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 0 ~OJ-! p
v _.., wee¥.plo.r\0e.l J

'.\
Preface to the First "'°~'~ P'°~ '
tin my 20 years as at inspirat
teacher, I have always relished teachin g Physiology. It was becaus e of my
love for the

r subject and constan ion from my student s that I could come up with Textbook of Physiology,
- hopefully would lack the inadequacies the student s face in other textboo
which
ks. 1n this age when the basic sciences
the functional
are being vastly update d, this book attemp ts to summa rize the current state of knowle dge about
subject an interest ing and enrichi ng
organiz ation of the human body, taking care to make learnin g of the
e 4>erien ce for the studen ts.
Some of the salient feature s of tlte book are:
eye view of the chapter 's content.
1. A rapid preview has been present ed to help the readers to have a bird's
been incorpo rated to make learnin g
.,. 2. Well labelled diagram s, flow charts and summa rizing tables have
easier.
letters or pin-poi ntin g import ant
3. Highlig hting of import ant terms has been done by using italics, bold
notes.
4. New concep ts and latest develop ments have been include d.
attemp t any questio ns in the form
5. The text has been so present ed that the studen t would find it easy to
of objective type, multipl e choice or essay type after going through the book.
6. Various system ic functions tests have been discuss ed in detail.
7. Applie d aspects of clinically related topics have been discuss ed .
8. The book has been present ed in two volume s for studen ts convenience.
related profess ions like medicine,
For whom is the book intende d? The book is geared to studen ts .in health
ogy. Because of its scope, the text
,. dentistry, nursing , occupa tional therapy, physiot herapy and medical technol
_is useful for students in biological sciences.
•- ! It is imposs ible task to come out with a balance d textboo
k of Physiology, the firs t time round. Still, 1 have
into this book. I am aware that I
tried m y very best by putting forth my life time's experie nces as a teacher
for further improv ement of this
Inly be having shortco mings in this first effort. Sugges tions and new ideas
- -
book shall always be welcom ed and widely appreciated.
and encour agemen t put forth by
1 could not have even conceived this book, had it not been for the help
ation is hereby express ed with
the underg raduate and postgra duate student s of Physiol ogy. Special appreci
rs of the Depart ment of Physiology,
gratitu de for the most assured coopera tion provide d by all the membe
the valuabl e time devoted by Dr
Maulana Azad Medical College, ew Delhi. I acknowledge with thanks
intern, deserve s special thanks for
(Mrs) Urvash i Gupta for correcting the vast manusc ript. Dr S. Suresh, an
his timely valuabl e contrib utions.
and Shri Rajiv Manch anda of M /s.
I extend my heartfe lt thanks and sincere regards to Shri V.K. Manch anda
ation of this book. I am gratefu l
Laser Tech Prints, New Delhi, for giving their valued views for better present
beautif ul diagram s through out the
to Shri Sunil Dutt, Artist, who has given form to my ideas by present ing
book.
me through out my endeav our.
I am immen sely gratefu l for the suppor t my family membe rs have given
Shailes h Jain, nephew Manish and
Indebtness is acknow ledged and appreci ation is express ed to my wife, Smt.
all day to day activities to enable
ns Ashish and Avnish, for providi ng all facilities and keeping me free from
1c to comple te this book. I owe a great deal of my achieve ments
to my respect ed mother Shrima ti Lajwanti
t have seen the light of the day.
· and Tauji Shri Man Singh. Withou t their blessin gs this book would no
a unique unmatc hed personality,
It will be unfair on my part if I fail to pay my gratitud e to Dr Yipin Gupta,
who constan tly and repeate dly inspired me to start the work on this project.
Withou t their sincere efforts my
Finally, I must thank my publish ers, M /s. Avichal Publish ing Compa ny.
dreams would not have materia lized.
Dr AK Jain
 /

Contents
General Physio logy ( ~e o"6'Q 1~'\- 1 r--\~z s~ J 1 -=45
I 1. The Structu re and Functio n of a Cell 3
•
2. Transp ort Across Cell Membr anes 14
• 3. Body Water and Body Fluids 27
• 4. The Memb rane Potenti als 34

47-13 2
• 5. Compo sition and Functions of Blood 49
• 6. The Plasma Proteins 52
7. Haemo globin 58 o

8. Erythrocyte - Red Blood Corpuscle (RBC) 64

9. Jaundi ce 77
• 10. Leucocyte - White Blood Corpus cle (WBC) 82
,.
• 11. Platelets or Thrombocytes 91
·• 12. Coagul ation of Blood 95
o 13. Blood Groups 106
• 14. Lymph oid Tissues and Lymph 114
• 15. Immun ity (The Immun e System) 120

•Q§1 f• ••• Nerve Muscl e Physio logy C e..:15~e 1,-,. · r.~ ~o& ) 133-1 93
® Structure and Function of Nervou s Tissues 135
• 17. Physiological Proper ties of erve Fibers 143
• 18. Nerve Fiber Types and Functions 146
19. Degene ration and Regeneration in Periph eral Nerves 150
• 20. Neurom uscula r Junction 155
21. Skeletal Muscle 160
 22. • Cardiac Muscle 175 }
23.' Smooth Muscle 186
"
1•

~fi~jiitii The Digestive System 195-27 4

: 4. Physiological Anatom y of Gastro- lntestinal Tract (GIT) 197

• 25. Physiolo gy of Salivary Secretio n 203
26. Mouth and Oesoph agus 209
27. The Stomach 214
28. Pancrea s 229
29. Liver and Gall Bladder 236
30. Small Intestine 245 \']9)
31. Large Intestine (Colon) 252
32. Digestio n and Absorp tion in the GIT 259
33. GIT Hormon es 272

··uNIT V 275-39 6
The Cardio-Vascular System (CVS)

