-S, 1, 3, 5, 7, 8, 24S 2.
Euolutionory grade
Phylogenically
3. Physiological function commences from
4. Number of neuron taking part in relay of impulses
5. Number of synapses
6. Functions carried out and nature of action
7. Velocity of conduction of motor impales

8. Body parts mostly controlled

9. Lesion of fibres causes

More evolved type

Newer system
Post natal life after 1 to 2 years of birth

2 or 3
Primitive type
Older system
Prenatal life, responsible for foetal movements
Many
One or two Many Skilled fine movements Gross movements provide
background for skilled movements Slow Fast
Upper limbs mostly finger and hands Lower limbs, mostly for locomotion
Flaccid paralysis of small muscles Paralysis of muscles with spasticity.

BROWN-SEQUARD SYNDROME It is a nervous disorder resulting from the

hemisection of spinal cord.

Causes:
The common causes are
1. Bullet injuries 2. Stabbing injuries 3. Traffic accidents. 4. Fall from heights.
This will show different changes in the body. The symptoms are seen.

Same side Severe sensory and motor loss 1. At the site of injury Opposite side
No serious problem Same side No serious sensory or moro loss 2. Above the site
of injury Opposite side Same side Loss of sensations like fine touch, vibration
presence of sensations like pain and temperature motor paralysis. 3. Below the
site of injury Opposite side Sensation like pain and temperature are lost
sensations like fine touch, vibration are present. No serious motor loss.
The neurophysiological changes taking place below the site of hemisection of
the spinal cord is known as BrownSequard syndrome.
Lesion on this side
Below the site of injury opposite side Below the site of injury same side
A. Senory changes

(i) Loss of pain, temperature and crude touch sensations.

(ii) Fine touch, vibration and stereognosy, proprioceptive sensations are present

A. Senory changes

(i) Loss of sensations of fine touch. Vibration, proprioceptive, stereognosy

(ii) Sensations present : crude touch, pain and temperature

B. Motor changes
No serious motor loss
B. Motor changes
(i) Spastic paralysis – upper motor neuron lesion
Site of injury

Fig. 8.51
Brown-Sequard syndrome
Same side: Loss of sensations like fine touch, vibration, touch discrimination
etc. but sensation of pain and temperature may be present.

Paralysis of muscles because of the cut of the pyramidal tract.

Opposite side: Loss of pain and temperature sensation, very little motor loss.
Fine touch vibration, strereognecy sensation are present.
Pyramidal tract
Right Left

Tract of goll from left side Tract of goll from right side

Lateral spinothalamic tract bringing pain and temp from left side Lateral spinothalamic tract bringing pain
and temp from right side

Medulla
Injury
Tract of goll Fine touch
pathway
Tract of goll
Fine touch pathway Pain, temp pathway lateral spinothalamic tract Pain, temp pathway lateral
spinothalamic tract

Pyramidal tract Pyramidal tract Fig. 8.52 Brown-Sequard syndrome Spinal Shock

Complete transection of the spinal cord and immediate loss of all the cord
functions is called spinal shock.

Causes of Spinal Shock

1. Automobile and other accidents.
2. Gun shot injuries during war.
3. Stabbing.
Signs and Symptoms
Depends upon site of transaction
There are three stages of spinal shock:
(i) A stage of spinal shock.
(ii) A stage of reflex activity (if patient survives the stage of spinal shock).
(iii) A stage of reflex failure.
I. A stage of spinal shock
Essential features are:
(a) Motor (below the level of lesion).
Hypotonia.
Flaccid paralysis—loss of all voluntary movements.
Loss of all tendon jerks.
Plantar stimulation gives no response. (b) Sensory:
Loss of all sensation below the level of lesion. (c) Vasomotor: Sharp fall of
blood pressure (about 40 mm Hg) depends upon site of lesion. Vasomotor
paralysis.
Venous return to heart falls. Cardiac output decreases.
Sluggish circulation.
Cyanosis (due to reduction of oxy Hb). Bed sores.
(d) Bladder and bowels:
Atonia of detrusor muscle(retention of urine). Hypotonia of bowel, resulting in
constipation. In man the duration of spinal shock lasts for several weeks—2
months.
II. A stage of reflex activity
Muscle tone
Tone of flexor muscles return first. Therefore lower limbs are in a state of
flexion (paraplegia of flexion).

Reflex

Babinski’s sign is positive, mass reflex present: (because spinal cord suddenly
becomes excessively active) when a scratch is made on the sole of other points
of a lower limb.

1. Major portion of the body goes into a strong flexor spasm.

2. Evacuation of bladder and colon.

3. Sharp rise in arterial BP.

4. Profuse sweating over large areas of the body. Tendon jerks begin to appear
after a lapse of few weeks, extensor muscles begin to get back their tone
(paraplegia in extension).
Bladder become automatic.
III. A stage of reflex failure
This is due to degeneration of the neural tissue of the spinal cord below the
lesion and infection.
Loss of reflex activities.
Hypotonia. Bed sores. Mass reflexes disappear. Patient dies.

Functions of Medulla Oblongata

1. It takes part in the regulation of cardiovascular functions. In the medulla
oblongata there is a group of neurons concerned with the regulation of
cardiovascular functions. This is known as cardiac center. The centre comprises
of neurons concerned with the regulation of heart rate as well as peripheral
resistance (TPR). Therefore this centre controls heart rate, controls cardiac
output as well as blood pressure.

2. Regulation of respiration: Two of the respiratory centers are situated at the

medulla oblongata. These centers are together called medullary rhythmic area
and are responsible for the maintenance of respiratory rhythm.

3. The medulla oblongata acts as a relay station for many of the sensory
pathways, e.g., Tract of Goll.
4. Medulla oblongata acts as a centre for many visceral reflexes. This includes
sneezing reflex, vomiting reflex, coughing reflex,deglution reflex etc.
5. The reticular activating system of the medulla wakefulness, alertness and
attention of the individual.
6. Some of cranial nerves arise from medulla oblongata.
7. Motor pathways from higher parts of the brain pass through medulla
oblongata to reach spinal cord.
Tract of burdach Nucleus ceneatus
Tract of goll
Nucleus gracilis
Trigeminal nucleus
Central canal

Crossed
corticospinal tract
Central
grey matter

Motor
decussation
Whitematter A. Shows motor crossing over Nucleus gracilis Tract of goll Nucleus cuneatus
Central grey matter Central canal Reticular formation
Sensory crossing over Pyramidal tract

Fig. 8.53
B. Shows sensory crossing over
Cross section of medulla oblongata
Functions of pons

1. It plays an important role in the regulation of respiration. Two of the

respiratory centresApneustic centre and pneumotaxic centre are situated in the
pons. These two centres are the highest centres for the regulation of respiration.

2. Reticular activating system of the pons is concerned with control of

wakefulness, alertness and attention of the individual.

3. Some of the cranial nerves originate from pons. 4. Sensory and motor
pathways pass through pons.
Motor cortex of cerebrum
Corrective feedback
Cortex of cerebellum Thalamus

Superior cerebellar peduncle

Middle
cerebellar

CEREBELLUM

The cerebellum lies dorsal to the brain stem in the posterior (occipital) fossa. It
is the largest part of hind brain. It is situated behind medulla and pons.
Cerebellum is usually called as “Silent area” because stimulation of it does not
produce any sensation or any motor activity. On each side it is connected to the
brain stem by 3 peduncles.

1. By inferior cerebellar peduncle or restiform body to medulla.

2. By middle cerebellar peduncle—brachium pontis to the pons.
3. By superior peduncle—brachium conjunctivum to the midbrain.
Hemispere Vermis
Reticular formation

Pons
Pontine
nuclel

Direct (pyramidal)
pathway
Indirect
(extrapyramidal) pathway

Provides signals to
lower motor neurons Spinocerebellar tracts carry sensory signals from
proprioceptors in muscles and joints
Fig. 8.55
Role of cerebellum in motor functions
Motor cortex
Corrective feedback
Superior cerebellar feduncle Thalamus
Primary fissure
Horizontal fissure
Anterior lobe
Posterior lobe Middle
cerebellar
feduncle Cerebellum
Inferior cerebellar peduncle Pontine nucleus

Reticular formation Direct (pyramidal) pathway

Poserior fissure Floculonodular lobe

Floculus

Spinocerebellar tract carry sensory signals from muscles and joints Indirect (extrapyramidal) pathway

Sends
impulses to
lower motor
cortex

Nodulus

Fig. 8.54 Cerebellum Fig. 8.56

Role of cerebellum in motor function

Anatomically cerebellum consists of two cerebellar hemispheres which are

connected by a medial vermis.
Each hemisphere is anatomically divided into three lobes.
1. Anterior lobe
2. Posterior lobe or middle lobe
3. Flocculonodular lobe
Physiologically cerebellum is divided into two parts.
(a) Corpus cerebellum: It has two lobes—anterior and posterior lobes separated
by fissura prima.
Inferior
cerebellar peduncle

(b) Flocculonodular lobe: It is divided into two parts: (i) Anterior lobe includes
lingula, lobulus centralis, culmen.
(ii) Posterior lobe includes lobulus simplex, declive, tuber, pyramid, uvula and
parafloccule. Phylogenetically—Paleo cerebellum—anterior lobe, lobulus
simplex, pyramid, uvula, parafloccule hemisphere.

Archi cerebellum-flocculonodular lobe.

Connections of Cerebellum
Afferent connections: Through inferior cerebellar peduncle

(a) Dorsal spinocerebellar tract—bring sensory impulses from muscle, skin and
joints—sensation of contraction of muscles, position of limbs.

(b) External arcuate fibres- bring cutaneous and deep sensations.

(c) Reticulo—cerebellar fibres.
(d) Olivo-cerebellar fibres.
(e) Vestibulo—cerebellar fibres.

Through middle cerebellar peduncle

Cerebroponto cerebellar fibres
Through superior cerebral peduncle
(a) Ventral spino cerebellar tract—proprioceptive sensations from muscles and
joints.
(b) Tecto cerebellar tract—visual and auditory information from the cortex.
Efferent connections
Efferents passing through superior cerebral peduncle (a) Cerebellum—to
motor cortex area 4 forming dentate rubrothalamo cortical path.
(b) Efferents to reticular formation.
Efferents passing through inferior cerebral peduncle Cerebello-vestibular
fibres pass to vestibular nuclei.
These two pathways indirectly control anterior horn cells.
Functions of Cerebellum
1. Cerebellum is not able to initiate any motor activities but assist the motor
actions initiated by

other parts of brain. But it plays an important role in controlling and

coordinating voluntary and involuntary movements.

(a) Control of involuntary movements:

Cerebellum controls unconscious, automatic and reflex movements or
involuntary movements. It coordinates subconscious gross movements.
Mechanism
1. The afferent pathways to the cerebellum

transmit proprioceptive, kinaesthetic and sensory informations from all over the
body.

2. Collateral extrapyramidal impulses from motor cortex, basal ganglia and

reticular formation are transmitted to cerebellum.

3. The cerebellum integrates these impulses and provides feedback impulses to

the cerebral cortex, basal ganglia and reticular formation that correct error in the
involuntary movements.

(b) Control of voluntary movements: The cerebellum guides and controls all
the voluntary movements on both execution of goal oriented voluntary
movements. The movements are accurate in time, rate, range, force and
direction. Mechanism

There is a triangular relationship between motor cerebral cortex, cerebellum and

skeletal muscles. Motor impulses are originated at motor cortex. From the motor
cortex impulses are transmitted to the skeletal muscles. This information is also
sent to the cerebellum. From the skeletal muscles and joints sensory impulses are
continuously transmitted to cerebellum. Cerebellum inturn sends feedback
impulses to the motor cortex. This modifies the furthur impulses transmitted to
the skeletal muscles. This acts as a error correcting mechanism. The
cerebellum ensures that muscular action is well co-ordinated, movements are
smooth and precise as to force, rate and extent.

Thereby cerebellum helps the cerebral cortex in timing and sequencing of next
successive movement. It also plays a role in predicting events like rates of
progression of auditory and visual actions.

Cerebellum controls body posture and equilibrium Cerebellum with the

spinal cord and brain stem helps
in control of posture and equilibrium. Cerebellum gets
feedback about tone of muscle or position of limbs in space.
It also gets feedback from vestibular and reticular nuclei
about the activities of extra pyramidal tracts. Through its
efferents to reticular and vestibular nuclei, it does necessary
correction for maintaining posture and equilibrium. Cerebelllum controls muscle
tone and stretch reflexes.
Causes of cerebellar disease or damage
1. Abscess
2. Hemorrhage
3. Trauma
4. Thrombosis of the artery supplying cerebellum 5. Degenerative changes in the
cerebellar cortex.
Signs of cerebellar lesion
Disturbaness in tone and posture.
1. Hypotonia or atonia cerebellar lesion produce atonia or hypotonia of skeletal
muscles. This will disturb the postural reflexes and balance.
2. Disturbances in the attitude: A marked change is observed in attitude in
unilateral lesions of cerebellum. The major attitude changes are (a) Rotation of
head towards unaffected side. (b) Lowering of shoulder to same side of lesion (c)
Abduction of legs to opposite side.
3. Deep reflexes while eliciting tendon jerks, some slow oscillatory to and fro
movements are produced instead of brisk movements. This is known as pendular
movement.
4. Disturbances in equilibrium: While standing the legs are kept spread to a
broad base, while moving staggering, drunken gait is observed.
5. Disturbance in movements
(a) Ataxia—in coordinated voluntary movements. (b) Asthenia: Easy
fatigability and slowness of movements.
(c) Dysmetria: Inability to adjust the strength and duration of a contraction
required to accomplish a given act, (e.g., when the subject is asked to touch a
point with his finger he overshoots the mark or fails to reach it).

Involuntary tremors occur during voluntary movements overshooting is called

hypermetria and falling short to reach is called hypometria.

(d) Rebound phenomenon: If the patient is asked to attempt a movement

against a resistance which is then suddenly removed, the limb moves forcibly in
the direction towards which the effort was made. This is due to absence of the
breaking action of antagonistic muscles.

(e) Dysdiadochokinesis: Inability to execute alternating movements rapidly,

e.g., Flexion and extension of the fingers.
(f) Cerebellar nystagmus: (deviation of the eyes) it occurs due to damage to
flocculonodular lobes. Tremor of eye balls occurs at rest. (When neither person
nor the visual scene is moving). This is due to ataxia of ocular muscle.

(g) Gait: It becomes awkwardly with the feet wide base, well apart, drunken
gait.
6. Speech: It is slow and lalling (baby like). This is known as
dysarthria.
MUSCLE SPINDLE

Definition: Muscle spindles are spindle shaped sense organs present inside the
skeletal muscles, they respond to change in muscle lengthening. The number of
muscle spindle in each muscles varies from a very few to several. The number of
spindles per muscle is more in muscles of fine movements and posture and
equilibrium.

Structure of muscle spindle: They are present inside the belly of skeletal
muscle. It has a length of 10 mm of diameter of 100 microns. The muscles of
spindle are intrafusal muscles which are arranged parallel, to skeletal muscles, or
extrafusal muscles. The distal part of intrafusal muscles are attached either to the
tendon or extrafusal muscles.
g -efferent fibresIa afferentAa fibres
Muscle spindle intrafusal muscles Extrafusal muscles
Fig. 8.57
Muscle spindle

The intrafusal muscles are of two types—nuclear bag fibres which are longer
and dilated at the centre giving a bag like appearance. They have multiple nuclei,
about 2 nuclear bag fibres per spindle. Nuclear chain fibres are thinner and
shorter. Nuclei are arranged in a row to from a chain. Usually 4 or more nuclear
chain fibres are seen in a single muscle spindle. Receptors are at the central parts
and the peripheral parts are contractile in nature.

Nerve innervation: Muscle spindle are innervated by two types of afferent

innervation Ia and II fibres. Ia afferents make primary ending on the centre of
intrafusal fibres Annulospiral ending. Type II afferent makes secondary afferent
flower spray ending.

Efferent innervation of muscles spindle is by gama motor neurons or fusimotor

gama fibres. The ending of motor neuron make endplate ending on nuclear bag
fibre I and make trial ending on nuclear chain fibres.

Functions of muscles spindle: They act as receptors for stretch there by take
part in stretch reflexes. This helps in control of posture and equilibrium.
g -efferent I a primary afferent II a primary afferent

Plate ending

Annulospiral ending
Nuclear bag fibre

Trial ending Nuclear chain fibre

Flower-spray
ending

Fig. 8.58 Structure of muscle spindle and its inneration

Muscle Tone
Definition: The partial contracted state of the muscles at rest is called muscle
tone.

Causes: It is due to the continuous discharge of asynchronous impulse from

motor neurons of ventral horn of spinal cord. Muscle tone is required for normal
posture, contraction of muscle (i.e., movement) and for normal stretch reflexes.
Increase or decrease in muscle tone causes abnormalities— which are
hypertonicity and hypotonicity.

1. Hyper tonicity: Characterised by increase in muscle tone.

Causes:
1. When the inhibitory influence on γ motor neuron discharge is abolished.
As seen in
(a) Parkinsonism: due to destruction of substantia niagra of Basal ganglia
causing rigidity.

(b) Upper motor neuron lesion, e.g., lesion of pyramidal tract causes spasticity.
Hence the activity of lower motor neuron increases.

2. Pain: Pain causes reflex stimulation of α motor neuron. This in turn increases
the muscle tone.
Hypotonicity
Characterised by decrease in muscle tone.
Causes

1. Due to decrease in γ motor neuron discharge. Seen in

(a) Tabes dorsalis, i.e., destruction of dorsal nerve

roots.
(b) Sleep and unconsciousness.
(c) Lower motor neuron lesion (causing flaccidity).

2. Drugs—like sedatives, and tranquilisers causes hypotonicity by their direct

influence on CNS.
3. Neuromuscular junction blockers like curare drugs decrease the muscle tone.
4. Cerebellar lesion.
Maintenance of constant muscle tone is very important. There are two
mechanisms for that
1. Spinal mechanism—it is mostly by the stretch reflex.
2. Supra spinal mechanism—pyramidal and extrapyramidal mechanism.

EQUILIBRIUM

Equilibrium results when the forces acting upon a body are perfectly balanced
and body remains at rest.
When the body is at rest in equilibrium there is
1. No tendency to move in any direction i.e., Result force = 0.
2. No tendency to rotate in any direction i.e., Resultant moment = 0.

Types
1. Stable equilibrium: If the forces acting upon a body at rest tend to restore it
to its original position after it has been displaced the body is said to be in Stable
equilibrium.

2. Unstable equilibrium: If a body is given an initial displacement and the

forces acting upon it increase this initial displacement the body is said to be in
unstable equilibrium.

3. Neutral equilibrium: If, in spite of displacement of body, the height and

position of its centre of gravity remain the same in relation to the base, the body
is said to be in neutral equilibrium.
POSTURE

Posture is the attitude assumed by the body either with support during muscular
inactivity or by means of the coordinated actions of many muscles working to
maintain stability.

Types

1. Inactive postures: These are attitudes adopted for resting or sleeping, and
they are most suitable for this purpose when all the essential muscular activity
required to maintain life is reduced to a minimum.

2. Active postures: These are the attitudes adopted by the integrated action of
many muscles.

There may be:

1. Static postures: A constant pattern of postures is maintained by the inter-
action of groups of muscles

which work more or less statically to stabilise the joints and in opposition to
gravity or other forces. In the errect postures they preserve a state of equilibrium.

2. Dynamic postures: This type of active posture is required to form an efficient

basis for movement. The pattern for the posture is constantly modified and
adjusted to meet the changing circumstances which arise as the result of
movement.

Postural Mechanism

Muscles: The groups of muscles must frequently employed are those which are
used to maintain the erect position of the body by working to counteract the
effects of gravity known an antigravity muscles.

Characteristics of antigravity muscle:

1. Action is usually extension.
2. The form of the muscle is multipimate and fanshaped.
3. Red or dark or slowly contracting fibres indicating their capacity and
capability of sustained contraction without fatigue.
4. Low metabolic rate.
Nervous control: Postures are maintained or adopted as a result of neuro
muscular co-ordination by the appropriate muscles being innervated by means of
a very complex mechanism.

Postural Reflexes

Afferent stimulation arise from a variety of sources from all over the body like
joints, muscles, eyes, and ears. The effector organ is usually muscles.

Two types of postural reflexes:

1. Static reflexes—When the body is not in locomotion.

2. Static kinetic reflexes—When the body is in locomotion.

(i) For example, Righting reflexes, Tonic neck, Tonic labyrinthine reflex
(ii) For example, Head reactions, Eye reactions. Role of vestibular apparatus
1. It takes part in the maintenance of muscle tone, equilibrium and posture.

2. Reflexly adjusts the relative position of head to that of trunk and limbs.
3. Maintains the erect position of head.
Semicircular canals: Semicircular canals give information about the direction,
degree, and the plane of movement of the head i.e., kinetic or dynamic
equilibrium. Otolithic organ: Otolithic organs give information about the static
equilibrium. The saccules give information regarding the position of the head in
the lateral plane while utricles in anterio-posterior plane.

Vestibulocerebellar tract: Connects the vestibular apparatus with the

flocculonodular lobe of the same side of cerebellum.

Role of cerebellum: (Archicerebellum) The flocculonodular lobe being

connected with vestibular apparatus through vestibular nerves help in regulation
of posture and equilibrium.

Lesions of cerebellum cause

1. Disturbance in posture and postural tone.
2. Lesions in flocculonodular lobe causes oscillation of the head, disturbance in
maintaining the posture and equilibrium.

TABLE 8.16
Postural reflexes
Sl.No. Reflex Centre Receptor Stimulus Response 1. Optical righting Cerebral
Cortex Rods and cones
2. Placing reaction Cerebral cortex

Proprioceptive Opening of eyes Visual cues

Pressure like touch, push etc.

Righting of head

Limb replaced on the supporting surface in position to support body.

3. Hopping reaction Cerebral cortex Stretch receptors

in muscles
Lateral pushing while standing Movements keep limbs in position to support
body.

4. Labyrinthine righting
Midbrain Otolithic organs Tilting of head Compensatory contraction of neck
muscle to keep head level.
5. Neck righting Midbrain

Stretch of neck muscle, muscle spindle

Righting of head and lifting of body Righting of thorax and shoulders then
righting of abdomen and hindquarter.

6. Tonic labyrinthine Medulla Otolithic organ Gravity via vestibular spinal tract
Extensory rigidity.
7. Stretch Spinal cord, medulla Muscle spindle Stretch Contraction of muscles.

DECEREBRATE RIGIDITY

It is a nervous disorder seen in animal in which the connection between cerebral

corex and brain stem is cut. This experimental operation was first demonstrated
by Sherrington.

Procedure: A surgical transection is made in between the superior and inferior

colliculi.

1. The inter collicular section causes total loss of the communications between
cerebral Hemisphere and Brain Stem.
Decerebration
2. Brain stem is free from the control of cerebral cortex and basal ganglia. It is
an example for release phenomenon.

3. Medullary vestibular inhibitor system becomes nonfunctional because of loss

of its usual excitatory drive.

Symptoms
(a) The animal stands hyper extended.
(b) All the four limbs become rigid like pillars. (c) It is because both extensors
and flexors of the

limbs show hypertonia.

Hypertonia of antigravity muscles are more dominant.

Muscles exhibit the phenomenon called spasticity as well as rigidity.

Any attempt to change the position of a limb is resisted by very powerful stretch
reflexes. This occurs mainly because the pontine and vestibular antigravity
signals to the cord selectively excite the gamma motor neurons of spinal cord
much more than alpha motor neurons.

HYPOTHALAMUS

The area of the brain which forms the floor and part of the lateral wall of the
third ventricle is called hypothalamus. It is composed of many nuclei scattered in
this area. Hypothalamus being the key region for maintenance of homoeostasis
forms a very important part of the CNS. It is intimately involved in regulation of
many vital functions and is also related with endocrine regulation. It not only
acts as the head ganglion of the ANS but also ensures co-ordination between
autonomic and somatic responses as in emotional expressions.

Nuclei of the Hypothalamus

Thalamus Periventricular

Dorsomedial Paraventricular

Anterior
hypothalamic Fornix
Lateral
hypothalamic
Optic tract Supraoptic
Arcuate Ventromedial
Fig. 8.59
Coronal view of the hypothalamus, showing the mediolateral positions of the
respective hypothalamic nuclei
Dorsal hypothalamic area
Paraventricul nucleus Anterior hypothalamic area

Preoptic area Posterior hypothalamic nucleus Dorsomedial nucleus

Ventromedial nucleus Premamillary nucleus

Supraoptic nucleus Medial mamillary nucleus
Suprachiasmatic nucleus Lateral mamillary nucleus

Arcuate nucleus Optic chiasm

Median eminence Superior hypophyseal artery

Portal hypophyseal vessel Primary piexus

Anterior lobePituitary gland Posterior lobe

Fig. 8.60
Structure of hypothalamus
Mamillary body
A. Preoptic group
(i) Medial preoptic preoptic nucleus (ii) Lateral nucleus
B. Supraoptic group

(i) Supraoptic nucleus

(ii) Suprachiasmatic nucleus (iii) Paraventricular nucleus
(iv) Anterior nucleus

C. Tuberal group
(i) Ventromedial nucleus
(ii) Dorsomedial nucleus

(iii) Arcuate nucleus

(iv) Posterior nucleus

D. Mammillary group
(i) Medial mammillary nucleus
(ii) Lateral mammillary nucleus

(iii) Premammillary nucleus

(iv) Supramammillary nucleus
To hypothalamus – Afferent connections

(i) Corticohypothalamic fibres (some of these fibres are believed to be

responsible for pre-exercise CVS changes).

(ii) Pallidohypothalamic fibres connect pallidum to hypothalamus.

(iii) Thalamo-hypothalamic fibres come through the periventricular path.

(iv) From amygdala via stria terminalis
(v) From hippocampus via fornix.
(vi) Fibres from olfactory area and from different parts of limbic cortex via the
medial forebrain bundle.
(vii) From midbrain via mammillary peduncle. (viii) From reticular activating
system.
(ix) Fibres from medulla come as
(a) Serotonergic fibres from raphe nucleus. (b) Noradrenergic fibres from locus
coeruleus. (c) Other adrenergic fibres.
(d) Also fibres from nucleus tractus solitarius (e) Collateral from the lemniscal
system.
(x) From habenular nucleus.

From hypothalamus – Efferent Connections

(i) Mammillothalamic tract (a part of Papez circuit). (ii) To limbic cortex via
medial forebrain bundle. (iii) To hippocampus via fornix.
(iv) To reticular formation of midbrain via

mammillothalamic tract.
(v) To thalamus.
(vi) To pituitary via hypothalamo-hypophyseal tract.

(vii) To various brainstem centres, e.g., CVS, respiratory etc.

(viii) To spinal cord (lateral horn cells).

Functions of hypothalamus
Hypothalamus is an important part of the brain. It is concerned with a wide
range of physiological functions.

Regulatory functions of hypothalamus

1. Regulation of body temperature.
There are two groups of animals depending upon their
ability to regulate their body temperature.
1. Homeotherms
2. Poikilotherms

Body Temperature Regulation

Cerebral cortex Voluntary response Core temperature

Core thermoreceptors
Skin thermo receptors Hypothalamus
Skin temperature
Environmental temperature TRF
Anterior Pituitary
TSH
Thyroid gland Adrenal medulla Skin sweat glands Skin arterioles Skeletal muscles
Thyroxine Adrenaline Sweating
Cellular metabolism Cellular metabolism

Heat loss Vasodilatation or

Vasoconstriction Shivering

Heat production
Heat production Heat production

Heat loss
or
heat conservation

Behavioural
Adjustments

1. Curling
3. Fanning
5. Drinking
7. Eating

2. Change of clothes
4. Change of place
6. Putting water on body

Homeotherms: Homeotherms are animals which can maintain a constant body

temperature irrespective of changes in environmental temperature.

Poikilotherms are animals in which body temperature fluctuates according to the

changes in the environmental temperature. Man is a homeotherm. The normal
body termperature is 37°C ± 0.5°C or 98.6°F ± 1°F.

Heat gain: The sources of heat gain in the body are: 1. Cellular metabolism 2.
Solar radiation. Heat loss: The important channels of heat loss for the

body are:
1. Conduction
3. Radiation 2. Convection 4. Evaporation.

A constant body temperature can be maintained by establishing an equilibrium

between heat gain and heat loss.

Physiological variation in body temperature: 1. Diurnal variation: Body

temperature will be least at the early morning hours, e.g., 5 AM and it will be
maximum in the late evening 5 to 6 pm. It shows a variation of about 1 to 1.5°C.
2. Exercise: During increased muscular activity and exercise more heat is
produced and it increases body temperature.
3. Menstrual cycle: Body temperature is minimum during menstrual period, it
gradually increases up to the day of ovulation. After that the basal body
temperature increases by about 0.5°C and remains high during the luteal phase
of ovarian cycle. It is due to the thermogenic action of progesterone.
Pathological variation
Significant rise in body temperature is known as fever. It is mostly caused by the
toxins produced by pyrogens. Role of hypothalamus in the regulation of body
temperature
Hypothalamus acts as a thermostatic centre. Body fixes a normal temperature. It
is known as setpoint. Suppose body temperature falls this will stimulate the
cold receptors present in the skin. From the cold receptors impulses are
transmitted to the Hypothalamus. Hypothalamus takes up the corrective
measures.
It will increase sympathetic activity. This will increase the secretion of
adrenaline. Increase in adrenaline level will

increase rate of cellular metabolism.This will increase heat production.

Hypothalamus also increases secretion of thyroxine from the thyroid gland.

Increase in thyroxine level will also increase cellular metabolism and heat
production.

Hypothalamus initiates shivering. Shivering produces increased muscular

contraction and increased heat production.

Hypothalamus produces vasoconstriction. This will reduce the flow of blood and
flow of heat energy to the skin. This will reduce heat loss from the body. All
these effects together increase the body temperature to normal.

Suppose body temperature increases. It will stimulate warm receptors of skin.

From these receptors impulses are trasmitted to hypothalamus. Hypothalamus
detects the body temperature is more than set point. It initiates corrective
measures.

1. Sympathetic discharge decreases, it may produce the following:

(a) decreased cellular metabolic rate, decreased heat production.

(b) decrease in the secretion of adrenaline, decrease in metabolic rate, decrease
in heat production.
(c) increased in vasodilatation of blood vessels of skin. This will increase blood
flow to skin, increase heat flow to skin, increase heat loss from skin.
2. Decrease in the secretion of thyrotropin releasing
factor, decrease in TSH secretion from anterior
pituitary, decrease thyroxine secretion from thyroid,
decrease in metabolic rate and decrease in heat
production.
3. Increase sweating. Sweat gets evaporated. This
increases heat loss. All these actions together bring
down the body temperature to normal.

Responses of the body when exposed to extremes of cold 1. Steps to decrease

heat loss, to conserve heat.

(a) Vasoconstriction of blood vessels of skin is produced by sympathetic

stimulation. Less blood flow to skin, less heat flow to skin, less heat loss from
the skin.

(b) Decreased sweating.

(c) Piloerection or horripilation by the contraction of piloerector museles—heat

loss is prevented.
(d) Behavioural responses.
(i) Curling up there by reduces the area expected to cold.
(ii) Change of place—seeking a warm place. (iii) Change in clothes.
2. Steps to increase heat production
(a) Increased muscular activity. Shivering during muscular contraction more than
70% of energy produced is discharged as heat energy. (b) Increase in appetite.
(c) Increased secretion of calorigenic hormones like thyroxin and adrenaline.
(d) Behavioural responses:
(i) Voluntary muscular movements like tapping of feet, hands.
(ii) Intake of calorigenic food
(iii) Use of appliances to increase the temperature surrounding the body, e.g.,
Heaters.

Responses of body when exposed to extremes of hot 1. Steps to increase heat

loss

(a) Decrease in sympathetic tone leading to vasodilatation, more blood flow, and
more heat low to skin. So more heat loss from skin.

(b) Increased sweating, evaporation—heat loss.

(c) Increased in heart due to rise in temperature increasing cardiac output.

(d) Behavioural responses:
(i) Change of clothing.
(ii) Use of appliances like fan.
(iii) Drinking of cool drinks/water. 2. Steps to decrease heat production
(a) Decrease in appetite—anorexia.
(b) Decreased secretion of calorigenic hormones.
(c) Behavioural responses
(i) Avoidance of muscular activity

2. Regulation of water balance

Hypothalamus plays an important role in the regulation of water balance. There

are 3 major mechanisms for the regulation of water balance. They are

1. Controlling water loss through urine.

2. Controlling water loss through sweat.
3. Controlling water intake through thirst mechanism. Hypothalamus is involved
in all these three mechanisms.
Osmoreceptors+
Hypothalamus Cerebral cortex
Osmotic concentration of blood
Thirst
Blood volume Drinking
Absorption Water intake
Fig. 8.61
Thirst mechanism—Water balance
Thirst mechanism

Stimulus for thirst are dehydration of buccal cavity and pharynx and increase in
the osmotic concentration of blood.
Suppose osmotic concentration of blood increases, that will stimulate certain
neurons of the Hypothalamus. These neurons are known as osmoreceptors.
Stimulation of this osmoreceptors will increase the neurophysiological activities
of the hypothalamus. This acts as the neurophysiological basis of thirst. Thirst
leads to drinking. Drinking is a behavioural act. It is controlled and coordinated
by the cerebral cortex. Drinking increases water intake. This will increase blood
volume. This will decrease the osmotic concentration of blood to normal.

3. Hypothalamus controls food intake

Regulation of food intake: Role of Hypothalamus

The control of food intake is important to keep the body weight relatively
constant and to maintain a constant glucose homeostasis. Body weight depends
upon balance between the food/caloric intake and energy expenditure. Both of
these parameters are regulated in such a way that generally maintains body
weight at a given set point.

Experiments conducted in animals have demonstrated that two regions of the

hypothalamus play major role in the regulation of feeding behaviour.

Interaction between two centres of hypothalamus control the food intake.

1. Satiety centre 2. Feeding centre

1. Satiety centre

Venteromedial nucleus of hypothalamus acts as satiety centre. Satiety is feeling

of fulfilment after food intake. Lesion of satiety centre leads to increased food
intake, i.e., hyperphagia. Obesity caused due to lesion to venteromedial nucleus
of hypothalamus is called hypothalamic obesity. Stimulation of satiety centre
causes sensation of food intake and therefore reduces the food intake by animal.
Recent studies have shown that venteromedial nucleus responds to the changes
in caloric intake.
2. Feeding centre

Lateral hypothalamic nucleus is referred to as feeding centre. It is located in the

bed nucleus of medial forebrain bundle at its junction with pallidohypothalamic
fibres. Lesion of lateral hypothalamic nucleus induces loss of appetite and
aphagia. On stimulation of lateral hypothalamic nucleus, there is increased food
intake in animals and thus leads to obesity.

Feeding centre is tonically active. Activity of feeding centre is inhibited by

activity of satiety centre. Feeding behaviour is also modulated by certain sensory
cues like olfaction and taste. Signals from these sensory modalities project to
amygdala, which in turn sends input to lateral hypothalamus and intensifies the
drive for food.

The feeding centre and satiety centre interact with each other and regulate the
food intake. Satiety centre decreases food intake by inhibiting tonically active
feeding centre. Hypothalamic feeding areas are modulated by the action of
neurotransmitters or hormones secreted from limbic area.

Mechanisms of regulation of food intake:

There are four hypotheses regarding the regulation of food intake.

1. Glucostatic theory
3. Gut peptide theory

1. Glucostatic theory
2. Lipostatic theory 4. Thermostatic theory

According to glucostatic theory the activity of satiety centre is regulated by the

utilisation of glucose by the cells within the satiety centre. Since these cells
sense and respond to the level the glucose in the blood, they are named as
glucoreceptors or glucostats.

When the glucose supply to the glucoreceptors is inadequate and when the
arteriovenous blood glucose difference is low, the activity of the cells decrease.
This leads to less inhibition of feeding centre and individual is hungry.

Inadequate glucose supply to the glucoreceptors of satiety centre

Decreased activity of satiety centre
Decreased inhibition of feeding centre
Glucostatic theory explains polyphagia in diabetes mellitus. In diabetes mellitus,
blood glucose level is high but there is inadequate utilisation of glucose by
glucoreceptors due to deficiency of insulin. The glucoreceptors require insulin
for the utilisation of glucose. This leads to decreased activity of satiety centre
leading to polyphagia. Glucostatic theory of feeding regulation is also explained
by the fact that hypoglycemeia is an appetite stimulant and it reduces utilisation
of glucose by glucoreceptors.

2. Lipostatic theory

Lipostatic theory provides explanation for long term regulation of food intake.
Evidence suggests that neurons of feeding centre respond to the levels of fatty
acids and amino acids. Signals from body's fat stores to the brain modulate
eating behaviour so that the body maintains particular weight.

A protein hormone produced by adipocytes interacts with venteromedial

hypothalamus. This protein hormone is called Leptin (Greek word, means thin).
Leptin contains 167 amino acids. It is a product of fat metabolism. Leptin binds
with leptin receptors present in arcuate nucleus of hypothalamus. It acts through
the secretion of Neuropeptide Y and thus reduces the food intake and increases
the energy consumption. Apart from hypothalamus, leptin receptors are found in
peripheral tissues like brown adipose tissue. Leptin is the key hormone to control
body weight and food intake; therefore, defective leptin receptors lead to obesity.
Leptin operates as a part of feedback loop by which body fat depots are
controlled.

Feeding of hunger
Increased food intake Increased activation of leptin receptors in hypothalamus

When there is adequate supply of glucose, the activity of cells satiety centre
increases. This leads to increased inhibition of feeding centre and the individual
feels satisfied.

Increased fat deposition

Increased leptin synthesis Increased plasma leptin

Adequate supply and utilisation of glucose by glucoreceptors

Increased activity of glucoreceptors of satiety centre
Increased inhibition of feeding centre
Sense of fulfilment (Satiety)
3. Gut peptide theory

Presence of food in gastrointestinal tract releases certain polypeptides and GIT

hormones like CCK, glucagon, GRP, somatostatin from the mucosa. These
hormones act on hypothalamic feeding centre and inhibit food intake. Gut
peptides provide short term control of food. Receptors for CCK are present in
brain and in peripheral tissues. CCK causes decreased intake of food.

4. Thermostatic theory

Fall in body temperature increases and rise in body temperature decreases food
intake. Therefore, fever due to any cause results in anorexia. However, there is
little evidence that body temperature is major regulator of food intake.

Hormonal regulation of food intake

Hypothalamus secrets hormones which increase the
food intake:
Neuropeptide Y
Orexin A and Orexin B
Ghrelin
Melanin concentrating hormone (MCH) Hypothalamic hormones which
decrease food intake: α-melanocyte stimulating hormone
Cocain and amphetamine regulated transcript (CART)
Corticotropin releasing hormone.
Neuropeptide Y
Neuropeptide Y is a polypeptide secreted by
hypothalamus. It contains 36 amino acids. NPY is mainly
secreted by the neurons of arcuate nucleus.These neurons
project into paraventricular nuclei. It stimulates the
hypothalamic feeding centre and thus increase the food
intake. NPY receptors are subdivided into five groups—Y1,
Y2, Y3, Y4 and Y5. Food intake is mainly mediated by Y5
receptor.
Interaction between NPY and Leptin
Increased food intake increases the fat store. When
fat store in increased, there is increased synthesis and
secretion of leptin by adipocytes. Leptin inhits the action of
Neuropeptide Y in a negative feedback pathway.
– Neuropeptide Y+ – +

Other neuropeptides and hormones

Hypothalamic+ – feeding
centre

Food intake
Fat stores
+– Leptin secretion

Orexin A and Orexin B: These polypeptides increase food intake. They are
secreted by the neurons lateral nucleus of hypothalamus.
Cerebral cortex Hypothalamus
Hunger centre
–
Blood glucose
–
Absorption
Satiety centre
Hunger
Eating
Digestion
Fig. 8.62
Regulation of food intake 4. Hypothalamus controls autonomic nervous
system

It acts as head ganglion of autonomic nervous system. By controlling autonomic

nervous system hypothalamus take part in the regulation of various visceral
functions.

5. Endocrine functions of hypothalamus

1. The hormones of the posterior pituitary- vasopressin and oxytocin are actually
synthesised in the hypothalamus. Hypothalamus controls the secretion of
posterior pituitary by direct nervous control.

2. Hypothalamus controls the secretion of hormones from anterior pituitary. It is

mediated through the secretion of releasing factors and inhibiting factors.

3. Hypothalamus controls the secretion of other endocrine glands like thyroid,

adrenal cortex and gonads.

6. Behavioural functions of the hypothalamus: Hypothalamus controls

emotional behaviour and sexual behaviour.

Role of hypothalamus in regulation of sleep-wake cycle

Hypothalamus plays an important role in sleep-wake cycle. First evidence for the
existence of sleep promoting area in hypothalamus was given by Von Economo
in 1930. He observed that patients of encephalitis lethargic had profound
insomnia. He published correlation between the insomnia and damage to anterior
hypothalamus in these patients. Later experiments revealed group of cells that
are concentrated in the ventrolateral preoptic area (VLPO) play major role in
sleep induction.

Sleep facilitatory centre

Venterolateral preoptic nucleus (VLPO) of hypothalamus acts as sleep
facilitatory centre.

Neurons of VLPO are active during REM and NREM sleep.

Neurotransmitters released by these neurons are GABA amd Galanin.
Inhibits the activity of neurons responsible for wakefulness.

Waking centre
Tuberomamillary neurons of posterior hypothalamus act as waking centre.
Increased activity of these neurons causes wakefulness.
These neurons inhibit the activity of VLPO neurons. Orexinergic neurons of
lateral hypothalamus facilitate the activity of neurons of posterior hypothalamus
and therefore stabilises sleep-wake cycle.
Fornix Anterior
commissure

Paraventricular Lateral nucleus hypothalamic area (orexin neurons)

Ventrolateral preoptic nucleus (VLPO)

Suprachiasmatic nucleus (SCN)

Tuber
cinereum Thalamus
Hypothalamic sulcus

Tubero
mammillary
nucleus (TMN)

Mammiliary body

THALAMUS

The diencephalon, the component of forebrain contains two major parts-

thalamus and hypothalamus. There are two thalami. Each thalamus is a large egg
shaped cluster of nuclei. It lies in the upper part of lateral wall of the third
ventricle of brain. It has anterior and posterior ends; and superior, inferior medial
and lateral surfaces.

Structure
(a) White matter: The external medullary lamina covers lateral surface.
The internal medullary lamina divides the thalamus into three parts—Anterior,
medial and lateral.

(b) Grey matter: It is divided to form several nuclei. They are divided into the
following groups.

1. Anterior nucleus—paleothalamus
2. Medial nucleus—paleothalamus
3. Lateral nucleus mass—neothalamus. It is divided into two groups:

(i) Ventral group of nuclei—ventral anterior, ventral lateral, ventral posterior,

medial and lateral geniculate bodies.
Optic
chiasm
 Fig. 8.62a
Ventral anterior

Ventral lateral Internal medullary lamina

Anterior

Reticular Lateral dorsal Medial dorsal

Ventral posterior Ventral lateral Lateral dorsal
Midline Midline
Lateral posterior
Pulvinar

(ii) Dorsal group of nuclei—pulvinar, lateral posterior and lateral dorsal nuclei.
A mass of grey matter called massa intermedia connects two thalami at three
anterior part.

Connections of thalamus
A. Sensory inputs or afferents:
Intralaminar nuclei

1. Extrinsic nuclei:
These are cortical relay nuclei. They receive afferents from extra thalamic
sources.
Ventral posterior lateral

Centromedian Ventral posterior

medial

Fig. 8.63
Nuclei of thalamus (a) Superior aspect (b) Coronal section

(a) Posterior ventral nucleus: This receives sensory inputs from tract of Goll,
tract of Burdach, trigeminal nerve, so receives sensory inputs of touch pressure,
temperature, vibration, taste etc.

(b) Lateroventral nuclei: Receives dentatothalamic fibres from cerebellum

carrying proprioceptive information.

(c) Anterior nuclei: It receives mammilothalamic tract which carries impulses

relayed in mammilary bodies from the hippocampus.

(d) Medial geniculate bodies receive auditory impulses from cochlear nuclei.
(e) Lateral geniculate bodies receive visual impulses.
2. Intrinsic nuclei:
These nuclei receive impulses from other structures
of thalamus.
3. Intralaminar nucleus which is situated within the
median nuclear mass receives impulses from
reticular activating system.
4. From Cerebral cortex:
(i) Anterior group of nucleus—from cingulate gyrus of cerebral cortex.
(ii) Medial group—from prefrontal area of frontal cortex.

Efferent connections—outputs
1. Specific thalamo cortical projection: From the cortical relay nuclei or
extrinsic nuclei efferent fibres arise and terminate at specific areas of sensory
cortex. Thalamo cortical projection fibres.

2. From the reticular nucleus efferent fibres proceed to terminate all over
cerebral cortex. These are nonspecific thalamo cortical projection fibres.

3. Thalamus to hypothalamus.
4. Thalamus to corpustriatum.
Functions of thalamus
1. Thalamus is a great sensory relay station and integrating centre for most
inputs before relaying them to the cerebral cortex, for example: (i) Relay station
in the pathway of somesthetic sensations usually from the opposite half of the
body.
(ii) Relay station for the impulses coming from opposite cerebellum on their way
to the motor cortex.
(iii) Relay station for the auditory and visual pathways.
(iv) Relay station for autonomic and emotional reactions due to its connections
with the hypothalamus and limbic lobe.
(v) Relay station in the inhibitory closed circuit between the basal ganglia and
cortical motor area.
2. It is responsible for maintaining conscious and altering responses of RAS.
3. It is responsible for sub cortical perception of sensation-organ for sensation.
4. It is an integrating centre for sleep.
5. It is concerned with recent memory and emotion. 6. It is concerned with
language and speech function. Integration between different cortical parts by
subcortical connections, the thalamus helps to achieve speech.
7. It is concerned with control over muscular movement via its various
connections with the basal ganglia cerebellum and motor cortex.
Thalamic syndrome or Dysfunctions of thalamus It is a nervous disorder
resulting from lesion of thalamus.

Degerine—Roussy Syndrome
Cause: Thrombosis of feeding artery to thalamus. The thalamogeniculate branch
of posterior cerebral artery is blocked due to thrombosis.
Signs and Symptoms

1. Disturbance in sensations—loss of light touch, touch localisation and

discrimination. Anesthesia.

2. Loss of appreciation of small movements of joints.

3. Severe spontaneous pain. This due to overactivity of medial mass nuclei of
thalamus which escapes the lesion.
4. Profound muscular weakness, decreased muscle tone, ataxia and tremor.
Tremor is usually intentional tremor due to damage of cerebellothalamic cortical
path.
5. Altered emotional effects-exaggerated pleasant and unpleasant feelings.
6. Ataxia. Incoordination of voluntary movements due to loss of kinesthetic
sensation. This is a type of sensory ataxia.
7. Astereognosy—Inability to recognise an object by touch. It is due to the loss
of tactile and kinesthetic sensations.
8. Intension tremor. Tremor of hands and fingers develop while attempting to do
voluntary act.

BASAL GANGLIA

A group of deep sub-cortical nuclei located at the base of fore brain and upper
part of brain stem. It is a primitive motor cortex.
It is an important part of motor system.

Peculiarity of basal ganglia

Basal ganglia do not receive inputs directly from the spinal cord.

Basal ganglia do not project to brain stem motor areas.

They receive inputs from cerebral cortex. They project to cerebral cortex via
thalamus. Through cortical connection basal ganglia project to brain stem areas
Influence extra pyramidal system.
Mostly concerned with control of posture and equilibrium.
Cerebral cortex
Putamen + Globus Pallidus = Lenticular Nucleus. 4. Substantia Nigra Pars
compacta

Pars reticulata 5. Subthalamic nucleus.

Red Nucleus is functionally associated with basal

ganglia.

Connections of basal ganglia

Afferent connections—inputs
No direct sensory input from spinal cord Inputs are mainly from cerebral cortex
Thalamus, dorsal raphe nucleus and
Pedunculo-pontine nucleus
Most afferent input enters through striatum Most of them are cholinergic.

