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for Dental Students

for Dental Students
Second Edition
K Sembulingam PhD
Madha Medical College & Research Institute
Kundrathur Main Road, Kovur, Thandalam, Chennai, Tamil Nadu, India
MR Medical College, Kalaburagi, Karnataka, India
Sri Ramachandra Medical College and Research Institute
Chennai, Tamil Nadu, India
School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, India
Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
Shri Sathya Sai Medical College and Research Institute
Nellikuppam, Tamil Nadu, India
Prema Sembulingam PhD
MR Medical College, Kalaburagi, Karnataka, India
Sri Ramachandra Medical College and Research Institute
Chennai, Tamil Nadu, India
School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia and
Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, India
Sathyabama University Dental College and Hospital, Chennai, Tamil Nadu, India
Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
Shri Sathya Sai Medical College and Research Institute
Nellikuppam, Tamil Nadu, India
Madha Medical College & Research Institute
Chennai, Tamil Nadu, India

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Essentials of Physiology for Dental Students

First Edition: 2011

Second Edition: 2016

ISBN 978-93-85999-46-8

Printed at
Our beloved students
Preface to the second edition
A Journey from Good to Better!
In 1990s, when the semester system was abolished for medical course and the 18 months
of first year course were reduced to 12 months, with the same voluminous syllabus, we
could realize the difficulties faced by the students in coping up with the shortened period
and the same bulk of subject. That made us venture into the way of making Physiology
easy, approachable, adjusting with the time reduction, but without compromising with
the essence and details of Physiology. That is how the textbook Essentials of Medical
Physiology emerged in 1999, and is serving the purpose continuously since then. What
started as a ‘national book’ has become an ‘international book’. Thanks to the faculty and
students of medical institutes, in and out of country, and the publishers.
Slowly, this book gained its due recognition among the students of other medical and
allied courses, such as homeopathy, Indian medicine, dental, nursing, physiotherapy and
other paramedical courses. In 2010, when, I, Dr Prema Sembulingam, happened to work
in Sathyabama University Dental College and Hospital at Chennai, Tamil Nadu, India
for a brief period of 20 months, another revelation occurred that Essentials of Medical
Physiology was too voluminous for the dental and paramedical courses. So, requests and
suggestions started pouring in to reduce the volume without compromising on the essence
of the subject. That is how the textbook Essentials of Physiology for Dental Students
emerged and the first edition successfully completed the five years of its journey. Now is
the time to venture into the task of upgrading the book into its second edition.
The primary aim of this book is to meet the needs of the students of dental, nursing,
physiotherapy and other paramedical and health science courses, precisely in getting
knowledge of the recent developments in the field of Physiology and in knowing the
important applied aspects on various topics.
The text is well supported with the descriptive diagrams, which are easily understood
by the students, and is reproduced wherever necessary. The explanation of the topics
is backed up with the flow charts and tables, which makes the reading pleasurable and
At the beginning of each chapter, we have included the topics that are to be learnt in
that particular chapter, which will help the reader remember the contents while revising
the topic. At the end of each section, the long as well as short questions are given for the
follow-up on the topics.
This venture is possible only because of the blessings of the professors, best wishes
and cooperation of our friends and fellow-teachers and the students, who know what they
want and where to get those from. We are grateful and also thankful to one and all for being
the well-wishers of us.
Our special thanks are due to Dr S Manikandan (Associate Professor of Physiology,
Tagore Medical College & Hospital, Chennai, Tamil Nadu, India) for his personal involvement
in interacting with the students and giving us the feedback, which helped us in shaping it as
per the need of time and necessity of the students.
viii Essentials of Physiology for Dental Students

We wish to continue our services to the students’ community through this book. We are
confident that the opinions, comments and valuable suggestions from one and all coming
across this book will help us improve it further to meet the needs of those students who
have Physiology as the subject in their career.

K Sembulingam

Prema Sembulingam
Preface to the first edition
We, the authors of Essentials of Medical Physiology are proud to bring out another textbook
in Physiology, titled Essentials of Physiology for Dental Students. This is the outcome of
requests, wishes and friendly orders from different category of people including the dental
and paramedical students and faculties.
Physiology is different from other biomedical sciences as it deals with the functional
aspects of various systems in the living body along with the emphasis on the regulatory
mechanism that maintain the normalcy of the functions within narrow limits. It forms the
strong foundation on which other medical fields are constructed.
The primary aim of this book is to meet the needs of the dental, paramedical and health
science students precisely in the examination point of view, in getting knowledge of recent
developments in the field of Physiology and in knowing the important applied aspects of
various topics.
The descriptive diagrams are given in such a way that the students can easily understand
and reproduce them wherever necessary. The explanation of the topics is supported with
the flowcharts and tables which makes the reading a pleasure and stress-free.
In the starting of each chapter, we have included the topics that are to be learnt in that
particular chapter which will help the reader to remember the contents while revising the
topic. At the end of each section, the long questions and short questions are given for the
follow-up of the topics.
This venture is possible only because of blessings of professors, best wishes and
cooperation of our friends and co-teachers and the students who know what they want and
where to get them. We are grateful and thankful to one and all for being the well-wishers
of us.
We wish to continue our services to the students’ community through this book. We are
confident that the opinions, comments and valuable suggestions from one and all coming
across this book will help us to improve it further to meet the needs of everyone who has
Physiology as subject in their career.

K Sembulingam

Prema Sembulingam
SECTION 1: General Physiology
1. Cell...............................................................................................................3
2. Cell Junctions.............................................................................................14
3. Transport Through Cell Membrane.............................................................17
4. Homeostasis...............................................................................................25

SECTION 2: Blood and Body Fluids

5. Body Fluids ................................................................................................33
6. Blood .........................................................................................................39
7. Plasma Proteins.........................................................................................42
8. Red Blood Cells..........................................................................................45
9. Erythropoiesis.............................................................................................51
10. Hemoglobin................................................................................................56
11. Erythrocyte Sedimentation Rate and Packed Cell Volume.........................59
12. Anemia.......................................................................................................62
13. Hemolysis and Fragility of Red Blood Cells................................................66
14. White Blood Cells.......................................................................................69
15. Immunity.....................................................................................................75
16. Platelets......................................................................................................85
17. Hemostasis.................................................................................................89
18. Coagulation of Blood..................................................................................91
19. Blood Groups............................................................................................101
20. Blood Transfusion.....................................................................................109
21. Reticuloendothelial System, Tissue Macrophage and Spleen.................. 111
22. Lymphatic System and Lymph.................................................................. 114
23. Tissue Fluid and Edema........................................................................... 117

SECTION 3: Muscle Physiology

24. Classification of Muscles..........................................................................123
25. Structure of Skeletal Muscle.....................................................................126
26. Properties of Skeletal Muscle...................................................................132
27. Electrical and Molecular Changes During Muscular Contraction.............138
28. Neuromuscular Junction...........................................................................145
29. Smooth Muscle.........................................................................................150
xii Essentials of Physiology for Dental Students

SECTION 4: Digestive System

30. Overview of Digestive System..................................................................159
31. Salivary Secretion.....................................................................................164
32. Gastric Secretion......................................................................................173
33. Pancreatic Secretion................................................................................185
34. Liver and Biliary System...........................................................................192
35. Functions and Secretions of Small Intestine............................................204
36. Functions and Secretions of Large Intestine............................................209
37. Movements of Gastrointestinal Tract........................................................212

SECTION 5: Renal Physiology and Skin

38. Overview of Kidney...................................................................................225
39. Nephron....................................................................................................228
40. Juxtaglomerular Apparatus.......................................................................234
41. Renal Circulation......................................................................................238
42. Urine Formation........................................................................................241
43. Concentration of Urine..............................................................................250
44. Acidification of Urine and Role of Kidney in Acid-base Balance...............256
45. Renal Function Tests................................................................................260
46. Micturition.................................................................................................263
47. Skin...........................................................................................................268
48. Body Temperature....................................................................................273

SECTION 6: Endocrinology
49. Overview of Endocrine System................................................................281
50. Pituitary Gland..........................................................................................286
51. Thyroid Gland...........................................................................................299
52. Parathyroid Glands and Physiology of Bone............................................310
53. Endocrine Functions of Pancreas.............................................................322
54. Adrenal Cortex..........................................................................................331
55. Adrenal Medulla........................................................................................342
56. Endocrine Functions of Other Organs......................................................347
57. Local Hormones.......................................................................................351

SECTION 7: Reproductive System

58. Male Reproductive System.......................................................................359
59. Female Reproductive System..................................................................374
60. Menstrual Cycle........................................................................................382
Contents xiii
61. Pregnancy................................................................................................391
62. Mammary Glands and Lactation...............................................................397
63. Fertility Control.........................................................................................400

SECTION 8: Cardiovascular System

64. Overview of Cardiovascular System.........................................................407
65. Properties of Cardiac Muscle...................................................................414
66. Cardiac Cycle...........................................................................................420
67. Heart Sounds............................................................................................425
68. Electrocardiogram (ECG).........................................................................430
69. Cardiac Output.........................................................................................437
70. Heart Rate................................................................................................444
71. Arterial Blood Pressure.............................................................................451
72. Venous Pressure and Capillary Pressure.................................................461
73. Arterial Pulse and Venous Pulse..............................................................463
74. Regional Circulation.................................................................................467
75. Fetal Circulation and Respiration.............................................................474
76. Hemorrhage, Circulatory Shock and Heart Failure...................................478
77. Cardiovascular Adjustments During Exercise...........................................481

SECTION 9: Respiratory System and Environmental Physiology

78. Respiratory Tract and Pulmonary Circulation...........................................487
79. Mechanics of Respiration.........................................................................493
80. Pulmonary Function Tests........................................................................499
81. Ventilation and Dead Space.....................................................................506
82. Exchange and Transport of Respiratory Gases........................................510
83. Regulation of Respiration.........................................................................519
84. Diseases and Disorders of Respiration....................................................526
85. High Altitude and Deep Sea Physiology...................................................533
86. Effects of Exposure to Cold and Heat.......................................................538
87. Artificial Respiration..................................................................................541
88. Effects of Exercise on Respiration............................................................543

SECTION 10: Nervous System

89. Overview of Nervous System...................................................................549
90. Neuron and Neuroglia..............................................................................552
91. Receptors.................................................................................................563
92. Synapse and Neurotransmitters...............................................................568
93. Reflex Activity...........................................................................................575
xiv Essentials of Physiology for Dental Students

94. Spinal Cord...............................................................................................582

95. Somatosensory System and Somatomotor System.................................599
96. Physiology of Pain....................................................................................608
97. Thalamus..................................................................................................612
98. Hypothalamus...........................................................................................616
99. Cerebellum...............................................................................................624
100. Basal Ganglia...........................................................................................631
101. Cerebral Cortex and Limbic System ........................................................636
102. Reticular Formation..................................................................................647
103. Posture and Equilibrium...........................................................................651
104. Vestibular Apparatus.................................................................................659
105. Electroencephalogram (EEG) and Epilepsy.............................................666
106. Physiology of Sleep..................................................................................670
107. Higher Intellectual Functions....................................................................673
108. Cerebrospinal Fluid..................................................................................679
109. Autonomic Nervous System.....................................................................683

SECTION 11: Special Senses

110. Eye...........................................................................................................693
111. Visual Process and Field of Vision...........................................................702
112. Visual Pathway.........................................................................................707
113. Pupillary Reflexes.....................................................................................712
114. Color Vision..............................................................................................716
115. Errors of Refraction..................................................................................719
116. Ear............................................................................................................723
117. Auditory Pathway......................................................................................728
118. Mechanism of Hearing and Auditory Defects...........................................731
119. Sensation of Taste....................................................................................735
120. Sensation of Smell....................................................................................738
Index ..................................................................................................................743
Section 1
General Physiology

1. Cell............................................................................................... 3
2. Cell Junctions............................................................................. 14
3. Transport Through Cell Membrane............................................ 17
4. Homeostasis.............................................................................. 25
Chapter 1




„„ CELL The tissue is defined as the group of cells

having similar function. The tissues are
Cell is defined as the structural and func­ classified into four major types which are
tional unit of the living body because it has called the primary tissues. The primary
all the characteristics of life. tissues include:
4 Section 1 ê General Physiology

1. Muscle tissue: Skeletal muscle, smooth „„ COMPOSITION OF CELL

muscle and cardiac muscle. MEMBRANE
2. Nervous tissue: Neurons and support­
ing cells. The cell membrane is composed of three
3. Epithelial tissue: Squamous, columnar types of substances:
and cuboidal epithelial cells. 1. Proteins (55%).
4. Connective tissue: Connective tissue 2. Lipids (40%).
proper, cartilage, bone and blood. 3. Carbohydrates (5%).

An organ is defined as the structure that
is formed by two or more primary types
of tissues. Some organs are composed of
all the four types of primary tissues. The
organs may be tubular like intestine or
hollow like stomach.

The system is defined as group of organs
functioning together to perform a specific FIGURE 1.1: Structure of the cell
function of the body. For example, digestive
system is made out of groups of organs
like esophagus, stomach, intestine, etc.,
which is concerned with digestion of food

„„ STRUCTURE OF THE CELL FIGURE 1.2: Diagram of the cell membrane

Each cell is formed by a cell body and a
cell membrane or plasma membrane that „„ STRUCTURE OF CELL MEMBRANE
covers the cell body. The important parts of
the cell are (Fig. 1.1): The cell membrane is a unit membrane
1. Cell membrane. having the ‘fluid mosaic model’, i.e. the mem­
2. Nucleus. brane is a fluid with mosaic of proteins
3. Cytoplasm with organelles. (mosaic means pattern formed by arrange­
ment of different colored pieces of stone,
„„ CELL MEMBRANE tile, glass or other such materials) lipids
The cell membrane is a protective sheath and carbohydrates. The electron micro­
that envelops the cell body. It separates the scopic study reveals three layers in the cell
fluid outside the cell called extracellular fluid membrane namely, one electron-lucent lipid
(ECF) and the fluid inside the cell called layer in the center and two electron-dense
intracellular fluid (ICF). It is a semiperme­ layers. The two electron-dense protein layers
able membrane and allows free exchange are placed on either side of the central
of certain substances between ECF and layer. Carbohydrate molecules are found
ICF (Fig. 1.2). on the surface of the cell membrane.
Chapter 1 ê Cell 5
Lipid Layer of Cell Membrane Protein Layers of the Cell Membrane
It is a bilayered structure formed by a thin The protein layers of the cell membrane are
film of lipids. It is fluid in nature and the the electron-dense layers situated on either
portions of the membrane along with the side of the central lipid layer. The protein
dis­solved substances move to all areas of substances present in these layers are
the cell membrane. The major lipids are: mostly glycoproteins. These protein mole­
1. Phospholipids. cules are classified into two categories:
2. Cholesterol. 1. Integral proteins.
1. Phospholipids 2. Peripheral proteins.
The phospholipid molecules are formed by 1. Integral proteins
phosphorus and fatty acids. Each phos­
The integral proteins, also known as trans­
pholipid molecule resembles the headed
membrane proteins, are tightly bound with
pin in shape (Fig. 1.3). The outer part of the
the cell membrane. These protein mole­
phospholipid molecule is the head portion
which is water soluble (hydrophilic) and cules pass through the entire thickness of
the inner part is the tail portion that is not the cell membrane from one side to the
soluble in water (hydrophobic). The hydro­ other side.
phobic tail portions meet in the center of 2. Peripheral proteins
the membrane. The hydrophilic head por­
tions of outer layer face the ECF and those The peripheral proteins also known as peri­
of the inner layer face the cytoplasm. pheral membrane proteins do not penetrate
the cell membrane but are embe­ dded
2. Cholesterol partially in the outer and inner surfaces
The cholesterol molecules are arranged in of the cell membrane. These protein mol­
between the phospholipid molecules. As ecules are loosely bound with the cell mem­
phospholipids are soft and oily in nature, brane and so dissociate readily from the
cholesterol helps to ‘pack’ the phospho­ cell membrane.
lipids in the membrane and maintain the
structural integrity of cell membrane. Functions of protein layers

Functions of lipid layer 1. Integral proteins provide structural

integrity of the cell membrane.
The lipid layer is semipermeable in nature 2. Channel proteins provide route for
and allows only the fat-soluble substances diffusion of water-soluble substances
like oxygen, carbon dioxide and alcohol to like glucose and electrolytes.
pass through it. It does not allow the water- 3. Carrier proteins help in transport of
soluble materials like glucose, urea and substances across the cell membrane.
electrolytes to pass through it. 4. Receptor proteins serve as receptor
sites for hormones and neurotran­
5. Enzymes: Some of the protein mole­
cules form the enzymes which control
chemical reactions within the cell
6. Antigens: Some proteins act as antigens
and induce the process of antibody
FIGURE 1.3: Lipids of the cell membrane formation.
6 Section 1 ê General Physiology

Carbohydrates of the Cell Membrane „„ CYTOPLASM

Carbohydrate molecules form a thin loose The cytoplasm is the fluid present inside the
covering over the entire surface of the cell cell. It contains a clear liquid portion called
membrane called glycocalyx. Some carbo­ cytosol which contains various substances
hydrate molecules are attached with pro­ like proteins, carbohydrates, lipids and
teins and form glycoproteins and some are electrolytes. Apart from these substances,
attached with lipids and form glycolipids. many organelles are also present in cyto­
plasm. The cytoplasm is distributed as peri­
Functions of carbohydrates pheral ectoplasm just beneath the cell
mem­brane and inner endoplasm between
1. The carbohydrate molecules are nega­
the ectoplasm and the nucleus.
tively charged and do not permit the
negatively charged substances to move
in and out of the cell. „„ ORGANELLES IN CYTOPLASM
2. The glycocalyx from the neighboring All the cells in the body contain some com­
cells helps in the tight fixation of cells mon structures called organelles in the
with one another. cyto­plasm. Some organelles are bound by
3. Some of the carbohydrate molecules limiting membrane and others do not have
form the receptors for some hormones. limiting membrane (Box 1.1). The organel­
les carry out the various functions of the cell
1. Protective function: Cell membrane BOX 1.1: Cytoplasmic organelles
pro­tects the cytoplasm and the orga­
nelles present in the cytoplasm. The organelles with limiting membrane
2. Selective permeability: Cell membrane 1. Endoplasmic reticulum
acts as a semipermeable membrane
2. Golgi apparatus
which allows only some substances to
3. Lysosome
pass through it and acts as a barrier
4. Peroxisome
for other substances.
5. Centrosome and centrioles
3. Absorptive function: Nutrients are
6. Secretory vesicles
absor­bed into the cell through the cell
7. Mitochondria
8. Nucleus
4. Excretory function: Metabolites and
other waste products from the cell are The organelles without limiting membrane
excreted out through the cell mem­
1. Ribosomes
2. Cytoskeleton
5. Exchange of gases: Oxygen enters the
cell from the blood and carbon dioxide
leaves the cell and enters the blood „„ ORGANELLES WITH LIMITING
through the cell membrane. MEMBRANE
6. Maintenance of shape and size of the
cell: Cell membrane is responsible for
the maintenance of shape and size of Endoplasmic reticulum is made up of
the cell. tubules and microsomal vesicles. These
Chapter 1 ê Cell 7
TABLE 1.1: Functions of cytoplasmic organelles

Organelles Functions
1. Synthesis of proteins
Rough endoplasmic reticulum
2. Degradation of worn out organelles
1. Synthesis of lipids and steroids
2. Role in cellular metabolism
Smooth endoplasmic reticulum
3. Storage and metabolism of calcium
4. Catabolism and detoxification of toxic substances
1. Processing, packaging, labeling and delivery of proteins
Golgi apparatus
and lipids
1. Degradation of macromolecules
2. Degradation of worn out organelles
3. Removal of excess of secretory products
4. Secretory function
1. Breakdown of excess fatty acids
2. Detoxification of hydrogen peroxide and other metabolic
3. Oxygen utilization
4. Acceleration of gluconeogenesis
5. Degradation of purine to uric acid
6. Role in the formation of myelin
7. Role in the formation of bile acids
Centrosome 1. Movement of chromosomes during cell division
1. Production of energy
Mitochondria 2. Synthesis of ATP
3. Initiation of apoptosis
Ribosomes 1. Synthesis of proteins
1. Determination of shape of the cell
Cytoskeleton 2. Stability of cell shape
3. Cellular movements
1. Control of all activities of the cell
2. Synthesis of RNA
3. Sending genetic instruction to cytoplasm for protein
Nucleus synthesis
4. Formation of subunits of ribosomes
5. Control of cell division
6. Storage of hereditary information in genes (DNA)

Types of Endoplasmic Reticulum

structures form an interconnected network The endoplasmic reticulum is of two types
which forms the link between the organelles namely, rough endoplasmic reticulum and
and cell membrane. smooth endoplasmic reticulum.
8 Section 1 ê General Physiology

Rough Endoplasmic Reticulum Functions of smooth

endoplasmic reticulum
Rough endoplasmic reticulum is the one to
which the granular ribosome is attached. i. It is responsible for synthesis of choles­
This gives the rough appearance and so, it terol and steroid.
is called the rough endoplasmic reticulum. ii. It is concerned with various metabolic
Attachment of the granular ribosome also processes of the cell because of the
gives the beaded or granular appearance presence of many enzymes on the
and so, it is also called granular endoplasmic outer surface.
reticulum (Fig. 1.4). iii. It is concerned with the storage and
metabolism of calcium.
Functions of rough
iv. It is also concerned with catabolism
endoplasmic reticulum
and detoxification of toxic substances
It is concerned with the protein synthesis in like some drugs and carcinogens
the cell especially those secreted from the (cancer producing substances) in liver.
cell such as insulin from ‘β’ cells of islets of Rough endoplasmic reticulum and
Langerhans in pancreas and antibodies in smooth endoplasmic reticulum are intercon­
leukocytes. nected and continuous with one another.
It also plays an important role in degra­ Depending upon the activities of the cells,
dation of worn out cytoplasmic organelles the rough endoplasmic reticulum changes
like mitochondria. It wraps itself around the to smooth endoplasmic reticulum and vice
worn out organelles and forms a vacuole versa.
which is often called the autophagosome. It
is digested by lysosomal enzymes. „„ 2. GOLGI APPARATUS
Golgi apparatus (Golgi body or Golgi com­
Smooth Endoplasmic Reticulum
plex) is present in all the cells except red
Smooth endoplasmic reticulum is also called blood cells. It consists of 5 to 8 flattened mem­
as agranular endoplasmic reticulum because branous sacs called cisternae (Fig. 1.5).
of its smooth appearance without the attach­ The Golgi apparatus is situated near the
ment of ribosome. It is formed by many inter­ nucleus. It has two ends or faces namely,
connected tubules. So, it is also called cis face and trans face. The cis face is posi­
tubular endoplasmic reticulum. tioned near the endoplasmic reticulum.

FIGURE 1.4: Endoplasmic reticulum FIGURE 1.5: Golgi apparatus

Chapter 1 ê Cell 9
The reticular vesicles from endoplasmic Functions of Lysosomes
reticulum enter the Golgi apparatus through
cis face. The trans face is situated near the i. Digestion of unwanted substances
cell membrane. The processed substances With the help of hydrolytic enzymes like
make their exit from Golgi apparatus through
proteases, lipases, amylases and nuclea­
trans face.
ses, lysosome digests and removes the
unwanted substances.
Functions of Golgi Apparatus
i. It is concerned with the processing and ii. Removal of excess secretory
delivery of substances like proteins products in the cells
and lipids to different parts of the cell. Lysosomes in the cells of the secretory
ii. It functions like a post office because, glands play an important role in the removal
it packs the processed materials into of excess secretory products by degrading
the secretory granules, secretory vesi­
the secretory granules.
cles, and lysosomes and dispatch
them either out of the cell or to another iii. Secretory function – secretory
part of the cell. lysosomes
iii. It also functions like a shipping depart­
ment of the cell because it sorts out Recently, lysosomes having secretory func­
and labels the materials for distribution tion called secretory lysosomes are found
to their proper destinations. in some of the cells, particularly in the
cells of immune system. The conventional
„„ 3. LYSOSOMES lyso­somes are modified into secretory
lyso­somes by combining with secretory
These are small globular structures filled
with enzymes. These enzymes are synthe­
sized in rough endoplasmic reticulum and Examples of secretory lysosomes:
transported to the Golgi apparatus. Here, a. In cytotoxic T lymphocytes and natural
these are processed and packed in the killer (NK) cells, lysosomes secrete
form of small vesicles. Then, these vesicles perforin and granzymes which destroy
are pinched off from Golgi apparatus and both virus infected cells and tumor
become the lysosomes. There are small cells.
granules containing the hydrolytic enzymes b. In melanocytes, secretory lysosomes
in the cytoplasm of the lysosome. secrete melanin.
c. In mast cells, secretory lysosomes
Types of Lysosomes secrete serotonin which is an inflam­
matory mediator.
Lysosomes are of two types
i. Primary lysosome which is pinched off „„ 4. PEROXISOMES
from Golgi apparatus. It is inactive in
spite of having the hydrolytic enzymes. Peroxisomes are otherwise called as micro­
ii. Secondary lysosome which is active bodies. These are pinched off from endo­
lysosome formed by the fusion of a plasmic reticulum. Peroxisomes contain some
primary lysosome with phagosome or oxidative enzymes such as catalase, urate
endosome. oxidase and D-amino acid oxidase.
10 Section 1 ê General Physiology

Functions of Peroxisomes are involved in respiration and ATP synthe­

sis. Because of these functions, the enzy­
mes and other protein molecules in cristae
i. Degrade the toxic substances like
hydrogen peroxide and other metabolic are collectively known as respiratory chain
products by means of detoxification. or electron transport system.
ii. Form the major site of oxygen utili­ The mitochondria move freely in the
zation in the cells. cytoplasm of the cell and are capable of
iii. Breakdown the excess fatty acids. reproducing themselves. The mitochondria
iv. Accelerate gluconeogenesis from fats. contain their own DNA which is responsible
v. Degrade purine to uric acid. for many enzymatic actions.
vi. Participate in the formation of myelin
and bile acids. Functions of Mitochondrion

i. Production of energy
CENTRIOLES The mitochondrion is called the ‘power
house of the cell’ because it produces the
The centrosome is situated near the center
energy required for the cellular functions.
of the cell close to the nucleus. It con­sists
The energy is produced by oxidation of the
of two cylindrical structures called cen­
food substances like proteins, carbohy­
trioles which are responsible for the move­
drates and lipids by the oxidative enzymes
ment of chromosomes during cell division.
in cristae. During oxidation, water and
carbon dioxide are produced with release
„„ 6. SECRETORY VESICLES of energy. The released energy is stored in
The secretory vesicles are globular struc­ mitochondria and used later for synthesis
tures, formed in the endoplasmic reticulum, of ATP.
and processed and packed in Golgi appa­
ii. Synthesis of ATP
ratus. When necessary, the secretory vesi­
cles rupture and release the secretory The components of respiratory chain in
substances into the cytoplasm. the mitochondrion are responsible for the
synthesis of ATP by utilizing the energy
„„ 7. MITOCHONDRION through oxidative phosphorylation. The ATP
molecules defuse throughout the cell from
The mitochondrion (plural ‘mitochondria’) is
mitochondrion. Whenever energy is needed
a rod or oval-shaped structure with a dia­
for cellular activity, the ATP molecules are
meter. It is covered by a double layered
broken down.
membrane (Fig. 1.6). The outer membrane
is smooth and encloses the contents of
mitochondrion. It contains various enzymes
such as acetyl-CoA synthetase and glycero­
phosphate acetyltransferase.
The inner membrane forms many folds
called cristae and covers the inner matrix
space. The cristae also contain many enzy­
mes and other protein molecules which FIGURE 1.6: Structure of mitochondrion
Chapter 1 ê Cell 11
iii. Apoptosis Microtubules
Mitochondria are involved in apoptosis (see Microtubules are straight and hollow tubu­
below) also. lar structures formed by bundles of globular
protein called α- and β-tubulin (Fig. 1.7A).
LIMITING MEMBRANE Functions of microtubules

„„ 1. RIBOSOMES Microtubules:
i. Determine the shape of the cell.
The ribosomes are small granular structures ii. Give structural strength to the cell.
with a diameter of 15 nm. Some ribosomes iii. Act like conveyor belts which allow the
are attached to rough endoplasmic reti­
movement of granules, vesicles, protein
culum while others are present as free
molecules and some organelles like
ribosomes in the cytoplasm. The ribosomes
mitochondria to different parts of the
are made up of proteins (35%) and RNA
(65%). The RNA present in ribosomes is
iv. Form the spindle fibers, which separate
called ribosomal RNA (rRNA).
the chromosomes during mitosis.
Functions of Ribosomes v. Responsible for the movements of cen­
trioles and the complex cellular struc­
Ribosomes are called protein factories tures like cilia.
because of their role in the synthesis of pro­
teins. Messenger RNA passes the genetic Intermediate Filaments
code for protein synthesis from nucleus to the
ribosomes. The ribosomes, in turn arrange The intermediate filaments form a network
the amino acids into small units of proteins. around the nucleus and extend to the peri­
The ribosomes attached with endo­plasmic phery of the cell. These are formed by
reticulum are involved in the syn­thesis of fibrous proteins (Fig. 1.7B) and help to main­
proteins like the enzymatic proteins, hormonal tain the shape of the cell. The adjacent cells
proteins, lysosomal proteins and the pro­ are connected by intermediate filaments by
teins of the cell membrane. desmosomes.
The free ribosomes are responsible for
the synthesis of proteins in hemoglobin, Functions or intermediate filaments
peroxisome and mitochondria.
Intermediate filaments help to maintain the
„„ 2. CYTOSKELETON shape of the cell. These filaments also
connect the adjacent cells through desmo­
The cytoskeleton of the cell is a complex somes.
network that gives shape, support and stability
to the cell. It is also essential for the cellular Microfilaments
movements and the response of the cell to
external stimuli. The cytoskeleton consists of Microfilaments are long and fine thread-
three major protein components, viz.: like structures, which are made up of non-
a. Microtubules. tubular contractile proteins called actin and
b. Intermediate filaments. myosin (Fig. 1.7C). Actin is more abundant
c. Microfilaments. than myosin.
12 Section 1 ê General Physiology

mostly spherical in shape. However, the

shape and situation of nucleus vary in dif­
ferent cells.

Nuclear Membrane
The nucleus is covered by a double laye­
red membrane called nuclear membrane.
It encloses the fluid called nucleoplasm.
Nuclear membrane is porous and perme­
able in nature and it allows nucleoplasm to
communicate with the cytoplasm.

It is a gel-like ground substance and con­
tains large quantities of the genetic mate­
rial in the form of DNA. The DNA is made
FIGURE 1.7: A. Microtubules; B. Intermediate up of chromatin threads. These chro­matin
filament; C. Microfilament of ectoplasm. threads become the rod-shaped chromo­
somes just before the cell division.
Functions or microfilaments
i. Give structural strength to the cell. One or more nucleoli are present in each
ii. Provide resistance to the cell against nucleus. The nucleolus contains RNA and
the pulling forces. some proteins, which are similar to those
iii. Responsible for cellular movements found in ribosomes. The RNA is synthe­
like contraction, gliding and cytokine­ sized by chromosomes and stored in the
sis (partition of cytoplasm during cell nucleolus.
„„ NUCLEUS Nucleus:
Nucleus is present in those cells which 1. Controls all the activities of the cell.
divide and produce enzymes. The cells with 2. Synthesizes RNA.
nucleus are called eukaryotes and those 3. Forms subunits of ribosomes.
without nucleus are known as prokaryotes 4. Sends genetic instruction to the cyto­
(e.g. red blood cells). Prokaryotes do not plasm for protein synthesis through
divide or synthesize the enzymes. mRNA.
Most of the cells have only one nucleus 5. Controls the cell division through genes.
(uninucleated). Few types of cells like 6. Stores the hereditary information (in
skeletal muscle cells have many nuclei genes) and transforms this information
(multi­nucleated). Generally the nucleus from one generation of the species to
is located near the center of the cell. It is the next.
Chapter 1 ê Cell 13
„„ CELL DEATH 2. Useful for removal of a cell that is
damaged by a virus or a toxin beyond
The cell death occurs by two distinct pro­
3. An essential event during the develop­
1. Necrosis.
ment and in adult stage. For example, a
2. Apoptosis.
large number of neurons are produced
during the development of central
nervous system. But up to 50% of the
Apoptosis is defined as the programmed neurons are removed by apoptosis
cell death under genetic control. Originally during the formation of synapses bet­
apoptosis (means ‘falling leaves’ in Greek) ween neurons.
refers to the process by which the leaves
fall from trees in autumn. It is also called „„ NECROSIS
‘cell suicide’ since the genes of the cell play Necrosis (means ‘dead’ in Greek) is the
a major role in the death. uncontrolled and unprogrammed death
This type of programmed cell death is a of cells due to unexpected and acciden­
normal phenomenon and it is essential for tal damage. It is also called ‘cell murder’
normal development of the body. because the cell is killed by extracellular or
external events. After necrosis, the harmful
Functional Significance of Apoptosis chemical substances released from the
The main function of apoptosis is to remove dead cells cause damage and inflammation
unwanted cells without causing any stress of neighboring tissues.
or damage to the neighboring cells. The
functional significance of apoptosis: Causes for Necrosis
1. Plays a vital role in cellular homeo­ Common causes of necrosis are injury,
stasis. About 10 million cells are pro­ infection, inflammation, infarction and cancer.
duced every day in human body by Necrosis is induced by both physical and
mitosis. An equal number of cells die chemical events such as heat, radiation,
by apoptosis. This helps in cellular trauma, hypoxia due to lack of blood flow,
homeostasis. and exposure to toxins.
Chapter 2

Cell Junctions




CLASSIFICATION The junction which prevents the movement
of ions and molecules from one cell to
Cell junction is defined as the connection
another cell is called the occluding junction.
between neighboring cells or the contact
Tight junctions belong to this category.
between the cell and extracellular matrix. It
is also called membrane junction. „„ TIGHT JUNCTION
Connection between two cells is called
intercellular junctions. Tight junction, gap Tight Junction is formed by the tight fusion of
junc­tion, adherence junction and desmo­ the cell membranes from the adjacent cells.
The area of the fusion is very tight and forms
some are intercellular junctions. Contact
a ridge. This type of junction is present in the
between the cell and extracellular matrix
apical margins of epithelial cells in intestinal
are focal adherence and hemidesmosome. mucosa, wall of renal tubule, capillary wall
Cell junctions are classified into three and choroid plexus (Fig. 2.1).
1. Occluding junction. Functions of Tight Junctions
2. Communicating junction. 1. The tight junctions hold the neigh­
3. Anchoring junction. boring cells of the tissues firmly and
Chapter 2 ê Cell Junctions 15
junctions. Gap junction and chemical syn­
apse are the communicating junctions.


The gap junction is also called nexus. It is
present in heart, basal part of epithelial
cells of intestinal mucosa, etc.

Structure of Gap Junction

The membranes of the two adjacent cells
lie very close to each other and the intercel­
lular space becomes a narrow channel. The
cytoplasm of the two cells is interconnected
and the molecules move from one cell to
another cell through these channels without
having contact with extracellular fluid (ECF).
The channel is surrounded by 6 subunits
of proteins which are called connexins or
FIGURE 2.1: Different types of cell junctions
thus provide strength and stability to
the tissues. Functions of Gap Junction
2. It provides the barrier or gate function
1. The diameter of the channel in the gap
by which the interchange of ions,
junction is about 1.5 to 3 nm. So, the
water and macromolecules between
substances having molecular weight
the cells is regulated.
less than 1,000 such as glucose also
3. It acts like a fence by preventing the
can pass through this junction easily.
lateral movement of integral mem­
2. It helps in the exchange of chemical
brane proteins and lipids from cell
messengers between the cells.
3. It helps in rapid propagation of action
4. By the fencing function, the tight junc­
potential from one cell to another cell.
tions maintain the cell polarity by keep­
ing the proteins in the apical region of
the cell membrane.
5. Tight junctions in the brain capillaries Chemical synapse is the junction between
form the blood-brain barrier (BBB) a nerve fiber and a muscle fiber or between
which prevents the entrance of many two nerve fibers, through which the signals
harmful substances from the blood are transmitted by the release of chemical
into the brain tissues. transmitter (refer Chapter 92 for details).


The junctions, which permit the movement Anchoring junctions are the junctions,
of ions and molecules from one cell to which provide firm structural attachment
another cell, are called communicating between two cells or between a cell and the
16 Section 1 ê General Physiology

extracellular matrix. There are four types of type of junction is seen in epithelia of
anchoring junctions: various organs.
1. Adherens junctions (cell to cell).
2. Focal adhesions (cell to matrix). „„ DESMOSOME
3. Desmosomes (cell to cell).
Desmosome is also cell to cell junction,
4. Hemidesmosomes (cell to matrix).
but here the membranes of the cells are
thickened and connected by intermediate
filaments. So, desmosome functions like
Adherens junction is a cell to cell junction tight junction. This type of junction is found
that is the junction found between the cells. in areas subjected for stretching such as
The connection occurs through the actin the skin.
filaments. Adherens junctions are present
in the intercalated disk of cardiac muscles „„ HEMIDESMOSOME
(refer Chapter 64) and epidermis of the
Hemidesmosome is also cell to matrix
junction and the connection is through
inter­mediate filaments. It is like half desmo­
some because here, the membrane of
Focal adhesion is a cell to matrix junc­ only one cell thickens. So, this is known
tion that is junction between the cell and as hemidesmosome or half desmosome.
the extracellular matrix. The connection Mostly, the hemidesmosome connects the
occurs through the actin filaments. This cells with their basal lamina.
Chapter 3

Transport Through Cell Membrane


„„ INTRODUCTION 1. Simple diffusion.

2. Facilitated diffusion.
Transport mechanism in the body is neces­
sary for the supply of essential substances
like nutrients, water, electrolytes, etc. and
to remove the unwanted substances like Simple diffusion is of two types:
waste materials, carbon dioxide, etc. from 1. Simple diffusion through lipid layer.
the tissues. 2. Simple diffusion through protein layer.

„„ BASIC MECHANISM OF Simple Diffusion Through Lipid Layer

Lipid-soluble substances like oxygen, car­
Two basic mechanisms for the transport of bon dioxide and alcohol are transported by
substances across the cell membrane are: simple diffusion trough the lipid layer of the
1. Passive mechanism. cell membrane (Fig. 3.1A).
2. Active mechanism.
Simple Diffusion Through Protein Layer
There are specific protein channels that
The transport of the substances along the extend from cell membrane through which
concentration gradient or electrical gradient the simple diffusion takes place. Water-
or both (electrochemical gradient) is called soluble substances like electrolytes are
passive transport. Here, the substances move transported through these channels. These
from the region of higher concentration to channels are selectively permeable to only
the region of lower concentration. It is also one type of ion. Accordingly, the channels
known as diffusion or downhill movement. It are named after the ions diffusing through
does not need energy. Diffusion or passive these channels like sodium channels, potas­
transport is of two types: sium channels, etc.
18 Section 1 ê General Physiology


The protein channels are of two types:
1. Ungated channels which are opened In this type of diffusion, some carrier proteins
continuously. help the transport of substances. The water-
2. Gated channels which are closed all
soluble substances with larger molecules
the time and are opened only when
required (Fig. 3.1B). cannot pass through the protein channels by
simple diffusion. Such substances are trans­
Gated channels ported with the help of carrier proteins. This
The gated channels are divided into three type of diffusion is faster than the simple
categories (Fig. 3.1C): diffusion. Glucose and amino acids are trans­
1. Voltage-gated channels which opens ported by this method (Fig. 3.2).
by change in the electrical potential.
Examples are the calcium channels „„ FACTORS AFFECTING RATE OF
present in neuromuscular junction (refer DIFFUSION
Chapter 28).
2. Ligand-gated channels that opens in Rate of diffusion of substances through the
the presence of hormonal substances cell membrane is directly proportional to the
(ligand). Examples are the sodium chan­ following factors:
nels which are opened by acetylcholine 1. Permeability of the cell membrane.
in neuromuscular junction. 2. Body temperature.
3. Mechanically gated channels which are
3. Concentration gradient or electrical
opened by some mechanical factors
like pressure and force. Examples are gradient of the substance across the
the sodium channels in pressure recep­ cell membrane.
tors called Pacinian corpuscles. 4. Solubility of the substance.