.. 34./ Physiological Anatom,y of the Heart 277 3U , -=l-

Properties of the Cardiac Muscle 282 3o, -;:i

36. • The Cardiac Cycle 283

291 30, -:t
37.v The Electroc ardiogram (ECG)
Principles of the Circulation 309 3.0, -=l

39. • Cardio-vascular Regulatory Mechan isms 321

40. • The Heart Rate 335 3o, -=t
;,-

41. • The Cardiac Output 339 30, -=t

42. Arterial Blood Pressure 346 3a ,.-:=t

43. • The Regional Circulat ion 355 '3 O.,

44. • Cardio-vascuJar Homeos tasis in Health and Disease 385 3o ,7

l§§nQ• The Respiratory System 397-49 8

45.11 Physiological Anatom y of Respira tory System 399 ld '.l. ?, 2- g• \

'S' T l
46.\/ Mechanics of Respiration 407 '.2- \ , 28'
 / 47. Transport of Gases 429 2 1., 2....,g
f 48. Regulation of Respiration 439 11.., '1
49. Hypoxia 456 21 , 2~
V 50. Physiology of High Altitude 465 1.., 2.~ .
=.I
v 51. Effects of High Atmosph erit Pressure 472 1.1., 2
I
V 52. Pulmona ry (Lung Function Tests 475 o'.21, .2.i ..
v 53. hysiology of Exercise 477 ~ , ..:2~
V 54. Physiology of Yoga 485 ~'.l..., i

•Q$1 fff•• The Excretor y System @ 499-590

55. Physiological Anatomy of the Kidney 501
56. Mechani sm of Formation of Urine 516
57. Renal Clearance 534
58. Mechanism of Concentration and Dilution of Urine - The Counter Current System 543
59. Acidification of Urine 551
60. Regulation of Volume and Concentration of Body Fluids 557
61. Kidney (Renal) Function Tests 568
62. Physiology of Micturition 573
63. Regulation of Body Temperature in Humans 581

Append ix I
Common ly Used Abbreviations and Symbols in the Textbook
(i)

Append ix II
Ranges of Normal Values in Human Whole Blood (B), Plasma (P) or Serum (S)
(As laid down by WHO) •
(vii)

Append ix III
Contribu tion of Scientists to Physiology

Index
 Unit I

• .. GENERAL PHYSIOLOGY

Chapter 1: The Structure and Function of a Cell

What is Physiology?
Physiological systems
Homeostatic regulation
Structure and function of a cell
Junctional Complexes: Cell junctions
Apoptosis-programmed cell death

Chapter 2: Transport Across Cell Membranes

Passive transport processes: Diffusion, simple, facilitated
Osmosis: Osmotic pressure, tonicity
Active transport processes: Primary (Na+-K+ pump), Secondary, Carrier type (Uniporters,
Symporters, Antiporters)
Vesicular transport processes: Endocytosis (phagocytosis), Pinocytosis Exocytosis
... lntercellular communication (chemical messengers): Protein Kinases, Role of Ca2+ as second
messenger, Receptor and G-protein diseases

• Chapter 3: Body Water and Body Fluids

Introduction
Distribution of total body water (TBW)
Measurement of body fluid volumes and with ionic composition
Units for measuring concentration of solutes: Moles, Equivalents, Osmoles, Concept of pH
and H+ concentration, Concept of buffer system

Chapter 4: The Membrane Potentials

Ionic Composition of body fluids
Gibbs-Donnan membrane equilibrium
Resting membrane potential: definition; genesis; equilibrium potential;
variations in membrane potential
Action potential: origin; phases; ionic basis; properties; electrotonic potentials (graded
potentials); e)ftraccllular (surface) recording - biphasic and monophasic; injury (demarcation)
potential

..
 !

...

,,,.

"'
 The Structure and Function of a Cell
!

.. I. Introduction - What is physiology?

II. Physiological Systems
Ill. Homeostatic Regulation
IV. The Structure and Function of a Cell
V. JunctionaJ Complexes Cell Junctions
VI. Apoptosis-pr ogrammed cell death

INTRODU CTION PHYSIOLOGICAL SYSTEMS

-WHAT IS PHYSIOLOGY? Fig. 1.1 shows the different levels of organization of living
The term physiology was originally derived from a Greek organisms. At a fundamenta l level, atoms of elements link
root with Latin equivalent Physiologia, which denoted together to form mocules. The smallest unit of structure
natural knowledge. It now denotes a study of theft!.nctions capable of carrying out all life processes is the cell. Simple
of the living ocgn1zism as a whole or its constituent parts. organisms are composed of only one celJ, but complex
.... 1. A study of mammalian plzysiologtJ, which is a study of organisms have many cells with different structural and
the dynamic inter-relatio nship among different tissues functional speciliazatio ns. Collection of ceIJs that carry
and organs, is mostly carried out at the oq~anism level. out related function are known as tissues. Tissues form
... structural and functional units known as organs, and
The knowledge of physiology is important to appreciate
the role of mechanism that control bodily functions. group of organs integrate their functions to create organ
2. Clinical Physiology is study of physiological responses system (Fig. 1.2) and (Table 1.1).
or compensatox:y mechanisms that occur in normal
systems when other parts of the body are diseased, HOMEOSTATIC REGULATION
for example, the study of changes in the lungs, liver or In the nineteenth century, Claude Bemard (a French
kidneys when the ~ _,t_goes ,into fajiure. Physiologist) was first to recognize the importance of
3. Applied Physiology is study of underlying mechanisms maintaining a stable intemal environment. The cells, tissues,
that control body functions with aging, during exercise, organs and organ systems of the body are interconnec ted
the effects of low or high barometric pressures, oxygen and live together in a shared (internal) environment. Blood
lack, yoga, meditation etc. forms internal environment of the cell i.e. Milliett foterieur
Physiology is, therefore, the discipline that deals with the in terms of volume, (water) composition, ion concentrations,
bodilv fu nctions and their control. It is Jwwever, only concerned pH and temperature. This is regulated to normal (narrow)
with the normal. physiologica l limits with respect to minor changes in the