Important Inputs to Basal Ganglia 1. Corticostriate projections Motor cortex

Sensory cortex

2. Thalamostriate projection Thalamus

3. Raphestriate projection Dorsal raphe nucleus
4. Pedunculostriate projection Pedunculopontine nucleus
– Caudate nucleus
– Putamen

– Striatum
– Striatum
– Striatum
Caudate nucleus
Putamen
Globus pallidus Thalamus
Superior
colliculus
Subthalamic nucleus

Pedunculo pontine nucleus

Putamen
Cerebral
cortex
Caudate nucleus Thalamus
Substantia nigra Nucleus

raphe
magnus Globus pallicus

Fig. 8.64 Organisation of basal ganglia Physiological Anatomy

Basal ganglia includes structures like

1. Caudate Nucleus—Corpus striatum

2. Putamen—Neostriatum
3. Globus pallidus (Paleostriatum) External segment
Internal segment
Subthalamic nucleus
Substantia nigra
Nucleus raphe magnus
Fig. 8.65
Major afferents or inputs to basal ganglia

1. From the motor area of cerebral cortex fibres arise mostly from small
pyramidal shaped neurons at the layer V. Cortical input to caudate nucleus and
putamen are mostly excitatory in nature and the neurotransmitter is glutamate.

2. The thalamo striate projections mainly arise from intralaminar nuclei of

thalamus these fibres topographically project on to the caudate nucleus as well as
putamen. They are also excitatory in nature.

3. Raphe striate projections arise from dorsal raphe nucleus send fibres
extensively to caudate nucleus and potamen. Serotonin is the neurotransmitter.

Efferent connections —Outputs.

Mainly from Globus pallidus.
Globus pallidus—Thalamic fasciculus— Thalamus.

From Thalamus—Prefrontal and premotor cortex.

Globus pallidus to Thalamus—Inhibitory— GABA.

Thalamus—Cerebral cortex—Excitatory—Ach.

An efferent connection of basal ganglia is mostly from internal segment of

globus pallidus and also from substantia nigra. The globus pallidus and
substantia nigra give rise two separate pathways ansa leuticularis and fasciculus
lenticularis. These two groups join to form the fasciculus thalamicus. These
fibres to pographically terminate at ventrolatoral and ventroanterior nuclei of
thalamus. These projections are inhibitory in nature and GABA is the
neurotransmitter. From the thalamus fibres arise and terminate at motor cortexes
which are excitatory.

This establishes an important motor loop. Connections within Basal Ganglia:

Intenuclear connections.
Pedunculo pontine nucleus
Cerebral
cortex
Caudate nucleus
Thalamus
Cerebral cortex Putamen Subthalamic nucleus Caudate nucleus

Pedunculo pontine nucleus

Thalamus

Putamen Subthalamic nucleus

Superior colliculus
Globus pallidus Substantia nigra

Nucleus raphe
magnus

Fig. 8.66
Major efferent connections of basal ganglia— output

Motor loop or Feedback circuit.

Cerebral cortex striatum Globus pallidus Thalamus Cerebral cortex.

Function: Inhibits excessive activity of motor cortex. Other Efferent

connections.
Via Ansa lenticularis tract to

Subthalamic Nucleus
Substantia Nigra
Red nucleus of midbrain
Reticular formation of brain stem.

Basal ganglia to – Habenula

– Superior colliculus.
Substantia nigra Globus pallidus

Nucleus raphe
magnus

Fig. 8.67
Connections with the nuclei of basal ganglia 1. Nigrostrial projection—Pars
compacta of substantia Nigra to Caudate Nucleus.

Neostriatum—Dopamine. Inhibitor NT. 2. Striato nigral projection—

Striatum to Substantia nigra – GABA – Inhibitory
NT.
Huntingtons disease.
3. Subthalamic nucleus – Globus pallidus.
Excitatory – Glutamate.
4. Subthalamic Nucleus – Substantia Nigra. Functions of basal ganglia
1. Acts as a primitive motor cortex.
2. Role in cognitive functions.
Caudate nucleus connected to Neo-cortex.
Learning of motor skills.

Control of voluntary motor activity: basal ganglia control the voluntary

movements which are initiated by the motor cortex.
Glutamate neuron
Corticospinal tract

GABA Thalamus
Striatum Gaba nergic
Globus pallidus
Cholinergic neuron Substantia nigra

Dopaminergic neuron Fig. 8.68 Neurotransmitters of basal ganglial circuit Such as:

Cognitive control of motor activity.

Planning and programming of motor activities. Prevents oscillation and after
discharge in motor systems—makes the movements smooth. Timing and scaling
of intensity of movements. Timing—how rapidly movements should be
performed.
Scaling—how large the movements should be. Subconscious execution of
some movements during the performance of trained motor activities i.e., skilled
activities.
Controls associated movements.
Swinging of arm while walking.
Crude movements of facial expression during emotions.
Movements of limbs while swimming.
Neostriatum regulates the subconscious gross movements occuring in groups of
muscles. Globus pallidus provides appropriate muscle tone for skilled
movements—Muscle spindle and the gamma motor neurons of spinal cord are
controlled by basal ganglia.
Pathway—projections from cortical inhibitory area —striatum—Pallidum—
substantia nigra—reticular formation—spinal cord.
Controls and coordinates reflex muscular activity – The basal ganglia exert
inhibitory effect on spinal reflexes and regulate activity of muscles which
maintain posture.

Visual and labyrinthine reflexes are also important.

The co-ordination and integration of impulses for these activity depend upon on
basal ganglia.
Helps to control posture and equilibrium. Role in arousal mechanism—Globus
pallidus and red nucleus are involved in arousal mechanism because of their
connections with reticular formation.

Disorders of Basal Ganglia

Parkinson’s Disease—Paralysis Agitans Chorea
Ballism
Athetosis
Willson’s disease

Parkinsonism, Paralysis Agitans, Shaking palsy. James Parkinson

Definition: It is a nervous disorders resulting from degeneration of nigrostriatal

dopaminirgic neurons.

Causes: Degeneration of substantia nigra, or globus pallidus or both—

Dopamine reduction.
1. Idiopathic—causes unknown
2. Infection complications of encephalitis.
3. Senile degeneration.
4. Drug induced degeneration, e.g., Phenothiazine.
5. Accumulation of Methyl Phenyl—Pyridinium (MPP).
Formed from Methyl phenyl – tetra hydro pyridinium by the action of Mono
Amino Oxidase – B.

Clinical features of Parkinsonism

Both hypokinetic and Hyper kinetic features
Hypokinetic symptoms
1. Akinesia – Difficulty in initiating movements. 2. Brady kinesia – Sluggish
movements.
3. Loss of associated movements.
4. Expression Less face – Mask like face. 5. Slow monotonous speech
Hyper-kinetic symptoms
Rigidity—Motor neuron discharge is increased in both agonist and antagonist
muscles – Limbs offer resistance to passive bending – Lead pipe rigidity.
or Cogwheel rigidity – serious of catches.
Tremor—Coarse tremors of head and hand. Static or Resting tremor –
Disappears during activity. Pill-rolling movement
Gait—Festinant gait—Shuffling gait.
Bent forward, quick jerky short steps as if trying to
catch centre of gravity.
Treatment
1. L – DOPA.
2. Anticholinergic—to establish acetylecholine— Dopamine ratio.
3. Deprenyl: Inhibits mono amino oxidase—B. —Prevents formation of MPP.
4. Implantation of foetal basal ganglia—Tissue transplant.
5. Transplantation of Glomus Cells.

Wilson’s Disease or progressive

Haepatolenticular degeneration
Cause

1. Copper poisoning
2. Decrease in ceruloplasmin.
Copper produce severe degeneration of lentiform nucleus and liver.
1. Muscular rigidity
2. Tremor.
3. Cirrhosis of liver
4. Mental disturbances.
Chorea
Chorea = Dance
Chorea = Nervous disorder

Definition: It is defined as rapid involuntary dancing movements.

Cause: Lesion of Caudate nucleus, Interruption of inhibitory control.
Features:

1. Rapid, irregular involuntary movements of short duration.

2. Decreased muscle tone.
3. In coordination of voluntary movements.
4. Distortion of face during speech.
5. Irregular gestures.

Types of Chorea
Child type
St. Vitus Dance
Cause—Rheumatic Fever

Huntington’s disease

Adult type
Huntington’s Disease Autosomal dominant genetic disorder

It is an autosomal dominant inherited disorder. Gene is situated at autosomal

chromosome 4. Cause: Degeneration of GABAnergic striatonigral pathway.
GABAnergic and cholinorgic neurons are lost in striatum.
Age of onset – 30 – 50 years. Progressive disease leading to death.

Features:
1. Chorea
2. Dementia
3. Slurring speech.
Ballism and Hemiballism
Definition: Ballism is defined as sudden involuntary intense and violent
movements;
Cause: Lesion of subthalamic nucleus.

Hemiballism: Seen in one side only. Haemoragic lesion on opposite side.

Athetosis
Defined as continuous but slow writing
Movements – one phase of movement get merged with

the next.
Cause: Damage of striatum.

RETICULAR FORMATION

The term reticular formation is used for those parts of the brain stem (the
medulla, pons and midbrain) which are characterised by interlacing network of
fibre bundles. It is composed of more than 50 nuclear masses, which together
constitute the reticular nucleus and scattered throughout the central part of the
brain stem.

1. It is the one part of the brain which is absolutely essential for life because:

(i) Some reticular formation neurons are clustered together, forming centres of
the brain stem nuclei and integrating centres. These include the cardio-vascular,
respiratory, swallowing and vomiting centres; (ii) It receives and integrates
information from

all regions in the CNS; and

(iii) Its neurons send axons to most regions of the
brain and spinal cord, which indicates the very
large influence the reticular formation has
over the other parts of the CNS.
2. The pathways that convey information from the reticular formation are
divided into two systems: ascending and descending reticular systems. (i) The
ascending reticular pathway is also called
reticular activating system (RAS)
(a) It is a complex polysynaptic pathway which extends from the lower pons to
the level of the thalamus.
(b) RAS throughout its course receives afferent collaterals from:
(i) the long somatic sensory pathways; (ii) the trigeminal, olfactory, auditory, and
visual pathways; and (iii) Visceral pathways.
(c) From RAS fibres are widely distributed to all parts of the cerebral cortex.
The reticular fibres that descend to the spinal cord from the reticulospinal tracts
they influence activity in both the efferent and afferent neurons.
Functions:
(i) The RAS and related reticular components are concerned with conscious alert
state that make perception possible.
(ii) There is a major input from the antero-lateral systems into the midbrain
reticular formation which activates the cortex in the alert state. (iii) The
descending fibres in it:
(a) Inhibit transmission in sensory pathways in the spinal cord and
(b) Are concerned with spasticity and adjustment of stretch reflexes that control
body movement and posture.
(iv) It contains many of the areas concerned with regulation of heart rate, BP and
respiration.
Radiations to cortex
Visual impulses
Auditory impulses Projection to spinal cord
Ascending
sensory tracts
Fig. 8.69 Reticular activating system

CEREBRAL CORTEX
Cerebral Cortex—Cerebrum

Cerebral cortex is the highest centre of human brain and it is concerned with
higher functions of nervous system. It is also called palllidum. As evolution
progresses the mass of cerebral cortex, which is considered as thinking cap,
increases and limbic system which is considered as emotional brain shrinks. The
grey matter with cell bodies is arranged outside and white fibre are arranged into
two hemispheres – right and left by a deep vertical fissure. The separation is
almost complete interiorly and posteriorly. But at the middle the two
hemispheres are connected each other by the broad band of fibres called corpus
callosum. The average thickness of cerebral cortex is about 2 to 4mm. The
cerebral cortex is highly convoluted structure consisting of many elevations or
ridges known as gyri and depressions known as sulci. This involutions provide a
great surface area for the cortex up to 2.2 sq.m. (more than the surface area of
total body).

Structurally cerebral cortex is divided into three types

1. Isocortex-Neocortex: Most evolved type. It consists of six layers of cells.

2. Mesocortex-Paleocortex: Evolutionary in between neocortex and allocortex.
It consists of four to five layers.
3. Allocortex- Archicortex: Most primitive cortex . It may have only three
layers. This includes uncus, hippocampus and dentat gyrus.

Cytoarchitecture of cerebral cortex- layers of cerebral cortex. The neo cortex

consists of six layers. From superficial to deep they are:

1. Molecular or flexiform layer.

2. Outer/external granular layer.
3. Outer/external pyramidal layer.
4. Inner granular layer.
5. Inner pyramidal layer.
6. Fusiform layer or polymorphic layer.
All the six layers are not uniform everywhere in cerebral cortex.
At the motor cortex area 4 internal granular layer is

very thin. In the visual cortex pyramidal cell layer is thin but granular cell layer
is predominant.

The important types of cells found in the cerebral cortex are:

1. Pyramidal cells both large and small.
2. Stellate cells or granule cells.
3. Multipolar cells or cells of Martinotti .
4. Horizondal cells of Cajal.

Lobes of cerebral cortex

Each cerebral hemisphere is divided into four lobes due to three deep fishers or
sulci.

1. Frontal lobe: Lies in front of central sulcus or sulcus of Rolandic Central

sulcus lies in between frontal and parietal lobe.

2. Parietal lobe: Lies in between central sulcus and parieto- occipital sulcus.
Parieto occipital sulcus lies in between parietal and occipital lobe.
Prefrontal areaPrecentral area
9, 10, 11, 12
4, 6, 8, 44 Central sulus
Broca's Frontal area lobe Layers
1

Molecular layer or
plexiform 2 layer

External granular layer

External 3
pyramidal layer
Internal 4 granular layer
5
Internal pyramidal layer
Fusiform layer 6
or polymorphic layer

Fig. 8.70
Cytoarchitecture of cerebral cortex

3. Temporal lobe: Lies below the Sylvion sulcus or lateral sulcus. Sylvian
fissure lies in between parietal and temporal lobes.

4. Occipital lobe: Lies behind the parieto- occipital sulcus.

Primary sensory area 3, 1, 2 Parietal lobe Association area 5, 7

Occipital lobe
Primary sensory area 17 Association area 18, 19

Occipital eyefield 19
Temporal lobe
Primary
auditory area Auditory40, 41 association area 20, 21 22 Wernicke's area

Fig. 8.71
Lobes of cerebral cortex

Each cerebral hemisphere is extensively mapped and given specific numbers by

Brodmann. These numbers ranging from 1 to 47 are known as area numbers or
Brodmann’s numbers.

Connections of cerebral cortex

Major cortical afferents:
1. Specific thalamo- cortical fibres
2. Non-specific thalamo- cortical fibres
3. Association fibres- inter connection between various lobes
4. Commissural fibres- connecting one hemisphere with other.
Major cortical efferents
1. Pyramidal tract fibres mostly to spinal cord. 2. To various parts of cerebral
cortex itself.
Motor Somatic sensory

Planing complex movements elaboration of thoughts Spatial coordinates of body and surroundings

Vision
Word information Broca s area
¢
Language comprehension intelligence
Wernicke’s areas
Auditory

Fig. 8.72
Functional areas in cerebral cortex
Premotor area Primary motor area

Frontal eye field (area 8)

Motor
speech
area of
broco
(area 44)

(area 6) (area 4) Central sulcus (Rolanlic) Primary somesthetic area (area 1, 2, 3)

(area 19) Angular gyrus

Primary motorPremotor

Primary somestheticarea area area

area 9 Cingulate gyrusarea 10

area
19 area 12 Secondary somesthetic

area

Secondary auditory area (area 22)

Primary auditory area (area 41, 42) Wernicke'sLateral area

(sylvion

sulcus) Secondary visual area

(area 18) area 11

Primary
visual area (area 17) Secondary
visual area

(area 18) Primary visual area (area 17)

Supramarginal gyrus

Fig. 8.73 Functional areas of cerebral cortex Frontal lobe It is divided into two
areas:

1. Precentral area and 2. Prefrontal area

The precentral area includes following area numbers—area numbers 4,6,8,44.

In the area number 4 there are large pyramidal shaped neurons knows as ‘Betz
cells’. These neurons contribute to the large myelintaed fibres of pyramidal tract.
The motor impulses generated in this area are responsible for controlling and
coordinating all the voluntary movements.

Area 6: It is also called premotor area. It generates motor impulses. It controls

the movements of lips, tongue and muscles of head and neck. This area also
controls the skilled movement of fingers and associated movements.

Area 8: It is also a motor area. The motor impulses generated in this area
controls the conjugated movements of the eyeball.

Area 44: It is a motor area. This area is also known as motor area for speech or
Broca’s area for speech. This area generates motor impulses. It is responsible
for production of words used in speech. Lesion of the Broca’s area produce
‘Motor Aphasia’ – can produce noise but no meaningful words.

Prefrontal area

This area includes following areas 9,10,11,12. These areas are considered as seat
of intelligence. It is concerned with the personality of the individual, thinking,
reasoning, planning. Controls social and moral sense.

Parietal lobe

It is a sensory cortex. It is concerned with general sensations like touch, pain,

pressure, cold, warmth etc. This area is also called somato sensory area. It is
divided into 2 areas.

1. Primary sensory area

2. Association area
Primary sensory area: This are includes following area numbers 3,1,2. These
areas receive impulses of general sensations and it is concerned with sensation of
touch, pain, pressure, temperature, cold, stretch, vibration etc. Association area:
This area includes area numbers 5,7. These areas are concerned with analysing,
interpretation and

integration of general sensation. So it is concerned with perception of general

senses.
Temporal lobe
It is also a sensory cortex. It is divided into primary sensory area and association
area.

Primary sensory area includes the area numbers-41, 42. These areas receive
auditory impulses. So they are responsible for sensation of hearing.

Association area includes area numbers 20,21,22. Area 22 is also called

Wernicke’s area. These areas are concerned with analysis, interpretation and
integration of auditory sensations. So it is also called audiopshychic area.
Perception of hearing.

Occipital lobe
It is the visual cortex for vision. It is also divided into 1. Primary sensory area
2. Association area.
Primary sensory area includes area number17. This
area receives visual impulses and is responsible for vision.

Association area includes area numbers 18 and 19. These areas are concerned
with analysis, interpretation and integration of visual impulses. It is known for
visual perception.

Dominant hemisphere

Though the two cerebral hemispheres are basically alike they have some
functional differences. One of the cerebral hemispheres show functional
dominance. That hemisphere is called as dominant hemisphere or categorical
hemisphere. The other hemisphere is representational hemisphere.

In about 90% of the right handed people left hemisphere in dominant. In the rest
10% of left handed persons, right hemisphere is dominant. However speech
centre is situated in the left hemisphere.

TABLE 8.17
Comparison between dominant and non-dominant hemispere
Sl.No. Categorical hemisphere or Dominant hemisphere Representational
hemisphere or Non-Dominant hemisphere

1. It is specialised with categorisation and symbolisation, i.e., for higher

functions of the nervous system and sequential- analysis processes.
It is specialised in the area of spatio-temporal relations such as with the
recognition of faces, identification of objects by their form.

2. Mostly concerned with language functions and speech. Mostly concerned with
musical skill. 3. Left side processes speech, language, time and sequence. Right
side processes patterns, creativity, spatial awareness, context.
4. It recognises letters, numbers, words. It recognises faces, places, objects. 5.
Deals with time. Deals with space. 6. Responsible for verbal expression and
language. Responsible for gestures, facial movements and body language.
7. Seat of reason. Seat of passion and dream.
Contd…
8. Its disorder or lesion produces:
(i) language disorders.
(ii) patients are disturbed about their disability and often depressed.

Its disorder or lesion produces:

(i) Astereognosis
(ii) Agnosia i.e., inability to recognise objects by a

particular sensory modality even though the sensory modality itself is intact
(This is generally seen with parietal lobe lesion).

(iii) Patients are unconcerned of their disability cheerful and have trouble
recognising emotions in other individuals.

Disorders of cerebral cortex

1. Frontal lobe syndrome
Cause: Lesion of frontal lobe
Symptoms
(a) Inability to perform two works at a time (b) Inability to follow the proper
sequence of work. (c) Lack of initiative
(d) Anosmia
(e) Impairment of moral sense
(f) Impairment of social sense
(g) Failure to realise the gravity of situation.

6. Dyslexia—Word blindness
Person may be able to see words, but not able to interpret their meanings.

Cause: Lesion of angular gyrus lying behind Wernicke’s area, but Wernicke’s
area is intact. Area 39 is damaged.

7. Acalculia: A selective impairment in mathematical ability.

Cause: Lesion of frontoparietal cortex.

8. Global aphasia: Both Broca’s and Wernicke’s area
are damaged. Person cannot comprehend words,
cannot speak or write.

2. Agnosia: Means inability to recognise the Alzheimer’s disease

important sensory impression. It is characterised by progressive loss of short
term memory Cause: Lesion in the representational hemiphere. followed by
general lose of cognitive functions in middle Symptoms age leading to death.
(a) Astereognosis A similar loss of memory in old age is known as senile
(b) Loss of two point discrimination
dementia of the Alzheimer type. About 60% of senile dementia belongs to this
type.
(c) Inability to recognise objects
It is a dangerous condition and these people need round
(d) Lack of perception of his own body parts (body the clock attention.
image) resulting in neglect of affected parts of This disease is depending on the premature aging ofthe body
as if it does not exist. Unilateral the brain. It usually begins at mid adult life and
progressingunattention and neglect. rapidly to extreme loss of mental powers.
3. Prosopagnosia/Prosophenosia CausesInability to recognise faces, can recognise people 1. Loss of
cholinergic neurons and nerve fibres inby voice. cerebral cortex.Cause: Localised lesion of the
medial portion of 2. Severe loss of cholinergic neurons in the nucleusright temporal lobe- representational
hemisphere. basalis of mynert and related nucleus which projet
4. Aprasia: Impairment of ability to use correct into hippocampus, amygdala
and neo cortex.
sequence of movement or work. It can be speech 3. Decreased secretion of acetylcholine.aprasia. 4.

Deficiency of other neuro transmitters like5. Aphasia: Abnormalities in language function.

somatostatin and substance P.
Motor aphasia: Cannot speak words. Major causes for nerve degeneration Cause: Lesion
of Broca’s area. Nonfluent aphasia. 1. Decreased blood flow and metabolism in

superiorSensory aphasia: Cannot interpret the meaning of parietal cortex.

word heard–Word Deafness. 2. Atrophy of cerebral cortex and enlargement ofCause:

Lesion of Wernicke’s area. Fluent aphasia. ventricles.
3. Fibres called Alzheimer’s.
4. Formation of neuritic plaques which are rich in Beta-amyloid protein
surrounded by altered nerve fibres and activated glial cells.
5. Biochemically synthesis of acetylcholine is hampered.
Signs and symptoms
1. In the beginning, symptoms include loss of memory particularly recent
memory.
2. As the disease advances various psychiatric symptoms begin to appear.
3. Loss of thinking power.
4. Loss of speech.
5. Inability to recognise people.
6. Passing of urine and stool in bed.
7. Leading to death.
Treatment
1. No effective treatment. Acetylcholine administration improves to some extent.
2. Physostigmine, a drug that inhibit acetylcholine esterase and hence decreases
the breakdown of acetylcholine improves to some extent.
3. Nicotine—which stimulates cholinergic receptors may improve the situation.
4. Grafting of neurons.

Cerebral Palsy

The term cerebral palsy (CP) refers to a group of motor disorders resulting in
muscular incoordination and loss of muscle control. It is caused by damage to
the motor areas of the brain during foetal life, birth, or infancy in about 2 of
every 1000 children.

Causes
1. Infection of the mother by the German measles (rubella) virus during her first
3 months of pregnancy.

2. Radiation during foetal life.

3. Temporary lack of oxygen during birth and
4. Hydrocephalus during infancy. Cerebral palsy is not a progressive disease; it
does not worsen as time elapses. Once the damage is done, however it is
irreversible.
Paralysis is the total loss of voluntary motor function that results from damage
of nervous or muscle tissue. Paralysis may be classified as follows:
Monoplegia (mono = one; plege = stroke), paralysis of one limb only;

Diplegia (di = two), paralysis of both upper limbs or both lower limbs;

Hemiplegia (hemi = half), paralysis of upper limb, trunk, and lower limb on one
side of the body;
Quadriplegia (quad = four), paralysis of all the four limbs.
Paraplegia—paralysis of lower part of body.

EPILEPSY

Epilepsy is the second common neurological disorder. Occurrence 1% of

population. It is characterised by short, recurrent periodic attacks of motor,
sensory and psychological malfunction. The attacks are called epileptic seizure.
It is initiated by abnormal non-synchronous electrical discharges perhaps
resulting from abnormal reverberating circuits.
Types: Depending upon causes.
Idiopathic Epilepsy – No definite cause for the disorder. Symtomatic epilepsy –
Caused due to tumor in the

brain, brain damage at birth, metabolic disturbances like hypoxia, ureamia,

infections like encephalitis or meningitis, vascular disturbances like haemorhage,
hypertension.

Depending upon EEG pattern-epilepsy is of two types i.e., grandmal and

petitmal.

TABLE 8.18
Comparison between grandmal and petitmal
Sl.No. Grandmal Petitmal 1. Loss of consciousness Brief loss of
responsiveness 2. Tonic spasm, clonic jerks
Not much
3. Convulsions Not much 4. High voltage waves in

EEG
Low voltage waves.

Epileptic seisure can be eliminated or alleviated by drugs that depress neuronal

excitability, e.g., Valproic acid.
Limbic System

It is an area of brain that includes both gray and white matter. It is formed by an
interconnected group of brain structures. This includes portions of frontal and
temporal lobes, thalamus, and hypothalamus as well as the pathway that connect
them.

TABLE 8.19
Important structures of limbic system Feelings direct behaviour = INSTINT
BEHAVIOUR. S.No. The cortical Structures The Subcortical Structures

1. Cingulate Gyrus
2. Restrosplenial Cortex Amygdale Hippocampus

Emotion— 1. Cognition
2. Affect
3. Conation Expression—Motor
3. Parahippocampal Cortex Fornix 4. Insular Cortex Septal Nuclei 5. Orbital
surfaces of the

Fronatal Lobes
Anterior Nucleus the of Thalamus

6. Subcallosal cortex Hypothalamus

Connections of limbic system Limbic system is a connection between Brain

Stem and Neocortex.

Papez Circuit: Cortex to limbic system – Influence of thoughts on emotions,

limbic system to cortex explains how emotions reach consciousness.
Cingulate gyrus
Concerned with Olfaction
Functions of Limbic System
Anterior nuclei of thalamus Hippocampus (Fimbria)
Mammillary body
Fig. 8.74
Papez circuit

Medial forebrain bundle—Efferent connections of Limbic structures to

Hypothalamus and from there to Reticular formation—Influencing autonomic
and endocrine activites.

Amygdala—To other regions of limbic system through Stria terminalis and

ventral amygdalofugal pathway.
Amygdala—Receive olfactory input.
Amygdala and Hippocampus—Asscoiation cortex. Subiculum—Reciprocal
connections between Hippocampus and Neocortex.

Functions of Limbic System (summary)

Generating emotions
Adds feeling to sensory experiences
Somatic Visceral

Affective Function— Pleasant Unpleasant

Preservation of Self Hunger Thirst

Defence
Preservation of Species Learning and Memory Sensory

FEAR
RAGE
MOTIVATION

– Reward
– Punishment

– Feeding
– Drinking
– Protection
– Sexual Urge
– Higher intellectual functions

All functions of limbic system primarily arise from fundamental role in

generating emotions.

Limbic system adds feelings to sensory experiences. These feelings direct

behaviour.
Emotion is characterised by—
1. Cognition 2. Affect 3. Conation 4. Expression.

Cognition, affect, conation together taken as sensory aspect of emotion.

Expression is the motor aspect of emotion.
Affective function: Limbic system adds an affective or emotional component to
sensory experience. It helps us to interpret a sensory experience as pleasant or
unpleasant. The neo cortex translates a pleasant experience as reward and
unpleasant experience as punishment.
Expression of emotions:
1. Fear
2. Rage Natural protective responses

3. Motivation
Fear: This reaction is associated with autonomic responses such as sweating,
pupillary dilatation, change in heart rate. This response is also known as fleing
or avoidance reaction. Rage: It is fighting or attaching reaction. It is associated
with heart rate, rise ABP, adrenaline level teeth bitting etc.

A balance between rage and its opposite placidity (tameness and mildness) is
maintained.
Motivation: That ‘which moves the will’ it is a factor of most of the behaviours.

Preservation of self: Activities which aid preservation of self such as

(a) Hunger-feeding
(b) Thirst-drinking
(c) Defence
Limbic system creates sexual urge or drive and

execution of sex behaviour.

Learning and memory

Emotions and memory are closely linked. After having a pleasant or unpleasant
experiences, one would like to remember it so that pleasant experience can be
repeated and unpleasant experience can be avoided.
Cingulate gyrus

Portions of basal ganglia

Anti
nuclei of thalamus

Septum area
Subcallosal gyrus

Hippothalamus campus
Hypo Paraolfactory area
AmygdalaUncus
Parahippocampal gyrus

Fig. 8.75
The limbic system
Orbitofrontal cortex
Cerebral cortex
Internal stimuli Limbic system Stimuli external
Reticular Formation Hypothalamus and pituitary

Somatic
Nervous system
Functions

1. Emotion
2. Behaviour
1. Instinctual

1. Sexual
2. Feeding
3. Maternal
4. Social
5. Protective

2. Motivational Autonomic Nervous system Hormonal

Effects
Protection of self and Protection of species
1. Reward of punishment

Fig. 8.76
Mechanism and functions of the limbic system

Hippocampus is responsible for immediate memory and for selecting the

experience which need to be transferred to long term memory.

Temporal limbic cortex is responsible for memory of complex sequences.

Left temporal cortex seems to specialise in remembering verbal material.
Right temporal cortex- remembers other sensory inputs. Amygdala is concerned
with olfaction amydala.

Disorders of limbic system

1. Psychosomatic illness
Man generally has to refrain from physical violence, verbal violence. But
autonomic and endocrine manifestations such as rise in B.P. or gastric secretion
occur uninhibited. So negative emotion lasts longer and autonomic
manifestations are prolonged some may became permanent increase in B.P.
Hypertension.
2. Korsakoff’s Psychosis

Due to nutritional deficiency related to alcoholism. Lesions in mammillary body

and Medial Dorsal Nucleus of halamus.

Signs:
(a) Confusion (b) Confabulation (c) Memory Deficit

3. Kluver—Bucy syndrome
Damage of Anterior Temporal Cortex and Amygdala
Signs and symtoms
(a) Tendency to examine objects orally
(b) Loss of fear
(c) Decreased aggressiveness
(d) Tameness
(e) Changes in dietary habits
(f) Excessive sex drive.

Electro encephalo gram—EEG

Brain is made up of billions of neurons. These neurons generate impulses and

these impulses are transmitted in various directions. This produces continuous
electrical activities of the brain. The electrical activities of the brain spread to the
skull. The graphical record of electrical activities of the brain is known as
Electro Encephalo Gram or Berger Rhythm.

Electro encephalo gram is recorded from the scalp using a set of 16–30
electrodes. A human Electro Encephalo Gram shows 4 different types of waves.
They are
1. α Wave 2. β Wave
3. δ Delta Wave 4. θ Theta Wave
Brain waves are recordings of fluctuating electrical changes that occur in the brain
Alpha waves
Beta
waves
Theta waves
Delta waves
50 Vm
Fig. 8.77 Electro encephalo gram
TABLE 8.20
Different waves of EEG
Wave Frequency Amplitude α 8-13 Hz 50 micro volt β 14-30 Hz 5–10 micro
volt
may have a brief response after each flash of light, but the brain waves are
normal.

Significance of Electro encephalo gram

1. It is an important diagnostic tool for the diagnosis of epilepsy.
EEG can be used for the classification of Epilepsy into
(a) Grandmal (b) Petitmal.
2. EEG can be used for detecting and locating brain lesions.
3. It is useful for the diagnosis of brain tumors and metabolic degeneration of
brain.
4. It is very important in the diagnosis and prognosis of psychotic disorders.
5. It is an important tool in the neuro physiological research.

Abnormal EEG
The two sides of the brain show different patterns of electrical activity.

This may mean a problem in one area or side of the brain is present.
The EEG shows sudden bursts of electrical activity (spikes) or sudden slowing
of brain waves in the brain. These changes may be caused by a brain tumor,
infection, injury, stroke or epilepsy. When a person has epilepsy, the location and
exact pattern of the abnormal brain waves may help show what type of epilepsy
or seizures the person has.

Keep in mind that in many people with epilepsy, the EEG may appear
completely normal between seizures. An EEG by itself may not diagnose or rule
out epilepsy or a seizure problem.

θ 4-7 Hz 10 micro volt δ 0.5-3.5 Hz 20–200 micro volt

Normal EEG In adults who are awake, the EEG shows mostly alpha waves and
beta waves.
The two sides of the brain show similar patterns of electrical activity.
There are no abnormal bursts of electrical activity and no slow brain waves on
the EEG tracing. If flashing lights (photic stimulation) are used during the test,
one area of the brain (the occipital region)

CEREBRO SPINAL FLUID (CSF)

It is a specialised extracellular fluid present inside the ventricles of the brain,

central canal of the spinal cord and at the sub arachnoid space.

CSF is formed as a result of filtration and secretion. About 20 ml of CSF is

formed per hour, 500 ml/day. CSF is formed by structure known as choroid
plexus. Choroid plexus are finger like projections in the floor of the ventricles.
Most of the CSF is secreted by the choroid plexus of lateral ventricles.
CSF is also secreted by the choroid plexus of 3rd ventricle.
Space Choroid plexus
Superior Arachnoid sagittal sinusVillus
Foramen of monro
Third ventricle
Cerebral aqueduct

(Sylvius) Inferior hornFourth ventricle

of lateral Median ventricle aperture

Fig. 8.78
Formation and circulation of CSF Circulation

From the lateral ventricle CSF passes through foramen of Monro and enters into
the 3rd ventricle. From the 3rd ventricle CSF passes through Aquiduct of Sylvie
and enters into 4th ventricle. From the 4th ventricle CSF escapes out through
foramen of Magendie and Luschka to enter into central canal of the spinal cord
and sub-archnoid space.

Reabsorption

About 80 % of CSF reabsorbed by the archnoid villi into venous (dural) sinuses.
Remaining 20 % of CSF is reabsorbed by spinal villi into spinal veins.

Functions

1. It acts as a mechanical shock absorber and protects the brain from the effects
of mechanical injuries.
2. CSF provides buoyancy(upward thrust) to the brain. Because of this the
weight of the brain is not felt.
3. It takes part in the supply of nutritents to certain parts of the brain.
4. It takes part in the removal of waste products from certain parts of the brain.
5. It acts as a substitute for lymphatic system in central nervous system.
6. It acts as a part of blood—CSF - brain barrier.
7. It serves as a fluid buffer there by provides optimum environment to neurons.

COMPOSITION OF CSF
CSF
Water 99.1% Solids 0.9%

Organic Inorganic Glucose = 50-80 mg %

Proteins = 20-50 mg % Cations Anions Amino acids = 1.5-3 mg % Na+ = 330 mg % Cl– =
700 mg %Urea = 10-30 mg % K+ = 12 mg % HCO– = 50 mg %Uric acid 8
= 0.5-2.2 mg % Ca++ = 5.3 mg %PO –– = 1.8 mg %Creatinine = 0.5-2.2 mg% 4 Mg
++ = 3mg%SO ––
4
= 0.6 mg % Cholesterol = 0.06-0.22 mg %

Lactic acid = 8-25 mg%

Properties of CSF
Volume

pH
Specific gravity
Pressure
Daily secretion
Appearance

Hydrocephalus
: 150ml
: 7.4
: 1005
: 130-150 mm of water
: 500 ml per day
: Colourless, odourless, watery

fluid

It is a nervous disorder resulting from accumulation of cerebro spinal fluid. It

may be due to
1. Excess production of CSF
2. Block in the circulation of CSF
3. Decreased reabsorption of CSF.
When the reabsorption of CSF at arachnoid villi is defective execs CSF
accumulates both outside and inside CNS. It is known as communicating or
external hydrocephalus. When there is an obstruction at the exit of foramen of
Magendie and Luschka or at aqueduct of Sylvie, accumulation of CSF occurs
with in whole or part of CNS. It is known as non-communicating or internal
hydrocephalus.
Signs and symptoms

1. In children it may produce the enlargement of the skull.

2. It may increase intracranial pressure.
3. It may produce severe headache.
4. It may produce periodic breathing.

Treatment
Removal of accumulated CSF by lumbar puncture.
Lumbar puncture
It is a technique of collecting CSF from the central canal of
the spinal cord by inserting a needle of the syringe in between
3rd and 4th lumbar vertebra. Lumbar puncture serves the
following functions.
1. For collecting CSF for diagnostic purpose. The CSF collected can be used for
microscopic, microbiological or biochemical investigations. 2. To release
pressure. Removal of accumulated CSF reduce the intracranial pressure.
3. It releives pain.
4. To inject drugs or anesthetic agents.
Spinal cord
Dura matter
1
2 2 Filum
terminale
3 3 Supracristal plane
Needle
Hip
bone Hip bone
Fig. 8.79 Lumbar puncture
BLOOD BRAIN BARRIER

It was demonstrated that when acidic dyes such as Trypan Blue was injected into
living animals, all the tissues were stained except the brain. The failure of the
entry of the dye to the brain-blood brain barrier was postulated by Paul Ehlrich.

There are two barriers exist:

(1) Blood-CSF- Barrier, between blood and CSF. The blood CSF barrier exists at
the choroid plexus epithelium and CSF fluid interface.

(2) Blood Brain Barrier between blood and brain. It exists in the endothelium of
cerebral capillaries.
There is considerable variation in capillary permeability from organ to organ in
the body. Substances are not totally excluded from the brain. However exchange
across the cerebral vessels is so different from that in other capillary beds and
the rate of exchange of many physiologically important substances are very low.
Blood brain barrier exists in all parts of the brain except in some areas of
hypothalamus, pineal body and the area postrema where substances diffuse with
ease into the tissue spaces. These areas are outside the blood brain barrier. It is
very important because these areas of the brain have sensory receptors that
respond to different changes in the body fluids such as changes in osmolality,
glucose concentration etc. These responses provide signals for feedback
regulation of these factors. These areas are collectively called
Circumventricular Organs.
The blood CSF and Blood Brain Barrier are hightly permeable to water, carbon
dioxide, oxygen, lipid soluble substances like alcohol, anaesthetics- slightly
permeable to electrolytes like Na+, Cl–, K+ etc.
But impermeable to proteins, large organic molecules, urea, bile salts, acidic dye,
dopamine.

Development of blood brain barrier

The cerebral capillaries are much more permeable at birth than in adulthood. The
blood brain barrier develops during the early years of life. In severely jaundiced
infants, bile pigments penetrate into the nervous system and in the presence of
asphyxia damage the basal ganglia – Kernicterus. However in jaundiced adults
bile pigments can not penetrate the brain.
Functions of blood brain barrier
The blood brain barrier probably maintains the constancy of the environment of
the neurons in the CNS. These neurons are so dependent upon the concentration
of K+, Ca++, Mg++, H+ and other ions in the fluid bathing them that even minor
variations have far reaching consequences. Cortical neurons are more sensitive
to ionic changes so an additional defence had evolved in the form of blood brain
barrier to protect them.

Blood brain barrier helps to protect the brain from endogenous and exogenous
toxins in the blood.It prevents the escape of neurotransmitters into the general
circulation.

Clinical Significance
The physician should know the permeability of the blood brain barrier to drugs
inorder to treat diseases of the nervous system. For example, among the
antibiotics penicillin and chlortetracycline enter the brain to a very limited
degree. Sulphadiazine and erythromycin enter quite easily.

Treatment of Parkinsonism by L-Dopa instead of Dopamine.

Blood Brain Barrier tends to break down in areas of brain which are irradiated,
infected or site of tumors. The break down helps in identifying the location of
tumors, substances such as radioactive iodine labeled albumin penetrate and
enter the tumor tissue and make the tumor stand out as an island of radioactivity
in the surrounding brain area.

SLEEP
Wakefulness is a condition during which a person can have subjective
experience and does voluntary work.

Sleep is defined as a reversible state of physical and mental rest during which
voluntary movements and subjective experience are partially or totally absent.

It is also defined as a state of unconsciousness from which a person can be

aroused using sensory stimulus. Wakefulness and sleep are not mutually
exclusive phenomenon. But they overlap to some extent.

Types of Sleep
There are two types of sleep.

1. Slow wave sleep/Synchronised sleep or Non REM sleep.

2. REM sleep (Rapid Eye Movement) or Paradoxical sleep/ non synchronised
sleep.

Slow wave sleep

It is the sleep in which a person enters into in the beginning. Duration is about
30-90 minutes at a time.
Physiological changes

1. Decrease in metabolic rate.

2. Decrease in heart rate. Decrease in blood pressure.
3. Decrease in rate and depth of respiration and alveolar ventilation.
4. Decrease in sympathetic activities and increase in parasympathetic activities.
5. Change in the EEG pattern - more of slow waves delta waves.
6. Dream may be felt but not remembered.
TABLE 8.21
Classification of stages of sleep based on EEG pattern
Sl.No. EEG pattern Stage of sleep Level of sleep and wakefulness 1.
Prominantly α rhythm, fast wave 8–13 Hz 0 Wakeful and alert no sleep 2. α
rhythm 8–13 Hz fast wave I No alert, dozing about to enter into sleep 3. (a)
Spindless of waves (b) Θ rhythm 4–7 Hz II First phase of sleep
4. (a) δ rhythm 0.5–3.5 hg III Deep slow wave sleep (b) Θ rhythm 4–7 Hz 5. δ
rhythm 0.5–3.5 Hz IV Deep slow wave sleep

6. Mixed frequency, mostly α and β waves of high frequency

REM sleep
Paradoxical sleep Rapid movements of eye ball fast waves resembling
wakefulness but more deeper in sleep, arousal is more difficult dreaming.

REM sleep/Paradoxical sleep

This type of sleep may appear in an interval of about 90 minutes. This type of
sleep lasts for about 5–30 minutes at a time.

Physiological changes
1. Rapid movements of the eyeball—saccadic eye movements.

2. Arousal from this type of sleep is more difficult. 3. Dream is felt and
remembered.
4. HR and BP depend upon the nature of the dream. 5. Brain metabolism
increases.

6. EEG pattern is more similar to wakefulness condition but more deeper in

sleep. This is why this type of sleep is called paradoxical sleep.

7. EEG pattern is desynchronised.

TABLE 8.22
Comparison between slow wave sleep and REM sleep
Sl. No. Features or Characteristics Non REM sleep or slow wave sleep REM
sleep or Paradoxical sleep 1. Muscle tone Hypotonia More hypotonia 2. EEG
Pattern More of slow, high voltage delta waves Fast waves, low voltage β waves
3. Movements of eye balls No rapid movements of eye balls Rapid movements
of eye balls. 4. Dreams Cannot be recalled or poor recalling Clear recalling of
dreams 5. Duration More 30 monutes to 90 minutes in a
spell. 75% of total sleep
Less, 5 to 30 minutes in a spell. 25% of total sleep

6. Threshold for a arousal by sensory stimulus

Moderate Elevated, stronger strength of stimulus is needed for arousal. So called
paradoxical. 7. Pulse, heart and respiratory rate
Commonly increases and irregular Lowest and regular
8. Brain activity Less More 9. O2 consumption Less More 10. Pontogeniculo
occipital spikes
Not seen Present. These spikes originates from pontine reticular formation.
11. Important neurotransmitter Serotonin content at Raphae nucleus Nor
adrenaline content at locus of coerulens

Functions
1. Sleep gives physical and mental rest.
2. It helps in the relaxation of body and mind.
3. It helps in the conservation of energy.
4. It helps to keep the person engaged.
Sleep disorders
1. Somnambulism: (Sleep walking)—Sleep walking with eyes open and avoid
obstacles.
2. Narcolepsy—Sudden involuntary attack of sleep

during work. It is due to inability to inhibit REM sleep.

3. Insomnia—Difficulty in falling asleep and frequent awakening—due to
medical and psychiatric causes.

4. Hypersomnia—Excessively long or deep sleep from which a person can be

awakened only by vigorous stimulation. Causes, head injuries, stroke,
encephalitis.

5. Sleeping sickness—Suffers from insomnia during night and sleeps during day
–cause: infection by trypanosome gambiens.

SPEECH

Language is the faculty which enables to understand the spoken and printed
words and to express ideas in speech and writing.

Speech is composed of four mechanical aspects:

1. Respiration
2. Phonation
3. Resonation,
4. Articulation. Phonation is mostly achieved by the

larynx whereas articulation is achieved by the structures of mouth.

Phonation
Phonation is the process by which the vocal cords produce certain sounds
through quasi-periodic vibration.

The vibrating element is the vocal cords. The vocal cords protrude from the
lateral walls of the larynx toward the center of the glottis; they are stretched and
positioned by several specific muscles of the larynx itself. The muscles are
vocalis muscles and cricothyroid muscles.

The basic features of the laryngeal adjustments to the different phonatory

settings can be summarised as:
1. Abduction or adduction of the vocal cords;
2. Constriction of supraglottal structures; adjustment of length,
3. Stiffness and thickness of the vocal folds;
4. Elevation and lowering of the larynx.
Glottal states/Types of phonation: It depends upon whether the vocal folds are
vibrating or not. Segments with vocal fold are voiced, all others are voiceless.
The vowel sounds are produced by the vibration of vocal cords. The consonant
sound is produced by obstructing the air stream partially or completely. So that it
cannot pass freely from mouth. The vocal cords do not vibrate to produce
consonants.
There is more than one way the vocal folds can vibrate. There is more than one
way they can fail to vibrate.
Thyroid cartilage
Cricoid
cartilage Longitudinal tension Longitudinal tension

Medial
compression Medial
compression

Adductive tension
Adductive tension
Fig. 8.80 Mechanism of phonation
Anyteniod cartilage

Not vibrating
Glottal stop: The vocal folds are held together without vibrating. No air escapes
from the lungs. Open breathing. The vocal folds pulled as far apart as possible—
no sound. Voiceless: The vocal folds are too far apart to vibrate, but close
enough that they can cause some turbulence in the airstreams under the right
circumstances. (This is what “voiceless” usually means.). This produces
consonants. Whisper: Type of sound is produced by the approximating of
anterior 2/3rd of vocal cord and allowing free escape of air posterior in between
the two arytenoids cartilages.

Vibrating

Breathy voice (or murmur): The vocal cords are vibrating, but there is also a
significant amount of air escaping through the glottis, causing turbulence.

Creaky voice: In creak, only the front parts of the vocal folds are vibrating,
giving a very low frequency. (Try speaking at the lowest pitch you can. Then go
even lower).

Articulation

The aspects of pronunciation that’s involves bringing articulatory organs

together so as to shape the sounds of speech.

The three major organs of articulation are the lips, tongue, and soft palate. They
play a major role during speech and other vocalisations. The resonators include
the mouth, the nose and associated nasal sinuses, the pharynx, and even the chest
cavity. For instance, the function of the nasal resonators is demonstrated by the
change in voice quality when a person has a severe cold that blocks the air
passages to these resonators.

The act of articulation, which means the muscular movements of the mouth,
tongue, larynx, vocal cords, and so forth that are responsible for the intonations,
timing, and rapid changes in intensities of the sequential sounds. The facial and
laryngeal regions of the motor cortex activate these muscles, and the cerebellum,
basal ganglia, and sensory cortex all help to control the sequences and intensities
of muscle contractions, making liberal use of basal ganglial and cerebellar
feedback mechanisms.

Speech mechanism: Physiology of phonation

All sounds which come from the mouth and nose are the result of interruptions
and/or modifications of a stream of air moving from the lungs through:

Trachea, larynx, pharynx, oral cavity and nasal cavity.

Air stream provides energy for speech production. Any constrictions which
create obstacles to free movement of air through larynx and/or above larynx
create sound.

Phonation/laryngeal system
Occurs at laryngeal level.
Primary structure is larynx—structure of cartilage and muscles situated atop the
trachea.
Major structure of larynx is vocal folds/cords. Phonation results from rapid
opening and closing of space (glottis) between vocal folds.
Accomplished by vocal fold vibration.

How it works?
When air stream enters larynx, subglottic pressure builds up.
When pressure great enough, vocal folds are pushed apart.
Air flows through glottis.
Reduction of pressure pulls vocal folds back together.
Aerodynamic principle related to pressure changes called Bernouli effect.

Regulation of Speech
The process of speech involves two principal stages of mentation:

1. formation in the mind of thoughts to be expressed as well as choice of words

to be used and then
2. motor control of vocalisation and the actual act of vocalisation itself. The
formation of thoughts and even most choices of words are the function of
sensory association areas of the brain.
Wernicke’s area in the posterior part of the superior temporal gyrus that is most
important for this ability.

Types of speech
Speech are of two types:
1. Spoken speech 2. Written speech.
Spoken speech: It means to understand the spoken words and expressing ideas
in speech.

