physiology for medical student (pdf form )

Medical Physiology
for Undergraduate Students
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Medical Physiology
for Undergraduate Students
Indu Khurana
Senior Professor, Department of Physiology,
Postgraduate Institute of Medical Sciences,
University of Health Sciences,
Rohtak, India
ELSEVIER
A division of
Reed Elsevier India Private Limited
New Delhi
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Medical Physiology for Undergraduate Students, 1/e
Indu Khurana
ELSEVIER
A division of
Reed Elsevier India Private Limited
Mosby, Saunders, Churchill Livingstone, Butterworth-Heinemann and
Hanley & Belfus are the Health Science imprints of Elsevier.
© 2012 Elsevier
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form
or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the
publisher.
ISBN: 978-81-312-2805-0
Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures,
equipment and the use of drugs become necessary. The authors, editors, contributors and the publisher have, as far as it is
possible, taken care to ensure that the information given in this text is accurate and uptodate. However, readers are strongly
advised to confirm that the information, especially with regard to drug dose/usage, complies with current legislation
and standards of practice. Please consult full prescribing information before issuing prescriptions for any product
mentioned in the publication.
Published by Elsevier, a division of Reed Elsevier India Private Limited.
Registered Office: 622, Indraprakash Building, 21 Barakhamba Road, New Delhi-110 001.
Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon-122 002, Haryana, India.
Managing Editor: Shabina Nasim
Copy Editor: Shrayosee Dutta
Manager – Publishing Operations: Sunil Kumar
Manager – Production: NC Pant
Production Executive: Arvind Booni
Cover Designer: Raman Kumar
Typeset by Olympus Infotech Pvt. Ltd., Chennai, India (www.olympus.co.in).
Printed and bound at
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To
the teachers and residents in physiology for their
endeavour to dissipate and acquire knowledge
My parents and teachers for their blessings
My children, Aruj and Arushi, for their patience and
tolerance shown to loss of many precious moments
My husband, Dr AK Khurana, for his understanding,
encouragement and invaluable guidance
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Medical Physiology for Undergraduate Students provides a thorough exposition of the text in such a balanced way that the
undergraduate medical students can easily cover the syllabus during the one-year period provided for the first professional
in the revised curriculum by Medical Council of India, and also find adequate material while preparing for various post-
graduate entrance tests. The text on core and applied aspects of human physiology has been skilfully intermingled for the
students to apply their learning in clinical situations.
The subject matter on various systems has been arranged into twelve sections and each section has been subdivided into
various chapters. Metabolism and Nutrition has purposely not been included in this book; since, it is mainly covered in
biochemistry books and there is no point in repeating the information here.
The salient features of this book which make it an indispensable tool for undergraduate medical students are:
Each section begins with brief overview highlighting the topics covered. The text is then organized in such a way that the
students can easily understand, retain and reproduce it.
Various levels of headings, subheadings, bold face and italics given in the text will be helpful for a quick revision of the subject.
Relevant functional anatomy given in the beginning of each chapter is quite useful in conceptualizing the subject.
The text is illustrated with plenty of diagrams. The illustrations mostly include clear line diagrams providing vivid and
lucid details.
To further enhance the lucidity of the book each section is presented in a different colour format and the text and the
figures are presented in four colour.
In order to emphasize the clinical significance of physiology, the relevant applied aspect has been covered adequately in
each chapter.
Tables and flowcharts given in abundance will help in quick comprehension of the text.
No venture of this kind is possible without the blessings of teachers and parents to whom I shall remain ever indebted. I owe
this arduous task to the love and patience of my children Aruj, Bhawna and Arushi. It would have not been possible for me
to complete this task without the unconditioned help of my inspirator Dr AK Khurana, Sr Prof and Head, RIO, Postgraduate
Institute of Medical Sciences (PGIMS), Rohtak, who has not only guided me during each and every step in the preparation
of this book but also authored the chapter on ‘Sense of Vision’.
I am extremely grateful to the faculty members and resident doctors of Department of Physiology, PGIMS, Rohtak for their
generous help (especially Dr Manjeet and Dr Jai).
I wish to place on record my deep appreciation for my sincere friend Dr Sushma Sood, Sr Prof and Head, Department
of Physiology, PGIMS, Rohtak for her invaluable guidance and support. I also acknowledge with gratitude the constant
encouragement and conducive working atmosphere provided by Dr CS Dhull, Director, Pt BD Sharma, PGIMS, Rohtak and
Dr SS Sangwan, Vice-chancellor, University of Health Sciences, Rohtak.
It is my special pleasure to acknowledge with gratitude the most assured, co-operation and skill from the staff of Elsevier,
A division of Reed Elsevier India Pvt. Ltd., especially Ms Shabina Nasim, Managing Editor, and Shrayosee Dutta, Copy Editor.
For a volume like this it is not possible to be entirely free from human errors, some inaccuracies, ambiguities and typo-
graphical mistakes. Feedback and suggestions from the teachers and the students for further improvement of the book will
be welcomed and dully acknowledged.
Indu Khurana
Preface
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Preface vii
SECTION 1: GENERAL PHYSIOLOGY 1
1.1 Functional Organization, Composition and Internal Environment of Human Body 3
1.2 The Cell Physiology 9
1.3 Transport Through Cell Membrane 15
1.4 Membrane Potential 25
1.5 Genetics: An Overview 28
SECTION 2: NERVE MUSCLE PHYSIOLOGY 43
2.1 The Nerve 45
2.2 Neuromuscular Junction 63
2.3 Skeletal Muscle 66
2.4 Smooth Muscle and Cardiac Muscle 85
SECTION 3: BLOOD AND IMMUNE SYSTEM 93
3.1 Plasma and Plasma Proteins 95
3.2 Red Blood Cells and Anaemias 100
3.3 White Blood Cells 121
3.4 Immune Mechanisms 132
3.5 Platelets, Haemostasis and Blood Coagulation 149
3.6 Blood Groups and Blood Transfusion 165
SECTION 4: CARDIOVASCULAR SYSTEM 173
4.1 Functional Anatomy of Heart and Physiology of Cardiac Muscle 175
4.2 Origin and Spread of Cardiac Impulse and Electrocardiography 185
4.3 Heart as a Pump: Cardiac Cycle, Cardiac Output and Venous Return 206
4.4 Dynamics of Circulation: Pressure and Flow of Blood and Lymph 225
4.5 Cardiovascular Regulation 249
4.6 Regional Circulation 265
4.7 Cardiovascular Homeostasis in Health and Disease 280
SECTION 5: RESPIRATORY SYSTEM 291
5.1 Respiratory Tract: Structure and Functions 293
5.2 Pulmonary Ventilation 297
5.3 Pulmonary Circulation 312
5.4 Pulmonary Diffusion 316
Contents

Contents
x
5.5 Transport of Gases 325
5.6 Regulation of Respiration 335
5.7 Respiration: Applied Aspects 349
5.8 Physiology of Exercise 367
SECTION 6: EXCRETORY SYSTEM 375
6.1 Kidneys: Functional Anatomy and Blood Flow 377
6.2 Mechanism of Urine Formation: Glomerular Filtration and Tubular Transport 386
6.3 Concentration, Dilution and Acidification of Urine 402
6.4 Regulation of Body Fluid Osmolality, Composition and Volume 413
6.5 Physiology of Acid–Base Balance 421
6.6 Applied Renal Physiology Including Renal Function Tests 432
6.7 Physiology of Micturition 442
SECTION 7: GASTROINTESTINAL SYSTEM 449
7.1 Functional Anatomy and General Principles of Functions of Gastrointestinal System 451
7.2 Physiological Activities in Mouth, Pharynx and Oesophagus 456
7.3 Physiological Activities in Stomach 464
7.4 Pancreas, Liver and Gall Bladder 481
7.5 Physiological Activities in Small Intestine 497
7.6 Physiological Activities in Large Intestine 503
7.7 Digestion and Absorption 510
SECTION 8: ENDOCRINAL SYSTEM 523
8.1 General Principles of Endocrinal System 525
8.2 Endocrinal Functions of Hypothalamus and Pituitary Gland 535
8.3 Thyroid Gland 551
8.4 Endocrinal Control of Calcium Metabolism and Bone Physiology 562
8.5 Adrenal Glands 581
8.6 Pancreatic and Gastrointestinal Hormones 601
8.7 Endocrinal Functions of Other Organs and Local Hormones 615
SECTION 9: REPRODUCTIVE SYSTEM 621
9.1 Sexual Growth and Development 623
9.2 Male Reproductive Physiology 634
9.3 Female Reproductive Physiology 645
9.4 Physiology of Coitus, Pregnancy and Parturition 660
9.5 Physiology of Lactation 674
9.6 Physiology of Contraception 679
SECTION 10: NERVOUS SYSTEM 685
Subsection-10A: Physiological Anatomy and Functions of Nervous System
10.1 Physiological Anatomy, Functions and Lesions of Spinal Cord 689
10.2 Physiological Anatomy, Functions and Lesions of Cerebellum and Basal Ganglia 713
10.3 Physiological Anatomy, Functions and Lesions of Thalamus and Hypothalamus 734
10.4 Physiological Anatomy and Functions of Cerebral Cortex and White Matter of Cerebrum 747
10.5 Autonomic Nervous System 761
10.6 Meninges, Cerebrospinal Fluid, Blood–Brain Barrier and Cerebral Blood Flow 773
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Contents xi
Subsection-10B: Neurophysiology
10.7 Synaptic Transmission 777
10.8 Somatosensory System 794
10.9 Somatic Motor System 816
10.10 Limbic System and Physiology of Emotional, Behavioural and Motivational Mechanisms 849
10.11 Reticular Formation, Electrical Activity of the Brain, and Alert Behaviour and Sleep 857
10.12 Some Higher Functions of Nervous System 872
SECTION 11: SPECIAL SENSES 885
11.1 Sense of Vision 887
11.2 Sense of Hearing 924
11.3 Chemical Senses: Smell and Taste 941
SECTION 12: SPECIALISED INTEGRATIVE PHYSIOLOGY 951
12.1 Physiology of Body Temperature Regulation 953
12.2 Physiology of Growth and Behavioural Development 963
12.3 Physiology of Fetus, Neonate and Childhood 967
12.4 Geriatric Physiology 976
Index 983
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Section
1
Section
1
General Physiology
1.1 Functional Organization, Composition and Internal Environment of Human Body
1.2 The Cell Physiology
1.3 Transport Through Cell Membrane
1.4 Membrane Potential
1.5 Genetics: An Overview
Physiology, in simple terms, refers to the study of normal functioning of the
living structures. The human physiology is concerned with the way the various
systems of the human body function and the way each contributes to the
functions of the body as a whole. In other words, the human physiology is concerned
with specific characteristics and mechanisms of the human body that make it a living
being and the mechanisms which help in adaptation and homeostasis which are the
two fundamental features of life.
The general physiology envisages the general concepts and principles that are basic
to the functions of all the systems. As we know, the fundamental unit of human body
is a cell, therefore, this section includes a short review of fundamental aspect of the
cell physiology. Before studying the general biophysiological processes and the cell
physiology, it will be worthwhile to have a brief knowledge about the functional
organization, composition and internal environment of the human body.
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Functional Organization,
Composition and Internal
Environment of Human Body
FUNCTIONAL ORGANIZATION OF THE HUMAN BODY
Skin and its appendages
Skeletal system
Muscle system
Nervous system
Cardiovascular system
Respiratory system
Digestive system
Excretory system
Reproductive system
Endocrine system
Blood and immune system
BODY COMPOSITION
Total body water
Body electrolytes
INTERNAL ENVIRONMENT AND HOMEOSTASIS
Internal environment
Homeostasis
Chapter
Chapter
1.1
1.1
FUNCTIONAL ORGANIZATION OF
THE HUMAN BODY
The human body is actually a social order of about 100 tril-
lion cells organized into different functional structures,
some of which are called organs, some organs combinedly
form a system. For convenience of description, the human
body can be considered to be functionally organized into
various systems.
1. Skin and its appendages
Skin is the outermost covering of the human body. Its
appendages include hairs, nails, sebaceous glands and sweat
glands. The skin performs following important functions:
It acts as a physical barrier against entry of microorgan-
isms and other substances.
It prevents loss of water from the body.
It is a very important sensory organ containing receptors
for touch and related sensations.
It plays an important role in regulating body temperature.
2. Skeletal system
The basic framework of the body is provided by a large
number of bones that collectively form the skeleton. At
joints, the bones are united to each other by fibrous bands
called ligaments. In addition to the bones and joints, the
skeletal system also includes the cartilages present in the
body.
3. Muscle system
Overlying and usually attached to the bones are various
muscles. Muscles are composed of many elongated cells
called muscle fibres which are able to contract and relax.
Three distinct types of muscles can be identified which are
skeletal muscles, smooth muscles and cardiac muscles.
4. Nervous system
The specialized cells that constitute the functional units of
the nervous system are called neurons. The nervous system
may be divided into: (i) the central nervous system, made up
of brain and spinal cord and (ii) the peripheral nervous
system, consisting of the peripheral nerves and the ganglia
associated with them. The nerves supplying the body wall
and limbs are often called cerebrospinal nerves. The nerves
supplying the viscera, along with the parts of the brain and
spinal cord related to them, constitute the autonomic ner-
vous system. The autonomic nervous system is subdivided
into two major parts: the sympathetic and the parasympa-
thetic nervous system.
5. Cardiovascular system
The cardiovascular system consists of the heart and the
blood vessels. The blood vessels that take blood from the