..,
Physiology

Molecular Cell
Chemistry Biology Biology

Molecules - Cells - Tlssues - Organs - Organ system - Organisms - Populations of one species
Atoms -

Fig. 1.1 Levels of organization ofliving organisms

3
4 0 UNIT I: GENERAL PHYSIOLOGY

l
Homeostat ic regulation usually involves a receptor,
sensitive to a p articular stimulus and an effector whose
Respiratory ,--- - - , activity affects the same stimulus.
system Nervous

- -
system (Also refer to pages 507, 557).

t
Circulatory
system. A. NEGATIVl~ FEEDBACK MECHANIS MS
Endocrine
Most homeostatic mechanisms involve Nega tive feedback
system i.e. a corrective mechanism involving an action that
(;
directly opposes a variation from normal limits. Therefore, •

--
an increase or decrease in the variable being regulated
brings about :responses that tend to push the variable
in the direction opposite (negative) the direction of the
original change. For example,

via negative feedback

Rise in blood Decrease in B.P.
mechanism
pressure (BF') to normal limits
(a stimulus) (response)

HM@
Here the initial stimulus produces a response that
depresses the stimulus i.e. stimulus and response
Fig. 1.2 Physiological o rgan systems in the h uman body _J are opposite to each other.

In general, the nervous system performs corrective

.... _
body. A variety of physiological mechanisms which act to managemen t by directing rapid, short-term and very
stabilize the internal environment, are called Homeostasis specific_response. On the other hand, the endocrine system
Mechanisms (A term coined by an American physiologis t releases chemical messengers (hormones) that affect tissues
W. B. Cannon in the twentieth century). The adjustments and organs throughout the body. The response may be
in physiological systems that are responsible for the slow to begin with but often persists for days or weeks.
preserva ti.on of h omeostasis are referred to as Homeostatic However, both systeim are usually cgntrolled by nega~ve
Regulation. feedback mech anisms.

Table! 1.1: Organ Systems of the Huma 1 Body

System Name Organs (or tissues) Function(s)
1. Circula tory Heart, blood vessels, blood Transp ort of mate.rials between all cells of the body
2. Digestive Stomach, intestines, liver, pancreas Conversion of food into particles that can be transported into
the body; elimination of wastes
3. Endocrine Thyroid gland, adrenal g land etc. Coordination of body function through synthesis and release of
regulatory molecules
4. Immune Thymus, spleen, lymph nodes Defence against foreign invaders
5. Integumentar y Skin Protection from external environment
6. Musculoskeletal Skeletal muscles, bones Support and movement
7. Nervous Brain, spinal cord Coordination of body function through electrical signals and
release of regulatory molecules
8. Reproductive Ovaries and ute rus, testes Production of the :species
.,.
9. Respiratory Lungs, airways Exchange of oxygen and carbon dioxide between the internal
and external envir,orunents
10. Urinary Kidneys, bladder Maintenance of water and solutes in the internal environment;
waste removal
 CHAPTER I: THE STRUCTURE AND FUNCTION OF A CELL O 5

8 . POSITIVE FEEDBACK MECHANIS MS Nucleus

In few instances homeostatic regulation involves Positive Cytoplasm
feedback mechanisms. i.e. an initial disturbance in a system
sets off a chain of events that increases the disturbance
even further. Therefore, it does not usually favour stability
and often abruptly displaces a system away from its
.._ steady state operating point.

Example Mar1(ed fall in B.P. (stimulus)

Decreased blood supply to the heart

Decrease in myocardial contraction

Further fall in the B. P. (response) ri4-- - Endoplasmic

Reticulum

UMN
Here, the initial stimulus produces response that
Mitochondrion
Microtubule
reinforces (exaggerate s) the original stimulus.
fig. 1.3 Structure of a Generalised Ceil
Positive feedback mechanism can sometimes be ----- ---~
useful:
(B) Nucleus and its chromosom es
(C) Cytoplasm and its organeUes
-· Example 1. Injury to blood vessels

Initiates clotting processes

The clear fluid portion of the cytoplasm in which the
Clotting proceeds
particles are dispersed is called cytosol.
•
Release of chemicals A. CELL MEMBRAN E or PLASMA MEMBRAN E
or UNIT MEMBRAN E
Enhances clotting processes
·-
-(,
Thickness
.· 70-100 Angstrom (A) or 7-10 nanometer (nm)
Seals break in blood vessel wall (1 nm = 10-9 mts; IA= 10-10 mts).
Example 2. Refer to page 805
Structure (Auid Mosaic Model) ( f 16 .••)
(Also refer to page 656)
1. All membranes consist of a double layer of lipid
molecules in which proteins are embedded. The lipids
mE STRUCTURE AND FUNCTIO N
OF A CELL Transmembrane Glycoproteins
The fundamenta l unit of life is a cell, since virtually proteins

all tissues and any organised activity can be equated

to the cellular level. Though no typical or generalised
cell exists, it is convenient to create one to serve as a
conceptual model within which most cell functions can
be incorporated . (Fig. 1.3)