Mechanism
1. First, we must be able to hear sounds. Auditory pathways carry impulses from
ear to area 41 in temporal lobe.

2. Second, we must be able to understand them with the help of auditory psychic
area 20, 21.

3. Third, we must be able to express. It involves the activity of auditory speech

center, called Wernicke’s area-area 22. It is concerned with comprehension i.e.,
interpretation and understanding of auditory and visual informations.
Exner s area
¢
[Lesion produces difficulty in writing - agraphial] Dejerine area
[Lesion produces word blindness] (area 39)

¢ Broca s area (area 44) [Lesion produces motor

aphasia]¢Wernicke s area (area22) [Lesion produces word

deafness or sensory aphasial]

Fig. 8.81
Brain areas concerned with language functions Written speech: This means
understanding written words and expressing the ideas in writing.
Mechanism

1. First, we must be able to see the words. This involves transmission of visual
impulses from eyes to primary visual cortex area 17.

2. Second, written symbols must be correctly interpreted. This involves visual

psychic area – area 18, 19.

3. Third, we must be able to express the ideas in writing. This involves the
activity of visual speech center called Dejerine area-no.39. Wernicke’s and
Dejerine area are together called the Sensory Speech Centers.

Mechanism of expression of speech:

Expression of speech requires the skilled use of many muscles, such as muscles
of the lip, tongue, larynx, hand or fingers.
Motor speech centers include:
1. Broca’s area 2. Exner’s area

Broca’s area—No. 44 in dominant hemisphere

It processes the information received from Wernicke’s area into a detailed and
coordinated pattern for vocalisation. This pattern is then projected to the motor
cortex which initiates the appropriate movements of lips, tongue, and larynx to
produce speech.

Exner’s area—Motor writing centre

It is located in the middle frontal gyrus in the dominant hemisphere. It processes

the informations from Broca’s area into detailed and coordinated pattern which
then along with motor cortex initiates the appropriate movements of hands and
fingers to produce written speech.

Speech disorders
Aphasia—Abnormalities in language function.

Motor aphasia—cannot speak words- lesion of Broca’s area.

Sensory aphasia—cannot interpret the word, word deafness meaning of words
cannot be made –lesion of Wernicke’s area.
Dyslexia—Word blindness—Person cannot interpret the meaning of word seen
—lesion of angular gyrus area 39.
Global aphasia—Both sensory and motor aspects of speech are lost.
Dysarthria is a motor speech disorder. The muscles of the mouth, face, and
respiratory system may become weak, move slowly, or not move at all after a
stroke or other brain injury. The type and severity of dysarthria depend on which
area of the nervous system is affected.
The signs and symptoms of dysarthria depends on the extent and location of
damage to the nervous system: “Slurred” speech.
Speaking softly or barely able to whisper. Slow rate of speech.
Rapid rate of speech with a “mumbling” quality. Limited tongue, lip, and jaw
movement. Abnormal intonation (rhythm) when speaking. Changes in vocal
quality (“nasal” speech or sounding “stuffy”).
Hoarseness.
Drooling or poor control of saliva.

LEARNING AND MEMORY

Learning

Definition: It means gathering of experience or knowledge. It is defined as the

ability to alter the behaviour on the basis of experience. Memory is ability to
retain knowledge for future use.

Learning—the simplest form of learning is habituation. It happens at all levels of

nervous system. By this we learn to ignore not so important information.

Sensitisation: By this we become more receptive or sensitive to some sorts of

information.

These types of learning are called non-associative learning because these are not
associated with any other stimulus.

Associative learning: It is also known as conditioning. Here a stimulus is

associated with another, e.g., Pavlov’s experiment.

In operant conditioning the animal learns to repeat a behaviour which is

rewarding or learns to avoid a behaviour associated with punishment. Reward
and punishment help to reinforce the process of learning.

TABLE 8.23
Types of memory

Habit memory or Reflexive memory or implicit memory, Non declarative

memory Declarative memory or Explicit memory

The part of the memory which is recalled and used automatically or

unconsciously, can be used reflexly. For example, remembering the keys of
computer, driving skills.
This part of memory is recalled by conscious effort. For example,remembering a
definition.

Motivation and attention expedite the process of learning. Motivation itself

draws attention. For example, a motivated and attentive student can quickly
learn many things. Reward and punishment bring about motivation and attention
through positive and negative reinforcement. Learning shows quick extinction or
wear off if not repeated or if some external stimulus is applied.

Physiological basis of learning

Hypothesis

(a) New neuronal circuits develop, which were not present before.
(b) If path is already present, new synapse is developed.
(c) If synapse was already present it may get activated.
(d) For this new neurotransmitter is synthesised or new receptors are developed.
(e) Changes in dendritic areas making newer and newer contacts-especially
purkinje, and pyramidal cells.

Memory
Memory is the ability to store what is learned or
experienced and can be recalled when in need in future. According to
W.M.Rhyburn-“Memory is the power to
store our experiences and to bring them into the field of
consciousness some time after the experience have occurred”.
Declarative memory: It is of three types depending upon
the duration of storage of information.
1. Sensory memory
2. Primary memory(short term)
3. Secondary memory(long term)
1. Sensory memory/Ultra short memory
It means the ability to retain sensory signals in the
sensory cortex for a very short interval of time following
the sensory experience. These instantaneous sensory
information remains in the brain for a short time and it can

be used during the period. It can be scanned to pick up important point. It is the
initial stage of memory process. For example, remembering a telephone number
noted from the book. It can be replaced by new sensory signals. 2. Primary
memory-short term memory

This includes events of immediate past. The information is stored and recalled
up to a few minutes, hours or days. Here information can be recalled with ease
without much search. It is actually a period through which the memory is made
permanent or consolidated. One important point about memory storage is
everything of short term memory do not go into long term memory. There is a
automatic selection, e.g., some experience associated with strong emotional
reactions is remembered well, e.g., death of a close friend, jokes related to a
topic is remembered but not the topic.

3. Long term memory-Secondary memory, Permanent memory, Fixed

memory: Here information is stored for a very long time even for several years
and can be recalled at any later time. It is permanent and can not be erased.

Mechanism of memory storage

Possible mechanism for primary memory:
It requires neuronal mechanisms that can hold specific

information signals for a few seconds or a few minutes.

Mechanism
1. Reverberating circuit theory

It is suggested that sensory signals reaching the cerebral cortex can set up
reverberating oscillations in the local back and forth areas of cortex itself or even
between cortex and thalamus and or other sub cortical areas.

As the reverberating circuit fatigues or as new signals interfere with the

reverberation, the primary memory fades away.

2. Post-Tetanic potentiation theory of primary memory

When a neuron is stimulated again and again it may cause a short period of
synaptic fatigue, but later it may produce increased excitability of synapse for a
few hours. During this period if the synapse is stimulated again the synapse
responds more vigorously than normal. This phenomenon is known as “post
tetanic potentiation”. It is caused by excessive accumulation of calcium ions in
the pre synaptic terminals. Calcium in turn increases the release of
neurotransmitter. This acts as a basis of short term memory.

3. Pre synaptic facilitation and inhibition

These effects are long lasting and it can form a basis of short term memory.

Mechanism of long term/Secondary memory

Many theories
1. Anatomical changes in the synapse
(a) Number of pre synaptic terminals may increase. (b) Size of pre synaptic
terminals may increase. (c) Increase in the number of dendritic spines. (d)
Establishes newer and newer neuronal circuits and connections.
2. Physical or chemical changes at pre synaptic

terminals and post synaptic membrane: The dendritic spines of the neurons
contain golgi complexes. These may produce new proteins associated with
memory.

RNA and proteins together make the general processes occurring at the neuron
forming the basis of memory.
Types of memory depending upon its characteristics

1. Immediate memory: This is a type of memory wherein one remembers some

immediate situation for some particular purpose and forgets it as soon the
purpose is served.

2. Permanent memory: It is related to long-term memory. Even if one tries to

forget the information, it will not be forgotten. It is stored permanently.

3. Rote memory: It comprises of things learnt without logical understanding. It

is mainly seen in students when they memorise things without knowing their
meaning.

4. Logical memory: In it, things are understood logically and then stored in our
minds. This type of memory can last for a longer time.

5. Associative memory: Things are memorised with the help of associations. In

order to remember something, it is associated with some other thing known very
well.

6. Active memory: Here memorisation is done with active participation of the

person. One has to consciously take effort to remember something.

7. Passive memory: Certain things come to our memory spontaneously without

our conscious effort and such type of memory is called passive memory.

8. Flash-bulb memory: Flash-bulb memory is a memory centered around a

specific important or surprising event that is so vivid. It is as if it represents a
snapshot of the event.

Types of forgetting
Depending upon its nature and intensity, forgetting may be classified as follows:

1 . Natural forgetting: Occurs with the lapse of time in a quite normal way.
2. Morbid forgetting: Occurs when one deliberately tries to forget something.
3. General forgetting: Occurs when one suffers a total loss in one’s recalling of
previous learning.
4. Specific forgetting: Occurs when the individual forgets only one or other
specific part of his earlier learning.
5. Physical forgetting: Occurs when one looses his memory on account of
factors of age, diseases, biological malfunctioning of the brain and nervous
system, accidents etc.
6. Psychological forgetting: Occurs when factors like stress, anxiety, conflicts,
lack of interest, aversion, apathy or other emotional or psychological factors
results in forgetting.

Process of forgetting
1. Decay: An input to sensory information storage either decays rapidly or is
wiped out by the next input.
If the learned informations are left unused for a long time, in course of time, it
will get decayed as the casting iron rod when kept unused for a long time.

2. Interference: In this process, some other information interferes with learned

information and fades it away. It is of 2 types.
(a) Retroactive interference: In this an already

existing matter in the brain is interfered by a newly learned matter and it

suppresses the older information. This is a backward effect.

(b) Proactive interference: In this, an already existing information, probably

one in the long term memory, interpret with the newly learnt information and
suppresses the new information. If the older information is very strong, then the
new one will be forgotten completely.

Memory disorders-Amnesia
Amnesia means loss of memory.

1. Anterograde amnesia: New information collected cannot be stored as

memory, no new memory formation. But memory already stored remains
unaffected.
Cause: Lesion of temporal lobe involving hippocampus and also in Korsakoff
psychosis.

2. Retrograde amnesia: Inability to recall memories of past.

Cause: Brain injuries of cerebral cortex or thalamus which is needed for search
of memory.

3. Senile dementia: Forgetting in old age.

AUTONOMIC NERVOUS SYSTEM (ANS) It is a functional branch of
nervous system concerned with control and co-ordination of visceral functions.
Autonomic nervous system is divided into two branches.
1. Sympathetic nervous system and
2. Parasympathetic nervous system
Sympathetic Nervous System

It is also called Thoraco-lumbar out flow. It is derived from thoracic and lumbar
segments of the spinal cord. Each sympathetic nerve is made up of two neurons.

1. Preganglionic neuron and

2. Postganglionic neurons
Preganglionic neurons secrete acetylcholine and postganglionic neurons secrete
mostly noradrenaline.
Superior cervical ganglion

Middle cervical ganglion

Inferior Cervical ganglion Eye

Lacrimal gland
Submaxillary gland Submandibular gland Parotid gland

Heart
Larynx
Trachea

Stomach
Celiac ganglion

Small intestine abdominal Blood vessels Liver

Pancreas
Lesser
splanchnicnv
Superior Adrenal
mesenteric
ganglion KidneyLesser splanchnicnv
Colon

Inferior
mesenteric Rectum ganglionBladder

Testis
Uterus

Fig. 8.82 Organisation of sympathetic nervous system Functions of

sympathetic nervous system

1. It plays an important role in the regulation of cardio vascular function.

Sympathetic nervous system shows a stimulatory control over the S.A node as
well as ventricular myocardium. Because of this, whenever sympathetic
activities increase it will increase heart rate as well as force of contraction of the
heart. This will increase cardiac output. It takes part in the regulation of cardiac
output. Sympathetic nervous system controls the degree of vasoconstriction,
thereby it controls total peripheral resistance and takes part in the regulation of
blood pressure.

2. Sympathetic nervous system controls cellular metabolic rate B.M.R.

3. It takes part in the regulation of body temperature. 4. It controls sweating.
5. It controls the secretion of adrenaline from the

adrenal medulla.
6. It is responsible for fight or flight response.
7. It shows an inhibitory control over the smooth muscles of GIT. Decreases
motility of GIT.
8. It inhibits the secretion of various digestive juices like saliva, gastric juice,
pancreatic juice.
9. It produces pupilary dilatation.
It is contributed by cranial nerves III, VII, IX and X and sacral segments of the
spinal cord S2, S3, S4. The parasympathetic nerves are made up of two neurons.
1. Preganglionic neuron
2. Postganglionic neuron.
Both of these neurons secrete acetylcholine as the neurotransmitter. The
parasympathetic fibres coming out through the cranial nerve III innervate the
eyeball and pupillary muscles. The fibres coming through VII cranial nerve
innervate nasal glands, tear glands and salivary glands. The fibres coming
through IX cranial nerve innervate parotid glands. X or vagus is the most
important parasympathetic nerve. It accounts for 75 % of parasympathetic
innervation. It innervates the heart, lungs, stomach, intestine, liver etc. Sacral
segments of the spinal cord S2, S3 and S4. The parasympathetic fibres coming
out of sacral segments of the spinal cord innervate the structures of urino genital
system.
Functions of parasympathetic nervous system

1. Vagus shows a continuous inhibitory action on the S.A. node and takes part in
the regulation of heart rate.

2. Parasympathetic system shows a stimulatory action on the GIT. It increases

the secretion of various digestive juices. It also increases the motility of GIT.

3. It produces pupillary constriction.

4. It controls the micturition reflex.
5. It controls sexual act.
Parasympathetic nervous system : (Cranio sacral outflow)
Ciliary ganglian Iris

Otic ganglion Parotid gland Lacrimal gland

Sublingual gland
Submaxillary gland
Heart

Trachea Bronchi Lungs

Liver bile duct Gall bladder

Spleen
Stomach
Small intestine
Colon
Rectum Kidney
Bladder
Male sex organ
Female sex organ

Fig. 8.83 Organisation of parasympathetic nervous system

TABLE 8.24
Comparison between sympathetic and parasympathetic systems
Sl.No. Sympathetic Parasympathetic 1. Site of preganglionic neurons
Thoracolumbar (Segmants T1-L3) Cranio sacral (Nuclei of cranial nerves III,
VII, IX and X; Segments S2-4)
2. Site of ganglia Paravertebral and prevertebral ganglia Within or very close to
the organ innervated 3. Preganglionic neurons Cholinergic Cholinergic 4.
Postganglionic neurons Adrenergic (Exceptions: In sweat glands and skeletal
muscle, cholinergic) Cholinergic
5. Activation In emergencies and in REM sleep When relaxed, and in slow wave
sleep 6. Effects Useful in emergencies substrates mobilised for providing energy
—

Catabolic and thermogenic Useful at rest. Substrates deposited for storage

Anabolic

TABLE 8.25
Autonomic effects on various organs
Sl.No. Organ Effect of

sympathetic stimulation Effect of

parasympathetic stimulation

1. Heart
2. Lungs
3. Gastrointestinal tract
4. Bladder
5. Blood vessels
6. Eyes
7. Sweat glands

Metabolic effects Increase in rate, Increase in force of contraction

Bronchodilatation
Inhibits secretion.

Decrease in motility, tone

and secretion
Contraction of sphincters

Relaxation of detrusor muscles Contraction of sphincter

Splanchnicnv and cutaneous vasoconstriction

Skeletal muscles: Constriction (adrenergic, alpha), dilatation (adrenergic beta -2)
dilatation (cholinergic)

Pupillary dilatation. Relaxation of ciliary muscles

Sweating (cholinergic)
Glycogenolysis, Lipolysis
Increases blood glucose
Decrease in rate, Decrease in force of contraction of atria.

constriction of bronchioles, secretion.

Increase in motility, tone

and secretion
Relaxation of sphincters

Contraction of detrusor muscles Relaxation of sphincter

None
None
Pupillary constriction. Contraction of ciliary muscles
Sweating on palms only Not significant

CRANIAL NERVES
These nerves come out from the parts of CNS present with in cranium. There are
twelve pairs of cranial nerves.
Occulomotor nerve (III) Mid brain Trigeminal nerrve (V) Pons
Fourth ventricle
Salivary nuclei Vestibulocochlear (VIII) Facial nerve (VII)

Medulla Abducent nerve (VI) Glossopharyngeal (IX) Vagus (X)

Hypoglossal (XII)
Acessory (XI)
Spinal cord Spinal nuclei of trigeminal nerve (V)
Fig. 8.84 Origin of cranial nerves
TABLE 8.26
Summary of the cranial nerves
Sl.No. Name Type Central
Connections Peripheral Connections Function Distribution
1. Olfactory nerve Sensory

Smell area in
temporal lobe of cerebrum through olfactory bulb. Mucous
membrane in the root of nose.
Sense of smell
Starts in the nose and
passes to the olfactory bulb.

2. Optic nerve Sensory

Visual area in occipital lobe of cerebral cortex

Retina of the eye Sense of sight

and balance Starts in the retina and

passes to the lateral
geniculate
body of
thalamus

3. Occulomotor nerve
Motor Midbrain

External eye muscles

Eye movement, Accomodation Muscles of eyes.

4. Trochlear nerve Motor

Nerve cells near the floor of aqueduct of midbrain

Superior oblique muscles of the eyes
Movement of the eyeball Ends in the
muscles which move the eye

5. Trigeminal nerve Motor

and
sensory Motor fibres from the pons varolii sensory fibres from the trigeminal
ganglion
Muscles of
mastication
sensory to gums, cheek, lower jaw Chewing
sensation from the face, head Proprioception Supplies the muscle of
mastication and has
three sensory branches – ophthalmic, maxillary and mandibular

6. Abducent nerve Motor

Floor of fourth ventricle

Lateral rectus muscle
movement of the eye Muscle of the eye

7. Facial nerve

8. Vestibulo
cochlear nerve Sensory
(a) vestibular (b) cochlear (a) Cerebellum (b) Hearing area

of cerebrum

(a) semicircular canals in the ear

(b) organ of corti in cochlea
(a) maintenance Starts from the of balance
(b) sense of hearing
ears and
reaches the temporal lobe of cerebral
cortex

9. Glossopharyngeal nerve
Motor fibres to the
pharynx
Motor and sensory

Medulla oblongata Parotid glands,

back of tongue and pharynx Secretion of

saliva, sense of taste. Movement of pharynx.

10. Vagus nerve Motor

and
sensory Medulla oblongata
11. Accessory nerve Motor

Medulla oblongata Pharynx, larynx organs,glands, ducts, blood

vessels in the
thoracic and
digestive tract

Muscles of the neck, most of the pharynx and soft palate

Movement and secretion
Heart,
G.I. tract

Movement of the head,

shoulders,
pharynx and larynx
Sternocleido mastoid, trapezium, laryngeal and pharyngeal
muscles.

12. Hypoglossal Motor and

sensory

Motor Pons vairolii

Medulla oblongata Motor fibres to the muscles of

the face, sensory from tongue

Tongue Movement of facial

expression. Sensory from the tongue
Muscles of the facial expression and is sensory
from the
tongue.

Movement of tongue
Tongue muscles
Special Senses
Thomas Young
13-6-1773–10-5-1829 Fields—Physics and Physiology
Theory of colour vision

Ernest Heinrich Weber 24-06-1795–26-01-1878 German Physician and

Physiologist
Known for Waber’s law and Waber-Fechner’s law.
Discovered the inhibitory Power of vagus nerve
Herman Ludwig Ferdinard von Helmholtz
31-08-1821–8-9-1894
German Physiologist and Physicist
Theory of colour vision, perception of sound,
chemical thermodynamics
Gustav Theodor Fechner 19-4-1801–28-11-1887
German Experimental
Psychologist
Known for Weber-Fechner’s law of intensity of sensation

(360)
Chapter
9
SPECIAL SENSES

Vision—Functional anatomy, Structure of retina, Rods and cones.

Aqueous humour, Vitreous humour, Intraoccular pressure.
Mechanism of formation of image—Basic optics. Refractive errors with
correction .
Mechanism of processing of image— Phototransduction.
Pupillary reflexes with pathways—Light reflexes and Accommodation reflex.
Argyl Robertsons Pupil. Strabismus or squint.
Movements of eye.
Physiology of colour vision and colour blindness. Visual-Adaptation—light and
dark, Visual acuity, Field of vision, Critical Fusion Frequency. Visual pathway
with lesions at various levels. Audition—Structure and function of external and
middle ear.
Structure of organ of Corti, Cochlear fluids, Cochlear potential.
Mechanism of Hearing, Activation of hair cell, Auditory pathway, Electrical
potentials from cochlea, Theories of hearing.
Frequency and Intensity discrimination.
Appreciation and localisation of sound
Applied aspect: Hearing tests, Deafness, Audiometry. Vestibular apparatus
functions.
Olfaction—Olfactory receptors, mechanism of stimulation, Olfactory pathway.
Gustation—Modalities of taste, Taste buds. Mechanism of stimulation and taste
pathway.

SPECIAL SENSES The special senses are: 1. Vision

3. Taste or Gustation 5. Equilibrium

2. Audition or Hearing 4. Smell or Olfaction

The receptors for special senses are usually organised as sense organs.
For example: Eyes for vision, Ears for hearing.
The receptors for the special senses are confined to the head.
Vision: Organ for vision are the eyes.
Iris Visual
Posterioraxis chamber
Ciliary body Optic Aqueous humour
axis
Cornea
Anterior chamber Conjunctiva Limbus Sclera Lens Lens Choroid
Zonule fibres Nodal point
Vitreous humour Retinal
Nasal retinaOptic Fovea Temporal retinadisc
Optic
disc Fovea Optic nerve

Fig. 9.1
Structure of the eye ball

Eyeballs are situated inside the orbit. Eyeballs are made up of three layers or
three coats.
1. Outer fibrous coat.
2. Middle vascular coat.
3. Inner nervous coat.
The outer fibrous coat, is made up of two parts.
1. The posterior 5/6th portion is opaque and is known as sclera.
2. Anterior 1/6th portion is transparent and it is called as cornea. Cornea is
covered by a double walled, mucous membrane known as conjunctiva. Cornea is
covered by two eyelids—Upper and lower eyelids.

Functions of eyelids
1. Protection of the eyeball from dust and excess light. Cornea
Cornea is transparent and it gives optic power.
Vascular coat
It is divided into two portions—posterior 2/3rd of the portion is choroid. Choroid
is rich with blood supply. Anterior portion is made up of ciliary muscles and
ciliary body. There is a muscular iris. It has got a central opening-pupil. The iris
is coloured and the colour of the eyes depend on the iris. The diameter of the
pupil can vary from 2-8 mm. This helps in controlling the amount of light
entering into the eyeball. Inner to the iris there is a lens. Lens is suspended by
the suspensory
ligament. Lens is made up of protein crystals arranged in layers. The lens is
biconvex. The presence of lens divides the cavity of eyeball into two
compartments. The anterior compartment is filled with aqeuous humour,
posterior compartment is filled with vitreous humor or body.

Nervous coat
It is made up of retina. The visual receptors rods and cones are present in the
retina.

Structure of retina
Retina is the inner most layer of the eyeball. It is made up of 10 different layers.

The outer most layer is pigmented cell layer. The second layer is a layer of visual
receptors—rods and cones. There are about 120 million rods and about 6 million
cones.

TABLE 9.1
Comparison between rods and cones
The 3rd layer is outer limiting membrane.

The 4th layer is known as outer nuclear layer. It is made up of the cell bodies of
rods and cones.
5th layer is outer plexiform layer. It is made up of synapse between rods and
cones and bipolar cells.
6th layer is inner nuclear layer. It is made up of the cell bodies of bipolar cells.
7th layer is inner plexiform layer. It is made up of the synapses between bipolar
cells and ganglion cells.
8th layer is ganglion cell layer. It is made up of nucleus of ganglion cells.
9th layer is a layer of optic nerve.
10th layer is inner limiting membrane.
Pigment cell layer -1

Horizontal cell Bipolar cell

Ganglion cell Rod and cone

layer - 2
Outer limiting
membrane - 3

Outer nuclear
layer - 4
Outer plexiform
layer - 5
Inner nuclear layer -6 Inner plexiform
layer - 7
Ganglion cell layer -8 Optic nerve layer - 9
Inner limiting membrane - 10
Fig. 9.2
Structure of retina

S.No. Features
1. Shape of outer segment
2. Visual pigment

Rods Rod shaped

Rhodopsin Or Visual purple

3. Pigment per receptor

4. Function
More
Dim light vision

5. Number
6. Type of vision
7. Distribution More 120 million
Scotopic vision
Well distributed except at Fovea

8. Threshold stimulus 9. Sensitivity to light 10. Light absorption ability Low

High More

Cones
Cone shaped

Porphyropsin — Red
Iodopsin — Green
Cyanopsin — Blue

Less
Bright light vision, Colour vision, Acuity of vision and Depth perception

Less 6 million
Photopic vision

All over but less at periphery

Only cones at Fovea.

High
Low
Less
Rod Cone
Plasma membrane
30 nm

Disks Sacs Outer

segment

Ciliary neck
Mitochondria
Nucleus

Incident light from lens Inner

segment

Synaptic terminal

Fig. 9.3 Schematic diagram of a rod and a cone

Photochemistry of vision
Rods are required for dimlight or night (scotopic) vision. Rods contain a pigment
called rhodopsin. Rhodopsin molecule is produced by combination of opsin (a
protein) molecule is produced by combination of opsin (a protein) cis retinal
retinal trans retinal. In rhodopsin, the retinal belongs to the cis variety.

variety.

cis retinal + scotopsin → rhodopsin → under the influence of light → alltrans

retinal + scotopsin.
When light strikes the rods, the cis retinal converted into trans retinal. This
conversion triggers a cascade of events leading to hyperpolarisation of the
photoreceptors and decreased neurotransmitter release from them. This leads
into conduction of impulse through the visual pathway towards the visual cortex.
Cones are required for photopic vision. When light of high intensity, strikes the
cones, it may be presumed, that the photochemical changes occur in the cone are
very similar to those of rods. Papilloedema: It is a clinical condition in which
there is a swelling of optic disc.

Causes
1. Increased pressure of CSF, increases pressure in optic sheath. Blood drainage
into retinal vein decreases. This increases pressure in the retinal capillary and
leads to oedema especially at optic disc.
2. Inflammation of optic nerve – optic neuritis. 3. Malignant hypertension.

Basics of optics
Principles of optics

Optics: The scientific study of light. Physical optics is concerned with the
creation, nature, and properties of light. Psychological optics pertains to the role
of light in vision. Geometrical optics deals with the properties of reflection and
refraction of light, as part of the study of mirrors, lenses, and optical fibres.

Light: The form of radiant energy that stimulates the organs of sight, having for
normal human vision wavelengths ranging from about 390 to 770 nm and
traveling at a speed of about 186,300 miles per second.

Refractive index: The refractive index of any transparent substances is the ratio
of velocity of light in air to velocity of light in the substance. When light rays
pass from one medium into other, velocity of light changes.

Refraction of light: Bending of light rays at an angulated interface is known as

refraction.
Size of the pupil: In dark light pupil dilates and in bright light, the pupil
constricts to a minimum diameter. The small size of pupil decreases spherical
and chromatic aberration by eliminating the peripheral light rays and depth of
focus.
Spherical aberration: It is defined as light rays that pass through the lens near
its periphery get refracted more than the rays that enter through its central
portion. Thus, light of a single wavelength get focused at different points of the
retina.
Chromatic aberration: It is defined as light rays with longer wavelength get
refracted more and light rays with shorter wavelength get refracted less. Thus,
light of different wavelengths get focused at different points on the retina.

Image formation and processing

1. The light rays coming from that objects are essentially parallel, and the rays
are focused on the retina without effort (an emmetropic eye does not need
corrective lenses). If the gaze shifts to something closer, light rays from the
source are too divergent to be focused without effort.

2. In other words, the eye is automatically focused on things in the distance

unless a conscious effort is made to focus elsewhere.

3. Emmetropia describes the state of vision where an object at infinity is in sharp

focus with the eye lens in a neutral or relaxed state.

4. This condition of the normal eye is achieved when the refractive power of the
cornea and the axial length of the eye balance out, which focuses rays exactly on
the retina resulting in perfect vision. An eye in a state of emmetropia requires no
correction.

5. The visual system in humans allows individuals to assimilate information

(light energy) from the environment.

6. The act of seeing starts when the lens of the eye focuses an image of its
surroundings onto a lightsensitive membrane in the back of the eye, called the
retina.

7. The retina is actually part of the brain that is isolated to serve as a transducer
for the conversion of patterns of light into neuronal signals.

8. The lens of the eye focuses light on the photoreceptive cells of the retina,
which detect the photons of light and respond by producing neural impulses. In
the visual system, retinal, technically called retinene1 or “retinaldehyde”, is a
light-sensitive retinene molecule found in the rods and cones of the retina.

9. Retinal is the fundamental structure involved in the transduction of light into

visual signals, i.e., nerve impulses in the ocular system of the central nervous
system. In the presence of light, the retinal molecule changes configuration and
as a result a nerve impulse is generated.

10. These signals are processed in a hierarchical fashion by different parts of the
brain, from the retina to the lateral geniculate nucleus, to the primary and
secondary visual cortex of the brain.
Phototransduction: Visual or phototransduction is the process by which the
light energy causes development of receptor potential in visual receptors. The
resting membrane potential in other sensory receptor cells is usually between 70
and -90 mV. When light falls on retina, the rhodopsin is excited leading to the
development of receptor potential in the rod cells. Following is the
phototransduction cascade of receptor potential.

1. When a photon (the minimum quantum of light energy) is absorbed by

rhodopsin, the 11-cis retinal is decommposed into meta-rhodopsin through few
reactions mentioned earlier. The metarhodopsin II is considered as the active
form of rhodopsin. It plays an important role in the development of receptor
potential.

2. Metarhodopsin II activates a G-protein called transsducin that is present in rod

discs.

3. The activated transducin activates the enzyme called cyclic guanosine

monophosphate (cGMP) phosphoodiesterase, which is also present in the rod
discs.

4. The activated cGMP phosphodiesterase hydrolyses cGMP to 5′-GMP. Now,

the concentration of cGMP is reduced in the rod cell.

5. The reduction in the concentration of cGMP immediately causes closure of

sodium channels in the membrane of visual receptors.

6. The sudden closure of sodium channels prevents the hyperpolarisation in

receptor cells reduced release of glutamate.

7. Response in bipolar and ganglionic cells entry of sodium ions leading to

hyperpolarisation. The potential reaches –70 to –80 mY. This is because of
sodium-potassium pump.

8. Thus, the process involved in receptor potential rod cells is unique in nature.
When other sensory receptors are excited, the electrical response is in the form
of depolarisation (receptor potential). However, in visual receptors the response
is in the form of hyperpolarisation.

9. The photosensitive pigment in the cone cells is of three types namely

porpyropsin, iodopsin and cyanopsin. Only one of these pigments is present in
each cone. The photopigment in cone cell also is a conjugated protein made up
of a protein and chromophore. The protein in cone pigment is called photopsin,
which is different from scotopsin, the protein part of rhodopsin.

Refractive Errors of Eye Errors of refraction of eye are: 1. Myopia

3. Presbyopia
Myopia or short sightedness

2. Hypermetropia 4. Astigmatism.

It is a type of refractive error of the eye in which the person can see near by
objects clearly but cannot see distant objects. The light rays coming from near by
objects are focused on the retina. But light rays coming from distant objects are
focused in front of the retina.

Causes
1. Elongation of the eyeball due to stress and strain.
2. Increase in the optical power of the lens. Treatment: Use of spectacles with
biconcave lens. The biconcave lens will diverge the light rays coming from
distant objects and it helps to push back the images on to the retina.
Retina
Light rays Emmetropia Normal eye
Lens
Myopia

Light rays fromP distant object

Light rays from near by object

Myopia Short sight

P
Myopia (corrected)

Biconcave lens
Correction for myopia
Light rays from near by object

Hypermetropia P
Light rays from distant object Hypermetropia Long sight

P Hypermetropia

(corrected) Correction for hypermetropia Biconvex lens

Fig. 9.4 Common errors of refraction of eye and correction
Hypermetropia or long sightedness

It is a type of refractive error of the eye. Here the person can see distant objects
clearly but connot see nearby objects clearly. The light rays coming from the
distant objects are focused on the retina. The light rays coming from the near by
objects are focused behind the retina.

Causes: Shortening of eyeball due to stress and strain. Decrease in the optical
power of the lens.
Treatment
1. Use of spectacles with biconvex lens. The convex lens converges light rays
coming from near by objects and focuses them on the retina.
Presbyopia

It is also known as long sightedness of old age. As age advances the near point
of vision receeds. The near point of vision increases. It usually starts around the
age of 45 years. Near point of vision is the closest distance from the eye at which
an object can be seen clearly. It receeds with age. At the age of 20 years near
point of vision is 10 cm. from the eyes. At the age of 60 years the near point of
vision receeds to 80 cm from the eyes.

Causes
1. Weakening of ciliary muscles and
2. Decrease in the elasticity of the lens. This will decrease the power of
accommodation. Treatment

Using spectacles with both biconcave and biconvex lens.

Astigmatism
It is a type of refractive error of the eye. It is due to the uneven surface of cornea.
The light rays are focused at different planes.
Treatment

Using spectacles with cylindrical lens.

Aqueous humour

Retina
Ora serrata Choroid
Sclera

Bulbar conjunctiva Ciliary Ciliary musclesbody Ciliary process

Vitreous chamber (vitreous body) Fiber of suspensory ligament of lens

Lens Scleral venous sinus

(canal of schlemm)

Posterior chamberAnterior cavity Anterior chamber (aqueous humour)

Iris
Cornea

Fig. 9.5
Circulation of aqueous humour

Aqueous humour is a clear liquid which fills the anterior and posterior chambers
of eye. It is formed by active transport and diffusion from capillaries in the
ciliary body. It has the same composition as that of blood plasma (only protein
concentration in it is much lower than that of plasma). It carries glucose, amino
acids and respiratory gases. It has high content of ascorbic acid.

The functions of aqueous humour:

1. Supplies nutrition to lens and cornea, both of which are avascular structures.
2. Maintains intraocular pressure and therefore the shape of the eye ball.

Circulation of aqueous humour

Aqueous humour is produced by ciliary body and enters the posterior chamber.
Then through pupil it enters the anterior chamber. From here it is reabsorbed
through a network of trabeculae called ‘canal of Schlemm’ (Present at
sclerocorneal junction) and goes to episcleral venous plexus where pressure

is always lesser than the pressure of aqueous humour in the eye. This acts as a
force causing continous outflow of aqueous humour. Blinking movements of eye
further increase this pressure gradient and help the outflow of aqueous humour.
There is consistant renewal of aqueous humour. Complete renewal of aqueous
humour occurs once every hour.

Intraocular pressure
Pressure of aqueous humour in the eye is 16–20 mm of Hg. It is called
intraocular pressure and is measured with the help of an instrument known as
tonometer. This pressure helps to maintain the shape of the eye ball.

Glaucoma
Glaucoma is the condition where there is increased
intraocular pressure. It is due to obstruction of the outflow of aqueous humour.
This obstruction usually occurs at “canal of Schlemm”.

Vitreous humour and its function

Vitreous humour is a clear gelatinous material which fills the space between lens
and retina. It has high viscosity. It consists of gel like substance that contains a
network of thin fibres of a highly hygroscopic protein analogous to gelatin.

The function of vitreous humour is to maintain the shape of the eye ball and to
refract light.

Pupillary Reflexes
There are two types of pupillary reflexes.
1. Pupillary light reflex and
2. Pupillary accommodation reflex.
Pupillary light reflex

When a strong beam of light is focused on to the eyes, the pupils constrict. It is
known as pupillary light reflex. There are two types of pupillary light reflex.

1. Direct pupillary light reflex and

2. Indirect pupillary light reflex or consensual pupillary light reflex.
That means when a beam of light is focused on to one eye the other eye’s pupil
also constrict.
Purpose
1. It cuts of excess light passing into the retina.
2. It provides clarity of vision.

Pathway for pupillary light reflex

The stimulus for pupillary light reflex is the stimulation of rods and cones by the
bright light.

Receptor for this reflex are the rods and cones. From the receptors impulses are
transmitted through the optic nerve. Optic nerve crosses at optic chiasma.
Afterwards it gives rise to optic tracts. Majority of the fibres of the optic tract
reach the lateral geniculate body of the thalamus. Some of the fibres reach
pretectal area and superior colliculi. These areas act as center for pupillary light
reflex. From the pretectal area and superior colliculi the efferent fibres are
transmitted to Edinger-Westpal nucleus. It is the nucleus of IIIrd cranial nerve.
From the Edinger-Westpal nucleus the
Light

pupil-constrictor pupillae. These mucles contract and this produces pupillary

constriction.
The pathway of light reflex
Receptors (of retina) → optic nerve → optic chiasma → optic tract → pretectal
nucleus → Edinger-Westpal.
Nucleus → occulomotor nerve (parasympathetic fibres) → ciliary gangilion-
short ciliary nerves-sphincter pupillae muscle causing constriction of pupil.
Constriction of pupilConstriction of pupil
Contraction Retina Contraction
Sphincter Optic nerve pupillaeOptic
chiasma
Sphincter pupillae
Retina rods and cones Ciliary ganglion
Optic nerve
Optic tract (same side) Optic chiasma
Pretectal nucleus Optic tract

IIIrd cranial
nucleus
(Edinger westpal nucleus)

Geniculate body thalamus

Optic tract (opposite side)
Fig. 9.7 Pathway for pupillary light reflex
Pretectal nucleus Pretectal nucleus
Mydriasis
Dilatation of pupil is knows as mydriasis. It occurs on sympathetic nerve
stimulation.
IIIrd cranial nerve nucleus (bilateral) Edinger - westpal nucleus
IIIrd cranial nerve occulomotor
Ciliary ganglion
Short ciliary nerve
Sphincter pupillae muscles
Contraction
Fig. 9.6
Pathway for pupillary light reflex

pre-ganglionic parasympathetic fibres comes out and reach the ciliary ganglion.
From the ciliary ganglion the post ganglionic neurone arise and innervate the
muscles of the
Accomodation Reflex
Human eyes are normally set for distant vision.

Suppose a person wants to see a near by object, a series of changes takes place in
the optical apparatus. These sudden changes taking place in the optical apparatus
for having a clear vision of near by objects is known as accommodation reflex.
The important changes are:

1. Constriction of the pupil

2. Convergence of the eye balls.
3. Bulging of lens

Pathway for accommodation reflex

The blurred vision of nearby objects is the stimulus for accommodation reflex.
The impulses from rods and cones are transmitted through the optic nerve. It
passes and crosses at the optic chiasma and gives rise to optic tract. The optic
tract reach the lateral geniculate body of the thalamus. From the thalamus
impulses are transmitted to the motor cortex area no. 8. from the motor cortex
the efferent impulses are transmitted to the Edinger-Westpal nucleus. From the
Edinger-Westpal nucleus the efferent impulses are carried through the occulo
motor nerve. These impulses reach the ciliary muscles and pupillary muscles.
When ciliary mucles contract the tension in suspensory ligaments is reduced.
This allows the lens to bulge. Bulging increases the curvature of the lens and it
also increases the optical power of the lens. Because of this light rays coming
from the near by objects can be focussed on the retina. It also produces pupillary
constriction.

Pathway for accommodation reflex is:

Receptors (of retina) → optic nerve → optic chiasma → optic tract → lateral
geniculate body → visual cortex → frontal eye field (area 8) → internal capsule
to opposite side Edinger-Westpal nucleus → occulomotor nerve → ciliary
ganglion → ciliary nerves → ciliary muscles, sphincter pupillae muscle and
medial rectus.
Convergence two eyeballs Constriction of pupil Bulgling of lens
Contraction Contraction Contraction
Medial rectus Constrctor pupillae Ciliary muscle
Ciliary ganglion ganglionOptic chiasma IIIrd cranial nucleus
(Edinger-WestpalLateralnucleus) geniculate
body (Thalamus) Acc. ciliary
Frontal eye fieldVisual cortex(area no. 8) (area 17, 18)

Fig. 9.8 Pathway for accommodation reflex

Light
Retina rods and cones
Blurred vision
Optic nerve
Lateral Geniculate body (Thalamus)
Visual cortex area no 17 and 18
Motor cortex area-8 (Frontal eye field)
IIIrd Cranial nerve nucleus Edinger-Westpal nucleus
ciliary ganglion Accessory ciliany ganglion Medial rectus
Short ciliary nerve Short ciliary nerve Contraction
Constrictor pupillae muscle Ciliary muscle contraction Convergence of two eye balls
Pupillary constriction response
Decrease in tension in suspensory ligaments
Bulging of lens
Anterior curvature of lens increases focussing power increases
Fig. 9.9
Pathway for accommodation reflex
Argyl—Robertson’s Pupil

It is a condition in which pupillary light reflex is absent but accomodation reflex

is present. Cause is lesion at pretectal area due to neurosyphilis.

Strabismus or squint

Lack of fusion of eyes in one or more coordinates is called squint or strabismus.

These may be horizontal, vertical or torsional.

The extrinsic muscles of the eye

There are three pairs of extrinsic muscles of the eye: 1. Medial and lateral recti.
2. Superior and inferior recti.
3. Superior and inferior oblique.
The nerve supply of eye muscles
These sets of eye muscles are reciprocally innervated.
Superior oblique is supplied by trochlear or 4th cranial nerve,
lateral rectus is supplied by abducent or 6th cranial nerve.
Rest of the eye muscles are supplied by occulomotor or third
cranial nerve. Nuclei of 3rd, 4th and 6th cranial nerves are
connected to each other through medial longitudinal
fasciculus.
Actions of various extrinsic muscles of the eye
50
(a) Medial rectus
(b) Lateral rectus
(c) Superior rectus
(d) Inferior rectus
(e) Superior oblique
(f) Inferior oblique
Control of eye muscles
– moves the eye medially (adduction).

– moves the eye laterally (abduction).

– causes elevation (upward movement), adduction and intorsion (medial
rotation) of the eye.
–causes depression (downward movement), adduction and extorsion (lateral
rotation) of the eye.
– causes depression, abduction and intorsion of eye.
– causes elevation, abduction and extorsion of the eye.

Eye muscles are controlled by occipital visual areas through occipitotectal and
occipitocollicular tracts going to pretectal and superior collicular areas of brain
stem. Frontal cortex also controls the movements through frontotectal tracts
passing from frontal cortex to pretectal nucleus. From pretectal and superior
collicular areas signals go to nuclei of 3rd, 4th, 6th cranial nerves. Signals are
also transmitted to these nuclei from vestibular nuclei through medial
longitudinal fasciculus.

Colour Vision and Colour Blindness

The ability to perceive different colours is known as colour vision. Colour vision
is a property of cones. Young– Helmholtz theory—The mechanism of colour
vision.

Theories of colour vision: Young-Helmholtz

Cones are responsible for colour vision. There are three types of photosensitive
chemicals present in three different types of cones. Special sensitiveness of three
photosensitive chemicals are different. Each photosensitive chemical is sensitive
to a small range of light wavelength and maximally sensitive to only one
wavelength (colour). The cones are labelled as green, red and blue cones
according to the sensitivity of their photosensitive chemicals to a particular
colour (435 nm blue, 535 nm green and 575 nm red).
Green Red
cone
100 Blue cone Rods cone
75
25
0 400 100 600 700 Wave length (nanometers)
Violet Blue Green Yellow Orange Red
Fig. 9.10
Light absorption by the respective pigments of the three colour-receptive cones

There is a trichromatic theory which explains the mechanism of colour vision.

According to this theory, blue, green and red are the basic colours and different
types of colour shades of spectrum can be obtained by different combinations of
these basic colours. When eye is stimulated with any colour, three different types
of cones are stimulated to a different extent.

Ratio of stimulation of red: green: blue is responsible for recognition of a

particular colour by CNS. For example, when monochromate orange light with
wave length 580 nm is stimulating the eye, red cones are stimulated to stimulus
value of 99, green cones are stimulated to a stimulus value of 42 and blue cones
are not stimulated, their stimulus value is zero. In this case ratio of stimulation of
red : green : blue : cones is 99 : 42 : 0. The nervous system interprets this as
orange colour. Likewise such multiple ratios are obtained with different wave
lengths and each ratio is interpreted as a particular colour.

Evidence for the trichromatic theory comes from colour matching and colour
mixing studies. Young and Helmholtz carried out experiments in which
individuals adjusted the relative intensity of 1, 2, or 3 light sources of different
wavelengths so that the resulting mixture field matched an adjacent test field
composed of a single wavelength. Individuals with normal colour vision needed
three different wavelengths (i.e., primaries) to match any other wavelength in the
visible spectrum. This finding led to the hypothesis that normal colour vision is
based on the activity of three types of receptors, each with different peak
sensitivity. Consistent with the trichromatic theory, we now know that the overall
balance of activity in S (short wavelength), M (medium wavelength), and L
(long wavelength) cones determines our perception of colour.
Hartridge’s polychromatic theory: This theory explains that human retina has
seven types of receptors. All seven receptors are classified into three units:

1. First unit: It is a tricolour unit consisting of receptors for orange, green and
blue.
2. Second unit: It is a dicolour unit with receptors for yellow and blue colours.
3. Third unit: It is another discolour unit with receptors for red and blue-green
colours. Granit’s modulator and Dominator theory: Granit observed that the
ganglionic cells of retina are stimulated by the whole of the visual spectrum. He
studied the action potentials in ganglionic cells stimulated by light and obtained
some sensitivity curves by using the different wavelengths of light both in light
adapted and dark adapted eyes. On the basis of the sensitivity curves, he
classified the ganglionic cells into two groups namely, Dominators and
Modulators. Dominators: The dominators are responsible for brightness of
light. Dominators are further divided into two types.
1. Dominators for cones, which respond in light adappted eye and a broad
sensitivity curve is produce with the maximum response around the wavelengths
55 A.
2. Dominators for rods, which respond in dark adapted eye and in the sensitivity
curve the maximum response is given at the wavelengths of 500 A.

Modulators: The modulators are responsible for different colour sensations.

There are three types of modulators: Modulators of blue, which are stimulated
by lights with wavelengths of 450 to 470 A.
Opponent-Process Theory: Developed by Ewald Hering (1920/1964), the
opponent-process theory states that the cone photoreceptors are linked together
to form three opposing colour pairs: blue/yellow, red/green, and black/white.
Activation of one member of the pair inhibits activity in the other. Consistent
with this theory, no two members of a pair can be seen at the same location,
which explains why we don’t experience such colours as “bluish yellow” or
“reddish green”. This theory also helps to explain some types of colour vision
deficiency. For example, people with dichromatic deficiencies are able to match
a test field using only two primaries. Depending on the deficiency they will
confuse either red and green or blue and yellow.

The opponent-process theory explains how we see yellow though there is no

yellow cone. It results from the excitatory and inhibitory connections between
the three cone types. Specifically, the simultaneous stimulation of red (L cones)
and green (M cones) is summed and in turn inhibits B+Y–, which results in the
perception of yellow. However, when blue light is present, the S cone is
activated, the B+Y– cell receives excitatory input and blue is perceived.

Colour blindness: It is the inability to perceive one or more than one primary
colour. It is a sex linked genetic disorder. There are 3 types of colour blindness.
It is inherited through x-chromosome and is more common in males than
females.

Problems of colour blindness

1. A colour blind person may not be able to perceive colour signals of the traffic.
Therefore colour blindness will be problematic to drivers, pilots, navigators etc.

2. It will decrease the aesthetic sensation of the person.

3. It will be problematic in electronic industry because strength of capacitors are
given in colour codes. Colour weakness: Sometimes person does not have
colour blindness but has colour weakness for a particular colour. In this case,
colour cones are not missing but they are under represented.
There are three types of such anomalies:
A. Red-weakness called protanomaly.
B. Green-weakness called deuteronomaly.
C. Blue-weakness called tritanomaly.
Tests for colour blindness
Colour blindness is tested by the following tests:
1. Holmgren’s wool test: Wool pieces of different colours are given and the
person is asked to pile pieces of the same colour in one pile. If there is no colour
blindness, the person would recognise that each piece is of different colour. If he
is red-green blind, he will keep yellow, green, orange, red coloured pieces in the
same pile because he would recognise them as having the same colour.