Section 1 ¶ General Physiology
4
1
SECTION
heart to various tissues are called arteries. The smallest
arteries are called arterioles. Arterioles open into a network
of capillaries that perfuse the tissues. Exchange of various
substances between the blood and the tissues take place
through the walls of capillaries. In some situations, capillar-
ies are replaced by slightly different vessels called sinusoids.
Blood from capillaries (or from sinusoids) is collected by
small venules which join to form veins. The veins return
blood to the heart.
6. Respiratory system
The respiratory system consists of the lungs and the pas-
sages through which air reaches them. The passages are
nasal cavities, the pharynx, the trachea, the bronchi and
their intrapulmonary continuations.
7. Digestive system
The digestive or the alimentary system includes all those
structures that are concerned with eating, and with diges-
tion and absorption of food. The system consists of an ali-
mentary canal which includes the oral cavity, pharynx,
oesophagus, stomach, small intestine and large intestine.
Other structures included in the digestive system are the
liver, the gall bladder and the pancreas.
8. Excretory system
Excretion is the removal of waste products of metabolism
from the body. Egestion (or defaecation) is the removal of
undigested food from the gut and is not regarded as excre-
tion because the material taken into the gut through the
mouth is not made by the body itself. The organs forming
excretory system are the kidney, the ureters, the bladder
and the urethra.
9. Reproductive system
Reproduction is the production of a new generation of indi-
viduals of the same species. It involves the transmission of
genetic material from one generation to the next. The male
reproductive organs are the testis, the epididymis, the duc-
tus deferens, the seminal vesicles, the prostate, the male
urethra and the penis. The female reproductive organs are
the ovaries, uterine tubes, the uterus, the vagina, the exter-
nal genitalia and the mammary glands.
10. Endocrine system
Endocrine tissue is made up essentially of cells that produce
secretions which are poured directly into blood called
hormones. Some organs are entirely endocrine in function.
They are referred to as endocrine glands (or ductless glands)
e.g. the hypophysis cerebri (pituitary gland), the pineal
gland, the thyroid gland, the parathyroid glands and the
suprarenal (adrenal) glands. Groups of endocrine cells may
be present in the organs that have other functions. These
include the islets of Langerhans of pancreas, the interstitial
cells of the testis, the follicles and corpora lutea of the ova-
ries. Hormones are also produced by some cells in the kid-
ney, the thymus and the placenta.
11. Blood and immune system
Blood is regarded as a modified connective tissue because
the cellular elements in it are separated by a considerable
amount of ‘intercellular substance’ and because some of
the cells in it have close affinities to cells in general connec-
tive tissue.
Circulating blood normally contains three main types of
cells which perform their respective physiologic functions:
(i) the red cells (erythrocytes) are largely concerned with
oxygen transport, (ii) the white cells (leucocytes) play vari-
ous roles in the body defence against infection and tissue
injury and (iii) platelets (thrombocytes) which are primarily
involved in maintaining the integrity of blood vessels and in
preventing blood loss. Detailed physiology of each organ
system is considered in the relevant chapters.
BODY COMPOSITION
The normal body in an average adult male is composed of
water (60%), minerals (7%), protein and related substances
(18%), and fat (15%). The water, denoted by the term total
body water (TBW), and the electrolytes need special
emphasis.
TOTAL BODY WATER
Water is the principal and essential constituent of the
human body. The total body water is about 10% less in a
normal young adult female (average 50%) than that in an
average adult male (60%) due to relatively greater amount of
adipose tissue in the females. In both sexes the value tends
to decrease with age.
THE BODY FLUID COMPARTMENTS
The total body water is distributed into two main com-
partments of the body fluids separated from each other
by membranes freely permeable to water (Fig. 1.1-1,
Table 1.1-1):
1. Intracellular fluid compartment
The intracellular fluid (ICF) compartment comprises about
40% of the body weight, the bulk of which is contained in
the muscles.

Chapter 1 ¶ Functional Organization, Composition and Internal Environment of Human Body 5
1
SECTION
Glands and secretory tissue
Plasma 3.5 litres
(5% of body weight)
Total
body
water
42
litres
(60%
of
body
weight)
Interstitial fluid including transcellular fluid
and mesenchymal fluid 10.5 litres
(15% of body weight)
Cell membrane
Lymphatics
Capillary membrane
Skin
Extracellular
fluid
14
litres
(20%
of
body
weight)
Intake
Stomach
Intestine
Kidney
Intracellular fluid 28 litres
(40% of body weight)
Faeces
Lungs
Fig. 1.1-1 Distribution of total body water in different compartments. Arrows indicate fluid movement.
Table 1.1-1 Distribution of total body water in a normal
70kg person
Compartment Volume (L)
Body
weight (%)
Body
water (%)
Total body water (TBW) 42 60 100
Intracellular fluid (ICF) 28 40 67
Extracellular fluid (ECF) 14 20 33
Plasma (25% of ECF) 3.5 5 8
Interstitial fluid,
transcellular fluid and
mesenchymal tissue
fluid (75% of ECF)
10.5 15 25
册
册
册
2. Extracellular fluid compartment
The extracellular fluid (ECF) compartment constitutes
about 20% of the body weight. The ECF compartment com-
prises following:
(i) Plasma. It is the fluid portion of the blood (intravascular
fluid) and comprises about 5% of the body weight (i.e. 25%
of the ECF). On an average out of 5L of total blood volume
3.5L is plasma.
(ii) Interstitial fluid including lymph. It constitutes the
major portion (about 3/4) of the ECF. The composition of
interstitial fluid is the same as that of plasma except it has
little protein. Thus, interstitial fluid is an ultrafiltrate of
plasma.
(iii) Transcellular fluid. It is the fluid contained in the secre-
tions of the secretory cells and cavities of the body e.g. saliva,
sweat, cerebrospinal fluid, intraocular fluids (aqueous
humour and vitreous humour), pericardial fluid, bile, fluid
present between the layers (pleura, peritoneum and syno-
vial membrane), lacrimal fluid and luminal fluids of the gut,
thyroid and cochlea.
Transcellular fluid volume is relatively small, about 1.5%
of the body weight, i.e. 15mL/kg body weight (about 1L in
a person of 70kg).
(iv) Mesenchymal tissue fluid. The mesenchymal tissues
such as dense connective tissue, cartilage and bones contain
about 6% of the body water.
The interstitial fluid, transcellular fluid and mesenchymal
tissue fluid combinedly form the 75% of ECF.
The normal distribution of total body water in the fluid
compartments is kept constant by two opposing sets of
forces: osmotic and hydrostatic pressure.
MEASUREMENT OF BODY FLUID VOLUMES
Theoretically, it is possible to measure the volume of each
fluid component by injecting a substance (indicator) that will
stay in only one compartment (provided the concentration of
the substance in the body fluid and the amount removed by
excretion and metabolism can be accurately measured) as:
V =
A1 – A2
C
where,
V = Volume of fluid compartment,

6
1
SECTION
A1 = Amount of indicator injected in the fluid,
A2 = Amount of indicator removed by excretion and
metabolism, and
C = Concentration of the indicator in the fluid.
For example, if 150mg of sucrose (A1) is injected into a
70kg man, 10mg sucrose (A2) has been excreted or metab-
olized and the concentration of plasma sucrose (C) mea-
sured is 0.01mg/mL; then the volume distribution of
sucrose is
150mg – 10mg
0.01mg/mL
= 14,000mL
Prerequisites for accurate body fluid measurement
Though the formula described above for measuring the
body fluid volume appears simple, the material injected
(indicator) should have following characteristics:
It should be non-toxic.
It must mix evenly throughout the compartment being
measured.
It should be relatively easy to measure its concentration.
It must have no effect of its own on the distribution of
water or other substances in the body.
Either it must be unchanged by the body during the mix-
ing period or the amount changed (excreted and/or
metabolized) must be known.
This method of measuring body fluids is called ‘indica-
tor dilution method’ and can be used to measure the vol-
ume of different compartments of the body fluid by using
the suitable indicator/marker which will get distributed in
that particular compartment as follows:
1. Measurement of total body water volume
The volume of TBW can be measured by injecting a marker
which will be evenly distributed in all the compartments of
body fluid. Such markers include:
Deuterium oxide (D2O),
Tritium oxide, and
Aminopyrine.
The volume of the TBW can be calculated from the
values of the concentration of the marker in the plasma.
2. Measurement of extracellular fluid volume
The volume of ECF can be measured by injecting those marker
substances which cannot enter the cells but can freely pass
throughthecapillarymembrane,andthuscandistributeevenly
in all the compartments of ECF. Such substances include:
Radioactive substances like sodium, chloride (36Cl−
and
38Cl−
), bromide (82Br−
), sulphate and thiosulphate; and
Non-metabolizable saccharides like inulin, mannitol and
sucrose.
Most accurate method of measuring the volume of ECF
is by using inulin (polysaccharide, MW 5200). The values of
ECF volume are calculated from the values of concentra-
tion of inulin in the plasma since it makes an important
component of the ECF.
3. Measurement of plasma volume
The plasma volume can be measured by injecting those
markers which bind strongly with the plasma protein and
either do not diffuse or diffuse only in small quantities into
the interstitium. These substances are:
Radioactive iodine – 131
I, and
The dye Evan’s blue – T-1824.
The plasma volume can also be calculated from the val-
ues of the Red Blood Cells which can be measured using
radioactive isotopes of chromium (51
Cr).
4. Measurement of intracellular fluid volume
The volume of ICF cannot be measured directly, since there is
no substance which can be confined exclusively to this com-
partment after intravenous injection. Therefore, values of ICF
volume are calculated from the values of TBW and ECF as
ICF volume = TBW volume − ECF volume.
5. Measurement of interstitial fluid volume
Like ICF volume, the volume of interstitial fluid also cannot
be measured directly for the same reasons. Its values can
be roughly calculated from the values of ECF volume and
plasma volume as
Interstitial fluid volume = ECF volume − plasma volume.
Note. The ECF volume/intracellular fluid volume ratio is
larger in infants and children as compared to adults, but
absolute volume of ECF in children is smaller than in adults.
Therefore, dehydration develops rapidly, more frequently
and severe in children than in adults.
BODY ELECTROLYTES
The electrolytes constitute about 7% of the total body
weight. The distribution of electrolytes in various compart-
ments differs markedly. Table 1.1-2 shows the distribution
of electrolytes in two major compartments of body fluid:
the ECF and the ICF.
From Table 1.1-2, it may be noted that in the ICF
the main cations are K+
and Mg2+
, and the main anions are
PO3−
4 and proteins. While in the ECF, the predominant cat-
ion is Na+
and the principal anions are Cl−
and HCO3
−
Besides these, a small proportion of non-diffusible proteins,