UM§
Most cells in a human being have diameters of
10-20 µm (range 2-120 µm).
Phosp 01p1d
bilayer
1
The three principal constituents of a cell are:
(A) Cell membrane
I_!~g. 1.4 Cell Membrane: Fluid Mosaic Model
 6 0 UNIT I: GENERAL PHYSIOLOGY

normally constitute 20-40% of the dry weight of the hydro phob ic), contains two fatty acid chains. The
membrane. hydrophobi c ends facing each other meet in the
2. Proteins make upto 60-70% of the dry weight of the water-poor interior of the membrane.
membrane and are of 2 types:
(i) Lipoproteins (proteins containing lipids): function Important Note
as enzymes and ion channels. The bimolecular lipid layer in the membrane has
(ii) Glycoproteins (proteins containing carbohydrat es the characterist ics of a fluid due to presence of
constituting 1-5% of the dry weight): function as cholesterol. This fluidity makes the membrane quite
receptors for hormones and neurotransm itters. flexible, thus allows cells to undergo considerabl e
Some proteins are located in the inner surface of the changes in shape without disruption of their
membrane (intrinsic proteins); some are located in the structural integrity.
outer surface of the membranes (extrinsic and peripheral
proteins); while some extend through the membrane Functions
(transmemb rane proteins): 1. Protective - it forms outermost boundary of the cell
(i) Intrinsic proteins serve mainly as 'enzymes'. organelles.
(ii) Extrinsic proteins contribute to the cytoskeleton 2. Digestive - takes in food and excretes waste products.
(framework of the cell). 3. Property of selective penneabilit y:
(iii) Transmemb rane proteins serve as: (i) No11-polar molecules (gases like 0 2, CO and N ,
2 2
(a) Channels, through which ions or small water lipids, steroid hormones, alcohol) can dissolve in
soluble substances can diffuse (pages 15 and the non-polar regions of the membrane and thus
521). move rapidly across the membrane. Polar molecules
(b) Carriers, which passively or actively transport (water soluble substances: ions, glucose, urea etc.)
materials across the lipid layer (pages 20 and have much lower solubility, therefore, penetrate
520). the membrane much more slowly.
(c) Pumps, which actively transport ions across (iii) Chemical and physical characteristics of the
the lipid layer (pages 18 and 520). membrane control the free passage of ions and
(d) Receptors, which when activated initiate
intracellular reactions. The number of
molecules into and out of the cell.
This property of selective permeability of the cell
..
receptors in a cell are not constant but their membrane helps ii"" maintaining the difference of
number increases and decreases in response composition between ECF and ICF (page 29).
to variou stimuli, and their properties change 4. lttsulating properties: It act as the cjj_electric material
with change in physiological condition. For ~ (such as rubber) of a charged condenser, thus the cetr
example, when a hormone or neurotransmitter~ membrane has a very high insulating value.
is present in excess, the number of active 5. It provides a framework for the arrangemen t of an
receptors decreases (called lo L 'i' l 1 , 1); ordered sequence of protein molecules (enzymes,
whereas during their deficiency, the number pumps, receptors, ions, channels, Co-factors, carriers)
of active receptors increases (called in a functionally meaningful pattern.
I ) (Also refer to page 651). These 6. It links adjacent cells together by junctional complexes
effects on receptors are of physiological to form tissues (page 10).
significance in explaining the phenomeno n
of denervation hypersensit ivity (pages 171 Summary: Cell membrane components and Functions
and 189) and tolerance to certain drugs. (Fig. 1.5)
3. The clear area formed by bimolecular thickness of lipid
molecules (phospholip ids, cholesterol and glycolipids) B. NUCLEUS AND ITS CHROMOS OMES
is arranged as follows: (Fig. 1.4) Structure
(i) Head end: contains phosphate portion, is positively 1. It is a spherical structure (10 µm diameter) surrounded
charged and quite soluble in water (i.e. polar or by a relatively permeable membrane called 1111clear
hydrophilic ). Polar groups of lipid molecules membrane (or envelope). This is composed of two unit
have affinity for water (water loving) and face the membranes and shows large pores of 1000 A diameter
aqueous phase i.e. exterior of the cell on one side which are closed by thin homogenou s membrane.
(ECF) and cytoplasm on the other (ICF). Therefore, passage of macromolecules like RNA can take
(ii) Tail end: quite insoluble in water (no affinity place through these pores. The space between the two
for water/ water fearing) (i.e. no n-polar or folds is 300 A and is called perim1clear cistern. (Fig. 1.6)
 CHAPTER I: THE STRUCTURE AND FUNCTION OF A CELL O 7

Cell Membrane

Consists of

Cholesterol Phospholipids, Sphingolipids Carbohydrates Proteins

•
Together form Together form Together form

t t t
Lipid bilayer Glycoliplds Glycoproteins

I
Functions as

i
Selective barrier t
Whose functions include

i t
between cytosol and Structural Cell Immune
external environment stability recognition response

Fig. 1.5 M embrane comp onents and functions

is conveyed from the nucleus to the cytoplasm by

messenger RNA where actually the synthetic work of
the cell takes place.

-· UMN
80% of the dry weight of nucleus is protein, the
! . remainder is made up by 18% DNA and 2% RNA.
.- Nuclear envelope

2. Genes are units of hereditary characteristics.

Nuclear pores - - - --¥ 3. It is concerned with cellular reproduction and
multiplication; the development of chromosomal
Fig. 1.6 Nucleus
threads form the network, being the first step towards
cell division.
2. It is made up of chromosomes (each chromosome is
made up of supporting protein plus giant molecule C. CYTOPLASM AND ITS ORGANELLES
of Deoxyribonucleic Acid-DNA), on which genes are 1. Endoplasmic Reticulum (ER)
present. Gene is a portion of DNA molecule which It is a complex series of tubules whose walls are made
carries a complete blue print for all the heritable species up of unit membrane. Through this network of tubules,
and individual characteristics of an animal. During cell substances may be delivered from the outer membrane
division, the pairs of chromosomes become visible, but of cell proper to the membrane of the nucleus or to other
between cell divisions the irregular clumps of dark inclusion bodies of the cells e.g. mitochondria (Fig. 1.7).
material called chromatin are the only evidence of
their presence.
3. It contains a nucleolus which is densest of all the
nuclear material i.e. a patch work of granules rich in
Ribonucleic Acid (RNA). N ucleoli are most prominent
and numerous in growing cells. They synthesize the
RNA for the ribosomes. Rough endoplasmic
reticulum
Functions
l. DNA in nucleus serves as a 'template' (block) for
Smooth endoplasmic
synthesis of RNA, which then moves to the cytoplasm
reticulum
where it regulates the synthesis of proteins by the
Fig. 1.7 Endoplasmi c Reticulum (E.R.)
cells. The information coded into the DNA molecules
8 O UNIT I: GENERAL PHYSIOLOGY