FIGURE 3.1: Hypothetical diagram of simple diffusion through the cell membrane. A. Diffusion through
lipid layer; B. Diffusion through ungated channel; C. Diffusion through gated channel.
Chapter 3 ê Transport Through Cell Membrane 19
Movement of water and solutes from an area
of high hydrostatic pressure to an area of low
hydrostatic pressure is called filtration. The
hydrostatic pressure is developed by weight
of the fluid. Filtration process is seen at the
arterial end of the capillaries where move­
ment of fluid occurs along with dissolved
substances from blood into the interstitial
fluid (refer Chapter 23). It also occurs in glome­
ruli of kidneys (refer Chapter 42).

FIGURE 3.2: Hypothetical diagram of facilitated Osmosis

diffusion from higher concentration [extracellular
fluid (ECF)] to lower concentration [intracellular Osmosis is defined as movement of water
fluid (ICF)]. Stage I: Glucose binds with carrier or any other solvent from an area of lower
protein. Stage II: Conformational change occurs in concentration to an area of higher concen­
the carrier protein and glucose is released into ICF. tration through a semipermeable membrane
(Fig. 3.3).
Rate of diffusion of substances through Osmosis is of two types:
the cell membrane is inversely proportional 1. Endosmosis by which water moves into
to the following factors: the cell.
1. Thickness of the cell membrane. 2. Exosmosis by which water moves out­
2. Charge of the ions. side the cell.
3. Size of the molecules.
Osmotic Pressure
The pressure created by the solutes in a fluid
is called osmotic pressure. During osmosis,
In additions to diffusion, there are some when water or any other solvent moves from
special types of passive transport, viz.: the area of lower concentration to the area
1. Bulk flow. of higher concentration, the solutes in the
2. Filtration. area of higher concentration, get dissolved
3. Osmosis. in the solvent. This creates a pressure which
is known as osmotic pressure.
Bulk Flow
Colloidal Osmotic Pressure and
Movement of large quantity of substances Oncotic Pressure
from a region of high pressure to the region The osmotic pressure exerted by the col­
of low pressure is known as bulk flow. Bulk loidal substances in the body is called
flow is due to the pressure gradient of the the colloidal osmotic pressure. And, the
substance across the cell membrane. The osmotic pressure exerted by the colloidal
best example for this is the exchange of substances (proteins) of the plasma is
gases across the respiratory membrane in known as oncotic pressure and it is about
lungs (refer Chapter 82). 25 mm Hg.
20 Section 1 ê General Physiology

The carrier protein that can carry only one
substance in a single direction is called
uniport. It is also known as uniport pump.

Symport or Antiport
The carrier protein that transports two
different substances in the same direction
is called symport. The carrier protein that
transports two different substances in oppo­
FIGURE 3.3: Osmosis. Red objects = Solute, site directions is called antiport.
Yellow shade = Water, Green dotted line =
Semipermeable membrane. A. Concentration
of solute is high in the compartment II and low
in compartment I. So, water moves from I to II BY ACTIVE TRANSPORT
through semipermeable membrane; B. Entrance The actively transported substances are
of water into II exerts osmotic pressure. in ionic form and non-ionic form. The sub­
stances in ionic form are sodium, potassium,
„„ ACTIVE TRANSPORT calcium, hydrogen, chloride and iodide. The
substances in non-ionic form are glucose,
Movement of substances against the chemical amino acids and urea.
or electrical or electrochemical gradient is
called active transport. It is also called uphill „„ TYPES OF ACTIVE TRANSPORT
transport. Active transport requires energy,
which is obtained mainly by breakdown of The active transport is of two types:
ATP. It also needs a carrier protein. 1. Primary active transport.
2. Secondary active transport.
When a substance that has to be transported In primary active transport, the energy is
across the cell membrane comes near the liberated directly from the breakdown of
cell, it combines with the carrier protein of the ATP. By this method, the substances like
cell membrane and forms substance- protein sodium, potassium, calcium, hydrogen and
complex. This complex moves towards the chloride are transported across the cell
inner surface of the cell mem­brane. Now, membrane.
the substance is released from the carrier
proteins. The same carrier protein moves Primary Active Transport of Sodium
back to the outer surface of the cell mem­ and Potassium: Sodium-potassium
brane to transport another molecule of the Pump
substance. Sodium (Na+) and potassium (K+) ions are
transported across the cell membrane by
sodium-potassium (Na+-K+) pump which
There are two types of carrier proteins: is also called Na+-K+ ATPase pump. This
1. Uniport. pump is formed by a carrier protein and it
2. Symport or antiport. is present in all cells of the body. Three
Chapter 3 ê Transport Through Cell Membrane 21
sodium ions from inside and two potassium „„ SECONDARY ACTIVE TRANSPORT
ions from outside get attached with the
The transport of a substance with sodium
carrier protein (Fig. 3.4, stage I). Some
ions by a common carrier protein is called
con­formational change occurs in the carrier
secondary active transport. It is of two types:
protein by which the attachment with
1. Cotransport: Transport of the substance
sodium ions faces the ECF and the attach­
in the same direction along with
ment with potassium ions faces the ICF.
Now the three sodium ions are released
2. Countertransport: Transport of the sub­
into ECF and two potassium ions are rele­
stance in the opposite direction to that
ased into ICF (Fig. 3.4, stage II). It is res­
of sodium.
ponsible for the establishment of resting
mem­brane potential (RMP) in the cell by
Sodium Cotransport
distributing more sodium ions outside and
more potassium ions inside. This action is In this, along with sodium, another sub­
called electrogenic activity of Na+-K+ pump. stance is carried with the help of a carrier
protein called symport (the protein that
Transport of Calcium Ions transports two different molecules in the
Calcium ions are actively transported from same direction across the cell membrane).
inside to outside the cell by calcium pump Glucose, amino acids, chloride, iodine, iron
with the help of a separate carrier protein. and urate ions are transported by this
The energy is obtained from ATP. method (Fig. 3.5).

Transport of Hydrogen Ions Sodium Countertransport

Hydrogen ions are actively transported In this process, the substances are trans­
across the cell membrane by hydrogen ported across the cell membrane in
pump with the help of another carrier pro­ exchange for sodium ions by the carrier pro­
tein. It also obtains energy from ATP. tein called antiport (the carrier protein that
transports two different ions or mole­cules in
opposite direction across the cell membrane).

FIGURE 3.4: Hypothetical diagram of sodium-

potassium pump. C = Carrier protein. Stage I:
Three Na+ from intracellular fluid (ICF) and two
K+ from extracellular fluid (ECF) bind with ‘C’. FIGURE 3.5: Sodium (Na+) cotransport. A. Na+
Stage II: Binding of Na+ and K+ to ‘C’ activates and glucose from extracellular fluid (ECF) bind
the enzyme ATPase. Stage III: Conformational with carrier protein; B. Conformational change
change occurs in ‘C’ followed by release of Na+ occurs in the carrier protein; C. Na+ and glucose
into ECF and K+ into ICF. are released into intracellular fluid (ICF).
22 Section 1 ê General Physiology

Examples of counter­transport systems are 1. Endocytosis.

sodium-calcium coun­ter­transport and sodium- 2. Exocytosis.
hydrogen coun­ ter­
transport in the tubular 3. Transcytosis.
cells (Fig. 3.6 and 3.7).
Endocytosis is the transport mechanism by
which the macromolecules enter the cell.
In addition to primary and secondary active The substances with larger molecules are
transport systems, some special categories called macromolecules and these cannot
of active transport systems also exist in pass through the cell membrane either by
the body. The special categories of active active or by passive transport mechanism.
transport are: Such substances are transported into the
cell by endocytosis.
Endocytosis is of three types:
1. Pinocytosis.
2. Phagocytosis.
3. Receptor-mediated endocytosis.

1. Pinocytosis
Pinocytosis is otherwise called the cell drin­
king. The macromolecules like bacteria and
antigens enter the cells by pinocytosis.
FIGURE 3.6: Sodium (Na+) countertransport. Mechanism of pinocytosis
A. Na+ from extracellular fluid (ECF) and
hydrogen (H+) from intracellular (ICF) bind
i. The macromolecules (in the form of
with carrier protein; B. Conformational change droplets of fluid) bind to the outer
occurs in the carrier protein; C. Na+ enters ICF surface of the cell membrane.
and H+ enters ECF. ii. Now, the cell membrane evaginates
and engulfs the droplets.
iii. The engulfed droplets are converted
into vesicles and vacuoles, which are
called endosomes (Fig. 3.8).
iv. The endosome travels into the interior
of the cell.
v. The primary lysosome in the cytoplasm
fuses with the endosome and forms
the secondary lysosome.

FIGURE 3.7: Sodium cotransport and

countertransport by carrier proteins FIGURE 3.8: Process of pinocytosis
Chapter 3 ê Transport Through Cell Membrane 23
vi. Now, hydrolytic enzymes present in 3. Receptor-mediated Endocytosis
the secondary lysosome are activated
Transport of macromolecules which is
resulting in digestion and degradation
medi­ated by a receptor protein is called the
of the endosomal contents.
receptor-mediated endocytosis. The sur­
face of cell membrane has some pits which
2. Phagocytosis
contain a receptor protein called clathrin.
The process by which the particles larger Together with a receptor protein, each pit
than the macromolecules are engulfed into is called receptor coated pit. The coated
the cells is called phagocytosis or cell eating. pits are involved in the receptor-mediated
Larger bacteria, larger antigens and other endocytosis.
larger foreign bodies are taken inside the cell
Mechanism of receptor-mediated
by means of phagocytosis. Only few cells
in the body like neutrophils, monocytes and
the tissue macrophages show phagocytosis. i. The receptor-mediated endocytosis
Among these cells, the macrophages are the is induced by substances like ligand
largest phagocytic cells. (hormone) which bind to the receptors
in the coated pits and form the ligand-
Mechanism of phagocytosis
receptor complexes.
i. When the bacteria or the foreign body ii. The ligand-receptor complexes get
enters the body, first the phagocytic cell aggregated in the coated pits.
sends cytoplasmic extension (pseudo­ iii. Then, the pit is detached from the cell
podium) around the bacteria or the membrane and becomes the coated
foreign substance. vesicle. This coated vesicle forms the
ii. Then, these particles are engulfed endosome.
and are converted into endosome-like iv. The endosome travels into the interior
vacuole. The vacuole is very large and of the cell (Fig. 3.10).
it is usually called the phagosome. Receptor-mediated endocytosis plays an
iii. The phagosome travels into the interior important role in the transport of various
of the cell. types of macromolecules such as hormones,
iv. The primary lysosome fuses with this antibodies, lipids, growth factors, toxins,
phagosome and forms secondary bacteria and viruses.
v. The hydrolytic enzymes present in „„ EXOCYTOSIS
the secondary lysosome are activated
Exocytosis is the process by which the
resulting in digestion and degradation substances are expelled from the cell. In
of the phagosomal contents (Fig. 3.9). this process, the substances are extruded
from the cell without passing through the
cell membrane. This is the reverse of endo­
Mechanism of exocytosis
Secretory substances from the cells are
released by exocytosis. The secretory sub­
FIGURE 3.9: Process of phagocytosis stances of the cell are stored in the form of
24 Section 1 ê General Physiology

FIGURE 3.10: Receptor-mediated endocytosis

secretory vesicles in the cytoplasm. When

required, the vesicles move towards the cell
membrane and get fused with it. Later, the
contents of the vesicles are released out of
the cell (Fig. 3.11).

Transcytosis is a transport mechanism in FIGURE 3.11: Process of exocytosis
which an extracellular macromolecule enters Examples are movement of proteins and
through one side of a cell, migrates across pathogens like HIV from capillary blood into
cytoplasm of the cell and exits through interstitial fluid through endothelial cells of
the other side by means of exocytosis. the capillary.
Chapter 4



‘Homeostasis’ means the maintenance of HOMEOSTATIC SYSTEM
constant internal environment. According The homeostatic system in the body acts
to Claude Bernard, multicellular organisms through self-regulating devices, which ope­
including man live in a perfectly organi­ rate in a cyclic manner (Fig. 4.1). This cycle
zed and controlled internal environment includes three components:
which he is called ‘Milieu intérieur’. The word 1. Detectors or sensors, which recognize
‘homeo­stasis’ was introduced by Harvard the deviation.
Professor, Walter B Cannon in 1930. 2. Transmission of this message to an
The internal environment in the body integrating unit or control center.
is the ECF which contains nutrients, ions
and all other substances necessary for the
survival of the cells and in this environment
the cells live. It includes the blood and
interstitial fluid.
For the operation of homeostatic mecha­
nism, the body must recognize the devi­
ation of any physiological activity from the
normal limits. Fortunately, body is provided
with appropriate detectors or sensors,
which recognize the deviation and alert the
integrating center. The integrating center
immediately sends information to the con­
cerned effectors to either accelerate or
inhibit the activity so that the normalcy is FIGURE 4.1: Components of homeostatic
restored. system
26 Section 1 ê General Physiology

3. Transmission of the information from system and excretory systems invol­

the control center to the effectors for ved in these activities.
correcting the deviation. 5. Many hormones are essential for the
The transmission of message or infor­ metabolism of nutrients and other sub­
mation may be an electrical process in the stances necessary for the cells. The
form of impulses through nerves or a chemi­ hormones are to be synthesized and
cal process in the form of mainly hormones released from the endocrine glands
through blood and body fluids. in appropriate quantities and, these
hormones must act on the body cells
appropriately. Otherwise, it leads to
abnormal signs and symptoms.
6. Water and electrolyte balance should
One or more systems are involved in homeo­ be maintained optimally. Otherwise it
static mechanism of each function. Some leads to dehydration or water toxicity
of the functions in which the homeostatic and alteration in the osmolality of the
mechanism is well established are given body fluids. Kidneys, skin, salivary
below: glands and gastrointestinal tract take
1. The pH of the ECF has to be maintai­ care of this.
ned at the critical value of 7.4. The 7. For all these functions, the blood, which
tissues cannot survive if it is altered. forms the major part of internal environ­
Thus, the decrease in pH (acidosis) ment must be normal. It should contain
or increase in pH (alkalosis) affects required number of normal red blood
cells and adequate amount of plasma
the tissues markedly. The respiratory
with normal composition. Only then, it
system, blood and kidney helps in the
can transport the nutritive substances,
regulation of pH.
respiratory gases, metabolic and other
2. The body temperature must be main­
waste products.
tained at 37.5°C. Increase or decrease
8. Skeletal muscles are also help in homeo­
in temperature alters the metabolic
stasis by helping the organism to move
activities of the cells. The skin, respi­ around in search of food and protect the
ratory system, digestive system, excre­ organism from adverse surroundings
tory system, skeletal muscles and of damage and destruction.
ner­vous system are involved in main­ 9. Central nervous system that includes
taining the temperature within normal brain and spinal cord also plays an
limits. impor­tant role in homeostasis. The sen­
3. Adequate amount of nutrients must be sory system detects the state of the
supplied to the cells for various acti­ body or surroundings. The brain inte­
vities and growth of the tissues. Diges­ grates and interprets the pros and cons
tive system and circulatory system play of these information and com­ mands
major roles in the supply of nutrients. the body to act accordingly through
4. Adequate amount of oxygen should be motor system so that, the body can
supplied to the cells for the metabolic avoid the damage.
processes. And carbon dioxide and 10. The autonomic nervous system regu­
other metabolic end products must be lates all the vegetative functions of the
removed from the cells. Respira­ tory body essential for homeostasis.
Chapter 4 ê Homeostasis 27
„„ MECHANISM OF ACTION OF increases in blood, it inhibits the secretion
HOMEOSTATIC SYSTEM of TSH from pituitary so that, the secretion
of thyroxine from thyroid gland decrea­
The homeostatic mechanism acts through ses (Fig. 4.2). On the other hand, if thyro­
feedback mechanism. Feedback is a pro­ xin secretion is less, it induces pituitary
cess in which some proportion of the output gland to release TSH. Now, TSH stimulates
signal of a system is fed (passed) back to thyroid gland to secrete thyroxin (refer
the input. There are two types of feedback Chapter 51 for details). Another example
mechanisms: for negative feedback mechanism is main­
1. Negative feedback mechanism. tenance of water balance in the body
2. Positive feedback mechanism. (Fig. 4.3).

Negative Feedback Mechanism Positive Feedback Mechanism

Negative feedback mechanism is the one Positive feedback mechanism is the one
by which a particular system reacts in such in which the system reacts in such a way
a way as to stop the change or reverse as to amplify (increase the intensity of)
the direction of change. After receiving a the change in the same direction. Positive
message, the effectors send the inhibitory feedback is less common than the nega­
signals back to the system. Now, the system tive feedback. However, it has its own
stabilizes its own function either by stopping significance, particularly during emergency
the signals or by reversing the signals. conditions.
For example, thyroid-stimulating hor­ One of the positive feedbacks occurs
mone (TSH) released from pituitary gland during the blood clotting. Blood clotting is
stimulates thyroid gland, which in turn necessary to arrest bleeding during injury
secretes thyroxin. When thyroxin level and it occurs in three stages:

FIGURE 4.2: Negative feedback mechanism – secretion of thyroxine.

TSH = Thyroid-stimulating hormone.
28 Section 1 ê General Physiology

FIGURE 4.3: Negative feedback mechanism – maintenance of water balance.

ADH = Antidiuretic hormone.

1. Formation of prothrombin activator.

2. Conversion of prothrombin into throm­
3. Conversion of fibrinogen into fibrin by
Thrombin formed in the second stage
stimulates the formation of more prothro­
mbin activator in addition to converting
fibrinogen into fibrin, (Fig. 4.4). It causes
formation of more and more amount of
prothrombin activator so that the blood
clotting process is accelerated and blood

FIGURE 4.5: Positive feedback

mechanism – parturition
loss is prevented quickly (refer Chapter 20).
FIGURE 4.4: Positive feedback mechanism – Other processes where positive feedback
coagulation of blood. Once formed, thrombin occurs are milk ejection reflex (refer Chapter
induces the formation of more prothrombin 50) and parturition (Fig. 4.5) and both the
activator. processes involve oxytocin secretion.
Questions in General Physiology 29


„„ LONG QUESTIONS 5. Mitochondria.

6. Golgi apparatus.
1. Describe the mechanism of active 7. Apoptosis.
transport of substances through cell 8. Tight junctions.
membrane. 9. Gap junctions.
2. Describe the mechanism of passive 10. Passive transport.
transport of substances through cell 11. Active transport.
membrane. 12. Primary active transport.
3. Explain the homeostasis in the body 13. Secondary active transport.
with suitable examples. 14. Sodium-potassium pump.
15. Facilitated diffusion or carrier-mediated
„„ SHORT QUESTIONS diffusion.
16. Factors affecting diffusion.
1. Cell membrane. 17. Pinocytosis.
2. Proteins of cell membrane. 18. Phagocytosis.
3. Endoplasmic reticulum. 19. Negative feedback.
4. Ribosomes. 20. Positive feedback.
Section 2
Blood and Body Fluids

5. Body Fluids................................................................................ 33
6. Blood.......................................................................................... 39
7. Plasma Proteins......................................................................... 42
8. Red Blood Cells......................................................................... 45
9. Erythropoiesis............................................................................ 51
10. Hemoglobin................................................................................ 56
11. Erythrocyte Sedimentation Rate and Packed Cell Volume........ 59
12. Anemia....................................................................................... 62
13. Hemolysis and Fragility of Red Blood Cells............................... 66
14. White Blood Cells....................................................................... 69
15. Immunity..................................................................................... 75
16. Platelets..................................................................................... 85
17. Hemostasis................................................................................ 89
18. Coagulation of Blood.................................................................. 91
19. Blood Groups........................................................................... 101
20. Blood Transfusion.................................................................... 109
21. Reticuloendothelial System,
Tissue Macrophage and Spleen................................................111
22. Lymphatic System and Lymph .................................................114
23. Tissue Fluid and Edema............................................................117
Chapter 5

Body Fluids



Body is formed by solids and fluids. The fluid
part is more than 2/3 of the whole body. Water
forms most of the fluid part of the body. Compartments and distribution of body
In human beings, the total body water fluids with the quantity is given in Table 5.1.
varies from 45 to 75% of body weight. In Water moves between different compart­
a normal young adult male, body contains ments (Fig. 5.1). Total body water (40 L)
60 to 65% of water and 35 to 40% of is distributed into two major fluid compart­
solids. In a normal young adult female, the ments:
water is 50 to 55% and solids are 45 to 1. Intracellular fluid (ICF) forming 55% of
50%. The total quantity of body water in an the total body water (22 L).
average human being weighing about 70 2. Extracellular fluid (ECF) forming 45%
kg is about 40 L. of the total body water (18 L).
34 Section 2 ê Blood and Body Fluids

TABLE 5.1: Different compartments of

body fluid

Extracellular Intracellular
fluid (ECF) fluid (ICF)

Sodium 142 mEq/L 10 mEq/L

Calcium 5 mEq/L 1 mEq/L
Potassium 4 mEq/L 140 mEq/L
Magnesium 3 mEq/L 28 mEq/L
Chloride 103 mEq/L 4 mEq/L
Bicarbonate 28 mEq/L 10 mEq/L
Phosphate 4 mEq/L 75 mEq/L
Sulfate 1 mEq/L 2 mEq/L
Proteins 2 g/dL 16 g/dL
Amino acids 30 mg/dL 200 mg/dL
Glucose 90 mg/dL 0 to 20 mg/dL
Lipids 0.5 g/dL 2 to 95 g/dL
FIGURE 5.1: Body fluid compartments and pressure 35 mm Hg 20 mm Hg
movement of fluid between different compart­ of oxygen
ments. Other fluids = transcellular fluid, fluid in
bones and fluid in connective tissue. Partial
46 mm Hg 50 mm Hg
of carbon
Water 15 to 20 L (18) 20 to 25 L (22)
pH 7.4 7.0
Body fluids contain water and solids. Solids
are organic and inorganic substances.
Volume of different compartments of the
Organic substances present in body fluids
body fluid is measured by indicator dilution
are glucose, amino acids and other proteins, method or dye dilution method.
fatty acids and other lipids, hormones and


A known quantity of a substance such as a
The inorganic substances present in body
dye is administered into a specific body fluid
fluids are sodium, potassium, calcium, mag­ compartment. These substances are called
nesium, chloride, bicarbonate, phosphate the marker substances or indicators (Table
and sulfate. The differences between ECF 5.2). After administration into the fluid, the
and ICF are given in the Table 5.1. substance is allowed to mix thoroughly
Chapter 5 ê Body Fluids 35
TABLE 5.2: Marker substances used to Characteristics of Marker Substances
measure body fluid compartments
The dye or any substance used as a mar­
Fluid ker substance should have the following
Marker substances
compartment qualities:
1. Deuterium oxide (D2O) 1. Must be nontoxic.
Total body
2. Tritium oxide (T2O) 2. Must mix with the fluid compartment
3. Antipyrine thoroughly within reasonable time.
1. Radioactive sodium, 3. Should not be excreted rapidly.
chloride, bromide, 4. Should be excreted from the body
sulfate and thiosulfate completely within reasonable time.
2. Non-metabolizable
fluid 5. Should not change the color of the
saccharides such
as inulin, mannitol, body fluid.
raffinose and sucrose 6. Should not alter the volume of body
1. Radioactive iodine (131I)
2. Evans blue (T-1824)
with the fluid compartment. Then, a sample TOTAL BODY WATER
of fluid is drawn and the concentration The marker substance for measuring TBW
of the marker substance is determined.
The substances whose concentration can should be distributed through all the com­
be determined by using colorimeter or part­ments of body fluid. Such substances
radioactive substances are generally used are:
as marker substances. 1. Deuterium oxide.
2. Tritium oxide.
Formula to Measure the Body Fluid 3. Antipyrine.
Volume by Indicator Dilution Method
Deuterium oxide and tritium oxide mix
The quantity of fluid in the compartment is with fluids of all the compartments within
measured by using the formula: few hours after injection. Since plasma is
M part of total body fluid, the concentration
V = of marker substances can be obtained
from sample of plasma. And, the formula
V = The volume of fluid in the compart­ for indicator dilution method is applied to
ment calculate total body water.
M = Mass or total quantity of marker
substance injected „„ MEASUREMENT OF
C = Concentration of the marker sub­ EXTRACELLULAR FLUID VOLUME
stance in the sample fluid
Correction factor: Some amount of marker ECF volume is measured by using the
substance is lost through urine during substances, which can pass through the
distribution. So, the formula is corrected as capillary membrane freely and remain only
follows: in the ECF but not enter into the cell. Such
M – Amount of the marker substances are:
substance excreted 1. Radioactive sodium, chloride, bromide,
Volume =
C sulfate and thiosulfate.
36 Section 2 ê Blood and Body Fluids

2. Non-metabolizable saccharides like Measurement of plasma volume by

inulin, mannitol, raffinose and sucrose. indicator or dye dilution technique
When any of these substances is injec­ The principles and other details of this
ted into blood, it mixes with the fluid of all technique are same as that of ECF volume.
subcompartments of ECF within 30 minutes The dye which is used to measure plasma
to 1 hour. The indicator dilution method is volume is Evans blue or T-1824.
applied to calculate ECF volume. Since
Procedure: A small quantity of blood (3 to
ECF includes plasma, the concentration of
4 mL) is drawn from the subject and a known
the marker substance can be obtained in quantity of the dye is added. This is used
the sample of plasma. as control sample in the procedure. Then,
Some marker substances such as a known volume of dye is injected intra­
sodium, chloride, inulin and sucrose diffuse venously. After 10 minutes, a sample of blood
more widely throughout all subcompart­ is drawn. Then, another 4 samples of blood
ments of ECF. So, the measured volume are collected at the interval of 10 minutes. All
of ECF by using these substances is called the 5 samples are centrifuged and plasma is
sodium space, chloride space, inulin space separated from the samples. In each sample
and sucrose space. of plasma, the concentration of the dye is
measured by colorimetric method and the
Example for Measurement of ECF average concentration is found. The subject’s
Volume urine is collected and the amount of dye
excreted in the urine is measured.
Quantity of sucrose
injected (M) : 150 mg Calculation
Urinary excretion of sucrose : 10 mg The plasma volume is determined by using
Concentration of sucrose in the formula:
plasma (C) : 0.01 mg/mL Amount of dye injected –
Mass – Amount Amount excreted
Volume =
lost in urine Average concentration
Sucrose space =
Concentration of of dye in plasma
sucrose in plasma
150 – 10 mg 140
0.01 mg/mL 0.01
Measurement of total blood volume involves
Sucrose space = 14,000 mL
two steps:
Therefore, the ECF volume = 14 L
1. Determination of plasma volume.
„„ MEASUREMENT OF PLASMA 2. Determination of blood cell volume.
VOLUME Plasma volume is determined by indi­
cator dilution technique as mentioned above.
The substance, which binds with plasma Blood cell volume is determined by hemato­
proteins strongly and diffuses into intersti­ crit value.
tium only in small quantities or does not It is usually done by centrifuging the
diffuse at all, is used to measure plasma blood and measuring the packed cell volume
volume. (refer Chapter 11). PCV is expressed in
Chapter 5 ê Body Fluids 37
percentage. If this is deducted from 100, Classification
the percentage of plasma is known. From
Basically dehydration is of three types:
this, and from the volume of plasma, the
1. Mild dehydration when fluid loss is
amount of total blood is calculated by using about 5% of total body fluids.
the formula: 2. Moderate dehydration when fluid loss
100 × Amount of plasma is about 10%.
Blood volume = 3. Severe dehydration when fluid loss is
100 – PCV
about 15%.

1. Severe diarrhea and vomiting.
Intracellular fluid volume cannot be measu­ 2. Excess water loss through urine.
red directly. It is calculated from the values 3. Insufficient intake of water.
of volume of total body water and ECF 4. Excess sweating.
volume: 5. Use of laxatives or diuretics.
ICF volume =
Total fluid volume – ECF volume Signs and Symptoms

„„ MEASUREMENT OF INTERSTITIAL Mild and moderate dehydration

FLUID VOLUME 1. Dryness of the mouth.
Interstitial fluid volume also cannot be 2. Excess thirst.
3. Decrease in sweating.
measured directly. It is calculated from the
4. Decrease in urine formation.
values of ICF volume and plasma volume
as given below: Severe dehydration
Interstitial fluid volume =
ICF volume – Plasma volume 1. Decrease in blood volume.
2. Decrease in cardiac output.
3. Cardiac shock.
BALANCE Very severe dehydration
Body has several mechanisms which work 1. Damage of organs like brain, liver and
together to maintain the water balance. kidneys.
The important mechanisms involve hypo­ 2. Mental depression and confusion.
thalamus (refer Chapters 4, 98) and kidneys 3. Renal failure.
(refer Chapter 43). 4. Coma.

Overhydration, hyperhydration, water excess
Significant decrease in water content of the or water intoxication is defined as the
body is known as dehydration. condition in which body has too much water.
38 Section 2 ê Blood and Body Fluids

Causes 5. Anemia, acidosis, cyanosis, hemor­

rhage and shock.
Overhydration occurs when more fluid is 6. Muscular weakness, cramps and para­
taken than that can be excreted. It also lysis.
develops in some conditions such as heart 7. Severe conditions of overhydration
failure, renal disorders and hypersecretion result in:
of antidiuretic hormone. i. Delirium (extreme mental condition
characterized by confused state
Signs and Symptoms and illusion).
ii. Seizures (sudden uncontrolled
1. Behavioral changes. involuntary muscular contractions).
2. Drowsiness and inattentiveness. iii. Coma (profound state of un-con­
3. Nausea and vomiting. sciousness in which person fails
4. Sudden loss of weight followed by to respond to external stimuli and
weakness and blurred vision. cannot perform voluntary actions).
Chapter 6



„„ BLOOD Specific gravity of

total blood : 1.052 to 1.061
Blood is a connective tissue in fluid form. It Specific gravity of
is considered as the fluid of life because it blood cells : 1.092 to 1.101
carries oxygen from lungs to all parts of the Specific gravity of
body and carbon dioxide from all parts of plasma : 1.022 to 1.026
the body to the lungs. 5. Viscosity: Blood is five times more
viscous than water. It is mainly due to
„„ PROPERTIES OF BLOOD red blood cells and plasma proteins.
1. Color: Blood is red in color. Arterial
blood is scarlet red because of more
O2 and venous blood is purple red Blood contains the blood cells which are
because of more CO2. called formed elements and the liquid por­
2. Volume: The average volume of blood tion known as plasma.
in a normal adult is 5 L. In newborn
baby it is 450 mL. It increases during Blood Cells
growth and reaches 5 L at the time of Three types of cells are present in the
puberty. In females it is slightly less blood:
and is about 4.5 L. It is about 8% of the 1. Red blood cells (RBCs) or erythrocytes.
body weight in a normal young healthy 2. White blood cells (WBCs) or leukocytes.
adult weighing about 70 kg. 3. Platelets or thrombocytes.
3. Reaction and pH: Blood is slightly
alkaline and its pH in normal conditions Plasma
is 7.4. Plasma is a straw colored clear liquid part
4. The Specific gravity: of blood. It contains 91 to 92% of water and
40 Section 2 ê Blood and Body Fluids

FIGURE 6.1: Composition of plasma

8 to 9% of solids. The solids are the organic TABLE 6.1: Normal values of some important
and the inorganic substances (Fig. 6.1). substances in blood
Table 6.1 gives the normal values of some
important substances in blood. Substance Functions

Glucose 100 to 120 mg/dL

Creatinine 0.5 to 1.5 mg/dL
Serum is the clear straw colored fluid that Cholesterol Up to 200 mg/dL
oozes out from the clot. When the blood
Plasma proteins 6.4 to 8.3 g/dL
is shed or collected in a container, it clots
because of the conversion of fibrinogen Bilirubin 0.5 to 1.5 mg/dL
into fibrin. After about 45 minutes, serum Iron 50 to 150 µg/dL
oozes out of the clot. For clinical investi­
Copper 100 to 200 mg/dL
gations, serum is separated from blood
cells by centrifuging. Volume of the serum Calcium
9 to 11 mg/dL
is almost the same as that of plasma (55%). 4.5 to 5.5 mEq/L
It is different from plasma only by the Sodium 135 to 145 mEq/L
absence of fibrinogen, i.e. serum contains
Potassium 3.5 to 5.0 mEq/L
all the other constituents of plasma except
fibrinogen. Fibrinogen is absent in serum Magnesium 1.5 to 2.0 mEq/L
because it is converted into fibrin during Chloride 100 to 110 mEq/L
blood clotting. Thus,
Serum = Plasma – Fibrinogen Bicarbonate 22 to 26 mEq/L
Chapter 6 ê Blood 41
„„ FUNCTIONS OF BLOOD in the regulation of water content of the
1. Nutrient Function
Nutritive substances like glucose, amino 6. Regulation of Acid-base Balance
acids, lipids and vitamins derived from
diges­ted food are absorbed from gastro­ The plasma proteins and hemoglobin act
intestinal tract and carried by blood to as buffers and help in regulation of acid-
different parts of the body for growth and base balance.
produc­tion of energy.
7. Regulation of Body Temperature
2. Respiratory Function Because of the high specific heat of blood,
Transport of respiratory gases is done by it is responsible for maintaining the thermo­
the blood. It carries O2 from alveoli of lungs regulatory mechanism in the body, i.e.
to different tissues and CO2 from tissues to balance between heat loss and heat gain
alveoli. in the body.

3. Excretory Function 8. Storage Function

Waste products formed in the tissues during Water and some important substances like
various metabolic activities are removed by proteins, glucose, sodium and potassium
blood and carried to the excretory organs are constantly required by the tissues. All
like kidney, skin, liver, etc. for excretion. these substances are present in the blood
are taken by the tissues during the conditions
4. Transport of Hormones and like starvation, fluid loss, electrolyte loss, etc.
Hormones which are secreted by ductless 9. Defensive Function
(endocrine) glands are released directly The WBCs in the blood provide the defense
into the blood. The blood transports these mechanism and protect the body from the
hormones to their target organs/tissues. invading organisms. Neutrophils and mono­
Blood also transports enzymes. cytes engulf the bacteria by phago­cytosis.
Lymphocytes provide cellular and humoral
5. Regulation of Water Balance immunity. Eosinophils protect the body by
Water content of the blood is freely inter­ detoxification; disintegration and removal of
changeable with interstitial fluid. This helps foreign proteins (refer Chapters 14 and 15).
Chapter 7

Plasma Proteins


„„ INTRODUCTION some liver and kidney diseases. Normal

A/G ratio is 2:1.
The plasma proteins are:
1. Serum albumin.
2. Serum globulin.
3. Fibrinogen. In embryonic stage, the plasma proteins are
synthesized by the mesenchyme cells. In
„„ NORMAL VALUES adults, the plasma proteins are synthesized
The normal values of the plasma proteins mainly from reticuloendothelial cells of liver
are: and also from spleen, bone marrow, disinte­
Total proteins : 7.3 g/dL (6.4 to 8.3 g/dL) grating blood cells and general tissue cells.
Serum albumin : 4.7 g/dL Gamma globulin is synthesized from B
Serum globulin : 2.3 g/dL lymphocytes.
Fibrinogen : 0.3 g/dL
Globulin is of three types, α-globulin, „„ VARIATIONS IN PLASMA
β-globulin and γ-globulin. PROTEIN LEVEL
The level of plasma proteins vary inde­
Albumin/Globulin Ratio
pendently of one another. Elevation of all
The ratio between plasma level of albu­ fractions of plasma proteins is called hyper­
min and globulin is called albumin/globulin proteinemia and decrease in all frac­tions of
(A/G) ratio. It is an important indicator of plasma proteins is called hypoproteinemia.
Chapter 7 ê Plasma Proteins 43
„„ 1. MOLECULAR WEIGHT Plasma proteins are essential for the trans­
port of various substances in the blood.
Albumin : 69,000
Albumin, alpha globulin and beta globu­lin
Globulin : 1,56,000
are responsible for the transport of the hor­
Fibrinogen : 4,00,000
mones, enzymes, etc. The alpha and beta
globulins transport metals in the blood.
The plasma proteins are responsible for the „„ 4. ROLE IN MAINTENANCE OF
oncotic or osmotic pressure in the blood. The OSMOTIC PRESSURE IN BLOOD
osmotic pressure exerted by proteins in the
plasma is called colloidal osmotic (oncotic) Plasma proteins exert the colloidal osmotic
pressure (refer Chapter 3). Normally, it is (oncotic) pressure. The osmotic pressure
about 25 mm Hg. Albumin plays a major exerted by the plasma proteins is about 25
role in exerting oncotic pressure. mm Hg. Since the concentration of albumin
is more than the other plasma proteins, it
„„ 3. SPECIFIC GRAVITY exerts maximum pressure.
The specific gravity of the plasma proteins
is 1.026. „„ 5. ROLE IN REGULATION OF
„„ 4. BUFFER ACTION Plasma proteins, particularly the albumin,
The acceptance of hydrogen ions is called play an important role in regulating the acid-
buffer action. The plasma proteins have 1/6 base balance in the blood. This is because
of total buffering action of the blood. of the virtue of their buffering action.


The plasma proteins provide viscosity to the
„„ 1. ROLE IN COAGULATION OF blood, which is important to maintain the
BLOOD blood pressure. Albumin provides maximum
Fibrinogen is essential for the coagulation viscosity than the other plasma proteins.
of blood (refer Chapter 18).
Globulin and fibrinogen accelerate the ten­
The γ-globulins play an important role in the dency of rouleaux formation by the red blood
defense mechanism of the body by acting cells. Rouleaux formation is responsible for
as antibodies. These proteins are also ESR, which is an important diagnostic and
called immunoglobulins (refer Chapter 15). prognostic tool (refer Chapter 8).
44 Section 2 ê Blood and Body Fluids

„„ 8. ROLE IN SUSPENSION substances are produced by leukocytes

STABILITY OF from the plasma proteins.
During circulation, the red blood cells remain
suspended uniformly in the blood. This During fasting, inadequate food intake
property of the red blood cells is called or inadequate protein intake, the plasma
the suspension stability. Globulin and fibri­ proteins are utilized by the body tissues
nogen help in the suspension stability of the as the last source of energy. The plasma
red blood cells. proteins are split into amino acids by the
tissue macrophages. The amino acids are
„„ 9. ROLE IN PRODUCTION OF taken back by blood and distributed throug­
TREPHONE SUBSTANCES hout the body to form cellular protein mole­
Trephone substances are necessary for cules. Because of this, the plasma proteins
nourishment of tissue cells in culture. These are called the reserve proteins.
Chapter 8

Red Blood Cells


„„ INTRODUCTION portion is thinner and periphery is thicker.