Chapter 1 ¶ Functional Organization, Composition and Internal Environment of Human Body 7
1
SECTION
nutrients and metabolites such as glucose and urea are also
present in ECF.
The essential difference between the two main subdivi-
sions of ECF is the higher protein content in plasma than in
the interstitial fluid which plays an important role in main-
taining fluid balance.
It is important to note that:
Essentially all of the body K+
is in the exchangeable pool.
Only 65–70% of the body Na+
is exchangeable.
Almost all of the body Ca2+
and Mg2+
are non-
exchangeable.
Only the exchangeable solutes are osmotically active.
Functions of electrolytes
1. Electrolytes are the main solutes in the body fluids for
maintenance of acid–base balance.
2. Electrolytes maintain the proper osmolality and volume
of body fluids.
3. The concentration of certain electrolytes determines
their specific physiologic functions, e.g. the effect of cal-
cium ions on neuromuscular excitability.
INTERNAL ENVIRONMENT AND
HOMEOSTASIS
INTERNAL ENVIRONMENT
Claude Bernarde (1949), the great French physiologist,
introduced the term internal environment of the body or
the milieu interieur for the ECF of the body. He said so since
all the body cells essentially depend upon the ECF for main-
tenance of cellular life. Cells are capable of living, growing
and performing their special functions so long as the proper
concentration of oxygen, glucose, different ions, amino acids,
fatty substances and other constituents are available in the
internal environment.
HOMEOSTASIS
Homeostasis, a term introduced by W. B. Cannon, refers to
the mechanism by which the constancy of the internal envi-
ronment is maintained and ensured. For this purpose, liv-
ing membranes with varying permeabilities such as vascular
endothelium and cell membrane play important role.
The factors involved in the maintenance of internal environ-
ment can be summarized as:
Transport of ECF,
Maintenance of pH of ECF (acid–base balance),
Regulation of temperature,
Maintenance of water and electrolyte balance,
Supply of nutrients, oxygen, enzymes and hormones,
Removal of metabolic and other waste products, and
Reproduction.
MODE OF ACTION OF HOMEOSTATIC CONTROL
SYSTEM
The homeostasis is a complex phenomenon. The mode of
operation of all the systems, which are involved in the
homeostasis is through ‘feedback’ mechanism and the
adaptive control system. Feedback mechanism is of two
types: the negative feedback mechanism and the positive
feedback mechanism.
Negative feedback mechanism
Most control systems of the body act by the negative feed-
back. That is, in general if the activity of a particular system
is increased or decreased, a control system initiates a nega-
tive feedback, which consists of a series of changes that
return the activity toward normal.
Examples of a feedback mechanism:
1. When the blood pressure suddenly rises or lowers, it ini-
tiates a series of reactions that tries to bring the blood
pressure to normal levels.
2. When thyroxine secretion is more, it inhibits the secre-
tion of thyroid stimulating hormone from pituitary so
that, thyroxine is not secreted from the thyroid gland.
Positive feedback mechanism
Positive feedback is better known as a vicious circle. Usually
it is harmful and in some instances even death can occur
due to positive feedback. For example, as shown in Fig. 1.1-2,
when a person has suddenly bled 2L of blood, a vicious
circle of progressively weakening of the heart is set which
ultimately causes death.
A mild degree of feedback can be overcome by the nega-
tive feedback control mechanisms of the body, and a vicious
cycle fails to develop. For example, when a patient bleeds
Table 1.1-2 Distribution of ions in the ECF and ICF
(Values are in mEq/L of H2O)
Ion Extracellular fluid Intracellular fluid
Cations
Na+
K+
Ca2+
Mg2+
142
5.5
5
3
14
150
1
58
Anions
Cl−
HCO3
−
PO4
3−
Proteins
103
28
4
1g/dL
4
10
75
5g/dL

8
1
SECTION
1L of blood instead of 2L, the negative feedback mecha-
nisms of controlling the blood pressure may overcome the
positive feedback, and the blood pressure will return to
normal, as shown in Fig. 1.1-2.
Further, sometimes positive feedback can serve useful
purposes, e.g. under following circumstances:
Clot formation followed by rupture of vessels is acceler-
ated by the vicious cycle of thrombin formation (for
details see page 153). This stops the bleeding.
Child birth during labour is facilitated by progressively
increasing uterine contractions due to positive feedback
from stretching of the cervix by head of the baby (for
details see page 671).
Generation of nerve signals by the vicious cycle of
progressive leakage of Na+
ions from the channels set up
following stimulation of membrane of nerve fibre is due
to the positive feedback.
Adaptive control system
Adaptive control system refers to a delayed type of negative
feedback mechanism. This is seen in the nervous system.
For example, when some movements of the body occur
very rapidly, there is not enough time for nerve signals to
travel from the peripheral parts of the body all the way to
the brain and then back to the periphery again in time to
control the movements. Under such circumstances brain
uses a principle called feed-forward control to cause the
required muscle contraction which retrospectively is con-
veyed to the brain by the sensory nerve signals from the
moving part. If the movement performed is found incor-
rect, then the brain corrects the feed-forward signals that it
sends to the muscle the next time the movement is required.
Such a correction made by successive retrospective feed-
back mechanism is called adaptive control.
Fig. 1.1-2 Flowchart showing how a positive feedback mech-
anism can cause death.
Bleeding (2 L blood)
Decreased blood pressure Death
Decreased flow of blood
to heart muscles
Weakening of the heart
Decreased pumping
power of the heart

The Cell Physiology
CELL STRUCTURE
Cell membrane
Cytoplasm
Nucleus
THE CELL MEMBRANE
Fluid mosaic model of membrane structure
Arrangement of different molecules in cell membrane
INTERCELLULAR JUNCTIONS
Tight junction
Adherens junction
Gap junction
Chapter
Chapter
1.2
1.2
CELL STRUCTURE
The cell is the smallest structural and functional unit of the
body. The human body contains about 100 trillion cells.
Different types of cells of the body possess features which
distinguish one type from the other and are specially adapted
to perform particular functions, e.g. the red blood cells
transport oxygen from lungs to the tissues, muscle cell is
specialized for the function of contraction.
A typical cell, as seen by the light microscope, consists of
three basic components:
Cell membrane,
Cytoplasm and
Nucleus.
CELL MEMBRANE
Cell membrane or the plasma membrane is the protective
sheath, enveloping the cell body. It separates the contents of
cell from the external environment and controls exchange
of materials between the fluid outside the cell (extracellular
fluid) and the fluid inside the cell (intracellular fluid). A
detailed knowledge of its structure (Fig. 1.2-1) is essential
for the understanding of cell functions. Therefore, it will be
discussed separately.
CYTOPLASM
Cytoplasm is an aqueous substance (cytosol) containing a
variety of cell organelles and other structures. The structures
dispersed in the cytoplasm can be broadly divided into
three groups: organelles, inclusion bodies and cytoskeleton.
A. ORGANELLES
The organelles are the permanent components of the cells
which are bounded by limiting membrane and contain
enzymes hence participate in the cellular metabolic activity.
These include:
1. Mitochondria
Mitochondria are the major sites for aerobic respiration.
These are oval structures and more numerous in metaboli-
cally active cells.
Structure. The mitochondria consist of:
Membrane. There are two layers of the membrane. The
outer smooth and inner folded into incomplete septa
called cristae (Fig. 1.2-1A).
Matrix of the mitochondria contains enzymes required
in Krebs’ cycle by which products of carbohydrate, fat
and protein metabolism are oxidised to produce energy
which is stored in the form of ATP in the lollipop-like
globular structures.
Functions. In addition to their role as power generating
units, the mitochondria may have a role in synthesizing
membrane bound proteins since they also possess deoxyri-
bonucleic acid (DNA) and ribosomes.
2. Endoplasmic reticulum
Endoplasmic reticulum (ER) is a system of flattened
membrane-bound vesicles and tubules called cisternae

10
1
SECTION
(Fig. 1.2-1B). It is continuous with the outer membrane of
the nuclear envelop, Golgi apparatus and possibly with the
cell membrane. Morphologically, two types of endoplasmic
reticulum can be identified: rough or granular and smooth
or agranular.
(i) Rough endoplasmic reticulum. The rough ER is charac-
terized by the presence of a number of ribosomes on its
surface and transports proteins made by the ribosomes
through the cisternae. Thus, the rough ER is especially
well developed in cells active in protein synthesis, e.g.
Russell’s bodies of plasma cells, Nissl granules of nerve
cells and acinar cells of pancreas.
(ii) Smooth endoplasmic reticulum. Smooth ER is devoid of
ribosomes on its surface. It is a site of lipid and steroid syn-
thesis.Therefore,itisfoundinabundancewiththeLeydig
cells and cells of the adrenal cortex. In the skeletal and
cardiac muscles, smooth ER is modified to form sarcoplas-
micreticulumwhichisinvolvedinthereleaseandseques-
tration of calcium ions during muscular contraction.
3. Golgi apparatus
The Golgi apparatus or complex is a collection of membra-
nous vesicles, sacs or tubules which is generally located
close to the nucleus. It is continuous with the endoplasmic
reticulum. Golgi apparatus is particularly well developed in
exocrine glandular cells (Fig. 1.2-1C).
Functions. Its main functions are:
Synthesis of carbohydrates and complex proteins.
Packaging of proteins synthesized in the rough ER into
vesicles.
Site of formation of lysosomal enzymes.
Transport of the material to the other parts of cell or to
the cell surface membrane and secretion.
Glycosylation of proteins to form glycoproteins.
4. Ribosomes
Ribosomes are spherical particles which contain 80–85%
of the cell’s ribonucleic acid (RNA). They may be present in
the cytosol as free (unattached) or in bound form (attached
to the membrane of endoplasmic reticulum). Slightly
smaller form of ribosomes is also found in mitochondria.
Functions. They are the site of protein synthesis. They syn-
thesize all transmembrane proteins, secreted proteins and
most proteins that are stored in the Golgi apparatus, lyso-
somes and endosomes.
5. Lysosomes
Lysosomes are rounded to oval membrane bound organ-
elles containing powerful lysosomal digestive (hydrolytic)
enzymes. They are formed by the Golgi apparatus. As many
as 40 different lysosomal enzymes have been synthesized.
Lysosomes are particularly abundant in cells involved in
Rough Smooth
Nucleolus
Globular head
A
F
C
D
E
B
Fig. 1.2-1 Structure of a typical cell (in the centre) showing various organelles: A, mitochondrion; B, endoplasmic reticulum (rough
and smooth); C, Golgi apparatus; D, centrosome; E, nucleus and F, secretory granules.