Types 4. It adds certain carbohydrates to proteins to form

(i) Agrmwlnr or Smootli ER: Contains no granules. glycoproteins, which play an important role in the
(a) It is site of steroid (Adrenocortical hormone) association of the cells to form tissues.
synthesis in steroid secreting cells and the site
of detoxification processes in other cells. 3. Mitochondriion
(b) As the sarcoplasmic reticulum, it plays Structure •
important role in skeletal and cardiac muscle (i) Length 5--12 µm; diameter 0.5-1 µrn; filamentous or
(page 160). globular in shape; occur in variable numbers from
(ii) Granular or Rough ER or Ergastoplasm.
(a) Contains granules called ribosomes (diameter
a few hul[ldred to few thousands in different cells.
(ii) Made up of outer membrane and inner membrane.
-
15 nm; contains 65% RNA and 35% protein: Inner membrane folded to form cristae (shelves)
Ribonucleoprotein) which are attached to the which project into the interior of the mitochondrion.
cytoplasmic side of the membrane. 3-5 ribosomes (Fig. 1.9)

I-
clump together to form polyribosomes or
polysomes. Outer membrane
(b) It is the site of protein synthesis e.g., hormones
Inner membrane
that are secreted by the cell; and proteins that
are found in enzymes.
rg c mole,cules i
and 0 2
(c) Free ribosomes are also found in the cytoplasm,
they synthesize cytoplasmic protein e.g.,
Haemoglobin.

2. Golgi Complex (or Golgi Bodies)

It is a collection of membranous tubules and vesicles found enzymes
always in the neighbourhood of the nucleus, prominent
in actively secreting gland cells. (Fig. 1.8)
- Matrix
Secretory ·-
vesicles Fig. 1.9 Mitochondrion

(iii) Outer memb ·ane: Studded with the enzymes

concerned! with biological oxidation (oxidation being
catalyzed by enzymes).
(iv) Interior (matrix) of mitochondrion contains enzymes

,,
.
Transport
vesicles
concerned w ith 'citric acid cycle' (page 604) and
'respiratory chain oxidation' (page 598).
(v) Inner membrane contains adenosine triphosphatase
(ATPase) and other enzymes concerned with
synthesis and metabolism of ATP.

Functions
IFig. 1.8 Golgi Co_m...:.
~_lex _ _ _ _ __ (i) Mitochondria are power generating units of the cells
and are plentiful and best developed in parts of
cells where energy requiring processes take place
Functions e.g. rapidly contracting skeletal muscles where they
1. Wrapping and packaging department of the cell. comprise 40-50% of the cell volume.
2. Produces sccrctio11 granules i.e. membrane enclosed
complexes, which store hormones and enzymes in
(ii) Also contain DNA and can synthesize proteins. ..
protein secreting cells; it packages proteins. 4. Lysosomes
3. Site of formation of lysosomes i.e. large irregular Structure
structures surrounded by membrane which are present 1. These are large irregular structures surrounded by
in the cytoplasm. unit membrane and are found in the cytoplasm;
 CHAPTER I: THE STRUCTURE AND FUNCTION OF A CELL D 9

250-750nm in diameter. A typical cell may contain 6. Centrioles or Centrosomes

several hundred lysosomes. Stnicture
2. It is filled with large number of small granules, (i) These are two short cylinders called 'centrioles' visible
5-8 run in diameter which contain variety of enzymes, only during cell division.
called lyso zymes (Table 1.2). (ii) They are located at each pole near the nucleus and
are so arranged such that they are at right angles to
!.
Table 1.2: Lysosomal enzymes (lysozymes) and the each other.
substrates on which they act (iii) Tubules in group of three (triplets) run longitudinally
• Enzymes Substrate in the walls of the centrioles. There are nine of
these trip)f.ts spaced at regular intervals around the
(i) Ribonuclease RNA
circumference.
(ii) Deoxyribo DNA
nuclease Function
(iii) Phosphatase Phosphate esters They are concerned with the movement of the
(iv) Glycosidase Complex carbohydrates, glycosides chromosomes during cell division.
and polysaccharides
(v) Arylsulphatases Sulphate esters 7. Microtubules and Microfilaments
Microhtbules are long hollow structures approx.
(vi) Collagenase Collagen proteins 25 run in diameter; make up stnl,dures ar tracts ao whir},
(vii) Cathepsins Proteins chromosomes, mitochondria and secretion g:ran~ move
from one part of the cell to another (Fig. 1.10 and 1.11).
3. The interior is kept acidic (near pH 5.0) by the action
of proton pump or H+ or ATPase. Lysozymes are all acid
hydrolases as they function be~ at the ~idic pH
..
Functions
(i) Acts as a form of digestive (lytic) system for the cell,
because enzymes present in it can digest essentiajJy
• a ll roacroroale~-
(ii) Engulf worn out components of the cells in which
they are located. .
(iii) Engulf exogenous substances e.g. bacteria etc. and
degrade them.
(iv) When a cell dies, lysosomal enzymes cause autolysis
of the remnant i.e. why lysosomes are called as
suicidal bags. Fig. I. JO Microtubule
----------
5. Peroxisomes
(i) Its structure is similar to that of lysosomes but Microfilaments are long solid fibers 4-6 nm in diameter.
with a diHerent chemical composition. It contain They comprise the contractile protein actin and are
oxidases (enzymes that produce H 20 2) rather than responsible for the cell motion. (Fig. 1.11)
hydro lases.
(ii) They consume oxygen in small amounts that is not
used in the chemical reactions associated with ATP Functions
formation. These are involved in the:
(iii) They destroy certain products formed from oxygen, (i) movements of the chromosomes;
especially hydrogen peroxide, that can be toxic to (ii) cell movement;
the cells, hence the name peroxisomes. (iii) processes that move secretion granules in the cell;
and
UMN (iv) movement of pr~ins within the cell membrane.
The alcohol, a person drinks is mainly detoxified by
the peroxisomes of the liver cells. 8. Secretion Granules: Page 8.
10 0 UNIT I: GENERAL PHYSIOLOGY

Rough endoplasmic - - - =::~

reticulum •
.1'
Mitochondrion

Intermediate

fllam)

Actin monomer

monomer
Tubulin
P•Tubulin dimer
Fig. 1.11 Cytoskeleton monomer

Important Note are subjected· to stretching, such as the skin.