The biconcave contour of RBCs has some
Red blood cells (RBCs) also known as
erythrocytes are the non-nucleated formed mechanical and functional advantages.
elements in the blood. The red color of the
RBC is due to the presence of hemoglobin. Advantages of Biconcave
Shape of RBCs
„„ NORMAL VALUE 1. It helps in equal and rapid diffusion of
The RBC count ranges between 4 and 5.5 oxygen and other substances into the
millions/cu mm of blood. In adult males, it is interior of the cell.
5 millions/cu mm and in adult females it is 2. Large surface area is provided for
4.5 millions/cu mm. absorption or removal of different sub­
„„ MORPHOLOGY OF 3. Minimal tension is offered on the mem­
RED BLOOD CELLS brane when volume of cell alters.
4. While passing through minute capil­
„„ NORMAL SHAPE laries, RBCs can squeeze through
Normally, the RBCs are disk shaped and the capillaries easily without getting
biconcave (dumbbell shaped). The central damaged.
46 Section 2 ê Blood and Body Fluids

Diameter : 7.2 µ (6.9 to 7.4 µ)
Thickness : At the periphery it is thicker
with 2.2 µ and at the center
it is thinner with 1 µ (Fig.
8.1). The difference in thick­
ness is because of the bicon­
cave shape
Surface area : 120 sq µ
Volume : 85 to 90 cu µ
FIGURE 8.2: Rouleau formation
„„ NORMAL STRUCTURE (Courtesy: Dr Nivaldo Medeiros)
RBC is non-nucleated cell. Because of
the absence of nucleus, the DNA is also „„ 2. SPECIFIC GRAVITY
absent. Other organelles such as mito­ The specific gravity of RBC is 1.092 to
chondria and Golgi apparatus also are 1.101.
absent in RBC. Since, mitochondria are
absent, the energy is produced from glyco­ „„ 3. PACKED CELL VOLUME
lytic process.
Packed cell volume (PCV) is the volume
of the RBCs expressed in percentage. It
„„ PROPERTIES OF is also called hematocrit value. It is 45% of
RED BLOOD CELLS the blood and the plasma volume is 55%
„„ 1. ROULEAUX FORMATION (refer Chapter 11).

When blood is taken out of the blood ves­ „„ 4. SUSPENSION STABILITY

sel, the RBCs pile up one above another
During circulation, the RBCs remain sus­
like the pile of coins. This property of the
pended or dispersed uniformly in the blood.
RBCs is called rouleaux (pleural = rouleau) This property of the RBCs is called the
formation (Fig. 8.2). It is accelerated by suspension stability.
plasma proteins namely globulin and
fibrinogen. „„ LIFESPAN OF RED BLOOD
Average lifespan of RBC is about 120 days.
After the lifetime, the senile (old) RBCs are
destroyed in reticuloendothelial system.


When the RBCs become older (120 days),
the cell membrane becomes very fragile.
So these cells are destroyed while trying
FIGURE 8.1: Dimensions of RBC. A. Surface to squeeze through the capillaries which
view; B. Sectioned view. have lesser or equal diameter as that of
Chapter 8 ê Red Blood Cells 47
RBC. The destruction occurs mainly in the in determination of blood group and enables
capillaries of spleen because these capil­ to prevent the reactions due to incompatible
laries are very much narrow. So, the spleen blood transfusion (refer Chapter 19).
is called graveyard of RBCs.
The destroyed RBCs are fragmented „„ VARIATIONS IN NUMBER OF
and hemoglobin is released from the frag­ RED BLOOD CELLS
mented parts.
Hemoglobin is degraded into iron, globin „„ PHYSIOLOGICAL VARIATIONS
and porphyrin. Iron combines with the pro­
tein called apoferritin to form ferritin which A. Increase in RBC Count –
is stored in the body and reused later. Polycythemia
Globin enters the protein depot for later use Increase in the RBC count is known as
(Fig. 8.3). The porphyrin is degraded into polycythemia. It occurs in both physiological
bilirubin, which is excreted by liver through and pathological conditions. When it occurs
bile (refer Chapter 34). in physio­logical conditions it is called physio­
Daily 10% of senile RBCs are destroyed logical polycythemia. The increase in number
in normal young healthy adults. It causes during this condition is marginal and tem­
release of about 0.6 g/dL of hemoglobin
porary. It occurs in the following condi­tions.
into the plasma. From this 0.9 to 1.5 mg/dL
bilirubin is formed. 1. Age
At birth, the RBC count is 8 to 10 millions/cu
mm of blood. The count decreases within
10 days after birth due to destruction of
1. Transport of O2 from the RBCs.
Lungs to the tissues
Hemoglobin combines with oxygen to form
oxyhemoglobin (refer Chapter 82).

2. Transport CO2 from the

Tissues to the Lungs
Hemoglobin combines with carbon dioxide
and form carbhemoglobin.

3. Buffering Action in Blood

Hemoglobin functions as a good buffer. By
this action, it regulates the hydrogen ion
concentration and thereby plays a role in
the maintenance of acid-base balance.

4. In Blood Group Determination

RBCs carry the blood group antigens like A
antigen, B antigen and Rh factor. This helps FIGURE 8.3: Fate of RBC
48 Section 2 ê Blood and Body Fluids

2. Sex
Before puberty and after menopause, in
females the RBC count is similar to that in
males. During reproductive period of fema­
les, the count is less than of males (4.5
millions/cu mm).
3. High altitude
In people living in mountains (above 10,000
feet from mean sea level), the RBC count
is more than 7 millions/cu mm. It is due
to hypoxia (decreased oxygen supply to
tissues) in high altitude. Hypoxia stimulates
kidney to secrete a hormone called erythro­
poietin which stimulates the bone marrow
to produce more RBCs (Fig. 8.4).
FIGURE 8.4: Physiological polycythemia
4. Muscular exercise in high altitude
RBC count increases after muscular exer­
cise. It is because of mild hypoxia which
increases the sympathetic activity secretion
of adrenaline from adrenal medulla. Adre­
naline contracts spleen and RBCs are
released into blood. Hypoxia also causes
secretion of erythropoietin which stimulates
the bone marrow to produce more RBCs.
5. Emotional conditions
The RBC count increases during the emo­
tional conditions such as anxiety. It is
because of increase in the sympathetic
activity and contraction of spleen (Fig. 8.5).
FIGURE 8.5: RBC count in emotional
6. Increased environmental conditions
Generally increased temperature increases B. Decrease in RBC Count
all the activities in the body including pro­ Decrease in RBC count occurs in the follow­
duction of RBCs. ing physiological conditions.
7. After meals 1. High barometric pressures
There is a slight increase in the RBC count At high barometric pressures as in deep
after taking meals. It is because of need for sea, where the oxygen tension of blood is
more oxygen for metabolic activities. higher, the RBC count decreases.
Chapter 8 ê Red Blood Cells 49
2. During sleep 5. Poisoning by chemicals like phosphorus
and arsenic.
Generally all the activities of the body are 6. Repeated mild hemorrhages.
decreased during sleep including produc­ All these conditions lead to hypoxia
tion of RBCs. which stimulates release of erythropoietin.
3. Pregnancy Erythropoietin stimulates the bone marrow
resulting in increased RBC count.
In pregnancy, the RBC count decreases.
It is because of increase in ECF volume. Anemia
Increase in ECF volume, increases the
plasma volume also resulting in hemodilu­ The abnormal decrease in RBC count is
tion. So, there is a relative reduction in the called anemia. This is described in refer
RBC count. Chapter 12.


Pathological Polycythemia
Under physiological conditions, the size
Pathological polycythemia is the abnormal of RBCs in venous blood is slightly larger
increase in the RBC count. The count incre­ than those in arterial blood. In pathological
ases above 7 millions/cu mm of the blood. conditions, the variations in size of RBCs are:
Polycythemia is of two types, the primary 1. Microcytes : Smaller cells.
polycythemia and secondary poly­cythemia. 2. Macrocytes : Larger cells.
3. Anisocytosis : Cells without uniform size.
Primary Polycythemia – Polycythemia
Vera 1. Microcytes
Primary polycythemia is otherwise known Microcytes are present in:
as polycythemia vera. It is a disease charac­ i. Iron deficiency anemia.
terized by persistent increase in RBC ii. Prolonged forced breathing.
count above 14 millions/cu mm of blood. iii. Increased osmotic pressure in blood.
This is always associated with increased
WBC count above 24,000/cu mm of blood. 2. Macrocytes
Polycythemia vera occurs because of red
bone marrow malignancy. Macrocytes are present in:
i. Megaloblastic anemia.
ii. Muscular exercise.
Secondary Polycythemia
iii. Decreased osmotic pressure in blood.
It is the pathological condition in which
polycythemia occurs because of diseases 3. Anisocytes
in some other system such as: Anisocytes occurs in pernicious anemia.
1. Respiratory disorders like emphysema.
2. Congenital heart disease.
3. Ayerza’s disease – condition associated
with hypertrophy of right ventricle and
obstruction of blood flow to lungs. The shape of RBCs is altered in many
4. Chronic carbon monoxide poisoning. conditions including different types of anemia:
50 Section 2 ê Blood and Body Fluids

1. Crenation: Shrinkage as in hypertonic is disturbed, the cells are affected. For

conditions. example, when the RBCs are immersed in
2. Spherocytosis: Globular form as in hypotonic saline the cells swell and rupture
hypo­tonic conditions. by bursting because of endosmosis (refer
3. Elliptocytosis: Elliptical shape as in Chapter 3). The hemoglobin is released
certain types of anemia. from the ruptured RBCs.
4. Sickle cell: Crescentic shape as in
sickle cell anemia. „„ CONDITIONS WHEN
5. Poikilocytosis: Unusual shapes due to HEMOLYSIS OCCURS
deformed cell membrane. The shape
1. Hemolytic jaundice.
will be of flask, hammer or any other 2. Antigen antibody reactions.
unusual shape. 3. Poisoning by chemicals or toxins.


Hemolysins or hemolytic agents are the
„„ DEFINITION substances, which cause destruction of
Hemolysis RBCs.
Hemolysins are of two types:
Hemolysis is the destruction of formed ele­ 1. Chemical substances.
ments. To define more specifically, it is the 2. Substances of bacterial origin or sub­
process, which involves the breakdown of stances found in body.
RBC and liberation of hemoglobin.
1. Alcohol.
The susceptibility of RBC to hemolysis or 2. Benzene.
tendency to break easily is called fragility 3. Chloroform.
(fragile = easily broken). 4. Ether.
Fragility is of two types: 5. Acids.
1. Osmotic fragility which occurs due to 6. Alkalis.
exposure to hypotonic saline. 7. Bile salts.
2. Mechanical fragility which occurs due 8. Saponin.
to mechanical trauma (wound or 9. Chemical poisons like arsenial pre­
injury). parations, carbolic acid, nitrobenzene
Normally, old RBCs are destroyed in and resin.
the reticuloendothelial system. Abnormal
hemolysis is the process by which even „„ SUBSTANCES OF BACTERIAL
younger RBCs are destroyed in large num­ ORIGIN OR SUBSTANCES
ber by the presence of hemolytic agents or FOUND IN BODY
1. Toxic substances or toxins from bac­
teria such as Streptococcus, Staphylo­
coccus, Tetanus bacillus, etc.
Normally, plasma and RBCs are in osmotic 2. Venom of poisonous snakes like cobra.
equilibrium. When the osmotic equilibrium 3. Hemolysins from normal tissues.
Chapter 9



„„ DEFINITION 2. Hepatic Stage

Erythropoiesis is the process of the origin, During the next 3 months (second trimester)
development and maturation of erythro­ of intrauterine life, RBCs are produced mainly
cytes. Hemopoiesis is the process of origin, from the liver. Some cells are produced from
development and maturation of all the the spleen and lymphoid organs are also.
blood cells.
3. Myeloid Stage
During the last 3 months (third trimester)
„„ IN FETAL LIFE of intrauterine life, the RBCs are produced
In fetal life, the erythropoiesis occurs in dif­ from red bone marrow and liver.
ferent sites in different periods.
1. Mesoblastic Stage AND ADULTS

During the first 2 or 3 months (first trimester) 1. Up to the age of 20 years: RBCs are
of intrauterine life, the RBCs are produced produced from red bone marrow of all
from mesenchymal cells of yolk sac. bones.
52 Section 2 ê Blood and Body Fluids

2. After the age of 20 years: RBCs are lymphocytes. When grown in cultures,
produced from all the membranous these cells form colonies hence, name
bones and ends of long bones. colony-forming blastocytes. The different
units of colony-forming cells are:
„„ PROCESS OF ERYTHROPOIESIS i. Colony-forming unit-erythrocytes
(CFU-E) from which RBCs develop.
„„ STEM CELLS ii. Colony-forming unit-granulocytes/
monocytes (CFU-GM) from which
RBCs develop from the hematopoietic stem granulocytes (neutrophils, baso­phils
cells (Fig. 9.1) in the bone marrow. These cells and eosinophils) and mono­cytes
are called uncommitted pluripotent hemato­ develop.
poietic stem cells (PHSC). The PHSC are iii. Colony-forming unit-megakaryo-
not designed to form a particular type of cytes (CFU-M) from which platelets
blood cell; hence the name uncommitted develop.
PHSC. When the cells are designed to form
a particular type of blood cell, the uncom­ „„ CHANGES DURING
mitted PHSCs are called committed PHSC. ERYTHROPOIESIS
The committed PHSCs are of two types: When the cells of CFU-E pass through
1. Lymphoid stem cells (LSC) which give different stages and finally become the
rise to lymphocytes and natural killer matured RBCs, four important changes are
(NK) cells. noticed:
2. Colony-forming blastocytes, which give 1. Reduction in size of the cell (from the
rise to all the other blood cells except diameter of 25 to 7.2 µ).

FIGURE 9.1: Stem cells. B = Basophil, E = Eosinophil, L = Lymphocyte, M = Monocyte,

N = Neutrophil, P = Platelets, R = Red blood cells.
Chapter 9 ê Erythropoiesis 53
2. Disappearance of nucleoli and nuc­ 1. Proerythroblast (Megaloblast)
Proerythroblast or megaloblast is very large
3. Appearance of hemoglobin.
4. Change in the staining properties of in size with a diameter of about 20 µ. A large
the cytoplasm. nucleus with two or more nucleoli and a
chromatin network is present. Hemoglobin
„„ STAGES OF ERYTHROPOIESIS is absent. The cytoplasm is basophilic in
nature. The proerythroblast multiplies seve­
The various stages between CFU-E cells ral times and finally forms the cell of next
and matured RBC are (Fig. 9.2): stage called early normoblast.
1. Proerythroblast.
2. Early normoblast. 2. Early Normoblast
3. Intermediate normoblast.
4. Late normoblast. It is smaller than proerythroblast with a
5. Reticulocyte. diameter of about 15 µ. The nucleoli dis­
6. Matured erythrocyte. appear from the nucleus and condensation

FIGURE 9.2: Stages of erythropoiesis. CFU-E = Colony-forming unit-erythrocyte, CFU-GM =

Colony-forming unit-granulocyte/monocyte, CFU-M = Colony-forming unit-megakaryocyte.
54 Section 2 ê Blood and Body Fluids

of chromatin network occurs. The conden­ In newborn babies, the reticulocyte

sed network becomes dense. The cyto­ count is 2 to 6% of RBCs, i.e. 2 to 6 reticulo­
plasm is basophilic in nature. So, this cell cytes are present for every 100 RBCs.
is also called basophilic erythroblast. This The number of reticulocytes decreases
cell develops into the next stage called during the 1st week after birth. Later, the
intermediate normoblast. reticulocyte count remains constant at or
below 1%. The number increases whenever
3. Intermediate Normoblast the erythropoietic activity increases. Reticulo­
cytes can enter the capillaries through the
It is smaller than the early normoblast with
capillary membrane from the site of pro­
a diameter of 10 to 12 µ. The nucleus is duction by diapedesis.
still present. But the chromatin network
shows further condensation. This stage is 6. Matured Erythrocyte
mar­ked by the appearance of hemoglobin.
Because of the presence of small quantity The cell decreases in size with the diameter
of acidic hemoglobin, the cytoplasm which of 7.2 µ. The reticular network disappears
is basophilic becomes polychromatic, i.e. and the cell becomes the matured RBC
both acidic and basic in nature. So this cell with biconcave shape and hemoglobin but
is called polychromophilic or polychromatic without nucleus. It requires 7 days for the
erythroblast. This cell develops into the next proerythroblast to become fully developed
stage called late normoblast. and matured of RBC.

4. Late Normoblast „„ FACTORS NECESSARY FOR

The diameter of the cell decreases further
to about 8 to 10 µ. Nucleus becomes very Development and maturation of erythrocytes
small with very much condensed chro­ require many factors which are classified
matin network and is called ink spot nuc­ into three categories:
leus. Quantity of hemoglobin increases 1. Stimulating factors.
making the cytoplasm almost acidophilic. 2. Maturation factors.
So, the cell is now called orthochromatic 3. Factors necessary for hemoglobin for­
erythroblast. At the end of late normoblastic mation.
stage, just before it passes to the next
stage, the nucleus disintegrates and dis­ „„ STIMULATING FACTORS
appears by the process called pyknosis.
1. Hypoxia
The final remnant is extruded from the cell.
Late normoblast develops into the next Reduced availability of oxygen to the tissues
stage called reticulocyte. is called hypoxia. It is the most important
stimulating factor for erythropoiesis. It stimu­
5. Reticulocyte lates erythropoiesis by inducing secre­tion
of erythropoietin from kidney.
It is slightly larger than matured RBC and
it is otherwise known as immature RBC. It
2. Erythropoietin
is called reticulocyte because, the reticular
network or reticulum that is formed from the Erythropoietin is a hormone secreted mainly
disintegrated organelles are present in the by peritubular capillaries in the kidney and
cytoplasm. a small quantity is also secreted from the
Chapter 9 ê Erythropoiesis 55
liver and the brain. Hypoxia is the stimulant the presence of intrinsic factor of Castle.
for the secretion of erythropoietin. Vitamin B12 is stored mostly in liver and in
Erythropoietin promotes the following pro­ small quantity in muscle. Its deficiency cau­
cesses: ses pernicious anemia (macrocytic anemia)
i. Production of proerythroblasts from in which the cells remain larger with fragile
CFU-E of the bone marrow. and weak cell membrane.
ii. Development of proerythroblasts into
matured RBCs through the several 2. Intrinsic Factor of Castle
iii. Release of matured erythrocytes into It is produced in gastric mucosa by the
blood. Some reticulocytes are also parietal cells of the gastric glands. It is essen­
rele­ased along with matured RBCs. tial for the absorption of vitamin B12 from
intestine. Absence of intrinsic factor also
3. Thyroxine leads to pernicious anemia because of failure
of vitamin B12 absorption. The deficiency of
Being a general metabolic hormone, thyro­
intrinsic factor occurs in conditions like severe
xine accelerates the process of erythro­
gastritis, ulcer and gastrectomy.
poiesis at many levels.
3. Folic Acid
4. Hematopoietic Growth Factors
Hematopoietic growth factors or growth Folic acid is also essential for the synthesis
indu­cers are the interleukins 3, 6 and 11 of DNA. Deficiency of folic acid decreases
and stem cell factor (steel factor). Generally the DNA synthesis causing maturation fai­
these factors induce the proliferation of lure. Here the cells are larger and remain
in megaloblastic (proerythroblastic) stage
which leads to megaloblastic anemia.
5. Vitamins
The vitamins A, B, C, D and E are necessary HEMOGLOBIN FORMATION
for erythropoiesis. Deficiency of these vita­
mins causes anemia. Various materials are essential for the for­
mation of hemoglobin in the RBCs such as:
„„ MATURATION FACTORS 1. First class proteins and amino acids of
high biological value: For formation of
Vitamin B12, intrinsic factor and folic acid are
necessary for the maturation of RBCs.
2. Iron: For formation of heme part of the
1. Vitamin B12 (Cyanocobalamin)
3. Copper: For absorption of iron from GI
Vitamin B12 is essential for synthesis of DNA, tract.
cell division and maturation in RBCs. It is 4. Cobalt and nickel: For the utilization of
also called extrinsic factor as it is obtained iron during hemoglobin synthesis.
mostly from diet. It is also produced in 5. Vitamins: Vitamin C, riboflavin, nicotinic
the large intestine by the intestinal flora. acid and pyridoxine: For hemoglobin
It is absorbed from the small intestine in synthesis.
Chapter 10



„„ INTRODUCTION At the time of birth, infants and growing

children, Hb content is high because of incre­
Hemoglobin (Hb) is the iron-containing colo­ ased number of RBCs (refer Chapter 8).
ring pigment of red blood cell (RBC). It
forms 95% of dry weight of RBC and 30 to Sex
34% of wet weight. The molecular weight of
In adult males : 15 g/dL
Hb is 68,000. In adult females : 14.5 g/dL
Average Hb content in blood is 14 to 16 g/dL. RESPIRATORY GASES
However, it varies depending upon age
The main function of Hb is the transport of
and sex of the individual and the number
respiratory gases. It transports:
of RBCs. 1. Oxygen from the lungs to tissues.
2. Carbon dioxide from tissues to lungs
Age (refer Chapter 82).
At birth : 25 g/dL
After 3rd month : 20 g/dL „„ BUFFER ACTION
After 1 year : 17 g/dL Hb acts as a buffer and plays an important
From puberty onwards : 14 to 16 g/dL role in acid-base balance.
Chapter 10 ê Hemoglobin 57
„„ STRUCTURE OF HEMOGLOBIN 1. Hemoglobinopathies
Hb is a conjugated protein. It consists of a Hemoglobinopathy is a genetic disorder
protein called globin and an iron-containing caused by abnormal polypeptide chains of
pigment called heme. Hb. Some of the hemoglobinopathies are
Iron is present in an unstable ferrous HbS, HbC, HbE and HbM.
(Fe2+) form. Heme part is called porphyrin. It
is formed by four pyrrole rings (tetrapyrrole). 2. Hb in Thalassemia and
The iron is attached to each pyrrole ring Related Disorders
and globin molecule. In thalassemia, different types of abnormal
Globin is made up of four polypeptide Hb are present. The polypeptide chains
chains. Among the four polypeptide chains, are decreased, absent or abnormal (refer
two are α-chains and two are β-chains. Chapter 12).


Hb is of two types: Abnormal Hb formed by the combination
1. Adult Hb (HbA). of Hb with some substances other than
2. Fetal Hb (HbF). oxygen and carbon dioxide is called Hb
Both the types of Hb differ from each derivative. Abnormal Hb derivatives are for­
other structurally and functionally. med by carbon monoxide poisoning or
due to the combination of some drugs like
Structural Difference nitrites, nitrates and sulfonamides.
The abnormal hemoglobin derivatives
In adult Hb, the globin contains two α-chains are carboxyhemoglobin, methemoglobins
and two β-chains. In fetal Hb, there are and sulfhemoglobin. The high levels of Hb
two α-chains and two γ-chains instead of derivatives in blood produce serious effects
β-chains. by preventing the transport of oxygen. It
results in oxygen lack in tissues, which may
Functional Difference be fatal.
Functionally, fetal Hb has more affinity for
oxygen than adult Hb. And, the oxygen- „„ CARBOXYHEMOGLOBIN
hemo­globin dissociation curve of fetal Carboxyhemoglobin or carbon monoxyhemo­
blood is shifted to left (refer Chapter 82). globin is the abnormal Hb derivative formed
by the combination of carbon monoxide with
„„ ABNORMAL HEMOGLOBIN Hb. Carbon monoxide is a colorless and
odorless gas. Since Hb has 200 times more
The abnormal types of Hb are produced affinity for carbon monoxide than oxygen, it
because of structural changes in the poly­ hinders the transport of oxygen resulting in
peptide chains caused by mutation in the tissue hypoxia (refer Chapter 82).
genes of the globin chains. There are two Some of the sources of carbon mono­
categories of abnormal Hb: xide are charcoal burning, coal mines,
1. Hemoglobinopathies. deep wells, underground drainage system,
2. Hb in thalassemia and related disorders. exhaust of gasoline engines, gases from
58 Section 2 ê Blood and Body Fluids

guns and other weapons, heating system the protein part (globin) is synthesized in
with poor or improper ventilation, smoke ribosomes.
from fire and tobacco smoking.
Signs and Symptoms of
Heme is synthesized from succinyl-CoA
Carbon Monoxide Poisoning
and the glycine in the mitochondria.
1. While breathing air with less than 1%
of carbon monoxide, the Hb saturation „„ FORMATION OF GLOBIN
is 15 to 20% and mild symptoms like
headache and nausea appear. The polypeptide chains of globin are pro­
2. While breathing air with more than 1% duced in the ribosomes. There are four types
carbon monoxide, the Hb saturation is of polypeptide chains namely, alpha, beta,
30 to 40%. It causes severe symptoms gamma and delta chains. Each globin mole­
like convulsions, cardiorespiratory arrest, cule is formed by the combination of 2 pairs
unconsciousness and coma. of chains. Adult Hb contains two alpha chains
3. When Hb saturation increase above and two beta chains. Fetal Hb contains two
50%, death occurs. alpha chains and two gamma chains.

Methemoglobin is the abnormal Hb deriva­ Each polypeptide chain combines with one
tive formed when iron molecule of Hb heme molecule. Thus, after the complete
is oxidized from normal ferrous state to configuration, each Hb molecule contains 4
ferric state. Methemoglobin is also called polypeptide chains and 4 heme molecules.
ferrihemoglobin. Normal methemoglobin
level is less than 3% of total Hb. „„ SUBSTANCES NECESSARY FOR
Some of the sources of methemoglobin HEMOGLOBIN SYNTHESIS
are contaminated well waters with nitrates and
nitrites, matchsticks, explosives, naphthalene Various materials are essential for the for­
balls and irritant gases like nitrous oxide. mation of Hb in the RBC (refer Chapter 9 for
Sulfhemoglobin is the abnormal Hb deri­ „„ DESTRUCTION OF
vative formed by the combination of hemo­ HEMOGLOBIN
globin with hydrogen sulfide. It is caused After the lifespan of 120 days, the RBC is
by drugs such as sulfonamides. Normal destroyed in the reticuloendothelial system,
sulfhemoglobin level is less than 1% of total particularly in spleen and the Hb is released
into plasma. Soon, the Hb is degraded in
the reticuloendothelial cells and split into
„„ SYNTHESIS OF HEMOGLOBIN globin, iron and porphyrin.
Synthesis of Hb actually starts in proery­ Globin is utilized for the resynthesis of
throblastic stage. However, Hb appears in Hb. Iron is stored in the body. Porphyrin is
the intermediate normoblastic stage only. converted into biliverdin. In human being,
The production of the Hb is continued until most of the biliverdin is converted into bili­
the stage of reticulocyte. The heme portion rubin. Bilirubin and biliverdin are together
of Hb is synthesized in mitochondria. And called the bile pigments (refer Chapter 34).
Chapter 11

Erythrocyte Sedimentation Rate and

Packed Cell Volume



„„ ERYTHROCYTE 1. Westergren method.

SEDIMENTATION RATE 2. Wintrobe method.
„„ DEFINITION Westergren Method
Erythrocyte sedimentation rate (ESR) is
In this method, Westergren tube is used
the rate at which the erythrocytes settle
down. Normally, when the blood is in circu­ to determine ESR. The tube is 300 mm
lation, the red blood cells (RBCs) remain long and opened on both ends (Fig. 11.1A).
suspended uniformly. This is called sus­ It is marked 0 to 200 mm from above down­
pension stability of RBCs. If blood is mixed wards. 1.6 mL of blood is mixed with 0.4
with an anticoagulant and allowed to stand mL of 3.8% sodium citrate (antico­agulant).
undisturbed on a vertical tube, the red cells The ratio of blood and anticoagulant is 4:1.
settle down due to gravity with a super­ This blood is loaded in the Westergren
natant layer of clear plasma. tube up to ‘0’ mark above. The tube is
placed vertically in the Westergren stand
and left undisturbed. The reading is taken
There are two methods to determine ESR: after 1 hour.
60 Section 2 ê Blood and Body Fluids

Wintrobe Method „„ NORMAL VALUES OF ESR

In this method, Wintrobe tube is used to By Westergren Method

determine ESR. This tube is a short and In males : 3 to 7 mm in 1 hour
opened on one end and closed on the other In females : 5 to 9 mm in 1 hour
end (Fig. 11.1B). It is 110 mm long with 3 Infants : 0 to 2 mm in 1 hour
mm bore. It is used for determining ESR
and PCV. It is marked on both sides. On By Wintrobe Method
one side, the marking is 0 to 100 (for ESR) In males : 0 to 9 mm in 1 hour
and on other side, 100 to 0 (for PCV) from In females : 0 to 15 mm in 1 hour
above downwards. Infants : 0 to 5 mm in 1 hour
About 1 mL of blood is mixed with an
anticoagulant called ethylenediaminetetra
acetic acid (EDTA). The blood is loaded in
the tube up to ‘0’ mark above. The tube is ESR is an easy, inexpensive test which
helps in diagnosis as well as prognosis.
placed on the Wintrobe stand and left undis­
Prognosis means monitoring the course
turbed. The reading is taken after 1 hour. of disease and response of the patient to
therapy. Determination of ESR is especially
helpful in assessing the progress of patients
treated for certain chronic disorders such
as pulmonary tuberculosis and rheumatoid

Physiological Variation
1. Age: ESR is less in children and infants
because of more number of RBCs.
2. Sex: It is more in females than in males
because of less number of RBCs.
3. Menstruation: The ESR increases during
menstruation because of loss of blood
and RBCs.
4. Pregnancy: From 3rd month to partu­
rition, ESR increases up to 35 mm in
1 hour because of hemodilution.

Pathological Variation
ESR increases in the following diseases:
1. Tuberculosis.
FIGURE 11.1: A. Westergren tube: This is used 2. All types of anemia, except sickle cell
for determining erythrocyte sedimentation rate anemia.
(ESR); B. Wintrobe tube: This is used to deter­ 3. Malignant tumors.
mine ESR and packed cell volume (PCV). 4. Rheumatoid arthritis.
Chapter 11 ê Erythrocyte Sedimentation Rate and Packed Cell Volume 61
5. Rheumatic fever.
6. Liver diseases.
ESR decreases in the following dise­
1. Allergic conditions.
2. Sickle cell anemia.
3. Peptone shock.
4. Polycythemia.
5. Severe leukocytosis.


Following factors increase the ESR:
1. Specific gravity of RBC.
2. Rouleaux formation.
3. Increase in size of RBC.
4. Decrease in RBC count.
Following factors decrease the ESR:
1. Viscosity of blood.
2. Increase in RBC count.


„„ DEFINITION FIGURE 11.2: Packed cell volume
Packed cell volume (PCV) is the volume of 1. Diagnosis and treatment of anemia.
the RBCs in the blood that is expressed in 2. Diagnosis and treatment of polycy­
percentage. It is also called hematocrit value. themia.
3. Determination of severity of dehydra­
„„ METHOD OF DETERMINATION tion and recovery from dehydration
Blood is mixed with the anticoagulant EDTA after treatment.
or heparin and filled in Wintrobe tube up 4. Decision of blood transfusion.
to the 100 or 0 mark above. The tube with
the blood is centrifuged at a speed of 3,000
revolutions per minute (rpm) for 30 minutes. Normal PCV:
At the end of 30 minutes, the tube is taken In males : 40 to 45%
out and the reading is taken. The RBCs are In females : 38 to 42%
packed at the bottom and this is the PCV.
The plasma remains above this. In between „„ VARIATIONS IN PCV
the RBCs and the plasma, there is a white PCV increases in:
buffy coat, which is formed by white blood 1. Polycythemia.
cells (WBCs) and the platelets (Fig. 11.2). 2. Dehydration.
PCV decreases in:
1. Anemia.
2. Cirrhosis of liver.
Determination of PCV helps in: 3. Pregnancy.
Chapter 12



„„ INTRODUCTION TABLE 12.1: Morphological classification

of anemia
Anemia is the blood disorder characterized
by the reduction in: Size of Color of
1. Red blood cell (RBC) count. Type of anemia RBC RBC
2. Hemoglobin content.
3. Packed cell volume (PCV). Normocytic
Normal Normal
Normal Less
Anemia is classified by two methods:
A. Morphological classification. Macrocytic
Large Less
B. Etiological classification.
Small Less
„„ MORPHOLOGICAL hypochromic

By this method, anemia is classified by the „„ ETIOLOGICAL CLASSIFICATION

morphology (size and color) of RBC. Size By this method, anemia is classified by the
of RBC is expressed as mean corpuscular cause. Etiology means the study of cause
volume (MCV). Color of RBC depends upon or origin of any disease. On the basis of
hemoglobin concentration in RBC and it is etiology, anemia is divided into five types.
expressed as mean corpuscular hemo­glo­
bin concentration (MCHC). By this method, 1. Hemorrhagic Anemia
the anemia is classified into four types as Hemorrhage means excessive loss of
given in Table 12.1. blood (refer Chapter 76). Anemia due to
Chapter 12 ê Anemia 63
hemor­rhage is known as hemorrhagic Sickle cell anemia
anemia or blood loss anemia. It occurs both
Sickle cell anemia is an inherited blood
in acute and chronic hemorrhagic condi­
disorder characterized by sickle-shaped
RBCs. It occurs when a person inherits two
Acute hemorrhage abnormal genes (one from each parent).
It is also called hemoglobin SS disease or
Acute hemorrhage means sudden loss of
sickle cell disease. It is common in people
large quantity of blood as in case of acci­
of African origin.
dents. The RBCs are normocytic and normo­
In sickle cell anemia, hemoglobin be­
chromic (Table 12.2).
comes abnormal with normal α-chains and
Chronic hemorrhage abnormal β-chains. Because of this, RBCs
attain sickle (crescent) shape and become
Chronic hemorrhage refers to loss of blood
more fragile leading to hemolysis (refer
over a long period of time. Blood loss
Table 12.2).
occurs by internal or external bleeding as in
conditions like peptic ulcer, purpura, hemo­ Thalassemia
philia and menorrhagia. The RBCs are micro­
Thalassemia is an inherited disorder cha­
cytic and hypochromic (refer Table 12.2).
racterized by abnormal hemoglobin. In
normal hemoglobin, the number of α- and
2. Hemolytic Anemia
β-polypeptide chains is equal. In thalas­
Hemolysis means destruction of RBCs. semia, the number of these chains is not
Anemia due to excess destruction of RBCs is equal. This causes the precipitation of the
called hemolytic anemia. Hemolysis occurs polypeptide chains leading to defective
because of the following reasons (refer formation of RBCs or hemolysis of the
Table 12.2): matured RBCs.
i. Liver failure. It is also known as Cooley’s anemia or
ii. Renal disorder. Mediterranean anemia. It is more com­mon
iii. Hypersplenism. in Thailand and to some extent in Mediter­
iv. Burns. ranean countries.
v. Infections like hepatitis, malaria and
Thalassemia is of two types:
i. α-thalassemia.
vi. Drugs such as penicillin, antimalarial
ii. β-thalassemia.
drugs and sulfa drugs.
The β-thalassemia is very common
vii. Poisoning by chemical substances like
among these two.
lead, coal and tar.
viii. Presence of isoagglutinins like anti-Rh.
3. Nutrition Deficiency Anemia
ix. Auto­immune diseases such as rheu­
matoid arthritis and ulcerative colitis. Anemia that occurs due to deficiency of a
x. Hereditary diseases. nutritive substance necessary for erythro­
poiesis is called nutrition deficiency anemia.
Hereditary disorders
Such substances are iron, proteins and
Hereditary diseases are the diseases trans­ vitamins like C, B12 and folic acid. The types
mitted from parents to children through of nutrition deficiency anemia are detailed
genes (inherited genetically). below.
64 Section 2 ê Blood and Body Fluids

Iron deficiency anemia Vitamin B12 deficiency – pernicious

Iron deficiency anemia is the most common
type of anemia. It develops due to inadequate Vitamin B12 is a maturation factor for RBC
availability of iron for hemoglobin synthesis. and deficiency of this causes pernicious
The RBCs are microcytic and hypo­ anemia, which is also called Addison’s
chromic (refer Table 12.2). anemia. It occurs because of less intake of
vitamin B12 or poor absorption of vitamin B12.
Protein deficiency anemia
Vitamin B12 is absorbed from the stomach
Protein deficiency decreases the hemo­ with the help of intrinsic factor of Castle,
globin synthesis and the RBCs become which is secreted in the gastric mucosa.
macro­cytic and hypochromic in nature (refer Decrease in the production of intrinsic factor
Table 12.2). causes poor absorption of vitamin B12. The

TABLE 12.2: Etiological classification of anemia

Type of anemia Causes Morphology of RBC

Acute hemorrhage – acute loss of
Normocytic, normochromic
Hemorrhagic anemia
Chronic hemorrhage – chronic loss
Microcytic, hypochromic
of blood
1. Liver failure
2. Renal disorder
3. Hypersplenism
4. Burns
5. Infections – malaria and
Normocytic normochromic
6. Drugs like penicillin, antimalarial
Hemolytic anemia drugs and sulfa drugs
7. Poisoning by lead, coal and tar
8. Isoagglutinins – anti-Rh
Sickle cell anemia – sickle shape
and hypochromic
9. Hereditary disorders
Thalassemia – small, irregular and
Iron deficiency Microcytic, hypochromic
Protein deficiency Macrocytic, hypochromic
Nutrition deficiency
anemia Macrocytic, normochromic/
Vitamin B12
Folic acid Megaloblastic, hypochromic
Aplastic anemia Bone marrow disorder Normocytic, normochromic
1. Rheumatoid arthritis
Anemia of chronic
2. Tuberculosis Normocytic, normochromic
3. Chronic renal failure
Chapter 12 ê Anemia 65
RBCs are macrocytic and normochromic/ „„ 3. CARDIOVASCULAR SYSTEM
hypochromic (refer Table 12.2).
There is increase in heart rate and cardiac
Folic acid deficiency – megaloblastic output. Heart is dilated and cardiac murmurs
anemia are produced. The velocity of blood flow is
Folic acid is necessary for the maturation of
RBC. Deficiency of this leads to defective „„ 4. RESPIRATION
DNA synthesis making the nucleus to remain
immature. The RBCs are megaloblastic and Rate and force of respiration increases.
hypochromic (refer Table 12.2). Sometimes, it leads to breathlessness and
dyspnea (difficulty in breathing). Oxygen-
hemoglobin dissociation curve is shifted to
4. Aplastic Anemia
Aplastic anemia is due to the bone marrow
disorder. The red bone marrow is reduced „„ 5. DIGESTION
and replaced by fatty tissues. In this condi­
Anorexia (loss of appetite), nausea, vomi­
tion, the RBCs are normocytic and normo­ ting, abdominal discomfort and constipation
chromic (refer Table 12.2). It occurs in condi­ are common. In pernicious anemia, there is
tions such as repeated exposure to X-ray atrophy of papillae in tongue. In aplastic
or γ-ray radiation, tuberculosis and viral anemia, necrotic lesions appear in mouth
infections like hepatitis and HIV infec­tions. and pharynx.

5. Anemia due to Chronic Diseases „„ 6. METABOLISM

Anemia occurs due to some chronic dise­ Basal metabolic rate increases in severe
ases such as rheumatoid arthritis, tuber­ anemia.
culosis and chronic renal failure. RBCs
are normocytic and normochromic (refer „„ 7. KIDNEY
Table 12.2).
Renal function is disturbed. Albuminuria is
„„ 1. SKIN In females, the menstrual cycle is disturbed.
There may be menorrhagia, oligomenorrhea
In anemic patients, the color of the skin
or amenorrhea (refer Chapter 60).
becomes pale which is observed promi­
nently in buccal cavity, pharyngeal mucous
membrane, conjunctivae, lips, ear lobes,
palm and nail bed. Skin also loses the The common neuromuscular symptoms
elasticity and becomes thin and dry. are headache, lack of concentration, rest­
lessness, irritability, drowsiness, dizziness
„„ 2. HAIR AND NAILS or vertigo, especially when standing, incre­
ased sensitivity to cold and fainting. Muscles
Loss of hair is common with thinning and become weak and the patient feels lack of
early graying. The nails become brittle and energy and fatigued quite often and quite
easily breakable. easily.
Chapter 13

Hemolysis and Fragility

of Red Blood Cells


„„ INTRODUCTION 2. Abnormal shape of RBCs.