TABLE 9.2
Classification of colour blindness
Trichromats Dichromats Monochromats (Rare)

Incidence 5.5%. Can see all colours but sensitiveness to one is subnormal. Tested
with anomaloscope
Protanomaly i.e.,less sensitiveness to Red Deuteranomaly i.e., Less sensitiveness
to Green Tritanomaly (very rare) i.e., less sensitiveness to Blue Incidence 2.5%
can see only two colours but not the third Protanopia or red blindness
Deuteranopia or green blindness Tritanopia : or blue blindness (Rarest)
They are totally colour blind. Only black and white vision.

2. Ishihara chart: This chart has a background of colour dots on which a letter
or a number is written with different colours. The colours in the charts are
arranged in such a way that only normal person can read all letters and numbers
correctly. Colour blind person is either not able to read or he reads wrongly.

Fig. 9.11
Ishihara chart

3. The Edridge-Green lantern: In this test, subject has to identify the colour of
the small illuminated area,size of which can be varied. This test is done during
selection of engine or lorry drivers for detecting the colour defective vision.

Cataract: It is a condition in which the lens becomes opaque. The proteins of

lens becomes denaturated.

Causes
1. Old age 2. Trauma
3. Exposure to u.v.rays 4. Diabetes mellitus

Treatment: Surgical removal of opaque lens and substitute appropriate optical

power through spectacles or by intraocular lens. In very old age the opaque lens
is removed surgically and left without any lens. An eye without any lens is called
as aphakic eye.

Dark adaptation When person remains in darkness for a longtime, there is

increased sensivity of retina to light which is known as dark adaptation
100,000
10,000
1000
100 Rod adaptation
10 Cone adaptation

1 010 20 30 40 50 Minutes in dark

Fig. 9.12 Dark adaptation curve

Dark adaptation occurs due to:

A. Increased sensitivity of retina to light: Sensitivity to light is directly

proportional to the antilogrithm of concentration of photosensitive chemicals on
rods and cones i.e., small change in concentration of chemicals brings about a
very great change in sensitivity of retina to light. In darkness there is synthesis of
photosensitive chemicals in rods and cones from retinal as well as from vitamin
A. Thus concentration of photosensitive chemicals in both the receptors
increases which causes increased sensitivity of retina to light. This is the main
mechanism of dark adaptation.

B. Dilatation of pupil: In darkness, pupil dilates and increases the amount of

light entering into the eye.

C. Neural mechanism: It involves adaptation in the retinal neurons, the degree

of adaptation is much less as compared to adaptation of photochemical system;
however, this adaptation occurs in seconds, i.e., more quickly as compared to
adaptation in the receptors.

The time required for dark adaptation

Moderate dark adaptation occurs in 40 minutes whereas complete dark
adaptation takes about 18 hours.

The factor on which rate of dark adaptation depends is rate of dark adaptation
depends on degree of previous exposure to light. If eye is exposed to light for a
long time, photosensitive chemicals in the receptors not only split into retinal
and opsin but vitamin A is formed from retinal. So vitamin A content in the eye
is high. When eye is exposed to darkness, vitamin A is first converted to retinal
and then to photosensitive chemical. Interconversion of retinal to vitamin A is a
slower process as compared to interconversion of retinal to photosensitive
chemical. Therefore dark adaptation takes a longer time when previous exposure
of eye to light is for a long time.

Light adaptation

When a person is exposed to light, there is decreased sensitivity of retina to light.

This is called light adaptation. It occurs only in a few minutes.

Light adaptation occurs due to reduction in the concentration of photosensitive

chemicals in rods and cones due to their splitting into retinal and opsin.
Therefore in light adaptation, slow reaction (interconversion between retinal and
vitamin A) does not play any role and thus it occurs quickly.

Negative after image

When a person steadily looks at a particular scene for a long time, bright areas of
the scene cause light adaptation in corresponding portion of retina and dark areas
of the scene cause dark adaptation in corresponding retinal areas. If a person
suddenly looks at a white screen, he sees the same scene but bright areas appear
dark and dark areas of the scene appear bright. This is due to dark and light
adaptation.

Flicker fusion frequency

Image of any object remains on the retina for some time so that if pictures are
shown one after the other, they give an appearance of being continuous. The
critical frequency at which fusion occurs is known as flicker fusion frequency.
Critical frequency is much higher in bright light as compared to in darkness.

Visual pathway
From receptor cells impulses are transmitted to bipolar cells and later to ganglion
cells. The axons of the ganglion cells are collected as the optic nerve and they
make exit from the eye through the optic disc then continue to proceed to their
destination as optic nerve.

Fibres of the each nerve partially decussate at optic chiasma; the fibres from the
nasal half of each retina cross to the opposite side but those of the temporal
halves do not cross. After decussation, what is formed is called optic tract. Each
optic tract contains fibres from nasal half of the opposite side and fibres from the
temporal half of the same side.
The optic tract fibres end in the following regions. (i) Lateral geniculate body,
LGB, also called lateral geniculate nucleus, LGN, this is the most important
relay station. This is a part of the thalamus.

(ii) Pretectal area, which is just in front of tectum of the brain (Tectum is the
dorsal portion of the midbrain).

(iii) Superior colliculi, a pair of elevations one on side of the dorsal side of the
midbrain.
NasalTemporal
field Left Rightfield
A eye
Left Right eye
B Ganglion cell

B Optic C nerve
A
optic
chiasm

C PretectalOptic Dregion tract

Lateral geniculate body Geniculocalcarine tract
D
Occipital cortex
Fig. 9.13
Visual pathway

Individual Sites, Where in Lesion Produces— (A) Blindness of one Eye (B)
Blinasal Hemianopia (C) Bitemporal Hemianopia (D) Homonymous
Hemianopia (E) Scotoma— Pathological blind spot.

Lateral Geniculate Body (LG/LGN)

The most important group of fibres from the optic nerve ends in the LGB, LGB
is a part of the thalamus. Informations of ganglion cells of the retina are thus
faithfully transmitted to the LGB cells.

From the LGB, further order neurons, arise and proceed as geniculocalcarine
tract also called ‘optic radiation’

Visual cortex
On the occipital lobe, near the posterior pole, lies the visual cortex, popularly
called Brodmann’s area 17. The area is concerned with the integrated vision. The
neighbouring areas, area 18 and area 19 are visual association areas.
Visual cortex receives fibres from the LGB.

Effects of lesions
Different lesions can occur at different sites of the neural tract carrying impulses
from the retina to brain. Common lesions are:

1. Destruction of one optic nerve causes blindness of the affected eye

(example: retrobulbar neuritis).

2. Lesion at the central part of the optic chiasma: Result is destruction of

fibres from both the nasal halves of retina causing bitemporal hemianopia. This
may be due to pituitary tumor pressing the chiasma.

3. A lesion of the lateral sides of the optic chiasma causes binasal hemianopia,
as fibres coming from the, temporal halves of the retina are lost.

4. Lesion of the optic tract: This causes homonymous hemianopia i.e., loss of
both right halves or both left halves of vision, depending upon which optic tract
is cut.

Visual Acuity

Visual acuity or acuteness of vision is defined as power of the eye to resolve two
stimuli separated in space. It is defined as minimum separable, i.e., minimum
distance between two stimuli at which they are just resolvable (can be perceived
as two separate stimuli). It is expressed as reciprocal of the angle subtended by
two stimuli at the nodal point of the eye at which they are recognised as separate
stimuli. In a normal person when angle subtended is ‘I minute’, stimuli are just
resolvable.
2 m 1mm
17 mm 10 meters

Fig. 9.14 Maximum visual acuity for two point sources of light

Importance of visual acuity

Visual acuity helps us in determining outline, form or shape and other minute
details of the object.

The factors affecting visual acuity

(a) Type of stimulus.
(b) Illumination of the surface.
(c) Time of exposure.
(d) Brightness contrast.
(e) Normal and abnormal errors of refraction.

(i) Chromatic aberration tends to reduce visual acuity and therefore use of
monochromatic light increases the visual acuity.

(ii) Errors of refraction such as myopia, hypermetropia and astigmatism reduce

visual acuity.

(f) Visual acuity also depends on the site of the retina where the image is formed.
Visual acuity is highest at fovea centralis where only cones are present and it
tends to reduce towards the periphery of retina.

Testing of visual acuity

To test the visual acuity for distant vision, visual chart Snellen’s chart, is used.
Such a chart contains letters (of the alphabet) of different sizes. For example, the
letter L on the topmost row has the biggest size and a normal man can see it
clearly from a maximum distance of 60 meters. Letters of the 2nd row can be
seen clearly with emmetropic eyes, from a maximal distances of 36 m and so on.
The subject stands (or sits), 6m away from such a chart. If he can see, a letter of
the top row, (which an emmetropic man can see from 60 m), but no more, then
his vision is 6/60. This means he can see an object, only when he stands at 6 m
distance which one should normally see from a distance of 60m. Obviously a
normal vision is 6/6.

T
60 Meters

EB
36 Meters

LND
24 Meters
TP R E
18 Meters
OL M N E
12 Meters
TE DL M N
6 Meters
LP O R D Z
5 Meters

Fig. 9.15 Snellen’s chart

Field of Vision

On looking straight ahead it is that part of external world which can be seen with
each eye is called the field of vision. Theorotically it should be circular but is cut
off medially by the nose and superiorly by the roof of the orbit. (medial and
superiorly 60°, lateral 100° and inferiorly 75°). Visual fields are mapped by an
instrument called perimeter. The process called perimetry. Field of vision is
recorded separately for each eye.
0°

Binocular field
of vision
90° 90°

Monocular Monocular
Lt Rt
180°

Fig. 9.16 Field of vision

Method of recording
1. Confrontation method: It is a simple but rough method of perimetry. The
examiner sits opposite to the patient at a distance of about 1 metre. Each eye is
tested separately. For testing the right eye the subject is asked to close the left
eye and should look steady at the left eye of the examiner. The examiner should
cover his right eye and should look at the patient’s right eye. The examiner now
should hold his left hand midway between himself and the patient almost at a
full arms length at the side. The fingers of the hand are slowly moved nearer
until the examiner himself sees the fingers with the tail of the eye. The patient is
asked whether he could see the fingers. If the patient fails to see the fingers the
hand is brought further nearer until he sees the fingers. The field of vision is
tested in this fashion in every direction right, left, upwards and downwards and
is compared with the examiner’s field of vision.

2. Lister’s perimetry: The Lister’s perimeter consists of a semi circular arc

which can be rotated in 360 degree and can be fixed in any meridian. A white
object is fixed at the centre point. On the back of the arc a paper fixing device is
present on which perimeter charts are fixed. One eye is closed and the other eye
is fixed on the centre white object. A small target is moved towards this centre
point along selected meridians and along each the location where the target first
becomes visible is plotted in degrees of arc away from the central point. All
these points when joined gives the peripheral field of vision for that eye.

Binocular vision: The central parts of the visual fields of the two eyes coincide.
This is binocular field of vision. The impulses set up in the two retinas by light
rays from an object are fused at the cortical level into a single image. The points
of the retina on which the image of an object must fall, if it is to be seen
binocularly as a single object are called coresponding points. If the image does
not fall on these points, then diplopia results. Binocular vision is useful for
perception of depth.

Advantages
1. Optical defect of one eye is corrected by the other.
2. Field of vision is increased.
3. Stereoscopic vision.
Field of vision is affected by the diseases of the retina.
1. Retinitis pigmentosa—Degeneration of retina and excessive melanin.

2. Scotomas—Additional blind spots—they may develop due to allergic reaction

in the retina. Seen in tobacco smokers and lead poisoning. This can be diagnosed
by perimetry.

3. Retinal detachment—Field of vision decreases. 4. Field of vision is influenced

by the size and colour of the object.
5. Effect of the lesion in the optic pathway on the field of vision:

(a) Optic nerve—Complete loss of field of vision on that side

(b) Optic chiasma—Central part—Heteronymous hemianopia (bitemporal)—
Peripheral—Binasal.
(c) Optic tract—Homonymous hemianopia.
(d) Optic radiation—Homonymous hemianopia.
(e) Visual cortex—quadrantanopia with macula sparing.

HEARING OR AUDITION

Ear: Ear is the organ for hearing and equilibrium. The organ for equilibrium is
the semicircular canal of the ear and is known as vestibular apparatus. The organ
for hearing is cochlea. Ear is divided into 3 parts.

1. Outer ear 2. Middle ear 3. Inner ear.

The outer ear is made of pinna. It is for collecting and directing sound vibrations
on to the tympanic membrane. The pinna leads to a small tube known as external
auditory meatus. This tube ends with tympanic membrane or ear drum.

Contents and functions of middle ear: It is an air filled chamber and consists
of the following:
1. Tympanic membrane.

2. Ear ossicles—malleus, incus and stapes.

3. Eustachian tube
4. Muscles—tensor tympani and stapedius Functions
1. Tympanic membrane:
(i) It acts as a pressure receiver.
(ii) It acts as a resonator.
(iii) it critically dampens the sound waves.
2. Ear ossicles:
(i) Magnify the intensity by 1.3 times of sound. (ii) The surface area of tympanic
membrane is 50 mm2 and that of oval window is 3 mm2 or sq. mm, thus
reduction in area by 17 times at the level of oval window. This leads to
corresponding increase in pressure at the oval window. 1 and 2 together increase
the pressure within the middle ear by 22 times (17 × 1.3). This is called as
impedance matching.
Malleus
Incus Helicotrema Stapes at
Oval window Scala vestibuli
Cochlea
Tympanic membraneScala tympani Basilar membrane
Round window
Fig. 9.17
Structure of ear

3. Eustachian tube: It connects the middle ear to nasopharynx. It helps to

equalise the pressure on the two sides of the tympanic membrane when
atmospheric pressure decreases or increases.

4. Two skeletal muscles: tensor tympani and stapedius (i) Tensor tympani: It is
attached to the neck of malleus. Its contraction increases the tension of tympanic
membrane by pulling the handle of the malleus medially. Thus it keeps the
tympanic membrane firmly attached.

(ii) Stapedius: It is attached to the neck of the stapes and to the posterior wall of
the middle ear and on contraction it pulls the foot plate of the stapes out from the
oval widow. Function: Both the muscles, the tensor tympani and stapedius can
be reflexly activated by loud sounds and this reflexly decreases the amplitude of
sound vibration of the tympanic membrane. Thus they serve protective function
by protection of the internal ear by loud sounds. Tympanic reflex or Acoustic
reflex.

Inner Ear/Cochlea

It is a snail like structure. It is made up of 2¾ turns or coils. The inner cavity of

the cochlea is divided into 3 chambers due to the presence of two membranes.
The membranes are Reissner’s membrane and Basilar membrane. The 3
compartments are:

1. Scala vestibuli
2. Scala media and
3. Scala tympani.
The scala vestibuli and tympani are connected through a small opening known as
helicotrema.
Scala vestibuli is covered with oval window and scala tympani is covered with
round window. The organ of corti

is situated on the basilar membrane. Organ of corti is made up of numerous

sensory receptors or hair cells. This hair cells are arranged in inner and outer
rows. At the base of hair cells the auditory nerve fibres orginate. Scala vestibuli
and scala tympani are filld with perilymph. Scala media is filled with
endolymph.
Scaia vestibuli Cochlear duct
Organ of corti
Cochlear
nerve Scala tympani Hair cells
Tectorial membrane

Blood vessel
Basalar membrane

Nerve fibers
Fig. 9.18 Organ of corti
MECHANISM OF HEARING

Steps in the generation of sensory impulses from the ear.

1. Sound waves enter the external auditory meatus.
2. Waves of changing pressures cause the ear drum to reproduce the vibrations
coming from the sound wave source.
3. Auditory ossicles amplify and transmit vibrations to the end of the stapes.
4. Movement of the stapes of the oval window transmits vibrations to the
perilymph in the scala vestibuli.
5. Vibrations pass through the vestibular membrane and enter the endolymph of
the cochlear duct.
6. Different frequencies of vibration in endolymph stimulate different sets of
receptor cells.
7. A receptor cell becomes depolarised; its membrane becomes more permeable
to calcium ions.
8. In the presence of calcium ions, vesicles at the base of the receptors cell
release neurotransmitter.
9. Neurotransmitter stimulates the ends of nearby sensory neurons.
10. Sensory impulses are triggered on fibres of the cochlear branch of the
vestibulocochlear nerve. 11. The auditory cortex of the temporal lobe interprets
the sensory impulses.

Cochlear Potential

1. It is the electrical response that represents the summated intracellular

potentials of many hair cells.
2. It is generated instantaneously due to large current flow across the apical
surface of the hair cells along a favourable electrical gradient.
3. Cochlear potential obeys all or none law and has a definite threshold and
refractory period.
4. When the stimulus intensity is severe, the rate of cochlear potential formation
is more than that of the action potential.
5. The recording of cochlear potential can be a positive or negative deflection
with the reversal of polarity of the stimulus.

Localisation of the sound

In normal human being, it is very easy to locate the direction of the source of
incoming sound waves, in localisation of sound various factors are involved such
as:
1. The difference in time between the arrivals of the

stimulus in two ears helps to decide the direction of sound.

2. The sound intensity is perceived more in the ear which is nearer to that
stimulus.
3. The shape of the ear pinna to attenuate certain sound frequencies depending
on the angle at which sound waves approach the ear.

THEORIES OF HEARING

A significant part of the history of the hearing sciences is bound up with two
“theories of hearing.” These two theories are mainly about how the peripheral
auditory system, the inner ear, codes for the frequency of sound, and how that
frequency code accounts for the perception of pitch. While sound contains more
information about its source than just frequency, frequency and the resulting
pitch perception are the key attributes of sound for most aspects of perception.
Discussions about how the inner ear codes for frequency stared in the mid 19th
century and continues in one form or another today.

The Place Theory suggests the each auditory nerve fibre is uniquely sensitive to
a particular frequency of sound stimulation. Thus, the code for frequency is
provided by which nerve fibre is firing. This is a like a telephone switch board.
The switch board operator (the brain) can determine what phone is ringing (the
frequency of the input) by which light on the switch board that lights up (nerve
fibre firing). That is, the light on the switchboard code for which phone is
actually ringing. George von Bekesy is often credited with espousing the place
theory of hearing.
The other theory is the “Temporal Theory.” This theory suggests that the
temporal pattern of neural discharges codes for frequency. For a periodic signal
the nerve discharges in synchrony with the stimulus’s periodicity, and thus the
reciprocal of that neural periodicity provides an estimate of frequency. Glen
Wever is often associated with the temporal theories, probably because of his
suggestion of the “volley principal.” The volley principal suggested a way in
which the nervous system could provide a temporal code for highfrequency
sounds, where the refractory properties of single auditory nerve fibres prevent
them for coding for the periodicities of high frequencies. The volley principal
suggests that if one fibre fired to every other periodic stimulus fluctuation, and
another fibre the every third fluctuation, and so on, then the sum of the activity
of all of the participating fibres could capture the actual periodicity of a high-
frequency sound. That is, no one nerve fibre can capture the periodicity of a
high-frequency sound, but the volley of neural activity from many different
nerve fibres might.

Today most hearing scientists appreciate that both the Place and the Temporal
Theories play a crucial role in coding for sound. The theories are still debated at
a more detailed level, especially in regard to neural mechanisms of complex
pitch perception.

Travelling wave theory: A wave travels from the base to the apex of the basilar
membrane of the cochlea in response to acoustic stimulation, and that the site of
maximal displacement of the basilar membrane depends on the frequency of the
stimulating tone with higher frequencies causing maximal displacement near the
base and lower frequencies causing maximal displacement near the apex.

Auditory pathway

The nerve cell bodies of the dendrites that arise from the hair cells, constitute the
spiral ganglion, situated within the internal ear. The axons arising from the spiral
gangilon (= the nerve fibres that costitute the cochelar division of the VIIIth
nerve) terminate in the ventral and dorsal cochlear nuclei. From these nuclei,
notably in the trapezoid body, further order neurons arise and ultimately
terminate in the inferior colliculi (i.e., in the dorsal side of the mid brain) from
where fresh order neurons arise to terminate on medial geniculate body (MGB)
of the thalamus. Each of the intermediate nuclei and MGB receive fibres from
both ears because extensive crossing of these afferent fibres from one side to the
other occurs.
From MGB, the final order neurons arise and terminate on the area 41 of
temporal lobe, which is popularly called, auditory cortex. Obviously, each
auditory cortex receives extensive connections from both the ears.

Fibres of the cochlear division of the auditory nerve are arranged according to
the auditory frequency. This ‘tonotopic’ pattern is seen even in the auditory
cortex.

Deafness
It is defined as inability to hear.
Deafness is classified into two types:
1. Conduction deafness and
2. Nerve deafness

Conduction deafness: Defect in the conduction of sound waves.

Causes

1. Block in the external auditory meatus due to hardening of wax, tumor or due
to presence of foreign particles.

2. Damage or perforation of tympanic membrane due to injury or infection.

3. Osteoporosis of bones of middle ear.
Cerebral cortex Auditory cortex
Bone conduction

Thalamus Medial
geniculate body
A

Midbrain Inferior
colliculus Tuning

Air fork conduction

Pons

Dorsal cochlear nucleus

Nucleus of the lateral
lemniscus

Lateral
lemniscus
Medulla

Cochlear branch of vestibulo cochlear nerve

Ventral cochlear nucleus
Olivary complex

Tropezoid body
Fig. 9.19 Auditory pathway

Nerve deafness
Causes
1. Lesion of auditory nerve due to infection or injury. 2. Congenital deformity of
organ of corti. 3. Lesion of temporal lobe of cerebral cortex.
Tests for deafness
1. Whisper test
2. Stop watch test
3. Rinne’s test
4. Weber’s test
5. Schwabach’s test
6. Audiometry.
Rinne’s test: A tuning fork of 512 Hz is vibrated and
kept on the mastoid process. When the subject stops hearing
it is kept in front of the ear. He will continue to hear provided
there is no conduction deafness. Air conduction is better
than bony conduction.
Weber’s test: Tuning fork of 512 Hz is vibrated and
kept at the vertex of the skull in midline. The normal person
will hear equally well in both the ears. The person suffering
BC

Rinne's test Weber's test Fig. 9.20 Tuning fork tests for deafner

from conduction deafness will hear louder in the defective ear. This is because
there is no background noise in the ear suffering from conduction deafness.

Schwabach’s test: This test is useful to compare bone conduction of patient

with a normal subject. In conduction deafness, bone conduction appears to be
better than normal. In nerve conduction deafness, bone conduction is work than
normal. This test is useful to differentiate between conduction deafness and
nerve deafness.

Audiometry
Audiometry is the key hearing test used to identify hearing threshold levels of an
individual, enabling determination of the degree, type and configuration of a
hearing loss. Thus, providing the basis for diagnosis and management.
Audiometry is a subjective, behavioural measurement of hearing threshold, as it
relies on patient response to sound pitch stimuli.

Therefore, audiometry is used on adults and children old enough to cooperate

with the test procedure. The test should be performed in a sound-proof room and
each ear should be tested separately. Audiometry only measures thresholds,
rather than other aspects of hearing such as sound localisation. However, there
are benefits of using audiometry over other forms of hearing test, such as click
auditory brainstem response. Audiometry provides ear specific thresholds, and
uses frequency specific pure tones to give place specific responses, so that the
configuration of a hearing loss can be identified.

As audiometry uses both air and bone conduction, the type of loss can also be
identified via the air-bone gap. Although audiometry has many clinical benefits,
it is not perfect at identifying all losses, such as dead regions. This raises the
question of whether or not audiograms accurately predict someone’s perceived
degree of disability.
0 10 Normal
20
30 40
50 Air
60 70

80
90
100
125 250 500 1000 2000 4000 8000 Frequency (Hz)
Fig. 9.21 Audiogram—Nerve deafness
–10
0
10

25
Slight mild moderate
moderately severe

40 severe
Profound55
70
85

100
500 1000 2000 3000 4000 6000 Low pitchedFrequency, hertz High pitched Sounds Sounds

Fig. 9.22
Audiogram
Decibels
160 Jet plane with afterburner Pain
120 Discomfort
Subway, live rock music

80 Heavy traffic
Normal conversation
40 Whisper
Threshold of hearing (0.0002 0 dyne/cm )2

Decibel scale for common sounds

Vestibular Apparatus

Vestibular apparatus is a sense organ detecting position and motion of the head
and body. So it is important in the maintenance of equilibrium at rest and
balancing the body during movement.

Structure of vestibular apparatus. Inside the internal ear there are two sense
organs:
1. Cochlea for audition.
2. Vestibular apparatus for sense of balancing.
The bony structure of inner ear is called as bony labyrinth. Within the bony
labyrinth the membraneous sac present is known as membraneous labyrinth. The
gap between membraneous and bony labyrinth is filled with perilymph. The
fluid inside the membraneous labyrinth is called as endolymph. The vestibular
apparatus consists of two parts.
1. Otolith organs—detects lenear accleration.
2. Semicircular canals—detect angular acceleration.
Otolith organs consist of two sac like structures— Saccule and utricle. The
saccule communicates with cochlea through ductus reuniens. These structures
contain stone like structures—otoliths made up of protein and calcium
carbonate. Semi-circular canals are three in number and they are arranged in
three mutually perpendicular planes. They are known as horizontal, anterior and
posterior semicircular canals.
The dilated end of semicircular canals are known as ampulla which contains
receptors—hair cells. Ampulla opens into utricle. Within the ampulla there is a
ridge in the inner wall of membraneous labyrinth. Each ampulla contains crista
ampullaries. It contains the receptor cells—hair cells. The hairs are embedded in
a gelatinous matrix, this structure hairs + gelatinous substance together is called
cupula. Hair cells with cupula together called cristae. Cristae are the end organs
or the receptors in the semicircular canal.
Anterior semicirular canal

Ampulla Utricle Saccule Otolith organs

Posterior semicircular canal

Cochlea

Horizontal
semicircular
canal Ampulla Endolymphatic sac

Fig. 9.23
A schematic diagram of the vestibular apparatus and cochlea
Macula and otolith organs

Utricle and saccule are round in shape. Within these structures there are ridge
like structures. From these ridges hair cells shoot out. The hairs are embedded in
a gelatinous material containing calcium carbonate crystals known as otoliths.
The gelatinous material and calcium carbonate crystals together known as otolith
membrane. The otolith membrane plus the hair cells together is called macula.
Maculae are often called otolith organs, they are end organs for gravity
reception.
Kinocilium Stereocilia
Nerve chalice
Neurotransmitter vesicles
Otoliths

Matrix Nucleus Supporting cell

Hair cells Macula

Fig. 9.24 Structure of otolith organs
Hair cell
Macula
Fig. 9.27
The hair cell

Structure of hair cells: Receptors of vestibular apparatus: The hair cells have
several cilia arranged according to their length. The longest cilia is kinocilium,
the other cilia are stereocilia arranged in graded length. The bending of cilia
leads to generation of action potential. From the bottom of these hair cells nerves
of vestibular branch of VIII cranial nerve arise.
Utricle Saccule Extraoccular muscle Cerebellum Occulomotor nuclei
Fig. 9.25
Position of macula and arrangement of hair cells.
VestibularVestibular nerve nuclel
Ampulla SCC Saccule Utricle
Cupula

Hair cell Vestibular ganglion

Crista
ampullaris Vestibulo spinal tract
Nerve fibres

Fig. 9.26 Structure of ampulla of semicircular canal

Afferent fibre
Efferent fibre
Skeletal muscles Spinal cord
Fig. 9.28
Vestibular pathways

Nerve Connection: Vestibular pathway

The nerve fibres arise from cristae and maculae. These nerve fibres form the
vestibular division of VIIIth cranial nerve. The cell bodies of VIII cranial nerve
is placed in the vestibular ganglion (scarpa’s ganglion). From the vestibular
ganglion the central axons proceed towards brain stem and reach vestibular
nucleus. It is situated on the dorsal surface of pons, in the floor of forth ventricle.
The vestibular nucleus has four subparts—lateral, medial, superior and inferior
vestibular nucleil.
1. Lateral vestibular nucleus: It receives inputs from utricle, cerebellum and
spinal cord. The afferents from their nucleus are mainly given to the antigravity
muscle.
2. Medial vestibular nucleus: It recieves input from otolith organs, semicircular
canals and cerebellum. Efferents from this nucleus make the vestibulor spinal
tract.
3. Superior vestibular nucleus also receive impulses from otolith organ,
semicircular canal and cerebellum. Efferent fibres from this nucleus gives to
cerebellum and occulomotor nerve nucleus.
4. Inferior vestibular nucleus: It receives afferant inputs from cerebellum. It
sends efferent impulses to spinal cord.
motion, when actually no rotation is occurring. Types: Physiological vertigo—
Motion Sickness. It is due to over

stimulation of vestibular apparatus and nonmatching of sensory inputs from eyes

and vestibular apparatus. It is commonly seen during travelling in a ship or fast
moving vehicle. The major symptoms of motion sickness are nausea, palpitation,
dizziness and vomiting.

Nystagmus: This is defined as involuntary jerky oscillations of eyes (one or

both). It is due to an ataxia or in coordination of movements of extrinsic muscles
of eye.

Caloric nystagmus: When vestibular apparatus is stimulated by irrigating ear

canal alternatively with cold and warm saline. This produces jerky movements
of eye which is known as caloric nystagmus.

Olfaction or Sense of Smell

It is a chemical sense.
Cribriform plate
Axons Basement membrane

Vestibular nucleus sends efferent outputs to cerebellum which is very important

for the maintenance of posture and equilibrium. The efferent outputs sent to the
occulomotor nucleus control eye movements. The efferent impulses sent to the
spinal cord motor nuclei helps in the control of postural reflexes.

Functions of vestibular apparants

1. Vestibular apparatus informs the brain about rotational acceleration
movements with the help of semicircular canals.

2. It informs the position of head related with gravity.

3. The vestibulo occular reflexes help to keep the eyes at a fixed gaze. This
provides stability of visual images inspite of bodily movements.
4. The righting reflex initiated by the vestibular apparatus helps to regain the lost
balance.

Disorders of vestibular apparatus

Meniere syndrome
Cause: Damage of vestibular apparatus and cochlea. Symptoms: Vertigo,
dizziness, ataxia, nystagmus. Vertigo: It is a condition in which an individual
has a sensation that his head is rotating in the absence of actual rotation of head.
It is the illusion of motion or rotational
Supporting cell Olfactory mucosa

Cilia Receptor cells

Fig. 9.29
Olfactory receptor

Mechanism of olfaction: Molecules emanating from an odorant substance

(every odorant must, thus, be atleast a little, volatile) are carried by air reach the
olfactory area get dissolved in the mucus in solution, it comes in contact with the
intramembranous particles (molecular receptive apparatus) contain within the
cilia of the receptor cells and combine with these particles lead to development
of receptor potential, development of impulses reach the appropriate part of the
brain concerned with perception of smell sense.

Olfactory pathway: The axons emerging from the receptor cells are collected
into fascicles and these filaments (usually 20 in number) pierce the cribriform
plate of the ethmoid bone to enter the cranial cavity. In the cranial cavity, these
primary neurons lying in the under surface of the brain end in the olfactory bulb.
In the olfactory bulb, they make complicated synapses called glomeruli.

Olfactory bulb: This is a flattened ovoid body present in the cribri form plate of
ethmoid bone. It is mode up of different types of cells:

(a) Mitral cells (c) Granule cells (b) Tufted cells

(d) Periglomerular cells.

Mitral cells: The axons of bipolar cells synapse with dendrites of mitral cells to
form complex glomerular synapse. It is called as olfactory glomeruli. The axons
of bipolar cells also synapse with Tufted cells. Axons from about 26000 receptor
cells converge on a singh glorreruli which in turn converge with dendrites of
mitral and tufted cells. The axons of mitral and tufted cells make the olfactory
tract.

Second order neurons emerge from the glomeruli and forms the olfactory tract
which ends as follows:
The medial olfactory stria crosses the midline and enters the opposite olfactory
tract to terminate on the olfactory bulb of the opposite side.
The lateral olfactory stria terminates on various areas, chiefly,
(i) Primary olfactory cortex showing part of the primary olfactory cortex
(ii) Amygdaloid complex and to many other areas.
Primary olfactory cortex includes
(a) prepyriform area
(b) pyriform cortex
(i) from the olfactory bulb and
(ii) from the substantra nigra of mid brain.
Efferent fibres from amygdala go to the hypothalamus thus olfaction is
associated with appetite and sexual behaviour.
1. Further, from the primary olfactory cortex, nerve impulses go to terminate on
secondary olfactory cortex and other parts of limbic system nuclei. Thus the
smell sensation influences various behaviour and arouses emotions (notably food
behaviour and sex behaviour).
2. To reach the cortex, the neurons do not have to relay at thalamus, which is
exceptional. Infact this is the only sense which does not relay at thalamus or
metathalamus.
Glomeruli: Within the olfactory bulb, complicated synapses called glomeruli,
are present. Axons from about 26,000 receptor cells converge on a single
glomerulus which in turn converge with several dendrites of mitral and tuft cells.
Therefore, in this way, the impulses coming from the olfactory nerve are handed
over to the mitral and tuft cells. The axons of the mitral and tuft cells form as
already stated, the olfactory tract.
Mitral and tufted cells Anterior olfactory nucleus

Entorhinal area
Primary
olfactory cortex Septal area

Crilbriform plate Fibre of olfactory nerve

Thalamus (medial and dorsal nucleus)

Olfactory cell Amygdala Orbitofrontal cortex

Fig. 9.30
Olfactory pathway

The primary smell sensations are:

1. camphorous 2. musky
3. floral 4. etherial
5. pepperminty 6. pungent (c) entorhinal cortex (which is adjascent to
hippocampus),
(d) olfactory tubercle and so on.
The olfactory tubercle receives inputs from 2 major sources.

7. putrid. Man can distinguish 2000 to 4000 different odors.

Physiological importance of olfactory sensation:

1. It plays a major role in selection of food.
2. It is a major factor initiating food intake.
3. It plays a major role in reproductive behaviour.
4. It helps in recognising objects, places and people.

Variation in sense of olfaction

1. Sex: Females are more sensitive to smell than male, especially at the time of
ovulation.
2. Hyperosmia: It is a condition of increased sensitivity to smell.
3. Hyposmia: It is condition of decreased sensitivity to smell, may be due to the
effect of adaptation.
4. Anosmia: Loss of sense of smell. Causes: Common cold, fracture of
cribriform plate, excess prolonged use of snuff.

Sense of Taste—Gustation
Taste buds

Taste buds are the oval structures in which taste receptors are located. There are
about 10,000 taste buds in man. Most of the taste buds are distributed over the
tongue, but a few of buds are seen in mucus membrane covering the soft palate,
epiglottis, larynx and pharynx. In the tongue taste buds are located in the walls
of fungi form, foliate and circumvallate papillae. The filiform papillae on the
dorsum of tongue are deprived of taste buds.
The fungiform papillae are round in shape and they are located mainly near the
tip and margins of the anterior 2/3 of the tongue. About 5 taste buds per papilla
are seen. They are innervated by chorda tympani nerve, the branch of facial
nerve. These taste buds are more sensitive to the sweet. The circumvallate
papillae are arranged in the form of alphabet “V” on the back of tongue. It
contains about 100 taste buds per papilla. These taste buds are sensitive for sour
and salty sensation. They are invervated by facial nerve. Foliate papillae are
located in the posterior 1/3rd of tongue and innervated by the glossopharyngeal
nerve. These taste buds are more sensitive to bitter taste. Pharyngeal and
laryngeal taste buds are innervated by vagus. Palatal taste buds are innervated by
greater petrossal branch of facial nerve.
Sour
Salt
Sweet

Fig. 9.32
Distribution of taste buds in tongue

Each taste bud is a oval shaped structure measurity about 50–70 um.
The taste bud is packed with cells and in its tip there is a pore, called the ‘taste
pore’.
The cells which fill the taste bud, are of two types: (i) Supporting or
sustentacular cells,
(ii) Taste (or receptor) cells.
In an individual bud the sustentacular and taste cells taken together number
about 40 to 50 cells of which about 12 cells belong to the taste cells. However, it
is now known that the taste cells and the supporting cells belong to the same
class of cells and represent merely different stages of development. From the
taste cells, hair like process, the ‘microvilli’ project out of the pores. It is
believed that the molecular receptors are present on these microvilli. The taste
cells, therefore, are the cells which receive the taste sensations.
Taste is one of the chemical sensations. There are five primary taste sensations.
They are sweet, salt, sour, bitter and umami. By the mixture of these basic
modality of more then 100 different types of taste can be perceived by man.

TABLE 9.3 Modality of taste and substances producing

Taste pore Sl.No. Modality of taste 1. Sweet
2. Sour
Taste receptor cell
3. Salty
Nerve fibres 4. Bitter
Fig. 9.31
Taste bud
Bitter
5. Umami
Substances producing the taste

Aldehydes, alcohols, sugars – glucose, fructose, sucrose, glycerol, saccharin.

Organic and inorganic acids, citric acid, fumeric acid.

Ionisable salts like NaCl, dipeptides like lysyl taurine
Alkaloids, like nicotine, quinine, caffeine, strychnine, theophilin Mono sodium
glutamate

Fine nerve fibres are found within each taste bud. These nerve fibres carry taste
sensation (from these buds) and constitute either the chorda tympani (in the
anterior 2/3rd of the tongue) or the glossopharyn geal nerve (in the posterior
1/3rd).

Throughout our life, the taste cells degenerate and are replaced by new cells
from the surrounding supporting cells. However, although the taste cells
degenerate regularly the nerve terminals do not. Conversely, if the nerve fibres
degenerate due to disease, the taste cells also die.

Taste pathway
Taste sensation, from anterior 2/3rd of the tongue, is carried by the chorda
tympani nerve and then proceeds in the sensory
Cerebral corted

division (nerve of Wrisberg) of the 7th cranial nerve (facial) and terminate on the
nuclei of the tractus solitarius (a structure situated in the medulla). From the
posterior 1/3rd of the tongue, the taste sensation is conveyed by the sensory
fibres of the glossopharyngeal nerve which also terminate on the nuclei of the
tractus solitarius (NTS).

The second order neurons arise from nucleus of tractus solitaries. The axons of
these neurons ascend in the ipsilateral medial lemniscus and reach ventral
postereo medial nucleus of thalamus. Third order neurons arise from the
thalamus and terminate on the post central gyrus at its lower lateral part which is
buried within the lateral sulcus. This is the highest cortical area for the sensation
of taste.
Third order neuron Somato sensory area

Thalamus Midline
Second order neuron

Nucleus tractus solitarius in medulla First order neuron

V
Anterior 2/3rd of tongue
Tongue
Posterior 1/3rd of tongue Epiglottis and pharynx region
Fig. 9.33
Taste Pathway

Synthetic sweeteners: Saccharin, dulcin, cyclamate. Saccharine is 500 times

sweeter than cane sugar but highly toxic. A substance called p-4000 is 5000
times sweeter than sucrose but very toxic.
Abnormalities of taste sensation

Ageusia
Hypogeusia Dysgeusia
– total absence of sensation of taste.
– decreased taste sensitivity.
– altered taste sensation.

Mechanism of taste sensation

The substance concerned must be in solution, ( e.g., in the saliva) and will attach
itself with the molecular receptors of the microvilli. This combination leads to
some electrophysiological changes so as to cause stimulation of the receptor cell
and then the nerve fibres which emerge from the taste buds are stimulated the
impulse then reaches the appropriate part of the brain. However, many details of
this process remain obscure till date.

Physiological functions of taste sensation

1. Taste sensation plays a major role in the selection of food.

2. Taste sensation is one of the driving force for eating. Taste increases desire for
food.
Muscle Physiology and Exercise Physiology

Sir Charles Scott

Sherington
27-11-1857–4-3-1952
English Physiologist
Study of integrated nervous system
Nobel Prize (1932)
Hugh Esmor Huxley
25-02-1924–25-7-2013 British Molecular Biologist known for myosin muscle
actin

(386) Chapter
10
Muscle—types.
MUSCLE PHYSIOLOGY AND EXERCISE PHYSIOLOGY

Comparison between skeletal, cardiac and smooth muscles.

Motor unit.

Physiological anatomy of skeletal muscle, sarcomere, contractile muscle

proteins.
Sarcoplasmic reticulum.
Properties of skeletal muscle.

Neuromuscular junction—structure, neuromuscular transmission, neuromuscular

blockers, myasthenia gravis.

Excitation contraction coupling, molecular basis of muscle contraction.

Experiments on properties of muscles.
Chemical changes during contraction.

Types of contraction—isometric and isotonic. Fast and slow muscle.

Muscle dystrophy, rigor mortis.

Smooth muscle—structure, types and functions. Mechanism of smooth muscle
contraction. Exercise physiology—isotonic and isometric exercise, gradation of
exercise.
Changes during exercise—cardiovascular, respiratory, metabolic, endocrine and
nervous. Effect of training on muscular performance, health benefits of exercise.

MUSCLE PHYSIOLOGY

Muscles are contracting tissues, which can contract. There are three types of
muscles. They are
Skeletal muscles (Voluntary, Striated)
Cardiac muscles
Smooth muscles (involuntary, non-striated).
TABLE 10.1
Comparison between cardiac, skeletal and smooth muscles
Sl.No. Property Cardiac muscles Skeletal muscles Smooth muscles 1.
Location Heart

Skeletal muscles are mostly attached to bones G.I.T, bladder,

uterus, ureter etc. (visceral)

2. Branching of muscle fibres Present Absent Absent

3. Inter calated disc Present Absent Absent 4. Regular sarcomere Present Present
Absent 5. Syncytium Functions as syncytium No Functions as syncytium 6.
Nucleus Centrally located

single nucleus Eccentrically located multi nuclei

Centrally located single nucleus

7. Sacro tubular system Well developed Well developed Poorly developed 8.

‘T’tubules Present Present Absent 9. Triads and Diads Present at the

‘Z’ line
Only triads present at A-I junction
Absent

Contd…
10. Gap junction Present at Inter calated disc Absent Present 11. Excitability
Depends on the nerve for its excitability
Self-excitatory Self excitatory (visceral)
12. Site of Ca++ regulation Troponin Troponin Calmodulin 13. Refractory period
Short Prolonged Short 14. Conducting system Absent Present Present 15. Pace
Maker Potential Absent Present Absent 16. Effect of stretch of contraction
No effect No effect Responds
17. Speed of contraction Fast Slow Very slow 18. Length tension relation Exists
Exists No definite relation

Motor Unit
A motor nerve fibre and the muscle innervated (supplied) by it is called as a
motor unit.

Number of muscle fibres controlled by a single motor neuron varies from a few
to two thousand. It depends upon the precision of work carried out by the
muscles, in the muscles of finger one neuron controls only a few fibres. In thigh
two thousand muscle fibres are supervised by a single motor neuron.
Grey matter Tendon
Muscle fibre Muscle spindle
White matter
Anterior horn cell (Motor neuron) Anterior nerve root
Motor nerve ending

Motor neuron (single fibre of each motor neuron cell)

Fig. 10.1 Motor unit

Motor unit
Structure of skeletal muscles

Skeletal muscle is made up of numerous muscle fibres.

Skeletal muscle is made up of numerous muscle fibres. 40mm), diameter 50-

100mm. This is covered by a membrane called as sarcolemma. These muscle
fibres are made up of numerous myofibrils. These myofibrils show a striated
appearance. Alternate dark and light bands are seen. Dark bands are known as
‘A’ bands, light bands are known as ‘I’ bands.
Sarcomere: It is the structural and functional unit of a

muscle. There are two types of filaments-thick and thin filament. Thick filament
is made up of myosin molecules, and thin filaments are made up of actin,
troponin and tropomyosin. Myosin, actin, troponin, tropomyosin are contractile
proteins. Thick and thin filaments are arranged alternatively.

types of tubular systems: T tubules–transverse tubules and L tubules –

longitudinal tubules.
Muscle
Muscle fiber

I band A bandMuscle Muscle fiber

Sarcomer
Z line M line Z line
Cross bridgeH zone
A bandI band
Thin (actin) filament Thick (Myosin) filament
Fig. 10.2 Sarcomere
A bandI band H band
Cross
bridges
Thin filamentM line Thick filament Fig. 10.3
Structure of Sarcomere

The portion of overlapping of thick and thin filament is known as ‘A’ band. The
portion where there is only thin filament is known as ‘I’ band. The ‘I’ band is
separated by ‘Z’ line. The portion of the muscle fibril in between 2 successive
‘Z’ line is known as sarcomere. The portion of ‘A’ band where there is only thick
filament is known as ‘H’ band. The central portion of ‘H’ band is known as ‘M’
line.

There are several cross bridges arising from thick filament. The fluid present
inside sarcolemma is sarcoplasm. The membrane shows invaginations. This
gives rise to two
Cisterne L - tubule T - tubule
A - I junction
Thick filament Thin filament
Fig. 10.4 Sarcoplasmic reticulum
SARCOPLASMIC RETICULUM

It is a complex network of tubules formed at the muscle membrane. This system

is well developed in skeletal muscle. It is well organised in a highly geometrical
pattern. It comprises of two types of tubules: 1. Running parallel to the length of
muscle fibre-longitudinal tubule L-tubule. 2. Some run from the surface towards
the centre of the fibretransverse tubule or T-tubule. The T-tubules are
invagination of sarcolemmal membrane within the cell. In the skeletal muscle T-
tubule is situated at the junction of A and I band. The space enclosed by the T-
tubules inside them is extracellular space filled with ECF. So the extracellular
space extends deep into the interior of muscle cell through the T-tubule. At the
junction of T-tubule and L-tubule there is a swelling called cisterne. This is filled
with calcium ions. T-tubule and two cisternes, one on either side of the T-tubules
are together called triad. The calcium are stored with the help of a protein called
calsequestrin. When action potential spreeds on the surface of sarcolemma,it
travels down the T-tubules up to the vicinity of the terminal cisterne. This leads
to the release of calcium ions which results in excitation contractions coupling
and eventually results in muscle contraction. Once the contraction is over
calcium ions are pushed back into the cistrene leading to the relaxation of
muscle.

Properties of Skeletal Muscles

1. Excitation/Excitability
2. Conduction
3. Contraction
4. Refractory period
5. All or none law
6. Length and force of contraction.
Excitation

This property is shown by muscle and nerves. Excitability is defined as ability to

respond to a stimulus by way of generating an action potential. Stimulus means
change in the energy level.

Resting membrane potential is defined as the potential or voltage difference

existing between inside and outside of a muscle membrane, when it is at rest. For
skeletal muscle RMP is -90mV. This polarity is due to unequal distribution of
ions or electrolytes between inside and outside of the membrane.

1. Sodium and chloride ions are more outside than inside.

2. K+ ions is more inside than outside.
3. Negatively charged protein ions are more inside the

membrane.

Outside Na
+ Cl −+
K

Inside Na Cl+− +K Protein−

The unequal distribution of ions is due to three reasons:

1. The membrane is more permeable to potassium ions than sodium ions.

2. Sodium-Potassium pump—it is a carrier mediated transport. Its an active
transport mechanism and takes place at the expenditure of metabolic energy.
3. Presence of net negatively charged non diffusable protein ions inside the
membrane.
When muscle is stimulated the permeability of membrane changes. The
membrane becomes more permeable to sodium ions. This leads to rushing of
sodium ions from outside to inside. Because of this inside of the membrane
becomes more and more +ve, less and less negative. The polarity is lost and for a
fraction of second inside of the membrane becomes positive (+ 30 mV). Once
again the polarity is reestablished. Action potential is defined as a changing
potential across the membrane with phase of depolarisation followed with
repolarisation spreading along the length of the muscle membrane.
Spike potential
+20
Overshoot
0
Firing level

–70
Point of After stimulus depolarisation
–90

Latent Afer
period hyperpolarisation Time (ms)
Absolute Relativerefractory
refractoryperiod period

Fig. 10.5 Action potential

Conduction
The action potential generated at any part of the muscle

membrane is not restricted to that site. Instead it is propagated throughout the

length of the muscle, membrane. This property is known as conduction of
impulses or transmission of action potential.
+ + – – +++++++
–– +–– – ––– – –RestingDepolarisation
during the action– + + – – – ––– – – membrane potential causes ++––++ ++++ potential adjacent Na+
channels to open
++ + + +++++++
–– – – – + + – – – – – –
– – – – –+ + – – – – – – + + + + + –– + + + + + +
+ + ++++ + + + + –– ++
– –––––––––––– ––
– –––––––––––– –– + + ++++ + + + + –– ++
Fig. 10.6 Mechanism of conduction
Contraction
Contraction means shortening of the length of the muscle fibres.

The gap between two ‘Z’ lines decreases. Contraction is a mechanical property
of the muscle. Contraction of muscle leads to movements of parts of the body
and helps in working.

Refractory period: Refractory period is defined as a period during which a

second stimulus cannot produce a fresh action potential.