..
All cells have a system of fibers called cytoskeleton 3. Gap Junction or Nexus: There is 2 nm to 20 nm space
that maintains the stn,icture of the cell. It allows a between the opposing membranes. This gap is filled
cell to change shape and also permits its movement. with d ~ v packed particles through each of which
The cytoskeleton comprises of microtubules and there appears to be a channel that connects the two
microfilaments, along with proteins that bind them cells. The diameter of each channel is regulated by
together (Fig. 1.11). intracellular Ca2+, pH and voltage.
Other advantages of gap junction:
(i) It permits rapid propagation of electrical potential
JUNCTIONAL COMPLEXES: changes from one cell to another, e.g . cardiac and
CELL JUNCTIONS smooth muscle cells (page 175).
The cells are associated into tissues by various means (ii) It permits the direct transfer of ions and other
(Fig. 1.12): small molecules upto MW 1000 (e.g. sugars, amino
l. Tiglzt Junction: In this, membranes of two cells become acids) b,etween the cells without traversing the
opposed and outer layers of the membranes fuse extracellular space.
strongly, thus obliterating the space between the cells.
This type of junction is characteristically seen along
the apical margins of cells in epithelium such as the
Important N m
Cells are attached to each other by cell adhesion
intestinal mucosa, the walls of the renal tubules, and molecules (CAMs).They also transmit signals into and
the choroid plexus. Tight junction forms a barrier to out of the cell. These adhesion proteins (viz. laminin,
the movement of ions and other solutes from one side intergin,IgG,cadherin,selectin)playimportantrolein:
of the epithelium to the other. (i) embryoniic development
2. Desmosomes or Adherens Junction: Here two membranes (ii) formation of the nervous system
are separated by a 150-350 A (15-20 nm) space. There (iii) holding ti ssues together
is dense accumwation of proteins on both the surfaces (iv) inflammattion and wound healing, and
of the membrane with fibers extending from the (v) metastasis of tumours.
cytoplasmic surface of each membrane into the cell. Cells with abnormal CAMs have a higher rate of
apoptosis (see below).
This holds adjacent cells firmly together in areas that
 • 1
CHAPTE R I: THE STRUCTURE AND FUNCTION OF A CELL O
11

--= t~~=~~_.,
.:

Plasma
Plasma membrane
membrane

"\~liNt.9
''f.,
! Tight - -~ - - ----,.,.• mw,r o.
junction
. ~'Ol'\":f
·- Extracellular - - -- ----1- • t~o'(IO\c\
space
'f>\e.J..~ Extracellular - -- --
space
- --.
Lumen
Extracellular - -- ~
side
pathway blocked
by tight junction Lumen
side

Blood
side Blood
Transcellular pathway
across epithelium side

(A) Tight Junction (B) Desmosome or Adherens Junction

Plasma membrane

- - -- - - 1.5 nm diameter channels linking

cytosol of adjacent cells

Lumen
side

Blood
side

(C) Gap junction or Nexus

lFig. 1.12 Junctiona l complexes (cell junctions)

--- --- --- --- -
Import ant Note
APOPI'OSIS:
PROGRAMMED CELL DEATH Cell necrosis or cell murder is a process in which
It is a Greek word which means looseni ng or neighb ouring healthy cells are destroy ed by a
disease such as inflamm ation. Howev er apoptos is
falling. (Apo means 'a.way' and Ptosis means 'f~ ')
is an orderly cell death in which neighbo uring cells
1. Apopto sis is a process of program med cell death in
usually remain healthy.
which body cells die and get absorbe d (phago cyt~ed)
under genetic control. Here cell's own gene pla~s an
active role on its death, therefore:-=also called as ~/ Mechan ism. Apopto sis may be initiated by:

-
suicide. (i) environ mental processes such as inflamm ation
12 D UNIT I: GENERAL PHYSIOLOGY

(ii) internal stimuli I,~ ~ f . i!.~ (i) it is responsible for regression of duct system
(iii) I a,, a transmembrane protein produced by natural during sex differentiation in the foetus;
killer cells (page 122) and T-,4unphocyes N Kc.-t.Ul (ii) it is responsible for degeneration and regeneration
(iv) Tumour necrosis factor. l1N P) of neurons within the CNS and for the formation
The ultimate pathway initiating apoptosis is acfivation of synapse;
of group of cysteine proteases inactivate enzymes (iii) it is responsible for removal of inappropriate clones
(together called as, (nspascs) within the mitochondria. · of immune cells· l~ .•
The activated apoptotic gene causes the cell to undergo (iv) it is responsible for cyclical ~ edding of
DNA fragmentation, condensation of cytoplasm and .. endometrium at the time of menstruation; and
chromatin; finally the cell break up and remnants are (v) it is responsible for cell shed from the tip of the
removed by phagocytes. villi in the small intestine. (;.11
2. Pltysiological sig11ifica11ce. Apoptosis plays an 3. Applied. Abnormal apoptosis occim""in autoimmune