3. Diseases.
Hemolysis is the rupture of the blood cells,
4. Mechanical factors.
particularly erythrocytes with the release of
hemoglobin into the blood. „„ 1. HEMOLYSINS
Hemolysis occurs both in normal and
abnormal conditions. Normally, rupture of Hemolysins or hemolytic agents are the
substances which cause destruction of RBCs.
red blood cells occurs after the life span
Hemolysins are of three types:
of 120 days. The cell membrane of the
i. Hemolysins of bacterial origin.
senile RBC becomes fragile and it cannot
ii. Hemolysins of animal origin.
withstand the stress of squeezing through iii. Hemolysins in the form of chemical
the thin capillaries. So the cell breaks and substances.
releases hemoglobin. In this way, only
10% of the total RBCs are hemolyzed and i. Hemolysins of Bacterial Origin
so it does not cause any adverse effect in
During bacterial infection, many bacteria
the body.
produce some toxic substances become
Hemolysis occurs during some abnor­
the hemolysins and destroy RBCs. Bacteria
mal conditions due to the presence of which produce hemolysins are gram-posi­
some external factors. In this process, even tive bacteria like Streptococcus species,
younger RBCs are broken down in large Staphylo­coccus aureus, Listeria species,
number and a large quantity of hemoglobin Bacillus cereus and Clostridium tetani and
is released into the blood. This may lead Gram-negative bacteria like E. coli, Serratia
to the clinical conditions like hemolytic species, Proteus spp and Pseudomonas
jaundice and hemolytic anemia. aeruginosa.

„„ CAUSES OF HEMOLYSIS ii. Hemolysins of Animal Origin

Abnormal hemolysis occurs because of: Venom of poisonous snakes like cobra and
1. Hemolysins. viper contain hemolysins.
Chapter 13 ê Hemolysis and Fragility of Red Blood Cells 67
iii. Hemolysins in the Form of Chemical hemo­dialysis or heart-lung bypass machine
Substances during cardiac surgery. In such conditions,
hemolysis might be induced either mechani­
Some of the chemical substances act as
cally or chemically.
hemolysins and cause the death of RBCs.
Example, alcohol, ether, benzene, chloro­form,
either, acids, alkalis, bile salts and saponin. „„ FRAGILITY
Some chemical poisons such as arsenic Fragility refers to tendency of RBC to break
preparations, carbolic acid, nitrobenzene easily or susceptibility (to be affected) of
and resin also act like hemolysins.
RBC to hemolysis (Fragile = easily broken).
Fragility is of two types:
1. Osmotic fragility, which occurs due to
Normal biconcave shape of RBC is essen­ exposure to hypotonic saline.
tial to prevent hemolysis. But in some here­ 2. Mechanical fragility, which occurs due to
ditary disorders such as sickle cell anemia mechanical trauma (wound or injury).
and thalassemia, RBCs attain abnormal Normally, plasma and RBCs are in
shape like sickle shape, oval shape, ellipti­ osmotic equilibrium. When the osmotic equi­
cal shape, round shape, etc. The cell mem­ librium is disturbed, the cells are affected.
branes of these cells become more fragile For example, when the RBCs are immersed
resulting in hemolysis. in hypotonic saline the cells swell and rup­
ture by bursting because of endosmosis
„„ 3. DISEASES (refer Chapter 5). The hemoglobin is rele­
ased from the ruptured RBCs.
Some diseases that cause hemolysis are
autoimmune diseases, infections, severe
renal failure that needs hemodialysis. Some „„ FRAGILITY TEST
medications like cephalosporins, levodopa, Fragility test is a test that measures the
non-steroidal anti-inflammatory drugs, peni­ resistance of erythrocytes in hypotonic
cillin can cause hemolysis by producing saline solution. It is done by using sodium
antibodies against red blood cells. chloride solution at different concentrations
from 1.2 to 0.2%. The solutions at different
„„ 4. MECHANICAL FACTORS concentrations are taken in series of Cohn’s
Some mechanical factors like physical tubes. Then one drop of blood to be tested
stress and compression of muscles during is added to each tube. The sodium chloride
severe exercise also can induce hemo­ solution and the blood in each tube are
lysis. This occurs in cases of repeated mixed well and left undisturbed for some
mechanical movements like prolonged time. Results can be analyzed by observing
marching, marathon running, and bongo the tubes:
drumming. Freezing the blood at near to 0° 1. If there is no hemolysis: Fluid in the
temperature is one of the most important tube appears turbid.
mechanical factors in causing hemolysis 2. If hemolysis is started: Turbidity is
of RBCs. reduced.
Rarely hemolysis occurs in condi­ 3. If hemolysis is completed: Fluid beco­
tions that involve using artificial kidney for mes clear.
68 Section 2 ê Blood and Body Fluids

Index for Fragility At 0.45%, only the older cells are destroyed
After 20 minutes: because, their membrane is fragile. So, these
No hemolysis = Up to 0.6% cells cannot withstand this hypotonicity. But,
Onset of hemolysis = Around 0.45% younger cells are not affected. At 0.35%,
Completion of hemolysis = Around 0.35% even the younger cells are destroyed.
Chapter 14

White Blood Cells


„„ INTRODUCTION 1. Granulocytes with granules.

2. Agranulocytes without granules.
White blood cells (WBCs) or leukocytes
are the colorless and nucleated formed
1. Granulocytes
elements of blood (leuko = white or color­
less). Depending upon the staining property of
Compared to RBCs, the WBCs are larger granules, the granulocytes are classified
in size and lesser in number. Yet func­tio­ into three types:
nally, these cells are as important as RBCs i. Neutrophils: Granules take both acidic
these play very important role in defense and basic stains.
mechanism of body by acting like soldiers ii. Eosinophils: Granules take acidic stain.
and protecting the body from invading iii. Basophils: Granules take basic stain.
2. Agranulocytes
Agranulocytes have plain cytoplasm without
Leukocytes are classified into two groups granules. Agranulocytes are of two types:
depending upon the presence or absence i. Monocytes.
of granules in the cytoplasm: ii. Lymphocytes.
70 Section 2 ê Blood and Body Fluids

Morphology of each white blood cell is
different from others. Regarding functions,
WBCs play an important role in defense
mechanism. These cells protect the body
from invading organisms or foreign bodies
either by destroying or inactivating them.
However, in defense mechanism, each type
of WBCs acts in a different way.

Neutrophils are also known as polymorpho­
nuclear leukocytes because the nucleus
is multilobed. The number of lobes in the
nuclei varies from 1 to 6 (Fig. 14.1). The
granules are fine or small in size. When
stained with Leishman’s stain (which con­
tains acidic eosin and basic methylene
blue), the granules take both the stains
equally. So, the granules appear violet in
color. The diameter of cell is 10 to 12 µ. The
neutrophils are ameboid and phagocytic in
FIGURE 14.1: Different white blood
Functions cells

Along with monocytes, the neutrophils provide

Pus and Pus Cells
the first line of defense against the invading
microorganisms. Neutrophils wander freely Pus is the whitish yellow fluid formed in the
all over the body through the tissue. infected tissue. During the battle against
Neutrophils move by diapedesis towards the bacteria, many WBCs are killed by
the site of infection by means of chemotaxis.
the toxins released from the bacteria. The
Chemotaxis occurs due to the attraction by
dead cells are collected in the center of
some chemical substances called chemo­
attractants, which are released from the infected area. The dead cells together with
infected area. After reaching the area, the plasma leaked from the blood vessel, lique­
neutrophils engulf the bacteria and then fied tissue cells and RBCs escaped from
destroy them by means of phagocytosis damaged blood vessel (capillaries) consti­
(refer Chapter 3). tute the pus.
Chapter 14 ê White Blood Cells 71
„„ EOSINOPHILS either in the center of the cell or pushed to
one side and a large amount of cytoplasm
is seen.
Eosinophils have coarse (larger) granules
in the cytoplasm, which stain pink or red Functions
with eosin. Normally the nucleus is bilobed
Monocytes are the largest cells among the
and spectacle shaped. Rarely trilobed nuc­
leus may be present. The diameter of the leukocytes. Like neutrophils, monocytes
also are motile and phagocytic in nature.
cell varies between 10 and 14 µ.
These cells wander freely through all
Functions tissues of the body and provide the first line
of defense along with neutrophils.
Eosinophils provide defense to the body by Monocytes are the precursors of the
acting against the parasitic infections and tissue macrophages. The matured mono­
allergic conditions like asthma. Eosinophils cytes stay in the blood only for few hours.
are responsible for detoxification, disinte­ Afterwards these cells enter the tissues from
gration and removal of foreign proteins. the blood and become tissue macropha­
Eosinophils attack the invading orga­
ges. Examples of tissue macrophages are
nisms by secreting some special type of
Kupffer cells in liver, alveolar macrophages
cytotoxic substances. These substances
in lungs and macrophages in spleen. The
become lethal and destroy the parasites.
functions of macrophages are discussed in
Chapter 21.
Morphology „„ LYMPHOCYTES
Basophils also have coarse granules in Morphology
the cytoplasm and the granules stain purple
Lymphocytes also do not have granules in
blue with methylene blue. Nucleus is bilobed.
the cytoplasm. The nucleus is oval, bean
Diameter of the cell is 8 to 10 µ.
shaped or kidney shaped and occupies the
Functions whole of the cytoplasm. A rim of cytoplasm
may or may not be seen.
Basophils play an important role in healing Depending upon the size, the lympho­
processes and acute hypersensitivity reac­ cytes are divided into two types:
tions (allergy). 1. Large lymphocytes – younger cells
Basophils execute the functions by rele­ with a diameter of 10 to 12 µ.
asing some important substances from their 2. Small lymphocytes – older cells with a
granules such as heparin and histamine. diameter of 7 to 10 µ.
„„ MONOCYTES Functions
Morphology The lymphocytes are responsible in deve­
Monocytes are the largest leukocytes with lopment of immunity. Depending upon the
diameter of 14 to 18 µ. The cytoplasm is function, the lymphocytes are divided into
clear without granules. The nucleus is round, two types:
oval, horseshoe shaped, bean shaped or 1. T lymphocytes which are concerned
kidney shaped. The nucleus is placed with cellular immunity.
72 Section 2 ê Blood and Body Fluids

2. B lymphocytes which are concerned 5. Sleep: Decreases slightly.

with humoral immunity. 6. Emotional conditions like anxiety:
The functions of these two types of Incre­ases slightly.
lympho­ cytes are explained in detail in 7. Pregnancy: Increases.
Chapter 15. 8. Menstruation: Increases.
9. Parturition: Increases.
1. Total leukocyte count (TC): 4,000 to „„ PATHOLOGICAL VARIATIONS
11,000/cu mm of blood. Leukocytosis
2. Differential WBC count (DC): Given in
Table 14.1. It occurs in the following pathological condi­
„„ VARIATIONS IN 1. Infections.
2. Allergy.
3. Common cold.
Leukocyte count varies both in physiological 4. Tuberculosis.
and pathological conditions. Increase in 5. Glandular fever.
leukocyte count is called leukocytosis and
decrease in the count is called leucopenia. Leukopenia
The term leukopenia is generally used only Leukopenia occurs in the following patho­
for pathological conditions. logical conditions:
1. Anaphylactic shock.
„„ PHYSIOLOGICAL VARIATIONS 2. Cirrhosis of liver.
1. Age: In infants and children, total WBC 3. Disorders of spleen.
count is more; it is about 20,000/cu mm 4. Pernicious anemia.
in infants and about 10,000 to 15,000/ 5. Typhoid and paratyphoid.
cu mm of blood in children. In adults it 6. Viral infections.
ranges between 4,000 and 11,000/cu
mm of blood. Leukemia
2. Sex: Slightly more in males than in The leukemia is the condition, which is charac­
females. terized by abnormal and uncontrolled incre­
3. Diurnal variation: Minimum in early ase in leukocyte count more than 10,00,000/
morning and maximum in the afternoon. cu mm. It is also called blood cancer.
4. Exercise: Increases slightly. However, all the WBCs may not increase
at a time. Leukocytosis occurs because of
TABLE 14.1: Normal values of different WBCs increase in any one of the WBCs.
Absolute value
Leukocyte Percentage „„ LIFESPAN OF
per cu mm
Neutrophils 50 to 70 3,000 to 6,000
Lifespan of WBCs is as follows:
Eosinophils 2 to 4 150 to 450
Neutrophils : 2 to 5 days
Basophils 0 to 1 0 to 100 Eosinophils : 7 to 12 days
Monocytes 2 to 6 200 to 600 Basophils : 12 to 15 days
Monocytes : 2 to 5 days
Lymphocytes 20 to 30 1,500 to 2,700
Lymphocytes : ½ to 1 day.
Chapter 14 ê White Blood Cells 73
„„ PROPERTIES OF 3. Chemotaxis
Chemotaxis is the attraction of WBCs
1. Diapedesis towards the injured tissues by the chemical
substances released at the site of injury.
Diapedesis is the process by which the leuko­
cytes squeeze through the narrow blood 4. Phagocytosis
Neutrophils and monocytes engulf the foreign
bodies by means of phagocytosis (refer
2. Ameboid Movement Chapter 3).
Neutrophils, monocytes and lymphocytes
show amebic movement characterized by „„ LEUKOPOIESIS
protrusion of the cytoplasm and change in Leukopoiesis is the development and matu­
the shape. ration of leukocytes (Fig. 14.2).

FIGURE 14.2: Leucopoiesis. E = Eosin, M = Macrophage, GM = Granulocyte/Macrophage,

RBC = Red blood cell.
74 Section 2 ê Blood and Body Fluids

„„ STEM CELLS Colony-stimulating Factors

The committed pluripotent stem cell gives Colony-stimulating factors are proteins which
rise to leukocytes through various stages. cause the formation of colony-forming blasto­
The details are given in Chapter 9. Colony-stimulating factors are of three
„„ FACTORS NECESSARY FOR 1. Granulocyte-CSF (G-CSF) secreted
LEUKOPOIESIS by monocytes and endothelial cells.
2. Granulocyte-monocyte-CSF (GM-CSF)
Leukopoiesis is influenced by hematopoietic
secreted by monocytes, endothe­ lial
growth factors and colony-stimulating factors cells and T lymphocytes.
(CSFs). Hematopoietic growth factors are 3. Monocyte-CSF (M-CSF) secreted by
discussed in Chapter 10. monocytes and endothelial cells.
Chapter 15



76 Section 2 ê Blood and Body Fluids

„„ DEFINITION AND TYPES OF Types of Acquired Immunity

IMMUNITY Two types of acquired immunity develop in
Immunity is defined as the capacity of the the body:
body to resist the pathogenic agents. It is 1. Cell-mediated immunity or cellular
the ability of the body to resist the entry of immunity.
different types of foreign bodies like bac­ 2. Humoral immunity.
teria, virus, toxic substances, etc.
Immunity is of two types: „„ DEVELOPMENT AND
I. Innate immunity. PROCESSING OF
II. Acquired immunity. LYMPHOCYTES
„„ INNATE IMMUNITY OR In fetus, lymphocytes develop from bone
NON-SPECIFIC IMMUNITY marrow. All the lymphocytes are released
in the circulation and are differentiated into
Innate immunity is the inborn capacity of two categories:
the body to resist the pathogens. By chance,
1. T lymphocytes.
if the organisms enter the body, innate
2. B lymphocytes.
immunity eliminates them before the deve­
lopment of any disease.
This type of immunity represents the first
line of defense against any type of pathogens. T lymphocytes are processed in thymus.
Therefore, it is also called non-specific immu­ The processing occurs mostly during the
nity. Examples of innate immunity are: period between just before birth and few
1. Destruction of toxic substances or orga­ months after birth.
nisms entering digestive tract through Thymus secretes thymosin, which acce­
food by enzymes in digestive juices. lerates the proliferation and activation of
2. Destruction of bacteria by salivary
lymphocytes in thymus. It also increases the
activity of lymphocytes in lymphoid tissues.
3. Destruction of bacteria by acidity in
urine and vaginal fluid.
Types of T Lymphocytes

„„ ACQUIRED IMMUNITY OR During the processing, T lymphocytes are

SPECIFIC IMMUNITY transformed into four types:
1. Helper T cells or inducer T cells.
Acquired immunity is the resistance deve­ 2. Cytotoxic T cells or killer T cells.
loped in the body against any specific
3. Suppressor T cells.
foreign body like bacteria, viruses, toxins,
4. Memory T cells.
vaccines or transplanted tissues. So, this
type of immunity is also known as specific
Storage of T Lymphocytes
It is the most powerful immune mecha­ After the transformation, all the types of
nism that protects the body from invad­ing T lymphocytes leave the thymus and are
organisms or toxic substances. Lympho­ stored in lymphoid tissues of lymph nodes,
cytes are responsible for acquired immunity spleen, bone marrow and the gastrointes­
(Fig. 15.1). tinal (GI) tract.
Chapter 15 ê Immunity 77

FIGURE 15.1: Schematic diagram showing development of immunity

„„ B LYMPHOCYTES and the processing of B lymphocytes takes

place in bone marrow and liver.
B lymphocytes were first discovered in the
bursa of Fabricius in birds, hence the name
Types of B Lymphocytes
B lymphocytes. The bursa of Fabricius is
a lymphoid organ situated near the cloaca After processing, the B lymphocytes are
of birds. The bursa is absent in mammals, transformed into two types:
78 Section 2 ê Blood and Body Fluids

1. Plasma cells. materials. These antigenic materials are

2. Memory cells. released from invading organisms and are
presented to the helper T cells by antigen-
Storage of B Lymphocytes presenting cells.
After the transformation, B lymphocytes are
stored in the lymphoid tissues of lymph
nodes, spleen, bone marrow and the GI Antigen-presenting cells are the special
tract. type of cells in the body which induce the
release of antigenic materials from invading
„„ ANTIGENS organisms and later present these materials
to the helper T cells. Major antigen-presen­
„„ DEFINITION AND TYPES ting cells are macrophages. Dendritic cells in
Antigens are the substances, which induce spleen, lymph nodes and skin also function
specific immune reactions in the body. The like antigen-presenting cells.
antigens are mostly the conjugated pro­
teins like lipoproteins, glycoproteins and Role of Antigen-presenting Cells
nucleoproteins. Invading foreign organisms are either engul­
Antigens are of two types as given below: fed by macrophages through phagocytosis
1. Autoantigens or self-antigens which or trapped by dendritic cells. Later, the
are present on the body’s own cells antigen from these organisms is digested
like ‘A’ antigen and ‘B’ antigen on the into small peptides. The antigenic peptide
RBCs. products are moved towards the surface of
2. Foreign antigens or non-self-antigens the antigen-presenting cells and loaded on
which enter the body from outside. a genetic matter of the antigen-presenting
cells called human leukocyte antigen (HLA).
„„ DEVELOPMENT OF CELL- The HLA is present in the molecule of class
MEDIATED IMMUNITY II major histocompatibility complex (MHC)
which is situated on the surface of the
„„ INTRODUCTION antigen-presenting cells.
The cell-mediated immunity is offered by T
Presentation of Antigen
lymphocytes. It involves several types of cells
such as macrophages, T lymphocytes and The antigen-presenting cells present their
natural killer cells and hence the name cell- class II MHC molecules together with anti­
mediated immunity. It is also called cellular gen bound HLA to the helper T cells. This
immunity or T cell immunity. It does not involve activates the helper T cells through series
antibodies. of events (Fig. 15.2).
Cellular immunity is the major defense
mechanism against infections by viruses, Sequence of Events During Activation
fungi and few bacteria. It is also responsible of Helper T Cells
for delayed allergic reactions and rejection 1. Helper T cell recognizes the antigen
of transplanted tissues. bound to class II MHC molecule which is
Cell-mediated immunity starts develop­ displayed on the surface of the antigen-
ing when T cells come in contact with the presenting cell. It recognizes the antigen
antigens. Usually, the invading microbial or with the help of its own surface receptor
non-microbial organisms carry the antigenic protein called T cell receptor.
Chapter 15 ê Immunity 79
ii. Gamma interferon which stimulates the
phagocytic activity of cytotoxic cells,
macrophages and natural killer (NK)

Role of TH2 Cells

TH2 cells are concerned with humoral
immunity and secrete interleukin-4 and
interleukin-5 which are concerned with:
i. Activation of B cells.
ii. Proliferation of plasma cells.
FIGURE 15.2: Antigen presentation. The antigen- iii. Production of antibodies by plasma cell.
presenting cells present their class II MHC
molecules together with antigen-bound HLA to „„ ROLE OF CYTOTOXIC T CELLS
the helper T cells. MHC = Major histocompatibility
The cytotoxic T cells that are activated
complex, HLA = Human leukocyte antigen.
by helper T cells circulate through blood,
2. The recognition of the antigen by the lymph and lymphatic tissues and destroy
helper T cell initiates a complex inter­ the invading organisms by attacking them
action between the helper T cell recep­ directly.
tor and the antigen. This reaction acti­
vates helper T cells. Mechanism of Action of
3. At the same time, macrophages (the Cytotoxic T Cells
antigen presenting cells) release inter­
leukin-1 which facilitates the activation 1. The receptors situated on the outer
and proliferation of helper T cells. membrane of cytotoxic T cells bind
4. The activated helper T cells proliferate the antigens or organisms tightly with
and the proliferated helper T cells cytotoxic T cells.
enter the circulation for further actions. 2. Then, the cytotoxic T cells enlarge and
5. Simultaneously the antigen bound to release cytotoxic substances like the
class II MHC molecules activate the B lysosomal enzymes, which destroy the
cells also resulting in development of invading organisms.
humoral immunity (see below). 3. Like this, each cytotoxic T cell can des­
„„ ROLE OF HELPER T CELLS troy a large number of microorganisms
one after another.
The helper T cells which enter the circu­
lation, activate all the other T cells and B Other Actions of Cytotoxic T Cells
cells. The helper T cells are of two types:
1. Helper-1 (TH1) cells. 1. The cytotoxic T cells also destroy can­
2. Helper-2 (TH2) cells. cer cells, transplanted cells such as
those of transplanted heart or kidney
Role of TH1 Cells or any other cells, which are foreign
TH1 cells are concerned with cellular bodies.
immunity and secrete two substances: 2. Cytotoxic T cells destroy even the body’s
i. Interleukin-2 which activates the other own tissues which are affected by the
T cells. foreign bodies, particularly the viru­ses.
80 Section 2 ê Blood and Body Fluids

Many viruses are entrapped in the lymphocytes and released into the blood
membrane of affected cells. The and lymph. The blood and lymph are the
antigen of the viruses attracts the T body fluids (humours or humors in Latin).
cells. And the cytotoxic T cells kill the Since the B lymphocytes provide immunity
affected cells also along with viruses. through humors, this type of immunity is
Because of this, cytotoxic T cell is called humoral immunity or B cell immunity.
called killer cell. The antibodies are the gamma globulins
produced by B lymphocytes. These anti­
„„ ROLE OF SUPPRESSOR T CELLS bodies fight against the invading organisms.
The suppressor T cells are also called regu­ The humoral immunity is the major defense
latory T cells. These T cells suppress the mechanism against the bacterial infection.
activities of the killer T cells. Thus, the sup­ As in the case of cell-mediated immunity,
pressor T cells play an important role in the macrophages and other antigen-
preventing the killer T cells from destroying presenting cells play an important role in
the body’s own tissues along with invaded the development of humoral immunity also.
organisms. The suppressor cells suppress
the activities of helper T cells also. „„ ROLE OF ANTIGEN-PRESENTING
Some of the T cells activated by an anti­ The ingestion of foreign organisms and
gen do not enter the circulation, but digestion of their antigen by the antigen-
remain in lymphoid tissue. These T cells presenting cells are already explained.
are called memory T cells.
In later periods, the memory cells migrate Presentation of Antigen
to various lymphoid tissues throughout the The antigen-presenting cells present their
body. When the body is exposed to the class II MHC molecules together with anti­
same organism for the second time, the gen bound HLA to B cells. This activates
memory cells identify the organism and the B cells through series of events.
immediately activate the other T cells. So,
the invading organism is destroyed very
Sequence of Events During
quickly. The response of the T cells is also
Activation of B Cells
more powerful this time.
1. The B cell recognizes the antigen
„„ SPECIFICITY OF T CELLS bound to class II MHC molecule which
Each T cell is designed to be activated only is displayed on the surface of the ant­
by one type of antigen. It is capable of igen-presenting cell. It recognizes the
developing immunity against that antigen antigen with the help of its own surface
only. This property is called the specificity receptor protein called B-cell receptor.
of T cells. 2. The recognition of the antigen by the
B cell initiates a complex interaction
„„ DEVELOPMENT OF between the B-cell receptor and the
HUMORAL IMMUNITY antigen. This reaction activates B cells.
3. At the same time, macrophages (the
„„ INTRODUCTION antigen-presenting cells) release inter­
Humoral immunity is the immunity mediated leukin-1 which facilitates the activation
by antibodies. Antibodies are secreted by B and proliferation of B cells.
Chapter 15 ê Immunity 81
4. The activated B cells proliferate and basic principle of vaccination against the
the proliferated B cells carry out the infections.
further actions.
5. Simultaneously the antigen bound to „„ ROLE OF HELPER T CELLS
class II MHC molecules activates the
Helper T cells are simultaneously activated
helper T cells also resulting in deve­ by antigen. The activated helper T cells
lopment of cell-mediated immunity secrete two substances called interleukin-2
(already explained). and B cell growth factor, which promote:
1. Activation of more number of B
Transformation B Cells lymphocytes.
The proliferated B cells are transformed 2. Proliferation of plasma cells.
into two types of cells: 3. Production of antibodies.
1. Plasma cells.
2. Memory cells. „„ ANTIBODIES
An antibody is defined as a protein that is
„„ ROLE OF PLASMA CELLS produced by B lymphocytes in response
to the presence of an antigen. Antibody
The plasma cells destroy the foreign orga­ is γ-globulin in nature and it is also called
nisms by producing the antibodies. Anti­ immunoglobulin (Ig). The immunoglobulins
bodies are globulin in nature. The rate of form 20% of the total plasma proteins. The
the antibody production is very high, i.e. antibodies enter almost all the tissues of
each plasma cell produces about 2,000 the body.
molecules of antibodies per second. The
antibodies are also called immunoglobulins. Structure of Antibodies
The antibodies are released into lymph
and then transported into the circulation. The antibodies are formed by two pairs of
The antibodies are produced until the end chains, namely one pair of heavy or long
of lifespan of each plasma cell which may chains and one pair of light or short chains.
be from several days to several weeks. Each heavy chain consists of about 400
amino acids and each light chain consists
of about 200 amino acids.
Actually, each antibody has two halves,
Memory B cells occupy the lymphoid tis­ which are identical. The two halves are
sues throughout the body. The memory held together by disulfide bonds (S–S).
cells are in inactive condition until the body Each half of the antibody consists of one
is exposed to the same organism for the heavy chain (H) and one light chain (L).
second time. The two chains in each half are also joined
During the second exposure, the memory by disulfide bonds (S–S). The disulfide
cells are stimulated by the antigen and bonds allow the movement of amino acid
produce more quantity of antibodies at a chains. In each antibody, the light chain
faster rate, than in the first exposure. The is parallel to one end of the heavy chain.
antibodies produced during the second The light chain and the part of heavy chain
exposure to the foreign antigen are also parallel to it form one arm. The remaining
more potent than those produced during part of the heavy chain forms another arm.
first exposure. This phenomenon forms the A hinge joins both the arms (Fig. 15.3).
82 Section 2 ê Blood and Body Fluids

Each chain of the antibody includes two 1. Direct Actions of Antibodies

Antibodies directly inactivate the invading
1. Constant region.
organism by any one of the following
2. Variable region.
Types of Antibodies i. Agglutination: In this, the foreign bodies
like RBCs or bacteria, with anti­gens on
Five types of antibodies are identified:
their surfaces, are held together in a
1. IgA (Ig alpha).
clump by the antibodies.
2. IgD (Ig delta).
ii. Precipitation: In this, the soluble anti
gens toxin are converted into insoluble
forms and then precipitated.
iii. Neutralization: During this, the anti­
bodies cover the toxic sites of antigenic
iv. Lysis: In this, the antibodies rupture
the cell membrane of organisms and
then destroy them.

2. Actions of Antibodies Through

Complement System
The complement system is the one that
enhances or accelerates various activities
during the fight against the invading orga­
nisms. It contains plasma enzymes, which
are identified by numbers from C1 to C9.

Functions of Different Antibodies

1. IgA plays a role in localized defense
mechanism in external secretions like
FIGURE 15.3: Structure of antibody [immuno­
globulin G (IgG)] molecule. CH1, CH2 and CH3 = tear.
Constant regions of heavy chains, VL = Variable 2. IgD is involved in recognition of the
region of light chain, VH = Variable region of antigen by B lymphocytes.
heavy chain, CL = Constant region of light chain. 3. IgE is involved in allergic reactions.
4. IgG is responsible for complement
3. IgE (Ig epsilon). fixation.
4. IgG (Ig gamma). 5. IgM is also responsible for complement
5. IgM (Ig mu).
Among these antibodies, IgG forms 75%
of the antibodies in the body.
Specificity of B Lymphocytes
Mechanism of Actions of Antibodies Each B lymphocyte is designed to be acti­
The antibodies protect the body from the vated only by one type of antigen. It is also
invading organisms in two ways: capable of producing antibodies against that
1. By direct actions. antigen only. This property of B lymphocyte
2. Through complement system. is called specificity.
Chapter 15 ê Immunity 83
Natural killer (NK) cell is a large granular Immune deficiency diseases are group of
cell with indented nucleus. It is considered diseases in which some components of
as the third type of lymphocyte. It is not a immune system is missing or defective. Nor­
phagocytic cell, but its granules contain mally, the defense mechanism protects the
hydrolytic enzymes which causes lysis of body from invading pathogenic organism.
cells of invading organisms. When the defense mechanism fails or
becomes faulty (defective), the organisms of
Functions of NK Cell even low virulence produce severe disease.
The NK cell: The organisms, which take advantage of
1. Destroys the viruses. defective defense mechanism, are called
2. Destroys the viral infected or damaged opportunists.
cells, which might form tumors. The immune deficiency diseases caused
3. Destroys the malignant cells and by such opportunists are of two types:
prevents development of cancerous 1. Congenital immune deficiency diseases.
tumors. 2. Acquired immune deficiency diseases.
4. Secretes cytokines such as inter­
leukin-2, interferons, colony-stimulating „„ CONGENITAL IMMUNE
factor (GM-CSF) and tumor necrosis DEFICIENCY DISEASES
Congenital diseases are inherited and
occur due to the defects in B cell or T cell,
„„ CYTOKINES or both. The common examples are Di
Cytokines are the hormone-like small pro­ George’s syndrome (due to absence of
teins acting as intercellular messengers thymus) and severe combined immune
(cell signaling molecules) by binding to deficiency (due to lymphopenia or the
specific receptors of target cells. These non- absence of lymphoid tissue).
antibody proteins are secreted by WBCs
and some other types of cells. Their major „„ ACQUIRED IMMUNE
function is the activation and regulation of DEFICIENCY DISEASES
general immune system of the body. Acquired immune deficiency syndrome
Cytokines are distinct from the other cell (AIDS) diseases occur due to infection
signaling molecules such as growth factors by some organisms. The most common
and hormones. Cytokines are classified disease of this type is acquired immune
into several types: deficiency syndrome (AIDS).
1. Interleukins.
2. Interferons. Acquired Immune Deficiency Syndrome
3. Tumor necrosis factors.
4. Chemokines. AIDS is an infectious disease caused by
5. Defensins. immune deficiency virus (HIV). AIDS is
6. Cathelicidins. the most common problem throughout
7. Platelet-activating factor. the world because of rapid increase in the
84 Section 2 ê Blood and Body Fluids

number of victims. Infection occurs when with respect to body’s own antigens that are
a glycoprotein from HIV binds to surface called self-antigens or autoantigens.
receptors of T lymphocytes, monocytes, Normally, body has the tolerance against
macrophages and dendritic cells leading self-antigen. However, in some occasions,
to destruction of these cells. It causes slow the tolerance fails or becomes incomplete
progressive decrease in immune function against self-antigen. This state is called
resulting in opportunistic infections of autoimmunity and it leads to the activation of T
various types. The common opportunistic lymphocytes or production of autoantibodies
infections which kill the AIDS patient are from B lymphocytes. The T lymphocytes
pneumonia and skin cancer. (cytotoxic T cells) or autoantibodies attack
the body’s normal cells whose surface
„„ AUTOIMMUNE DISEASES contains the self-antigen or autoantigen.
Autoimmune disease is defined as condition Common Autoimmune Diseases
in which the immune system mistakenly
attacks body’s own cells and tissues. 1. Diabetes mellitus.
Normally, an antigen induces the immune 2. Myasthenia gravis.
response in the body. The condition in which 3. Hashimoto’s thyroiditis.
the immune system fails to give response to 4. Graves’ disease.
an antigen is called tolerance. This is true 5. Rheumatoid arthritis.
Chapter 16




Platelets or thrombocytes are the formed
elements of blood. Platelets are small, color­ Platelets are constituted by cell membrane
less, nonnucleated and moderately refrac­ or surface membrane, microtubules and cyto­
tive bodies, which are considered to be the plasm.
fragments of cytoplasm.
Size of Platelets
It is 6 nm thick and contains lipids in the form
Diameter : 2.5 µ (2 to 4 µ) of phospholipids, cholesterol and glycolipids,
Volume : 7.5 cu µ (7 to 8 cu µ) carbohydrates as glycocalyx, and glycopro­
teins and proteins.
Shape of Platelets
Normally, platelets are of several shapes,
viz. spherical or rod shaped and become Microtubules form a ring around cytoplasm
oval or disc shaped when inactivated. Some­ below cell membrane. Microtubules are made
times, the platelets have dumbbell shape, up of proteins called tubulin. These tubules
comma shape, cigar shape or any other provide structural support for inactivated plate­
unusual shape. lets to maintain the disk-like shape.
86 Section 2 ê Blood and Body Fluids

„„ CYTOPLASM Other Chemical Substances

The cytoplasm of the platelets contains the 1. Glycogen.
cellular organelles, Golgi apparatus, endo­ 2. Substances like blood group antigens.
plasmic reticulum, mitochondria, microtu­ 3. Inorganic substances such as calcium,
bule, microvessels, filaments and different copper, magnesium and iron.
types of granules. Cytoplasm also contains
Platelet Granules
some chemical substances as given as
given below. Granules present in cytoplasm of platelets
are of two types, alpha granules and dense
Proteins granules. Alpha granules contain clotting
factors V and XIII, fibrinogen and platelet-
1. Contractile proteins: derived growth factor, and the dense granules
i. Actin and myosin which are res­ contain nucleotides, serotonin, phospholipid,
ponsible for contraction of platelets. calcium and lysosomes (Fig. 16.1).
ii. Thrombosthenin the third contrac­
tile protein which is responsible for „„ NORMAL COUNT AND
clot retraction. VARIATIONS
2. von Willebrand factor: Responsible for
Normal platelet count is 2,50,000. It ranges
adherence of platelets.
between 2,00,000 and 4,00,000/cu mm of
3. Fibrin-stabilizing factor: It is a clotting
4. Platelet-derived growth factor (PDGF): „„ PHYSIOLOGICAL VARIATIONS
Responsible for repair of damaged-
blood vessels and wound healing. 1. Age: Platelets are less in infants
5. Platelet-activating factor (PAF): Causes (1,50,000 to 2,00,000/cu mm) and
aggregation of platelets during the injury
of blood vessels.
6. Vitronectin (serum-spreading factor):
Promotes adhesion of platelets and
spreading of cells in culture.
7. Thrombospondin: Inhibits angiogene­
sis (formation of new blood vessels).

1. ATPase.
2. Enzymes necessary for synthesis of

Hormonal Substances
1. Adrenaline.
2. 5-HT (serotonin). FIGURE 16.1: Platelet under
3. Histamine. electron microscope
Chapter 16 ê Platelets 87
reaches normal level at 3rd month contains the contractile proteins namely
after birth. actin, myosin and thrombosthenin which are
2. Sex: There is no difference in the plate­ responsible for clot retraction (refer Chap­
let count between males and females. ter 18).
In females, it is reduced during men­
struation. „„ 3. ROLE IN PREVENTION OF
3. High altitude: Platelet count increases. BLOOD LOSS (HEMOSTASIS)
4. After meals: After taking food, the plate­
let count increases. Platelets accelerate hemostasis by three
„„ PATHOLOGICAL VARIATIONS i. Platelets secrete 5-HT, which causes
the constriction of blood vessels.
Refer applied physiology of this chapter. ii. Due to the adhesive property, the
platelets seal the damage in blood
„„ PROPERTIES OF PLATELETS vessels like capillaries.
„„ ADHESIVENESS iii. By formation of temporary plug also
platelets seal the damage in blood
Adhesiveness is the property of sticking to vessels (refer Chapter 17).
a rough surface. While coming in contact
with any rough surface the platelets are „„ 4. ROLE IN REPAIR OF
activated and stick to the surface. RUPTURED BLOOD VESSEL

„„ AGGREGATION (GROUPING OF The platelet-derived growth factor (PDGF)

PLATELETS) formed in cytoplasm of platelets is useful
for the repair of the endothelium and other
Aggregation is the grouping of platelets.
structures of the ruptured blood vessels.
Activated platelets group together and
become sticky.
„„ AGGLUTINATION By the property of agglutination, platelets
Agglutination is the clumping together of encircle the foreign bodies and destroy
platelets. them by phagocytosis.