Chapter 1.2 ¶ The Cell Physiology 11
1
SECTION
phagocytic activity, e.g. neutrophils and macrophages.
There are three forms of lysosomes:
Primary lysosomes or storage vacuoles are formed
from the various hydrolytic enzymes synthesized by
rough ER and packaged in the Golgi apparatus.
Secondary lysosomes or autophagic vacuoles are
formed by fusion of primary lysosomes with parts of
damaged or worn out cell components.
Residual bodies are undigestible materials in the
lysosomes.
6. Peroxisomes
Peroxisomes, also known as microbodies, are spherical
structures enclosed by a single layer of unit membrane.
These are predominantly present in hepatocytes and tubu-
lar epithelial cells.
Functions. They essentially contain two types of enzymes:
Oxidases which are active in oxidation of lipid and
Catalases which act on hydrogen peroxide to liberate
oxygen.
7. Centrosome
The centrosome consists of two short cylindrical structures
called centrioles (Fig. 1.2-1D). It is situated near the centre
of the cell close to the nucleus. The centrioles are respon-
sible for movement of chromosomes during cell division.
B. CYTOPLASMIC INCLUSIONS
The cytoplasmic inclusions are the temporary components
of certain cells. These may or may not be enclosed in the
membrane. A few examples of cytoplasmic inclusions are:
Lipid droplets. These are seen in the cells of adipose
tissue, liver and adrenal cortex.
Glycogen. It is seen in the cells of liver and skeletal
muscles.
Proteins as secretory granules are seen in the secretory
glandular cells (Fig. 1.2-1F).
Melanin pigment is seen in the cells of epidermis, retina
and basal ganglia.
Lipofuscin. It is a yellow brown pigment believed to be
derived from secondary lysosomes and is seen in the
cardiac muscle and brain cells of elderly people.
C. CYTOSKELETON
The cytoskeleton is a complex network of fibres that main-
tains the structure of the cell and allows it to change shape
and move. It primarily consists of (Fig. 1.2-2):
Microtubules
Microtubules are long hollow tubular structures without
limiting membrane about 25nm in diameter. These are
made up of two globular protein subunits α- and β-tubulin.
The bundles of tubulin give structural strength to the cells.
Microtubules form the transport system of the cells. Some
of the other organelles and protein molecules move to a dif-
ferent part of the cell through the microtubules. Kinesin and
dynein known as molecular motors help in the movement
of molecules through the microtubules.
The cilia and flagella which project from surface of certain
cells (spermatozoa, respiratory mucosa and fallopian tubes)
are also composed of microtubules enclosed in the plasma
membrane and are active in the locomotion of the cells.
Intermediate filaments
Intermediatefilamentsarefilamentousstructuresabout10nm
in diameter. Some of these filaments connect the nuclear
membrane to the cell membrane. Their main function is to
mechanicallyintegratethecellorganelleswithinthecytoplasm.
In their absence, cells rupture more easily; and when they
are abnormal in human, blistering of the skin is common.
Microfilaments
Microfilaments are long solid filamentous structures hav-
ing a diameter of 6–8nm. These are made up of contractile
proteins, actin and myosin. Actin is the most abundant pro-
tein in the mammalian cell. It attaches to various parts of
Adducin Cell membrane Anion exchanger
(Band 3)
Ankyrin
4.2
Glycophorin 4.1
Tropomodulin
4.9
α chain spectrin
β chain
Tropomyosin
Fig. 1.2-2 Cytoskeleton showing various proteins.

12
1
SECTION
cytoskeleton by other proteins (anchor proteins). These are
identified by numbers as 4.1, 4.2 and 4.9. Extension of micro-
filaments along with the plasma membrane on the surface
of the cells forms microvilli which increase the absorptive
surface of the cells (e.g. intestinal epithelium). In the skeletal
muscle, presence of actin and myosin filaments is respon-
sible for their contractile property.
MOLECULAR MOTORS
Molecular motors help in the movement of different pro-
teins, organelles and other cell parts (their cargo) to all parts
of the cell. These can be divided into two types:
1. Microtubule-based molecular motors. This is a super-
family of molecular motors that produce motion along
microtubules. Two important molecular motors are:
(i) Conventional kinesin.
(ii) Dyneins.
2. Actin-based molecular motors. This is a super-family of
molecular motors that produce motion along the actin. The
important example of this group is myosin.
NUCLEUS
Nucleus is present in all the eukaryotic cells. It controls all
the cellular activities including reproduction of the cell.
Most of the cells are uninucleated except few types of cells
like skeletal muscle cells which are multinucleated. The
nucleus consists of (Fig. 1.2-1E):
1. Nuclear membrane
The nuclear membrane is double layered porous structure
having a 40,270nm wide space called perinuclear cistern
which is continuous with the lumen of endoplasmic reticu-
lum. The outer layer of the nuclear membrane is continu-
ous with endoplasmic reticulum. The exchange of materials
between the nucleoplasm and cytoplasm occurs through
the nuclear membrane.
2. Nucleoplasm
The nucleoplasm or the nuclear matrix is a gel-like ground
substance containing a large quantity of genetic material in the
form of DNA. When a cell is not dividing, the nucleoplasm
appears as dark staining thread-like material called nuclear
chromatin. During cell division, the chromatin material is con-
verted into rod-shaped structures, the chromosomes. There
are 46 chromosomes (23 pairs) in all the dividing cells of the
body except the gamete (sex cells) which contain only 23 chro-
mosomes (haploid number). Each chromosome is composed
of two chromatids connected at the centromere to form ‘X’
configuration having variation of the location of centromere.
The chromosomes are composed of three components: DNA,
RNA and other nuclear proteins. The nuclear DNA carries the
genetic information which is passed via RNA into the cyto-
plasm for synthesis of proteins of similar composition.
3. Nucleolus
The nucleus may contain one or more rounded bodies
called nucleoli. The nucleoli are the site of synthesis of ribo-
somal RNA. The nucleoli are more common in growing
cells or in cells that actively synthesize proteins.
THE CELL MEMBRANE
An understanding of the structure and properties of the cell
membrane is most essential to understand the various physio-
logicalactivitiesofthecell.Electronmicroscopyhasshownthat
cell membrane/plasma membrane has a trilayer structure hav-
ing a total thickness of 7–10nm (70–100 Å) and is known as
unit membrane. The three layers consist of two electron dense
layers separated by an electron lucent layer (clear zone).
Biochemically the cell membrane is composed of a complex
mixture of lipids (40%), proteins (55%) and carbohydrates (5%).
A few hypotheses have been proposed to explain the dis-
tribution of various biochemical components in the cell
membrane. The most important hypothesis is the fluid
mosaic model of Singer and Nicholson.
FLUID MOSAIC MODEL OF MEMBRANE STRUCTURE
In 1972, Singer and Nicholson put forward the fluid mosaic
model of membrane structure (Fig. 1.2-3), which is pres-
ently most accepted. According to this model:
Phospholipid bilayer is the basic continuous structure
forming the cell membrane. The phospholipids are pres-
ent in fluid form. This fluidity makes the membrane quite
flexible and thus allows the cells to undergo considerable
changes in the shape without disruption of structural
integrity.
The protein molecules are present as a discontinuous
mosaic of globular proteins which float about in the fluid
phospholipid bilayer forming a fluid mosaic pattern.
ARRANGEMENT OF DIFFERENT MOLECULES IN
CELL MEMBRANE
Arrangement of lipid bilayer of the cell membrane
Each lipid molecule in the lipid bilayer of the cell membrane
primarily consists of phospholipid, cholesterol and glycolipids.
The lipid molecule is clothes pin shape and consists of a head
end and a tail end.

Chapter 1.2 ¶ The Cell Physiology 13
1
SECTION
The head end or the globular end of the molecule. It is
positively charged and quite soluble in water (i.e. polar or
hydrophilic). The tail end consists of two chains of fatty
acids or steroid radicle of cholesterol. It is quite insoluble in
water (nonpolar or hydrophobic). These lipid molecules are
arranged as bilayer in such a way that their nonpolar hydro-
phobic tail ends are directed towards the centre of the
membrane whereas their polar hydrophilic head ends are
directed outwards on either side of the membrane (Fig. 1.2-3).
In this way head ends of molecules face the aqueous phase,
i.e. extracellular fluid on outside and the intracellular fluid
(cytoplasm) on inner side.
Functional significance of the lipid bilayer. The lipid bilayer of
the cell membrane makes it a semipermeable membrane
which constitutes the major barrier for the water soluble
molecules like electrolytes, urea and glucose. On the other
hand, fat soluble substances like oxygen, fatty acids and
alcohol can pass through the membrane with ease.
Arrangement of proteins in the cell membrane
Most protein molecules float about in the phospholipid
bilayer forming a fluid mosaic pattern. The two types of
proteins recognized in the cell membrane are:
Lipoproteins, i.e. the proteins containing lipids which
function as enzymes and ion channels, and
Glycoproteins, i.e. the proteins containing carbohydrates
which function as receptors for hormones and
neurotransmitters.
The proteins in the cell membrane are described to be
arranged as:
1. Peripheral proteins. These are present peripheral to the
lipid bilayer both inside and outside to it.
(i) Intrinsic proteins. These are located in the inner surface
of the lipid bilayer and serve mainly as enzymes. Some
of these are anchored to the cytoskeleton of the cell
(Fig. 1.2-2).
(ii) Extrinsic or surface proteins. These are the proteins
located on the outer surface of the lipid bilayer. These
protein molecules are not associated tightly with the
cell membrane and thus can dissociate readily from the
cell membrane. Some of these proteins serve as cell
adhesion molecules (CAMs) that anchor cells to neigh-
bouring cells and to the basal lamina.
2. Integral proteins or transmembrane proteins. These are
the proteins which extend into the lipid bilayer (Fig. 1.2-3).
Some proteins penetrate only part of the way into the mem-
brane while others penetrate all the way through. The inte-
gral proteins, on the basis of functions they serve are:
Channel proteins. Some of the integral protein molecules
serve as channels for water soluble substances like glucose
andelectrolytes.Thesearealsocalledthechannelproteins.
Carrier proteins. The protein molecules which help in
transport of substances across the cell membrane by
means of active and passive (facilitated diffusion) trans-
port are called carrier proteins.
Receptor proteins. Some of the proteins function as
receptors that bind neurotransmitters and hormones,
initiating physiologic changes inside the cell.
Antigens. Some proteins in the cell membrane also act
as antigens. These are glycoproteins with branching
carbohydrate side chains like antennae.
Pumps. There are certain proteins in the cell membrane
which act as pumps and form active transport system
of the cell, e.g. Na+
–K+
ATPase pump, K+
–H+
ATPase
pump and Ca2+
pump.
Arrangement of carbohydrates in the cell membrane
The carbohydrates are attached either to the proteins (gly-
coproteins) or the lipids (glycolipids). Throughout the sur-
face of cell membrane, carbohydrate molecules form a thin
loose covering called glycocalyx.
Functions of cell membrane carbohydrates
Being negatively charged the carbohydrate molecules of
the cell membrane do not allow the negatively charged
particles to move out of the cell.
The glycocalyx helps in tight fixation of the cells with
one another.
Some of the carbohydrate molecules also serve as receptors.
INTERCELLULAR JUNCTIONS
The cell membranes of the neighbouring cells are con-
nected with one another through the intercellular junctions
or the junctional complexes, which are of three types.
Fig. 1.2-3 Fluid mosaic model of the structure of cell
membrane.
Peripheral proteins
Phospholipid
molecules
Integral proteins
Peripheral proteins
Tail
Head
Channel protein
Carbohydrate side chain