It is divided into two parts:

1. Absolute refractory period
2. Relative refractory period
Absolute refractory period: It is the first portion of the refractory period during
which a second stimulus of whatever higher intensity cannot generate a fresh
action potential. Relative refractory period: It is the later part of the refractory
period during which a second stimulus of higher intensity can produce a fresh
action potential but a second stimulus of same intensity cannot produce a fresh
action potential.
All or none law: The minimum strength of stimulus required to generate an
action potential is known as threshold stimulus, any strength of stimulus below
the threshold level is known as subthreshold. Strength of stimulus above the
threshold is known as suprathreshold. There is no response for subthreshold
stimulus, when the strength of a stimulus reaches a threshold level, there will be
a response and the magnitude of response is maximum. When the strength of a
stimulus is increased above the threshold level, there will be

a response but there is no proportionate increase in the magnitude of response. If

the muscles respond it will respond maximaly otherwise not at all. This
phenomenon is known as all or none law.

Length of muscles and force of contraction— Starling’s law: This law states
that the force of contraction of a muscle fibre is proportional to its initial length.

Strength duration curve or excitability curve: It is a graphical representation

of relationship existing between strength of stimulus and duration of its
application. Chronaxie is defined as the minimum duration of time required to
bring about response with twice or double the rheobasic current.

Rheobase: Minimum strength of stimulus required to bring about

response/action potential in a tissue.

1Excitability ∝chronaxie

Strength duration curve: The curve which can represent the excitability of
tissue.
Utilisation time: It is the duration of time for which a strength of stimulus equal
to rheobase has to be applied to generate an action potential.
6R
5R
4R
3R
2R C
RU R

Fig. 10.7 Duration of stimulus strength duration curve of an excitable tissue, R,

rheobase, C, chronaxie, U-utilisation time

Motor Unit Neuromuscular Junction

Neuromuscular junction is the junction formed between the motor neurons and
the muscle fibres. This junction consists of the motor nerve end and the muscle
end which is called the motor end plate.
Myelin sheath
Mitochondria

Acetylcholine receptors
Synaptic vesicles

Axon terminal
in synaptic trough
Mitochondria
Subneural clefts

Fig. 10.8 Neuromuscular junction

Structure of neuromuscular junction

The motor neuron before it reaches the motor end plate looses its myelin sheath
and becomes naked.

The motor axon branches at the neuromuscular junction to form several rounded
or flattened terminals, which fit into depressions on the surface of skeletal
muscles. The myelin sheath terminates just before the neuromuscular junction,
but the junction is insulated by Schwann cells, called teloglia. The neuronal
membrane participating in neuromuscular junction is called presynaptic
membrane, the muscle fibre membrane is called post synaptic membrane. The
portion of muscle fibre is called motor end plate, space between pre and post
synaptic membrane is called synaptic cleft (25 nm wide).

Axon terminal has large number of mitochondria, neurotransmitter vesicles.

Neuromuscular transmission

1. Arrival of action potential at the motor nerve axon terminal.

2. Opening of voltage gated calcium channels at axon terminal.
3. Influx of calcium ions.
4. Movement of acetylcholine-vesicles towards presynaptic membrane.
5. Fusion of vesicles with presynaptic membrane.
6. Release of acetylcholine into synaptic cleft by exocytosis.
7. Diffusion of acetylcholine molecules through the synaptic cleft.
8. Binding of acetylcholine to the acetylcholine receptors present at postsynaptic
membrane (the Ach receptors are proteins which are shaped like tubes or
channels).
9. Opening of chemically gated(or ligand gated) ionic channels.

10. Influx of sodium.

11. Depolarisation of post-synaptic membrane gives rise to end plate
potential(EPP) (Magnitude of EPP depends on how many Na+ ions enter the
muscle cells, which in turn depends upon the amount of acetylcholine released
which depends upon the number of voltage gated Ca++ channels that open,
which in turn depends upon the frequency of action potential arriving at axon
terminal.
12. When EPP crosses critical firing threshold level, an action potential is
obtained.
Even when the motor nerve fibre and muscle are completely at rest, small
amount of acetylcholine are released from axon terminals, which gives rise to
small degrees of depolarisation called Miniature End Plate Potential (MEPP).

Synthesis and fate of acetylcholine

Acetylcholine is synthesised from acetyl CoA and choline using the enzyme
choline acetyl transferase in the cytosol of motor neurons. It is transported along
the axon for being packaged into vesicles in axon terminal.

After its release from vesicles, acetylcholine binds with muscle membrane. Later
the enzyme acetylcholine-sterase hydrolyses acetylcholine into acetate and
choline. This hydolysis is useful because it prevents prolongation of the action
and for the reformation of vescicles.

Neuromuscular blocking agents

Neuromuscular blocking agents are of two types: (a) Depolarising type and
(b) Non-depolarising type
Depolarising type
These agents act like acetylcholine, but are resistant to
the action of acetylcholine esterase. Their initial action is to
depolarise (like Ach) but since they are not hydrolysed by
acetylcholine esterase, their prolonged action leads to block,
due to inactivation of voltage gated sodium channels. For example, succinyl
choline
Non-depolarising type
These drugs act by competing with acetylcholine for
acetylcholine receptors. They block acetylcholine receptors
but do not have the biological activity of acetylcholine. By preventing
acetylcholine from attaching to its receptors, these
drugs block N-M transmission.
For example, Gallamine, Curare
Acetylcholine esterase inhibitors: Anticholine
esterase.
There are of two types—reversible and irreversible
type. In large doses they produce depolarising block.
(a) Reversible Inhibitors
These are competitive inhibitors of acetylcholine
esterase. They inactivate the choline esterase enzyme, and
this prolong muscular contractions in small doses. For example, Neostigmine,
physostigmine etc.

This block can be overcome by curare which can compete with acetylcholine for
acetylcholine receptor and thereby reduce the intensity of action of accumulated
acetylcholine at neuromuscular junction.
(b) Irreversible blockers (Inhibitors)

These agents bind to acetylcholine esterase so tightly that the block is virtually
irreversible. For example, some pesticides and insecticides, e.g., parathrone,
maltione, baygon, tic20—Organophosphorus.

Botulinum toxin: It is a bacterial toxin produced by clostridium botulinum. It

inhibits the release of acetylcholine by the nerve terminals at the neuromuscular
junction. If it happens at the respiratory muscles it leads to death.

MYASTHENIA GRAVIS

Myo = muscle Asthenia = weakness Gravis = grave

So myasthenia gravis means muscle weakness. It is an autommune disease
where antibodies are

produced against acetylcholine receptors or acetylcholine gated channels in

NMJ. It is, therefore, called a NMJ disorder. There is inability to transmit
impulse from nerve to muscle. The antibodies destroy the acetylcholine
receptors present on the muscle membrane. The number of receptors becomes
less. This will decrease the influx of Na+ in muscle. So no action potential is
formed in muscle in response to nerve impulse.

Signs and symptoms

1. The disease is characterised by rapid onset of fatigue with marked weakness

of muscles.
2. The most commonly affected muscles are extraocular muscles, facial muscles,
masticatory muscles, and swallowing muscles—Drooping of eye lids, difficulty
in deglutition, loss of facial expression, difficulty speaking.
3. In severe form the patient becomes bed ridden. 4. Difficulty in raising the
hand above shoulders. 5. Involvement of respiratory muscles results in
myasthenia crisis leading to death.

Physiological basis of treatment

1. Administration of anticholinesterase, e.g., Neostigmine, Pysostigmine. These
drugs inhibit the enzyme acetylcholine esterase. This slows down the breakdown
of acetylcholine thereby acetylcholine is allowed to act for a longer time.

2. Thymectomy
3. Immunosuppression with drugs.

Mechanism of Muscle Contraction

The skeletal muscle is voluntary in nature i.e., it contracts when excited.

Excitation (depolarisation) of muscle fibre causes development of action

potential (“Electrical” phenomenon), which through sequence of events
produces muscular contraction (“Mechanical” phenomenon). These two
phenomena are coupled (linked) together by coupling agent, i.e., Ca2+.
Therefore, the process by which depolarisation of the muscle fibre initiates
contraction is called “Excitation contraction coupling”.

Sequence of events in excitation contraction coupling:

A. Steps in muscular contraction

1. Stimulation of motor nerve with threshold intensity produce propagated action

potential.
2. Release of Acetylcholine (Ach) into “synaptic cleft” which binds with
“nicotinic Ach receptors” concentrated on motor end plate causing generation of
end plate potential.
3. Depolarisation of muscle membrane (sarcolemma) by increasing permeability
to Na+.
4. Generation of action potential in the muscle fibre.
5. Inward spread of action potential along T-system.
6. Spread of depolarisation to terminal cisternae with release of Ca2+ in the
myofibrils.
7. Increase in concentration of Ca2+ in ICF by 2000 times from 10–7 mole/L to 2
× 10-4 moles/L.
8. (a) Ca2+ binds to troponin to saturation point causing tropomyosin to move
laterally. This exposes the binding sites for myosin heads on actin.
(b) Activates prosthetic group of myosin filament which acts as enzyme ATPase
catalysing the breakdown of ATP to produce energy for: (i) contraction of
actomyosin complex and (ii) activating sliding filament system. 9. Muscular
contraction.
2 Sarcomeres
I band A band
H zone
Thick filamentZ disc Z discZ disc Thin filament
(a) Relaxed
(b) Partially contracted
(c) Maximally contracted

Fig. 10.9 Shortening of length muscle during contraction

B. Steps in muscular relaxation

1. A few milliseconds after the action potential is over, sarcoplasmic reticulum
begins to reaccumulate Ca++. The Ca++ are ‘actively’ pumped by Ca++ – Mg++
ATPase (i.e., Ca++ pump) into longitudinal portion of the reticulum and from
there discharges into the terminal cistern for storage.

2. Once Ca++ concentration decreases in ICF sufficiently to 10–7 moles/L,

chemical interaction between myosin and actin ceases and muscle relaxes.

Notes: (i) If the active transport of Ca++ is inhibited, relaxation does not occur
eventhough there is no action potential. This results in sustained contraction of
the muscle, called contracture.

(ii) It is thus obvious from above that both contraction and relaxation of muscle
are active processes and require energy which is provided mainly by ATP.

Molecular basis of muscle contraction

Sliding filament theory of A.F. Huxley and H.E. Huxley— 1954. The process by
which the shortening of the contractile elements in the muscle is brought about
by the sliding of actin filament over the thick (myosin) filaments. The sliding of
filaments is brought about by formation of the crossbridges between the head of
myosin and actin molecules.
Actin
filament
Myosin filament Active site Active site Actin filament
Cross bridges Power stroke
Hinge
Hinge Body Myosin filament Fig. 10.10
Molecular basis of muscle contraction

Events during the formation of the “cross-bridges” 1. In resting muscle, no

cross-bridges are formed since troponin ‘I’ is lightly bound to actin and

tropomyosin covers the actin sites where myosin heads binds to actin. Therefore,
the “troponintropomyosin” complex constitutes a relaxing protein which inhibits
the interaction between actin and myosin.

2. Ca++ released from the terminal cisterns by the action potential binds to
troponin ‘C’ and causes: (a) The binding of troponin ‘I’ to actin is weakened,

this permits tropomysin to move laterally, uncovering the binding sites for
myosin heads on actin filaments, and

(b) Hydrolysis of ATP by ATPase activity in the myosin heads to produce

energy.

3. Seven myosin binding sites on actin filaments are uncovered for each
molecules of troponin that binds a Ca++.

4. The heads of the myosin molecules (which serves as the cross linkages) link
to the actin at 90 degree angle, produce movement of myosin on actin by
swiveling (revolving), and then disconnect and reconnect at the next linking site.

Mechanism of sliding of thin filaments over thick filaments

1. The sliding during muscle contraction is produced by breaking and reforming

of cross-bridges (crosslinkages) between actin and myosin, repeating the process
in serial fashion for 5-6 times.

2. The width of ‘A’ bands is constant, whereas the ‘Z’ lines move closer together
when the muscle contracts and farther apart when it is stretched. As the muscle
shortens, the actin filament from the opposite end of the sarcomere approach
each other; when the shortening is marked, these filaments apparently overlap.
Each single cycle of attaching, swiveling and detaching shortens the muscle by
1% maximum shortening that can occur is 30% of total length of the muscle.

Types of muscle contraction

1. Isometric contraction: It is a type of muscle contraction where there is no
change in the length of the muscle fibre. No shortening of muscle fibre. Only
tension increases. No work is done. Example: Attempt to lift ‘a’ bucket of water
which cannot be lifted.

2. Isotonic contraction: In this type of contraction, tension developed in the

muscle remains same but length decreases. In this case, work is done. Example:
Walking, running, lifting a bucket of water.

Simple muscle curve/twitch

It is the graphical record of a single muscle contraction. A single adequate

stimulus applied to a motor nerve gives rise to a single action potential which
causes a brief contraction followed by relaxation. This is known as simple
muscle curve or twitch.
E
AB C D

A. Point of stimulus
B. Point of contraction
C. Point of maximum contraction D. Point of ending of relaxation AB = Latent period
BC = Contraction period
CD = Relaxation period

Fig. 10.11 Simple muscle curve

Beneficial SuperSummation effect position
PS1 PS2 PS1 PS2 PS1 PS2
Fig. 10.12
Effects of two successive stimuli. PS1—Point of first stimulus. PS2—Point of
second stimulus Latent period is the gap between application of stimulus and
commencement of contraction.
Relaxation period is usually longer than contraction period.
Effect of two successive stimuli

Suppose the second stimulus is applied during the refractory period, there will
not be any response. If the second stimulus is applied during the contraction
period the height of contraction increases—summation effect.

If the second stimulus is applied during the relaxation period it will produce
second contraction of higher magnitude. This effect of second stimulus is known
as beneficial effects.

Causes
(a) increase in temperature
(b) accumulation of metabolites
(c) decrease in viscosity of muscle.

Therefore, second stimulus produces “Beneficial effect”.

Effect of increaisng strength of stimuli

If a single brief stimulus applied is of threshold strength it can (theoretically)

excite one motor unit which gives rise to a brief contraction followed by
relaxation. As the strength of the stimulus applied to the nerve is increased, more
motor units are stimulated. Therefore, more groups of muscle fibres respond, and
strength of resulting contraction is correspondingly greater. With maximal
stimulation, all the motor units are excited and therefore, all the muscle fibres
supplied by the motor nerve contract. Thereafter, further increase in the strength
of stimulus does not increase the height of contraction.
E
D
TensionC
B
A
Time (msec)
Fig. 10.13 Effect of increasing strength of stimulus
5 stimuli/sec 10 stimuli/sec 20 stimuli/sec
Clonus Tetanus
30 stimuli/sec 35 stimuli/sec 40 stimuli/sec Fig. 10.14
Genesis of tetanus and clonus
Effect of multiple stimuli

Suppose multiple stimuli are applied at a rate of 5–10/ sec, it will produce
multiple contractions. The magnitude of contractions gradually increases. This is
known as staircase phenomenon or treppe.

Suppose the rate of stimulation is increased to 15–25/ sec, the muscles may not
completely relax. It shows partial contractions. This phenomena is clonus or
incomplete tetanus. If the rate of stimulation is 30-40/sec. the muscles will
remain in a permanent state of contraction. This is known as tetanus.

Effect of temperature on muscle contraction

When temperature increases latent period decreases and height of contraction

increases. When muscle is exposed to cold, latent period increases and height of
contraction decreases. Cold retards some metabolic processes. Hence
depolarisation is slow and decreases the speed of response. Increase in
temperature reduces the inertia and synaptic delay and there by decreases latent
period and increases the magnitude of contraction. When temperature is
increased above 450C height of contraction increases but muscle proteins get
denatured. Muscle remains in a permanent state of contraction known as heat
rigor.
Heat 60°C rigor
40°C
Room temperature
10°C

Fig. 10.15 Effect of temperature on muscle contraction Fatigue

Fatigue is a temporary reduction of the working of muscles resulting from

prolonged exertion. When a muscle is repeatedly stimulated, initially the
amplitude of contraction gradually increases becauses of beneficial effect, then it
gradually falls to zero and the muscle no longer responds to stimulation. This
phenomenon is known as fatigue. This could be due to:

1. Lack of nutrition.
2. Accumulation of waste metabolites.
3. Depletion of acetylcholine.
4. Lack of oxygen.
5. Lack of ATP.
Fatigue is a temporary reversible phenomenon and passes off after a rest.

Fig. 10.16 Fatigue

Rigor mortis
It is a permanent state of muscular rigidity occurring after death. It is a state of
irreversible muscular contraction and stiffness due to the deficiency of ATP after
death. Muscle fails to relax.
Changes during rigor mortis

1. Muscle length becomes short.

2. Thickness increases.
3. Looses translucency and becomes opaque.
4. Change in pH. Alkalinity to acidity.
5. Depletion of glycogen content.
Timings- Rigor Mortis starts approximately during the 2nd hour of death and it
completes by 3rd and 4th hour.
After 24-36 hours of death rigor mortis disappears. This is due to autolysis.
Causes for rigor mortis

Non availability of ATP. The calcium ions which come out of sarcoplasmic
tubules cannot be pushed back into the tubules. Muscles fail to relax and remains
in a contracted state.

Significance: By examining the time of rigor mortis, time of death can be

estimated.
Changes taking place during muscular contraction

1. Mechanical changes
2. Chemical changes
3. Changes in pH
4. Thermal changes
5. Electrical changes

1. Mechanical changes
During muscle contraction the muscle fibre shortens in

length, thickness increases. Volume remains same or slightly increases, in

isometric contraction, length remains same, but tension increases.

2. Chemical changes
(a) Glycolysis and oxidative breakdown
Glycogen
Embden - Meyerhof pathway
2ATP
2 Pyruvic acid
Aerobic Anaerobic
Citric acid cycle (kreb's cycle) Lactic acid
36 ATP (2x18)
HO+CO 22
Cori cycle
Fig. 10.17
Breakdown of glycogen

End products are pyruvate and lactic acid. Out of the total quantity of the lactic
acid formed under anaerobic conditions 1/5th of it is oxidised to CO2 and H2O,
4/5th is resynthesised into glycogen in the liver.
Cori cycle
Pyruvic acid
Lactic acid
Muscle glycogen Cori cycle Liver
glycogen
Blood glucose

Fig. 10.18
Cori cycle

In the presence of O2 pyruvate acid is oxidised through Krebs TCA cycle.

There is net production of 38ATP per glucose molecule, under aerobic condition
and under anaerobic conditions only 2ATP molecules are formed.
Utilisation of other fuels during muscle contraction.
– β oxidation of fatty acids for the synthesis of ATP.
– Ketone bodies.

3. Changes in H+ concentration or pH

During muscular activities both acidic and alkaline products are formed. They
try to neutralise each other, and try to maintain constant pH. However, in the
initial stages of muscle contraction the pH becomes more alkaline due to the
release of creatinine (which is highly alkaline). In prolonged activity pH
becomes acidic due to the accumulation of lactic acid.

4. Thermal changes
During muscle contraction heat is produced in two stages: (i) Initial heat occurs
at the onset of contraction. (ii) Recovery heat-delayed heat—occurs following
contraction.

Initial heat is rapid out burst of heat, recovery heat is slow and prolonged
production. Heat production is in 3 stages:

1. Heat of activation
2. Heat of contraction
3. Recovery heat
5. Electrical changes
This includes generation and spread of action potential or impulses in the
muscle. Spread of action potential is followed with contraction.
Efficiency of muscle contraction
Total energy out put = work done + heat liberated

Efficiency = Work done × 100Total energy output

TABLE 10.2
Comparison between white and red muscle fibres
Sl. No. White (fast) muscle fibres Red (slow) muscle fibres

1. Here muscle fibres are large in diameter with high These muscle fibres are of
moderate diameter and glycogen capacity and ATPase activity: because they are
moderate glycogen capacity with low ATPase activity; pale, therefore, called
‘white’ muscle fibres. because they are darker than other muscle fibres,

therefore, called ‘red’ muscle fibres.

2. They are innervated by large, fast conducting motor They are innervated by
small, slow conducting motor neurons (“size principle”) neurons, therefore, also
called neurons, therefore, also called “slow” muscle fibres. ‘fast’ muscle fibres.

3. Their muscles have short twitch durations and are These muscles respond
slowly and have long latency and specialised for fine skilled movements
e.g.,extraocular are adapted for long, slow posture maintaining muscles and
muscles of the hand. contractions e.g.,long muscles of limb and muscles of

the back.
These muscles are resistant to fatigue and are the most4. These muscles get
fatigued easily.
used muscles.
Muscular dystrophy is a hereditary muscle disease It is type of syncytial
muscle. which leads to a progressive muscle weakness. TheFunctionally it is similar to
cardiac muscle.characteristic features of muscular dystrophy are: skeletal For example, Visceral smooth
muscle, wall ofmuscle weakness, defects in muscle proteins, and the death different blood vessels.of muscle
cells and tissue.

The common type of muscular dystrophy is DuchenneTABLE 10.3 Types of smooth

muscles muscular dystrophy which a hereiditary disorders that affect
mostly children. Duchenne muscular dystrophy results into Features Single unit
Multiunit progressive muscular weakness and enlargement of calfLocationmuscles.

Baker’s muscular dystrophy which is rarest type of

Urinary bladder,
intestine, etc.
Iris, ciliary muscles

muscular dystrophy shows similar kind of features but stillInnervationexact cause is

unknown. Both parasympathetic and sympathetic
Either of the division
Smooth muscle: Smooth muscle is responsible for the Generation APcontractility of hollow
organs, such as blood vessels, theSpontaneous
gastrointestinal tract, the bladder, or the uterus. Its structure
Nonspontaneous differs greatly from that of skeletal muscle, although it can
Cell to cell
develop isometric force per cross-sectional area that is equal
propagationto that of skeletal muscle. However, the speed of smooth
Present (through gap Absent junctions)
of actionmuscle contraction is only a small fraction of that of skeletal
potentialmuscle.
There are two types of smooth muscles:Acts as Functional syncytium 1. Multiunit
smooth muscle:

Each fibre contracts separately

Each fibre in a muscle can contractRegulationsindependently. Nerve regulated

It rarely exhibits spontaneous contraction.
Nerve operated
Functionally it is similar to skeletal muscle. Mechanism of smooth muscle contraction
For example, Ciliary muscle of eye, muscle of Smooth muscle is primarily under the control ofiris.
autonomic nervous system, whereas skeletal muscle is under2. Single unit smooth
muscle: the control of the somatic nervous system. The single-unit
Mass of hundreds of muscle fibres contracts smooth muscle has pacemaker
regions where contractions simultaneously as a single unit. are spontaneously
and rhythmically generated. The fibres
Relaxed Increase cytosolic calcium concentration
Contracted Dose body Calcium binds to calmudilin in cytoplasm

Thick and thin

filaments

Calcium - calmudilin complex binds to myosin light chain kinase

Myosin light chain kinase utilises ATP to phosphorylate myosin cross - bridges
Phosphorylate myosin cross-bridges
Cross-bridge cycle producing tension and shortning

Fig. 10.19
Smooth muscle

contract in collectively, which is the single unit of smooth muscle is syncytial.

The fibres of multiunit smooth muscle are innervated by sympathetic and
parasympathetic nerve fibres and respond independently from each other upon
nerve stimulation.

Nerve stimulation in smooth muscle causes membrane depolarisation, like in

skeletal muscle. Excitation, the electrochemical event occurring at the membrane
is followed by the mechanical event, contraction. In the case of smooth muscle,
this excitation-contraction coupling is termed electromechanical coupling; the
link for the coupling is Ca2+ that permeates from the extracellular space into the
intracellular water of smooth muscle. There is another excitation mechanism in
smooth muscle, which is independent of the membrane potential change; it is
based on receptor activation by drugs or hormones followed by muscle
contraction. This is termed pharmacomechanical coupling. The link is Ca2+ that
is released from an internal source, the sarcoplasmic reticulum.

Molecular mechanism of smooth muscle contraction Contraction is initiated

by the increase of Ca2+ in the sarcoplasm; this happens in the following ways:

1. Ca2+ may enter from the extracellular fluid through channels in the
sarcolemma. These channels open, when the muscle is electrically stimulated or
the sarcolemma is depolarised by excess K+.

2. Due to agonist induced receptor activation, Ca2+ may be released from the
sarcoplasmic reticulum (SR). In this pathway, the activated receptor interacts
with a G-protein (G) which in turn activates phospholipase C (PLC). The
activated PLC hydrolyses phosphatidyl inositol bisphosphate; one hydrolyses
phosphatidyl inositol bisphosphate; one trisphosphate (IP3). IP3 binds to its
receptor on the surface of SR, this opens Ca2+ channels and Ca2+ from SR is
entering the sarcoplasm.

3. Ca2+ combines with calmodulin (CaM) and the Ca2+-CaM complex activates
MLCK, which in turn phosphorylates LC. The phosphorylated myosin filament
combines with the actin filament and the muscle contracts.

Functions of smooth muscles

(i) They control the movement of material through most of the hollow organs.

(ii) They propel material in the gastrointestinal tract. (iii) They control flow in
the arteriolar blood vessels. (iv) Material is expelled from the bladder and vas

deferens.
(v) They are responsible for controlling piloerection. (vi) They regulate the input
of sensory information

into receptors (dilatation and constriction of the muscles of the iris affect the
amount of light reaching the retina).

EXERCISE PHYSIOLOGY

Exercise is defined as intentional increased muscular activities, planned,

structured and basically repetitive contraction and relaxation of groups of
muscles. Exercise is a purposeful increased physical activity with great health
benefits. Health benefits include prevention of certain diseases, promotion of
physical fitness and improvement in the performance is the sportsfield. The
study of exercise physiology deals with the physiochemical processes of various
body systems, their adaptation in handling increased conversion of chemical
energy to mechanical work.

Classification of Exercise
Types of exercise are two—Isotonic and Isometric.
TABLE 10.4 Comparison between isotonic and isometric exercise
Sl.No. Isotonic exercise Isometric exercise 1. Also known as Dynamic
exercise. Adynamic exercise. Static exercise. 2. No change in the tension.
Change in tension. 3. Length changes - Muscle shortening taken place. No
change in length. No shortening of muscle. 4. External work is done. No external
work is done. 5. Example: Walking, running, jogging, swimming. Trying to lift
something which cannot be lifted. 6. On extra load on heart. It puts greater load
on heart, so should be avoided in heart patients and elderly people.
The severity of exercise can be graded based upon—1. energy expenditure—O2
uptake, 2. Power or rate of doing work, which is expressed as watt. 1 watt = 1
Joule / sec. Gradation of exercise TABLE 10.5
Classification of exercise
Sl.No. Class of Exercise O2 uptake litres/min Power-Watt Pulse rate per min
1 Rest 0.25 100–150 70–80 2. Mild or Light
e.g., slow walking
3. Moderate
e.g., fast walking
4. Heavy
e.g., jogging for long time 5. Very heavy
e.g., fast running

6. Maximal
e.g., very fast running, Fast swimming
0.5 to 1
2 to 4 times of rest

1 to 1.5
4 to 6 times of rest
1.5–2
6 to 8 times of rest
2 to 2.5
8 to 10 times of rest
Above 2.5
more than 10 times of rest 170–340 100
Increase by 25% of rest 340–510 100–120
Increase by 50% of rest 510–680 120–150
Increase by 75% of rest 680–850 150–180
Increase by 100% of rest 850 or more Above 180–190 Increase by 120% of rest

The response of body may be acute or chronic. Acute response of the body to
exercise is generally referred simply as response to exercise. The long term
response of body to chronic exercise is referred as effect of training.

Energy source for exercise

Exercise demands a great amount of energy. The metabolic rate increases during
exercise, chemical energy is converted to mechanical work. The major sources
of energy are 1. ATP 2. Phosphocreatinine 3. Fatty acids 4. Glucose and
glycogen 5. Lactic acid. The immediate source of energy for muscular activities
is derived by the breakdown of ATP and regeneration of ATP by
phosphocreatinine. During aerobic exercise sufficient oxygen is made available.
During this period ATP is regenerated by the oxidation of glucose, fatty acids
and ketone bodies.

During anaerobic conditions glycolysis and phsphocreatinine can generate ATP

to some extent. During the prolonged exercise stored energy is derived from
triglycerides and tree fatty acids. Greater availability of fatty acids also made by
the actions of growth hormone and catecholamines. When large amount of fatty
acids are available for breakdown, it decreases the demand on breakdown of
muscle glycogen and glucose for energy. During anerobc exercise glucose
breakdown produce lactate. From the muscles lactate is collected and carried to
liver by the blood. In the liver lactate is converted to glucose by
gluconeogenesis. This forms the cori’s cycle. Later glucose is released from liver
to blood to be carried to the muscle.

Physiological changes during exercise. Exercise generates a great metabolic

stress on the body. It is faced by adaptations by different organs and systems.

Blood and cardiovascular system

During exercise the cardiovascular system take up the responsibility of
supplying adequate oxygenated blood to the exercising muscles; so that it meets
the oxygen demand of the muscles. This can be achieved by following
adjustments.

1. Increasing the heart rate

2. Increasing the stroke volume
3. Increasing cardiac output
4. Reallotment of blood flow to various tissues based upon their need.

5. Increasing the blood flow to the muscle which are inaction

6. Adjusting the blood pressure and

7. Changing the blood volume.
A. Heart and Exercise
Prolonged and systematic exercise causes enlargement of the heart and this
happens only to cope with the excessive work load imposed upon the heart
during work. In athletes, the hypertrophy of heart is caused by physiological
processes. The hypertrophied athletic heart is more powerful, efficient and
capable of greater increase in stroke volume but the dilated diseased heart is less
efficient and has a limited capacity for work.
B. Heart rate changes during exercise

The acceleration of the heart rate is observed immediately following exercise. It

has been observed that heart rate is increased slightly even before the onset of
exercise and it is due to the influence of cerebral cortex on the medullary cardiac
center. A short rise in heart rate is observed at first minute of exercise but after
that rate of rise is slightly decreased within 4–5 min. of starting of exercise. In
athletes, the rate of rise of heart rate will be slower. Besides these, the maximum
heart rate depends upon emotional, environmental, humidity and physical
condition of the subject.

Initial rise of heart rate just before exercise is due to the influence of cerebral
cortex and the other higher brain centers. With the onset of exercise the rise of
heart rate is due to

(a) Reflexes originating in the receptors of moving joints or contracting muscles.

(b) Stimulation of chemoreceptors in muscles by the metabolites.
(c) Sympathetic adrenal axis causing secretion of much larger amount of
epinephrine to the blood.
(d) Decreased secretion of thyroxine in response to stress.
(e) Rise of body temperature.
(f) Stimulation of stretch receptors in atrium by the rapid venous return, thus
causing Bain—Bridge reflex.
The return of heart rate to initial resting level depends upon the intensity of
workload and also on the physical condition of the subject.

C. Sroke volume
Force of contraction of heart and stroke volume
increases during exercise. It is achieved by
(a) increased sympathetic tone
(b) increased adrenaline level
(c) incrased end diostolic volume.
A trained athlete increases cardiac output mostly by
increasing stroke volume rather than by increasing heart rate.
D. Cardiac output
During exercise the cardiac output is greatly increased.
In trained athletes it may achieve a maximal output of
30 L/min. at an O2 uptake of 4 L/min but in non athletes the
output may be an average of 22 L at an O2 uptake of 3.3 L/
min. It is the result of increaseed in stroke volume and heart
rate. Stroke volume increases to about 130 to 140 ml.

E. Venous return
Venous return is greatly increased during exercise for
the following reasons:
(i) Milking or massaging action of skeletal muscles: During exercise, the
alternative contraction and relaxation of the muscle act as a booster pump for
directing blood towards the heart. Due to the presence of valves in the veins, the
blood is squeesed out from the vein towards the heart during contraction and
allowed to fill blood during relaxation of the muscle. This pumping mechanism
depends upon the intensity and type of exercise.
(ii)Respiratory movements: Respiratory movements exert a sucking effect over
the right heart and great veins so that greater venous return may occur. During
inspiration the thoracic cavity is enlarged causing fall of intrathoracic pressure as
well due to descent of diaphragm causes rapid return of blood into the heart.
Expiration has got the opposite effect. (iii) Contraction of limb veins: It is
claimed that

limb veins undergo reflex venoconstriction during exercise thus facilitating rapid
venous return to the heart.

F. Blood pressure

Blood pressure is raised with the onset of exercise. There may be an anticipatory
blood pressure due to nerve impulses originating from the cerebral cortex to the
medullary cardiac and vasoconstrictor centers. Other factors that may participate
in the rise of B.P. during exercise are due to activation of sympathetic adrenal
gland systems causing shifting of blood from splanchnic beds to the other parts
of the body.

So the rise of arterial systolic blood pressure during exercise is due to

(i) Increase of cardiac output, causing greater distension of aorta and large
arteries.
(ii) Increase of heart rate.
(iii) Compensatory vasoconstriction in the nonactive organs and vasodilatation in
the active organ so as to perfuse the active organ with a greater pressure.

Diastolic blood pressure

1. Diastolic blood pressure may decrease or there may be no change in diastolic
B.P. during mild and moderate exercise because total peripheral resistance falls
considerably due to drastic vasodilatation in working muscles.
2. Slight increase in diastolic B.P. in severe exercise

due to severe vasoconstriction in non-working muscles and skin.

Mean B.P.—This increases.

G. Blood flow

During exercise, the circulation is adjusted in such a way that the active muscles
as well as the vital organs get blood supply to a greater proportion than that of
inactive organs and the non vital organs.

During exercise the blood flow in the active tissues like muscle, lung, heart is
increased, but the same in the abdominal organs, kidneys, in the skin is greately
decreased due to compensatory vaso constriction. This happens possibly through
the chemoreceptor reflex initiated by the accumulated metabolites during
exercise so as to cause redistribution of blood from abdominal organs to the
excercising muscle, heart, lung and skin.

Blood flow to the brain is relatively under normal state. Cutaneous blood flow
decreases first due to vasoconstriction but later increases due to vasodilatation.
This is required for the regulation of body temperature.

Coronary blood flow: Increases from a resting value of 200 to 250 ml/min. to
1000 ml/min. This 4 to 5 times increase is due to:

1. Hypoxia
2. Sympathetic nerve stimulation.
3. Release of catecholamines from the adrenal medulla.
4. Rise in carbondioxide.
Muscular blood flow: Under resting condition it is 2 to 4 ml/100 gm/min. This
increases to 30-fold during muscular exercise 100 ml/100 gm/min. The increase
in the muscular blood flow is due to:
1. Increase in blood pressure
2. Vasodilatation in the muscular vascular bed due to the action of
(a) increased cholinegic sympathetic discharge. (b) metabolities like lactic acid,
Kt, Ht.
3. Opening up of capillaries.
Peripheral resistance: It is the resistance offered by the peripheral blood
vessels, mainly the arterioles to the blood flow. PR decreases a little in a mild
exercise. PR does not change in a moderate exercise as vasodilatation and
vasoconstriction in some parts of the vascular bed get neutralised. PR decreases
in a severe exercise, as there is more vasodilatation than vasoconstriction.
Muscular
Coronary Blood
flow
Cerebral
Renal, sphlanchnic

Blood volume: Blood volume decreases during prolonged exercise and this
produce hemoconcentration. The decrease in blood volume is mostly due to

(a) Increased flow of water from blood vessel to interstitial space due to the
accumulation of osmotically active metabolites.

(b) Loss of water by sweating.

(c) Increased cutaneous vasodilatation.
Duration
Fig. 10.20
TABLE 10.6
Summary of cardiovascular changes during muscular exercise
Sl.No. Value at rest Attainable value during exercise Cause or how it is
produced ?
1. Heart
(a) Rate 72/min 180/min
(b) Force of contraction Normal Increases

Stroke volume (c) Cardiac output 70 ml/beat 5 L/min

(d) Venous return 5 L/min

140 ml/beat
Increases 25 to
30 L/min
25 to 30 L/min (i) Sympathetic discharge increases which will stimulate S.A.
Node. (ii) Increase in adrenaline level also stimulates S.A. Node.
(iii) Decrease in Vagal tone.
(iv) Increase in temperature.
Increase in sympathetic activity and increase in catecholamine level.
Increase myocardial contractility. Effect of Starlings law, i.e.,when venous return
increases it will
increase the initial length of muscle fibre, this inturn increases force of
contraction there by increases stroke volume and cardiac output.
Combination of rise in heart rate and increased force of contraction together
increase cardiac output.

2. Blood pressure (a) SBP

(b) DBP
(c) Pulse pressure (d) Mean BP
120 mm of Hg 80 mm of Hg 40 mm of Hg 93 mm of Hg 150–180 mm of Hg
60–70 mm of Hg 90–100 mm of Hg 110–130 mm of Hg

3. Blood capillaries Arterio-venous oxygen difference

Optimum use 5 ml/100 ml of blood
More recruitment 16 ml/100 ml of blood
Increase in cardiac output
Fall in total peripheral resistance due to vasodilation in muscles.
Because of great increase in systolic blood pressure.

Relaxation of resistance vessels like arterioles and increase in perfusion

pressure.

Contd…
4. Blood flow 200 ml/min (a) Coronory blood flow

(b) Pulmonory blood flow 5 L/mt (c) Blood flow to the 2–4 ml/ vessels of active
100 gm/min skeletal muscles

(d) Blood flow to kidneys 1200 ml/min (e) Blood flow to GIT 500 ml/min 5.
Blood volume 5000 ml

25-30 L/min
Severe
Vasodilatation
100 ml/100 gm/min Increases about 25 times
Decreases
Decreases
4000–4500 ml Decreases by
15–20%
(i) Vasodilatation due to vasodilator sympathetic cholinergic activity (ii) Due to
local metabolities and local hypoxia

Local vasoconstriction Local vasoconstriction

(i) Loss of water by sweating (ii) Shifting of water from blood vessel to
interstitial space

Respiratory changes during exercise

1000 ml/min

Increases 5 times (i) Local oxygen lack

(ii) Increased sympathetic tone

(iii) Increased level of adrenaline.

During maximum exercise oxygen consumption and CO2 production increases

by about 25 times. The respiratory system meets this challenge by (a) increased
ventilation (b) increased perfusion (c) increased diffusion of oxygen. By these
way the increased metabolic demand of oxygen is met with and O2 and CO2
level in the blood is maintained at constant.

Pulmonary ventilation

With exercise both rate and depth of respiration increases. In a trained athlete the
respiratory minute volume RMV (V° E) may rise from a resting value of about 7
litre/ minute to 80–100 L/minute. The O2 uptake (= the volume of O2 utilised by
the body V°O2) rises from a resting 0.25 l/min to about 4 l/minute in world class
athletes.

The increase in pulmonary ventilation during exercise is due to

(a) increase in respiratory rate 40-45 breaths per minute
(b) increase in tidal volume to about 2500 ml. The major causes are
1. During exercise, movements of joints cause reflex rise of respiration. The
proprioceptive receptors are situated in joints and muscles. 2. The sympathetic
stimulation that occurs during muscular exercise may cause constriction of the
vessel that feeds the carotid body. As a result the carotid bodies feel that there is
hypoxia and respiratory drive increases. 3. Blood PO2 and PCO2 normally
oscillate a little and in case where there is a sharp rise of tidal air volume (VT)
osciltation increases. These 4. oscillation in some unknown way may produce
respiratory drive which therefore increases when the VT increases.
In case of severe exercise where there is lactic acid accumulation, the blood pH
falls and this increases respiratory drive.
5. During exercise impulses descend via the pyramidal tract nerves arising from
the cerebral cortex. According to one theory collaterals of these nerves terminate
on the respiratory centre, when these motor nerves are stimulated these
collaterals are also stimulated an increase in ventilation.
6. Rise of body temperature due to exercise may stimulate respiratory centres
either directly or through reticular formation.
For practical purposes it may be said, blood PCO2 and PO2 do not change with
exercise, therefore the hyperventilation of exercise cannot be explained by
assuming that there occurs hypoxia, further excepting straineous exercise, the
lactic acid accumulation is not sufficient to cause a fall of pH.
Ventilation perfusion ratio. Oxygen is very rapidly utilised by muscles during
exercise. This greatly decreases PO2 in venous blood returning to lungs. The
decreased PO2 in pulmonary arterial blood stimulates ventilation. Pulmonary
bloodflow increases during exercise, but increase in pulmonary ventilation is
much more than increase in pulmonary blood flow. Therefor ventilation
perfusion ratio rises from resting value of 0.8 to 4 during severe exercise.
Oxygen uptake at the lungs during severe exercise increases upto 20 fold of rest
250 ml/mt. at rest to 4000 ml/min. This is achieved by
(a) Increased pulmonary blood flow.
(b) Increased difference in PO2 in alveoli and blood. Venous blood reaching the
long may have only about 3 ml of O2/100 ml of blood.
(c) Increased diffusion of O2 across respiratory membrane mostly due to opening
up of many capillaries. Oxygen diffusion capacity increases about 3 times.
Oxygen diffusion capacity increases from about 21 ml/min/mm of Hq. to about
65 ml/ min/mm of Hg during severe exercise. Changes in general metabolism.
O2 requirement, O2 consumption and V°O2 maximum.
Oxygen requirement increases with exercise. More severe is the exercise more
intense is the O2 requirement. O2 consumption (also called O2 uptake or O2
utilisation) is the volume of O2 that has been actually consumed during exercise,
no matter what the requirement was.
V°O2 maximum (maximal O2 consumption ability)
The amount of O2 that can be actually consumed by a person, when he/she is
working maximally hard (no matter what the requirement) is called V°O2
maximum.
The value of V°O2 maximum is dependent on the efficiency of
(i) circulatory
(ii) respiratory and the
(iii) muscular system.
Increased oxygen demand of tissues is met with (a) Rise in pulmonary
ventilation (b) Oxygen uptake in the lungs increases by several times. (c) Blood
flow to tissues increases due to increase in cardiac output and due to
vasodilatation in muscle blood vessels. (d) Oxygen release to tissue increases
due to greater partial pressure gradient, Bohr’s effect and effect of temperature.
CO2 output increases proportionate to exercise. Oxygen release from the blood
to tissues or oxygen extraction increases tremendously. At rest 100 ml of arterial
blood with 19.4 ml of oxygen releases 5 ml of oxygen to the tissues. Coeficient
of O2 utilisation is 25% but during exercise blood releases almost all oxygen to
the tissues venous blood contain very low—3 ml of O2 / 100 ml of blood, O2
utilisation increases to about 80%
Oxygen deficit: At the begining of musculer exercise (2–4 minutes) O2
consumption increases linearly and reaches to VO2 max. This is adaptation
phase. The VO2 max is much lesser than the actual oxygen demand. This
establishes the oxygen deficit during exercise. So the energy requirement over
and above the limits of oxygen consumption is met by anerobie pathway.
Oxygen debt: Oxygen debt may be defined as the amount of excess oxygen that
is consumed during recovery after an exercise. There are several causes as to
why the O2 debt develops.
(i) At the onset of exercise, the muscles get a ready supply of O2 from its own
myoglobin. During recovery myoglobins again re oxygenated and the amount of
oxygen required for this purpose contributes towards O2 debt.
(ii) During exercise, resynthesis of high energy phosphate bonds like creatine
phosphate and ATP may be incomplete. During recovery CP resynthesis occurs
fully and the resynthesis
requires oxygen.
(iii) Lactic acid accumulates in severe forms of
exercise and its removal requires oxygen.
Quantitatively this is the most important cause
of O2 debt and this fraction of oxygen debt is
called lactic acid O2 debt, the rest is alactic acid
O2 debt.

Respiratory Quotient (RQ)

During a severe exercise the RQ rises from a normal value of about the 0.8 to 1.5
or more. After the exercise is stopped the value of RQ falls and may attain
values around 0.6 or even less and then finally becomes normal again.
Endocrine changes during exercise

Hormonal adjustments are very essential to face the stress of exercise.

Anti Diueretic Hormone: Secreation of ADH increases during exercise. This
helps to reduce urine output and thereby help to maintain fluid balance. This
compensates the water loss through sweating.
Growth hormone secretion increases during exercise. This stimulate protein
synthesis in muscles. Adrenocortieotropie hormone (ACTH) increased seeretion
of ACTH will inturn increase the secretion of cortisol. This mobilises fat for
extra energy production. Cortisol also helps to overcome the stress related with
exercise. Aldosterone secretion increases during exercise. This decreases water
and sodium loss through urine. This enables the fluid and electrolyte balance.
Increased sympathetic activity during exercise stimulate adrenal medulla. This
increases the secretion of adrenaline and noradrenaline. The elevated catechola
mine in the blood increases the mobilisation of fat and glucose of liver and there
by improve the availability of fuel.
Pancreatie hormones: Insulin secretion decreases and glucagon secretion
increases during exercise. This increases glycogenolysis in the liver and
mobilises the glucose to muscles. It promotes lipolysis and mobilises fatty acids
from liver, make fuels available.
Endorphins: Endorphin secretion increases during exercise. Endorphins
stimulate food intake which in turn replenishes fuel. It relieves pain caused due
to severe exercise and relieve stress.
Changes in the renal system: Renal blood flow decreases during exercise. So it
decreases GFR. Increased secretion of ADH and aldosterone increase the
reabsorption of water. This will decrease urine output.

Metabolic adjustments in exercise

For short duration of intense muscular exercise like 100 meter
running, weight lifting etc. energy is derived from ATP and creatinine phosphate.
These substances are broken down one aerobically. Little longer duration of
exercise needs ATP creatinine phosphates and glycogen as energy source.
Further longer duration of exercise meets its energy demand mostly by fats.

Skin and body temperature changes during exercise. At the beginning of

exercise there is a cutaneous vasoconstriction due to sympathetic activity. But
prolonged exercise produces more heat initiating thermoregulatory mechanisms.
As a result blood vessels to skin dilate, increases blood flow and heat flow to
skin. Increased heat loss through skin leads to cooling. Sweat glands become
active and secrete large quantities of sweat. Evaporation of sweat leads to a
greater loss of heat from the body.

Body fluid and electrolyte balance. During exercise sweating increases leading
to loss of lot of water and sodium from the body. The loss of water is
considerable in a prolonged exercise in a humid atmosphere. This is partially
compensated by increased secretion of ADH and aldosterone. These hormones
reduces water and sodium loss through urine and maintains fluid and electrolyte
balance to some extent.

Muscles and exercise

Regular use of a muscle group leads to its hypertrophy. It is known as work
hypertrophy and there is no increase in the number of muscle cells. But size of
muscle increases by increase in the size of individual muscle fibres.

Nervous system
Exercise produces stress on nervous system. This initiates stress managing
mechanisms. Hypothalamus secretes CRF which enhances the secretion of
ACTH and cortisol. Mental activity during exercise like encouragements can
delay the onset of fatigue in muscle.
Fatigue: Muscular fatigue can be defined as inability of muscle to maintain or
repeat a task involving muscular contraction as a result of preceeding
performance of a similar task. The general fatigue seen during severe exercise
prevents continuation of any further more and in this way prevents possible
injury. Sites of fatigue—there are four major sites of fatigue—central nervous
system, motor neuron, neuromuscular junction and the muscle. Influence of
central nervous system on fatigue is a major psychological factor. The fatigue at
neuromuscular junction is mostly due to exhauction of acetylcholine. The fatigue
of muscle is mostly due to following reason:
(a) Depletion of ATP and other energy reserves. The failure to replenish ATP
contributes to fatigue.

(b) Accumulation of metabolites like lactic acid. Increased lactic acid lowers ptt.
At low ptt the affinity of calcium ions for troponin is reduced. Further fall in ptt
inhibits some key glycolytic enzymes. This decreases energy availability and
leads to fatigue.

Other factors influencing fatigue are increased body temperature, pain, blood
sugar level, adrenal exhaustion.
Effect of training on muscular performance: Training means doing heavy
physical exercise regularly under the guidance. Training improves the physical
working capacity of an individual and enhances the performance of athletes and
sports persons.
1. Increases cardio respirating efficiency. Increases cardiac output, oxygen
supply to muscles and oxygen unloading to muscles.

2. Size of regularly working muscle increases and power increases.

3. Training produces several metabolic adjustments which are specially useful

for prolonged exercise. This includes
(a) Increases the size of energy stores for creatinine

and glycogen.
(b) Increases the activity of energy producing
enzymes—like creatinine kinase.
(c) Size and number of mitochondria increases
leading to increased activity of mitochondrial
enzymes.
(d) Increases the ability of muscles to extract
oxygen.
(e) This improved oxygen extraction shift the
metabolism from anerobic to aerobic type.
Aerobic type is more efficient than anerobic
metabolism.
(f) This decreases the accumulation of lactic acid;
rise in blood lactate becomes less fall in pH. (g) Tolerance to lactic acid
increases with exercise. (h) Reduced accumulation of lactic acid facilitates
mobilisation and utilisation of fats. (i) Shifting of metabolism towards fat
utilisation
is very useful adaptation because fat store in
body is very great compared with extremely
megre glycogen availability.