„„ 1. ROLE IN BLOOD CLOTTING Platelets are formed from bone marrow.
The pluripotent stem cell gives rise to the
The platelets are responsible for the forma­ CFU-M. This develops into megakaryocyte.
tion of intrinsic prothrombin activator. This The cytoplasm of megakaryocyte form pseu­
substance is responsible for the onset of dopodium. A portion of pseudopodium is
blood clotting (refer Chapter 18). detached to form platelet, which enters the
circulation (refer Fig. 9.2).
„„ 2. ROLE IN CLOT RETRACTION Production of platelets is influenced by
In the blood clot, the blood cells including thrombopoietin. Thrombopoietin is a glyco­
platelets are entrapped in between the protein like erythropoietin, which is secreted
fibrin threads. The cytoplasm of platelets by liver and kidneys.
88 Section 2 ê Blood and Body Fluids


PLATELETS The increase in platelet count is called throm­
bocytosis. It occurs in the following condi­
Average lifespan of platelets is about 10 days.
Older platelets are destroyed by tissue macro­ i. Allergic conditions.
phage system in spleen. ii. Hemorrhage.
iii. Bone fractures.
„„ APPLIED PHYSIOLOGY – iv. Surgical operations.
vi. Rheumatic fever.
„„ 1. THROMBOCYTOPENIA vii. Trauma (wound or injury or damage
produced by external force).
Decrease in platelet count is called throm­
bocytopenia. It leads to thrombocytopenic „„ 3. THROMBOCYTHEMIA
purpura (refer Chapter 18). Thrombocyto­
penia occurs in the following conditions: It is the condition with persistent and abnormal
increase in platelet count. It occurs in:
i. Acute infections.
i. Carcinoma.
ii. Acute leukemia. ii. Chronic leukemia.
iii. Aplastic and pernicious anemia. iii. Hodgkin’s disease.
iv. Chickenpox.
v. Smallpox. „„ 4. GLANZMANN’S
vi. Splenomegaly. THROMBASTHENIA
vii. Scarlet fever. Glanzmann’s thrombasthenia is an inherited
viii. Typhoid. hemorrhagic disorder caused by structural or
ix. Tuberculosis. functional abnormality of platelets. It leads to
x. Purpura. thrombasthenic purpura (refer Chapter 18).
Chapter 17



„„ DEFINITION by von Willebrand factor. This factor acts

as a bridge between a specific glycoprotein
Hemostasis is defined as arrest or stoppage
present on the surface of platelet and
of bleeding.
collagen fibrils.
When a blood vessel is injured, the injury PLATELET PLUG
initiates a series of reactions resulting in The platelets get adhered to the collagen
hemostasis. It occurs in three stages: of ruptured blood vessel and secrete ADP
1. Vasoconstriction. and thromboxane A2. These two substan­
2. Platelet plug formation. ces attract more and more platelets and
3. Coagulation of blood. activate them. All these platelets aggregate
together and form a loose temporary plate­
„„ 1. VASOCONSTRICTION let plug or temporary hemostatic plug,
Immediately after injury, the blood vessel which closes the vessel and prevents fur­
constricts and decreases the loss of blood ther blood loss. The platelet aggregation
from damaged portion. Usually, arterioles is accelerated by platelet-activating factor
and small arteries constrict. The vasocons­ (PAF).
triction is purely a local phenomenon. When
the blood vessels are cut, the endothelium „„ 3. COAGULATION OF BLOOD
is damaged and the collagen is exposed. During this process, the fibrinogen is con­
The platelets adhere to this collagen, and verted into fibrin. The fibrin threads get
get activated. The activated platelets sec­ attached to the loose platelet plug, which
rete serotonin and other vasoconstrictor blocks the ruptured part of blood vessels
substances which cause constriction of the and prevents further blood loss completely.
blood vessels (Fig. 17.1). The adherence The mechanism of blood coagulation is
of platelets to the collagen is accelerated explained in the next chapter.
90 Section 2 ê Blood and Body Fluids

FIGURE 17.1: States of hemostasis. ADP = Adenosine diphosphate,

PAF = Platelet-activating factor.
Chapter 18

Coagulation of Blood



„„ DEFINITION OF BLOOD factors. Thirteen clotting factors are identi­

COAGULATION fied and listed in Table 18.1.
The clotting factors were named after the
Coagulation or clotting is defined as the scientists who discovered them or as per the
process in which blood loses its fluidity
activity except factor IX. Christmas factor
and becomes a jelly-like mass few minutes
or factor IX was named after the patient in
after it is shed out or collected in a con­
whom it was discovered.
Coagulation of blood occurs through a
series of reactions due to the activation Most of the clotting factors are proteins in the
of a group of substances. The substances form of enzymes. Normally, all the factors are
necessary for clotting are called clotting present in the form of inactive proenzyme.
92 Section 2 ê Blood and Body Fluids

TABLE 18.1: Clotting factors 1. Formation of prothrombin activator.

2. Conversion of prothrombin into thrombin.
Factors Name 3. Conversion of fibrinogen into fibrin.
I Fibrinogen
III Thromboplastin (tissue factor)
Blood clotting commences with the forma­
IV Calcium tion of a substance called prothrombin acti­
vator. Its formation is initiated by substances
V Labile factor (proaccelerin or
produced either within the blood itself or
accelerator globulin)
outside the blood. Thus, formation of pro­
VI Presence has not been proved throm­bin activator occurs through two path­
VII Stable factor
i. Intrinsic pathway.
VIII Antihemophilic factor ii. Extrinsic pathway.
(antihemophilic globulin)
IX Christmas factor Intrinsic Pathway for the Formation
of Prothrombin Activator
X Stuart-Prower factor
XI Plasma thromboplastin
In this, the formation of prothrombin acti­
antecedent vator is initiated by platelets, which are
within the blood itself (Fig. 18.1).
XII Hageman factor (contact factor)
Sequence of events in
XIII Fibrin-stabilizing factor
i. During the injury, the blood vessel is
These proenzymes must be activated into ruptured. The endothelium is damaged
enzymes to enforce clot formation. It is car­ and collagen beneath the endothelium
ried out by series of proenzyme – enzyme is exposed.
conversion reactions. The first one of the ii. When factor XII (Hageman factor) comes
series is converted into an active enzyme in contact with collagen, it is con­verted
that activates the second one, which acti­ into activated factor XII in the presence
vates the third one; this continues till the final of kallikrein and high molecular weight
active enzyme thrombin is formed. (HMW) kininogen.
Enzyme cascade theory explains how iii. The activated factor XII converts factor
various reactions involved in the conversion XI into activated factor XI in the pre­
of proenzymes to active enzymes take sence of HMW kininogen.
place in the form of a cascade. Cascade iv. The activated factor XI activates factor
refers to a process that occurs through a IX in the presence of factor IV (calcium).
series of steps, each step initiating the next, v. Activated factor IX activates factor X in
until the final step is reached. the presence of factor VIII and calcium.
vi. When platelet comes in contact with
Stages of Blood Clotting
collagen of damaged blood vessel, it
In general, blood clotting occurs in three gets activated and releases phospho­
stages: lipids.
Chapter 18 ê Coagulation of Blood 93
vii. Now the activated factor X reacts with The initially formed thrombin activates
platelet phospholipid and factor V to factor V. Factor V in turn accelerates
form prothrombin activator. This needs formation of both extrinsic and intrinsic
presence of calcium ions. prothrombin activator which converts
viii. Factor V is also activated by positive prothrombin into thrombin. This effect
feed­back effect of thrombin (see below). of thrombin is called positive feedback
effect (refer Fig. 18.1).
Extrinsic Pathway for the
Formationof Prothrombin Activator „„ STAGE 3: CONVERSION OF
In this, the formation of prothrombin activa­ FIBRINOGEN INTO FIBRIN
tor is initiated by the tissue thromboplastin The final stage of blood clotting involves
which is formed from the injured tissues. the conversion of fibrinogen into fibrin by
Sequence of events in thrombin.
extrinsic pathway
Sequence of Events in Stage 3
i. The tissues that are damaged during
injury release factor III, i.e. tissue throm­ i. Thrombin converts fibrinogen into acti­
boplastin. The thromboplastin con­tains vated fibrinogen which is called fibrin
proteins, phospholipid and glyco­pro­tein, monomer.
which act as proteolytic enzy­mes. ii. Fibrin monomer polymerizes with other
ii. The glycoprotein and phospholipid monomer molecules and form loosely
components of thromboplastin convert arranged strands of fibrin.
factor X into activated factor X, in the iii. Later these loose strands are modified
presence of factor VII. into dense and tight fibrin threads by
iii. The activated factor X reacts with fibrin-stabilizing factor (factor XIII) in
factor V and phospholipid component the presence of calcium ions (refer Fig.
of tissue thromboplastin to form pro­ 18.1). All the tight fibrin threads are
thrombin activator. This reaction requi­ aggregated to form a meshwork of
res the presence of calcium ions. stable clot.


Blood clotting is all about thrombin forma­
tion. Once thrombin is formed, it definitely Blood clot is defined as the mesh of fibrin
leads to clot formation. entangling RBCs, WBCs and platelets.

Sequence of Events in Stage 2 „„ CLOT RETRACTION

i. Prothrombin activator that is formed in After the formation, the blood clot starts con­
intrinsic and extrinsic pathways converts tracting. And after about 30 to 45 minutes,
prothrombin into thrombin in the pre­ the straw colored serum oozes out of the
sence of calcium ions (factor IV). clot. The process involving the contraction
ii. Once formed thrombin initiates the for­ of blood clot and oozing of serum is called
mation of more thrombin molecules. clot retraction.
94 Section 2 ê Blood and Body Fluids

FIGURE 18.1: Stages of blood coagulation. + = Thrombin induces formation of more thrombin
(positive feedback), a = Activated, HMW = High molecular weight.

The contractile proteins namely, actin, „„ FIBRINOLYSIS

myosin and thrombosthenin in the cyto­
plasm of platelets are responsible for clot The lysis of blood clot inside the blood vessel
retraction. is called fibrinolysis. It helps to remove the
Chapter 18 ê Coagulation of Blood 95
clot from the lumen of the blood vessel. thrombin binding protein. It binds with
This process requires a substance called thrombin and forms a thrombomodulin
plasmin or fibrinolysin. – thrombin complex. This complex acti­
Plasmin is formed from inactivated vates protein-C. Activated protein-C along
glyco­protein called plasminogen. Plasmi­ with its cofactor protein-S inactivates
no­gen is synthesized in liver and it is factor V and factor VIII. Inactivation of
incor­porated with other proteins in the these two clotting factors prevents clot
blood clot. Plasminogen is converted into formation.
plasmin by tissue plasminogen activator iii. All the clotting factors are in inactive
(t-PA), lysosomal enzymes and thrombin. state.
Plasmin causes lysis of clot by dissolving
and digesting the fibrin threads. „„ ANTICOAGULANTS
Significance of Lysis of Clot The substances, which prevent or post­
pone coagulation of blood are called anti­
In vital organs, particularly the heart, the coagulants.
blood clot obstructs the minute blood ves­ Anticoagulants are of three types:
sel leading to myocardial infarction. The 1. Anticoagulants used to prevent blood
lysis of blood clot allows reopening of affec­ clotting inside the body, i.e. in vivo.
ted blood vessels and prevents the deve­ 2. Anticoagulants used to prevent clotting
lopment of infarction. of blood that is collected from the body,
The fibrinolytic enzymes like streptoki­ i.e. in vitro.
nase are used for the lysis of blood clot, 3. Anticoagulants used to prevent blood
during the treatment in early stages of myo­ clotting both in vivo and in vitro.
cardial infarction.
„„ ANTICLOTTING MECHANISM Heparin is a naturally produced anticoagulant
IN THE BODY in the body. It is produced by mast cells, which
are the wandering cells situated immediately
Under physiological conditions, intravascular
outside the capillaries in many tissues or
clotting does not occur. It is because of the
organs that contain more connective tissue.
presence of some physicochemical factors These cells are abundant in liver and lungs.
in the body. Basophils also secrete heparin.
Heparin is a conjugated polysaccharide.
„„ 1. PHYSICAL FACTORS The commercial heparin is prepared from
i. Continuous circulation of blood. the liver and other organs of animals. The
ii. Smooth endothelial lining of the blood commercial preparation is available in liquid
vessels. form or dry form as sodium, calcium, ammo­
nium or lithium salts.
Mechanism of Action of Heparin
i. Presence of natural anticoagulant called
heparin that is produced by the liver.
ii. Production of thrombomodulin by endo­ i. Prevents blood clotting by its anti­
thelium of the blood vessels (except in thrombin activity. It directly suppresses
brain capillaries). Thrombomodulin is a the activity of thrombin.
96 Section 2 ê Blood and Body Fluids

ii. Combines with antithrombin III (a pro­ iv. To preserve the blood before trans­
tease inhibitor present in circulation) fusion.
and removes thrombin from circulation.
Use in the laboratory
iii. Activates antithrombin III.
iv. Inactivates the active form of other Heparin is also used as anticoagulant in
clotting factors like IX, X, XI and XII vitro while collecting blood for various inves­
(Fig. 18.2). ti­gations. Heparin is the most expensive
Uses of Heparin
Heparin is used as an anticoagulant both in
vivo and in vitro. Dicoumoral and warfarin are the derivatives
of coumarin.

Mechanism of Action
The coumarin derivatives prevent blood
clotting by inhibiting the action of vitamin
K. Vitamin K is essential for the formation
of various clotting factors namely, II, VII, IX
and X.

Dicoumoral and warfarin are the commonly
used oral anticoagulants in clinical practice
(in vivo).

„„ 3. EDTA
FIGURE 18.2: Mechanism of action of heparin Ethylenediaminetetra acetic acid (EDTA) is
a strong anticoagulant. It is available in two
Clinical use forms:
i. Disodium salt (Na2 EDTA).
Intravenous injection of heparin (0.5 to 1 ii. Tripotassium salt (K3 EDTA).
mg/kg body weight) postpones clotting for
3 to 4 hours (until it is destroyed by the
Mechanism of Action
enzyme heparinase). So, it is widely used
as an anticoagulant in clinical practice for These substances prevent blood clotting by
many purposes such as: removing calcium from blood.
i. To prevent intravascular blood clotting
during surgery. Uses
ii. During dialysis when blood is passed
through artificial kidney. EDTA is used as an anticoagulant both in
iii. During cardiac surgery, that involves vivo and in vitro:
passing the blood through heart lung i. It is administered intravenously in
machine. cases of lead poisoning (in vivo).
Chapter 18 ê Coagulation of Blood 97
ii. It is also used as an anticoagulant in i. Used to store blood in the blood bank.
the laboratory (in vitro). It is available in two forms:
a. Acid citrate dextrose (ACD).
b. Citrate phosphate dextrose (CPD).
Oxalate compounds prevent coagulation ii. Used in laboratory in vitro or RBC and
by forming calcium oxalate, which is preci­ platelet counts.
pitated later. Thus, these compounds reduce
the blood calcium level. „„ 6. OTHER SUBSTANCES, WHICH
Earlier sodium and potassium oxalates PREVENT BLOOD CLOTTING
were used. Nowadays, mixture of ammo­
nium oxalate and potassium oxalate in the Peptone, proteins from venom of copper­
ratio of 3:2 is used. Each salt is an anti­co­ head snake and hirudin (from leech) are the
agulant by itself. But potassium oxalate alone known anticoagulants.
causes shrinkage of RBCs. Ammonium
oxalate alone causes swelling of RBCs. „„ PHYSICAL METHODS TO
But together, these substances do not alter PREVENT BLOOD CLOTTING
the cellular activity.
The coagulation of blood is postponed or
Mechanism of Action prevented by the following physical methods.

Oxalate combines with calcium and forms „„ 1. COLD

insoluble calcium oxalate. Thus, oxalate
removes calcium from blood and lack of Reducing the temperature to about 5°C
cal­cium prevents coagulation. postpones coagulation of blood.


Oxalate compounds are used as in vitro
anticoagulants. Oxalate is poisonous so it
cannot be used in vivo. Collecting the blood in a container with
smooth surface like a silicon-coated con­
„„ 5. CITRATES tainer prevents clotting. The smooth surface
inhibits the activation of factor XII and
Sodium, ammonium and potassium citrates
platelets. So, the formation of prothrombin
are used as anticoagulants.
activator is prevented.
Mechanism of Action
Citrate combines with calcium in blood to
form insoluble calcium citrate. Like oxalate, Procoagulants or hemostatic agents are the
citrate also removes calcium from blood substances, which accelerate the process
and prevents coagulation. of blood coagulation. Procoagulants are:
1. Thrombin.
Uses 2. Snake venom.
3. Extracts of lungs and thymus.
Citrates are used as an anticoagulant both 4. Sodium or calcium alginate.
in vivo and in vitro: 5. Oxidized cellulose.
98 Section 2 ê Blood and Body Fluids

„„ TESTS FOR CLOTTING clotting time. The bleeding disorders are of

three types.
Bleeding time is the time interval from 1. Hemophilia
oozing of blood after a cut or injury till arrest
of bleeding. Usually, it is determined by Hemophilia is a group of sex-linked inheri­
Duke method using blotting paper or filter ted blood disorders characterized by pro­
paper method. Its normal duration is 3 to 6 longed clotting time. In this disorder males
minutes. It is prolonged in purpura. are affected and the females are the
carriers. Because of prolonged clotting
„„ 2. CLOTTING TIME time, even a mild trauma causes excess
bleeding which can lead to death. Damage
Clotting time is the time interval from oozing of skin while falling or extraction of a tooth
of blood after a cut or injury till the formation may cause excess bleeding for few weeks.
of clot. It is usually determined by capillary Easy bruising and hemorrhage in muscles
tube method. Its normal duration is 3 to 8 and joints are also common in this disease.
minutes. And it is prolonged in hemophilia.
Cause for hemophilia
„„ 3. PROTHROMBIN TIME Lack of prothrombin activator is the cause
It is the time taken by blood to clot after for hemophilia. The formation of prothrom­
adding tissue thromboplastin to it. Blood is bin activator is affected due to the deficiency
collected and oxalated so that, the calcium of factor VIII, IX or XI.
is precipitated and prothrombin is not con­ Types of hemophilia
verted into thrombin. Thus, the blood clotting
is prevented. Then a large quantity of tissue Depending upon the deficiency of the factor
thromboplastin with calcium is added to this involved, hemophilia is classified into three
blood. Calcium nullifies the effect of oxa­late. types:
The tissue thromboplastin activates pro­ i. Hemophilia A or classic hemophilia
thrombin and blood clotting occurs. that is due to the deficiency of factor
VIII. 85% of people with hemophilia
During this procedure, the time taken by
are affected by hemophilia A.
blood to clot after adding tissue thrombo­
ii. Hemophilia B or Christmas disease
plastin is determined. Prothrombin time
which is due to the deficiency of factor
indicates the total quantity of prothrombin
IX. 15% of people with hemophilia are
present in the blood.
affected by hemophilia B.
The normal duration of prothrombin time
iii. Hemophilia C which is due to the
is about 12 seconds. It is prolonged in defi­
deficiency of factor XI. It is a very rare
ciency of prothrombin and other factors like
blood disorder.
factors I, V, VII and X. However, it is normal
in hemophilia.
2. Purpura
„„ APPLIED PHYSIOLOGY It is a disorder characterized by prolonged
bleeding time. However, the clotting time
is normal. The characteristic feature of this
Bleeding disorders are the diseases charac­ disease is spontaneous bleeding under the
terized by prolonged bleeding time or skin from ruptured capillaries. It causes
Chapter 18 ê Coagulation of Blood 99
small tiny hemorrhagic spots under the that occurs during platelet dysfunction or
skin which are called purpuric spots (purple hemophilia.
colored patch-like appearance). That is why
this disease is called purpura. „„ THROMBOSIS

Types and causes of purpura Thrombosis or intravascular blood clotting

refers to coagulation of blood inside the
The purpura is classified into different types blood vessels. Normally, blood does not clot
depending upon the causes. in the blood vessel because of some factors
Thrombocytopenic purpura which are already explained. But some
abnormal conditions can cause throm­bosis.
Thrombocytopenic purpura is due to the
defi­ciency of platelets (thrombocytopenia). Causes of Thrombosis
In bone marrow disease, platelet production
is affected leading to deficiency of platelets. 1.
Injury to blood vessels.
Roughened endothelial lining.
Idiopathic thrombocytopenic purpura 3.
Sluggishness of blood flow.
Purpura due to some unknown cause is 4.
Agglutination of RBCs.
called idiopathic thrombocytopenic purpura. 5.
Poisons like snake venom, mercury,
It is believed that platelet count decreases and arsenic compounds.
due to the development of antibodies against 6. Congenital absence of protein C.
platelets, which occurs after blood trans­
fusion. Complications of Thrombosis

Thrombasthenic purpura 1. Thrombus

It purpura is due to structural or functional During thrombosis, lumen of blood vessels

abnormality of platelets. However, the plate­ is occluded. The solid mass of platelets, red
let count is normal. It is characterized by cells and/or clot, which obstructs the blood
normal clotting time, normal or prolonged vessel, is called thrombus. The thrombus
bleeding time but defective clot retraction. formed due to agglutination of RBC is called
agglutinative thrombus.
3. von Willebrand Disease 2. Embolism and embolus
von Willebrand disease is a bleeding dis­
Embolism is the process in which the throm­
order characterized by excess bleeding
even with a mild injury. It is due to inherited bus or part of it is detached and carried in
defi­ciency of von Willebrand factor which bloodstream and occludes the small blood
is a protein secreted by endothelium of vessels resulting in arrests of blood flow to
dam­aged blood vessels and platelets. This any organ or region of the body. Embolus is
protein is responsible for adherence of the thrombus or part of it, which arrests the
platelets to endothelium of blood vessels blood flow. The obstruction of blood flow by
during hemostasis after an injury. It is also embolism is common in lungs (pulmonary
responsible for the survival and mainte­ embolism), brain (cerebral embolism) or
nance of factor VIII in plasma. heart (coronary embolism).
The deficiency of von Willebrand factor
3. Ischemia
suppresses platelet adhesion. It also causes
deficiency of factor VIII. This results in excess Insufficient blood supply to an organ or area
bleeding which resembles the bleeding of body by the obstruction of blood vessels
100 Section 2 ê Blood and Body Fluids

is called ischemia. Ischemia results in tissue injury, infection, inflammation, physical agents
damage because of hypoxia (lack of oxy­ or chemical substances.
gen). Ischemia also causes discomfort, Infarction means the tissue death due
pain and tissue death. Death of body tissue to loss of blood supply. Loss blood supply
is called necrosis. is usually caused by occlusion of an artery
by thrombus or embolus and sometimes
4. Necrosis and infarction by atherosclerosis (refer Chapter 51). The
area of tissue that undergoes infarction is
Necrosis is a general term that refers to called infarct. Infarction commonly occurs
tissue death caused by loss of blood supply, in heart, brain, lungs, kidneys and spleen.
Chapter 19

Blood Groups


„„ INTRODUCTION honored with Nobel Prize in 1930 for this

Blood groups are determined by the
presence of antigen in RBC membrane. „„ ABO BLOOD GROUPS
When blood from two individuals is mixed,
sometimes clumping (agglutination) of Determination of ABO blood groups
RBCs occurs. This clumping is because depends upon the immunological reaction
of the immunological reactions. But, why between antigen and antibody. Lands­
clumping occurs in some cases and not in teiner found two antigens on the surface of
other cases remained a mystery until the RBCs and named them as A antigen and
discovery of blood groups by the Austrian B antigen. These antigens are also called
Scientist Karl Landsteiner in 1901. He was agglutinogens because of their capacity to
102 Section 2 ê Blood and Body Fluids

cause agglutination of RBCs. He noticed AB group and serum of this group does not
the corresponding antibodies or agglutinins contain any antibody. If both antigens are
in the plasma and named them anti A absent, the blood group is called O group
or α antibody and anti B or β antibody. and both α and β antibodies are present
However, a particular agglutinogen and the in the serum. The antigens and antibodies
corresponding agglutinin cannot be present present in different groups of ABO system
together. If present, it causes clumping of the are given in Table 19.1. Percentage of
blood. Based on this, Landsteiner classified people among Asian and European popu­
the blood groups. Later it has become the lation belonging to different blood group is
‘Landsteiner’s Law’ for grouping the blood. given in Table 19.2.
‘A’ group has two subgroups namely
„„ LANDSTEINER’S LAW ‘A1’ and ‘A2’. Similarly ‘AB’ group has two
Landsteiner’s law states that: subgroups namely ‘A1B’ and ‘A2B’.
1. If a particular antigen (agglutinogen)
is present in the RBCs, corresponding TABLE 19.1: Antigen and antibody present in
ABO blood groups
antibody (agglutinin) must be absent in
the serum.
Antigen in Antibody in
2. If a particular antigen is absent in the Group
RBC serum
RBCs, the corresponding antibody must
be present in the serum. A A Anti B (β)
Though the second part of Landsteiner’s
B B Anti A (α)
law is a fact, it is not applicable to Rh factor.
AB A and B No antibody
„„ BLOOD GROUP SYSTEMS O No antigen Anti A and anti B
More than 20 genetically determined blood
group systems are known today. But, Lands­ TABLE 19.2: Percentage of people having
teiner discovered two blood group systems different blood groups
called ABO system and Rh system. These
two blood group systems are the most Population A B AB O
important ones that are determined before Europeans 42 9 3 46
blood transfusions.
Asians 25 25 5 45
Based on the presence or absence of anti­ „„ DETERMINATION OF
gen A and antigen B, blood is divided into THE ABO GROUP
four groups: Determination of the ABO group is also
1. ‘A’ group.
called blood grouping, blood typing or blood
2. ‘B’ group.
3. ‘AB’ group.
4. ‘O’ group.
Principle of Blood Typing –
The blood having antigen A is called
A group. This group has β antibody in the
serum. The blood with antigen B and α The blood typing is done on the basis of
antibody is called B group. If both the anti­ agglutination. Agglutination means the col­
gens are present, the blood group is called lec­tion of separate particles like RBCs into
Chapter 19 ê Blood Groups 103
clumps or masses. Agglutination occurs
if an antigen is mixed with its correspond­
ing antibody which is called isoagglutinin.
Agglutination occurs when A antigen is
mixed with anti A or when B antigen is
mixed with anti B.

Requisites for Blood Typing

To determine the blood group of a person,
a suspension of his RBC and testing anti­
sera are required. Suspension of RBC is
prepared by mixing blood drops with iso­
tonic saline (0.9%). The test sera are:
1. Antiserum A, containing anti A.
2. Antiserum B, containing anti B.

1. One drop of antiserum A is placed on
one end of a glass slide (or a tile) and
one drop of antiserum B on the other
end. FIGURE 19.1: Determination of blood group
2. One drop of RBC suspension is mixed
with each antiserum. The slide is slightly 3. If agglutination occurs with both antisera
rocked for 2 minutes. The presence or A and B: The RBC contains both A and
absence of agglutination is observed B antigens to cause agglutination. And,
by naked eyes and if necessary it is the blood group is AB.
confirmed by using microscope. 4. If agglutination does not occur either
3. Presence of agglutination is confir­ with antiserum A or antiserum B: The
med by the presence of thick masses agglutination does not occur if the
(clump­ing) of RBCs. RBC does not contain any antigen.
4. Absence of agglutination is confirmed The blood group is O.
by clear mixture with dispersed RBCs.
1. If agglutination occurs with antiserum
A: The antiserum A contains anti A or During blood transfusion, only compatible
α antibody. The agglutination occurs blood must be used. The one who gives
if the RBC contains A antigen. So, the blood is called the donor and the one who
blood group is A (Fig. 19.1). receives the blood is called recipient.
2. If agglutination occurs with antiserum While transfusing the blood, antigen of
B: The antiserum B contains anti B or the donor and the antibody of the recipient
β antibody. The agglutination occurs if are considered. The antibody of the donor
the RBC contains B antigen. So, the and antigen of the recipient are ignored
blood group is B. mostly.
104 Section 2 ê Blood and Body Fluids

Thus, RBC of ‘O’ group has no antigen TABLE 19.3: Inheritance of ABO group
and so agglutination does not occur with
any other group of blood. So, ‘O’ group Gene from Group of the
blood can be given to any blood group per­ parents offspring
sons and the people of this group blood are A+A A AA or AO
called universal donors. A+O
The plasma of AB group blood has no B+B B BB or BO
antibody. This does not cause agglutination B+O
of RBC from any other group of blood. A+B AB AB
The people of AB group can receive blood O+O O OO
from any blood group persons. So, people
with this group blood are called universal
recipients. „„ H ANTIGEN
H antigen is the precursor of ABO group
„„ MATCHING AND CROSSMATCHING antigens, i.e. antigen A and antigen B. H
antigen is present in red blood cells of all
Blood matching (typing) is a laboratory test
individuals. If a person has the gene for A
done to determine the blood group of a person.
antigen or B antigen or both, these antigens
When the person needs blood transfusion,
are formed from H antigen. If there is no
another test called crossmatching is done
gene for A and B antigens, the person will
after the blood is typed. It is done to find out
not have A or B antigen in spite of having H
whether the person’s body will accept the
antigen. The blood of this person belongs
donor’s blood or not.
to ‘O’ group.
For blood matching, RBC of the indi­
Rarely, in some persons A, B and H
vidual (recipient) and test sera are used.
antigens are absent in red blood cells. This
Crossmatching is done by mixing the serum
group is called Bombay group, since it was
of the recipient and the RBCs of donor. first discovered in Bombay.
Crossmatching is always done before
blood transfusion. If agglutination of RBCs „„ TRANSFUSION REACTIONS
from a donor occurs during crossmatching, DUE TO ABO INCOMPATIBILITY
the blood from that person is not used for
transfusion. Transfusion reactions are the adverse
Matching = Recipient’s RBC + Test sera reactions in the body which occur due to
Crossmatching = Recipient’s serum + transfusion of incompatible (mismatched)
Donor’s RBC blood. The reactions may vary from fever
and hives (skin disorder characterized by
„„ INHERITANCE OF ABO itching) to renal failure, shock and death.
AGGLUTINOGENS AND In mismatched transfusion, the trans­
fusion reactions occur between donor’s
RBC and recipient’s plasma. So, if the donor’s
Blood group of a person depends upon the plasma contains antibody against recipient’s
two genes inherited from each parent. Gene RBC, agglutination does not occur because
A and gene B are dominant by themselves these antibodies are diluted in recipient’s
and gene O is recessive. The inheritance blood.
of blood group is represented schematically But, if recipient’s plasma contains anti­
as given in Table 19.3. bodies against donor’s RBCs, the immune
Chapter 19 ê Blood Groups 105
system launches a response against the
new blood cells. Donor RBCs are aggluti­
nated and hemolyzed.
The hemolysis of RBCs results in release
of large amount of hemoglobin into the
plasma. This leads to the following compli­

1. Jaundice
Normally, hemoglobin released from des­
troyed RBC is degraded and bilirubin is
FIGURE 19.2: Complications of mismatched
formed from it. When the serum bilirubin blood transfusion
level increases above 2 mg/dL, jaundice
occurs (refer Chapter 34). There are many Rh antigens but only the D
is more antigenic in human.
2. Cardiac Shock The persons having D antigen are called
Rh positive and those without D antigen
Simultaneously, the hemoglobin released
are called Rh negative. Among Asian popu­
into the plasma increases the viscosity of
lation, 85% of people are Rh positive and
blood. This increases the workload on the
15% are Rh negative.
heart leading to heart failure.
Rh group system is different from ABO
group system because, the antigen D does
3. Renal Shutdown
not have corresponding natural antibody
Dysfunction of kidneys is called renal shut­ (anti D). However, if Rh positive blood is
down. The toxic substances from hemo­ transfused to a Rh negative person for the
lyzed cells cause constriction of blood first time, then anti D is formed in that person.
ves­sels in kidney. In addition, the toxic sub­ On the other hand, there is no risk of com­
stances along with free hemoglobin are plications if Rh positive person receives Rh
filtered through glomerular membrane and negative blood.
enter renal tubules. Because of poor rate
of reabsorption from renal tubules, all these „„ INHERITANCE OF Rh ANTIGEN
substances precipitate and obstruct the
renal tubule. This suddenly stops formation Rhesus factor is an inherited dominant
of urine (anuria). factor. It may be homozygous Rhesus posi­
If not treated with artificial kidney, the tive with DD or heterozygous Rhesus posi­
person dies within 10 to 12 days because tive with Dd (Fig. 19.3). Rhesus negative
of jaundice, circulatory shock and more occurs only with complete absence of D
specifically due to renal shutdown and (i.e. with homozygous dd).
anuria (Fig. 19.2).
Rh factor is an antigen present in RBC. The When a Rh negative person receives Rh
antigen was discovered by Landsteiner and positive blood for the first time, he is not
Wiener. It was first discovered in rhesus affected much, since the reactions do not
monkey and hence the name Rh factor. occur immediately. But the Rh antibodies
106 Section 2 ê Blood and Body Fluids

are agglutinated and severe transfusion

reactions occur immediately (Fig. 19.4).
These reactions are similar to the reactions
of ABO incompatibility (see above).

Hemolytic disease is the disease in fetus
and newborn characterized by abnormal
hemolysis of RBCs. It is due to Rh incom­
patibility. Hemolytic disease leads to erythro­
blastosis fetalis.
Erythroblastosis fetalis is a disorder in
fetus characterized by the presence of
erythroblasts in blood. When a mother is
Rh negative and fetus is Rh positive
(the Rh factor being inherited from the
father), first child of the lady escapes the
complications of Rh incompatibility. This is
because the Rh antigen cannot pass from
fetal blood into the mother’s blood through
the placental barrier.
However, at the time of parturition (deli­
very of the child) the Rh antigen from
fetal blood may leak into mother’s blood
because of placental detachment. During
postpartum period, i.e. within a month after
delivery, the mother develops Rh antibody
in her blood.

FIGURE 19.3: Inheritance of Rh antigen

develop within one month. The transfused
RBCs, which are still present in recipient’s
blood are agglutinated. These agglutinated
cells are lysed by macrophages. So, a
delayed transfusion reaction occurs. But,
it is usually mild and does not affect the
recipient. However, antibodies developed
in the recipient remain in the body for ever.
So, when this person receives Rh positive
blood for the second time, the donor RBCs FIGURE 19.4: Rh incompatibility
Chapter 19 ê Blood Groups 107
When the mother conceives for the Prevention or treatment for
second time and if the fetus happens to erythroblastosis fetalis
be Rh positive again, the Rh antibody from
i. If mother is found to be Rh negative
mother’s blood crosses placental barrier
and fetus is Rh positive, anti D (anti­
and enters the fetal blood. Thus, the Rh
body against D antigen) should be
antigen cannot cross the placental barrier administered to the mother at 28th and
whereas Rh antibody can cross it. 34th weeks of gestation as prophy­
The Rh agglutinins which enter the fetus lactic measure. If Rh negative mother
cause agglutination of fetal RBCs resulting delivers Rh positive baby, then anti D
in hemolysis. should be administered to the mother
The severe hemolysis in the fetus causes within 48 hours of delivery. This deve­
jaundice. To compensate the hemolysis of lops passive immunity and prevents the
more and more number of RBCs, there is formation of Rh antibodies in mother’s
rapid production of RBCs, not only from blood. So the hemolytic disease of new
bone marrow, but also from spleen and born does not occur in a subsequent
liver. Now, many large and immature cells pregnancy.
in proerythroblastic stage are released into ii. If the baby is born with erythroblastosis
circulation. Because of this, the disease is fetalis, the treatment is given by means
called erythroblastosis fetalis. of exchange transfusion (refer Chapter
Ultimately due to excessive hemolysis 20). Rh negative blood is transfused
severe complications develop, viz.: into the infant replacing infant’s own
1. Severe anemia. Rh positive blood. It will now take at
2. Hydrops fetalis. least 6 months for the infant’s new Rh
3. Kernicterus. positive blood to replace the transfused
Rh negative blood. By this time all the
1. Severe Anemia molecules of Rh antibody derived from
the mother get destroyed.
Excessive hemolysis results in anemia.
And the infant dies when anemia becomes
In addition to ABO blood groups and Rh
2. Hydrops Fetalis factor, many more blood group systems were
found. However, these systems of blood
It is a serious condition in fetus characteri­
groups do not have much clinical impor­
zed by edema. Severe hemolysis results in
tance. Other blood groups include:
the development of edema, enlargement of
1. Auberger groups.
liver and spleen and cardiac failure. When
2. Diego group.
this condition becomes more severe it may
3. Bombay group.
lead to intrauterine death of fetus.
4. Duffy group.
5. Lutheran group.
3. Kernicterus
6. P group.
Kernicterus is the form of brain damage in 7. Kell group.
infants caused by severe jaundice. If the 8. I group.
baby survives anemia in erythroblastosis 9. Kidd group.
fetalis (see above) then kernicterus deve­ 10. Sutter group.
lops because of high bilirubin content. 11. Xg group.
108 Section 2 ê Blood and Body Fluids

„„ IMPORTANCE OF KNOWING the Blood Donor’s Club so that he/she

BLOOD GROUP can be approached for blood donation
during emergency conditions.
Nowadays, knowledge of blood group is
very essential medically, socially and judi­ 3. It is general among the couples, know­
cially. The importance of knowing blood ledge of blood groups helps to pre­vent
group is: the complications due to Rh incompati­
1. Medically, it is important during blood bility and save the child from the dis­
transfusions and in tissue transplants. orders like erythroblastosis fetalis.
2. Socially, one should know his/her own 4. Judicially, it is helpful in medicolegal
blood group and become a member of cases to sort out parental disputes.
Chapter 20

Blood Transfusion



Blood transfusion is the process of trans­
ferring blood or blood components from one 1. Apparatus for transfusion must be
person (the donor) into the bloodstream of
another person (the recipient). Transfusion
may be done as a lifesaving procedure to 2. The temperature of blood to be trans­
replace blood cells or blood products lost fused must be same as body tempe­
through bleeding. rature.
Blood transfusion is essential in the condi­­ 3. The transfusion of blood must be slow.
tions like anemia, hemorrhage, trauma, burns The sudden rapid infusion of blood
and surgery.
into the body increases the load on
„„ PRECAUTIONS TO BE the heart resulting in many compli­
1. Donor must be healthy without any „„ BLOOD SUBSTITUTES
diseases like syphilis, AIDS, etc.
Substances infused in the body instead of
2. Only compatible blood must be trans­
fused and Rh compatibility must be whole blood are known as blood substi­
confirmed. tutes. The commonly used blood substi­
3. Both matching and crossmatching must tutes are human plasma, 0.9% sodium
be done. chloride solution (saline) and 5% glucose.
110 Section 2 ê Blood and Body Fluids


Exchange transfusion is the procedure
which involves removal of patient’s blood Autologous blood transfusion is the collection
and replacement with fresh donor blood and reinfusion of patient’s own blood. It is also
or plasma. It is otherwise known as called self-blood donation. The conventional
replacement transfusion. It is carried out in transfusion of blood that is collected from
conditions such as severe jaundice, sickle persons other than the patient is called
cell anemia, erythroblastosis fetalis, etc. allogeneic or heterologous blood transfusion.
Chapter 21

Reticuloendothelial System,
Tissue Macrophage and Spleen



„„ DEFINITION AND DISTRIBUTION 1. Fixed reticuloendothelial cells or tissue

2. Wandering reticuloendothelial cells.
Reticuloendothelial system or macrophage „„ FIXED RETICULOENDOTHELIAL
system is the system of primitive phagocytic CELLS – TISSUE MACROPHAGES
cells which play important role in defense The fixed reticuloendothelial cells are
mechanism of the body. also called tissue macrophages or fixed
histiocytes, because these cells are usually
„„ MACROPHAGE located in the tissues.
Macrophage is a large cell derived from The tissue macrophages are:
mono­cyte. It has the property of phago­cyto­ i. Reticuloendothelial cells in connective
sis. So, macrophage is also defined as a tissues and in serous membranes like
large phagocytic cell (refer Chapter 17). pleura, omentum and mesentery.
ii. Endothelial cells of blood sinusoid in
„„ CLASSIFICATION OF bone marrow, liver, spleen, lymph nodes,
RETICULOENDOTHELIAL adrenal glands and pituitary glands.
Kupffer cells in liver belong to this
The reticuloendothelial cells are classified iii. Cells in the reticulum of spleen, lymph
into two types: node and bone marrow.
112 Section 2 ê Blood and Body Fluids

iv. Meningocytes of meninges and micro­ 2. Secretion of Bactericidal Agents

glia in brain.
v. Alveolar cells in lungs. Tissue macrophages secrete many bacteri­
vi. Subcutaneous tissue cells. cidal agents, which kill the bacteria. The
important bactericidal agents of macro­pha­
„„ WANDERING ges are the oxidants. An oxidant is a sub­
RETICULOENDOTHELIAL CELLS stance that oxidizes another substance.
The oxidants secreted by macrophages
The wandering reticuloendothelial cells are
also called free histiocytes. There are two
i. Superoxide (O2–).
types of wandering reticuloendothelial cells:
ii. Hydrogen peroxide (H2O2).
1. Free histiocytes of blood:
i. Neutrophils. iii. Hydroxyl ions (OH–).
ii. Monocytes, which become macro­
phages and migrate to the site of 3. Secretion of Interleukins
injury or infection.
Tissue macrophages secrete interleukin-1,
2. Free histiocytes of solid tissue.
During emergency, the fixed histiocytes 6 and 12 which help in immunity.
from connective tissue and other organs
become wandering cells and enter the 4. Secretion of
circulation. Tumor Necrosis Factors

Tissue macrophages secrete TNF-α and

„„ FUNCTIONS OF TNF-β which cause necrosis of tumor.
SYSTEM 5. Secretion of Transforming
Reticuloendothelial system plays an impor­ Growth Factor
tant role in the defense mechanism of the
Tissue macrophages secrete transform­
body. Most of the functions of the reticulo­
ing growth factor which plays an important
endothelial system are carried out by the
tissue macrophages. role in preventing rejection of transplanted
The functions of tissue macrophages are tissues or organs.
detailed below.
6. Secretion of Colony-stimulating
1. Phagocytic Function Factor
Macrophages are the large phagocytic cells, Macrophages secrete the colony-stimulating
which play an important role in defense of factor (M-CSF) which accelerates growth of
the body by phagocytosis. When any foreign granulocytes, monocytes and macrophages.
body invades, macrophages ingest them by
phagocytosis and liberate the antigenic pro­ 7. Secretion of Platelet-derived
ducts of the organism. The antigens activate Growth Factor
the helper T lymphocytes and B lymphocytes
(refer Chapter 17 for details). Tissue macrophages secrete the platelet-
The lysosomes of macrophages con­ derived growth factor (PDGF), which acce­
tain proteolytic enzymes and lipases which lerates repair of damaged blood vessel and
digest the bacteria and other foreign bodies. wound healing.
Chapter 21 ê Reticuloendothelial System, Tissue Macrophage and Spleen 113
8. Removal of Carbon Particles produces the blood cells along with liver
and Silicon and bone marrow.
The macrophages ingest the substances
2. Destruction of Blood Cells
like carbon dust particles and silicon which
enter the body. The older RBCs, lymphocytes and thrombo­
cytes are destroyed in the spleen. When
9. Destruction of Senile RBC the RBCs become old (120 days), the cell
membrane becomes more fragile. The dia­
The reticuloendothelial cells, particularly meter of most of the capillaries is less or
those in spleen destroy the senile RBCs equal to that of RBC. The fragile old cells
and release hemoglobin (refer Chapter 9). are destroyed while trying to squeeze
through the capillaries because these cells
10. Destruction of Hemoglobin cannot withstand the stress of squeezing.
The hemoglobin released from broken senile The destruction occurs mostly in the
RBCs is degraded by the reticuloendothe­ capillaries of spleen because the splenic
lial cells (refer Chapter 11). capillaries have a thin lumen. So, the spleen
is known as graveyard of RBCs.
11. Hemopoietic Function
3. Blood Reservoir Function
The reticuloendothelial cells also play an
In animals, spleen stores large amount of
important role in the production of blood
blood. However, this function is not signi­
ficant in humans. But, a large number of
RBCs are stored in spleen. The RBCs are
„„ SPLEEN released from spleen into circulation during
Spleen is the largest lymphoid organ in the emergency conditions like hypoxia and
the body and it is highly vascular. It also hemorrhage.
contains reticuloendothelial cells.
4. Role in Defense of Body
„„ FUNCTIONS OF SPLEEN Spleen filters the blood by removing the
1. Formation of Blood Cells microorganisms. The macrophages in sple­nic
pulp destroy the microorganisms and other
The spleen plays an important role in the foreign bodies by phagocytosis. Spleen
hemopoietic function in embryo. During contains about 25% of T lympho­cytes and
the hepatic stage, spleen produces blood 15% of B lymphocytes and forms the site of
cells along with liver. In myeloid stage, it antibody production.
Chapter 22

Lymphatic System and Lymph


„„ LYMPHATIC SYSTEM paracortex and medulla of the lymph node.