14
1
SECTION
Types of intercellular junctions
1. Tight junction. This is also called zona occludens or the
occluding zone (Fig. 1.2-4A). In this type of intercellular
junction, the outer layer of the cell membrane of the neigh-
bouring cells fuse with each other, thus obliterating the space
between the cells. Such junctions form a barrier to the move-
ment of ions and other solutes from one cell to another.
2. Adherens junction. This is also called zonula adherens. In
this type of junction, cell membranes of the adjacent cells
are separated by a 15–20nm wide space which is at focal
places obliterated by the dense accumulation of the pro-
teins at the cell surface. Bundles of intermediate filaments
project from the intercellular junctional areas and radiate
into the cytoplasm. This holds the adjacent cells at these
focal places. These are of two types:
Desmosomes are the adherens junctions where thick-
ened focal areas are formed on both the apposing cell
membranes (Fig. 1.2-4B).
Hemidesmosomes are the adherens junctions where focal
thickening is seen only on the membrane of one of the
Desmosome
Normal intercellular
space (20 nm)
Zona
occludens
A
B
C
Fig. 1.2-4 Schematic diagram of a cell to show various inter-
cellular junctions: A, tight junction; B, adherens junction and C,
gap junction.
two adjacent cells. So, this is also known as half desmo-
some.Adherensjunctionsareseeninthecellsofepidermis.
3. Gap junction. Gap junctions or the nexus are the chan-
nels on the lateral surfaces of the two adjacent cells through
which the molecules are exchanged between the cells (Fig.
1.2-4C). Each half of the channel is surrounded by six sub-
units of proteins (the connexins). The intercellular space is
reduced from the usual size of 15–20nm to 2–3nm at such
junction. The gap junctions are seen in the heart and basal
part of epithelial cells of intestinal mucous membrane. Gap
junctions serve the following functions:
These permit the intercellular passage of glucose, amino
acids, ions and other substances which have a molecular
weight of about 1000.
These permit rapid propagation of electrical potential
changes from one cell to another as seen in cardiac mus-
cle and other smooth muscle cells.
These help in the exchange of chemical messengers
between the cells.
Cell adhesion molecules
Cell adhesion molecules (CAMs) are the prominent parts
of the intercellular connections by which the cells are
attached to the basal lamina and to each other.
Types of CAMs. CAMs have been variously classified.
Most simply they can be divided in four broad families:
1. Integrins. These are molecules that bind to various
receptors.
2. Adhesion molecules of IgG subfamily. Through these
molecules the IgG immunoglobulins bind to various
antigens.
3. Cadherins. These are Ca2+
dependent molecules that
mediate cell-to-cell adhesions.
4. Selectins. These are lectin-like domains that bind
carbohydrates.
Functions of CAMs. In addition to binding the neighbouring
cells to each other the CAMs perform following other
functions:
They transmit signals into and out of the cells.
They play a role in embryonic development and forma-
tion of the nervous system and other tissue.
They hold tissue together in adults.
They play an important role in inflammation and wound
healing.
They also play a role in metastasis of tumours.

Transport Through Cell
Membrane
PASSIVE TRANSPORT
Diffusion
Simple diffusion
Facilitated diffusion
Osmosis
Osmotic pressure
Osmole, osmolality and osmolarity
Tonicity of fluids
ACTIVE TRANSPORT
Primary active transport processes
Sodium–potassium pump
Calcium pump
Potassium–hydrogen pump
Secondary active transport processes
Sodium co-transport
Sodium counter-transport
VESICULAR TRANSPORT
Endocytosis
Exocytosis
Transcytosis
OTHER TRANSPORT PROCESSES
Transport across epithelia
Ultraﬁltration
Chapter
Chapter
1.3
1.3
The physiological activities of a cell depend upon the sub-
stances like nutrients, oxygen and water, which must be
transported into the cell, and at the same time metabolic
waste must be transported out of the cell. Various processes
involved in the transport of substances across the cell mem-
brane may be grouped as under:
Passive transport,
Active transport and
Vesicular transport.
PASSIVE TRANSPORT
Passive transport refers to the mechanism of transport of
substances along the gradient without expenditure of any
energy. It depends upon the physical factors like concentra-
tion gradient, electrical gradient and pressure gradient.
Since the transport of substances occurs along the gradient,
this process is also called down-hill movement. The passive
transport mechanisms operating at the cell membrane level
are diffusion and osmosis.
DIFFUSION
Diffusion refers to passive transport of molecules from
areas of higher concentration to areas of lower concentration.
Diffusion through cell membrane is divided into two sub-
types called: simple diffusion and facilitated diffusion.
SIMPLE DIFFUSION
In simple diffusion, transport of atoms or molecules occurs
from one place to another due to their random movement.
Due to constant random movement, the molecules collide
with each other and also strike with the cell membrane. The
frequency of collision and the probability of striking to the
cell membrane will be higher on the side of the membrane
having higher concentration of that particular molecule. In
this process there occurs a net flux of the molecules from
the areas of high concentration to areas of low concentra-
tion. The net movement of the molecules ceases when the
concentration of molecules equals, and there occurs a con-
dition of diffusional equilibrium. Quantitatively, the net
movement of the molecules across a permeable membrane
where only simple diffusion is occurring is expressed by
Fick’s law of diffusion, which states that rate of diffusion (J)
is directly proportional to the difference in the concentra-
tion of the substance in two regions (concentration gradi-
ent, i.e. C1 −C2) and cross-sectional area (A) and inversely
proportional to the distance to be travelled, i.e. thickness of
the membrane (T).
Thus, J = D
A(C1−C2)
T
, where D is the diffusion coefficient.
8/8/2011 12:28:45 PM

Section 1 General Physiology
16
1
SECTION
The diffusion of molecules across the biological mem-
branes differs depending upon the lipid solubility, water
solubility, type of electrical charge and size of the mole-
cules. Further, selective permeability of the semipermeable
cell membrane also affects the diffusion of different mole-
cules. How the different molecules diffuse across a cell
membrane are discussed below.
Simple diffusion of lipid soluble substances through
the cell membrane
The rate of diffusion through the lipid bilayer of the cell
membrane is directly proportional to the solubility of a sub-
stance in lipids. Therefore, molecules of substances like oxy-
gen, nitrogen, carbon dioxide, alcohol, steroid hormones
and weak organic acids and bases, being lipid soluble, diffuse
very rapidly through the lipid bilayer of the cell membrane.
Simple diffusion of water and other lipid insoluble
molecules through the cell membrane
Astonishingly, water and other lipid insoluble substances
can also pass easily through the cell membrane. It has been
shown that it is possible due to the presence of the so-called
protein channels (made from transmembrane proteins) in
the cell membrane.
Diffusion through protein channels
The protein channels are tube-shaped channels which
extend in the cell membrane from the extracellular to the
intracellular ends (Fig. 1.3-1). Therefore, even the highly
lipid insoluble substances can diffuse by simple diffusion
directly through these channels of the cell membrane.
The protein channels have been equipped with follow-
ing characteristics:
Selective permeability and
Gating mechanism.
Selective permeability of protein channels
The protein channels are highly selective, i.e. each channel
can permit only one type of ion to pass through it. This
results from the characteristics of the channel itself, such as
its diameter, its shape and nature of electrical charges along
its inside surfaces. Examples of some selective channels are:
Sodium channels are specifically selective for the passage
of sodium ions. These are 0.3 by 0.5nm in size and their
inner surfaces are strongly negatively charged (Fig. 1.3-2).
Potassium channels are specifically selective for the pas-
sage of potassium ions. These are 0.3 by 0.3nm in size
and are not negatively charged (Fig. 1.3-3).
Gating mechanism in protein channels
Some protein channels are continuously open, whereas
most others are ‘gated’, i.e. they are equipped with actual
gate-like extensions of the transport protein molecule
which can open and close as per requirement. This gating
mechanism is a means of controlling the permeability of the
channels. The opening and closing of gates are controlled
by three principal ways:
1. Voltage-gated channels. These respond to the electri-
cal potential across the cell membrane. As shown in Fig.
1.3-2 in the case of sodium channels the gates are located
at the outer end of the channels and these remain tightly
closed, when there is a strong negative charge on the
inside of cell membrane. When the inside of cell mem-
brane loses its negative charge, these gates open and
there occurs a tremendous inflow of sodium ions. This
is the basis of occurrence of action potentials in nerves
that are responsible for nerve signals.
In the case of potassium channels, the gates are located
at inner end of the channel (Fig. 1.3-3) and they too open
when inside of the cell membrane loses its negative charge,
but this response is much slower than that for sodium
channel. The opening of potassium channel gates is partly
responsible for terminating the action potential.
2. Ligand-gated channels. Gates of these channels open
when some other chemical molecule binds with the
gate proteins that is why this is also called chemical gat-
ing. One of the most important example of ligand chan-
nel gating is the effect of acetylcholine on the so-called
Cell
membrane
Channel protein
ECF
ICF
Fig. 1.3-1 Simple diffusion.
Gate closed Gate open
Na⫹
ECF
ICF
Cell
membrane
Fig. 1.3-2 Voltage-gated sodium channels.
8/8/2011 12:28:48 PM

Chapter 1.3 Transport Through Cell Membrane 17
1
SECTION
acetylcholine channels. This gate plays an important role
in transmission of nerve signals from one nerve cell to
another and from nerve cells to muscle cells.
3. Mechanical-gated channels. Some protein channels are
opened by mechanical stretch. These mechano-sensitive
channels play an important role in cell movements.
FACILITATED DIFFUSION
The water soluble substances having larger molecules such
as glucose cannot diffuse through the protein channels by
simple diffusion. Such substances diffuse through the cell
membranewiththehelpofsomecarrierproteins.Therefore,
this type of diffusion is called facilitated or the carrier-
mediated diffusion. There are many types of carrier proteins
in the cell membrane, each type having binding sites that are
specific for a particular substance. Among the most important
substances that cross cell membranes by facilitated diffusion
are glucose and most of the amino acids.
Mechanism of facilitated diffusion
Postulated mechanism for facilitated diffusion is shown in
Fig. 1.3-4. As shown in the figure, a conformational change
occurs in the carrier protein after the molecule to be trans-
ported is bound at the receptor site. The repetitive sponta-
neous configurational changes allow the diffusion of the
molecule.
Types of carrier protein systems
Three types of carrier protein systems are known: uniport,
symport and antiport (Fig. 1.3-5). The symports and anti-
port are together known as co-transport.
1. Uniport. In this system the carrier proteins transport
only one type of molecules (Fig. 1.3-5A).
2. Symport. In this system transport of one substance is
linked with transfer of another substance. For example,
facilitated diffusion of glucose in the renal tubular cells
is linked with the transport of sodium (Fig. 1.3-5B).
ECF
Closed
K+
+ + + + +
+ + + +
+ + + + +
− − − − − − − − − −
ECF
ICF
Open
− − − − − − − − − −
+ + + + + + + + + +
+
+
+
+
K+
A
B
Fig. 1.3-3 Voltage-gated potassium channels.
Molecules to be transported
Binding site on the carrier protein
Molecules released from binding site
Conformational change in the carrier protein
Cell
membrane
ECF
ICF
Fig. 1.3-4 Postulated mechanism of facilitated diffusion.
ECF
A B C
ICF
Cell membrane
Fig. 1.3-5 Various types of carrier protein systems: A, uniport; B, symport and C, antiport.
8/8/2011 12:28:48 PM