TABLE 10.7 Comparison between the responses of trained and untrained

persons to exercise A trained person can achieve much larger cardiac output
than untrained person. Sl.No. Before training After training Rest Exercise
Rest Exercise 1. Heart Rate 70 180 60 180 2. Stroke volume
ml/beat
3. Cardic Output
ml/min
4. Oxygen uptake
ml/min
5. O2 diffusion capacity ml/min/mm of Hg
6. Maximum breathing capacity L/min
7. Breathing reserve
L/min
Health benefit of exercise
70 80 85 120
4900 14400 5100 21600
250 3600 300 4500
23 48 23 65
7 80 7 120
73 113

Drugs and Athletes 1. Regular exercise reduces insulin resistance. Exercise

increases the number of insulin receptors and increases the activity of glucose
transporters. So it is useful in the management of diabetes mellitus.

2. It decreases sympathetic tone, so beneficial in controlling hypertension.

3. It increases coronary perfusion, so useful in coronary occlusion heart diseases.
4. It decreases body fat mass so useful in preventing obesity and to avoid obesity
induced diseases.
5. Exercise causes an improvement in diseases of joints like osteoarthritis.
6. Exercise has prophylactic or preventive values against many diseases like
osteoporosis, hypercholesteremia.
The regular physical exercise is likely to slow the aging process, help to prevent
several degenerative and metabolic disorders. Exercise may make life healthier
and happier. Drug use and abuse: Many athletes use pharmacological agents
believing that a specific drug, can improve skill, strength, power or endurance.
The ingest of synthetic pharmacological agents produce adverse effects ranging
from nausea, hair loss, itching, nervous irritability to severe consequences like
sterility, liver disease and even death due to liver and blood cancer.
International Olympic Association bans following categories of drugs.

1. Stimulants
2. Narcotic analgesics
3. Androgenic—anabolic steroids
4. Beta blocker
5. Diuretics
6. Peptide hormone analogues
7. Substance that alter urine sample integrity Athletes use these drugs in several
combinations.

TABLE 10.8 Common drugs used by athletes

1. Amphetamines Stimulants 2. Anabolic steroids Improves muscle protein
content 3. Caffeine Ergogenic boost 4. Ginseng and Epidrine Plant extract
Optimise mental and physical stress. 5. Glutamine Anticatabolic effect that
augment protein synthesis, improves immunity 6. Phosphatidyl serene Modifies
neuroendocrine response to stress 7. Beta, hydroxy, methyl, butyrate Decreases
protein loss during stress by inhibiting protein catabolism
Reproductive System
Sir Alam Lloyd Hodgkin 5-02-1914–20-12-1998 British Physician
Known for Hodgkin’s disease
Nobel Prize (1963)

Prof Sir Ian Wilmut

7-7-1944
English Embryologist
Leader of the research group that in 1996 first cloned a mammal (lamb)

Harry Fitch Kleinfelter 1912

United States Physician first described the
XXY-syndrome
Caspar Friedrich Wolff (18-1-1733–22-2-1794) German Physiologist and one
of the founders of embryology wolffian duct is named after him

Dr John Langdon Down (1828–1896)

English Physician
First person to recognise Down syndrome as a ‘syndrome’

Johannes Peter Müller 14-7-1801–28-4-1858) German Physiologist

comparative anatomist and ichthyologist
Mullerian duct is named after him

Chapter
11 REPRODUCTIVE SYSTEM
Introduction
Puberty—Pubertal changes in male and female. Male reproductive system—
Functional anatomy. Spermatogenesis—Steps and factors influencing. Abnormal
spermatogenesis, semen.Sertoli cells. Functions and regulation of secretion of
testosterone. Cryptorchidism, Hypogonadism.
Female reproductive system—Functional anatomy. Oogenesis—Steps and
factors influencing. Menstrual cycle—Ovarian and uterine changes. Tests for
ovulation.
Hormonal control of menstrual cycle.

Female sex hormones, oestrogen, progesterone, relaxin.

Infertility.
Physiology of pregnancy—Fertilisation, implantation. Placenta, hormones of
placenta and functions. Pregnancy diagnostic tests.
Maternal changes during pregnancy.
Parturition: initiation and onset of labour. Lactation—Role of oestrogen and
progesterone in development of breast.
Role of prolactin and oxytocin in milk ejection process.
Manopause.
Family planning, Physiology of contraception— Physiological basis of different
methods of contraception in males and females.
Sex determination, Sex differentiation.
Chromosomal aberrations of sexual development.

REPRODUCTIVE SYSTEM
Functions of Reproductive System

1. Production of new young ones or offsprings— procreation. This helps to

maintain the continuity of species.

2. Deriving sexual pleasure—This is known as recreation.

Puberty: At the time of birth human infants are not capable of reproduction. The
ability to reproduce is attained at a later stage in life. The onset of reproductive
capacity is known as puberty. Puberty is defined as the period in which
gametogenic and endocrine functions of gonads have first developed to the point
where reproduction is possible.

Age of puberty
In female—around 11–13 years.
In male—13–16 years.

Factors influencing age of puberty

1. Climate—Age of puberty is lower in people at tropical climate than those

living at cold climate.
2. Nutrition—Proper nutrition is essential for the growth and development of
gonads therefore it influences the age of puberty.
3. Social and psychological exposure during the developmental period.

Puberty changes in male

1. Appearance of hairs on the body —at the axilla, pubic regions and on the face.
Public hairs lying convex.

2. Change in the voice, voice becomes rough or harsh due to thickening of vocal
cords.
3. Growth of accessory male sex organs like seminiferous tubule, prostate, bulbo
urethral gland and penis.
4. Commencement of spermatogenesis.
5. Increase in the length of the bones, increase in the height of the individual.
6. Broadening of shoulders
7. Muscles becomes larger and stronger
8. This gives masculine appearance to the body.
9. Formation of acne or pimples.
10. Mental changes or psychological changes This includes attraction towards
opposite sex and desire for sex.

Puberty changes in the female

1. Appearance of hairs on the body at the axilla and pubic regions. This is known
as pubarche. Pubic hairs lying concave.

2. No change in the voice.

3. Growth of accessory female sex organs like fallopian tube, uterus, vagina.
4. Growth of breast or mammary gland. This is the first event in female
reproductive growth and known as thelarche.
5. Commencement of menstrual cycle is called menarche.
6. Deposition of fats on the body.
7. Broadening of pelvis. This gives feminine curvature to the body.
8. Adrenal cortex secretes large amounts of androgens with no change in cortisol
secretion. This change in adrenals is known as adrenarche.
9. Mental changes: This includes desire for sex and attraction towards opposite
sex.
Reproductive life in female is restricted between menarchy and menopause.
Menopause is the stoppage of menstrual cycle at the age of about 45 years.
Reproductive life in male starts from the age of puberty and it lasts atleast
theoretically till death.

Male Reproductive System

It comprises of primary sex organ testis, accessory sex organs like seminal
vesicle, prostate gland, bulbo urethral gland or Cowper’s gland and penis.

Testis
Testis is made up of highly coiled tubular structures and interstitial cells.

Seminiferous tubule Function—Spermatogenesis

Epididymis—Storage and maturation of sperms. Vas deferens—storage of

sperms.
Interstitial cells of Leydig or testis—secretion of male sex steroids i.e.,
androgens—testosterone.

Functions of testis are two:

1. Endocrine function—secretion of male sex steroids or androgens.

2. Exocrine function—production of male sex gamete or sperms -
spermatogenesis.

TABLE 11.1
Functions of male reproductive organs
S.No. Parts of male sex organ 1. Seminiferous tubules Germ cells
Sertolicells
Functions
Production of sperms support.
Nutrition and secretion.

2. Epididymis Store house of sperm cells

and maturation of sperm cells. Transports sperms to vas deferens.

3. Vas deferens Transports sperms to ejaculatory duct. 4. Seminal vesicle

Uretur Seminal vesicle
Epididymis Bladder 5. Prostate gland
Seminiferous tubule
Lobules
Prostrate
Ejaculatory duct
6. Bulbourethral gland
Cowper's gland
7. Scrotum
Urethra
8. Penis
Vas defernce
Fig. 11.1
Male reproductive system

Prostaglandins and nutrients are produced which are helpful to neutralise acidic
semen.

Secretes alkaline fluid which helps to neutralise acidic semen and also promotes
motility of sperms.

Secretes a type of fluid which helps in the lubrication of the penis.

Protects testis.

(i) Carries urine. (ii) Conveys semen outside the body. (iii) During sexual
intercourse, penis is inserted in the vagina.

Urinary bladderVas Seminal Rectumdeferens vesicle

Urethra
Penis Prostate
Bulbourethral gland
ScrotumTestis Epididymis
Fig. 11.2 Male reproductive organs

Spermatogenesis
Spermatogenesis is the physiological process of production

of male sex gamete or sperms. Spermatogenesis commences from the age of

puberty. It takes place in the seminiferous tubule of testis. Duration—about 74
days.

Stages of spermatogenesis

It starts from germinal epithelial cells—spermatogonia. These cells have 23 pairs

of chromosomes or 46
chromosomes or diploid number of chromosomes i.e., 22
pairs of autosomes and one pair of sex chromosome (xy). These cells undergo
mitosis and give rise to primary spermatocyte having diploid number of
chromosomes. Primary spermatocyte undergoes meiosis and gives rise to
secondary spermatocyte. These cells have got haploid number of chromosomes
(n). Secondary spermatocyte gives rise to spermatid. Spermatid matures into
spermatozoa or sperms. This process is known as spermiogenesis. The entire
process takes about 60-70 days. The spermatozoa stored in the epidymis takes
about 2 months for maturation.

Basement membrane Daughter cell spermatogoniumof seminiferous tubule remains as a precursor stem cell
Spermatogonium 2n
Mitosis
2n Superficial
2n
Daughter cell spermatogonium
pushed away from basment membrance
Differentiation
Primary spermatocyte
DNA replication 2ntetrad formation,
and crossing-over
Reduction division (Melosis I)
Secondary spermatocytesMeiosis

Each n nchromosome
has two
chromatids

Equatorial divison (Meiosis II)

Spermatids
n n n Cytoplasmic bridge

n
Spermiogenesis Spermatozoa
n n n n Deep
Lumen
Fig. 11.3
Stages of spermatogenesis

Germinal epithelial cells or spermatogonia A 23 pairs 2n = diploid number 22

pairs of autosomes + xy

Mitosis
↓
Soermatogonia B 2n
↓

Primary spermatocyte—diploid, 2n. Growth ↓

Meiosis
↓

Secondary spermatocyte—haploid n, 22 autosomes and one sex chromosome

either X or Y ↓
Spermatid

↓
Spermiogenesis
Sperms or Spermatozoa.

Factors influencing spermatogenesis

1. Temperature: Ideal temperature for spermatogenesis is 2–5oC lower than

body temperature. To attain this low temperature testis descend from abdominal
cavity into the scrotum. The failure of the testis to descend from the abdominal
cavity is known as cryptorchidism. It is corrected at early life by surgically
pulling the testis out of the abdominal cavity.

2. Hormones
(a) Hormones of anterior pituitary—gonadotropic hormones—FSH, and LH.
(b) Thyroid hormone or thyroxine.
(c) Hormones of testis—testosterone.
3. Nutrition—Proper nutrition is essential for
development of testis and spermatogenesis.
Factors adversely affecting spermatogenesis:
1. High body temperature.
2. Repeated exposure to x-rays and other radiations.
3. Chronic alcoholism.
4. Mental depression.
5. Viral infection—mumphs. It causes infection and inflamation of testis and
damages seminiferous tubules.
6. Vasectomy: Ligation of vas deferens leads to degeneration of seminiferous
tubules and stop the spermatogenesis.
Hypothalamus GnTHRF
Anterior pituitary + Posterior pituitary
– TSH GnTH
GH+ FSH LH
Sertoli cells Leydig cells Thyroxine Oestrogen Testosterone
Inhibin+ + + + Spermatogensis

Fig. 11.4 Hormonal influence of spermatogenesis. GnTHRF gonado trophic

hormone releasing fector, GnTH -Gonado tropic hormones. TSH - hyroid
stimulating hormone. GH - growth hormone.

Middle Principal piece

Head Neck piecetail Endpiece
Nucleus
Centriole Axial filament
MitochondriaAcrosomal cap
Fig. 11.5
Sperm

The matured human sperm is 55–65 µm long and can be divided into two parts,
a head and a tail. Head is about 5 µm in length, 3 µm in width. It consists of
nucleus copped by an acrosome. Acrosome contains mucopolysaccharides and
acid phosphatase Tail comprises of

(a) the neck (b) the middle piece (c) the principal piece and (d) the end piece.
The tail shows ciliary movement which gives motility

to sperm.
Abnormal spermatogenesis

1. Problems with sperm production, motility, or count may lead to infertility. In

immotile cilia syndrome, this is an autosomal recessive defect, immobile or poor
motility of the cilia of the airways and sperm result. Consequently, an egg cannot
be fertilised and male infertility results.

2. Azoospermia can also lead to infertility. In males afflicted with azoospermia, a

non-measurable amount of sperm is present in the semen.

3. Azoospermia has two forms: obstructive azoospermia, where sperm are

created but cannot be mixed with the rest of the ejaculatory fluid due to a
physical obstruction, and non-obstructive azoospermia, where there is a problem
with spermatogenesis.

4. Non-obstructive azoospermia can be caused by cystic fibrosis, obstruction of

various sperm pathways, chemotherapy, and Klinefelter syndrome.

5. Impairment of sperm transport, may lead to infertility as well. It can be caused

by a variety of factors such as obstruction of the epididymis or vas deferens and
cystic fibrosis.

Semen
Semen contains secretions of seminal vesicle, prostate, bulbourethral gland
(Cowper’s gland).
Property

Volume — 2-5 ml per ejaculation

pH — 7.4
Specific gravity — 1028
Colour — Greyish white
Appearance — Opalacent
Sperm count — 60–150 million/ml. Average is 100

million/ml.
Whenever sperm count falls below 20 million per ml it leads to sterility.
TABLE 11.2
Composition of semen
Seminal vesicle Bulbourethral and
Prostate Vas deferens

60%
Fructose
Flavine
Ascorbic acid
Prostalgandins
Phosphoryl choline 30%
Calcium
Acid phosphatase Spermine
Cholesterol
Phosphate
Bicarbonate
10%
Spermatozoa Hyaluronidase

SERTOLI CELLS

These are special tall columnar cells attached to the basement membrane of
seminiferous tubule. Sertoli cells are different from the germ cells in three
respects.

(a) They remain fixed to basement membrane. (b) They are long lived and
robusts.
(c) They stop dividing before puberty.

Functions of Sertoli Cells

1. They support the constantly moving population of proliferating cells.

2. Nutrition: Fluids reach the inner germ cells only via the sertoli cells because
no blood vessels enter the tubule.
3. Spermiation: Controlled release of clusters of fully formed sperms from time
to time.
4. Phagocytosis: Removal of defective cells and cytoplasmic debris.
5. Blood testis barrier: It acts as a blood testis barrier. This barrier now and
then allows the inward passage of clusters of dividing spermatocytes. The Sertoli
cell also helps to isolate haploid gametes from the immune system of the body
which would other wise recognise these cells with 23 chromosomes as nonself
and destroy them.
6. Synthesis and Secretion: Sertoli cells secrete the following substances which
regulate male reproduction.
(a) Androgen binding protein (ABP) synthesised under FSH stimulation.
(b) Inhibin—a protein hormone which depresses anterior pituitary from secreting
FSH by acting as a negative feedback mechanism. (c) Oestrogen—small
quantity.

Androgens: They are male sex steroids. Important androgens are

1. Testosterone
2. Androstenedione
3. Dehydroepiandrosterone (DHEA).
Testosterone: It is an important male sex steroid. Functions of testosterone in
foetal life
1. Sex differentiation in foetus: Testosterone is responsible for the degeneration
of Mullerian duct and development of male sex organs like epididymis, vas
deferens, prostate and seminal vesicle from the Wolffian duct. Stimulates sertoli
cells to secrete Mullerian regression factor.
OO
5 HO
O Dehydroepiandrosterone Androstenedione
OH OH
5 HO
O
Androstenediol Testosterone
Fig. 11.6
Androgens

2. Produces the growth of external genitalia penis and scrotom.

3. Responsible for pushing of testis from the abdominal cavity into the scrotom.
This is known as descent of testis. If testis fail to descend that condition is called
as cryptorchidism.

Functions and actions of testosterone in adult life

1. It is responsible for appearance and maintenance of secondary sexual

characteristics in male.
2. It produces growth and development of accessory male sex organs. This
includes growth of seminal vesicle, prostate, bulbourethral gland and penis.
3. It produces broadening of shoulder and narrowing of pelvis.
4. Voice change: Testosterone produces change in voice by producing
hypertrophy of laryngeal muscles, enlargement of larynx and lengthening and
thicking of vocal chords. This produces craking of voice at the time of
adolescene. Later it changes into adult type.
5. Bone growth—After puberty bones grow in thickness.
6. Muscle growth—Muscle mass increases due to the anabolic actions of
testosterone.
7. Hair growth—Testosterone produces male type of hair distribution on the
body—hair growth on pubis, on face and chest. It decreases the growth of hair
on scalp leading to baldness.
8. It produces thickening of skin mainly due to increased deposition of proteins.
9. It increases sweating, increases secretion of sebum-leading to appearance of
pimples . 10. Stimulates bone marrow and increases rate of erythropoiesis,
increases RBC count, increases blood volume.
11. Increases metabolic rate.
12. Increases protein synthesis, decreases protein breakdown leading to positive
nitrogen balance. 13. Promotes spermatogenesis.
14. Responsible for male aggressive behaviour. Male psyche.

Regulation of secreation of testosterone

Hypothalamus secretes a small peptide known as Gonadrotropic hormone

releasing factor. GnTHRH stimulates the anterior pituitary. This increases the
secretion of FSH and LH. These hormones stimulate the testis. This increases the
secretion of testosterone. Increased level of testosterone in the blood exerts a
negative feedback effect at the hypothalamus and anterior pituitary. This inhibits
further secretion of hormones of this axis.
Hypothalamus
–
Gn THRF
+ Anterior pituitary
–
FSH&LH
+
Testis
Testosterone
Fig. 11.7
Regulation of secretion of testosterone
FSH also stimulates sertoli cells to increase the secretion of inhibin. Inhibin
exerts negative feedback at anterior pituitary and suppresses the further secretion
of FSH. This prevents excess spermatogenesis.

Hypogonadism—Removal of testes (Castration) There are two main types of

hypogonadism, primary hypogonadism occurs due to defective testis, which
results into increased level of circulating gonadotrophin. Secondary
hypogonadism results due to impairment of hypothalamus or pituitary gland,
which significantly reduces the concentration of circulating gonadotropins.
Following are the clinical conditions related with hypogonadism.
Before Puberty—Results into permanent infertility called as Eunuchoidism.

After Puberty—Sexual desire and penis erection is hampered leads to

psychological changes such as depression, irritability.

Infertility: The diminished ability or the inability to conceive and have

offspring. Infertility is also defined in specific terms as the failure to conceive
after a year of regular intercourse without contraception.

Infertility is not always a woman’s problem. In only about one-third of cases is

infertility due to the woman. In another one third of cases, infertility is due to the
man (male factors). The remaining cases are caused by a mixture of male and
female factors or by unknown factors.

Infertility in men is most often caused by: 1. Problems production of sperm

(Spermatogenesis)

—producing too few sperm or none at all. 2. Problems with the sperm’s ability to
reach the egg
and fertilise it—abnormal sperm.
3. Shape or structure prevents it from moving correctly. 4. Sometimes a man is
born with the problems that
affect his sperm. Other times problems start later

in life due to illness or injury. For example, cystic fibrosis often causes infertility
in men.

5. Erectile dysfunction and abnormal ejaculation also contribute for male

infertility.
Infertility in women: Problems with ovulation account for most cases of
infertility in women. Without ovulation, there are no eggs to be fertilised. Some
signs that a woman is not ovulating normally include irregular or absent
menstrual periods. Less common causes of fertility problems in women include:
1. Blocked fallopian tubes due to pelvic inflammatory disease, endometriosis, or
surgery for an ectopic pregnancy.
2. Physical problems with the uterus—Endometriosis.
3. Uterine fibroids.
4. In some females ovulation does not occur due to hyposecretion of
gonadotropic hormones.
Most types of infertility are treatable. In some cases, in vitro fertilisation and
other lab procedures may be used to ensure fertilisation, and special medical care
or medication may be required to enable the pregnancy to come to term.

FEMALE REPRODUCTIVE SYSTEM

Female reproductive system comprises of primary sex organ– ovaries and

accessory sex organs like fallopian tube, uterus, vagina, cervix and breast.

Ampulla Isthmus Fendus fo uterusFibriae Fallopian tube

Infundibulum Uterine cavity
Body of uterus
Cervix Cervical canal
Vagina

Fig. 11.8 Female reproductuve system

Primordial follicle Primary follicle
Arnetic follicle Vesicular follicle
Corpus Luteum Corpus hemorrhagicum
Corpus albicans Graffian follicle Fig. 11.9
Ovarian cycle

Functions of ovary: Endocrine function – production of hormones – oestrogen,

progesterone, relaxin.
Exocrine function – production of female sex gamete
– ovum.

Landmarks in development of female reproductive life Telareche:

Appearance of breast buds during second stage of puberty at the age of around
10–11 years.

Pubarche: Appearance of pubic and axillary hairs during the 3rd stage of
puberty at the age 11–12 years.
Menarche: It is the first menstrual cycle which normally occurs at the age of
12–14 years.

Adrenarche: An increase in the secretion of adrenal androgens at the time of

puberty without any increase in ACTH or cortisol age 12–14 years.

Menopause: Stoppage of menstrual cycle at the age of about 45 years.

Hypothalamus releases GnRH Oogonium 1st - 3rd month of 2n intrauterine life
Mitosia Anterior lobe of the pituitary gland releases Gonadotropins - FSH and LH

Primary oocyte Tetrad formation

and crossing-over 2n reduction division
(meiosis I)
Just prior
to ovulation

Ovaries release oestrogen Secondary oocyte

n First polar bodyMeiosis n
May or
may not
divide again
Breasts develop
Accessory reproductive organs enlarge Ovulation n n

nn Increased vascularisation

of the skin
Sperm Fertilisation

Increased deposition of adipose tissue in breasts, thighs and buttocks feminine shape of the body
Fertilised ovum

nn
Equatiorial division
(Meiosis II)

Maturation

Fig. 11.10 Hormonal control of reproductive growth in female

Menstrual Cycle

Menstrual cycle is defined as a female reproductive cycle. It is a sequence of

series of changes taking places in the female reproductive system. Changes are
seen in
1. Ovary – Ovarian cycle
2. Uterus – Uterine cycle
3. Vagina –
4. Hormonal changes.
Duration of menstrual cycle—20 days to 40 days, average is 28 days.
Ovarian cycle: Duration 28 days.
Ovarian cycle is divided into 2 phases:
1. Follicular phase 2. Luteal phase. Follicular phase: Preovulatory phase
duration 14 days. During this period one of the ovarian follicle or graafian

follicle starts growing from one of the ovary. The maturation of ovarian follicles
is brought about by the action of FSH. Number of cells of follicles increases. An
empty space is formed known as antrum. Maturation of ovarian follicle is
completed around 14th day of menstrual cycle. Under the combined action of
FSH and LH, the matured follicle ruptures and releases the ovum. This process
is known as ovulation.

Oogenesis: The designation 2n means diploid (46 chromosomes); n means

haploid (23 chromosomes).
Zygote Second polar body 2n n

Fig. 11.11 Stages of oogenesis

Test for Ovulation or Test for time of Ovulation
Time of ovulation or day of ovulation can be found out by various methods.

1. Recording of basal body temperature: Body temperature is recorded from

rectum or vagina every day immediately after getting from bed. Body
temperature shows a rise by 0.5oC on the day of ovulation and remains high
throughout. It is due to the thermogenic effect of progesterone.

2. Examination of cervix: Secretion from cervix is very thin on the day of

ovulation, afterwards it becomes thick. A smear is made out of cervical mucus
on a glass slide. When the slide is examined under the microscope it shows a
fern like appearance before ovulation. After ovulation it does not form fern like
pattern.

3. Endometrial biopsy shows the presence of functioning corpus luteum

(secretary pattern) indicating ovulation is over.

4. Examination of vagina: It reveals that after ovulation vaginal cornification

disappears.

5. Estimation of plasma concentration of LH: Sharp increase in LH

concentration just before ovulation. Progesterone shows gradual rise after
ovulation.

6. Urine examination: Pregnanediol, a metabolite of progesterone appears in

urine after ovulation.
7. Estimation of FSH and LH: Concentration of FSH and LH are high just
before ovulation. A sharp rise in LH level in blood known as LH surge is
observed about 9 to 16 hours before ovulation.

Significance of knowing day of ovulation: It is important both for promoting

chance of conception as well as to avoid conception. Sexual intercourse is be to
done on and around the day of ovulation to enchance the chance of fertilisation
and pregnancy. Sexual intercourse is avoided around the day of ovulation to
avoid fertilisation and pregnancy.

Luteal phase: Post ovulatory phase duration is 14 days. During this period the
cells of the ruptured follicle,
are retained as corpus luteum. These changes are influenced
by the action of LH. LH also stimulates the corpus luteum
to secrete, progesterone. Fate of corpus luteum depends upon
the fate of the ovum. If ovum fails to get fertilised, the corpus
luteum starts to disintegrate and disappear. This ends one
ovarian cycle and the next ovarian cycle begins.
Uterine cycle: Duration 28 days.
It is divided into three phases.
1. Menstrual period – 4 days
2. Proliferative phase – 10 days
3. Secretory phase – 14 days.

Menstrual period
Menstrual phase

Definition of menstruation: Menstruation is a process of discharge of

unfertilised dead ovum, along with pealed off cells of wall of uterus, secretions
of uterus and vagina and blood.

Also known as menses, emmania, catamenia.

Day of onset of bleeding is considered as first day of menstrual cycle.
Menstruation stops between 3rd and 7th day of menstrual cycle.

Cause

If the ovum is not fertilised it causes regression of corpus luteum and hence there
is sudden reduction in the release of oestrogen and progesterone from corpus
luteum of ovary. This reduction is responsible for menstruation.

Endometrial changes during menstrual phase

Lack of oestrogen & progesterone
Involution of uterus (upto 65% of original thickness)
More coiling of spiral arteries
Vasoconstriction
Hypoxia resulting in necrosis of endometrium
Necrosis results in release of prostaglandins
Further spasm of spiral artery
Rupture of blood vessels - hemorrhages
Superficial layers of endometrium is sloughed off
Rupture of blood capillaries
Menstrual flow
Fig. 11.12
Endometrial changes

– Complete studding occurs within 4–5 days.

– Blood lost is mainly arterial (25% venous).

– In normal menstruation – about 35 to 50 ml of blood is lost and 35 ml of

serous fluid is expelled. The blood clots immediately after it oozes, into the
uterine cavity. But soon the fibrinolytic system causes the lysis of blood clot. So
the expelled blood and menstrual fluid do not clot. The final thickness of
endometrium is about 1mm after the end of menstrual phase.

Proliferative phase

This phase occurs following the menstrual phase and lasts up to the day of
ovulation i.e., usually 5th to 14th day of menstrual cycle.

During this phase as the endometrium continuously proliferates it is called

proliferative phase.
This corresponds to follicular phase of ovarian cycle. Cause: Increasing
concentration of oestrogen which is released from ovary.
Endometrial changes during proliferative phase
1. Rapid proliferation of endometrial cells.

2. Newly formed cells get arranged in layers there by increases the thickness of
wall

3. Epithelialisation of endometrium.
4. Growth of endometrial stroma.
5. Blood vessels and uterine glands develop within the stroma.
The thickness of endometrium is about 4-5 mm at the end of proliferative phase.
Secretory phase or Progesterone phase: This phase occurs following ovulation
and lasts up to menstruation of next menstrual cycle.
i.e., 15th to 28th day of menstrual cycle.
Cause: It corresponds to luteal phase of ovarian cycle. Duration of this phase is
fixed, it will not vary. Ovulation occurs on 14th day, under the influence of LH.

Within about 3 days the corpus luteum develops in the ovary.

It secrets large amount of progesterone and a small quantity of oestrogen and the
changes occurring in the secretory phase is under the influence of these two
hormones.

Endometrial changes during secretory phase

1. Endometrial glands become larger and more tortuous.
2. Glands are filled with secretion.
3. Appearance of new blood vessels which become tortuous.
4. Increase deposition glycogen and lipid in the stromal and epithelial cells of
endometrium.

Some secretions may be exudated from endometrium which comes out through
vagina and is called uterine milk. Secretion of uterine cervix becomes thicker.
Thickness of endometrium is about 5-6 mm at the end of secretory phase.

TABLE 11.3
Major changes taking place during mensteal cycle
Sl.No. Stages and days of menstrual cycle Ovary Uterus Hormones

1. Menstrual period 1–4 days

Regression of corpus luteum. A fresh follicle is activated to grow.
Peeling off of wall of uterus, thickness wall becomes least. Fall in oestrogen and
progresterone level, FSH and LH secretion increase.

2. Preovulatory period Proliferative phase 5–7

3. 7–12
Preovulatory period, Proliferative phase

4. 12–13
Preovulatory phase, Proliferative phase

Dominant follicle is released. Proliferation of endometrium

starts.
Plasma oestrogen, FSH level increases.

Follicle grows and mature proliferation of granulose cells of the follicle.

Thickness of wall of uterus increases.
Plasma oestrogen further increases.

Maturation of follicle takes place granulose cells secretes follicular fluid. This
forms a cavity in the granulose— antrum forms graafian follicle. Thickness of
wall of uterus further increases. Endometria becomes more vasculer. Cervix
secretes thin mucus in large quantity. Blood vessels become more spiral.
Concentration of FSH increases. LH surge occurs just before ovulation.

5. 14

Ovulation Rupture of follicle, release of ovum.

Endometrium becomes ready for implantation.
LH surge causes release of

prostaglandins leading to ovulation.

Contd…

6. 15–25
Postovulatory phase Luteal phase
Secretory phase Cells of the ruptured follicle enlarge in diameter and get

filled with lipid and forms corpus luteum.

Additional proliferation of endometrium producing further increase in thickness.
Vascularisation further increases. Secretes thick viscuous nutritive fluid.
Thickness reach 5–6 mm. Plasma concentration of oestrogen and progesterone
increase.

7. 25–28
Post ovulatory Luteal phase Corpus luteum starts to involute and get converted

into corpus albicans. Corpus luteum degenerates.

Wall of the uterus fail to sustain its integrity, spiral arteries becomes vasospastic.
Significant fall in oestrogen and progesterone level in plasma.
LH
FSH
Follicular phase Luteal phase
Developing follicles Ovulation Corpus Luteal luteum regression
Estrogen
Progesterone
Uterine changes
Basal
body temperature
2 4 68 10 12 16 18 20 22 24 26 28 days
Menstrual Postmenstrual phase (proliferative) phase Ovulation Premenstrual Menstrual (secretory) phase
phase

Fig. 11.13 Menstrual cycle

HORMONAL CHANGES OR HORMONAL INFLUENCE OF
MENSTRUAL CYCLE

There are four hormones directly involved in menstrual cycle. They are:
1. FSH 2. LH
3. Oestrogen 4. Progesterone
1. FSH: It is secreted from anterior pituitary. FSH promotes the maturation of
ovarian follicle. It is also responsible for the rupture of matured follicle leading
to the release of ovum. The concentration of FSH in the blood shows a peak
before the day of ovulation.
2. LH: It is secreted from anterior pituitary. This hormone is responsible for the
maintenance of the cells of ruptured follicle as corpus luteum. LH also
stimulates the corpus luteum to secrete progesterone. Concentration of LH
shows a sharp increase just before the day of ovulation. This is known as LH
surge.
3. Oestrogen: It is secreted both from maturing ovarian follicle as well as corpus
luteum. Oestrogen is responsible for the proliferative changes in the wall of
uterus during the menstrual cycle. The concentration of oestrogen in blood
shows two peaks i.e.,
(a) first peak is before the day of ovulation. (b) second peak is in the middle of
luteal phase. 4. Progesterone: It is secreted by the corpus luteum. It is
responsible for the secretory changes in the wall of uterus during the menstrual
cycle. The concentration of progesterone shows a peak around the middle of
luteal phase. Withdrawal of progesterone is responsible for uterine bleeding.

Some common terms related to menstruation

Menarche: The appearance of first menstrual cycle is called menarche. This is

due to sufficient release of gonadotrophin releasing hormone from the
hypothalamus.

Menorrhagia: Excess discharge of first blood during menstruation is called

menorrhagia.

Dysmenorrhea: Excessive pain and other difficulties associated with the

menstrual cycle.
Oligo menorrhea: Scanty menstrual bleeding.
Amenorrhea: No menstrual cycles.
Primary amenorrhea: Menstrual cycles do not appear at all.
Secondary amenorrhea: Menstrual cycle appears but again disappears due to
various reasons. The important cause for this is pregnancy.
Metrorrhagia: Bleeding in the middle of the menstrual cycle.
Phases of the female reproductive cycle Ovulation Menstrual
phase Preovulatory
phase
Postovulatory phase
LH
Progesterone
Oestrogens
FSH
02 4 6 8 1012 14 16 1820 22 242628 Days

Fig. 11.14 Days of menstrual cycle and hormonal changes CORPUS LUTEUM
clot forms at the site of the ruptured follicle forming what is

Corpus luteum is a structure which grows on the remains ofknown as Corpus

haemorrhagicum. The follicular cells grow the ruptured graffian follicle. When ovulation
occurs, therapidly and fill up the cavity. This forms corpus luteum— follicle ruptures along
with rupture of blood vessels. A bloodwhich is yellow in colour.

It consists of columns of large conical cells with distinct nucleus and yellowish
pigment granules the lutein. The corpus luteum attains its maximum size on the
19th day of menstrual cycle. In the absence of pregnancy it persists upto 27th
day and degenerates on the 28th day, when menstruation begins. This corpus
luteum is called corpus luteum of menstruation or false corpus luteum.

The corpus luteum of menstruation ultimately makes a white scar in the ovary
known as Corpus albicans. If pregnancy takes place, the corpus luteum
continues to grow attaining its largest size about the 3rd to 4th month. This is
known as corpus luteum of pregnancy. It is maintained by the action of HCG
secreted by placenta. It degenerates in the latter months forming a fibrous scar.

Functions of corpus luteum

It is an endocrine structure and secretes:
1. Progesterone 2. Oestrogen
Progesterone secreted by corpus luteum produces
secretary changes in the wall of the uterus. The uterine
endometrium becomes thick, highly vascular, soft, warm and
moist—ideal for the implantation of fertilised ovum. So
promotes pregnancy.
Corpus luteum is essential for the maintenance of

pregnancy at least during early days of gestation. At the earliest stage of

pregnancy it provides oestrogen for the growth of uterus and progesterone
producing relaxing effect upon the uterus, which suppresses contraction. So
progesterone is essential for the maintenance of established pregnancy.

Later functions of corpus luteum is taken over by placenta.

Female Sex Hormones

Oestrogen
Source: 1. Growing ovarian follicle

2. Corpus lutea and

3. Placenta
Chemistry: It is a steroid hormone. The naturally occuring oestrogens in
humans are
(a) β-Estradiol (b) Estrone (c) Estriol Oestrogen: Functions and actions
On breast: Oestrogen stimulates the growth of ducts of breasts, and stromal
tissue there by cause enlargement of breasts at the time of puberty. It also
promotes the deposition of fat in the breasts there by prepares the breast for milk
production. It causes pigmentation of areola.
H CH3 OH CH3 O
HO HO
Estradiol Estrone
CH3 O
H OHH CH CCH OH
3 3 CH3

HO O
Estriol Progesterone Fig. 11.15 Female sex steroids

Acetate
Cholesterol
a17 -hydroxypregnenolone Pregnenolone
Dehydroepiandrosterone Progresterone
a17 -hydroxypregosterone Corticoteroids
Androstenedione Testosterone
Estrone Estradiol
Estriol
Fig. 11.16
Biosynthetic pathway of sex steroids

Vagina: Oestrogen produces cornification of vaginal epithelium. Under the

oestrogen influence vaginal epithelium changes from cuboidal to stratified type.

Fallopian tube: Oestrogen causes proliferation of epithelial cells and increases

the activity of cilia of fallopian tube.

Uterus: Myometrium: Oestrogens increases the size and vascularity

endometrium—Oestrogen is responsible for the proliferative changes during
menstrual cycle. Cervix: Oestrogen makes the secretion of cervix thin, alkaline
and elastic. It produces fern pattern.
(a) It produces change in body shape - narrowing of

shoulder, broadening of pelvis, convergence of thighs, and divergence of arms.

(b) It promotes the deposition of fats in the body and gives a feminine curvature
to the body.
(c) It helps in childbirth or parturition; oestrogen makes the muscles of uterus
more sensitive to the binding of oxytocin.
Voice: The larynx remains prepubertal stage, which produces high pitch voice.
3. Metabolic function: It promotes protein synthesis —it is an anabolic steroid.
It produces positive nitrogen balance.
It causes deposition of fat in the subcutaneous tissue, breasts, buttocks and thigh.
4. It controls the secretion of FSH and LH from anterior pituitary.
5. Skin: Oestrogen makes the sebaceous glands to secrete more fluid, makes the
skin move vascular and causes the skin to develop soft texture. It prevents the
formation of acne. It produces hair growth at axilla and pubic regions.
6. Effect on skeleton: Oestrogen causes an increase in osteoblastic activity,
which results in growth spurt at puberty. It hastens bone maturation and
promotes the closure of epiphysial plates in the long bones more effectively than
testosterone.
Effect on electrolyte balance-like minerelocorticoids it retains sodium and water
in the body.
Endocrine glands: It exerts a negative feedback effect on hypothalamus and
anterior pituitary and inhibits the secretion of gonadotroptic hormones.

Progesterone
Source: It is secreted from
1. Corpus luteum of the ovary.
2. Placenta.
Chemistry: It is a C21steroid hormone.

CH3
C=0
O
Fig. 11.17
Progesterone
Progesterone: Functions and actions
Actions on uterus

Myometrium: Progesterone shows anti estrogenic action. It decreases the

activity and excitability and makes myometrium less sensitive for oxytocin
binding. This prevents the expulsion of implanted zygote. This promotes the
chances of pregnancy.
Endometrium: It produces the wall of uterus more vascular and responsible for
the secretary changes in the uterine endometrium during menstrual cycle.

It promotes the secretion of nutritive fluid by the wall of uterus. This fluid
provides nutrition to zygote.
Cervix: It makes the cervical secretion more thick, tenacious and cellular. Fern
pattern disappears.
Vagina: It produces proliferation of vaginal epithelium and produces its
enlargement during pregnancy.
Fallopian tube: It stimulates fallopian tube to secrete nutritive fluid.
Breast: Progesterone stimulates the growth of lobules and alveoli of breast.
Endocrine gland: Progesterone exerts a negative feedback mechanism at
hypothalamus and anterior pituitary and there by inhibits the secretion of LH.
Metabolic action: Progesterone produces greater protein breakdown—catabolic
steroid.
Thermogenic action: It increases basal metabolic rate and there by increases
body teruperature. Because of this body temperature increases by 0.5°C after
ovulation and it remains at this temperature throughout the luteal phase. It forms
a basis for test for ovulation.
Sodium and water retention: Progesterone blocks the action of aldostorone
there by increases loss of sodium and water form the body. This leads to lesser
retention of salt and water in the body.
Role in parturition: Progesterone produces enlargement of birth canal by:
(a) Enlarging vagina.
(b) Decreasing tension in the pelvic ligaments. This helps in parturition.
Hypothalamus
–
Gn THRF
+ Ant. pituitary
–
Gn. TH (FSH & LH)
+
Ovary

Regulation of secretion of oestrogen and progesterone Hypothalamus secretes

Gonadotropic hormone releasing factor. Gn THRF—this stimulates anterior
pituitary and increases the secretion of Gonadotropic hormones—FSH and LH.
These hormones stimulate the ovary. This increases the secretion of female sex
steroids. When the concentration of female sex steroids in the blood increases
that exerts a negative feedback effect at the level of hypothalamus and anterior
pituitary. This inhibits further secretion of hormones of this axis—hypothalamo
hypophysial gonadal axis.
Oestrogen progesterone
Fig. 11.18 Regulation of secretion of female sex steroids
TABLE 11.4
Comparison of effects of oestrogen and progesterone on the reproductive
system
Sl. No. Organ Oestrogen Progesterone 1. Oviducts
Muscular wall

2. Uterus
Endometrium Myometrium Cervical glands

3. Vagina
Contractility Contractility

Proliferation
Growth and contractility Watery secretion

Epithelial proliferation Glycogen deposition Differentiation and secretion

Contractility
Dense, viscous secretion

Differentiation
Proliferation

Relaxin
Source: Corpus luteum placenta and uterus. Chemistry: It is a polypeptide.
Functions: It facilitates delivery by:

(a) relaxation of symphysis pubis and other pelvic joints.

(b) softening and dilatation of cervix.

Physiology of pregnancy

Fertilisation is the union of a human egg and sperm, usually occurring in the
ampulla of the fallopian tube. It is also the initiation of prenatal development.
Scientists discovered the dynamics of human fertilisation in the nineteenth
century.
Fertilisation constitutes the penetration of the oocyte (egg) which the sperm
performs, fusion of the sperm and oocyte, succeeded by fusion of their genetic
material.

Fertilisation starts with a man and a woman initiating sexual intercourse. The
man inserts the penis into the woman’s vagina. Upon orgasm, the man ejaculates
semen, which contains millions of sperm, from his penis into the woman’s
vagina. Propelled through the female reproductive tract by flagellation, some of
these sperm may reach the cell membrane of the oocyte, and a single sperm may
penetrate the membrane. To reach the oocyte, the sperm must pass through the
corona radiata and the zona pellucida; two layers covering and protecting the
oocyte from fertilisation by more than one sperm.

Implantation is an event that occurs early in pregnancy in which the embryo

adheres to the wall of uterus. At this stage of prenatal development, the embryo
is a blastocyst. It is by this adhesion that the fetus receives the oxygen and the
nutrients from the mother to be able to grow.

Implantation happens within 1–2 days after arrival of the blastocyst in the uterus,
usually around 9 days after ovulation with a range of 6–12 days. At that time, the
blastocyst is barely visible to the naked eye, probably smaller than the dot above
the letter. Once implantation happens the blastocyst becomes the embryo.

Pregnancy test or pregnancy diagnosis test

Pregnancy test means tests conducted for the confirmation of pregnancy. Early
indication of pregnancy is missing of the menstrual cycle. But this may be due to
various other psychological, physiological or pathological reasons. Therefore
confirmation of pregnancy is important. Uses of early confirmation of
pregnancy.

1. It gives more time for the proper nutritional care of the mother and child.
2. It helps in giving better medical care to the mother and child avoiding
hazardous work, avoiding exposure to radiations, chemicals and harmful drugs.
3. Early confirmation of pregnancy is useful for the termination of unwanted
pregnancies with minimum risk to the life and health of the person.

Principle: If a lady is pregnant, placenta will be present. Placenta secretes

human chorionic gonadotropin (HCG). No other structure in the body is capable
of secreting HCG. If HCG is detected either in the plasma or in the urine, it
indicates the presence of placenta and it confirms pregnancy.

Procedure
Two reagents are available:
(a) HCG antibody
(b) Latex particles coated with HCG.
Morning urine sample of the lady is collected, to a

drop of urine, HCG antibody is added and mixed. To this mixture, latex-HCG is
added and mixed. Look for agglutination. If no agglutination it indicates the
presence of HCG in the urine sample. This indicates the presence of placenta and
it confirms pregnancy.
Human chorionic gonadotropin (hCG)
Oestrogen
Progesterone
04 8 12 16 20 24 28 32 36 40 Age of embryo/fetus (weeks)

Fig. 11.19 Blood level of hormones during pregnancy

PLACENTA

Placenta is a functional connection between the embryo and the uterus of

mother. It consists of both embryonic and maternal tissues. It allows for
nutritional, respiratiry and excretory interchange of materials between the
embryonic and maternal circulatory system.

Placenta consists of two parts (1) Maternal part (2) Foetal part. Maternal part
consists of large blood sinuses, Maternal blood circulates through these sinuses
—arterial blood entering through the uterine arteries and venous blood passing
out through the uterine veins. The foetal part consists of numerous finger like
processes—the chorionic villiprojecting into the maternal sinuses and being
bathed all around by the maternal blood.

The maternal blood is separated from the foetal blood by the two layers—the
cytotrophoblastic layer and the outer trophoblastic layer. Exchange of gases,
nutrients and metabolites take place through these membranes.

Table 11.5
Sources and functions of hormones of pregnancy
Placenta Sl.No. Relaxin Human chorionic somatomammotropin (hCS)
Oestrogen and progesteron Human chorionic gonadotropin (hCG)

1. • Symphysis pubis relaxation. • Mammary glands are

2. • Dilatation of uterine cervix. prepared for lactation.
• Protein anabolism is increased.
• Mammary glands are prepared for lactation.
• Endometrium is
maintained.
• Maintenance of corpus luteum.
• Stimulates corpus
luteum to secrete
progesterone
• tropical hormone for foetal adrenal cortex
Gland in
endometrium

Endometrium Branch of umbilical artery and vein

Myometrium
Yolk sac Umbilical vein

Umbilical arteries Umbilical cord

to fetus

Main stem of chorionic villus

Chorionic villi

Uterine artery and vein

Pool of maternal blood

AmnioticPlacenta cavity

Fig. 11.20 Placenta

Functions of Placenta

1. Nutritive function
2. Respiratory function
3. Excretory function
4. Endocrine function
5. Protection of foetus.
1. Nutritive functions: All the nutritive elements from the maternal blood pass
into the foetal through placenta. Besides this placenta can store glycogen and
lipids for emergency.
2. Respiratory functions: Oxygen diffuses from mother’s blood to foetal blood
and carbondioxide diffuses from foetal blood to mother’s blood.
3. Excretory functions: The foetal metabolites and waste products diffuse into
maternal blood through placenta and are excreted by the mother.
4. Storage functions: Glycogen fat and inorganic ions are stored in placenta.
5. Endocrine functions: Placenta secrets the following hormones:
(a) Human chorionic gonadotrophin or placental gonadotrophin.
(b) Progesterone.
(c) Oestrogen.
(d) Human placental lactogen or Human chorionic somatomammotrophin.
(e) Relaxin.

(a) HCG
It is a glycoprotein.
Functions

(i) Maintains the corpus luteum until placenta becomes autonomous in terms of
hormone synthesis.

(ii) Converts corpus luteum of menstruation to corpus luteum of pregnancy.

(iii) Stimulates corpus luteum to secrete 17-hydroxyl progesterone.
(iv) Stmulates foetal testes to secrete testosterone. (v) Serves as tropic hormone
for foetal adrenal cortex.
The detecting the presence of HCG in plasma or urine sample forms the basis of
pregnancy test.
Progesterone
(i) Decreases uterine motility by causing hyperpolarisation of uterine
myometrium. (ii) Converts endometrium to deciduas.
(iii) Synergetic action of progesterone with oestrogen prepares the breast for
lactation.
Oestrogen functions
(i) Causes growth and development of the maternal reproductive organs mainly
uterus.

(ii) Stimulates the development of ductal system in the breast.

Relaxin: It causes relaxation of pelvic ligaments and ligaments of symphysis
pubis - helps in childbirth.

Human chorionic somatomammotrophin or human placental lactogen.

(i) It acts as growth hormone.
(ii) Produces nitrogen, calcium and potassium

retention.
(iii) Promotes the growth and development of breast
during pregnancy.
(iv) Promotes milk production.
Protection of Foetus: Placenta acts as a barrier which prevents the entry of
harmful substances into the foetal circulation.

MATERNAL CHANGES DURING PREGNANCY The physiological

changes which pregnancy induces in the mother have been described briefly
below.
Body weight and water balance

The mother may put on 10 to 12 kg during her pregnancy. This is mainly on

account of formation of new tissue (foetus and placenta), accumulation of water,
and fat deposition. The distribution generally is:

Baby
Placenta and amniotic fluid Enlargement of uterus and breasts Increase in blood
volume
Fat deposition
3.0 Kg. 1.5 Kg. 1.0 Kg. 1.5 Kg. 4.0 Kg.