-
important role during embryonaJ development and diseases (page 128), degenerative diseases and
aJso in adulthood. It removes un-needed cells. For cancers.
example,

tMN-MiiiH:ti
1. Give physiological significance of:
(i) cellular cytoskeleton (ii) Millieu interieur (iii) homeostatic regulation (iv) Junctional complexes
2. Give the electron microscopic structure of the cell membrane.
3. Justify the term 'fluid mosaic model' for the cell membrane structure. Which cell membrane component is responsible
for its fluidity? --
4. Give the role of the cell membrane in maintaining the difference of composition between ECF and TCF.
5. List the prominent cell organelles. Briefly describe the structure and functions of any one of them.
6. Describe the structure and function of the different types of junctions found between cells.
7. Give an account of programmed cell death. How is it initiated? Give its physio-clinical significance.
8. Write sh ort notes on:
(i) Peroxisomes (ii) Lysosomes (iii) Cell adhesion molecules
(iv) Negative versus positive feedback mechanisms. (v) Caspascs

Hti·I
1. On weight basis, the cell membrane contains protein and lipid in the ratio of:
(a) 1:2 (b) 1:1 (c) 2:1 (d) 4: 1
2. One major function of the cell membrane is:
(a) Protective (b) Digestive
(c) Property of selective permeability (d) Links adjacent cells together to form tissues
3. Main function of nucleus is:
(a) To control chemical and physical characteristics of the cell
(b) To bring about cellular reproduction and multiplication
(c) To synthesize protein for the cell
(d) To help in cellular mo~ment
4. Endoplasmic reticulum is associated with all of the followings except:
(a) Enzymatic secretion (b) Lipid secretion
(c) Glycogen synthesis (d) Glyc@genolysis
5. Mitochondria are plentiful and best developed in parts of cells where:
(a) Active protein synthesis takes place (b) Energy requiring processes take place
(c) Active detoxification process is going on (d} Active secretion occurs
 CHAPTER I: THE STRUCTURE ANO FUNCTION OF A CELL O 13

6. Peroxisomes:
(a) Their structure and chemical composition is similar to that of lysosomcs
(b) They destroy products formed from oxygen, cspecrally hydrogen peroxide
(c) They engulf exogenous substances and degrade them
., • (d) They consume oxygen in large amounts, hence the name peroxisomes
7. Cytoskeleton comprises:
(a) Microtubules and microfilaments (b) Cell membrane
(c) Golgi complex (d) Cell junctions
• 8. All are hue for gap junction, except:
(a) It permits rapid propagation of electrical potential changes from one cell to another
(b) It permits direct transfer of ions between the cells
(c) It is traversed by a channel that connects the two cells
(d) It is plentiful in skeletal muscle cells
9. Which of the following is false about apoptosis?
(a) It is a process of programmed cell death
(b) It is also called as cell suicide
(c) It plays an important role during embiyonal development
(d) It occurs as a natural process in autoimmune diseases
10. Which of the following m oves rapidly across the cell membrane?
(a) CO2 (b) Water (c) Glucose (d) Urea
11. The bimolecular lipid layer in the cell membrane has the characteristics of a fluid due to presence of:
(a) Phospholipids (b) Cholesterol (c) Glycolipids (d) Glycoproteins

.. 14,tt#Ui
1. (d) 2. (c) 3. (b) 4. (c) 5. (b) 6. (b) 7. (a) 8. (d) 9. (d) 10. (a) 11. (b)

---CXX)I----
Transport Across Cell Membranes
I. Passive Transport Processes:
(A) Diffusion: simple, facilitated (B) Osmosis: osmotic pressure, tonicity ·"
II. Active transport processes:
(A) Primary (Na+-K+ pump)
(B) Secondary
(C) Carrier type (uniporters, symporters, antiporters)
(D) Vesicular transport processes: endocytosis (phagocytosis), pinocytosis, exocytosis
III. Intercellular communication: chemical messengers

Substances move through the cell membrane by two major (iv) It is the only form of transport that is not carrier
processes: passive and active. Passive transport requires no mediated.
energy; active transport on the other hand does consume (v) Factors affectmg diff11sio11. The 'rate' at which a
energy. material diffuses through a membrane (flux) is given
by Fick's law of diff11sio11 i.e.
PASSIVE TRANSPORT PROCESSES Net rate of diffusion (flux) =
Here substances move across the cell membrane without
...
Diffusion coefficient (D) x
any energy expenditure by the cell. It includes: Diffusion Area of the membrane (A)
and Osmosis. - - -- - - - -- - X (Cin- cout)
Thickness of membrane
(or diffusion distance) (T)
A. DIFFUSION
Diffusion is a passive process (i.e. no external source of Cin and Cout = Concentration of the material inside and
energy is required) by which molecules move from areas outside of the membrane. The negative sign indicates that
of high concentration to areas of low concentration (down the material is moving down its concentration gradient.
their 'chemical gradient'); and cations (positively charged (Also see to page 355)
molecules) move to negatively charged areas whereas (a) Distance: The greater the distance, the longer
anions move to the positively charged areas (down their the time required. 1n the human body, diffusion
'electrical gradient'). It is of two types: distances are usually small as diffusion of
(1) simple diffusion, and substances occurs across the cell membranes of
(2) facilitated diffusion. uniform thickness (10nm).
(b) Size o_r tlze gradie11t: The larger the concentration
1. Simple Diffusion gradient, faster the diffusion proceeds.
Characteristic features (c) frmperature: The higher the temperature, faster
(i) It occurs because the heat content of the solution the diffusion rate. At normal body temperature of
keeps the solvent and the solute particles of the 37°C diffusion is optimal (maximum).
solution in constant motion. (d) ,\,JoleC11larsize:Thepermeabilityofcellmembrane to
(ii) Net movement stops when the concentration of the a substance falls rapidly with increase in molecular
molecules is equal everywhere within the solution weight in the range between 10,000 to 60,000. This
(diffusional equilibrium). is why glucose diffuses faster than large proteins.
(iii) Although random movements of the molecules (e) Lipid solubility.
continue after diffusional equilibrium is achieved, - Lipid soluble molecules (02, CO2, N 2 and alcohols)
the concentration of the molecules throughout the diffuse rapidly with ease through the lipid layer
solution remains the same. of the membrane.