18
1
SECTION
3. Antiport. In this system the carrier proteins exchange
one substance for another. For example, Na+
–K+
exchange
or Na+
–H+
exchange in the renal tubules (Fig. 1.3-5C).
Differences between simple and facilitated diffusion
1. Specificity. The carrier proteins are highly specific for
different molecules.
2. Saturation. As shown in Fig. 1.3-6, in simple diffusion
the rate of diffusion increases proportionately with the
increase in the concentration of the substance and there
is no limit to it. However, in facilitated diffusion the rate
of diffusion increases with increase in concentration
gradient to reach a limit beyond which a further increase
in the diffusion cannot occur. This is called saturation
point and here all the binding sites on the carrier pro-
teins are occupied and the system operates at its maxi-
mum capacity.
3. Competition. When two molecules, say A and B are
carried by the same protein there occur a competition
between the two molecules for the transport. Thus, an
increase in the concentration of ‘A’ molecule will decrease
the transport of molecule ‘B’ and vice versa. No such
competition is known to occur in simple diffusion.
FACTORS AFFECTING NET RATE OF DIFFUSION
The diffusion of the substance can occur either way, i.e.
extracellular fluid (ECF) to intracellular fluid (ICF) or vice
versa depending upon the prevailing environment. The fac-
tors which affect the net rate of diffusion in the desired
direction are:
1. Cell membrane permeability. Permeability of the cell
membrane (P) is the major determining factor for the
net diffusion, which in turn depends upon the following
factors:
Thickness of the membrane. The diffusion is inversely
proportional to the thickness of the cell membrane.
Lipid solubility. Diffusion is directly proportional to
the lipid solubility of the substance.
Distribution of protein channels in the cell membrane.
The rate of diffusion of lipid insoluble substance is
directly proportional to the number of channels per
unit area of the cell membrane.
Temperature. Rate of diffusion increases with increase
in the temperature. This is because of the increased
motion of the molecules and ions of the solution with
increase in temperature.
Size of the molecules. Rate of simple diffusion is
inversely proportional to the size of molecules.
Area of the membrane. The net diffusion of the sub-
stance is directly proportional to the total area of the
membrane.
2. Concentration gradient. The simple diffusion is directly
proportional to the concentration gradient (Fig. 1.3-7)
but, the facilitated diffusion, however, has certain limita-
tions beyond certain level of concentration gradient
(Fig. 1.3-6B).
Rate
of
diffusion
Saturation point
Extracellular concentration of the substance
50%
100%
A
B
Fig. 1.3-6 Effect of concentration of substance on rate of
diffusion in: A, simple diffusion and B, facilitated diffusion.
Cell membrane
C0
C1
A
B
C
⫹
⫺
Outside
Inside
P1
P2
Fig. 1.3-7 Factors affecting net rate of diffusion: A, concentra-
tion gradient; B, electrical gradient and C, pressure gradient.
8/8/2011 12:28:49 PM

1
SECTION
3. Electrical potential gradient. Electrical potential across
the cell membrane is another important factor which
affects the diffusion of ions across the cell membrane.
As shown in Fig. 1.3-7B, the concentrations of nega-
tive ions are the same on both sides of the membrane,
but there is an electrical gradient across the cell mem-
brane because of positive charge outside and negative
charge inside the membrane. The positive charge
attracts the negative ions, whereas the negative charge
repels them. Therefore, net diffusion occurs from inside
to outside till the concentration gradient created bal-
ances the electrical gradient.
4. Pressure gradient. It has been observed that the
increased amounts of energy are available to cause net
movements of molecules from the high pressure side
towards the low pressure side. The pressure gradient
effect is demonstrated in Fig. 1.3-7C, which shows that
high pressure developed by the piston on one side of the
cell membrane causes greater number of molecules
to strike the membrane resulting net diffusion to the
other side.
OSMOSIS
Osmosis refers to diffusion of water or any other solvent
molecules through a semipermeable membrane (i.e. mem-
brane permeable to solvent but not to the solute) from a
solution containing lower concentration of solutes towards
the solution containing higher concentration of solutes; Fig.
1.3-8 shows osmosis across a selective permeable mem-
brane. When a sodium chloride solution is placed on one
side of the membrane and water on the other side (Fig. 1.3-
8A) the net movement of water occurs from the pure water
into the sodium chloride solution (Fig. 1.3-8B).
OSMOTIC PRESSURE
Osmotic pressure refers to the minimum pressure which
when applied on the side of higher solute concentration
prevents the osmosis. Figure 1.3-8C shows that when
appropriate pressure is applied the net diffusion of water
into the sodium chloride solution is prevented.
The osmotic pressure in the body fluids refers to the
pressure exerted by the solutes dissolved in water or other
solvents. The osmotic pressure exerted by the colloidal sub-
stances in the body is called colloidal osmotic pressure. The
colloidal osmotic pressure due to plasma colloids (proteins)
is called oncotic pressure.
The osmotic pressure depends upon the number of mol-
ecules or ions dissolved in a solution rather than their size,
type or chemical composition.
OSMOLE, OSMOLALITY AND OSMOLARITY
Osmole is the unit used in place of grams to express the
concentration in terms of number of osmotically active par-
ticles in a given solution. One osmole is equal to the molec-
ular weight of a substance in grams divided by the number
of freely moving particles liberated in solution by each
molecule. Thus:
A molar solution of glucose contains 1 mole and exerts
osmotic pressure of 1 atm.
A molar solution of NaCl contains 2 osmoles (1 mole
of Na+
and 1 mole of Cl−
) and exerts osmotic pressure of
2 atmospheres.
A molar solution of CaCl2 contains 3 osmoles (1 mole of
Ca2+
and 2 moles of Cl−
) and thus exerts osmotic pres-
sure of 3 atm.
One milli osmole (mOsm) is 1/1000 of an osmole.
B
A C
Sodium
chloride solution
Osmotic
pressure
Semipermeable
membrane
Water
M
Fig. 1.3-8 Diagrammatic representation of phenomenon of osmosis: A, semipermeable membrane ‘M’ separates sodium chlo-
ride solution from pure water; B, net movement of water occurs through (M) from pure water side into the sodium chloride solution
side and C, demonstration of osmotic pressure (net movement of water from pure water side to sodium chloride solution is
prevented by applying appropriate pressure on the solution side).
8/8/2011 12:28:49 PM