Some oedema is common, particularly in the lower limbs. This may partly be
due to pressure of the enlarging uterus on abdominal veins and partly due to
excessive retention of water.

Blood

Although erythropoeisis increases during pregnancy to meet the additional

demands for oxygen. Water retention and haemodilution lower the hemoglobin
concentration. This should be kept in mind; a pregnant woman with 10 g/100 ml.
Hemoglobin is not necessarily anaemic.

Some iron supplementation, either through iron – rich foods or in the form of
iron – folic acid tablets, may sometimes be needed in late pregnancy as the
foetus draws considerable amount of iron from the mother for its own
erythropoietic activity.
Blood has a higher concentration of fibrinogen and factors VII, VIII and IX
during pregnancy. It coagulates more easily, perhaps a precaution against
excessive hemorrhage during childbirth. But the change also makes thrombosis
more likely. Increase in ESR is seen. Total plasma protein concentration
decreases.

Circulatory system
Heart rate increases, the cardiac output increases by about

30 per cent. The systolic blood pressure usually does not change but the diastolic
may fall slightly as the large placental blood pool lowers the peripheral
resistance.

Endocrine organs

The anterior pituitary remains markedly depressed by the high levels of

circulating placental progesterone and oestrogen during pregnancy. Very little
FSH, LH and GH are secreted. The thyroid increases in size. Blood
concentration of oestrogen, progesterone, cortisol, thyroxine, prolactin and
oxytocin increases. HCG appears.

Respiratory system
Oxygen consumption increases by about 20% during pregnancy and to meet this
demand the respiratory rate and tidal volume increase. This increases minute
respiratory volume, vital capacity decreases because movement of diaphragm is
restricted. Respiration becomes more of costal type—depending more on
intercoastal muscles.

Kidneys
Pregnant women may show some glucose in their postprandial urine although
they have no diabetes. This is at least partly because the glomerular filtration rate
is significantly increased. As a result the tubular load of glucose exceeds the
tubular maximum for glucose reabsorption. GFR increases, urine output
increases, frequency of micturition increases.

Skeleton
Contrary to general belief, pregnancy does not normally

produce any decalcification of teeth or bones. The fully grown foetus contains
30 g calcium and this is easily available through a normal diet without any need
for encroaching on the mother’s tissues.

Digestive system
In early pregnancy there may be morning sickness, nausea and vomiting. Change
in appetite is commonly observed.

Heart burn and acidity due to relaxation of the gastrooesophageal sphincter.

Reproductive system

Increase in the size and weight of uterus. Endometrium, now called decidua,
forms part of placenta, decidua basalis and covers the foetal sac—decidua
capillaries. The cervix becomes soft and increases secretion. Blood flow to
vagina increases. Ovaries stop ovulation. Mammary glands develop further and
get transformed into a secretory organ.

Metabolism: Basal metabolic rate increases by 25% positive calcium balance is

seen.
Nervous system: Excitement, irritability, depression are seen in early pregnancy
and last stage of pregnancy. Mood changes, desire for strange items and foods
are common.

MAMMARY GLANDS AND LACTATION

The mammary glands are the features of females and are provided for the supply
of nutrition to the baby. These are modified apocrine glands formed by
invagination of the surface epithelium. The solid columns later on become
canalised and there is also development of alveoli.

Each gland is composed of several lobes (15 to 25), each drained by a lactiferous
duct. These ducts open separately to the exterior through the nipple. Each lobe is
a miniature compound racemose type of gland and looks like a bunch of grapes.
There are contractile myoepithelial cells on the outer surface of the alveoli.

During childhood no change is seen in the mammary glands. First change is seen
at adolescence in the form of deposition of fat and increase in size. With the start
of the reproductive cycles after puberty, glandular tissues show changes with
changes in the concentrations of oestrogen and progesterone in each cycle.
Ultimately during pregnancy the final maturation of the glands takes place and
they become ready for milk secretion.
Oestrogen is responsible for the growth of the duct systems and also for
accumulation of fat. With increased oestrogen secretion during each follicular
phase there is some development each time. During pregnancy high amount of
placental oestrogens is produced, which leads to the full development of the
glands.

Progesterone similarly causes acinar growth in each cycle. But progesterone

needs oestrogen along with it. It also causes the final development of the acini
during pregnancy when sufficient progesterone is secreted from the placenta.

Prolactin level is not very high in non-pregnant state, hence it is important for
the mammary glands. During pregnancy its level increases to make the alveolar
cells ready for milk production. Prolactin needs prior activity of oestrogen and
progesterone and presence of other hormones. But prolactin can not lead to milk
production in presence of high levels of oestrogen and progesterone.

Other hormones like cortisol, GH, thyroxin, insulin etc. should also be present in
normal concentration to cause final maturation and milk secretion. Placental
oestrogen, progesterone and particularly the somatomammotrophin (placental
lactogen) are useful for the final development as stated above.

Lactation

Lactation is the process of milk output from the mammary glands. It can be
divided into two stages: secretion and ejection.

Milk secretion
It is the process of production of milk. It involves (i) initiation and (ii)
maintenance of secretion.

1. Initiation of secretion: It is also called lactogenesis. It starts when

progesterone decreases towards the end of the pregnancy, but in the presence of
low level of oestrogen. Oestrogen at low concentration probably helps by
inhibiting PIF (Prolactin inhibiting factor) and thus increasing prolactin
secretion. Prolactin secretion increases effectively during breast feeding.

2. Maintenance of secretion: It is also called galactopoiesis. This is the

function of prolactin mainly. But presence of other hormones, e.g., GH, thyroxin,
insulin, cortisol etc. are also necessary.
Milk ejection
It means expulsion of the formed milk from the gland. It becomes possible due
to

(i) Suckling action by the baby,

(ii) Contraction of myoepithelial cells by oxytocin initiated by suckling reflex,
Fig. 11.21
Suckling reflex

(iii) Continuous production of milk creates a positive pressure which pushes the
milk out. It is also helped by increased prolactin secretion due to suckling by the
baby.

Suckling Reflex
It is a neuroendocrine reflex, i.e., one limb of the reflex arc

is formed by neural and the other by endocrine communication. Due to suckling

by the baby, the nerve endings in the nipple are stimulated. Nerve impulse then
travels via the afferent nerves and ultimately reach the hypothalamus. The
hypothalamus; inturn stimulates posterior pituitary. This increases the secretion
of oxytocin. Oxytocin then reaches the mammary gland via blood. It then causes
contraction of the myoepithelial cells and ejection of milk (also called milk
ejection reflex). The same reflex increases the prolactin secretion also. Prolactin
also leads to inhibition of ovulation in lactating mother.
Suckling
Stimulates anterior pituitary gland to secrete
Stimulates posterior pituitary gland to secrete
Prolactin Oxytocin
Stimulates breast alveoli to Stimulates breast alveoli to
Secrete milk Eject milk into ducts
Keeps the breast ready for next lactation Myoepithetial cells contract maintains milk flow
Infant receives milk
Fig. 11.22 Mechanism of lactation TABLE 11.6 Comparison between human
and cow’s milk (Values in gm%)
Sl.No. Major Contents Human colostrum Mature human milk Cow’s milk
1. Protein 8.5 1.0–2.0 3.5 2. Carbohydrate 3.5 6.5–8.0 4.7 3. Fat 2.5 3.0–5.0 3.5
4. Ash (Ca++, Na+, K+, PO-- -, Cl-–)4 0.37 0.18–0.25 0.75 5. Calcium
– 0.03 0.14 (Whenever milk secretion is to be stopped it is usually achieved by
using heavy dose of oestrogen) PARTURITION, LABOUR, DELIVERY OR
CHILDBIRTH
The birth of the baby is almost a miracle; only it is too common to attract our
admiration. It involves close and complex interaction between the passenger
(baby), the passage (pelvis and uterus cervical canal-vagina) and the power
(Uterine contractions).

The uterine muscle is kept in a quiescent, inactive state during pregnancy by

high progesterone. At term it is released from this inhibition by progesterone
withdrawal and several other endocrine and mechanical factors. One interesting
fact which has emerged in recent years is that the foetus itself plays an important
role in initiating its own delivery.

Factors influencing uterine contraction

Factors decreasing uterine contractility Factors increasing uterine
contractility
1. Progesterone 1. Fall in progesterone.

2. Oestrogen from foetal adrenals.

3. Prostaglandin F from placenta.
4. Oxytocin from foetal pituitary.

5. Mechanical stretching of uterus and cervix.

Oxytocin is the posterior pituitary hormone which stimulates powerful uterine

contractions. The sensitivity of the uterus to circulating oxytocin increases as the
pregnancy approaches full term. Hormonal and chemical factors are more
important in initiation of labour than neural factors. Distension of the uterus and
cervix by the growing foetus does reflexly stimulate uterine contraction.

Relaxin, a polypeptide hormone produced by the corpus luteum of pregnancy,

relaxes the pelvic joints and softens the cervix of the uterus for easy delivery.
Relaxin resemble insulin in the structure, and is perhaps produced by the uterus
as well as placenta and ovary.
+ Hypothalamus ++
Hypothalamus
Posterior pituitary
Oxytocin

Posterior pituitary Blood

Oestrogen increases oxytocin receptors on

+ uterine muscles
Oxytocin Muscles of uterus Prostagladinins are Contraction of uterusreleased from uterus
+
Uterus fallopiantube Head of the baby is pressed against cervix
Sensory impulses Stimulation of stretch receptors
Stretch
receptors Stronger and stronger uterine contractions
Cervical - dilatation - Relaxin softens cervix

Vagina Impulses from the vagina

Pushing of baby into vaginal canal

Delivery of child
Fig. 11.23 Mechanism of parturition
MENOPAUSE OR FEMALE CLIMATERIC

Menopause is the physiological or natural stoppage of menstrual cycle with

characteristic changes or atrophy of breasts, uterus, uterine tube and ovaries. Age
around 45 years.

Cause: It is due to senile changes in ovary which no longer responds to the

pituatary gonadotropins.

Secretion of oestrogen and progesterone decreases. Negative feedback

mechanism at the pituitary level decreases so the secretion of gonadotropins
increases.

Changes or signs and symptoms

1. Menstrul cycle stops permanently.
2. Gametogenesis stops.
3. Cyclical changes in uterine endometrium is not observed.
4. Ovaries become smaller, graafian follicle disappears and replaced by fibrous
tissue.
5. Atrophy of uterus and uterine tube.
6. Vasomotor changes like
(a) Flushing of skin of the face, neck and upper chest, called Hot Flushes.
(b) Marked increase in sweating especially at head and neck.
7. Effects on the breast - variable
(a) They may increase in size due to the local accumulation of fat or
(b) They may shrink due to atrophy of glandular tissue.

8. Obesity develops due to diffused deposition of fat, due to decreased caloric

expenditure.
9. Effects on sexual desire—variable, but often unaffected, because it is
independent of sex hormones and largely determined by psychological factors.

10. Osteoporosis due to decresing protein anabolism, causing a loss of protein

matrix particularly in the vertebral column.

11. Osteroporosis causes decalcification which may result in compression

fractures of bones.
12. Emotional disturbance of varying degree ranging from irritability, depression
or insanity.

Family Planning

Family planning means restricting the number of children in the family or it

means controlling the birth rate. It has got two aspects:

1. Family interest
2. National or global interest.

Family interest

In olden days a bigger family was considered as an asset. But now a days a
larger family is a liability or burden. If number of children are more, it will be
difficult to provide them with proper food, clothing, shelter and educational
opportunities.

Repeated pregnancies may spoil the health of the mother.

If number of children are more, each of them may not get adequate parental care,
love, affection, guidance and attention. Therefore there is a risk of these children
becoming antisocials. Therefore there is a compulsion in the family to restrict
the number of children.

National interest: Global interest

According to Malthu’s theory of economics physical facilities like food, shelter,
clothing etc. increases in arithmetic progressions where as population increases
in geometric progression. Because of this the gap between demand and supply of
materials will increase. This leads to conflicts, civil war and war between
countries.

Over population will lead to over exploitation of natural resources like water,
minerals, forest etc. It will produce environmental degradation and ecological
imbalance. It will result in a serious situation known as population explosion.
This is very harmful for mankind. Therefore the number of children in the family
and population of the world should be controlled.

Methods of Family Planning

Natural methods

Here no instrument, drugs or devices are used, the common natural methods are
1. Abstaining from sex or coitus.
2. Withdrawal method/coitus interruptus.
3. Safe period or calender method/Rhythm method.

1. Abstaining from sex

Avoid sexual intercourse or practice celibacy.
Mechanism of action
No chance of fertilisation, no chance of pregnancy and
childbirth.
Merits
No instruments, drugs or devices are needed. Therefore no side effects due to
chemicals and materials.
It’s a cheap method.
Protection against STD and AIDS.
Demerits
Its is easy to preach but difficult to practice. Theoretically a good method but
practically difficult to practice.
It leads to sexual starvation or deprivation. This leads to psychological and
sociological disturbances.
2. Withdrawal method
In this method, sexual intercourse is permitted. Male
sex organ or penis is withdrawn from vagina just before
ejaculation. Semen is not deposited in the vagina, no chance

of fertilisation because sperms are not available. No pregnancy, no childbirth.

Merits
No instruments, drugs or materials are needed. No side effects due to chemicals
or materials. It’s a cheap method.
There is no total sexual starvation.
Sexual pleasure is enjoyed.

Demerits
It is difficult to practice.
There is a risk of fertilisation and pregnancy. It is not a very reliable method.
Fear of pregnancy will decrease sexual pleasure. No protection against STD and
AIDS.

Safe period
During menstrual cycle of about 28 days, ovulation takes place around 14th day
of menstrual cycle. The ovum released is physiologically alive for about 2 days.
The sperms deposited in the vagina will be alive for about 2 days. Therefore if
sexual intercourse takes place, during a period around the day of ovulation there
is a high risk of fertilisation and pregnancy. Avoid coitus during this fertile
period.

Safe period is a period during the menstrual cycle during which ovum may not
be available for fertilisation. Sexual intercourse is permitted during this period,
the chance of fertilisation is negligible.

In a menstrual cycle of 28 days, upto first 10th day of menstrual cycle and 17th
day onwards is safe period. The unfertile period (safe period) during pre
ovulatory phase is calculated by subtracting 18 from duration of shortest
menstrual cycle.

The unfertile period during post ovulatory phase is obtained by subtracting 11

from longest menstrual cycle.

Merits
1. No instruments, drugs or devices are needed.
2. No side effects due to chemicals or materials.
3. Not a expensive method.
4. No total sexual starvation.
5. For an educated group its a fairly reliable method if practised carefully.
Demerits
1. It is not 100 % reliable.
2. There is a risk of fertilisation and pregnancy, even

if sexual intercourse takes place during the so called safe period.

3. The duration of menstrual cycle may fluctuate.
4. It is difficult to practice, because sexual behaviour has got a strong emotional
component.
5. It is difficult to follow a strict and rigid sexual behavioural pattern.
6. There is no protection against AIDS and STD. Barrier methods
In this method the entry of sperms to the site of fertilisation is prevented. There
are two types of barriers.
1. used by males. 2. used by females. The barriers used by males are popularly
known as condoms. Condoms are put on the penis during sexual intercourse. It
prevents the deposition of semen in the vagina. No fertilisation, no pregnancy, no
childbirth.
Barriers used by females are known as diaphragm. It’s a device placed inside the
vagina before sexual intercourse. Diaphragm prevents the entry of sperms to the
site of fertilisation, so no fertilisation, no pregnancy, no childbirth. Merits
1. It is an easy method to practice.
2. It is a fairly reliable method.
3. The materials are easily available.
4. It is a cheap method.
5. Gives protection against STD and AIDS. Demerits
1. Psychological dissatisfaction.
2. There is a minor risk of fertilisation and pregnancy.

3. It is embarassing to buy, carry and store these materials.

Chemical methods

This includes use of spermicidal chemicals. These chemicals are used in the
form of creams, jellies and foams. These materials are used before and
immediately after sexual intercourse. Vagina is irrigated with spermicidal agents.
This chemicals kill the sperms. So sperms are not available for fertilisation, no
pregnancy, no childbirth.

Merit
1. Easy to practice.
Demerits
1. Not a reliable method.
2. There is a risk of fertilisation and pregnancy. 3. Fear of pregnancy decreases
sexual pleasure. 4. May cause irritation.
Hormonal methods
Oral contraceptive pills or oral pills.
It involves oral intake of tablets containing female sex
steroids.
Types of pills
1. Combination pills—mixture of oestrogen and progesterone.

2. Sequential pills—oestrogen pills are followed with progesterone.

3. Mini pills mild dose of progesteron throughout menstrual cycle.

4. Non hormonal pills—centchroman. “SAHELI”.
5. Morning after pill—heavy dose of pills after unprotected coitus.
Tubectomy Vaginal cap Intra uterine devices
Oral contraceptive pills Condoms Vasectomy
Fig. 11.24
Methods of family planning Mechanism Merits

The oral intake of hormones will increase the blood concentration of steroid
hormone. It will exert a strong negative feedback effect at the level of
hypothalamus and anterior pituitary. This inhibits the secretion of FSH and LH.
So ovulation is inhibited. No fertilisation, no pregnancy, no childbirth.

Merits
1. Easy method to practice.

2. Cheap method—these drugs are available at a very low cost.

3. Drugs are easily available.
4. Fairly reliable method.

5. No fear of pregnancy.
6. This increases sexual pleasure.
Demerits
1. Side effects—this increases hormonal concentration in the blood. It interferes
with metabolism. It leads to deposition of fats in the body and disfiguration. It
produces wrinkles. Lead to weight gains.
2. No protection against AIDS and STD.
3. Sometimes carcinogenic.
4. Embarassment in buying and storing these materials. Intra urerine
contraceptive devices—IUCDS OR IUDS In this method certain materials are
implanted on the wall of the uterus. Examples: Copper ‘T’, ‘S’ loop etc.
Presence of these foreign materials on the wall of uterus produce uterine
contraction. This will not allow the zygote to settle down and development of
placenta and pregnancy is prevented.
1. It is semi permanent method.
2. No daily botheration of family planning. 3. Fairly dependable method.
4. No fear of pregnancy this enhances sexual happiness.
5. Easily reversible method. When the couple decide to have a child, the device
can be removed and they can have child.
Demerits
1. It requires the help of a qualified medical person. 2. Cannot be practised by
self.
3. It is an expensive method.
4. May produce side effects – like.
(a) Infection and inflammation of uterus. (b) Uterine bleeding.
(c) Severe pain and discomfort.
(d) Rejection of the material
5. No protection against AIDS and STD.
Permanent methods—Surgical methods
Surgical methods in males is known as vasectomy, in females it is known as
tubectomy.
Vasectomy: It’s a surgical procedure. The vas deferens

of both the sides are cut and ligated (tied). Because of this, sperms may not be
present in the semen. So sperms are not available for fertilisation, no pregnancy,
no childbirth.

Tubectomy: It’s a surgical procedure. The fallopian tubes are cut and ligated
bilaterally. Because of this ovum may not reach the site of fertilisation, no
fertilisation, no pregnancy, no childbirth.

Merits
1. It’s a permanent method.
2. Its fairly reliable method.
3. There is no daily botheration of family planning.
4. No fear of pregnancy. This increases sexual pleasure.
5. At least theoretically it is a reversible method. Demerits
1. It requires hospitalisation.
2. Cannot be practised by self.
3. It’s a costly procedure.
4. There is a risk of infection.
5. No protection against AIDS and STD.
MTP (Medical Termination of Pregnancy)
Abortion: MTP means termination of unwanted pregnancy or abortion. It should
be done as early as possible to avoid any risk to the health and life of the mother.
The commonly used method of abortion is D and C (Dilatation and Curettage).

SUMMARY

1. Natural methods: By controlling sexual intercourse according to

physiological principles.
(a) Abstaining from sex.
(b) Withdrawal method. Coitus interpretus. (c) Rhythm Method “Safe Period” or
Calender

method.
2. Use of some barriers to the entry of sperms into the cervix
(a) Use of rubber sheaths (condoms)over the penis

during intercourse.
(b) Use of rubber diaphragm on the cervix by

females. Often combined with spermicidal jelly or foams.

3. Use of chemical spermicidal agents before or after intercourse

(a) Creams, Jellies, foams, suppositors etc. are used

before coitus.
(b) Vaginal douches—used for irrigating vagina to
wash out sperms after coitus.
4. Intrauterine Contraceptive Device (IUCD)— Presence of a foreign body on
the uterus prevents implantation of zygote in the uterus.
5. Interruption of normal paths of sperms or ovum— Surgical methods—
Permanent methods. (a) Vasectomy in males.
(b) Tubectomy in females.
6. Oral Contraceptive Methods:
Hormonal method or pills.
(a) Combination pills.
(b) Sequential pills
(c) Mini pills.
(d) Post coital pill or “Morning After” pill
(e) Non Hormonal – Centchroman – “Saheli” 7. Progestin Implants.
8. Abortion – or Medical Termination of Pregnancy
(MTP) as a last resort.
(a) Dilatation and curettage
(b) Vacuum aspiration
(c) Administration of prostaglandin

TABLE 11.7 Determination of sex

Sperm Ovum Off spring Sex geno type X X XX Genetic female Y X XY
Genetic male

Sex Determination, Sex Differentiation Sexual development in the embryo

involved the processes 1. sex determination and
2. sex differentiation
1. Sex determination

Female oogonia contains 22 pairs of autosomes and 1 pair of sex chromosome –

44+xx.

Male spematogonia contains 22 pairs of autosomes. one pair of sex

chromosomes – 44+xy.
During the production of ovum the number reduced to haploid-23, i.e., 22
autosomes and X chromosome. During the production of sperm the number of
chromosome becomes half with 22 autosomes + X or Y sex chromosome.
Genetic sex is entirely decided by sperm.
During cell division of zygote usually one of X chromosome becomes inactive,
one remains active. The inactivated X-sex chromosome forms sex chromatin or
Barr body. It can be seen as drumstick.
F-body: It is a portion of Y-chromosome which can be stained with
flurochrome.

Sex differentiation
It takes place in stages:

1. Testicular hormone produces masculine characteristic.

2. Mere absence of testis produces development of female sex organs.
– primitive gonads develop and they are identical upto 6 weeks.
– In males, testicular differentiation starts at seventh week-seminiferous tubule
form by 8-9 week leydig cells appear.
– Y chromosome produces early testicular development which prevents
subsequent ovarian formation.

In female
Oogonia forms by around 10 week Development of ovary require XX 11-12
week –oocyte forms

Genital duct and external genitalia

8th week—primordial genital ducts. Wolffian ducts and

Mullerian ducts not yet differentiated.

If ovary develops Mullerian duct develops as fallopian tube, uterus, and vagina.

3rd-4th month external genitalia appear.

If the primitive gonad becomes a testis.
1. The Wolffian ducts become epididymis, vas deferens, seminal vesicle
Mullerian ducts degenerate. 5th month external genitalia arise.

1. Mullerian ducts
Wolffian ducts Reproductive organs

Role of testis in sex differentiation

1. It suppresses the growth of Mullerian duct by secreting Mullerian regression
factor/ Mullerian inhibiting substance.

2. It produces continued growth of Wolffian duct and related structures.

3. Essential for differentiation and growth of male external genitalia.

TABLE 11.8
Male sex differentiation
XY Chromosomes Gonads of fetus (Primordial gonads) are differentiated
Sertoli cells Leydig cells

Sl.No. Mullerian inhibiting hormone Testosterone

1. Regression of Mullerian ducts

Wolffian ducts Reproductive

organs (via Dihydrotestosterone)

Transformation for:
• Epididymis
• Ductus deferens
• Seminal vesicles Development of
• Penis
• Scrotum

TABLE 11.9
Female sex differentiation
XX Chromosomes Ovaries of fetus (Primordial ovaries) are differentiated

Sl.No. Mullerian inhibiting hormone is absent

2. Uterus, uterine tubes and

vagina develop

Testosterone is absent

Regression of Wolffian ducts

Vagina and
female external genitalia are
developed.

Abnormalities of sex development 1. Klinefelter’s syndrome or seminiferous

tubule dysgenesis.
Sex chromosome karyotype 47, XXY+44

Features
(a) Genitical female.
(b) Presence of Y chromosome produces testicular

development early in life.

(c) Sufficient secretion of testosterone at puberty. (d) Abnormal seminiferous
tubule.
(e) Small testis.
(f) Primary hypogonadism and infertility. (g) Mental retardation.

Genetic sex - Female due to XX chromosome. Gonadal sex - Male due to the
presence of testis. No spermatogenesis, so sterility.
2. 44+XXXY 48
44+XXXYY 49 Severe mental retardation. 3. YO-Intrauterine foetal death.
Turner’s Syndrome – Ovarian Dysgenesis

Karyotype pattern 44+XO 45 chromosomes

Sex chromatin test is negative.
Diminished sexual development of female type. Dwarfism
Primary amenorrhea
Phenotype—female, Geneticsex—sexless. Gonadal sex—nil no testis, no ovary.
Genitalia—Female type internal and external

genitalia due to the absence of testosterone. No breast development due to the

absence of oestrogen.
TABLE 11.10
Levels of sex
1. Genetic sex Chromosomes Male Female XY XX 2. Gonadal sex Gonads
Testis Ovary 3. Anatomical sex Physical featueres

Masculine
Broad-shoulder Narrow-Pelvis Feminine
Narrow-Shoulder Broad-Pelvis

4. Hormonal sex Sex hormones

Androgens Testosterone Female sex steroids Oestrogen and

progesterone

5. Pshychological sex Behaviour

Male like agressive behaviour

Female like shy behaviour

Super female Chromosome pattern – 44++XXX

Total number of chromosomes – 47
Phenotype = Female
Genetic sex – Female, Gonadal sex – female Sex chromatin test – 2 Barr bodies
Genitalia – Female type.
No sexual abnormality.

Hermophrodites: Two types

1. True Hermophrodites
44+XX/XY have both gonads- ovary and testis. Some cells have XX, other cells
have XY. This condition is due to no-disjunction of sex chromosomes during
early mitotic division after fertilisation.

Pseudohermophrodites—have genetic make up and gonads of one sex but

external genitalia of other. This is of two types.

1. Female pseudohermophrodites: An individual with feminine intergenitalia.

– Ovaries, oviducts etc. and masculine external

genitalia–penis, testis.
– Chromosomal sex is female.
Cause: Congenital virilizing adrenal hyperplasia. Exposure of genetic female to
androgens between 8th and 13th week of intrauterine life.

2. Male Pseudohermophrodites: Male chromosomal sex-genetic male with

defective testis.
Has female internal and/or external genitalia.

Causes
(a) embryonic testis are defective –less production of

MRF.
(b) Androgen resistance–male hormones cannot exert
their full effect on tissues.
(c) Deficiency of adrenal androgens.

PHYSIOLOGICAL NORMAL VALUES

1. RBC count, male 5 million/mm3 of blood, female 4.5 million/c.mm of blood.

New born infants – 7 million/c.mm.

2. Haemoglobin concentration adult male — 14 – 17 g/100 ml. of blood, adult

female 12-15g /100 of blood. In foetus — 23 gm/100 ml. of blood.

3. Size of RBC — Diameter 7.2 M. Surface area = 120 sq.µ, volume: 90 cubic
micron.
4. Total Leuhocyte count 4000 - 11000/mm3 of blood.

TABLE 11.11 DLC and absolute count

Percentage Absolute count/ mm3 of blood Neutrophils 40 –70 2000 – 8000
Lymphocytes 20 – 45 1500 – 4000 Monocytes 2 – 8 90 – 1100 Eosinophils 1 – 5
0 – 800 Basophils 0 – 1 0 – 200
TABLE 11.12
Arneth Count

Nucleus Stage Normal percentage Unlobed I 5

Two - lobed II 30
Three - lobed III 45
Four - lobed IV 18
Five - lobed V 2

7. Platelet count 1.5 to 4 lacs/mm3 of blood. 8. Blood volume: 5–6 litres 78 ml.
to 98 ml./kg body weight.
9. Blood pH 7.35–7.45 average 7.4.
10. ESR Westergrens method in males 1–4 mm at the end of 1 hr, in female 4–9
mm at the end of 1 hr.

11. PCV in males 45 % ± 3 in females 42 % ± 3. Haematocrit male 0.45, female

0.42.
12. Bleeding time—2 to 5 minutes by Duke’s method.
13. Clotting time—5 – 8 mts. by capillary tube method.
14. Mean Corpuscular Volume, MCV = 82 – 92 cubic micron average 90 cu.
micron.
15. Mean Corpuscular Haemoglobin, MCV = 27 – 32 picogram, average 30
picogram.
16. Mean Corpuscular Haemoglobin Concentration, MCHC = 32 to 37%.
17. Colour index 0.85 – 1.15.
18. Heart rate 70 – 80/min, stroke volume = 70 ml/ beat.
19. Cardiac output = 5 L/min. Cardiac index = 3 L/ min/m2 of body surface area.
20. Blood pressure: Systolic 110–130 mm of Hg, average 120 mm of Hg.
Diastolic 70 – 90 mm of Hg, average 80 mm of Hg.
Pulse pressure 40 mm of Hg.
Mean arterial blood pressure = 93 mm of Hg. Cardiac cycle time = 0.8 sec.
21. pH of saliva = 6.0 – 7.0,
Gastric juice = 1.0 – 2.0,
Pancreatic juice = 8.0 – 8.3,
Liver bile = 7.8 – 8.3,
Gall bladder bile = 7.1 – 7.5,
Intestinal juice = 7.5 – 8.0.
22. Respiratory rate 12–18/min. Tidal volume: 500 ml. Inspiratory reserve
volume = 3000 ml. Expiratory reserve volume = 1100 ml, Residual volume =
1200 ml. Inspiratory capacity = 3500 ml. Vital capacity = 4600 ml. Total lung
capacity = 5800 ml. Minute respiratory volume = 6000-9000 ml/min. Maximum
breathing capacity = 120 to 140 L/min. Alveolar ventilation = 4200 ml/min.
Anatomical dead space = 150 ml. Respiratory Quotient = 0.8.
23. Glomerular filtration rate. GFR = 125 ml/min. Tubular load for glucose =
125 mg/min. Transport maximum for glucose = TMG = Theoritical value = 320
– 375 mg/min. Practical value 225 mg/min. Renal threshold for glucose = 180
mg%, Urine output = 1500 ml/day. pH of urine 6.0.
24. Volume of CSF = 150 ml, pressure of CSF = 130
– 150 mm of water. pH of CSF = 7.35 – 7.4.

25. Duration of menstrual cycle 20–40 days, average 28 days.

Sperm count 60–160 million/ml, average 100 million/ml.

Biochemical normal values in adult human whole blood or serum

Ascorbic acid

Bilirubin
Calcium
Chloride
Cholesterol Creatinine Glucose

Iron
Magnecium

Phosphorus
(inorganic)

Protein (plasma) Albumin

Globulin
Sodium
Urea
Uric Acid
Potassium
Bicarbonate
0.4 to 1.5 mg % in fasting period of Serum
0.2 to 1.5 mg % serum
9 to 11 mg % serum
340 to 380 mg % serum
150 to 250 mg % serum
0.6 to 1.15 mg % serum
80 to 120 mg % blood in
random period
80 to 100 mg % Fasting
50 to 150 mg % serum
1 to 2 mg % serum
3 to 4.5 mg % serum

6 to 8 gm % plasma
4 to 5 gm % serum
2 to 3 gm % serum
300 to 350 mg % serum
15 to 40 mg % serum
3 to 7 mg % serum
14 to 22 mg % serum
55 to 72 mg % serum

Normal Concentration of hormones in blood/serum/ plasma

Growth Hormone — in children – 500 ng %
Prolactin —
LH —
FSH —

Cortisol
Aldosterone Epinephrine in adults – 300 ng % in male – 500 ng % in female –
800 ng % Male – 0.5–10 mIU/ml Female – 15–80 mIU/ml Male – 1–12 mIU/ml
Female – 9–26 mIU/ml

— 14 µg %
— 0.006 µg %
— 3µg %

Nor Epinephrine — 30µg % Dopamine Insulin

Glucagon. T3
T4
TSH 0.2 PTH
Calcitorin

Oestrogen
Progesterone
Testosterone

DHEA — 3.5 µg %
— 10–50 µU/ml

— Free 0.3 ng % Total – 0.15 µg % — Free 2 ng % Total 3.8 µg % — 5µ IU/ml

— 100 ng%
— 0–200 ng%
F— 5–30 µg %

M — 3 µg %
M — 30 ng %
F — 90 ng %
M — 0.4–08 µg % F — 0.4 µg % — 150–200 µg %
Question Bank
CHAPTERS

1. Introduction and General Physiology

2. Blood and Body Fluids
3. Cardio Vascular System
4. Respiratory System
5. Excretory System
6. Digestive System
7. Endocrine System
8. Nervous System
9. Special Senses
10. Muscle Physiology and Exercise Physiology 11. Reproductive System

QUESTION BANK

1. INTRODUCTION AND GENERAL PHYSIOLOGY

Essays:
1. Explain the structure of cell membrane.
2. Give an account of regulation of body temperature.

Write short notes on:

1. Role of skin in body temperature regulation.
2. Role of shivering in body temperature regulation.
3. Homeostasis.
4. Write briefly on Na+-K+ pump.
5. Donnan’s equilibrium.
6. Define homeostasis with feedback control mechanism.
7. Give the difference between graded potential and action potential.
8. What are the factors effecting diffusion across a membrane?
9. What is facilitated diffusion?
10. List the functions of ribosomes.
11. List the functions of nucleus.
12. List the functions of endoplasmic reticulum. 13. What are the types of
endoplasmic reticulum? 14. What is Fick’s law?
15. What is solvent drag?
16. What is exocytosis?
17. What is secondary active transport?
18. What is symport?
19. What is co-transport?
20. What is counter transport?
21. What is osmosis?
22. What is diffusion?
23. List the functions of cell membrane.
24. List the functions of mitochondria.
25. What is phagocytosis?
26. What is pinocytosis?
27. What is apoptosis?
28. What is autocoides?
29. What is osmolarity?
30. What is osmolality?
31. What is gap junction?
32. What is desmosome?
33. What are the problems of dehydration?
34. Responses of body when exposed to extremes of hot. 35. Responses of body
when exposed to extremes of cold.

2. BLOOD AND BODY FLUIDS

Essay:
1. Explain the mechanism of blood clotting. 2. Explain the ABO system of blood
grouping.

3. Define anemia. Classify and explain the causes and symptoms of individual
types of anemia.(2 + 4 + 4)
4. What is erythropoiesis? Explain the stages. How erythropoiesis is regulated?
And what are the factors essential for erythropoiesis? (1 + 4 + 3 + 2)
5. What is the normal blood volume? How can you determine it and how it is
regulated? Give brief account on edema. (2 + 3 + 2 + 3)
6. Define the term hemostasis. Mention the steps. Explain the intrinsic and
extrinsic mechanism of blood coagulation. (1 + 1 + 4 + 4)
7. Give the classification of blood groups. Describe the physiology of ABO
blood group and Rh blood group system. Enumerate the effects of mismatched
blood transfusion. (2 + 2 + 2 + 4)
8. Describe the morphology and function of platelets. Name two tests for platelet
functions. (7 + 3)
9. Define hemostasis. Mention the steps. Explain the mechanism of blood
coagulation. (2 + 1 + 7)

Write short notes on:

1. Functions of blood
3. Neutrophils
5. Eosinophils
7. Monocytes
9. Erythropoitin
2. Composition of blood 4. Basophils
6. Lymphocytes
8. Erythropoiesis - Stages 10. Regulation of
erythropoiesis
11. Factors essential for erythropoiesis 12. E.S.R. 14. Platelets 13. P.C.V.
(Haematocrit) 15. Plasma proteins 16. Rh. factor
17. ABO blood group
18. Significance of blood groups
19. Rh incompatibility
20. Erythroblastosis foetalis
21. Blood bank
22. Blood transfusion—indications
23. Incompatible blood transfusion
24. Haemophilia
25. Anticoagulants and their uses
26. Intrinsic mechanism of blood clotting
27. Extrinsic mechanism of blood clotting
28. Anemia
29. Haemoglobin types—concentration
30. R.B.C. count and its physiological variations 31. Leukemia—Leukocytosis
32. Functions of W.B.C.
33. Bleeding time and clotting time
34. Differential leukocyte count
35. Arneth count
36. Fate of R.B.C./Haemoglobin
37. M.C.V.,M.C.H. Haematocrit, MCHC
38. Pernicious anemia
39. Sickle cell anemia
40. What is hemoglobinopathy?
41. Describe the medicolegal importance of blood groups 42. Name
anticoagulants. Describe the differences in action between heparin and
dicoumarol.
43. Composition and function of lymph.
44. Mismatched blood transfusion.
45. Cross matching.
46. Intravascular blood clotting.
47. Haemolytic anemia.
48. Thrombosis and embolism.
49. How blood is not allowed to clot inside the blood vessel?
50. What precautions should be taken before blood transfusion?
51. Thrombocytopenic purpura
52. Vit.K deficiency bleeding
53. Vit.K antagonist anticoagulants.
54. Prothrombin time
55. Give the difference between active and passive immunity.
56. Principle of measurement of total body water.
57. Principle of measurement of extracellular fluid volume.
58. What are the compartments of body fluids? Give the principle of
measurement of total body water.
59. Dehydration.
60. Overhydration.
61. Enumerate the difference between extracellular fluid and intracellular fluid.
62. Hazards of stored blood.
63. What is graft rejection?
64. How plasminogen is activated?
65. Disseminated intravascular coagulation.
66. What is major thalassemia?
67. What is minor thalassemia?
68. What is pitting oedema ?
69. What is non pitting oedema?
70. Auto immune disorder.
71. Functions of reticuloendothelial system.
72. AIDS.
73. Determination of body fluids.
74. Body fluid compartments.
75. Determination of extracellular fluid volume.
76. What is oedema? Mention the types.
77. What is the principle of immunisation?
78. What is anaphylactic shock?
79. Fibrinolytic system.
80. Von Wille brand’s disease.
81. What is antologus blood transfusion?

3. CARDIO VASCULAR SYSTEM Essays Question:

1. Define cardiac cycle. Describe the events of cardiac cycle with the help of a
neat diagram. (2 + 8)
2. With the help of the left intraventricular pressure curve explain the events of a
cardiac cycle.
3. Define ECG. Explain with help of a neat diagram. Explain the different
methods by which ECG is determined, add a note on PR interval. (3 + 4 + 3)
4. Give the normal heart rate. Explain the regulation of heart rate.
5. Define cardiac output. Give the normal values. Explain how cardiac output is
regulated and explain the methods of determining cardiac output (Ficks principle
and dye dilution method). (2 + 5 + 3) 6. Define blood pressure. Give the normal
values. Explain the regulation of B.P. How it is determined in man? (2 + 1 + 7)
7. Define blood pressure. Explain the factors effecting B.P.
8. Define blood pressure. Give the normal values. Explain the hormonal
regulation of B.P. (2 + 1 + 7) 9. What is shock? Explain different causes,
symptoms, signs and treatment of shock. (2 + 2 + 2 + 2 + 2) 10. Describe the
cardiovascular and respiratory changes during exercise.
11. Draw a labelled diagram showing the innervations of heart. Describe the
regulation of heart rate. Give two conditions each for tachycardia and
bradycardia. (2 + 6 + 2) 12. Draw a labelled diagram of venous pulse tracing and
mention the cause for each wave. What is central venous pressure and how it is
measured? Name the forces involved in venous return. (3 + 4 + 3) 13. Define the
terms cardiac output, cardiac index and cardiac reserve. Describe the intrinsic
regulation of cardiac output and explain its significance. List two methods of
determination of cardiac output. (3 + 6 + 1) 14. Explain the cardiovascular
changes during exercise.

Write short notes on:

1. Properties of cardiac muscle
2. Prepotential or pacemaker potential
3. Heart sounds
4. Marey’s reflex
5. Bainbridge reflex
6. Venous return
7. Vagal tone and vagal escape
8. Radial pulse
9. Jugular venous pulse
10. Baroreceptor mechanism for the regulation of B.P. 11. Chemoreceptor
12. Junctional tissue of heart
13. Peripheral resistance
14. Renin-angiotensin mechanism
15. Coronary circulation
16. Haemorrhagic shock
17. Long term regulations of B.P.

18. What is the normal heart rate? What are the physiological variation of heart
rate?

19. What is Fick’s principle?

20. Intrinsic regulation of cardiac output.
21. Autonomic control of heart rate
22. Hormonal regulation of B.P.
23. Pulmonary circulation
24. Valves of the heart
25. What is peripheral resistance ? How does it influence blood pressure ?

26. What is the normal blood volume ? Mention the methods for determining the
blood volume. Explain any one method.

27. What is circulation time? Give its normal values and describe the factors
which are influencing it.
28. Discuss the cardiac and vascular adjustment that occur when there is a
moderate degree of haemorrhage.
29. Explain cardiovascular changes during exercise.
30. Define Frank - Starling’s law.
31. Mention the properties of cardiac muscle. Explain any one.
32. Explain the effect of musclar exercise on B.P.
33. Compare first and second heart sound.
34. Write a note on Sino - aortic baroreceptors.
35. Peculiarities of coronary circulation.
36. Einthovan’s triangle.
37. Define Marey’s law
38. Factors effecting peripheral resistance.
39. Origin and spread of cardiac impulses.
40. What is the pacemaker of the heart?
41. What you mean by ectopic pacemaker?
42. Define Einthovan’s law
43. What is standard lead I?
44. Cerebral circulation,peculiarity
45. Pulmonary circulation
46. Triple response
47. What is lymphatic oedema?
48. Give an account of formation and functions of lymph.
49. Lymph
50. Lymph nodes
51. Composition of lymph.
52. Lymphatic oedema.
53. Circulation of lymph.
54. List the major location of Lymph nodes.
55. What is central venous pressure?
56. Starling’s forces.
57. What is hyperemia?
58. What is the effect of gravity on circulatory system? 59. What is positive G?
60. What is negative G?
61. What is Stokes- Adam’s Syndrome?
62. What is murmur? Mention the types.

4. RESPIRATORY SYSTEM

Essays:
1. Give an account of transport of Oxygen in the blood. 2. Give an account of
transport of CO2 in the blood. 3. Give an account of nervous regulation of
respiration. 4. Give an account of chemical regulation of respiration. 5. Explain a
normal spirogram.
6. Explain the mechanism of respiration.

7. Name the respiratory muscles. Explain their role in breathing.

8. Name the different respiratory centers. Explain the nervous regulation of
respiration and add a note on Hearing Breuer’s Reflex. (2 + 5 + 3)
9. Describe cardiorespiratory changes during muscular exercise.
10. What is hypoxia? Describe different types of hypoxia and add a note on
effects of hypoxia on the body. (2 + 5 + 3) 11. Describe the mechanism of
inspiration. Define lung compliance and give its normal value. Mention two
conditions in which lung compliance is reduced. (6 + 2 + 2)

Short Notes:
1. Oxygen Hb dissociation curve
2. Bohr’s effect.
3. Hyalilne membrane disease.
4. Intrapleural pressure.
5. Surfactant
6. Hypoxia.
7. Cyanosis
8. Dyspnea.
9. Asphyxia.
10. Dysbarism or caisson’s disease.
11. Vital capacity.
12. Residual volume and its significance.
13. Timed vital capacity.
14. Spirogram.
15. Respiratory centres.
16. Periodic breathing.
17. Hearing Breur reflex.
18. Dead space.
19. Artificial respiration.
20. Causes and effect of-asphyxia.
21. Role of chemoreceptors in regulation of respiration. 22. Pneumotaxic centre
23. Compare the composition of inspired air, alveolar air, and expired air.
24. Factors effecting oxygen Hb disociation curve. 25. Respiratory muscles,
26. Respiratory movements.
27. Explain the functions of upper respiratory tract. 28. Functional residual
capacity.
29. Biot’s respiration.

30. Name the different types of hypoxia, explain the effects of hypoxia on
respiration.

31. Lung volumes.

32. Lung capacities.
33. Manual methods of artificial respiration.
Write Very Briefly:
1. Define maximum ventilatory volume.
2. What is dysponic index?
3. What is dysponic point? .
4. Define expiatory reserve volume.
5. What is respiratory distress syndrome?
6. What is chloride shift?
7. Define tidal volume.
8. What is Haldane effect?
9. What is Bohr’s effect?
10. What is alveolar ventilation?
11. What is minute respiratory volume?
12. What is forced expiratory volume?
13. What is stagnant hypoxia?
14. What is respiratory quotient?
15. What is the normal respiratory rate?
16. What is inspiratory capacity?
17. What is inspiratory reserve volume?
18. What is lung compliance?
19. What is thoracic compliance?
20. Ventilation purfusion ratio.
21. Cheyne—Stokes breathing.
22. Bucket—handle movement.
23. List the non-respiratory functions off respiratory system.

5. EXCRETORY SYSTEM
Essays:

1. What is glomerular filtration rate? Give the normal value. How is it

calculated?
What are the factors influencing G.F.R?

(2 + 1 + 1 + 6)
2. Describe the mechanism of urine formation.
3. What is effective filtration pressure? Give its normal value. State how this
value is obtained. (2 + 1 + 7)
4. Give brief account of micturition reflex in man.
5. Describe the functions of renal tubule.
6. Describe the nerve supply to the urinary bladder. What role do they play in
micturition?
7. Describe the counter current mechanism of urine concentration.
8. Describe the volume, reaction, specific gravity and composition of normal
urine.
9. Describe the role of kidney in pH regulation. 10. Describe the role of kidney
in homeostasis. 11. Describe the role of kidney in regulation of B.P. 12. What is
normal value of renal blood flow? How is it calculated?

13. What are the hormones acting on the kidney? Explain their functions.

14. Define renal threshold. Give normal threshold value for glucose. Describe
the reabsorption of glucose in the renal tubule. Add a note on polyuria in
diabetes mellitus and diabetes insipidus. (1 + 1 + 4 + 4)

15. What is the normal body water content? How it is regulated?

Write short notes on:

1. Enumerate causes for polyurea.
2. Define tubular load for glucose with normal value. 3. Nephron
4. Give normal values of TMG and renal threshold for glucose.
5. Symport
6. Juxtaglomerular apparatus
7. Renin-angiotensin mechanism
8. Osmotic diuresis and water diuresis
9. Renal plasma clearance
10. Cystometrogram
11. Compare facultative and obligatory reabsorption of water
12. Glucose reabsorption
13. Sodium reabsorption.
14. Compare superficial and jutxramedullary nephrons 15. Functions of kidney
16. Non-excretory functions of kidney
17. Renal circulation
18. Role of kidney in regulation of water balance 19. Renal function tests
20. Plasma clearance.
21. Automatic bladder
22. Atonic bladder
23. Renal threshold for glucose.
24. Innervation of urinary bladder
25. Functions of skin.
26. Functions of skin in body temperature regulation 27. Functions of sweat.
28. What is vasa recta? Mention its function. 29. Functions of PCT.
30. Name the renal function tests.
31. Functions of loop of henle.
32. Functions of DCT.
33. Renal function tests based on urine analysis. 34. Renal function tests based in
blood analysis. 35. Urea clearance test
36. Inulin clearance test.
37. Secondary active transport mechanism
38. Define renal threshold for glucose and give its normal value.
39. What is nephrotic syndrome?
40. What is artificial Kidney?
41. What is the principle of artificial kidney?
42. What is renal failure?
43. What is kidney transplant?

44. Name the hormons acting on the kidney. Mention their actions.

45. What are the endocrine functions of kidney?

46. How osmolality of body fluid is regulated?
47. Functions of sebaceous gland.
48. Functions of skin.
49. Role of skin in body temperature regulation.
50. Sweat-composition and functions.
51. Sensory functions of skin.
52. Storage function of skin
53. What is Laplace’law?