From medulla, the lymph leaves the node
Lymphatic system is a closed system of
via one or two efferent vessels.
lymph channels or lymph vessels through
The lymph nodes are present along the
which lymph flows. It is a one-way system
course of lymphatic vessels in elbow, axilla,
and allows the lymph flow from tissue spaces
towards the blood. knee and groin. The lymph nodes are also
present in certain points in abdomen, thorax
and neck where many lymph vessels join.
Lymph nodes are small glandular structures „„ FUNCTIONS OF LYMPH NODES
located in the course of lymph vessels. The
lymph nodes are also called lymph glands Lymph nodes serve as filters which filter bac­
or lymphatic nodes. teria and toxic substances from the lymph.
Each lymph node constitutes masses The functions of the lymph nodes are:
of lymphatic tissue covered by a dense 1. When lymph passes through lymph
connective tissue capsule. The structures are nodes, it is filtered, i.e. the water and
arranged in three layers cortex, paracortex elec­­tro­lytes are removed. But, proteins
and medulla (Fig, 22.1). and lipids are retained in the lymph.
The lymph node receives lymph by one 2. Bacteria and other toxic substances
or two lymphatic vessels called afferent are destroyed by macrophages of
vessels. Afferent vessels divide into small lymph nodes. Because of this, lymph
chan­nels. Lymph passes through afferent nodes are called defense barriers.
vessels and small channels and reaches 3. Bacteria are phagocytozed by the
the cortex. It circulates through cortex, macro­phages of lymph node.
Chapter 22 ê Lymphatic System and Lymph 115
When blood passes via blood capillaries
in the tissues, 9/10th of fluid passes into
venous end of capillaries from arterial
end. And, the remaining 1/10th of the fluid
passes into lymph capillaries, which have
more permeability than blood capillaries.
So, when lymph passes through lymph
capillaries, the composition of lymph is
more or less similar to that of interstitial fluid
including protein content. Proteins present
in the interstitial fluid cannot enter the blood
capillaries because of their larger size. So,
FIGURE 22.1: Structure of a lymph node
these proteins enter lymph vessels, which
are permeable to large particles also.

Lymph is formed from interstitial fluid, due About 120 mL of lymph flows into blood
to the permeability of lymph capillaries. per hour. Out of this, about 100 mL/h flows

FIGURE 22.2: Composition of lymph

116 Section 2 ê Blood and Body Fluids

through thoracic duct and 20 mL/h flows 3. Through lymph, bacteria, toxins and
through the right lymphatic duct. other foreign bodies are removed from
„„ COMPOSITION OF LYMPH 4. Lymph flow is responsible for the
Usually, lymph is a clear and colorless fluid. maintenance of structural and func­
It is formed by 96% water and 4% solids. tional integrity of tissue. Obstruction
Some blood cells are also present in lymph to lymph flow affects various types
(Fig. 22.2). of tissues, particularly myocardium,
nephrons and the hepatic cells.
„„ FUNCTIONS OF LYMPH 5. Lymph flow serves as an important
1. The important function of lymph is to route for intestinal fat absorption. This
return proteins from tissue spaces into is the reason for the milky appearance
the blood. of lymph after fatty meal.
2. Lymph flow plays an important role in 6. It plays an important role in immunity
redistribution of fluid in the body. by transport of lymphocytes.
Chapter 23

Tissue Fluid and Edema


Tissue fluid is the medium in which cells are Tissue fluid is formed by the process of
bathed. It is otherwise known as interstitial filtration. Normally, the blood pressure (also
fluid. It forms about 20% of ECF. called hydrostatic pressure) in arterial end
of the capillary is about 30 mm Hg. This
„„ FUNCTIONS OF TISSUE FLUID hydrostatic pressure is the driving force
for filtration of water and other substances
Because of the capillary membrane, there is from blood into tissue spaces (Fig. 23.1).
no direct contact between blood and cells.
And the tissue fluid acts as a medium for „„ REABSORPTION
exchange of various substances between
the cells and the blood in the capillary loop. The fluid filtered at the arterial end of capil­
Oxygen and nutritive substances diffuse laries is reabsorbed back into the blood at
from the arterial end of capillary through the the venous end of capillaries. Here also,
tissue fluid and reach the cells. Carbon the pressure gradient plays an important
dioxide and waste materials diffuse from role. At the venous end of capillaries, the
the cells into the venous end of capillary hydrostatic pressure is less (15 mm Hg)
through this fluid. and the oncotic pressure is more (25 mm
Hg). Due to the pressure gradient of 10
„„ FORMATION OF TISSUE FLUID mm Hg, the fluid is reabsorbed along with
waste materials from the tissue fluid into
Formation of tissue fluid involves two the capillaries. About 10% of filtered fluid
processes: enters the lymphatic vessels.
1. Filtration. Reabsorption at the venous end helps
2. Reabsorption. to maintain the volume of tissue fluid.
118 Section 2 ê Blood and Body Fluids

FIGURE 23.1: Formation of tissue fluid. Plasma proteins remain inside the blood capillary, since the
capillary membrane is not permeable to plasma proteins.

„„ APPLIED PHYSIOLOGY – i. Malnutrition.

EDEMA ii. Poor metabolism.
iii. Inflammation of the tissues.
Edema is defined as the swelling caused by 2. Extracellular Edema
excessive accumulation of fluid in tissues.
Extracellular edema is defined as the accu­
It may be generalized or local. Edema that
mulation of fluid outside the cell. It occurs
involves the entire body is called general­
ized edema. Local edema is the one that because of abnormal leakage of fluid from
occurs is specific areas of the body such as capillaries into interstitial space and obstruc­
abdomen, lungs and extremities like feet, tion of lymphatics that prevents return of fluid
ankles and legs. The accumulation of fluid from interstitial fluid back into blood.
may be inside or outside the cell. The common conditions which leads to
extracellular edema are:
„„ TYPES OF EDEMA 1. Heart failure.
2. Renal disease.
Edema is classified into two types depend­
3. Decreased amount of plasma proteins.
ing upon the body fluid compartment where
4. Lymphatic obstruction.
accumulation of excess fluid occurs:
1. Intracellular edema. 5. Increased endothelial permeability.
2. Extracellular edema.
Pitting and Non-pitting Edema
1. Intracellular Edema Interstitial fluid is present in the form of a gel
Intracellular edema is the accumulation of that is almost like a semisolid substance.
fluid inside the cell. It occurs because of It is because the interstitial fluid is not pre­
three reasons: sent as fluid, but is bound in a proteoglycan
Chapter 23 ê Tissue Fluid and Edema 119
meshwork. It does not allow any free space of fluid occurs producing a depression or pit.
for the movement of fluid. When the finger is removed, the pit remains
When interstitial fluid volume increases, for few seconds, sometimes as long as 1
most of the fluid becomes free fluid that is not minute, till the fluid flows back into that area.
bound to proteoglycan meshwork. It flows Edema also develops due to swelling of
freely through tissue spaces, producing a the cells or clotting of interstitial fluid in the
swelling called edema. This type of edema is presence of fibrinogen. This is called non-
known as pitting edema, because when this pitting edema, because it is hard and a pit
area is pressed with the finger, displacement is not formed by pressing.
120 Questions in Blood and Body Fluids


„„ LONG QUESTIONS 9. Functions of blood.

10. Plasma proteins.
1. What are the compartments of body
11. Functions of RBCs.
fluid? Enumerate the differences bet­
12. Fate of RBCs.
ween ECF and ICF and explain the
13. Lifespan of RBCs.
measurement of ECF volume.
14. Physiological variations of RBC count.
2. What is indicator dilution technique?
15. Polycythemia.
How is it applied in the measurement
16. Factors necessary for erythropoiesis.
of total body water? Describe dehy­
17. Destruction of hemoglobin.
dration briefly.
18. Abnormal hemoglobin.
3. Give a detailed account of erythro­
19. Abnormal hemoglobin derivatives.
20. Pernicious anemia.
4. Define erythropoiesis. List the different
21. Erythrocyte sedimentation rate.
stages of erythropoiesis. Describe the
22. Packed cell volume or hematocrit.
changes, which take place in each
23. Anemia.
stage and the factors necessary for
24. Hemolysins.
25. Types and morphology of WBCs.
5. Describe the morphology, development
26. Functions of WBCs.
and functions of leukocytes.
27. T lymphocytes.
6. Describe the development of cell-medi­
28. B lymphocytes.
ated immunity.
29. Role of macrophages in immunity.
7. Describe the development of humoral
30. Immunoglobulins or antibodies.
31. Immune deficiency diseases.
8. Define blood coagulation. Describe the
32. Autoimmune diseases.
mechanisms involved in coagulation.
33. Platelets.
Add a note on anticoagulants.
34. Hemostasis.
9. Enumerate the factors involved in blood
35. Fibrinolysis.
coagulation and describe the intrinsic
36. Tests for coagulation.
mechanism of coagulation.
37. Anticoagulants.
10. Give an account of extrinsic mechanism
of coagulation of blood. Give a brief 38. Hemophilia.
description of bleeding disorders. 39. Purpura.
40. Thrombosis.
41. ABO blood groups.
42. Rh factor.
1. Dye or indicator dilution technique. 43. Transfusion reactions.
2. Measurement of total body water. 44. Erythroblastosis fetalis.
3. Measurement of ECF volume. 45. Tissue macrophage.
4. Measurement of ICF volume. 46. Functions of spleen.
5. Measurement of blood volume. 47. Lymph.
6. Measurement of plasma volume. 48. Lymph nodes.
7. Dehydration. 49. Tissue fluid.
8. Water intoxication. 50. Edema.
Section 3
Muscle Physiology

Classification of Muscles.......................................................... 123
Structure of Skeletal Muscle.................................................... 126
Properties of Skeletal Muscle................................................... 132
Electrical and Molecular Changes
During Muscular Contraction.................................................... 138
28. Neuromuscular Junction.......................................................... 145
29. Smooth Muscle........................................................................ 150
Chapter 24

Classification of Muscles



There are more than 600 muscles in our Non-striated Muscle

body. Muscles perform many useful functions The muscle which does not have cross
and help us in doing everything in day to day striations is called non-striated muscle. It is
life. Muscles are classified by three different also called plain muscle or smooth muscle.
methods based on different factors: It is found in the wall of the visceral organs.
1. Depending upon the presence or
absence of striations. „„ DEPENDING UPON CONTROL
2. Depending upon the control. Depending upon the control, the muscles
3. Depending upon the function. are classified into two types:
1. Voluntary muscle.
„„ DEPENDING UPON STRIATIONS 2. Involuntary muscle.

Depending upon the presence or absence Voluntary Muscle

of the cross striations, muscles are divided Voluntary muscle is the muscle that is con­
into two groups: trolled by the will. Skeletal muscles are
1. Striated muscle. the voluntary muscles. These muscles are
2. Non-striated muscle. innervated by somatic nerves.

Striated Muscle Involuntary Muscle

The muscle that cannot be controlled by the
Striated muscle is the muscle which has a
will is called involuntary muscle. Cardiac
large number of cross striations (transverse muscle and smooth muscle are involuntary
lines). Skeletal muscle and cardiac muscle muscles. These muscles are innervated by
belong to this category. autonomic nerves.
124 Section 3 ê Muscle Physiology

„„ DEPENDING UPON 1. Skeletal muscle.

SITUATION 2. Cardiac muscle.
3. Smooth muscle.
The muscles are classified into three types The features of these muscles are given
depending upon the situation: in Table 24.1.

TABLE 24.1: Features of skeletal, cardiac and smooth muscle fibers

Features Skeletal muscle Cardiac muscle Smooth muscle

In association with
Location In the heart In the visceral organs
Cylindrical and Spindle shaped
Shape Branched
unbranched unbranched
Length 1 to 4 cm 80 to 100 μ 50 to 200 μ
Diameter 10 to 100 μ 15 to 20 μ 2 to 5 μ
Number of nucleus >1 1 1
Cross striations Present Present Absent
Myofibrils Present Present Absent
Sarcomere Present Present Absent
Troponin Present Present Absent
Sarcotubular system Well developed Well developed Poorly developed
T-tubules Long and thin Short and broad Absent
Depolarization Upon stimulation Spontaneous Spontaneous
Fatigue Possible Not possible Not possible
Summation Possible Not possible Possible
Tetanus Possible Not possible Possible
Resting membrane
Stable Stable Unstable
For trigger of
contraction, Troponin Troponin Calmodulin
calcium binds with
Source of calcium Sarcoplasmic reticulum Extracellular
Speed of contraction Fast Intermediate Slow
Well defined Not well defined Not well defined
Action Voluntary action Involuntary action Involuntary action
Neurogenic and
Control Only neurogenic Myogenic
Nerve supply Somatic nerves Autonomic nerves Autonomic nerves
Chapter 24 ê Classification of Muscles 125
Skeletal Muscle Cardiac Muscle
Skeletal muscle is situated in association Cardiac muscle forms the musculature of
with bones forming the skeletal system. the heart. These muscles are striated and
The skeletal muscles form 40 to 50% of involuntary. Cardiac muscles are supplied
body mass and are voluntary and striated. by autonomic nerve fibers.
These muscles are supplied by somatic
nerves. Smooth Muscle
The fibers of the skeletal muscles are Smooth muscle or visceral muscle is situ­ated
arranged in parallel. In most of the skeletal in association with viscera. Smooth muscle
muscles, the muscle fibers are attached to is nonstriated and involuntary. Because of
tendons on either end. The skeletal mus­ the absence of cross striations it is called
cles are anchored to the bones by the smooth or plain muscle. It is supplied by auto­
tendons. nomic nerve fibers.
Chapter 25

Structure of Skeletal Muscle


The muscle mass (or tissue) is made up of
a large number of individual muscle cells or
myocytes. The muscle cells are commonly
called muscle fibers because these cells are
long and slender in appearance. The skele­
tal muscle fibers are multinucleated and
arranged parallel to one another with some
connective tissue in between.
The muscle mass is separated from the
neighboring tissues by the thick fibrous tissue
layer known as fascia. Beneath the fascia,
the muscle is covered by a connective tissue
sheath called epimysium. In the muscle, the
muscle fibers are arranged in various groups
called the bundles or fasciculi. The connective
tissue sheath that covers each fasciculus is
called perimysium. Each muscle fiber is cove­ FIGURE 25.1: Diagram showing. A. Skeletal
red by the connective tissue layer called the muscle mass; B. Cross-section of muscle; C.
endomysium (Fig. 25.1). One muscle fasciculus.
Chapter 25 ê Structure of Skeletal Muscle 127
„„ MUSCLE FIBER These are the fine parallel filaments pre­
sent in sarcoplasm of the muscle cell. The
Each muscle cell or muscle fiber is cylindri­ myofibrils run through the entire length of
cal in shape. The length of the fiber is bet­ the muscle fiber.
ween 1 and 4 cm depending upon the length
of the muscle. The diameter of the muscle „„ MICROSCOPIC STRUCTURE OF A
fiber varies from 10 to 100 µ. The muscle MYOFIBRIL
fibers are attached to bone by a tough cord
Light microscopic studies show that, each
of connective tissue called tendon. myofibril consists of a number of two alter­
Each muscle fiber is enclosed by a cell nating bands. The two bands are:
membrane called plasma membrane that 1. Light band or ‘I’ band.
lies beneath the endomysium. It is also cal­ 2. Dark band or ‘A’ band.
led sarcolemma (Fig. 25.2). The cytoplasm
of the muscle is known as sarcoplasm. Light Band or ‘I’ band
Many structures are embedded within the
The light band is called ‘I’ band because it is
sarcoplasm: isotropic to polarized light. When the polari­
1. Nuclei. zed light is passed through the muscle fiber
2. Myofibril. at this area the light rays are refracted at
3. Golgi apparatus. the same angle.
4. Mitochondria.
5. Sarcoplasmic reticulum. Dark Band or ‘A’ band
6. Ribosomes.
The dark band is called ‘A’ band because
7. Glycogen droplets. it is anisotropic to polarized light. When
8. Occasional lipid droplets. the polarized light is passed through the
muscle fiber at this area, the light rays are
„„ MYOFIBRIL refracted at different directions (an = not,
iso = it, trops = turning).
Myofibrils or myofibrillae are the special In an intact muscle fiber, ‘I’ band and ‘A’
structures present only in muscle fibers. band of the adjacent myofibrils are placed
side by side. It gives the appearance of
characteristic cross striations in the muscle
‘I’ band is divided into two portions by
a narrow dark line called ‘Z’ line or ‘Z’ disk
(in German zwischenscheibe = between
disks). The ‘Z’ line is formed by a protein
disk which does not permit passage of light.
The portion of myofibril in between two ‘Z’
lines is called sarcomere.

FIGURE 25.2: A. One muscle cell; Sarcomere is the structural and functional
B. One myofibril. unit of the skeletal muscle.
128 Section 3 ê Muscle Physiology

Extent Actin Filaments

Each sarcomere extends between two ‘Z’ Actin filaments are the thin filaments that
lines of myofibril. Thus, each myofibril con­ extend from either side of the ‘Z’ lines, run
tains many sarcomeres arranged in series across ‘I’ band and enter into ‘A’ band up to
throughout its length. When the muscle is ‘H’ zone.
in relaxed state, the average length of each
sarcomere is 2 to 3 microns. Myosin Filaments
Myosin filaments are thick filaments and
Components are situated in ‘A’ band.
Each myofibril consists of alternate dark Some lateral processes (projections) or
‘A’ band and light ‘I’ band (Fig. 25.3). In cross bridges arise from myosin filaments.
the middle of ‘A’ band, there is a light area These bridges have enlarged structures
called ‘H’ zone (H = hell = light—in German, called myosin heads at their tips. The myosin
H = Henson – discoverer). In the middle heads attach themselves to actin filaments.
of ‘H’ zone lies the middle part of myosin These heads pull the actin filaments during
filament. This is called ‘M’ line (in German contraction of the muscle by means of a
mechanism called sliding mechanism or
mittel = middle). ‘M’ line is formed by myosin
ratchet mechanism (refer Chapter 27).
binding proteins.


The electron microscopic studies reveal The myosin filaments are formed by protein
that the sarcomere consists of many thread- molecules called myosin molecules. The
like structures called myofilaments. Myofila­ actin filaments are formed by three types
ments are of two types: of proteins called actin, tropomyosin and
1. Actin filaments. troponin. These four proteins together cons­
titute the muscle proteins or the contractile
2. Myosin filaments.
elements of the muscle.
In addition to the contractile proteins,
the sarcomere contains some more pro­

Each myosin filament consists of about
200 myosin molecules. Myosin is a globulin
which is made up of 6 polypeptide chains.
Out of these, two are heavy chains and
four are light chains. The two heavy chains
twist around each other to form a double
helix (Fig. 25.4). At one end, the two chains
remain twisted around one another and form
FIGURE 25.3: Sarcomere. A = A band, the tail portion. At the other end, both the
I = I band. chains turn away in opposite directions and
Chapter 25 ê Structure of Skeletal Muscle 129
There are about 40 to 60 tropomyosin mole­
cules situated along the double helix strand
of actin filament. In relaxed condition of the
muscle, the tropomyosin molecules cover
all the active sites of F actin molecules.

It is formed by three subunits:
1. Troponin I which is attached to F-actin.
FIGURE 25.4: Myosin molecule formed by 2. Troponin T which is attached to tropo­
two heavy chains and four light chains of poly­ myosin.
peptides. 3. Troponin C which is attached to cal­
form the globular head portion. To each part cium ions.
of this head, are attached two light chains.
Each myosin head has two attachment „„ SARCOTUBULAR SYSTEM
sites. One site is for actin filament and the Sarcotubular system is a system of membra­
other one is for one ATP molecule (Fig. nous structures in the form of vesicles and
25.5). In the central part of the myosin fila­ tubules in the sarcoplasm of the muscle
ment, i.e. in the ‘H’ zone, the myosin head fiber. It surrounds the myofibrils embedded
is absent. in the sarcoplasm.
The sarcotubular system is formed mainly
„„ ACTIN MOLECULE by two types of structures:
Actin molecules are the major constituents 1. T-tubules.
of the thin actin filaments. Each actin mole­ 2. L-tubules or sarcoplasmic reticulum.
cule is called F-actin and it is derived from
G-actin. There are about 300 to 400 actin
molecules in each actin filament. The actin T-tubules or transverse tubules are narrow
molecules in the actin filament are also tubules formed by invagination of the sarco­
arranged in the form of a double helix. Each lemma. These tubules penetrate all the way
F-actin molecule has an active site to which from one side of the muscle fiber to other side.
the myosin head is attached (Fig. 25.6). Because of their origin from sarcolemma,

FIGURE 25.5: Diagram showing FIGURE 25.6: Part of actin filament. Troponin
myosin filament has three subunits T, C and I
130 Section 3 ê Muscle Physiology

T-tubules open to the exterior of the muscle

cell. Therefore, the ECF runs through their
Function of T-tubules
The T-tubules are responsible for rapid trans­
mission of impulse in the form of action
potential from sarcolemma to the myofibrils.

The L-tubules or longitudinal tubules are
the closed tubules that run in long axis of
the muscle fiber forming sarcoplasmic reti­
culum. These tubules form a closed tubular
system around each myofibril and do not
open to exterior like T-tubules.
The L-tubules correspond to the endo­
plasmic reticulum of other cells. At regular FIGURE 25.7: Diagram showing the relation
intervals, throughout the length of the myo­ between sarcotubular system and parts of sar­
fibrils, the L-tubules dilate to form a pair comere. Only few myofilaments are shown in the
of lateral sacs called terminal cisternae. myofibril drawn on the right side of the diagram.

FIGURE 25.8: Composition of skeletal muscle

Chapter 25 ê Structure of Skeletal Muscle 131
Each pair of terminal cisternae is in close ions trigger the processes involved in con­
contact with T-tubule. The T-tubule along traction of the muscle. The process by which
with the cisternae on either side is called the calcium ions cause contraction of muscle
the triad of skeletal muscle. Calcium ions is called excitation contraction coupling
are stored in L-tubule and the amount of (refer Chapter 27).
calcium ions is more in cisternae (Fig. 25.7).
Functions of L-tubules
The skeletal muscle is formed by 75% of
The L-tubules store a large quantity of cal­ water and 25% of solids. Solids are 20% of
cium ions. When the action potential reaches proteins and 5% of organic substances other
the cisternae of L-tubule, the calcium ions are than proteins and inorganic substances
released into the sarcoplasm. The calcium (Fig. 25.8).
Chapter 26

Properties of Skeletal Muscle


„„ EXCITABILITY 3. Thermal stimulus (by applying heated

glass rod or ice piece).
4. Chemical stimulus (by applying chemi­
Excitability is defined as the reaction or cal substances like acids).
response of a tissue to irritation or stimu­ Electrical stimulus is commonly used for
lation. It is a physicochemical change. experimental purposes.

„„ STIMULUS Intensity of Stimulus

Stimulus is the change in environment. It The intensity or strength of a stimulus is of
is defined as an agent or influence or act, five types:
which brings about the response in an exci­ 1. Subminimal stimulus.
table tissue. 2. Minimal stimulus.
3. Submaximal stimulus.
Types of Stimulus 4. Maximal stimulus.
There are four types of stimuli, which can 5. Supramaximal stimulus.
excite a living tissue: The stimulus whose strength (or voltage)
1. Mechanical stimulus (pinching). is sufficient to excite the tissue is called
2. Electrical stimulus (electric shock). threshold or liminal or minimal stimulus.
Chapter 26 ê Properties of Skeletal Muscle 133
Contractility is the response of the skeletal The muscles which contain large number of
muscle to a stimulus by change in either the type I fibers are called red muscles. These
length or tension of the muscle fibers. muscles are also called slow muscles or
slow twitch muscles. The red muscles have
„„ TYPES OF CONTRACTION longer contraction time. Back muscles and
gastrocnemius muscles are red muscles.
Muscular contraction is classified into two
types based on change in the length of Pale Muscles
muscle fibers or tension of the muscle: The muscles which have large number
1. Isotonic contraction. of type II fibers are called pale muscles.
2. Isometric contraction. These muscles are also called white mus­
cles, fast muscles or fast twitch muscles.
Isotonic Contraction The pale muscles have shorter contraction
Isotonic contraction is the type of muscular time. Hand muscles and ocular muscles
contraction in which the tension remains the are pale muscles.
The characteristic features of red and
same and the length of the muscle fiber is
pale muscles are given in Table 26.1.
altered (Iso = same, Tonic = tension). For
example, the simple flexion of arm, where
shortening of muscle fibers occurs but the CONTRACTION
tension does not change.
The force of contraction of the skeletal
Isometric Contraction muscle is affected by the following factors:
A. Strength of stimulus.
Isometric contraction is the type of muscular B. Number of stimulus.
contraction in which the length of muscle C. Temperature.
fibers remains the same and the tension is D. Load.
increased. Example is pulling any heavy
object when muscles become stiff and strai­ A. Effect of Strength of Stimulus
ned with increased tension but the length
Force of contraction is directly proportional
does not change.
to strength of stimulus.
B. Effect of Number of Stimulus
Based on the contraction time, the skeletal The response of the muscle in the form
muscles are classified into two types, the of contraction differs depending upon the
red (slow) muscles and pale (fast) mus­ number of stimuli. If a single stimulus is given,
cles. Similarly, the muscle fibers are also the muscle gives response only once. If two
divided into two types, type I and type II stimuli are given with sufficient time interval
fibers. Type I fibers (slow fibers or slow it gives response twice.
twitch fibers) have small diameter. Type When a muscle is stimulated by multiple
II fibers (fast fibers or fast twitch fibers) stimuli, two types of effects are obtained
have large diameter. Most of the skeletal depen­ding upon the frequency of stimuli:
muscles in human beings contain both the 1. Fatigue.
types of fibers. 2. Tetanus.
134 Section 3 ê Muscle Physiology

TABLE 26.1: Features of red and pale muscles

Red (slow) muscle Pale (fast) muscle

1. Type I fibers are more Type II fibers are more
2. Myoglobin content is high. So, it is red Myoglobin content is less. So, it is pale
3. Sarcoplasmic reticulum is less extensive Sarcoplasmic reticulum is more extensive
4. Blood vessels are more extensive Blood vessels are less extensive
5. Mitochondria are more in number Mitochondria are less in number
6. Response is slow with long-latent period Response is rapid with short-latent period
7. Contraction is less powerful Contraction is more powerful
This muscle is involved in prolonged and This muscle is not involved in prolonged
8. continued activity as it undergoes and continued activity as it relaxes
sustained contraction immediately
9. Fatigue occurs slowly Fatigue occurs quickly
Depends upon cellular respiration for Depends upon glycolysis for ATP
adenosine triphosphate (ATP) production production

1. Fatigue Recovery of the muscle after fatigue

Definition The fatigue is a reversible phenomenon. The
fatigued muscle recovers if given rest and
Fatigue is defined as the decrease in mus­
cular activity due to repeated stimuli with
low frequency. When the stimuli are applied Causes of recovery
continuously, after some time, the muscle i. Removal of metabolites.
does not show any response to the stimulus. ii. Formation of acetylcholine at the neuro­
This condition is called fatigue. muscular junction.
Causes for fatigue iii. Re-establishment of normal polarized
state of the muscle.
i. Exhaustion of acetylcholine in motor
iv. Availability of nutrients.
v. Availability of oxygen.
ii. Accumulation of metabolites like lactic
acid and phosphoric acid. In the intact body, all the processes
iii. Lack of nutrients like glycogen. involved in recovery are achieved by circu­
iv. Lack of oxygen. lation itself.

Site (seat) of fatigue 2. Tetanus

In the intact body, the sites of fatigue are in Definition
the following order:
i. Betz (pyramidal) cells in cerebral Tetanus is defined as the sustained con­
cortex. traction of muscle due to repeated stimuli
ii. Anterior gray horn cells (motor neu­ with high frequency. When the multiple
rons) of spinal cord. stimuli are applied at a higher frequency in
iii. Neuromuscular junction. such a way that the successive stimuli fall
iv. Muscle. during contraction period of previous twitch,
Chapter 26 ê Properties of Skeletal Muscle 135
the muscle remains in state of tetanus, i.e. Other types of rigors are:
all the contractions are fused. The muscle 1. Cold rigor that occurs due to the expo­
relaxes only after the stoppage of stimulus sure to severe cold. It is a reversible
or when the muscle is fatigued. phenomenon.
If the frequency of stimuli is less, partial 2. Calcium rigor which is due to increased
fusion of contractions takes place leading calcium content. It is also reversible.
to incomplete tetanus or clonus. 3. Rigor mortis which develops after
Frequency of stimuli necessary to
cause tetanus and clonus Rigor mortis
In gastrocnemius muscle of human being, Rigor mortis refers to after death condition
the frequency required to cause tetanus is of the body which is characterized by stiff­
60/second. And for clonus, the frequency of ness of muscles and joints (Latin word,
stimuli necessary is 55/second. rigor = stiff). It occurs due to stoppage of
aerobic respiration, which causes changes
C. Effect of Variations in Temperature in the muscles.
Soon after death, the cell membrane
If the temperature of muscle is altered, the
becomes highly permeable to calcium. So
force of contraction is also affected.
a large number of calcium ions enters the
Warm temperature muscle fibers and promotes the formation of
actomyosin complex resulting in contraction
At warm temperature of about 40°C, the
of the muscles.
force of contraction increases because of
the following reasons: Few hours after death, all the muscles
1. The excitability of muscle increases. of body undergo severe contraction and
2. The chemical processes involved in become rigid. The joints also become stiff
muscular contraction are accelerated. and locked.
3. The viscosity of muscle decreases. Normally for relaxation, the muscle
needs to drive out the calcium which requi­
Cold temperature res ATP. But during continuous muscular
At cold temperature of about 10°C, the force contraction and other cellular processes
of contraction decreases because of the after death, the ATP molecules are com­
following reasons: pletely exhausted. New ATP molecules
1. Excitability of muscle decreases. cannot be produced because of lack of
2. Chemical processes are slowed or oxygen. So in the absence of ATP, the mus­
delayed. cles remain in contracted state until the
3. Viscosity of the muscle increases. onset of decomposition.
High or hot temperature – heat rigor Medicolegal importance of rigor mortis
At high temperatures, heat rigor occurs in Rigor mortis is useful in determining the
the muscle. Rigor refers to shortening and time of death. Onset of stiffness starts bet­
stiffening of muscle fibers. Heat rigor is the ween 10 minutes and 3 hours after death
rigor that occurs due to increased tempe­ depending upon the condition of the body
rature above 60°C. The cause of heat rigor and environmental temperature at the time
is the coagulation of muscle proteins actin of death. If the body is active or the environ­
and myosin. It is an irreversible pheno­ mental temperature is high at the time of
menon. death, the stiffness sets in quickly.
136 Section 3 ê Muscle Physiology

The stiffness develops first in facial mus­ Frank-Starling law

cles and then spreads to other muscles. The
Frank-Starling law states that the force of
maximum stiffness occurs around 12 to 24
contraction is directly proportional to the
hours after death. The stiffness of muscles
initial length of muscle fibers within physio­
and joints continues for 1 to 3 days.
logical limits.
Afterwards, the decomposition of the
general tissues starts. Now the lysosomal „„ REFRACTORY PERIOD
intracellular hydrolytic enzymes like cathe­
psins and calpains are released. These Refractory period is the period at which the
enzy­mes hydrolyze the muscle proteins, muscle does not show any response to a
actin and myosin resulting in breakdown stimulus. It is because already one action
of actomyosin complex. It relieves the stiff­ potential is in progress and the muscle is
ness of the muscles. This process is known in depolarized state during this period. The
as resolution of rigor. muscle is unexcitable to further stimulation
until it is repolarized. Refractory period is of
D. Effect of Load two types:
1. Absolute refractory period.
The load acting on muscle is of two types: 2. Relative refractory period.
1. After load.
2. Free load. 1. Absolute Refractory Period
After load Absolute refractory period is the period
After load is the load, that acts on the during which the muscle does not show
muscle after the beginning of muscular con­ any response at all, whatever may be the
strength of stimulus.
traction. Example, after load is lifting any
object from the ground. The load acts on
2. Relative Refractory Period
muscles of arm only after lifting the object
off the ground, i.e. only after beginning of Relative refractory period is the period, dur­
the muscular contraction. ing which the muscle shows some res­ponse
if the strength of stimulus is increased to
Free load maximum.
Free load is the load, which acts on the
muscle freely, even before the onset of „„ MUSCLE TONE
contraction of the muscle. It is otherwise
called fore load. Example of free load is
filling water from a tap by holding the bucket Muscle tone is defined as continuous and
in hand. partial contraction of the muscles with certain
Muscle in free loaded condition works degree of vigor and tension. More details on
better than the muscle in after loaded condi­ muscle tone are given in Chapter 103.
tion. It is because, in free loaded condition,
the muscle fibers are stretched and the „„ MAINTENANCE OF MUSCLE TONE
initial length of muscle fibers is increased.
In Skeletal Muscle
So, the force of contraction and the work
done by the muscles are increased. It is in Maintenance of tone in skeletal muscle is
accordance with Frank-Starling law. neurogenic. It is due to continuous discharge
Chapter 26 ê Properties of Skeletal Muscle 137
of impulses from gamma motor neurons in In Smooth Muscle
anterior gray horn of spinal cord. The gamma In smooth muscle, tone is myogenic. It
motor neurons in spinal cord are con­trolled depends upon calcium level and number of
by higher centers in brain. cross bridges.

In Cardiac Muscle „„ APPLIED PHYSIOLOGY –

In cardiac muscle, maintenance of tone is ABNORMALITIES OF
purely myogenic, i.e. the muscles themsel­ MUSCLE TONE
ves control the tone. The tone is not under 1. Hypertonia: Increased muscle tone.
nervous control in cardiac muscle. 2. Hypotonia: Decreased muscle tone.
Chapter 27

Electrical and Molecular Changes

During Muscular Contraction


„„ ELECTRICAL CHANGES muscle during resting membrane potential

DURING MUSCULAR is called polarized state. In human skeletal
CONTRACTION muscle, the resting membrane potential is
– 90 mV.
When the muscle is in resting condition, the
electrical potential is called resting membrane „„ ACTION POTENTIAL
potential (RMP). When the muscle is stimu­
lated, electrical changes occur which are Action potential is defined as a series of
collectively called action potential. electrical changes that occur when the mus­
cle or nerve is stimulated. Action potential
„„ RESTING MEMBRANE POTENTIAL occurs in two phases:
1. Depolarization.
Resting membrane potential is the elec­ 2. Repolarization.
trical potential difference (voltage) across
the cell membrane (between inside and Depolarization
outside of the cell) under resting condition.
It is also called membrane potential, trans­ Depolarization is the initial phase of action
membrane potential, transmembrane poten­ potential in which the inside of the muscle
tial difference or transmembrane poten­tial becomes positive and outside becomes
gradient. negative. That is, the polarized state (resting
Resting muscle shows negativity inside membrane potential) is abolished resul­ting
and positivity outside. The condition of the in depolarization.
Chapter 27 ê Electrical and Molecular Changes During Muscular Contraction 139
Repolarization zero potential (isoelectric base) up to + 55
mV. It is called overshoot.
Repolarization is the phase of action potential
when the potential inside the muscle reverses
back to the resting membrane potential. That
is, within a short time afterdepolarization, When depolarization is completed (+ 55 mV),
the interior of muscle becomes negative and the repolarization starts. Initially, the repo­
outside becomes positive. So, the polarized larization occurs rapidly and then it beco­
state of the muscle is re-established. mes slow.

Properties of Action Potential

The properties of action potential are listed
in Table 27.1.


Stimulus Artifact
The resting membrane potential is recorded
as a straight baseline at – 90 mV (Fig. 27.1).
When a stimulus is applied, there is a slight
irregular deflection of baseline for a very
short period. This is called stimulus artifact.
The artifact is due to leakage of current
from stimulating electrode to the recording
electrode. The stimulus artifact is followed by
latent period.