20
1
SECTION
Osmolality of a solution refers to the number of osmoti-
cally active particles (osmoles) per kilogram (kg) of a solu-
tion, whereas, osmolarity refers to the number of osmoles
per litre (L) of a solution. Therefore, osmolarity is affected
by the volume of the various solutes in the solution and the
temperature, while the osmolality is not. The osmotic pres-
sure is determined by the osmolality and not the osmolar-
ity. However, the quantitative differences between the
osmolarity and osmolality are less than 1%. In practice,
osmolarity is more frequently used in physiological studies,
since it is far more easier to measure osmolarity vis-a-vis
osmolality.
Normal plasma osmolality. The normal osmolality of
the extracellular and intracellular fluids is 290 milliosmoles
per kilogram (mOsm/kg). In the plasma of the total osmo-
lality 270mOsm are contributed by Na+
, Cl−
and HCO3
−
.
The remaining 20mOsm are contributed by glucose and
urea. Because of the large molecular weight and hence
lesser number of particles, plasma proteins (70g/L) con-
tribute 2mOsm to the total plasma osmolality.
TONICITY OF FLUIDS
In clinical practice, the word tonicity always refers to tonic-
ity of a solution with respect to that of plasma (290mOsm).
In other words, it is the red blood cell (RBC) membrane
across which the tonicity is tested. Thus:
Isotonic fluids are those which have osmolality similar to
plasma. RBCs neither shrink nor swell in such solution
(Fig. 1.3-9A). A solution of 0.9% NaCl is isotonic with
plasma.
Hypertonic fluids have osmolality higher than the
plasma. The RBCs shrink in such solutions by losing
water by osmosis (Fig. 1.3-9B).
Hypotonic fluids are those whose osmolality is lower
than that of plasma. The RBCs swell up in hypotonic
solutions by gaining water by osmosis (Fig. 1.3-9C).
APPLIED ASPECTS
The total plasma osmolality may increase in patients
having severe dehydration.
Increased blood glucose levels in patients with severe
diabetes also increase the plasma osmolality.
Excessive intravenous administration of 5% glucose
decreases plasma osmolality leading to swelling of the
body tissues.
Hyperosmolality can cause coma by causing water to
flow out of the brain cells (hyperosmolar coma).
Raised plasma levels of urea in patients with renal dis-
eases also cause hyperosmolality.
ACTIVE TRANSPORT
Active transport refers to the mechanism of transport of
substances against the chemical and/or electrical gradient.
Active transport involves expenditure of energy which is
liberated by breakdown of high energy compounds like ade-
nosine triphosphate (ATP). Since the transport of sub-
stances occur against the chemico-electrical gradient, this
process is also called up-hill movement. Substances trans-
ported actively across the cell membrane include:
Ionic substances such as Na+
, K+
, Ca2+
, Cl−
and I−
, and
Non-ionic substances like glucose, amino acids and
urea.
TYPES OF ACTIVE TRANSPORT
The active transport is of two types:
Primary active transport and
Secondary active transport.
A B C
Fig. 1.3-9 Tonicity of fluids: A, isotonic fluid (0.9% NaCl) has osmolarity similar to plasma, RBCs neither shrink nor swell in it;
B, hypertonic fluid (2% NaCl) has osmolarity higher than plasma, RBCs shrink in it and C, hypotonic fluid (0.3% NaCl) has osmolarity
lower than plasma, RBCs swell in it.
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1
SECTION
A. PRIMARY ACTIVE TRANSPORT PROCESSES
In primary active transport process, the energy is derived
directly from the breakdown of ATP or some other high-
energy phosphate compound. Some of the important pumps
involved in the primary active transport processes are:
Sodium–potassium pump,
Calcium pump and
Potassium–hydrogen pump.
1. Sodium–potassium pump
Sodium–potassium (Na+
–K+
) pump is present in all the
cells of the body. It is involved with the active transport of
sodium ions outwards through the cell membrane and
potassium ions inwards simultaneously. Thus, this pump is
responsible for maintaining the Na+
and K+
concentration
differences across the cell membrane and for establishing
a negative electrical potential inside the cells.
Structure of Na+
–K+
pump (Fig. 1.3-10). The carrier pro-
tein involved in Na+
–K+
pump is a complex consisting of
two separate protein units, a larger α subunit (molecular
weight approximately 100,000) and a smaller β subunit
(molecular weight approximately 55,000). The α subunit is
mainly concerned with Na+
–K+
transport. It has got follow-
ing binding sites:
Three intracellular sites, one each for binding sodium
ions (3Na+
) and ATP, and one phosphorylation site.
Two extracellular sites, one each for binding potassium
ions (2K+
) and ouabain.
Mechanism of operation of Na+
–K+
pump (Fig. 1.3-11).
The functioning of Na+
–K+
pump involves the use of
enzyme ATPase. The enzyme ATPase is activated when
three sodium ions and one ATP molecule bind to their
respective binding sites. The activated ATPase catalyzes the
hydrolysis of ATP to ADP and liberates a high-energy phos-
phate bond of energy (phosphorylation). The energy so lib-
erated is believed to cause a conformational change in the
carrier protein molecule extruding sodium into the extra-
cellular fluid. This is followed by binding of two potassium
ions to the receptor site on extracellular surface of the car-
rier protein and dephosphorylation of a subunit which
returns to its previous conformation, releasing potassium
into the cytoplasm.
Functions of Na+
–K+
pump. The Na+
–K+
pump subserves
two main functions:
1. Controlling the cell volume. It is the most important
function of the Na+
–K+
pump, without which most of
cells of the body will swell up until they burst. When the
Na+
–K+
pump fails the cells swell up and burst.
2. Electrogenic activity. Na+
–K+
pump acts as an electro-
genic pump since it produces a net movement of posi-
tive charge out of the cell (3Na+
out and 2K+
in); thus
creating electrical potential across the cell membrane.
This is basic requirement in nerves and muscles to
transmit the signals.
2. Calcium pump
The calcium pump forms another important active trans-
port mechanism. Like Na+
–K+
pump, it also operates
through a carrier protein which has ATPase activity. But
the difference from Na+
–K+
pump is that the carrier protein
binds calcium ions rather than sodium and potassium ions.
The calcium pump helps in maintaining extremely low con-
centration of calcium in the intracellular fluid (10,000 times
less than the ECF).
3. Potassium–hydrogen pump
The primary active transport system of hydrogen ion also
operates through ATPase (K+
–H+
ATPase) activity. These
are present at following two places in the human body:
Parietal cells of gastric glands (see page 465) and
Renal tubules (see page 395).
Cell membrane
ECF
ICF
ATPase
3Na+ binding site
Phosphorylation site
ATP binding site
Ouabain binding site
2K+ binding site
␣
␤
Fig. 1.3-10 Structure of sodium–potassium ATPase pump.
Cell membrane
ECF
ICF
␤
3Na+
2K+
α
Fig. 1.3-11 Mechanism of operation of sodium–potassium
ATPase pump.
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22
1
SECTION
B. SECONDARY ACTIVE TRANSPORT PROCESSES
In secondary active transport processes, the energy is
derived secondarily from the energy which has been stored
in the form of ionic concentration differences between the
two sides of a membrane, created in the first place by pri-
mary active transport. At many areas in the body, transport
of some other substance is coupled with the active trans-
port of Na+
, i.e. the same carrier protein which is involved
in the active transport of Na+
also secondarily transports
some other substance. The secondary active transport of
substance may occur in the form of sodium co-transport or
sodium counter-transport.
Sodium co-transport
The carrier protein here acts as a symport, i.e. transports
some other substance along with the sodium. Substances
carried by sodium co-transport include glucose, amino
acids, chloride and iodine.
Sodium co-transport of glucose. The glucose is transported
into most cells against large concentration gradient. As
shown in Fig. 1.3-12A, the carrier protein has two receptor
sites on the outer surface, one for sodium and other for glu-
cose. The special feature of the carrier protein is that the
conformational change in it occurs only when both the
sodium and glucose molecules are attached to it. Due to
conformational change in the carrier protein both the
sodium and the glucose are transported simultaneously
inside the cell (Fig. 1.3-12B). The co-transport of glucose
occurs during its absorption from the intestine into the
blood and during the reabsorption of glucose from renal
tubule in the blood.
Sodium co-transport of amino acids. Occurs especially in the
epithelial cells of intestinal tract and renal tubules during
absorption of the amino acids into the blood. The mechanism
of sodium co-transport of amino acids is similar to that of
glucose, except that the carrier proteins involved are different.
Sodium counter-transport
The carrier protein involved here acts as an antiport, i.e.
sodium ion is exchanged for some other substance. Some of
the sodium counter-transport mechanism occurring in the
body are:
1. Sodium–calcium counter-transport is known to occur
in almost all cell membranes with sodium ions moving
inside and calcium outside the cell (Fig. 1.3-13).
2. Sodium–hydrogen counter-transport is especially
known in the proximal tubules of kidney. Here the
Na+
ions move inside the cell and the H+
ions move out
of the cell by the same carrier protein.
3. Other counter-transport systems which exist somewhere
in the body are sodium–potassium counter-transport
system, sodium–magnesium counter-transport, calcium–
magnesium counter-transport system and chloride–
bicarbonate counter-transport system.
VESICULAR TRANSPORT
Vesicular transport mechanisms are involved in the trans-
port of macromolecules such as large protein molecules
Cell membrane
ECF
ICF
Na+ binding site
Glucose binding
site
Na+
Glucose
Na+
Glucose
A
B
Fig. 1.3-12 Postulated mechanism of sodium co-transport of
glucose (secondary active transport): A, carrier protein has two
receptor sites, one for sodium and one for glucose and B, con-
formational change in carrier proteins causes transport of both
glucose and sodium inside the cell simultaneously.
3Na+
Counter-transport
Active transport
Co-transport
Passive transport
K+
Cl⫺
Ca++
H+
ATP ADP + Pi
⫺70 mV
Na+
H+
2K+
3Na+
Na+
Na+
K+
K+
Cl⫺
Na+
Na+
K+
Sugar or
amino acid
Fig. 1.3-13 Composite diagram of the cell showing the vari-
ous co-transport and counter-transport mechanisms and main-
tenance of membrane potential as an effect of primary active
transport of Na+
and K+
.
8/8/2011 12:28:50 PM

1
SECTION
which can neither pass through the membrane by diffusion
nor by active transport mechanisms. The vesicular trans-
port mechanisms include endocytosis, exocytosis and
transcytosis.
ENDOCYTOSIS
Endocytosis is the process in which the substance is trans-
ported into the cell by infolding of the cell membrane
around the substance and internalising it (Fig. 1.3-14). It is
further categorized into three types:
1. Pinocytosis, i.e. cell drinking refers to the process of
engulfing liquid substances by the enfolding of cell
membrane, e.g. reabsorption by renal tubular epithelial
cells.
2. Phagocytosis, i.e. cell eating is the process of engulfing
of solid particles, such as bacteria, dead tissue and for-
eign particles by the cells. The process of phagocytosis
involves three steps: (i) the attachment stage, (ii) the
engulfment stage and (iii) killing or degradation stage
(see page 126).
3. Receptor-mediated endocytosis. In this process the
substance to be transported binds with the special
receptor protein present on the cell surface. The recep-
tor protein–substance complex is then engulfed by the
cell membrane by the process of endocytosis. Transport
of iron and cholesterol into the cells occurs by receptor-
mediated endocytosis.
EXOCYTOSIS
Exocytosis (Fig. 1.3-15) is reverse of endocytosis, i.e. by this
process the substances are expelled from the cell without
passing through the cell membrane. In this process, the
substances which are to be extruded are collected in the
form of granules or vesicles which move towards the cell
membrane. Their membrane then fuses to the cell mem-
brane. The area of fusion breaks down releasing the con-
tents to the exterior and leaving the cell membrane intact.
Release of hormones and enzymes by secretory cells of the
body occurs by exocytosis. The process of exocytosis
requires Ca2+
and energy along with docking proteins.
TRANSCYTOSIS
Vesicular transport within the cell is called transcytosis or
cytopempsis. It is quite similar to exocytosis and endocyto-
sis. Three basic steps involved in this process are: (i) vesicle
formation, (ii) vesicle transportation and (iii) docking in
the cell.
OTHER TRANSPORT PROCESSES
So far we have considered transport across the cell mem-
brane, i.e. movement of substances between the ICF and
the ECF through the cell membrane. In addition to this,
there are many situations in the body where transport of
substances occurs through the epithelia and the capillary
endothelial cell membrane. Some of these processes dis-
cussed briefly are:
Transport across epithelia and
Ultrafiltration.
TRANSPORT ACROSS EPITHELIA
Transport across epithelia involves movement of the sub-
stances from one side of the epithelium to the other. The
transepithelial transport occurs in body cavities lined by
continuous sheet of cells, such as in gastrointestinal tract,
renal tubules, pulmonary airways and other structures. For
transepithelial transport to occur, the cells need to be
bound by tight junctions and have different ion channels
and transport protein in different parts of their membrane.
ULTRAFILTRATION
When a solution of protein and salt is separated from plain
water or a less concentrated salt solution by a membrane
permeable to salt and water and not to the protein, there
will be a net movement of water on the protein side by
Endocytic vesicle
Fusion of
non-cytoplasmic
sides
Fig. 1.3-14 Endocytosis.
Cytoplasmic sides of two membranes fuse
Cell membrane
ECF
ICF
Fig. 1.3-15 Exocytosis.
8/8/2011 12:28:50 PM

24
1
SECTION
diffusion and a movement of salt away from the protein
side. This process is called dialysis.
Ultrafiltration refers to occurrence of dialysis under
hydrostatic pressure (see page 441). Ultrafiltration is occur-
ring at the capillary level in the body. The capillary blood is
under hydrostatic pressure. The pressure is 35mm Hg near
the arteriolar end and gradually declines to 12mm Hg near
the venous end of the capillary. Through the capillaries
there occurs ultrafiltration of all the constituents of the
plasma except the proteins into the interstitial spaces.
Ultrafiltration plays important role in the formation of
body fluids (see page 238) (Fig. 4.4-19).
8/8/2011 12:28:51 PM

Membrane Potential
INTRODUCTION
GENESIS OF MEMBRANE POTENTIAL
Selective permeability of the cell membrane
Gibbs’–Donnan membrane equilibrium
Nernst equation
Goldmann–Hodgkin–Katz equation
Role of Na+
–K+
ATPase pump
RECORDING OF MEMBRANE POTENTIAL
Instruments used for recording
Technique of recording
Chapter
Chapter
1.4
1.4
INTRODUCTION
There exists a potential difference across the membrane of
all living cells with the inside being negative in relation to
the outside. This potential difference is named membrane
potential because the cations and anions arrange themselves
along the outer and inner surfaces of the cell membrane.
The magnitude of membrane potential varies from cell to
cell and in a particular cell varies according to its functional
status. For example, a nerve cell has a membrane potential
of –70mV (inside negative) at rest, but when it gets excited
the membrane potential becomes about +30mV (inside
positive). The membrane potential at rest is called resting
membrane potential or resting transmembrane potential or
simply resting potential. The term rest does not imply that
cell is metabolically quiescent but that it is not undergoing
any electrical change. The membrane potential measured
during excited state of the cell is called action potential.
GENESIS OF MEMBRANE POTENTIAL
Membrane potential is basically due to unequal distribu-
tion of ions across the cell membrane, which in turn results
due to the combined effect of various forces acting on
the ions. The factors involved in genesis of membrane
potential are:
Selective permeability of the cell membrane,
Gibbs’–Donnan membrane equilibrium,
Nernst equation,
Constant field Goldmann equation and
Sodium–potassium ATPase pump.
SELECTIVE PERMEABILITY OF THE CELL
MEMBRANE
The cell membrane is selectively permeable, that is, to some
ions it is freely permeable, to others impermeable and to
some others it has variable permeability as:
Ions like Na+
, K+
, Cl−
and HCO3
−
are diffusible ions. The
cell membrane is freely permeable to K+
and Cl−
and
moderately permeable to Na+
.
The cell membrane is practically impermeable to intra-
cellular proteins and organic phosphate which are
negatively charged ions.
Presence of gated channels in the cell membrane is
responsible for the variable permeability of certain ions
in different circumstances.
GIBBS’–DONNAN MEMBRANE EQUILIBRIUM
According to Gibbs’–Donnan membrane equilibrium, when
two ionized solutions are separated by a semipermeable
membrane at equilibrium:
Each solution shall be electrically neutral, i.e. total charges
on cations will be equal to total charges on anions.
The product of diffusible ions on one side of the mem-
brane will be equal to product of diffusible ions on the
other side of the membrane.