14
 CHAPTER 2: TRANSPORT ACROSS CELL MEMBRANES O 15

- Water soluble molecules (ions, glucose, urea) can Gated cliamrels have gates that open or close either:
cross the cell membrane slowly as they diffuse (i) by alteration in membrane potential (voltage
through the aqueous channels formed by gated) e.g. Na+ and Ca2+ channels (page 156); or
transmembrane proteins. (ii) when they bind a ligand i.e. either an ion or a
specific molecule (ligatz1 §.:!/aJ- The ligand is
Ion channels ?o~€ ~' '11\ou...\ Qo}t_. either external (e.g. neuN>~ansmitter - page 156 "">
'Ions' also utilize ionic diannels to cross th~ cell membrane. or a hormone) or intern~ (e.g. intracellular Ca 2+, U 't
·- Some channels are continuously open, whereas others are cAMP, or G protein pro uced in the cells - page
• 'gated' (Fig. 2.1). 654) (fig. 2.2). ~r6W\~
Some channels are also opened by mechanical

I
Ions stretch (mechanosensitive cha1111el - pages 190,867), -f>V-.
i
• Cell membrane
which play an important role in cell movement.

• i r
• • • • • • • ••
• • • •• Ligand• --+

•••• •
i
•• Cytosol

Closed
Fig. 2.1 Ion channels
Open

_J
•
Closed Open

,'\l Fig. 2.2 Ligand gated channels

There af'ion chann~ls specific (for Na+, K+, Ca2 + and
cl-) and non-specific (for cations or anions). Each type of
channel exists in multiple forms with different properties.
Most are made up of identical or very similar protein lmP.ortant Notes
-- subunits. For example: I\) 0 N, Gtoie!l '\Ont~ 1. The variation in the membrane permeability in
1. K+ channels are tetramers with four different cell membranes reflects differences in
similar protein subunits through the number of ion channels in th membranes.
which K+ pass. Similarly aquaporin 2. Thee tracellular liga s are calle rst messengers
water channels (page 530) are and the · tracellular m ·a tors are IJed second
tetramcrs with an intracellular messengers. e second essengers enerally
activate prate· kinases (page 654).
channel in each protein subunit.

2. Ligand gated cations or anion

channels (see below) have five 2. Facilitated Diffusion
identical protein subunits. Clzaraderistic features
(i) It is a carrier-medi.ated process that enables molecules
that are too large to flow through membrane channels
by simple diffusion (Fig. 2.3). For example,
3. Several types of c 1- channels arc (a) glucose transport by the glucose transporter (GLUT)
dimers with an intracellular pore in across intestinal epithelium (page 260), and
each subunit. {b) the transport of glucose into RBCs, muscles and
adipose tissue in the presence of insulin.
(ii) It is more rapid than simple diffusion.
Applied: Ion channel mutations cause a variety of (iii) The carrier protein undergoes repetitive spontaneous
channelopatl1ies - diseases that mostly affect muscle and configurational changes during which the binding
brain tissu e and produce: periodic paralysis, myotonia, site for the substance is alternately exposed to the
myasthenia or convulsions. ICF and ECF.
 16 D UNIT I: GENERAL PHYSIOLOGY

• • • Glucose molecules
•••••
• Binding site

'·

.. -·
1·
'
!• ...i ' •••
I
I
I

Transmembrane carrier protein •• • • •

Fig. 2.3 The facilitated diffusion of glucose

(iv) Its rate of diffusion increases with increase in from one side of the membrane to another, called No11-
concentration gradient to reach a plateau when all io11iL 1lirJ11 io11 . This phenomenon is seen in the GIT and
the binding sites on the carrier proteins are filled kidneys.
(Fig. 2.4). This is called 'saturation'.
B. OSMOSIS
Simple diffusion
Definition: Osmosis is the passive flow of the solvent
e.g. water across a selectively permeable membrane (i.e.
membrane permeable to so~yent but not to the solute),
Facilitated diffusion
into a region where there is a higher concentration of a
solute to which the membrane is impermeabfe.

The Osmotic Pressure

• 0 The tendency for m9vemenf of solvent molecules to pass
across a membrane from a low concentration of solute to a
a: ,.__ _ _ _ _ _ _ _ _ _ _ _ _ _ __ region of greater solute concentration can be prevented by
Concentration gradient applying pressure to the more concentrated solution. The
Fig. 2.4 The diffusion rate (simple and facilitated) compared amount of pressure exactly required to prevent solvent
migration (i.e. osmosis) is called the osmotic pressure of the
solution (fig. 2.5).
(v) There are many types of carrier proteins in membranes, Osmotic pressure of a solution is related to the:
each type having binding.sites that are specific for a (1) Number of particles (molecules or ions) dissolved in
particular substance. the solution rather than their size, type, molecular
weight or chemical composition.
Important Notes
(2) Temperature and volume in the same way as the
1. Diffusion is a major force affecting the pressure (P) of a gas i.e.
distribution of water and solutes in different body
compartments. P= nRT
2. In diabetes mellitus, glucose uptake by muscle v·
and fat cells is impaired because the carrier for
facilitated diffusion of glucose require insulin. where n = number of particles; R = gas constant;
T = absolute temperature and V = volume of
solution.
Some substances (weak acids and weak bases) that If 'T' is kept constant then osmotic pressure is
are quite soluble in cell membr~es in the undissociated proportionate to the number of particles in a solution per
form, cross the membrane with difficulty in the ionic form. unit volume of solution.
However, if an undissociated substance diffuses from one Since the body fluids are not ideal solutions, the number
side of the membrane to the other end and then dissociates, of particles free to exert an osmotic effect is reduced due to
there occurs net movement of the undissociated substance interaction among the ions. Thus, it is actually the effective
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