Latent Period
Latent period is the period when no change
occurs in the electrical potential. It is a
very short period with duration of 0.5 to 1

Firing Level and Depolarization

Depolarization starts after the latent period.
Initially, it is very slow. After the initial slow depo­
larization for about 15 mV (up to – 75 mV),
the rate of depolarization increases sud­denly.
The point at which the depolarization incre­
ases suddenly is called firing level. FIGURE 27.1: Action potential in a
skeletal muscle
Overshoot A = Opening of few Na+ channels
B = Opening of many Na+ channels
From firing level, the curve reaches iso­ C = Closure of Na+ channels and opening of K+
electric potential (zero potential) rapidly and channels
then shoots up (overshoots) beyond the D = Closure of K+ channels
140 Section 3 ê Muscle Physiology

Spike Potential energy from ATP. Since more positive ions

(cations) are pumped outside than inside, a
The rapid rise in depolarization and the rapid
net deficit of positive ions occurs inside the
fall in repolarization are together called spike
cell. It leads to negativity inside and posi­
potential. It lasts for 0.4 millisecond.
tivity outside the cell. More details of this
pump are given in Chapter 3.
Afterdepolarization or
Negative Afterpotential 2. Selective permeability of
The rapid fall in repolarization is followed cell membrane
by a slow repolarization. It is called after­ The permeability of cell membrane depends
depolarization or negative afterpotential. Its largely on the transport channels. The trans­
duration is 2 to 4 milliseconds. port channels are selective for move­ment
of some specific ions. Most of the channels
Afterhyperpolarization or are gated channels and the specific ions
Positive Afterpotential can move across the mem­brane only when
After reaching the resting level (– 90 mV), these gated channels are opened.
it becomes more negative beyond resting
Channels for major anions (negatively
level. This is called afterhyperpolarization or
charged substances) like proteins
positive afterpotential. This lasts for more
than 50 milliseconds. After this, the normal However, channels for some of the nega­
RMP is restored slowly. tively charged large substances such as
proteins and negatively charged organic
„„ IONIC BASIS OF phosphate and sulfate compounds are
ELECTRICAL EVENTS absent or closed. So, such substances
remain inside the cell and play a major role
Resting Membrane Potential
in the development and maintenance of
The development and maintenance of res­ nega­tivity inside the cell (resting membrane
ting membrane potential in a muscle fiber potential).
or a neuron are carried out by movement of
ions, which produce ionic imbalance across Channels for ions
the cell membrane. This results in the deve­ In addition, the channels for three important
lopment of more positivity outside and more ions, i.e. sodium, chloride and potassium
negativity inside the cell. The ionic imba­ also play an important role in maintaining
lance is produced by two factors: the resting membrane potential.
1. Sodium-potassium pump.
2. Selective permeability of cell mem­ Action Potential
During the onset of depolarization, voltage-
1. Sodium-potassium pump gated Na+ channels open resulting in slow
Sodium and potassium ions are actively influx of Na+. When depolarization reaches
transported in opposite directions across the 7 to 10 mV, the voltage-gated Na+ channels
cell membrane by means of an electroge­ start opening at a faster rate. It is called Na+
nic pump called sodium-potassium pump. It channel activation. When the firing level is
moves three sodium ions out of the cell and reached, the influx of Na+ is very great and
two potassium ions inside the cell by using it leads to overshoot.
Chapter 27 ê Electrical and Molecular Changes During Muscular Contraction 141
But the Na+ transport is short-lived. This 1. Endplate potential in neuromuscular
is because of rapid inactivation of Na+ junction (refer Chapter 28).
chan­nels. Thus, the Na+ channels open and 2. Receptor potential (refer Chapter 91).
close quickly. At the same time, the K+ 3. Excitatory postsynaptic potential (refer
channels start opening. This leads to efflux Chapter 92).
of K+ out of the cell, causing repolarization. 4. Inhibitory postsynaptic potential (refer
Unlike the Na+ channels, the K+ chan­ Chapter 92).
nels remain open for longer duration. These
channels remain opened for few more milli­
seconds after completion of repo­larization.
It causes efflux of more number of K+ pro­ DURING MUSCULAR
ducing more negativity inside. It is the cause CONTRACTION
for hyperpolarization. „„ ACTOMYOSIN COMPLEX

„„ GRADED POTENTIAL In the relaxed state of the muscle, the thin

actin filaments from the opposite ends of
Graded potential is a mild local change in the sarcomere are away from each other
the membrane potential that develops in leaving a broad ‘H’ zone.
receptors, synapse or neuromuscular junc­ During the contraction of the muscle, the
tion when stimulated. It is also called graded
actin (thin) filaments glide over the myosin
membrane potential or graded depo­ lari­
(thick) filaments and form actomyosin com­
zation. The graded potential is distinct from
the action potential and the properties
of these two potentials are given in Table
27.1. In most of the cases, the graded poten­ „„ MOLECULAR BASIS OF
tial is responsible for the generation of MUSCULAR CONTRACTION
action potential. However, in some cases The molecular mechanism is responsible
the graded potential hyperpolarizes the for formation of actomyosin complex that
mem­brane potential (more negativity than results in muscular contraction. It includes
resting membrane potential). three stages:
The graded potentials include: 1. Excitation contraction coupling.
TABLE 27.1: Properties of action potential and 2. Role of troponin and tropomyosin.
graded potential 3. Sliding mechanism.

Action potential Graded potential 1. Excitation Contraction Coupling

Propagative Nonpropagative Excitation contraction coupling is the pro­
Long distance signal Short distance signal cess that occurs in between the excitation
and contraction of the muscle. This pro­
Both depolarization Only depolarization or cess involves series of activities which are
and repolarization hyperpolarization
responsible for the contraction of the exci­
Obeys all-or-none Does not obey all or ted muscle.
law none law
Stages of excitation contraction
Summation is not Summation is coupling
possible possible
When the impulse passes through a motor
Has refractory period No refractory period neuron and reaches the neuromuscular
142 Section 3 ê Muscle Physiology

junction, acetylcholine is released from motor tropomyosin. Therefore, the myosin head can­
endplate. Acetylcholine causes open­ing of not combine with actin molecule.
ligand-gated sodium channels. So, sodium Large number of calcium ions, which
ions enter the neuromuscular junction. It are released from L-tubules during the exci­
leads to the development of endplate poten­ tation of the muscle, bind with troponin ‘C’.
tial. Endplate potential causes generation The loading of troponin ‘C’ with calcium
of action potential in the muscle fiber. ions produces some change in the position
The action potential spreads over sarco­ of troponin molecule. It in turn, pulls tropo­
lemma and also into the muscle fiber myosin molecule away from F-actin. Due to
through the T-tubules. The T-tubules are the movement of tropomyosin, the active
res­ponsible for the rapid spread of action site of F-actin is uncovered and immediately
potential into the muscle fiber. When the the head of myosin gets attached to the
action potential reaches the cisternae of actin.
L-tubules, these cisternae are excited. Now,
the calcium ions stored in the cisternae are 3. Sliding Mechanism and
released into the sarcoplasm. The calcium Formation of Actomyosin
ions from the sarcoplasm move towards the Complex – Sliding Theory
actin filaments to produce the contraction.
Sliding theory explains how the actin fila­
Thus, the calcium ion forms the link or
ments slide over myosin filaments and form
coupling material between the excitation
the actomyosin complex during muscular
and the contraction of muscle. Hence, the
contraction. It is also called ratchet theory
calcium ions are said to form the basis of
or walk along theory.
excitation contraction coupling.
Each cross bridge from the myosin fila­
ments has got three components namely, a
2. Role of Troponin and Tropomyosin
hinge, an arm and a head.
Normally, the head of myosin molecules has After binding with active site of F-actin,
a strong tendency to get attached with active the myosin head is tilted towards the arm,
site of F-actin. However, in relaxed condition, so that the actin filament is dragged along
the active site of F-actin is covered by the with it (Fig. 27.2). This tilting of head is
cal­led power stroke. After tilting, the head

FIGURE 27.2: Diagram showing power stroke by myosin head. Stage I: Myosin head binds with
actin. Stage II: Tilting of myosin head (power stroke) drags the actin filament. ATP = Adenosine
triphosphate, ADP = Adenosine diphosphate.
Chapter 27 ê Electrical and Molecular Changes During Muscular Contraction 143
immediately breaks away from the active adenosine triphosphate (ATP) into adeno­
site and returns to the original position. sine diphosphate (ADP) and inor­ ganic
Now, it combines with a new active site on phos­phate (Pi).
the actin molecule. And tilting movement The head of myosin has a site for ATP.
occurs again. Thus, the head of cross bridge Actually the head itself can act as the enzyme
bends back and forth, and pulls the actin ATPase and catalyze the breakdown of
filament towards the center of sarcomere. ATP. Even before the onset of contraction,
In this way, all the actin filaments of both an ATP molecule binds with myosin head.
the ends of sarcomere are pulled. So, the When tropomyosin moves to expose
actin filaments of opposite sides overlap
the active sites, the head is attached to the
and form actomyosin complex. Formation of
active site. Now ATPase cleaves ATP into
actomyosin complex results in contraction
ADP and Pi, which remains in head itself.
of the muscle.
When the muscle shortens further, the The energy released during this process is
actin filaments from opposite ends of the utilized for contraction.
sarcomere approach each other. So, the When head is tilted, the ADP and Pi are
‘H’ zone becomes narrow. And, the two ‘Z’ released and a new ATP molecule binds
lines come closer with reduction in length with head. This process is repeated until the
of the sarcomere. However, the length of muscular contraction is completed.
‘A’ band is not altered. But, the length of ‘I’
band decreases.
When the muscular contraction becomes
severe, the actin filaments from oppo­site
ends overlap and, the ‘H’ zone disappears.
Thus, during the contraction of the
muscle, the following changes occur in the
1. The length of all the sarcomeres dec­
reases, as the ‘Z’ lines come close to
each other.
2. The length of the ‘I’ band decreases,
since the actin filaments from opposite
side overlap.
3. The ‘H’ zone either decreases or
4. The length of ‘A’ band remains the
The summary of sequence of events
during muscular contraction is given in
Figure 27.3.

Energy for Muscular Contraction

The energy for movement of myosin head FIGURE 27.3: Sequence of events during
(power stroke) is obtained by breakdown of muscular contraction
144 Section 3 ê Muscle Physiology

Relaxation of the Muscle

The relaxation of the muscle occurs when
the calcium ions are pumped back into the
L-tubules. When calcium ions enter the
L-tubules, calcium content in sarcoplasm
decre­ases leading to the release of calcium
ions from the troponin. It causes detach­ment
of myosin from actin followed by relaxa­
tion of the muscle (Fig. 27.4). The detach­
ment of myosin from actin obtains energy
from breakdown of ATP. Thus, the chemical
process of muscular relaxation is an active
FIGURE 27.4: Sequence of events during process, although the physical process is
muscular relaxation said to be passive.
Chapter 28

Neuromuscular Junction



„„ DEFINITION AND STRUCTURE Axon Terminal and Motor End Plate

„„ DEFINITION Terminal branch of nerve fiber is called axon
Neuromuscular junction is the junction bet­ terminal. When the axon comes close to the
ween the terminal branch of the nerve fiber muscle fiber, it loses the myelin sheath. So,
and muscle fiber. the axis cylinder is exposed. This portion
of the axis cylinder is expanded like a bulb
„„ STRUCTURE which is called motor endplate.
Skeletal muscle fibers are innervated by the The axon terminal contains mitochon­
motor nerve fibers. Each nerve fiber (axon) dria and synaptic vesicles. The synaptic
divides into many terminal branches. Each vesi­cles contain the neurotransmitter sub­
terminal branch innervates one muscle stance, acetylcholine. The acetylcholine is
fiber through the neuromuscular junction synthesized by mitochondria present in the
(Fig. 28.1). axon terminal and stored in the vesicles.
146 Section 3 ê Muscle Physiology

Neuromuscular transmission is defined as
the transfer of information from motor nerve
ending to the muscle fiber through neuro­
muscular junction. It is the mechanism by
which the motor nerve impulses initiate
muscle contraction. A series of events take
place in the neuromuscular junction during
this process (Fig. 28.3):
FIGURE 28.1: Longitudinal section of 1. Release of acetylcholine.
neuromuscular junction 2. Action of acetylcholine.
The mitochondria contain ATP which is the 3. Development of endplate potential.
source of energy for the synthesis of acetyl­ 4. Development of miniature endplate
5. Destruction of acetylcholine.
Synaptic Trough or Gutter
The motor end plate invaginates inside the
When the action potential reaches the axon
muscle fiber and forms a depression which terminal, it opens the voltage-gated calcium
is known as synaptic trough or synaptic channels in the membrane of the axon
gutter. The membrane of the muscle fiber termi­nal. Calcium ions enter the axon
below the motor endplate is thickened. termi­nal from extracellular fluid and cause
bursting of the vesicles. Now, acetylcholine
Synaptic Cleft is released from the vesicles and diffuses
through presynaptic membrane and enters
The membrane of the nerve ending is called
the synaptic cleft.
the presynaptic membrane. The membrane
Each vesicle contains about 10,000
of the muscle fiber is called postsynaptic acetyl­choline molecules.And, at a time, about
membrane. The space between these two 300 vesicles open and release acetylcho­
is called synaptic cleft. The synaptic cleft line.
contains basal lamina. It is a thin layer of
spongy reticular matrix through which, the
extracellular fluid diffuses. Large quantity of
an enzyme called acetylcholinesterase is
attached to the matrix of basal lamina.

Subneural Clefts
The postsynaptic membrane is the mem­
brane of the muscle fiber. It is thrown into
numerous folds called subneural clefts.
The postsynaptic membrane contains the
receptors called nicotinic acetylcholine recep­ FIGURE 28.2: Structure of neuromuscular
tors (Fig. 28.2). junction
Chapter 28 ê Neuromuscular Junction 147
Endplate potential is the change in the resting
membrane potential when an impulse
reaches the neuromuscular junction. The
resting membrane potential at the neuro­
muscular junction is – 90 mV. When sodium
ions enter inside, slight depolarization
occurs up to – 60 mV which is called end­
plate potential.
The endplate potential is a graded poten­
tial (refer Chapter 27) and it is not action
potential. It is nonpropagative. But it causes
the development of action potential in the
muscle fiber.

Miniature endplate potential is a weak end­
plate potential in neuromuscular junction
that is developed by the release of a small
quantity of acetylcholine from axon terminal.
And, each quantum of this neurotransmitter
produces a weak miniature endplate poten­
tial. The amplitude of this potential is only
up to 0.5 mV.
Miniature endplate potential cannot pro­
duce action potential in the muscle. When
FIGURE 28.3: Sequence of events during neuro­ more and more quanta of acetylcholine
muscular transmission. ACh = Acetylcholine, ECF are released continuously, the miniature
= Extracellular fluid. endplate potentials are added together and
finally produce endplate potential resulting
„„ 2. ACTION OF ACETYLCHOLINE in action potential in the muscle.
After entering the synaptic cleft, the acetyl­
choline molecules bind with nicotinic recep­
tors present in the postsynaptic mem­ Acetylcholine released into the synaptic cleft
brane and form the acetylcholine-receptor is destroyed very quickly within 1 millisecond
complex. It opens the ligand-gated channels by the enzyme, acetylcholinesterase. How­
ever, the acetylcholine is so potent, that
for sodium in the postsynaptic membrane.
even this short duration of 1 millisecond
Now, sodium ions from extracellular fluid
is sufficient to excite the muscle fiber. The
enter the neuromuscular junction through rapid destruction of acetylcholine is func­
these channels. And there, the sodium tionally significant because it prevents
ions produce an electrical potential called repeated excitation of the muscle fiber and
the endplate potential. allows the muscle to relax.
148 Section 3 ê Muscle Physiology

Reuptake Process keeping the muscle in a depolarized state.

But, these drugs are not destroyed by
Reuptake is a process in neuromuscular cholinesterase. So, the muscle remains in
junction, by which a degraded product of a depolarized state for a long time.
neurotransmitter re-enters the presynaptic
axon terminal where it is reused. Acetylcho­ 4. Botulinum Toxin
linesterase splits (degrades) acetylcholine
into inactive choline and acetate. Choline It is derived from the bacteria Clostridium
is taken back into axon terminal from syn­ botulinum. It prevents release of acetyl­
aptic cleft by reuptake process. There, it choline from axon terminal into the neuro­
is reused in synaptic vesicle to form new mus­cular junction.
acetylcholine molecule.
Neuromuscular blockers are the drugs,
The single motor neuron, its axon terminals
which can prevent the transmission of
and the muscle fibers innervated by it are
impul­ses from nerve fiber to the muscle
together called motor unit. Each motor
fiber through the neuromuscular junctions.
neuron activates a group of muscle fibers
Follo­wing are the neuromuscular blockers
through the axon terminals. Stimulation
commonly used in surgery and in research.
of a motor neuron causes contraction of
all the muscle fibers innervated by that
1. Curare
Curare prevents the neuromuscular trans­
mission by combining with acetylcholine „„ NUMBER OF MUSCLE FIBERS IN
receptors. So, the acetylcholine cannot com­ MOTOR UNIT
bine with the receptors. And, the endplate
The number of muscle fiber in each motor
potential cannot develop. Since curare blocks unit varies. The number of muscle fiber
the neuromuscular transmission by acting is small in the motor units of the muscles
on the acetylcholine receptors, it is called concerned with fine, graded and precise
receptor blocker. move­ments. Examples are:
Laryngeal muscles : 2 to 3 muscle fibers
2. Bungarotoxin per motor unit
It is a toxin from the venom of deadly Pharyngeal muscles : 2 to 6 muscle fibers
snakes. It affects the neuromuscular trans­ per motor unit
mission by blocking the acetylcholine recep­ Ocular muscles : 3 to 6 muscle fibers
tors. per motor unit
The muscles concerned with crude or
coarse movements have motor units with
3. Succinylcholine and
large number of muscle fibers. There are
about 120 to 165 muscle fibers in each
These drugs block the neuromuscular trans­ motor unit in these muscles. Examples are
mission by acting like acetylcholine and the muscles of leg and back.
Chapter 28 ê Neuromuscular Junction 149
„„ APPLIED PHYSIOLOGY – characterized by grave weakness of the
DISORDERS OF muscle due to the inability of neuromuscular
NEUROMUSCULAR JUNCTION junction to transmit impulses from nerve to
the muscle.
The disorders of neuromuscular junction
1. Myasthenia gravis.
2. Eaton-Lambert syndrome. Eaton-Lambert syndrome is also an auto­
immune disorder of neuromuscular junc­
„„ 1. MYASTHENIA GRAVIS tion. It is caused by antibodies to calcium
channels in axon terminal. This disease is
Myasthenia gravis is an autoimmune characterized by features of myasthenia
disorder of neuromuscular junction caused gravis. In addition the patients have blurred
by antibodies to cholinergic receptors. It is vision and dry mouth.
Chapter 29

Smooth Muscle


„„ DISTRIBUTION 7. Mammary glands, uterus, genital ducts,

SMOOTH MUSCLE prostate gland and scrotum in repro­
ductive system.
Smooth muscles are nonstriated (plain) and 8. Iris and ciliary body of the eye.
involuntary muscles present in almost all
the organs in the form of sheets, bundles „„ STRUCTURE OF
or sheaths around other tissues. These SMOOTH MUSCLE
muscles form the major contractile tissues
Smooth muscle fibers are fusiform or elon­
of various organs.
gated cells. The nucleus is single and elon­
Smooth muscle fibers are present in the
gated and it is centrally placed. Normally,
following structures: two or more nucleoli are present in the
1. Wall of organs like esophagus, stomach nuc­leus
(Fig. 29.1). Smooth muscle fibers
and intestine in gastrointestinal tract. are generally very small, measuring 2 to 5
2. Ducts of digestive glands. microns in diameter and 50 to 200 microns
3. Trachea, bronchial tube and alveolar in length. Smooth muscle fibers are covered
ducts of respiratory tract. by connective tissue, but tendons are absent.
4. Ureter, urinary bladder and urethra in
excretory system. Myofibrils and Sarcomere
5. Wall of the blood vessels in circulatory Well-defined myofibrils and sarcomere are
system. absent in smooth muscles. So the alter­
6. Arrector pilorum of skin. nate dark and light bands are absent.
Chapter 29 ê Smooth Muscle 151
are absent and L-tubules are poorly deve­
loped (refer Table 24.1).

Smooth muscle fibers are of two types:
1. Single-unit or visceral smooth muscle
2. Multiunit smooth muscle fibers.

FIGURE 29.1: Smooth muscle fibers. A. Visceral Single-unit smooth muscle fibers are the
(single unit) tissue; B. Multiunit tissue. fibers with interconnecting gap junctions.
The gap junctions allow rapid spread of
Absence of dark and light bands gives
action potential throughout the tissue so
the non-striated appearance to the smooth that all the muscle fibers show synchronous
muscle. contraction as a single unit. Single-unit
smooth muscle fibers are also called vis­
Myofilaments and Contractile Proteins ceral smooth muscle fibers.
The contractile proteins in smooth muscle The features of single-unit smooth muscle
fiber are actin, myosin and tropomyosin. fibers:
But troponin or troponin-like substance is i. The muscle fibers are arranged in sheets
absent. or bundles.
Thick and thin filaments are present in ii. The cell membrane of adjacent fibers
smooth muscle. However, these filaments fuses at many points to form gap
are not arranged in orderly fashion as in junctions. Through the gap junctions,
skeletal muscle. Thick filaments are formed ions move freely from one cell to the
by myosin molecules and have more num­ other. Thus a functional syncytium is
ber of cross bridges than in skeletal mus­ developed. The syncytium contracts as
cle. Thin filaments are formed by actin and a single unit. In this way, the visceral
tropomyosin molecules. smooth muscle resembles cardiac
muscle more than the skeletal muscle.
Dense Bodies The visceral smooth muscle fibers are
in the walls of the organs such as gastro­
Dense bodies are the special structures of intestinal organs, uterus, ureters, respira­
smooth muscle fibers to which the actin and tory tract, etc.
tropomyosin molecules of thin filaments are
Sarcotubular System
The multiunit smooth muscle fibers are
Sarcotubular system in smooth muscle the muscle fibers without interconnecting
fibers is in the form of network. T-tubules gap junctions. These smooth muscle fibers
152 Section 3 ê Muscle Physiology

resemble the skeletal muscle fibers in many known. It is suggested that it may be due
ways. The features of multiunit smooth to the rhythmic modulations in the activities
muscle fibers: of sodium-potassium pump. The slow wave
i. The muscle fibers are individual fibers. is not action potential and it cannot cause
ii. Each muscle fiber is innervated by a contraction of the muscle. But it initiates the
single nerve ending. action potential (see below).
iii. Each muscle fiber has got an outer
membrane made up of glycoprotein, „„ ACTION POTENTIAL
which helps to insulate and separate
Three types of action potential occur in visce­
the muscle fibers from one another.
ral smooth muscle fibers:
iv. The control of these muscle fibers is
mainly by nerve signals. 1. Spike potential.
v. These smooth muscle fibers do not 2. Spike potential initiated by slow-wave
exhibit spontaneous contractions. rhythm.
The multiunit muscle fibers are in ciliary 3. Action potential with plateau.
muscles of the eye, iris of the eye, nictitating
membrane (in cat), arrector pili and smooth 1. Spike Potential
muscles of the blood vessels and urinary The spike potential in visceral smooth muscle
bladder. is different from that in skeletal muscles.
In smooth muscle, the average duration of
„„ ELECTRICAL ACTIVITY IN spike potential varies between 30 and 50
SINGLE-UNIT SMOOTH MUSCLE milliseconds. Its amplitude is very low and
it does not reach the isoelectric base. It
Usually 30 to 40 smooth muscle fibers are
is due to nervous and other stimuli and it
simultaneously depolarized which leads
leads to contraction of the muscle.
to development of self-propagating action
poten­tial. It is possible because of gap junc­
2. Spike Potential Initiated by
tions and syncytial arrangements of single-
Slow-wave Rhythm
unit smooth muscles.
Sometimes the slow-wave rhythm of resting
„„ RESTING MEMBRANE POTENTIAL membrane potential initiates the spike
potentials, which lead to contraction of the
Resting membrane potential in visceral smooth
muscle. The spike potentials appear rhythmi­
muscle is very much unstable and ranges
cally at a rate of about one or two spikes at
between – 50 and – 75 mV. Sometimes, it
the peak of each slow wave. These poten­
reaches low level of – 25 mV.
tials initiated by the slow-wave rhythm
cause rhythmic contractions of smooth
mus­ cles. This type of potentials appears
mostly in smooth muscles, which are self-
excitatory and contract themselves without
The unstable is caused by the appearance any external stimuli. So, the spike potentials
of some wave-like fluctuations called slow initiated by slow-wave rhythm are otherwise
waves. The slow waves occur in a rhythmic called pacemaker waves. The smooth mus­
fashion at a frequency of 4 to 10 per minute cles showing rhythmic contractions are
with the amplitude of 10 to 15 mV (Fig. 29.2). present in some of the visceral organs such
The cause of the slow-wave rhythm is not as intestine.
Chapter 29 ê Smooth Muscle 153

FIGURE 29.2: Electrical activities in smooth muscle. A. Slow-wave rhythm of resting membrane
potential; B. Spike potential; C. Spike potential initiated by slow-wave rhythm; D. Action potential
with plateau.

3. Action Potential with Plateau long depolarized state, slow repolarization

This type of action potential starts with
rapid depolarization as in the case of
skeletal muscle. But, repolarization does
not occur immediately. The muscle remains
depolarized for long periods of about 100
to 1,000 milliseconds. This type of action The smooth muscles of some visceral organs
potential is responsible for sustained con­ maintain a state of partial contraction called
traction of smooth muscle fibers. After the tonus or tone. It is due to the tonic contraction
154 Section 3 ê Muscle Physiology

of the muscle that occurs without any action „„ CONTRACTILE PROCESS IN

potential or any stimulus. Sometimes, the SMOOTH MUSCLE
tonic contraction occurs due to the action of
some hormones. Compared to skeletal muscles, in smooth
muscles, the contraction and relaxation pro­
„„ IONIC BASIS OF cesses are slow.
The important difference between the action MUSCLE CONTRACTION
potential in skeletal muscle and smooth
The process of excitation and contrac­
muscle lies in the ionic basis of depo­lari­
tion is very slow in smooth muscles is
zation. In skeletal muscle, the depolarization
occurs due to opening of sodium channels because of poor development of L-tubules
and entry of sodium ions from extracellular (sarcoplasmic reticulum). So, the calcium
fluid into the muscle fiber. But in smooth ions, which are responsible for excitation-
muscle, the depolarization is due to entry contraction coupling, must be obtained from
of calcium ions rather than sodium ions. the extracellular fluid. It makes the process
Unlike the fast sodium channels, the cal­ of excitation-contraction coupling slow.
cium channels open and close slowly. It
is responsible for the prolonged action Calcium-calmodulin Complex
potential with plateau in smooth muscles. The stimulation of ATPase activity of myosin
The calcium ions play an important role in smooth muscle is different from that in
during the contraction of the muscle. the skeletal muscle. In smooth muscle, the
myosin has to be phosphorylated for the
„„ ELECTRICAL ACTIVITY IN activation of myosin ATPase. The phos­pho­
MULTIUNIT SMOOTH MUSCLE rylation of myosin occurs in the following
manner (Fig. 29.3).
The electrical activity in multiunit smooth
muscle is different from that in the single-
unit smooth muscle. The electrical changes
leading to contraction of multiunit smooth
muscle are triggered by nervous stimuli.
The nerve endings secrete the neurotrans­
mitters like acetylcholine and noradrenaline.
The neurotransmitters depolarize the mem­
brane of smooth muscle fiber slightly leading
to contraction. The action potential does not
develop. This type of depolarization is called
local depolarization of junctional potential.
The local depolarization travels throughout
the entire smooth muscle fiber and causes
contraction. The local depolarization is deve­
loped because the multiunit smooth muscle
fibers are too small to develop action FIGURE 29.3: Molecular basis of smooth
potential. muscle contraction
Chapter 29 ê Smooth Muscle 155
Calcium, which enters the sarcoplasm from resting length of the muscle fiber. In other
the extracellular fluid combines with a pro­ words, Starling’s law is not applicable to
tein called calmodulin and forms calcium- smooth muscle. In skeletal and cardiac mus­
calmodulin complex. It activates an enzyme cles, Starling’s law is applicable and the
called calmodulin-dependent myosin light tension or force of contraction is directly
chain kinase. This enzyme in turn causes proportional to initial length of the muscle
phosphorylation of myosin followed by acti­ fibers.
vation of myosin ATPase. Now, the sliding
of actin filaments starts. „„ CONTROL OF
The phosphorylated myosin gets atta­ SMOOTH MUSCLE
ched to the actin molecule for longer period.
Smooth muscle fibers are controlled by:
It is called latch-bridge mechanism and it is
1. Nervous factors.
responsible for the sustained contraction of
2. Humoral factors.
the muscle with expenditure of little energy.
Relaxation of the muscle occurs due
to the dissociation of calcium-calmodulin
complex. Smooth muscles are supplied by both
sym­pathetic and parasympathetic nerves,
Length-Tension which act opposite to each other in con­
Relationship – Plasticity trolling the activities of smooth muscles.
However, these nerves are not responsible
Smooth muscle fibers have the property
for the initiation of any activity in smooth
of plasticity. Plasticity is the adaptability
of smooth muscle fibers to a wide range
of lengths. If the smooth muscle fiber is
stretched, it adapts to this new length and
contracts when stimulated. This adap­ta­bi­lity The activity of smooth muscle is also con­
exists to a wide range of lengths. Because trolled by humoral factors which include
of this property, tension pro­duced in the hormones, neurotransmitters and other
muscle fiber is not directly proportional to humo­ral factors.
156 Questions in Muscle Physiology


„„ LONG QUESTIONS 9. Differences between pale and red

1. Explain the molecular basis of con­ 10. Rigor.
traction. 11. Effects of repeated stimuli on skeletal
2. Describe the electrical changes during muscle.
muscular contraction. 12. Fatigue.
3. Explain the ionic basis of electrical 13. Tetanus.
events during contraction of skeletal 14. Starling’s law of muscle.
muscle. 15. Refractory period.
4. Describe the neuromuscular junction 16. Muscle tone.
with a suitable diagram. Add a note on 17. Resting membrane potential.
neuromuscular transmission. 18. Action potential.
19. Graded potential.
„„ SHORT QUESTIONS 20. Actomyosin complex.
21. Excitation-contraction coupling.
1. Compare skeletal muscle and cardiac 22. Sliding theory of muscular contraction.
muscle. 23. Electrical activity in smooth muscle.
2. Compare skeletal muscle and smooth 24. Molecular basis of smooth muscular
muscle. contraction.
3. Sarcomere. 25. Neuromuscular junction.
4. Contractile elements of the muscle. 26. Neuromuscular transmission.
5. Muscle proteins. 27. Endplate potential.
6. Sarcotubular system. 28. Neuromuscular blockers.
7. Sarcoplasmic reticulum. 29. Motor unit.
8. Composition of muscle. 30. Myasthenia gravis.
Section 4
Digestive System

30. Overview of Digestive System................................................. 159
31. Salivary Secretion.................................................................... 164
32. Gastric Secretion...................................................................... 173
33. Pancreatic Secretion................................................................ 185
34. Liver and Biliary System........................................................... 192
35. Functions and Secretions of Small Intestine............................ 204
36. Functions and Secretions of Large Intestine............................ 209
37. Movements of Gastrointestinal Tract........................................ 212
Chapter 30

Overview of Digestive System


„„ INTRODUCTION of digestion and absorption (Fig. 30.1). GI

tract is a tubular structure exten­ding from the
Digestion is defined as the process by which
mouth up to anus with a length of about 30
food is broken down into simple chemi­ feet. It opens to the external environment
cal substances that can be absorbed and on both ends. GI tract is formed by two types
used as nutrients by the body. Most of the of organs:
substances in the diet cannot be utilized as 1. Primary digestive organs.
such. These substances must be broken 2. Accessory digestive organs.
into smaller particles. Then only these sub­
stances can be absorbed into blood and „„ 1. PRIMARY DIGESTIVE ORGANS
distri­buted to various parts of the body for
utilization. The digestive system is respon­ Primary digestive organs are the organs
sible for these functions. where actual digestion takes place. These
organs are:
2. Pharynx.
3. Esophagus.
Digestive system is made up of gastrointes­ 4. Stomach.
tinal tract (GI tract) or alimentary canal and 5. Small intestine.
accessory organs, which help in the process 6. Large intestine.
160 Section 4 ê Digestive System

gastrointestinal mucosa or mucous mem­

brane. It faces the cavity of GI tract.
The mucosa has three layers of struc­
i. Epithelial lining, which is in contact
with contents of GI tract.
ii. Lamina propria formed by connective
iii. Muscularis mucosa formed by smooth
muscle fibers.

This is present in all parts of GI tract except
mouth and pharynx. This layer contains
loose collagen fibers, elastic fibers, reticular
FIGURE 30.1: Gastrointestinal tract fibers and few cells of connective tissue.
Blood vessels, lymphatic vessels and nerve
„„ 2. ACCESSORY DIGESTIVE plexus are present in this layer.
Accessory digestive organs are the organs
which help the primary digestive organs in This in lips, cheeks and wall of pharynx have
the process of digestion. These organs are: skeletal muscle fibers. The esophagus has
1. Teeth. both skeletal and smooth muscle fibers.
2. Tongue. Wall of the stomach and intestine is formed
3. Salivary glands. by smooth muscle fibers.
4. Exocrine part of pancreas. The smooth muscle fibers in stomach
5. Liver. are arranged in three layers:
6. Gallbladder. i. Inner oblique layer.
ii. Middle circular layer.
„„ WALL OF GASTROINTESTINAL iii. Outer longitudinal layer.
TRACT The smooth muscle fibers in the intestine
are arranged in two layers:
In general, the wall of the GI tract is formed i. Inner circular layer.
by four layers, which are from inside out: ii. Outer longitudinal layer.
1. Mucus layer. The smooth muscle fibers present in
2. Submucus layer. inner circular layer of anal canal constitute
3. Muscular layer. internal anal sphincter. The external anal
4. Serous or fibrous layer. sphincter is formed by skeletal muscle fibers.


The mucus layer is the innermost layer Outermost layer of the wall of GI tract is
of the wall of GI tract. It is also called either serous or fibrous in nature. The serous
Chapter 30 ê Overview of Digestive System 161
layer is formed by connective tissue and fibers of this plexus inhibit the GI motility by
mesoepithelial cells. It is also called serosa secreting the inhibitory neurotransmitters
or serous membrane. It covers stomach, such as vasoactive intestinal polypeptide
small intestine and large intestine. (VIP), neurotensin and enkephalin.
The fibrous layer is otherwise called
fibrosa. It is formed by connective tissue. It Meissner’s Nerve Plexus
covers pharynx and esophagus. Meissner’s plexus is otherwise called sub­
mucus nerve plexus. It is situated in between
„„ NERVE SUPPLY TO the muscular layer and submucosal layer of
GI tract has two types of nerve supply: Functions of Meissner’s plexus
1. Intrinsic nerve supply.
2. Extrinsic nerve supply. The function of Meissner’s plexus is the
regulation of secretory functions of GI tract.
„„ 1. INTRINSIC NERVE SUPPLY – And these nerve fibers cause constriction
ENTERIC NERVOUS SYSTEM of blood vessels of GI tract.

The enteric nervous system is present „„ EXTRINSIC NERVE SUPPLY

within the wall of GI tract from esophagus
to anus. The nerve fibers of this system The extrinsic nerves that control the enteric
are interconnected and form two major net­ nervous system are from autonomic nervous
system. Both sympathetic and parasym­
works called:
pathetic divisions of the autonomic nervous
i. Auerbach’s plexus.
system innervate GI tract (Fig. 30.3).
ii. Meissner’s plexus.
These nerve plexus contain nerve cell Sympathetic Nerve Fibers
bodies, processes of nerve cells and the
receptors. The receptors in the GI tract are Preganglionic sympathetic nerve fibers to
stretch receptors and chemoreceptors. The GI tract arise from lateral horns of spinal
enteric nervous system is controlled by cord between fifth thoracic and second
extrinsic nerves. lumbar segments (T5 to L2). From here, the
fibers leave the spinal cord, pass through
Auerbach’s Plexus the ganglia of sympathetic chain without
It is also known as myenteric nerve plexus.
It is present in between the inner circular
muscle layer and the outer longitudinal
muscle layer (Fig. 30.2).
Functions of Auerbach’s plexus
The major function of this plexus is to
regulate the movements of GI tract. Some
nerve fibers of this plexus accelerate the
movements by secreting the excitatory
neurotransmitter substances like acetyl­ FIGURE 30.2: Structure of intestinal wall with
choline, serotonin and substance P. Other intrinsic nerve plexus
162 Section 4 ê Digestive System

FIGURE 30.3: Extrinsic nerve supply to GI tract. T5 = 5th thoracic segment of spinal cord, L1 = 1st
lumbar segment of spinal cord, S2 = 2nd sacral segment of spinal cord.

having any synapse and then terminate Parasympathetic Nerve Fibers

in the celiac and mesenteric ganglia. The
Parasympathetic nerve fibers to GI tract
postganglionic fibers from these ganglia
pass through some of the cranial nerves
are distributed throughout the GI tract.
and sacral nerves. The preganglionic and
Functions of sympathetic nerve fibers postganglionic parasympathetic nerve fibers
to mouth and salivary glands pass through
Sympathetic nerve fibers inhibit the move­ facial and glossopharyngeal nerves.
ments and decrease the secretions of GI The preganglionic parasympathetic nerve
tract by secreting the neurotransmitter fibers to esophagus, stomach, small intes­
nora­drenaline. It also causes constriction of tine and upper part of large intestine pass
sphincters. through vagus nerve. The preganglionic
Chapter 30 ê Overview of Digestive System 163
nerve fibers to lower part of large intestine Functions of parasympathetic
arise from second, third and fourth sacral nerve fibers
segments (S2, S3 and S4) of spinal cord
and pass through pelvic nerve. All these Parasympathetic nerve fibers accelerate move­
preganglionic parasympathetic nerve fibers ments and increase the secretions of GI
synapse with the postganglionic nerve cells tract. The neurotransmitter secreted by the
in the myenteric and submucus plexus. parasympathetic nerve fibers is acetylcholine.
Chapter 31

Salivary Secretion



„„ FUNCTIONAL ANATOMY OF 4. Transfer of food (bolus) to the eso­

MOUTH phagus by swallowing.
5. Role in speech.
The mouth is otherwise known as oral cavity 6. Social functions such as smiling and
or buccal cavity. It is formed by cheeks, lips other expressions.
and palate. It encloses the teeth, tongue
and salivary glands. It opens anteriorly to
the exterior through lips and posteriorly
through fauces into the pharynx. In humans, the saliva is secreted by three
Digestive juice present in the mouth is pairs of major (larger) salivary glands and
saliva which is secreted by the salivary some minor (small) salivary glands in the
glands. oral and pharyngeal mucous membrane.
The major glands are:
„„ FUNCTIONS OF MOUTH 1. Parotid glands.
2. Submaxillary or submandibular glands.
The primary function of mouth is eating. It
3. Sublingual glands.
has few other important functions also. The
functions of the mouth are:
1. Ingestion of food materials.
2. Chewing the food and mixing it with Parotid glands are the largest of all salivary
saliva. glands situated at the side of the face just
3. Appreciation of the taste. below and in front of the ear. Secretions
Chapter 31 ê Salivary Secretion 165
from these glands are emptied into the oral TABLE 31.1: Ducts of major salivary glands
cavity by Stensen’s duct that opens inside
the cheek against the upper second molar Gland Duct
tooth (Fig. 31.1). Parotid gland Stensen’s duct
Submaxillary gland Wharton’s duct
Ducts of Rivinus/
Submaxillary glands or submandibular glands Sublingual
Bartholin’s duct
are located in submaxillary triangle medial
to mandible. Saliva from these glands is „„ MINOR SALIVARY GLANDS
emptied into the oral cavity by Wharton’s
duct. The duct opens at the side of frenulum 1. Lingual mucous glands situated in pos­
of tongue by means of a small opening terior 1/3 of the tongue, behind circum­
on the summit of papilla called caruncula vallate papillae and at the tip and mar­
sublingualis. gins of tongue.
2. Lingual serous glands located near cir­
cumvallate papillae and filiform papillae.
3. Buccal glands present between the
Sublingual glands are the smallest salivary mucous membrane and buccinator
glands situated in the mucosa at the floor of muscle. Four to five of these are larger
mouth. Saliva from these glands is poured and situated outside buccinator around
into 5 to 15 small ducts called ducts of terminal part of parotid duct. These
Rivinus. These ducts open on small papillae glands are called molar glands.
beneath the tongue. One of the ducts is 4. Labial glands situated beneath the
larger and it is called Bartholin’s duct (Table mucous membrane around the orifice
31.1). It drains the anterior part of the gland of mouth.
5. Palatal glands found beneath the
and opens on caruncula sublingualis near
mucous membrane of the soft palate.
the opening of submaxillary duct.
Salivary glands are classified into three
types based on the type of secretion.