26
1
SECTION
To understand let us consider ‘M’ is a semipermeable
membrane separating two ionized solutions of sodium
chloride A and B (Fig. 1.4-1). Then according to the Gibbs’–
Donnan equilibrium:
1. Each solution is electrically neutral, i.e. (cations)A =
(anions)A and (cations)B = (anions)B
OR
(Na+
)A = (Cl−
)A and (Na+
)B = (Cl−
)B.
2. The product of diffusible ions on both sides will be
equal, i.e. (diffusible cations)A × (diffusible anions)A =
(diffusible cations)B × (diffusible anions)B
OR
[(Na+
)A × (Cl−
)A] = [(Na+
)B × (Cl−
)B]
From the above, the concentration ratio of diffusible ions at
equilibrium will be as below:
(diffusible cations)A
(diffusible cations)B
=
(diffusible anions)B
(diffusible anions)A
OR
[Na+
]A
[Na+
]B
=
[Cl−
]B
[Cl−
]A
Thus there will be symmetrical distribution of ions at
equilibrium. But if one or more non-diffusible ions ‘X−
’ are
present on one side (A side) of the membrane, then according
to Gibbs’–Donnan equilibrium the distribution of diffusible
ions will be as under:
1. Both solutions will be electrically neutral, i.e. (Na+
)A =
(Cl−
)A + (X−
)A and (Na+
)B = (Cl−
)B
So, (Na+
)A + (Cl−
)A + (X−
) (Na+
)B + (Cl−
)B …………... (1)
2. The product of diffusible ions on two sides will be equal,
i.e. (Na+
)A × (Cl−
)A = (Na+
)B × (Cl−
)B …….…………….. (2)
From the relationship of (1) and (2), it is found that:
(Na+
)A (Na+
)B and
(Cl−
)A (Cl−
)B.
Hence there is unequal distribution of diffusible ions
(asymmetrical). At equilibrium, Na+
being greater on the
side which contains non-diffusible anions ‘X−
’ (side A) and
anion Cl−
is greater on the other side (side B). However,
their concentration ratio are equal.
Since the intracellular fluid (ICF) contains non-diffusible
anions like proteins and organic phosphate, so, according to
Gibbs’–Donnan equilibrium there should be an asymmetri-
cal distribution of diffusible ions across the cell membrane
with cations being more inside than the outside. However,
in reality interior of the cell is negatively charged which will
be explained in the ensuing discussion.
NERNST EQUATION
The asymmetrical distribution of diffusible ions across the
cell membrane in the form of excess diffusible cation inside
due to the Gibbs’–Donnan equilibrium (as explained above)
results in concentration gradient. As a result of which dif-
fusible cations (K+
) will try to diffuse back into the ECF
from ICF, but it is counteracted by the electrical gradient,
which will be created due to the presence of non-diffusible
anions inside the cell. Thus equilibrium will be reached
between the concentration gradient and the electrical gra-
dient resulting in diffusion potential (equilibrium potential)
across the cell membrane. The magnitude of this equilibrium
potential can be determined by the Nernst equation as:
E(m) = ±61 log
(conc)o
(conc)i
where,
E(m) = Equilibrium potential (in millivolts) of the ions at
which efflux and influx of the ions are equal
R = The natural gas constant and its value is 8.316 joules/
degree.
T = The absolute temperature
F = The Faraday constant and its value is represented as
Number of coulomb/mole of charge =
96,500 coulomb/mole
Z = The valency of the ion
ln = Symbol for natural logarithm
(conc)i = The concentration of the ions in the intracellular
fluid (inside).
(conc)o = The concentration of the ions in the extracellular
fluid (outside).
The equilibrium potential, E(m), for some of the important
ions in the mammalian spinal motor neuron calculated from
the simplified Nernst equation is shown in Table 1.4-1.
GOLDMANN–HODGKIN–KATZ EQUATION
The Nernst equation helps in calculating the equilibrium
potential for each ion individually. However, the magnitude
of the membrane potential at any given time depends on
the distribution of Na+
, K+
and Cl−
and the permeability of
each of these ions. The integrated role of different ions in
Solution A Solution B
Na⫹
Cl⫺
X⫺
M
Na⫹
Cl⫺
Fig. 1.4-1 Semipermeable membrane ‘M’ separates ionic
solutions of sodium chloride A and B.

Chapter 1.4 ¶ Membrane Potential 27
1
SECTION
the generation of membrane potential can be described
accurately by the Goldmann’s constant field equation or the
so-called Goldmann–Hodgkin–Katz (GHK) equation:
V =
RT
F
ln
Pk [K+
]i + PNa+ [Na+
]i + PCl− [Cl−
]o
Pk [K+
]o + PNa+ [Na+
]o + PCl− [Cl−
]i
V = The membrane potential
R = The gas constant
T = The absolute temperature
F = The Faraday constant and
Pk+, PNa+ and PCl− = The permeabilities of the membrane to
K+
, Na+
and Cl−
, and brackets signify concentration and i
and o refer to inside and outside of the cell, respectively.
Inferences of the Goldmann constant field equation
Following important inferences can be drawn from the
Goldmann constant field equation:
1. Most important ions for development of membrane
potentials in nerve and muscle fibres are sodium, potas-
sium and chloride. The voltage of membrane potential is
determined by the concentration gradient of each of
these ions.
2. Degree of importance of each of the ions in determin-
ing the voltage depends upon the membrane permeabil-
ity of the individual ion. For example, if the membrane is
impermeable to K+
and Cl−
then the membrane poten-
tial will be determined by the Na+
gradient alone and the
resulting potential will be equal to the Nernst potential
for sodium.
3. Positive ion concentration from inside the membrane
to outside is responsible for electronegativity inside the
membrane. This is because of the fact that due to con-
centration gradient, the positive ions diffuse outside
leaving the non-diffusible negative ions inside the cell.
4. Signal transmission in the nerves is primarily due to
change in the sodium and potassium permeability because
their channels undergo rapid change during conduction
of the nerve impulse and not much change is seen in the
chloride channels.
ROLE OF NA+
–K+
ATPASE PUMP
The role of Na+
–K+
ATPase lies in building the concentra-
tion gradient. It serves to pump back the Na+
that diffuses
into the cell and K+
that diffuses out of the cell. In the resting
membrane, these diffusions are negligible, so the Na+
–K+
pump works very feebly in this stage. Further, although the
Na+
–K+
pump potentially electrogenic (since it pumps out
3Na+
ions for 2K+
ions), at no stage the pump is able to build
up a significant membrane potential. This is because of the
fact that, as soon as the pump creates a negative potential
inside the cell, chloride ions rush out of the cell and restore
electroneutrality. Thus, in other words, the pump, pumps
out 3Na+
ions and one Cl−
ion for every 2K+
ions it pumps in.
RECORDING OF MEMBRANE POTENTIAL
INSTRUMENTS USED FOR RECORDING
The essential instruments used in recording the activity of
an excitable tissue are:
Microelectrodes,
Electronic amplifiers and
Cathode ray oscilloscope.
Basic principles of the functioning of these instruments
are described on page 55.
TECHNIQUE OF RECORDING
Technique of recording of membrane potential is described
on page 56.
Table 1.4-1 Equilibrium potential, E(m), for important
ions in a mammalian spinal motor neuron
Ion
Concentration
(mmol/L of H2O)
Equilibrium
potential (mV)
Outside the cell Inside the cell
Na+
150 15 +60
K+
5.5 150 −90
Cl−
125 9 −70
Ca2+
5 1 +130

Genetics: An Overview
STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF
SUBSTRATE FOR GENETICS
Chromosomes
Structure and function of DNA and RNA
Genes
General considerations
Gene expression: central dogma
Regulation of gene expression
APPLIED GENETICS
Molecular genetics and biotechnology
Genetic engineering/recombinant DNA technology
Polymerase chain reaction
Blotting techniques
Cloning
Apoptosis
Molecular genetics and medicine
Mutations and genetic human diseases
Genetic screening
Genetics and cancer
Gene therapy
Chapter
Chapter
1.5
1.5
Genetics may rightly be claimed to be one of the most
important branches of biology. Foundation for the present
day genetics was laid by the Mendel’s work published in
1866. He demonstrated that characteristics do not blend
but pass from parents to offsprings as discrete (separate)
units. These units, which appear in the offspring in pairs,
remain discrete and are passed on to subsequent genera-
tions by the male and female gametes each of which contain
a single unit. The Danish botanist Johannied called these
units genes in 1909 and the American geneticist Morgan, in
1912, demonstrated that they are carried on chromosomes.
Since early 1900, the study of genetics has made great
advances. An overview of which is given here in brief.
STRUCTURAL AND FUNCTIONAL
CHARACTERISTICS OF SUBSTRATE
FOR GENETICS
CHROMOSOMES
Waldeyer in 1888 coined the term chromosomes to denote
the thread-like structures present in the nucleus of eukar-
yotic cells during division. It is now established that the
chromosomes are responsible for the transmission of the
hereditary information from one generation to next. There
are 46 chromosomes (23 pairs in all the dividing cells of
the body except the gametes (sex cells which contain only
23 chromosomes) haploid number.
Morphology of chromosomes
Each chromosome is composed of two chromatids con-
nected at the centromere. Each chromatid consists of two
chromonemes. Telomeres are the terminal ends of chromo-
somes DNA molecule.
Morphological types of chromosomes. Depending upon
the location of centromere four morphological types of
chromosomes are recognized (Fig. 1.5-1):
Metacentric chromosomes in which the centromere divides
the chromosomes into two equal arms (Fig. 1.5-1A).
Submetacentric chromosomes. The centromere divides
the chromosomes into two unequal arms (Fig. 1.5-1B).
Acrocentric chromosomes. The centromere is located in
such a way that a very short arm of chromosomes is
visible (Fig. 1.5-1C).
Telocentric chromosomes. The centromere is located at
one end (Fig. 1.5-1D).
Functional types of chromosomes. There are three types of
eukaryotic chromosomes:
Autosomes are the chromosomes present in somatic
cells. The number of autosomes in a cell is fixed and is
expressed as 2n or diploid number.

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