6. DIGESTIVE SYSTEM
Essays:

1. Give an account of composition and function of saliva and control of its

secretion. (3 + 3 + 4)
2. Give an account of composition, functions of gastric juice and regulation of
gastric juice formation. (3 + 3 + 4)
3. Explain composition and functions of bile. Add a note on regulation of bile
emptying. (3 + 3 + 4)
4. Give an account of composition, functions of pancreatic juice. Explain the
regulation secretion of pancreatic juice. (3 + 3 + 4)
5. Give an account of composition and functions of intestinal juice.
6. Name the gastrointestinal hormones and describe the functions of each.
7. Give an account of digestion and absorption of carbohydrates.
8. Give an account of digestion and absorption of proteins.
9. Give an account of digestion and absorption of fats and lipids.
10. Name the gastrointestinal hormones. Explain their functions.
11. Give an account of digestion and absorption of (a) Carbohydrates, (b)
Proteins, (c) Fats. (3 + 3 + 4)

Short Notes:
1. Deglutition (Swallowing)
2. Pharyngeal stage of deglutition
3. Deglutition apneoa
4. Gastric emptying time (GET) - Mechanisum of emptying of stomach
5. Movements of stomach
6. Functions of stomach
7. Functions of liver
8. Functions of bile
9. Formation and fate of bile pigments
10. Cholegogue action
11. Endopeptidase and expopeptidase
12. Trypsin
13. Cholecystokinin (pancreozymin)
14. Secretin and gastrin
15. Movements of small intestine
16. Peristalsis
17. Villikinin
18. Functions of large intestine
19. Defaecation
20. Vomiting reflex, outline the movements involved in vomiting
21. Absorption of fat
22. Name the phases of gastic juice secretion. Explain the first phase with
experimental support. 23. Cholecystography.
24. Stetorrhea.
25. Functions of gall bladder.
26. Enterohepatic circulation.
27. Draw the cross-section of alimentary canal. 28. Role of fibre in diet.
29. Functions of mucus.
30. Proteolytic enzymes of GIT.
31. Digestion of carbohydrates.
32. Digestion of fat.
33. Digestion of protiens.
34. Choleretic action
35. Gastric emptying
36. Functions of saliva
37. Functions of small intestine
38. Pavlov’s Pouch
39. Sham feeding.
40. What is achalasia?
41. Malabsorption syndrome.
42. What is achalasia cardia?
43. Factors inhibiting salivary secretion.
44. Compare liver bile and gall bladder bile. 45. Zollinger-Ellison syndrome
46. Pancreatitis
47. Physiological basis of management of peptic ulcer 48. What is inflammatory
bowel syndrome?
49. What is gastro oesophageal reflux disease? 50. Hirschprung’s disease.
51. What is appendicitis?
52. What is pre hepatic jaundice?
53. What is obstructive jaundice?
54. What is irritable bowel syndrome?
55. What is constipation?
56. What is dumping syndrome?
57. Mechanism of secretion of hydrochloric acid. 58. Gastritis.

7. ENDOCRINE SYSTEM
Essays:

1. Enumerate the hormones secreted from pituitary gland. Explain the functions
and regulation of secretion of growth hormone. Add a note on acromegaly. (2 +
5 + 3)

2. Enumerate the hormones secreted from thyroid gland. How the secretion of
the thyroid gland is controlled? What are the functions of thyroxine? (2 + 4 + 4)

3. What are the hormones secreted from adrenal gland? Explain the functions
and regulation of secretion of cortisol. Add a note on endocrine disorders related
to cortisol. (2 + 5 + 3)
4. Explain the role of pancreatic hormones in blood glucose regulation.
5. Explain the functions of posterior pituitory gland.
6. Explain the hormonal regulation of blood calcium.
7. Describe the biosynthesis and functions of catecholamines.
8. Explain hormonal regulation of blood glucose level.
9. Enumerate the hormones of hypophysis. Explain the functions of
gonadotropic hormones.
10. Enumerate the hormones of pituitary gland. Explain the functions of
hormones of posterior pituitary. (3 + 7) 11. What are the tropic hormones of
anterior pituitary? Explain their functions.
12. Describe the steps of biosynthesis of thyroid hormones. Explain the
functions of thyroxine. (6 + 4) 13. List the hyperglycemic and hypoglycenic
hormones. Explain their role in the regulation of blood glucose level. (2 + 8) 14.
What is the normal blood glucose level? Explain the hormonal regulation of
blood glucose. (2 + 8) 15. What is the normal blood calcium level? Explain the
hormonal regulation of blood calcium. (2 + 8) 16. Name six local hormones.
Explain the site of secretion, actions of any two. (2 + 4 + 4) 17. Describe the
physiological role of insulin in the body. How is its secretion regulated? Add a
note on diabetes mellitus. (4 + 3 + 3) 18. Describe the synthesis, function and
regulation of thyroxin. (3 + 4 +3) 19. Give an account of hormones affecting
human growth. 20. Describe the chemistry, functions and regulation of secretion
of insulin. Discribe the patho physiology of diabetes mellitus. (1 + 3 + 2 + 4)

Write Short Notes:

1. Insulin
2. Diabetes mellitus
3. A.D.H.
4. Acromegaly
5. Dwarfism
6. Gigantism
7. Addisson’s disease
8. Cretinism
9. Myxoedema
10. Goitre
11. Cushing syndrome
12. Growth hormone
13. Gonadotropins
14. Islets of Langerhans of pancreas
15. Regulation of secretion of growth hormone. 16. Regulation of secretion of
insulin.
17. Regulation of secretion of thyroid hormone. 18. Regulation of secretion of
cortisol.
19. Regulation of secretion of aldosterone.
20. Regulation of secretion of A. D. H.
21. Regulation of secretion of calcitonin.
22. Regulation of secretion of parathormone. 23. Regulation of secretion of
gonadotropins. 24. Regulation of secretion of prolactin.
25. Gastrointestinal hormones.
26. Functions of growth hormone.
27. Functions of thyroid hormones.
28. Functions of parathormone.
29. Functions of thyrocalcitonin.
30. Functions of cortisol.
31. Thyroid function tests.
32. Compare cretinism and pituitary dwarfism. 33. First messenger and second
messenger.
34. Cyclic AMP.

35. What is negative feedback mechanism for hormone secretion regulation?

36. Enumerate the hormones acting on bones. Explain the functions of any one.
37. Functions of aldosterone.
38. Oxytocin.
39. Hormones of adrenal medulla and their functions.
40. Prolactin.
41. A.C.T.H.
42. T.S.H.
43. Hypothalamo Hypophysial Thyroid Axis.
44. Hypothalamic releasing factors.
45. Hyperthroidism.
46. Androgens
47. Formation of thyroxine.
48. F.S.H.(Follicular Stimulating Hormone).
49. Leutinizing hormone (L.H.).
50. Hormones of ovary.
51. Hormones of testis
52. Hormones of placenta.
53. Diabetes insipidus.
54. Mechanism of action of a hormone.
55. Mechanism of action of steroid hormones.
56. Tetany.
57. Conn’s syndrome.
58. General properties of hormones
59. Regulation of secretion of oxytocin.
60. Compare adrenaline and nor-adrenaline
61. Compare diabetis mellitus and diabetis insipidus.
62. Negetive feedback mechanism
63. Positive feedback mechanism for regulation of secretion of hormone

64. Name local hormones. Explain the action of any one.

65. Compare the actions of adrenaline and nor-adrenaline on cardiovascular
system
66. Actions of thyroxine on CVS and CNS
67. Compare type1 and type 2 Diabetes mellitus.
68. Cushing’s disease
69. Insulin receptor.

8. NERVOUS SYSTEM

Essay:
1. Give an account of pathway for fine touch. 2. Give an account of pathway for
pain.

3. Name the ascending tracts. Explain the lateral spinothalamic tract.

4. Give an account of origin, course, termination and function of pyramidal tract.
(2 + 2 + 2 + 4)
5. Name the extrapyramidal tracts. Explain their functions.

6. Give an account of classification, function and properties of reflex action. (2 +

3 + 5)
7. Give an account of definition, classification with examples and properties of
receptors. (2 + 3 + 5)
8. Give an account of anatomical organisation and functions of sympathetic
nervous system. (3 + 7)
9. Give an account of anatomical organisation and functions of parasympathetic
nervous system. (3 + 7) 10. Give an account of functions hypothalamus. 11. Give
an account of secretion, circulation, composition and functions of C.S.F. Add a
note on lumbar puncture. (2 + 2 + 4 + 2) 12. What are the different lobes of
cerebral cortex? Explain their functions.
13. Give an acconut of organisation and functions of autonomic nervous system.
14. Name the sensory tracts of dorsal column. Explain any one.
15. Name the sensory tract carrying pain sensation. Explain it.

16. Describe the structure, connections and functions of basal ganglia. (3 + 3 +

4)
17. Describe the structure, connections and functions of cerebellum. (3 + 3 + 4)
18. Describe the structure, connections and functions of thalamus. (3 + 3 + 4) 19.
Describe the structure, connections and functions of hypothalamus. (3 + 3 + 4)
20. Name the different nuclei of basal ganglia. Explain the functions and
disorders of basal ganglia. (2 + 4 + 4) 21. Explain the pathway for crude touch.
22. Explain the pathway for pressure.
23. Describe the functions of different lobes of cerebral cortex.
24. Explain origin, course, termination and function of cortico-spinal tract with
neat labelled diagram. (2 + 2 + 2 + 2 + 2) 25. Define synapse. Write the steps of
synaptic transmission. Write difference between action potential and EPSP.
26. Name the functional divisions of the cerebellum. Describe the structure,
connections and functions of cerebellum. Mention two signs of cerebellar
lesions. (2 + 6 + 2) 27. Describe the neurological changes that are seen four
weeks after complete transection of the spinal cord at L-1 level.
28. What are the components of a monosynaptic reflex? Explain the role of
muscle spindle in the regulation of muscle length.
29. Define and classify pain. Explain the pathway for pain. Add a note on central
pain analgesic system.

Short Notes :
1. Sympathetic nervous system.
2. Parietal lobe of cerebral cortex.
3. Motor cortex.
4. Sensory cortex.
5. Dominant hemisphere.
6. Neuron—structure
7. Reflex action.
8. Parkinsonism.
9. C.S.F.—composition and functions.
10. Functions of medulla oblongata.
11. Parasympathetic nervous system.
12. Frontal lobe of cerebral cortex.
13. Properties of synapse.
14. Neurotransmitters.
15. Receptors. Definition and classification.
16. Reticular activating system.
17. Functions of thalamus.
18. Functions of cerebellum.
19. Endocrine function of hypothalamus.
20. Conditioned reflex.
21. Pathway for fine touch.
22. Spinothalamic tract.
23. Pyramidal tracts.
24. Extrapyramidal tracts.
25. Pathway for crude touch.
26. Properties of reflex action.
27. Roll of hypothalamus in body temperature regulation. 28. Role of
hypothalamus in water balance.
29. Upper motor neuron lesions.
30. Lesions of lower motor neuron (LMN)
31. Basal ganglia. Functions.
32. Referred pain.
33. Pain pathway
34. Lumbar puncture.
35. Compare conduction along myelinated and unmyelinated fibre.
36. With a labelled diagram illustrate major types of synaptic junctions.
37. Describe the changes produced in a neuron in Wallerian degeneration.
38. Visceral pain.
39. Functions of pons.
40. Neuromuscular junctions.
41. Tract of Goll.
42. Tract of Burdach.
43. What is Chorea?
44. Synapse—structure.
45. Plantar reflex.
46. Broca’s area.
47. Hemisection of spinal cord.
48. Brown—Sequard—Syndrome.
49. Sensory homonculus
50. Motor homonculus
51. Blood Brain Barrier
52. What is aphasia? Mention the types.
53. Functions of reticular formation
54. Functions of frontal lobe of cerebral cortex. 55. Functions of temporal lobe
of cerebral cortex.
56. Functions of limbic system.
57. Sensory homonculus
58. Motor homonculus
59. Significance of Electro Encephalogram
60. Mention the types of waves of EEG and their frequency.
61. Clasifficatin of neuron
62. Classification of nerve fibre
63. Properties of sensory receptor
64. Properties of reflex action.
65. Functions of parasympathetic nervous system
66. Compare the actions of sympathetic and parasympathetic nervous system.
67. Saltatory conduction.
68. Synaptic inhibition
69. Inhibitory post synaptic potential
70. Excitatory post synaptic potential
71. Compare somatic pain with visceral pain
72. Phantom pain
73. Effects of cerebellar lesion
74. Draw a reflex arc
75. Disorders of basal ganglia
76. What is Wilson’s disease?
77. Name the structures included in the limbic system
78. What is hemiplegia, paraplegia, monoplegia, and quadriplegia?
79. Define learning and memory
80. Classify memory
81. Pathway of pain from face
82. What is adaptation of a receptor?
83. Define Weber—Fechner’s law
84. What is spatial summation?
85. Gaser—Erlanger classification of nerve fibre.
86. Summation at synapse.
87. Compare upper motor neuron lesion with lower motor neuron lesion.
88. List the physiological effects of parasympathetic nervous system on GIT.
89. Compare the actions of sympathetic and parasympathetic nervous system on
GIT.
90. What is spinal shock?
91. What is power law?
92. Cerebellar lesion.
93. Afferent connecitons of basal ganglia.
94. Afferent connections of cerebellum.
95. What is global aphasia?
96. Structures of limbic system
97. Thalamic syndrome
98. What is occlusion
99. What is subliminal fringe?
100. Disorders related to limbic system
101. Papez circuit
102. Frontal lobe syndrome
103. Factors effecting synaptic transmission
104. Synaptic blockers
105. Co-transmitters
106. Structure of muscle spindle
107. Innervation of muscle spindle.
108. Stretch reflex.
109. EEG changes during sleep
110. What is epilepsy? Mention the types.
111. What is cerebral palcy?
112. Kluver-Bucy syndrome
113. Alziemer’s disease
114. What is amnesia? Mention the types.

9. SPECIAL SENSES
Essay:

1. Give an account of visual pathway. Add a note on the effects of lesion of

visual pathway at different sites.

2. Explain the auditory pathway.

3. Explain the olfactory pathway.
4. Explain the taste pathway.
5. Explain the structure of retina and explain its functions.

6. Describe the process of accommodation in the eye and its neural pathway.
How is it affected by age?

(7 + 3) 7. Describe the mechanism of colour vision. How do you classify and test
colour blindness? (5 + 2 + 3)

Write Short Notes on:

1. Errors of refraction of the eye.
2. Colour vision.
3. Colour blindness.
4. Functions of retina.
5. Pupillary reflexes.
6. Accommodation reflex
7. Structure of retina.
8. Presbyopia.
9. Deafness.
10. Cochlea.
11. Contents and functions of middle ear.
12. Primary tastes.
13. Taste buds.
14. Olfactory epithilia.
15. Primary olfaction.
16. Structure of eye ball.
17. Compare rods and cones.
18. Organ of Corti.
19. Tests for colour blindness.
20. Mechanism of hearing.
21. Tests for deafness.
22. Myopia.
23. Hypermetropia.
24. Cataract.
25. Glaucoma.
26. Genetics of colour blindness.
27. Tympanic reflex
28. Conduction deafness
29. What is blind spot? Why is it called so?
30. What are the changes taking place during accomodation reflex?
31. Tuning fork tests for deafiness.
32. Argyl—Robertson pupil.
33. Pathway for pupillary light reflex
34. Rinne’s test
35. Weber’s test
36. Audiometry
37. Swabach’s test
38. Theories of colour vision.
39. What is protanopia?
40. What is deuteranopia?
41. What is protonomaly?
42. What is deuteronomaly?
43. What is perimetry?
44. What is field of vision?
45. How to test acuity of vision?
46. Functions of aqueous humour
47. Functions of vitreous body
48. Formation and circulation of aqueous humour 49. How to test field of
vision?
50. What is scotoma?

10. MUSCLE PHYSIOLOGY AND EXERCISE PHYSIOLOGY

Essay:
1. Explain the structure and transmission of impulses across neuromuscular
junction. Add a note on NMJ blockers. (3 + 4 + 3) 2. Explain the excitation-
contraction coupling in a skeleton muscle.
3. Explain the mechanism of contraction in a smooth muscle.

Short Notes:

1. Responses of the body when exposed to extremes of cold.

2. Responses of the body when exposed to extremes of hot.
3. Describe briefly how the resting membrane potential is maintained.
4. What is normal RMP in a human nerve fibre? Discuss its ionic basis.
5. Events in neuromuscular transmission.
6. Strength duration curve.
7. Describe the changes produced in a neuron in Wallerian degeneration.
8. Excitation contraction coupling.
9. Myasthenia gravis
10. Rigor mortis
11. Compare three different types of muscles. 12. Molecular basis of muscle
contraction.
13. Chemical changes taking place during muscle contraction.
14. Compare cardiac and skeletal muscles.
15. Compare skeletal and smooth muscles.
16. Neuromuscular blockers—and their clinical significance
17. Medicolegal significance of rigor mortis. 18. Electromyogram. Factors
affecting force of muscle contraction.
19. Muscular dystrophy.
20. Compare fast muscle and slow muscle
21. Structure of sarcomere
22. Contractile proteins of muscle
23. Neuromuscular blockers.
24. Excitation contraction coupling.
25. Health benefits of exercise.
26. How to grade the exercise?
27. Isotonic and isometric exercise.
28. Respiratory changes during exercise.
29. Cardiomuscular changes during exercise
30. Endocrine changes during exercise
31. Nervous changes during exercise
32. Metabolic changes during exercise
33. Effect of training on muscle performance. 34. What are the types of smooth
muscle?
35. What is multi unit smooth muscle?
36. What is single unit smooth muscle?

11. REPRODUCTIVE SYSTEM Essay:

1. Give an account of various changes taking place during menstrual cycle.

2. Explain the process of ovulation and explain the role of hormones.
3. What are the gonadotrophic hormones? Explain their functions.
4. Describe the spermatogenesis. What are the factors influencing
spermatogenesis? (7 + 3)
5. What is puberty? Briefly explain the puberty changes in male and female. (2 +
4 + 4)
6. Descibe uterine changes taking place during menstrual cycle and explain their
hormonal basis. (7 + 3)
7. Describe secretion and functions of ovarian hormones and regulation of their
secretion. (6 + 4)
8. What is testosterone? Describe its functions and regulation. (2 + 4 + 3)
Write short notes on:
1. Testosterone—androgen.
2. Oestrogen.
3. Progesteron.
4. Ovulation.
5. Functions of ovary.
6. Placenta.
7. Placental hormones.
8. Pregnancy tests.
9. Corpus luteum.
10. Physiological changes in female during pregnancy 11. Hormones controlling
lactation.
12. Functions of testis.
13. Foetal circulation.
14. Parturition.
15. Menarche and menopause.
16. Milk ejection reflex.
17. “Safe Period”.
18. Oral pills—Describe the mechanism of action of contraceptive pills.
19. Temporary family planning methods.
20. Permanent family planing methods.
21. IUCDs or IUDs.
22. Oogenesis.
23. Semen.
24. Relaxin.
25. Human chorionic gonadotropin.
26. In what way mother’s milk is superior?
27. Hormonal control of menstruation
28. Explain briefly the contraceptive techniques available to the male.
29. Tests for ovulation.
30. Ovarian hormones.
31. Physiological changes in male during puberty. 32. Family planning methods
used by female. 33. Sperm count.
34. Sertoli cells.
35. Hormonal influence of parturition.
36. Principle of pregnancy test.
37. Follicular phase of ovarian cycle.
38. Luteal phase of ovarian cycle.
39. Proliferatie phase of uterine cycle.
40. Secratary phase of uterine cycle.
41. Day of ovulation.
42. Vasectomy.
43. Tubectomy.
44. LH surge.
45. Human milk.
46. Colostrum.
47. Significance of family planning
48. Population explosion
49. Cryptorchidism
50. Inhibin
51. What is infertility?
52. Causes of infertility in male.
53. Causes of infertility in female.
54. What is super female?
55. Chromosomal aberrations of sexual development. 56. What is menopause?
57. Role of testis in sex differenciation.
58. Klinefelter’s syndrome
59. Turner’s syndrome
60. What are the causes for male hypogonadism? 61. What is hermaphrodites?

Compare:
1. Diabetes Insipidus — Diabetes Mellitus
2. Rods — Cones
3. Ist Heart sound — IInd Heart sound
4. Cretinism — Dwarfism
5. Cortical nephron — Juxtamedullary nephron
6. Adrenaline — Nor-Adrenaline

7. Sysmpathetic Nervous System — Parasympathetic Nervous System

8. Conditioned Reflex — Unconditioned Reflex.

9. Obligatory Water Reabsorption — Facultative Water Reabsorption

10. Plasma — Serum.
11. Intrinsic mechanism of blood clotting — Extrinsic

mechanism of blood clotting

12. Peristalsis — Segmentation.
13. Eccrine sweat gland — Apocrine sweat gland.
14. Agglutination — Clotting.
15. Upper Motor Neuron Lesion — Lower Motor Neuron Lesion
16. Secretin — CCK— Pancreozymin.
17. Choleretic action — Cholagogue action
18. Renin — Rennin
19. Haemophilia — Thrombocytopenic purpura
20. Simple Goitre — Exophthalmic goitre
21. Bleeding Time — Clottiong time.
22. Artery — Vein
23. Local hormone — General hormone
24. Greater circulation — Lesser circulation.
25. Continuous conduction — Saltatory conduction.
26. Receptor Potential — Action Potential
27. Conduction Deafness — Nerve Deafness.
28. RBC. — WBC.
29. Non-REM Sleep — REM Sleep.
30. Left Hemisphere — Right Hemisphere.
31. Active transport–Passive transport
32. Diffesion — Osmosis
33. Hemoral immunity — Cell mediated immunity
34. B lymphocyte — T lymphocyte
35. Active immunity — Passive immunity

BIBLIOGRAPHY

1. Text Book of Medical Physiology—Hall & Guyton 11th Ed., W.B. Saunders
Company, London.
2. Review of Medical Physiology—Ganong, W.F. 22nd Edition, McGraw Hill.
INC, New York.
3. Applied Physiology—Samson –Wright 10th Oxford University Press,
London.
4. Physiological Basis of Medical Practice—Best & Tayler, 12th Ed., Williams
Wilkins, London.
5. Text Book of Anatomy & Physiology—Tortora. Harper Collins College
Publications, 1996.
6. Text Book of Anatomy & Physiology—Patton & Thibodiau. 2nd Mosby, St
Louis, 1993.
7. Concise Medical Physiology—Chaudhuri S.K. 6th Ed., New Central Book
Agency, Culcutta-2008.
8. Text Book of Physiology—Vol. 1 and Vol. 2, Chatterjee, C.C. Medical Allied
Agency, Culcutta.
9. Physiology—Sharada Subramaniam & Madhavan Kutty, 4th Ed., S.Chand &
Company, Ram Nagar, New Delhi.
10. Text Book of Physiology: Bell Emslie, Smith, Peterson, 10th Ed., English
Language Book Society, Churchill Livingstone.
11. Human Physiology—Vander, Sherman, Luciano, 6th Ed., McGraw Hill INC
New York.
12. Physiology—Berne-Levy 5th Ed., Mosby Year Book, St. Louis.
13. Essentials of Medical Physiology—Mahapatra, Current Books International
Culcutta-1998. 14. Text Book of Physiology vol 1 & vol 2 – A.K. Jain— 3rd Ed,
Avichal Publishing Company, New Delhi, 2005.
15. Essentials of Medical Physiology—Sembulingam 4th Ed., J.P.Brothers
Medical Publishers, New Delhi.
16. Fundamentals of Medical Physiology—L. Prakasham Reddy, Paras
Publishing, Hyderabad.
17. Understanding Medical Physiology—Bijilani R.L., 2nd Ed., J.P. Brothers
Medical Publishers (P) Ltd., 1997.
18. Physiology—Vijaya D. Joshi, 2nd Ed., B.I.Churchil Livingstone, New Delhi.
19. Human Physiology—A.K. Das Books and Allied Pvt. Ltd., Calcutta.
20. Text Book of Practical Physiology—Ranade, 4th Ed., Pune Vidyarthi Griha
Prakashana, Pune.
21. The Principles of Physiology—David Jenson. 22. Text Book of Physiology
—Indu Khurana, Elsevier. 23. Essential Medical Physiology—Leonard Johnson,
2nd Ed., Lippincott, Raven.
24. Medical Physiology—S.Sircar, CBS Publishers and Distributors, New Delhi.
25. Principles of Anatomy and Physiology—Sheely P.R, Stephen TD. Philip
Tats, 2nd Ed., Mosby St. Louis, Missouri.
26. Essentials of Human Physiology—Ross G., 2nd Year Book, Medical
Publishers, INC Chicago.
27. Text Book of Medical Physiology, G.K. Pal Ahuja Publishing House, New
Delhi.
28. Fundamentals of Neurophysiology, R.F. Schmidth Springer, Verlag, New
York.
29. Text book of Physiology, N.Geetha, Paras Publishing, 2009.
30. Review of Applied Physiology, Shrikant L. Patil, Suman Publications, 2009.
31. Understanding Biophysics, Shrikant L. Patil, Suman Publications, 2009.
32. Text Book of Physiology, A.P. Krishna, 6th edition, Suman Publications,
2009.
INDEX
A

‘A’ band, 389

Abnormal spermatogenesis, 414 ABO blood groupings 47
Absolute refractory perioid, 77, 278 Absorption of carbohydrates, 211
Absorption of fats, 212
Absorption of proteins, 212
Acclimatization, 24
Accommodation reflex, 367
Accouncher’s hand, 260
Achalasia cardia, 203
Achalasia, 203
Acidosis, 173
Acromegaly, 226
Actin, 388
Action potential, 15, 77, 390 Active transport, 14
Acute moiuntain sickness, 149 Addison’s disease, 242
Adenohypophysis, 222
Adrenal crisis, 242
Adrenal medulla, 243
Adrenaline, 243
Adrenarche, 412
Adrenogenital syndrome, 243 Afibrinogenemia, 43
Agglutinins, 48
Agglutinogen, 48
Aging, 265
Agranulocytes, 30, 32
Agranulocytosis, 35
AIDS, 70
Airways resistance, 135
Alarm reaction, 245
Aldosterone, 238
Aldosterone escape, 240
Alkalosis, 173
Allergy, 35
Allocortex Archicortex, 335
Alveolar air, 135
Alveolar ventilation, 133
Alzheimer’s disease, 339 Amnesia, 352
Amygdala, 341
Anaemia, 53
Anal sphincter, 207
Anaphylactic shock, 114 Anatomical dead space, 133 Angina Pectoris, 111
Angiotensin, 100
Anisocytosis, 24
Anosmia, 383
Anti diuretic hormone, 228 Antibody, 48, 49
Anticholinesterase, 393
Anticoagulants, 44
Antidepresants, 290
Antigen, 49
Antithyroid substances, 237 Apex beat, 106, 118
Aphakic eye, 371
Aphasia global, 339
Aphasia motor, 339
Aphasia sensory, 339
Aplastic anemia, 55
Apneustic centre, 142
Apoptosis, 16
Appendicitis, 209
Aqueous humour, 366
Argyll-Robertson pupil, 369 Arneth count, 31
Artificial kidney, 179
Artificial respiration, 151 Asphyxia, 148
Asthenia, 319
Asthma, 150
Astigmatism, 364, 365
Astrocyte, 282
Ataxia, 319
Athetosis, 334
Atonic bladder, 169
ATP, 394
Atrial diastole, 80
Atrial natriuretic peptide, 176 Atrial systole, 80
Audiometry, 378
Auditory pathway, 377, 378 Autacoids, 263
Autocrine, 218
Autoimmune disease, 70 Automatic bladder, 169 Autonomous bladder, 169 AV
nodal delay, 78
AV node, 79
Axon-reflex, 105

Babinski’s sign, 297 Bain-Bridge reflex, 86 Baroreceptor, 95

Barr body, 435
Barrier methods, 433 Basal ganglia, 332
Basilar membrane, 376 Basophilia, 35
Bathmotropic effect, 84 Bell-Megendie law, 292 Bends, 148
Benedict’s test, 171 Benzidine test, 171
Berger rhythm, 342 Betz cell, 337
Bicuspid valve, 74
Bile, 197
Bile pigments, 197
Biot’s breathing, 151 Bipolar leads, 90
Black out, 116
Bladder-Urinary, 166 Bleeding time, 46
Blood, 19
Blood bank, 52
Blood brain barrier, 345 Blood pressure, 93
Body fluid, 63
Bohr’s effect, 139
Bombay blood group, 48 Bradycardia, 85
Bradykinin, 263
Breathing reserve, 134
Broca’s area, 337
Brown-sequard Syndrome, 314 Buffalo hump, 243
Buffer, 171
Bulbourethral gland, 412 Bundle of His, 78

Caisson’s disease, 148

Calcitonin, 257, 259
Calcitriol, 255
Calcium metabolism, 257 Carboxyhaemoglobin, 29 Cardiac arrhythmia, 117
Cardiac cycle, 83
Cardiac failure, 115
Cardiac index, 87
Cardiac muscle, 76
Cardiac output, 87, 89
Cardiac sphincter, 203
Cardio vascular shock, 112 Carpopedal spasm, 257
Castration, 416
Cataract, 371
Catecholamines, 243
Caudate nucleus, 331
Cell junctions, 9
Cell membrane, 6
Cell signaling, 10
Cells, 6
Cellular receptors, 10
Cellulose, 213
Central chemoreceptors, 96 Central excitatory state, 296 Central venous
pressure, 106 Cerebellar peduncles, 317 Cerebellum, 317
Cerebral cortex, 335
Cerebral palsy, 340
Cerebrospinal fluid, 343
Chemoreceptor reflex, 96 Chemotaxis, 33
Cheyne-Stokes respiration, 151 Chloride shift, 140
Chokes, 148
Cholagogue, 198
Choleretic agents, 198
Chorea, 333
Christmas disease, 44
Chromatic aberration, 363 Chromatin, 437
Chromosomes, 436
Chronaxie, 279
Chronic mountain sickness, 149 Chronotropic effect, 84
Chylomicron, 213
Chyme, 205
Ciliary body, 361
Ciliary muscles, 365
Circulation, 75
Circulation time, 106
Circulatory shock, 112
Clonus, 395
Clot retraction, 39
Clotting time, 47
CNS ischaemic response, 97 Co-transmitters, 290
Coagulation, 40
Cochlea, 376, 379
Cochlear potential, 376
Colour blindness, 369
Colour index, 60
Colour weakness, 370
Complete AV block, 78
Conditioned reflex, 295
Conduction, 280
Conduction deafness, 377 Cone, 362
Conn’s syndrome, 240
Constipation, 207
Continence, 169
Contraception, 432
Contraction, 390
Convection, 325
Convergence, 307
Coole’s anemia, 57
Coombs’ test, 53
Cori’s cycle, 397
Cornea, 362
Coronary artery disease, 111 Coronary circulation 109
Corpus luteum, 423
Corticobulbar tract, 309
Corticospinal tract, 310
Corticotropin releasing factor, 239 Co-transport, 163
Counter current mechanism, 165 Cranial nerves, 356
Cretinism, 235
Crista, 379
Cross bridges, 388
Cross matching, 51
Cryptorchidism, 414
Cuneatus fasciculus, 301
Capula, 379
Cushing’s reflex, 86
Cushing’s syndrome, 242
Cyanosis, 147
Cystometrogram, 167
Cytoskeleton, 9

Dark adaptation, 371

Dead space air, 133
Deafness, 377
Decibel, 377
Decompression sickness, 148
Defecation, 206
Deglutition, 202
Dehydration, 16
Delta waves, 343
Dementia, 339, 353
Depolarisation, 390
Depth perception, 362
Dermatome, 307
Desmosome, 9
Deuteronamaly, 370
Deuteronopia, 371
Diabetes insipidus, 229
Diabetes mellitus, 248
Dialysis, 179
Diapedesis, 33
Diaphragm, 125
Diarrhea, 207
Dichromats, 371
Dicoumarol, 44
Dietary fibres, 213
Diffusion, 11
Digestion of carbohydrate, 210
Dilator pupillae muscle, 367
Disseminated intravascular coagulation, 46 Diuretics, 177
Divergence, 287
Dominant hemisphere, 338 Drinker’s method, 153 Drooling, 189
Dumping Syndrome, 214 Dwarfism, 225
Dysarthria, 319
Dysbarism, 161
Dysdiadochokinesis, 319 Dysguisia, 384
Dyslexia, 339
Dysmetria, 319
Dyspnoea, 150

Echocardiography, 117
Ectopic pacemaker, 78
Edinger-Westpal nucleus, 368
Eicosanoids, 220
Einthovan’s law, 90
Einthovan’s triangle, 90
Electrical synapse, 285
Electrocardiogram (ECG), 89
Electro-Encephalogram, 343
Embolism, 46
Emotion, 341
Emphysema, 151
Emptying of stomach, 204
End diastolic volume, 83
End systolic volume, 83
Endoplasmic reticulum, 8
Endorphin, 308
Enkepalin, 308
Eosinopenia, 35
Eosinophilia, 35
Epilepsy, 340
Equilibrium, 320
Erythroblastosis foetalis, 51
Erythrocytes, 21
Erythrocyte sedimentation rate (ESR), 59 Erythrocytosis, 58
Erythropoisis, 24, 25
Erythropoientin, 27
Essential hypertension, 99
Eustachian tube, 375
Evaporation, 325
Excitation-contraction couling, 393 Exocytosis, 14
Exophthalmus, 236
External auditory meatus, 375 External intercostal muscles, 125 Extrafusal
muscle, 319
Extrapyramidal tracts, 311
Eye muscles, 369
Golgi body, 8
Gracilis, tract of Goll, 299 Graft rejection, 70
Graves disease, 236
Grey-out, 116
Growth hormone, 222

Facilitated diffusion, 11
Facts, 212
Family planning, 432
Fasciculus Gracilis, 299
Female sex organs, 417
Fertilisation, 425
FEV 1, 132
Fibrinolytic system, 45
Fick’s principle, 88
Field of vision, 374
Filtration coefficient, 162 Filtration fraction, 162
Flush, 105
Fouchet’s test, 171
Frank-Starling law of heart, 89 Frontal lobe, 336
Functional Syncytium, 77

Galactopoiesis, 429
Gall bladder, 199
Gall stones, 199
Gap junctions, 9
Gastric juice, 191
Gastric secretion, 191
Gastrin, 192
Gastritis, 193
Gastro Esophageal Reflux disease, 210 Gastrocolic reflex, 201
Gating of pain, 307
Genotype, 48, 49
Gibbs-Donnan equilibrium, 16
Gigantism, 225
Glaucoma, 366
Glomerular capillaries, 159
Glomerular filtration rate (GFR), 161 Glomerulus, 159
Glucagon, 251
Glucocorticoids, 240
Glycosuria, 170

Habituation, 296
Haematocrit, 60
Haematuria, 170
Haemoglobin, 27
Haemoglobinopathies, 30
Haemolysis, 26
Haemophilia, 44
Haemopoiesis, 25
Haemostasis, 39
Hair cells, 379
Haldane’s effect, 141
Hay’s test, 171
Hazards of mismathced blood transfusion, 50
Heart, 73, 74
Heart rate, 84
Heart sounds, 91
Heat regulation, 324
Heat rigor, 396
Heiden-Hain’s pouch, 192
Hemianopia, 373, 375
Hemiplegia, 340
Hemodynamics, 107
Heparin, 44
Hering-Bruer reflex, 143
Hermaphrodite, 437
Hippocampus, 341
Hirsehsprung’s disease, 211
Histamine, 262
Holger-Nielson method, 152
Holmgreen’s wool test, 370
Homeostasis, 4
Homeothermic animal, 325
Human chorionic gonado tropin, 426 Hydrocephalus, 377
Hyperbaric oxygen therapy, 154
Hyperalgesia, 309
Hypercapnia, 147
Hyperemia, 109
Hypermetropia, 364
Hypogcusia, 384 Hypogonadism, 416 Hypothalamus, 324 Hypoventilation, 145
Hypoxia, 145

I band, 388
Immunity, 67
Immunisation, 69
Immunoglobulins, 67, 68
Impedance matching, 375
Implantation, 425
Incontinence, 169
Incus, 375
Infertility, 417
Inflammatory bowels disease, 209 Insulin, 247
Insulin receptor, 247
Inter cellular communictions, 10 Intra cellular communications, 10 Intra occular
pressure, 366
Inra pleural pressure, 128
Inra uterine contraceptive devices, 434 Intrafusal muscle, 319
Intrinsic factor, 191
Inulin clearance test, 177
Ionoropic effect, 84
Iris, 361
Irritable bowel syndrome, 209
Ishihara chart, 371
Isocortex, 335

Labelled line hypothesis, 285 Laci’s cells, 161

Lactation, 429
Lactogenesis, 429
Laminar flow, 119
Landsteiner’s law, 48
Laplace law, 185
Large intestine, 201
Laron Dwarf, 225
Laten period, 15
Lateral spinothalamic tract, 305 Learning, 350
Left heart failure, 115
Lenses, 364
Leucocytes, 21
Leucocytosis, 30
Leucopenia, 30
Leukaemia, 30, 36
Light adaptation, 372
Limbic system, 341
Lobes of cerebral cortex, 336 Local anesthetics, 290
Loop of Henle, 158
Lumbar puncture, 345
Lung capacities, 131
Lung compliance, 131
Lung volumes, 128
Lymph, 117
Lymphocytosis, 34
Lymphoid organs, 117
Lysosomes, 8

Jaundice, 207
Junctional tissues of heart, 78 Juxtaglomerular complex, 161 Juxtamedullary
nephrons, 158

Kernicterus, 208
Klinefelter’s syndrome, 436 Kluver-Bucy syndrome, 342 Korasakoff psychosis,
342 Korotkoff’s sound, 103 Krause’s end bulb, 283

Macula desna, 161

Major thalassaemia, 57
Mal absorption syndrome, 213 Male sex organs, 412
Malleus, 375
Marye’s reflex, 85
Margination, 33
Mastication, 201
MCH, 60
MCHC, 60
MCV, 60
Mean arterial pressure, 93
Measurement of blood volume, 61

Mechanism of regulation of blood volume, 61

Mechanism of respiration, 125
Mechanisms of coagulation 40
Medulla oblongata, 316
Megakaryocyte, 37
Melatonin, 261
Memory, 351
Menarche, 412
Meniere syndrome, 381
Menopause, 431
Menstrual cycle, 418
Menstruation, 419
Mesocortex, 335
Methaemoglobin, 29
Micro circulation, 108
Microglia, 282
Microvilli, 199
Micturition, 166
Middle ear, 375
Mineralocorticoids, 237
Minor thalassaamia, 57
Mitochondria, 7
Mitral valve, 74
Monochromats, 371
Monocytosis, 36
Motor homunculus, 311
Motor unit, 388
Mouth to mouth method, 153
Muller’s law, 284
Mullerian duct, 436
Murmur tricusphid stenosis, 93
Muscle, 387
Muscle contraction, 394
Muscle proteins, 388, 389
Muscle spindle, 319
Muscular dystrophy, 398
Myasthenia gravis, 392
Mydriasis, 367
Myeloperoxidase, 33
Myocardial infraction, 111
Myopia, 364
Myosin, 388
Mysoedema, 235

Near point, 364, 367 Negative G, 116

Neocortex, 335
Nephron, 158
Nephrotic syndrome, 180
Nernst equation, 15
Nerve deafness, 378
Nerve fibres, 279
Nerve tracts—motor, 309
Nerve tracts—sensory, 299
Neurocrine, 218
Neurohypophysis, 222
Neuroma, 282
Neuromuscular junction, 391 Neuromuscular transmission, 391 Neuron, 277
Neurotransmitters, 287, 291 Neurotrophins, 283
Neutropenia, 35
Neutrophilia, 35
Non pitting oedema, 66
Noradrenaline, 243
Nucleus raphae magnus, 308 Nystagmus, 319

Obesity, 242
Occipital lobe, 336
Occlusion, 295
Oedema, 66
Oestrogen, 422, 423
Ohm’s law, 107
Olfactory epithelium, 381 Olfactory pathway, 381
Oligodendroglia, 282
Opiod drugs, 309
Opponent—process theory, 370 Opsonisation, 33
Oral contraceptive pills, 433 Oral pills, 433
Organ of Corti, 376
Osmolality, 15
Osmolarity, 15
Osmosis, 12
Osmotic diuresis, 177
Osmotic fragility, 61
Otolith organ, 380
Ovarian cycle, 418
Over hydration, 16
Oxygen debt, 405
Oxygen dissociation curve, 138 Oxygen therapy, 154
Oxygen toxicity, 154
Oxytocin, 229

P
P wave, 90
P50, 139
Pacemaker, 78
Packed cell volume, 60
Pain, 304
Paleocortex, 335
Pancreatic juice, 195
Pancretitis, 196
Papez circuit, 341
Papilloedema, 363
Paracrine, 218
Parahaemophilia, 43
Paralysis, 340
Paraplegia, 340
Parasympathetic nervous system, 359 Parathyroid gland, 255
Parkinson’s disease, 333
Parturition, 430
Passive transport, 14
Pavlov’s pouch, 193
Paptic ulcer, 194
Periaquedectal grey, 308
Perimetry, 374
Peripheral chemoreceptors, 143 Peripheral resistance, 94
Peristaltic movements, 205
Permissive action, 241
Pernicious anemia, 56
pH of blood, 20
Phagocytosis, 14, 33
Phantom limb, 285, 307
Pheochromocytoma, 245
Phonation, 348
Phonocardiogram, 93
Phonocardiography, 93
Phototherapy, 207
Phototransduction, 364
Pineal gland, 261
Pinocytosis, 14
Pitting oedema, 66
Place theory, 377
Placenta, 426
Plantar reflex, 297
Plasma membrane, 6
Plasma proteins, 21
Plasminogen, 45
Platelets, 37
Platelets derived growth factor, 37, 38 Pneumotaxic centre, 142
Poikilotherms, 325
Poiseuille’s law, 94
Polycythemia, 58
Polydipsia, 249
Polyphagia, 249
Polyuria, 229, 249
Pons, 317
Positive G, 116
Post tetanic potentiation, 288, 351 Posterior pituitary, 227
Postural reflex, 321
Posture, 320
Power law, 285
P-P interval, 90
P-R interval, 90
Pregnancy test, 426
Presbyopia, 364
Primary hyper aldosteroidism, 240 Primary visual cortex, 373
Progesterone, 424
Projected pain, 207
Prostaglandins, 263
Protein, 211
Prothrombin time, 47
Protanomaly, 371
Pseudohermaphrodite, 437
Puberty, 411
Pulmonary capacities, 131
Pulmonary circulation, 75
Pulmonary incompetency, 93
Pulmonary volumes, 130
Pulse, arterial, 103
Pulse venous, 104
Pulsus alterans, 104
Pulsus paradoxus, 104
Pupillary light reflex, 367
Pyramidal tract, 311

Q wave, 90
QRS complex, 90
Q-T-interval, 90

Radiation, 325
Rapid eye movement (REM) sleep, 346 Receptor potential, 284
Receptors, 283
Referred pain, 306
Reflex action, 293
Reflex arc, 293
Refractive period, 77
Refractory error, 364
Refractory index, 363
Relative refractory period, 77, 278 Relaxin, 426
Renal glycosuria, 170
Renal tubules, 158
Renin, 97
Repolarization, 390
Respiration, 123
Respiratory distress syndrome, 130 Respiratory membrane, 125
Respiratory quotient, 141
Respiratory volumes—spirogram, 131 Resting membrane potential, 77 Reticular
activating system, 335 Reticular formation, 334
Reticulo endothelial system, 65
Reticulocyte, 25
Reticulocytosis, 25
Retina, 362
Retrograde amnesia, 353
Reverberation, 287, 351
Rh factor, 48
Rheobase, 279, 391
Rhodopsin, 362
Rigor mortis, 396
Rinne’s test, 378
Rod, 362
Rothera’s test, 171
R-R interval, 90
Ruffini end organ, 283

SA node, 78
Saccule, 379
Safe period, 433
Saliva, 187
Saltatory conduction, 280 Sarcomere, 388
Sarcophasmic reticulum, 389
Satiety centre, 326
Schafer’s method, 153
Schwann’s cell, 277
Scotoma, 372, 375
Scrotum, 412
SCUBA, 148
Sebacious gland, 181
Semen, 415
Semicircular canals, 379
Semilunar valves, 74
Seminal vesicles, 412
Seminiferous tubules, 412
Sensitisation, 296
Sensory homunculus, 300
Septic shock, 113
Serotonin, 262
Sertoli cells, 412, 415
Sham feeding, 192
Sheehan’s syndrome, 225
Shivering, 325
Shock-neurogenic, 113
SIADH, 229
Sickle cell anemia, 57
Silent area, see Cerebellum, 317
Simple muscle twitch, 394
Sino-aortic reflex, 95
Sleep, 346
Sliding filament hypothesis, 394
Smooth muscle multi unit, 398
Smooth muscles, 398
Snellen ’s chart, 373
Sodium co-transport mechanism, 163 Somatostatin, 248
Sommambulism, 347
Spastic neuropathic bladder, 169
Specific gravity of blood, 20
Speech, 348
Sperm, 414
Sperm count, 414, 415
Spermatogenesis, 413
Spermatozoa, 413
Spherical aberration, 363
Spinal cord, 291
Spinal shock, 315
Spino cerebellular tract—drosal (Gower),

302, 303
Spirogram, 130
Splanchnic circulation, 111
Splay, 180
Spleen, 209
Staircase phenomenon, 78, 396 Starling forces, 108
Starling’s law, 89
Static cystometry, 168
Steatorrhea, 209
Stereognosy, 300
Stokes Adam’s syndrome, 114 Strabismus–squint, 369
Stroke volume, 87
Subliminal fringe, 295
Substantia nigra, 331
Succus entericus, 200
Suckling reflex, 430
Sulcus of Rolandic, 336
Summation – Spatial, 287
Super female, 437
Surface tension, 128
Surfactant, 129
Sylvester’s method, 153
Sylvian fissure, 336
Sympathetic nervous system, 353 Symport, 163
Synapse, 285
Synaptic inhibition, 288
Syncope, 114
Synthetic Sweerteners, 384 Systemic circulation, 74

T wave, 90
Tachycardia, 85
Target cell, 218
Taste bud, 383
Taste sensation, 384
Temperature regulating centre, 324 Temporal lobe, 336
Temporal summation, 287
Temporal theory, 377
Testis, 412
Testosterone, 415
Tetanus, 396
Tetany, 256
Thalamic syndrome, 330
Thalamus, 329
Thalassemia, 57
Thelerche, 412
Theories of hearing, 377
Thermoreceptors, 283
Thrombocytopenia, 38
Thrombocytopenic purpura, 38 Thromboplastin, 40
Thrombosis, 46
Thrombus, 46
Thymus, 261
Thyroid function test, 237
Thyroid gland, 236
Thyroid hormone, 231
Thyroid stimulating hormone, 227 Thyrotoxicosis, 236
Thyrotropin releasing factor, 234 Tight junctions, 10
Times vital capacity, 132
Tissue thromboplastin, 41
T-Lymphocytes, 34
Transfusion of blood, 49
Transport mechanism, 11
Transpoulmonary pressure, 128 Travelling wave theory, 377 Trichromatic
theory, 369
Trichromats, 371
Tricuspid valve, 74
Trigeminal pain pathway, 306 Triple response, 105
Tritanomaly, 371
Tropomysosin, 388
Troponin, 388
Tubectomy, 434
Tubular load, 163
Tubular transport maximum, 163 Turbulent flow, 107
Turner’s syndrome, 437
Tympanic membrane, 375
Tympanic reflex, 376

Ulcer, 194
Unconditioned reflex, 229 Unipolar chest leads, 89 Universal donor, 50
Universal recipient, 50 Uraemia, 178
Urea clearance test, 177 Urodynamic studies, 168 Urokinase, 45
Uterine cycle, 419
Utilization time, 391
Utricle, 379

Vagal tone, 86
Vas deference, 412
Vasectomy, 434
Vasomotor centre, 95
Venous return, 88
Ventral spino cerebellar tract (Flechsig’s),

303
Ventircular systole, diastole, 80, 81 Vertigo, 381
Vestibular apparatus, 379
Vestibular pathway, 379
Visceral pain, 307
Viscosity of blood, 20
Vision, 361
Visual acuity, 373
Visual cortex, 373
Visual pathway, 372
Vital capacity, 131
Vitamin D, 259
Vitreous humor, 366
Voiding cystometry, 168
Volume of blood, 61
Vomiting, 203
Von Willebronds disease, 43

Waber’s law, 285

Wallerian degeneration, 281 Weber-Fechner’s law, 285 Weber’s test, 378
Weibel’s model, 124
Wernicke’s area, 337
Westergren’s method, 59 Wheal, 105
Wilson’s disease, 333
Wintrobe’s melthod, 59 Wolfian duct, 436
Word blindness, 339
Work of breathing, 135

X X-Chromosome, 435 Xerostomia, 189

Y
Y-Chromosome, 435
Young-Helmholtz theory, 369
Z
Z-line, 389
Zollinger-Ellison Syndrome, 194 Zona fasciculata, 238
Zona glomerulosa, 238
Zona reticularis, 238