1. Serous Glands
This type of gland is predominately made
up of serous cells. These glands secrete
thin and watery saliva. Parotid glands and
lingual (serous) glands are the serous

2. Mucous Glands
This type of gland is made up of mainly
the mucous cells. These glands secrete
FIGURE 31.1: Major salivary glands thick, viscus saliva with high mucin content.
166 Section 4 ê Digestive System

Lingual mucous glands, buccal glands and „„ PROPERTIES AND

palatal glands belong to this type. COMPOSITION OF SALIVA
Properties of Saliva
3. Mixed Glands
1. Volume: 1,000 to 1,500 mL of saliva is
Mixed glands are made up of both serous
secreted per day and it is approximately
and mucus cells. Submandibular, sublingual
about 1 mL/min. Contribution by each
and labial glands are the mixed glands.
major salivary gland is:
i. Parotid glands : 25%
„„ STRUCTURE AND DUCT SYSTEM ii. Submaxillary glands : 70%
OF SALIVARY GLANDS iii. Sublingual glands : 5%
Salivary glands are made up of acini or 2. Reaction: Mixed saliva from all the
alveoli. Each acinus is formed by a small glands is slightly acidic with pH of 6.35
group of cells which surround a central to 6.85.
globular cavity. The central cavity of each 3. Specific gravity: It ranges between 1.002
acinus is continuous with the lumen of the and 1.012.
duct. The fine duct draining each acinus is 4. Tonicity: Saliva is hypotonic to plasma.
called intercalated duct. Many intercalated
Composition of Saliva
ducts join together to form intralobular duct.
Few intralobular ducts join to form interlo­ Mixed saliva contains 99.5% water and
bular ducts, which unite to form the main 0.5% solids. Composition of saliva is given
duct of the gland (Fig. 31.2). The gland with in Figure 31.3.
this type of structure and duct system is
called racemose type (racemose = bunch „„ FUNCTIONS OF SALIVA
of grapes).
Saliva is a very essential digestive juice.
Since it has many functions, its absence leads
to many inconveniences.

When food is taken into the mouth, it is
moistened and dissolved by saliva. The
mucous membrane of mouth is also mois­
tened by saliva. It facilitates chewing. By
the movement of the tongue, the moistened
and masticated food is rolled into a bolus.
The mucin of saliva lubricates the bolus
and facilitates the swallowing.

Taste is a chemical sensation. Saliva, by its
FIGURE 31.2: Diagram showing acini and duct solvent action, dissolves the solid food sub­
system in salivary glands stances, so that the dissolved substances
Chapter 31 ê Salivary Secretion 167
can stimulate the taste buds. The stimulated in the stomach, because food stays only for
taste buds recognize the taste. a short time in the mouth.
The optimum pH necessary for the acti­
„„ 3. DIGESTIVE FUNCTION vation of salivary amylase is 6. The sali­
The saliva has three digestive enzymes vary amylase cannot act on cellulose. The
namely, salivary amylase, maltase and lingual enzyme maltase is present only in traces
lipase (Table 31.2). in human saliva. It converts maltose into
Salivary Amylase
Lingual Lipase
Salivary amylase is a carbohydrate-diges­
ting (amylolytic) enzyme. It acts on cooked Lingual lipase is a lipid-digesting (lipolytic)
or boiled starch and converts it into dex­ enzyme. It digests milk fats (pre-emulsified
trin and maltose. Though starch digestion fats). It hydrolyzes triglycerides into fatty
starts in the mouth, major part of it occurs acids and diacylglycerol (Table 31.2).

FIGURE 31.3: Composition of saliva

TABLE 31.2: Digestive enzymes of saliva

Enzyme Source of secretion Activator Action

Salivary amylase All salivary glands Acid medium Converts cooked starch into maltose
Maltase Major salivary glands Acid medium Converts maltose into glucose
Converts triglycerides of milk fat into
Lingual lipase Lingual glands Acid medium
fatty acids and diacylglycerol
168 Section 4 ê Digestive System

„„ 4. CLEANSING AND found in saliva under normal conditions

PROTECTIVE FUNCTIONS such as glucose in diabetes mellitus. In
certain conditions, some of the normal
i. Due to the constant secretion of saliva,
consti­tuents of saliva are excreted in large
the mouth and teeth are rinsed and kept
quantities. For example, excess urea is
free of food debris, shed epithelial cells
and foreign particles. In this way, saliva excreted in saliva during nephritis and excess
prevents bacterial growth by removing calcium is excreted during hyper­ para­
materials, which may serve as culture thyroidism.
media for the bacterial growth.
During hyposalivation, the bacterial „„ 7. REGULATION OF
growth is accelerated and the common BODY TEMPERATURE
consequence is dental caries.
In dogs and cattle, excessive dripping of
ii. The enzyme lysozyme of saliva kills
saliva during panting helps in loss of
some bacteria such as Staphylococcus,
heat and regulation of body temperature.
Streptococcus and Brucella.
However, in human being, sweat glands
iii. The proline-rich proteins and lacto­
play major role in temperature regulation
ferrin present in saliva possess anti­
microbial property. These proteins also and saliva does not play any role in this
protect the teeth by stimulating enamel function.
iv. Saliva also contains secretory immuno­ „„ 8. REGULATION OF
globulin IgA which has antibacterial WATER BALANCE
and antiviral actions.
When the body water content decreases,
v. Mucin present in the saliva protects
salivary secretion also decreases. This
the mouth by lubricating the mucous
causes dryness of the mouth and induces
membrane of the mouth.
thirst. When the water is taken, it quen­
ches the thirst and restores the body water
By moistening and lubricating soft parts of
mouth and lips, saliva helps in speech. If „„ REGULATION OF
the mouth becomes dry, articulation and SALIVARY SECRETION
pronunciation become difficult.
Salivary secretion is regulated only by
„„ 6. EXCRETORY FUNCTION nervous mechanism. Autonomic nervous
system is involved in the regulatory func­
Many substances, both organic and inorga­ tion.
nic, are excreted in saliva. It excretes sub­
stances like mercury, potassium iodide, „„ NERVE SUPPLY TO
lead and thiocyanate. Saliva also excretes SALIVARY GLANDS
some viruses such as those causing rabies
and mumps. Salivary glands are supplied by parasympa­
In some pathological conditions, saliva thetic and sympathetic divisions of auto­
excretes certain substances, which are not nomic nervous system.
Chapter 31 ê Salivary Secretion 169
„„ PARASYMPATHETIC FIBERS medulla oblongata. From here, the fibers
pass through the tympanic branch of glos­
Parasympathetic Fibers to sopharyngeal nerve, tympanic plexus and
Submandibular and Sublingual Glands lesser petrosal nerve, and end in otic gang­
The parasympathetic preganglionic fibers lion (Fig. 31.5).
to submandibular and sublingual glands The postganglionic fibers arise from
arise from the superior salivatory nucleus otic ganglion and reach the parotid gland
by passing through the auriculotemporal
situated in pons. After taking origin from this
branch in mandibular division of trigeminal
nucleus, the preganglionic fibers run through
nervus intermedius of Wrisberg, geniculate
ganglion, the motor fibers of facial nerve, Functions of Parasympathetic Fibers
chorda tympani branch of facial nerve and
lingual branch of trigeminal nerve and finally When the parasympathetic fibers of salivary
reach the submaxillary ganglion (Fig. 31.4). glands are stimulated, a large quantity of
watery saliva is secreted with less amount
The postganglionic fibers arise from this
of organic constituents. It is because the
ganglion and supply the submaxillary and
parasympathetic fibers activate the acinar
sublingual glands.
cells and dilate the blood vessels of sali­
vary glands. The neurotransmitter is acetyl­
Parasympathetic Fibers to choline.
Parotid Gland
The parasympathetic preganglionic fibers „„ SYMPATHETIC FIBERS
to parotid gland arise from inferior saliva­ The sympathetic preganglionic fibers to
tory nucleus situated in the upper part of salivary glands arise from the lateral horns

FIGURE 31.4: Parasympathetic nerve supply to submaxillary and sublingual glands

170 Section 4 ê Digestive System

1. Unconditioned Reflex
Unconditioned reflex is the inborn reflex that
is present since birth. It does not need any
previous experience. This reflex induces sali­
vary secretion when any substance is placed
in the mouth. It is due to the stimulation of
nerve endings in the mucous membrane of
the oral cavity.
Examples include:
i. When food is taken.
ii. When any unpleasant or unpalatable
substance enters the mouth.
iii. When the oral cavity is handled with
instruments by dentists.

2. Conditioned Reflex
Conditioned reflex is the one that is acquired
FIGURE 31.5: Parasympathetic nerve supply to by experience and it needs previous expe­
parotid gland rience (refer Chapter 107). Presence of
food in the mouth is not necessary to elicit
of first and second thoracic segments this reflex. The stimulus for this reflex is the
of spinal cord. The fibers leave the cord sight, smell, hearing or thought of food. It
through the anterior nerve roots and end is due to the impulses arising from eyes,
in superior cervical ganglion of the sympa­ nose, ears, etc.
thetic chain.
The postganglionic fibers from this gang­
lion are distributed to the salivary glands „„ EFFECTS OF DRUGS AND
along the nerve plexus around the arteries CHEMICALS ON
supplying the glands. SALIVARY SECRETION
Substances which Increase the
Functions of Sympathetic Fibers
Salivary Secretion
The stimulation of sympathetic fibers causes
1. Sympathomimetic drugs like adrenaline
less secretion of saliva, which is thick and rich
and ephedrine.
in mucus. It is because these fibers activate
2. Parasympathomimetic drugs like acetyl­
the acinar cells and cause vasoconstriction
choline, pilocarpine, muscarine and
by secreting noradrenaline.
3. Histamine.
Substances which Decrease the
Salivary secretion is regulated by nervous Salivary Secretion
mechanism through reflex action. Salivary
1. Sympathetic depressants like ergota­
reflexes are of two types:
mine and dibenamine.
1. Unconditioned reflex.
2. Parasympathetic depressants like atro­
2. Conditioned reflex.
pine and scopolamine.
Chapter 31 ê Salivary Secretion 171
„„ HYPOSALIVATION In addition to hyposalivation and hyper­
vation, salivary secretion is affected
The reduction in the secretion of saliva is cal­
by other disorders also which include the
led hyposalivation. It is of two types, namely,
the temporary hyposalivation and the perma­
nent hyposalivation:
1. Xerostomia
1. Temporary hyposalivation occurs in:
i. Emotional conditions like fear. Xerostomia means dry mouth. It is also
ii. Fever. called pasties or cottonmouth. It is due to
iii. Dehydration. hyposalivation or absence of salivary secre­
2. Permanent hyposalivation occurs in: tion (aptyalism). The causes of this disease
i. Obstruction of salivary duct (sialo­ are:
lithiasis). i. Dehydration or renal failure.
ii. Congenital absence or hypoplasia ii. Sjögren’s syndrome (see below).
of salivary glands. iii. Radiotherapy.
iii. Paralysis of facial nerve (Bell’s iv. Trauma to salivary gland or their ducts.
palsy). v. Side effect of drugs like antihistamines,
Dental caries is the common consequ­ antidepressants and antiparkinsonian
ence of hyposalivation. drugs.
vi. Shock.
„„ HYPERSALIVATION vii. After smoking marijuana (psychoactive
The excess secretion of saliva is known as compound from the plant cannabis).
hypersalivation. The physiological condition Xerostomia causes difficulties in masti­
when hypersalivation occurs is pregnancy. cation, swallowing and speech. It also causes
Hypersalivation in pathological conditions halitosis (bad breath).
is called ptyalism, sialorrhea, sialism or
sialosis. 2. Drooling
Hypersalivation occurs in the following
conditions: Uncontrolled flow of saliva outside the mouth
1. Decay of tooth or neoplasm (abnormal is called drooling. It is often called ptyalism.
new growth or tumor) in mouth or Drooling occurs because of excess pro­
tongue – due to continuous irritation of duction of saliva in association with inability
nerve endings in the mouth. to retain saliva within the mouth.
2. Disease of esophagus, stomach and Drooling occurs in the following condi­
intestine. tions:
3. Neurological disorders such as mental i. During teeth eruption in children.
retardation, cerebral stroke and ii. Upper respiratory tract infection or
parkinsonism. nasal allergies in children.
4. Some psychological and psychiatric iii. Difficulty in swallowing.
conditions. iv. Tonsillitis.
5. Nausea and vomiting. v. Peritonsillar abscess.
172 Section 4 ê Digestive System

3. Chorda Tympani Syndrome disease is paramyxovirus. It is common in

children who are not immunized. It occurs
Chorda tympani syndrome is the condition in adults also. Features of mumps are
characterized by sweating while eating. puffiness of cheeks (due to swelling of
During trauma or surgical procedure, some parotid glands), fever, sore throat and weak­
of the parasympathetic nerve fibers to sali­ ness. Mumps affects meninges, gonads
vary glands may be severed. And during and pancreas also.
regeneration, some of these nerve fibers,
which run along with chorda tympani branch 5. Sjögren’s Syndrome
of facial nerve, may deviate and join with
the nerve fibers supplying sweat glands. It is an autoimmune disorder in which the
When the food is placed in the mouth, immune cells destroy exocrine glands such
salivary secretion is associated with sweat as lacrimal glands and salivary glands.
secretion. Common symptoms of this syndrome are
dryness of the mouth due to lack of saliva
4. Mumps (xerostomia), persistent cough and dryness
of eyes. In severe conditions, the organs
Mumps is the acute viral infection affecting like kidneys, lungs, liver, pancreas, thyroid,
the parotid glands. The virus causing this blood vessels and brain are affected.
Chapter 32

Gastric Secretion




STOMACH In humans, stomach has four parts:
Stomach is a hollow organ situated just 1. Cardiac region.
below the diaphragm on the left side in 2. Fundus.
the abdominal cavity. Volume of empty 3. Body or corpus.
stomach is 50 mL. Under normal condi­ 4. Pyloric region.
tions, it can expand to accommodate 1 to
1.5 L of solids and liquids. However, it is 1. Cardiac Region
capable of expanding still further up to 4 It is the upper part of the stomach where
liters. esophagus opens. Opening is guarded by
174 Section 4 ê Digestive System

a sphincter called cardiac sphincter which Stomach has two curvatures. The one on
opens only towards stomach. This portion is the right side is lesser curvature and the
also known as cardiac end. one on the left side is greater curvature.


It is a small dome-shaped structure. It is The wall of the stomach is formed by four
elevated above the level of esophageal layers of structures:
opening. 1. Outer serous layer formed by perito­
3. Body or Corpus 2. Muscular layer made up of three layers
of smooth muscle fibers namely, inner
It is the largest part of stomach forming about
oblique, middle circular and outer longi­
75 to 80% of the whole stomach. It extends
tudinal layers.
from just below the fundus up to the pyloric
3. Submucus layer formed by areolar
region (Fig. 32.1).
tissue, blood vessels and lymph
4. Pyloric Region
4. Inner mucus layer lined by mucus-
The pyloric region has two parts, antrum secreting columnar epithelial cells. The
and pyloric canal. The body of the stomach gastric glands are situated in this layer.
ends in antrum. The junction between body The inner surface of mucus layer is
and antrum is marked by an angular notch covered by 2 mm thick mucus.
called incisura angularis. Antrum is conti­
nued as the narrow canal which is called „„ GLANDS OF STOMACH
pyloric canal or pyloric end. Pyloric canal
Glands of the stomach or gastric glands are
opens into first part of small intestine called
tubular structures made up of different types
duodenum. The opening of pyloric canal is
of cells. These glands open into the stomach
guarded by a sphincter called pyloric sphinc­
ter. It opens towards duodenum. cavity through gastric pits.

Gastric glands are classified into three types
depending upon their situation:
1. Fundic glands situated in body and
fundus of stomach. Fundic glands are
also called main gastric glands or oxyntic
2. Pyloric glands present in the pyloric part
of the stomach.
3. Cardiac glands located in the cardiac
region of the stomach.
All the gastric glands open into the cavity
FIGURE 32.1: Parts of stomach of stomach through gastric pits.
Chapter 32 ê Gastric Secretion 175
„„ STRUCTURE OF GASTRIC GLANDS TABLE 32.1: Secretory functions of cells in
gastric glands
Fundic Glands
The fundic glands are considered as the Cell Secretory products
typical gastric glands (Fig. 32.2). These Pepsinogen
glands are long and tubular glands. Each Rennin
gland has three parts, viz. body, neck and Chief cells Lipase
isthmus. The cells present in the fundic glands Gelatinase
are: Urase
1. Chief cells or pepsinogen cells. Hydrochloric acid
Parietal cells
2. Parietal cells or oxyntic cells. Intrinsic factor of Castle
3. Mucus neck cells.
Mucus neck cells Mucin
4. Enterochromaffin (EC) cells.
5. Enterochromaffin-like (ECL) cells. G cells Gastrin
Secretions of these cells are given in Enterochromaffin
Table 32.1. Serotonin
(EC) cells
Parietal cells are different from other
cells of the gland because of the presence like (ECL) cells
of canaliculi (singular = canaliculus). The
parietal cells empty their secretions into the
lumen of the gland through the canaliculi, glands are G cells, mucus cells, EC cells
whereas other cells empty their secretions and ECL cells.
directly into lumen of the gland.
Cardiac Glands
Pyloric Glands Cardiac glands are also short and tortuous
The pyloric glands are short and tortuous in structure with many mucus cells. EC
in nature. The cells that form the pyloric cells, ECL cells and chief cells are also pre­
sent in the cardiac glands.

Enteroendocrine Cells
Enteroendocrine cells are the hormone-
secreting cells present in the glands or
mucosa of gastrointestinal tract particularly
stomach and intestine. The enteroendocrine
cells present in gastric glands are G cells,
enterochromaffin cells and enterochroma­
ffin-like cells.

i. Storage Function
The food is stored in the stomach for a long
FIGURE 32.2: Gastric glands period, i.e. for 3 to 4 hours and emptied into
176 Section 4 ê Digestive System

the intestine slowly. The maximum capacity „„ FUNCTIONS OF GASTRIC JUICE

of stomach is up to 1.5 L. The slow emp­
tying of stomach provides enough time for „„ 1. DIGESTIVE FUNCTION
proper digestion and absorption of food
The gastric juice acts mainly on proteins.
substances in the small intestine.
The proteolytic enzymes of the gastric juice
ii. Formation of Chyme are pepsin and rennin (Table 32.2). Gastric
juice also contains some other enzymes like
The peristaltic movements of stomach mix
gastric lipase, gelatinase, urase and gastric
the bolus with gastric juice and convert it
into the semisolid material known as chyme.


Refer functions of gastric juice. Pepsin is secreted as inactive pepsinogen.
Pepsinogen is converted into pepsin by hydro­
„„ 3. PROTECTIVE FUNCTION chloric acid which is secreted by parietal
Refer functions of gastric juice. cells. The optimum pH for activation of pep­
sinogen is below 6.
„„ 4. HEMOPOIETIC FUNCTION Action of pepsin
Refer functions of gastric juice.
Pepsin converts proteins into proteoses, pep­
„„ 5. EXCRETORY FUNCTION tones and polypeptides. Pepsin also causes
curdling and digestion of milk (casein).
Many substances like toxins, alkaloids and
metals are excreted through gastric juice. Gastric Lipase
„„ PROPERTIES AND Gastric lipase is a weak lipolytic enzyme. It
COMPOSITION OF needs acidic medium with pH is between 4
GASTRIC JUICE and 5 for its action. But it becomes inactive
Gastric juice is the mixture of secretions when the pH falls below 2.5. Gastric lipase
from different gastric glands. acts on tributyrin (butter fat) and hydrolyzes
it into fatty acids and glycerols.
Properties of Gastric Juice
Volume : 1,200 to 1,500 mL/day Actions of Other Enzymes of
Specific gravity : 1.002 to 1.004 Gastric Juice
Reaction : Gastric juice is highly
acidic with pH of 0.9 to 1.2 i. Gelatinase degrades gelatin and colla­
due to hydrochloric acid gen into peptides.
ii. Urase acts on urea and produces
Composition of Gastric Juice ammonia.
Gastric juice contains 99.5% of water and iii. Gastric amylase degrades starch (but
0.5% solids. The solids are organic and its action is insignificant).
inorganic substances. Refer Fig. 32.3 for iv. Rennin curdles milk (present in animals
composition of gastric juice. only).
Chapter 32 ê Gastric Secretion 177

FIGURE 32.3: Composition of gastric juice

TABLE 32.2: Digestive enzymes of gastric juice

Enzyme Activator Acts on End products
Proteoses, peptones
1. Pepsin Hydrochloric acid Proteins
and polypeptides
Fatty acids and
2. Gastric lipase Acid medium Triglycerides of butter
Dextrin and maltose
3. Gastric amylase Acid medium Starch
(negligible action)
Gelatin and collagen
4. Gelatinase Acid medium Peptides
of meat
5. Urase Acid medium Urea Ammonia

„„ 2. HEMOPOIETIC FUNCTION of intrinsic factor in gastric juice causes

deficiency of vitamin B12 leading to perni­
The intrinsic factor of Castle secreted by
cious anemia (refer Chapter 12).
parietal cells of gastric glands plays an
important role in erythropoiesis. It is neces­
sary for absorption of vitamin B12 (which is
called extrinsic factor) from GI tract into the
blood. Vitamin B12 is an important matu­ The mucus present in the gastric juice
ration factor during erythropoiesis. Absence protects gastric wall as mentioned below.
178 Section 4 ê Digestive System

Mucus: In the parietal cells, the carbon dioxide

is formed from metabolic activity. It is also
i. Protects the stomach wall from irrita­
derived from blood. Carbon dioxide com­
tion or mechanical injury by virtue of its
bines with water to form carbonic acid in
high viscosity.
the presence of carbonic anhydrase. This
ii. Prevents the digestive action of pepsin
enzyme is present in high concentration
on gastric mucosa.
in parietal cells. Carbonic acid is the most
iii. Protects the gastric mucosa from hydro­
unstable compound and, immediately it
chloric acid of gastric juice because
splits into hydrogen ion and bicarbonate ion.
of its alkaline nature and its acid-com­
The hydrogen ion is actively pumped into
bining power.
the canaliculus of parietal cell.
Simultaneously, the chloride ion is also
„„ 4. FUNCTIONS OF pumped into canaliculus actively. The chlo­
HYDROCHLORIC ACID ride is derived from sodium chloride in the
Hydrochloric acid present blood. Now, the hydrogen ion combines
in the gastric juice: with chloride ion to form hydrochloric acid.
To compensate the loss of chloride ion, the
i. Activates pepsinogen into pepsin. bicarbonate ion from parietal cell enters
ii. Kills some of the bacteria entering the the blood and combines with sodium to
stomach along with food substances; form sodium bicarbonate. Thus, the entire
this action is called bacteriolytic action. process is summarized as (Fig. 32.4):
iii. Provides acid medium which is nece­
CO2 + H2O + NaCl HCl + NaHCO3
ssary for the actions of the hormones.
Regulation of gastric secretion and intestinal
Pepsinogen is synthesized from amino acids secretion is studied by some experimental
in the ribosomes attached to endoplasmic procedures.
reticulum in chief cells. The pepsinogen mole­
cules are packed into zymogen granules by „„ METHODS OF STUDY
Golgi apparatus.
1. Pavlov Pouch
When zymogen granule is secreted into
stomach from chief cells, the granule is Pavlov pouch is a small part of the stomach
dissolved and pepsinogen is released into that is incompletely separated from the main
gastric juice. Pepsinogen is activated into portion and made into a small bag-like pouch
pepsin by hydrochloric acid. (Fig. 32.5). Pavlov pouch was designed by
the Russian scientist Pavlov in dog during
„„ SECRETION OF his studies on conditioned reflexes.
Nerve supply of Pavlov pouch
Hydrochloric acid secretion is an active
process that takes place in the canaliculi of Pavlov pouch receives parasympathetic
parietal cells in gastric glands. The energy (vagus) nerve fibers through isthmus and
for this is derived from oxidation of glucose. sympa­thetic fibers through blood vessels.
Chapter 32 ê Gastric Secretion 179
Use of Pavlov pouch of abdominal wall or thoracic wall in the
same animal. It is used for experimental
Pavlov pouch is used to demonstrate the
different phases of gastric secretion parti­ purpose, when the new blood vessels are
cularly the cephalic phase and used to developed.
demonstrate the role of vagus in cephalic Uses of Farrell and Ivy pouch
This pouch is useful to study the role of hor­
mones during gastric and intestinal phases
of gastric secretion.

3. Sham Feeding
Sham feeding means the false feeding. It
is another experimental procedure devised
by Pavlov to demonstrate the regulation of
gastric secretion.
i. A hole is made in the neck of an anes­
thetized dog.
ii. Esophagus is transversely cut. The cut
FIGURE 32.4: Secretion of hydrochloric acid in ends are drawn out through the hole in
parietal cell of gastric gland the neck.
iii. When the dog eats food, it comes out
through the cut end of the esophagus.
iv. But the dog has the satisfaction of eating
the food. It is called sham feeding.
This experimental procedure is suppor­
ted by the preparation of Pavlov pouch with
a fistula from the stomach. The fistula opens
to the exterior and it is used to observe the
gastric secretion. The animal is used for
experimental purpose after a week time
when healing is completed.
Advantage of sham feeding
It is useful to demonstrate the secretion of
gastric juice during cephalic phase. In the same
animal after vagotomy, sham feeding does
FIGURE 32.5: Pavlov pouch
not induce gastric secretion. It proves the role
of vagus nerve during cephalic phase.
2. Farrell and Ivy Pouch
This pouch is prepared by removing the „„ PHASES OF GASTRIC SECRETION
part of Pavlov pouch from the stomach and Gastric juice is secreted in three different
transplanting it in the subcutaneous tissue phases:
180 Section 4 ê Digestive System

1. Cephalic phase. During this phase, the gastric secretion

2. Gastric phase. occurs even without the presence of food in
3. Intestinal phase. the stomach. The quantity of the juice is less
In human beings, a fourth phase called but it is rich in enzymes and hydrochloric
interdigestive phase exists. All the phases acid. The nervous mechanism that regula­
are regulated by neural mechanism or tes cephalic phase operates through reflex
hormonal mechanism or both. action. Two types of reflexes occur:
a. Unconditioned reflex.
„„ CEPHALIC PHASE b. Conditioned reflex.
Secretion of gastric juice by the stimuli
Unconditioned Reflex
arising from head region (cephalus) is called
cephalic phase (Fig. 32.6). This phase is Unconditioned reflex is the inborn reflex.
regulated by nervous mechanism. During When food is placed in the mouth, it induces
this phase 30% of total amount of gastric salivary secretion (refer Chapter 31). Simul­
juice is secreted. taneously, gastric secretion also occurs.

FIGURE 32.6: Schematic diagram showing the regulation of gastric secretion.CCK-PZ =

Cholecystokinin-pancreozymin, GIP = Gastroinhibitory peptide, VIP = Vasoactive intestinal peptide.
Chapter 32 ê Gastric Secretion 181
Stages of the reflex action Pavlov pouch and bell dog experiment
refer Chapter 107).
i. The presence of food in the mouth
stimulates the taste buds and other
receptors in the mouth.
ii. The sensory (afferent) impulses from The secretion of gastric juice when the food
mouth pass via afferent nerve fibers of enters the stomach is called gastric phase.
glossopharyngeal and facial nerves to This phase is regulated by both nervous and
appetite center present in amygdala hormonal mechanisms. The gastric juice
and hypothalamus. secreted during this phase is rich in pep­
iii. From here, efferent impulses pass sinogen and hydrochloric acid. During gas­
through dorsal nucleus of vagus and tric phase 60% of total amount of gastric
juice is secreted.
vagal efferent nerve fibers to the wall
The mechanisms involved in this phase
of the stomach.
iv. Acetylcholine is secreted at the vagal
1. Nervous mechanism through local
efferent nerve endings stimulates gastric
myen­teric reflex and vagovagal reflex.
glands to increase the secretion. 2. Hormonal mechanism through gastrin.
This is experimentally proved by Pavlov
pouch and sham feeding. 1. Nervous mechanism

Conditioned Reflex Local myenteric reflex

Conditioned reflex is the reflex response Local myenteric reflex is elicited by stimulation
acquired by previous experience (refer of myenteric nerve plexus in stomach wall.
Chapter 107). Presence of food in the mouth After entering stomach, the food particles
is not necessary to elicit this reflex. The stimulate the local nerve plexus (refer Chapter
sight, smell, hearing or thought of food 31) present in the wall of the stomach. These
which induce salivary secretion also induce nerve fibers release acetylcholine, which
gastric secretion. stimulates the gastric glands to secrete a
large quantity of gastric juice. Simultaneously,
Stages of reflex action
acetylcholine-stimulates G cells to secrete
i. Impulses from the special sensory gastrin (see below).
organs (eye, ear and nose) pass through
Vagovagal reflex
afferent fibers of neural circuits to the
cerebral cortex. Thinking of food stimu­ Vagovagal reflex is the reflex in which both
lates the cerebral cortex directly. afferent and efferent vagal fibers are invol­
ii. From cerebral cortex the impulses pass ved. Presence of food in stomach stimulates
through dorsal nucleus of vagus and the sensory (afferent) nerve endings of
vagal efferents and reach stomach vagus which generate sensory impulses.
wall. The sensory impulses are transmitted to
iii. The vagal nerve endings secrete acetyl­ the brainstem via sensory fibers of vagus.
choline. It stimulates the gastric glands Brainstem in turn sends efferent impulses
to increase its secretion (conditioned through the motor (efferent) fibers of vagus
reflex of gastric secretion is proved by back to stomach and cause secretion
182 Section 4 ê Digestive System

of gastric juice. Since, both afferent and is transported to stomach through blood.
efferent impulses pass through vagus, this There, it increases gastric secretion. During
reflex is called vagovagal reflex. this phase 10% of total amount of gastric
juice is secreted.
2. Hormonal Mechanism – Gastrin Later stage of intestinal phase
Gastrin is a gastrointestinal hormone sec­ After the initial increase, there is decrease
reted by the G cells which are present in or complete stoppage of secretion of gastric
pyloric glands of stomach. Small amount of juice. Two factors are responsible for the
gastrin is also secreted in mucosa of upper inhibition:
small intestine. Gastrin is a polypeptide con­ 1. Enterogastric reflex.
taining G14, G17 or G34 amino acids. 2. GI hormones.
Gastrin is released when food enters
stomach. The mechanism involved in the 1. Enterogastric reflex
release of gastrin may be the local ner­ It is a reflex that inhibits the secretion and
vous reflex or vagovagal reflex. The nerve movements of stomach due to the disten­
endings release the neurotransmitter called tion or irritation of intestinal mucosa. It is
gastrin-releasing peptide which stimulates mediated by myenteric nerve (Auerbach’s)
the G cells to secrete gastrin. plexus and vagus.
Actions of gastrin on gastric secretion 2. GI hormones
Gastrin stimulates the secretion of pepsi­ The presence of chyme in the intestine
nogen and hydrochloric acid by the gastric stimulates the secretion of many GI hor­
glands. mones from intestinal mucosa and other
structures. All these hormones inhibit the
Experimental evidences of gastric secretion. Some of these hormones
gastric phase inhibit the gastric motility also.
The nervous mechanism of gastric secre­ GI hormones which inhibit gastric
tion during gastric phase is proved by
i. Secretin: Secreted by the presence of
Pavlov pouch. Hormonal mechanism of
acid chyme in the intestine.
gastric secretion is proved by Farrell and ii. Cholecystokinin: Secreted by the
Ivy pouch (see above). presence of chyme containing fats and
amino acids in intestine.
„„ 3. INTESTINAL PHASE iii. Gastric inhibitory peptide (GIP): Secre­
Intestinal phase is the secretion of gastric ted by the presence of chyme contain­
ing glucose and fats in the intestine.
juice when chyme enters the intestine.
iv. Vasoactive intestinal polypeptide (VIP):
When chyme enters the intestine initially
Secreted by the presence of acidic
the gastric secretion increases and later it chyme in intestine.
stops. Intestinal phase of gastric secretion v. Peptide YY: Secreted by the presence
is under both nervous and hormonal control. of fatty chyme in intestine.
Initial stage of intestinal phase In addition to these hormones, pancreas
also secretes a hormone called somato­
The chyme entering intestine stimulates the statin during intestinal phase. It also inhibits
duodenal mucosa to release gastrin which gastric secretion.
Chapter 32 ê Gastric Secretion 183
The intestinal phase of gastric secretion weak. The gastric glands also shrink resul­
is demonstrated by Farrell and Ivy pouch. ting in the deficiency of gastric juice.


Secretion of small amount of gastric juice in Gastric atrophy is caused by chronic gas­
between meals (or during period of fasting)
tritis and autoimmune disease.
is called interdigestive phase. Gastric secre­
tion during this phase is mainly due to the
hormones like gastrin. This phase of gastric Features
secretion is demonstrated by Farrell and Gastric atrophy causes achlorhydria (absence
Ivy pouch.
of hydrochloric acid in gastric juice) and
pernicious anemia. Some patients develop
gastric cancer.
Inflammation of gastric mucosa is called „„ 3. PEPTIC ULCER
gastritis. It may be acute or chronic. Ulcer means the erosion of the surface of
any organ due to shedding or sloughing
Causes of Gastritis of inflamed necrotic tissue that lines the
i. Infection with bacterium Helicobacter organ. Peptic ulcer means an ulcer in the
pylori. wall of stomach or duodenum caused by
ii. Excess consumption of alcohol. digestive action of gastric juice. If peptic
iii. Excess or long term administration ulcer is found in stomach, it is called gastric
non-steroidal anti-inflammatory drugs ulcer and if found in duodenum it is called
(NSAIDs). duodenal ulcer.
iv. Trauma by nasogastric tubes.
v. Autoimmune disease.
Features i. Increased peptic activity due to exces­
Features of gastritis are: sive secretion of pepsin in gastric juice.
i. Abdominal upset or pain. ii. Hyperacidity of gastric juice.
ii. Nausea. iii. Reduced alkalinity of duodenal content.
iii. Vomiting. iv. Decreased mucin content in gastric
iv. Anorexia (loss of appetite). juice or decreased protective activity
v. Indigestion. in stomach or duodenum.
vi. Discomfort or feeling of fullness in the v. Constant physical or emotional stress.
epigastric region. vi. Food with excess spices or smoking
vii. Belching (process to relieve swallowed (classical causes of ulcers).
air that is accumulated in stomach).
vii. Long term use of NSAIDs (see above)
such as aspirin, ibuprofen and nap­
Gastric atrophy is the condition in which the viii. Chronic inflammation due to Helico­
muscles of the stomach shrink and become bacter pylori.
184 Section 4 ê Digestive System

Features i. Nausea.
ii. Vomiting.
The most common feature of peptic ulcer iii. Hematemesis (vomiting blood).
is severe burning pain in epigastric region. iv. Heartburn (burning pain in chest due
In gastric ulcer, pain occurs while eating or to regurgitation of acid from stomach
drinking. In duodenal ulcer, pain is felt 1 or into esophagus).
2 hours after food intake and during night. v. Anorexia (loss of appetite).
Other symptoms accompanying pain are: vi. Loss of weight.
Chapter 33

Pancreatic Secretion



„„ FUNCTIONAL ANATOMY AND duct to form ampulla of Vater, which opens

NERVE SUPPLY OF PANCREAS into duodenum (refer Fig. 34.3).

Pancreas is a dual organ having two func­ „„ NERVE SUPPLY TO PANCREAS

tions, the endocrine function and the exo­
crine function. The endocrine function is Pancreas is supplied by both sympathetic
concerned with production of the hormones and parasympathetic fibers. The sympathe­
tic fibers are supplied through splanchnic
(refer Chapter 53). The exocrine function is
nerve and parasympathetic fibers are sup­
concerned with secretion of digestive juice
plied through vagus nerve.
called pancreatic juice.
Exocrine part of pancreas is made up of
acini or alveoli like salivary glands. Each Properties of Pancreatic Juice
acinus has a single layer of acinar cells with Volume : 500 to 800 mL/day
a lumen in the center. The acinar cells con­ Reaction : Highly alkaline with pH of
tain zymogen granules, which possess diges­ 8 to 8.3
tive enzymes. Specific gravity : 1.010 to 1.018
A small duct arises from lumen of
each alveolus. Some of these ducts from Composition of Pancreatic Juice
neighboring alveoli unite to form intralobular Pancreatic juice contains 99.5% of water and
duct. All the intralobular ducts unite to form 0.5% of solids. The solids are the organic and
the main duct of pancreas called Wirsung’s inorganic substances. Composition of pan­
duct. Wirsung’s duct joins common bile creatic juice is given in Fig. 33.1.
186 Section 4 ê Digestive System

FIGURE 33.1: Composition of pancreatic juice

The bicarbonate content is very high in proteolytic enzymes are carboxypeptidases,

pancreatic juice. It is about 110 to 150 mEq/L nuclease, elastase and collagenase.
against the concentration of 24 mEq/L in
plasma. This high concentration of bicar­ 1. Trypsin
bonate is responsible for the alkalinity of Trypsin is a single polypeptide with a mole­
pancreatic juice. cular weight of 25,000. It contains 229
amino acids.
„„ FUNCTIONS OF It is secreted as inactive trypsinogen
PANCREATIC JUICE which is converted into active trypsin by
enterokinase. Enterokinase is also called
Pancreatic juice has digestive functions and enteropeptidase and it is secreted by the
the neutralizing action. brush bordered cells of duodenal mucus
membrane. Once formed, trypsin itself acti­
„„ DIGESTIVE FUNCTIONS OF vates trypsinogen by means of autocatalytic
PANCREATIC JUICE or autoactive action.
Pancreatic juice plays an important role in Actions of trypsin
the digestion of proteins and lipids. It also
has mild action on carbohydrate digestion. i. Digestion of proteins: Trypsin is the
most powerful proteolytic enzyme. It
„„ DIGESTION OF PROTEINS is an endopeptidase and breaks the
interior bonds of the protein molecules.
The major proteolytic enzymes of pancreatic And it converts proteins into proteoses
juice are trypsin and chymotrypsin; and other and polypeptides.
Chapter 33 ê Pancreatic Secretion 187
ii. Curdling of milk: It converts caseino­ 4. Nucleases
gens in the milk into casein.
The nucleases of pancreatic juice are
iii. It accelerates blood clotting.
iv. It activates other enzymes of pan­ ribonuclease and deoxyribonuclease, which
creatic juice: are responsible for the digestion of nucleic
a. Chymotrypsinogen into chymo- acids. These enzymes convert the ribonu­
trypsin. cleic acid (RNA) and deoxyribonucleic acid
b. Procarboxypeptidases into carboxy- (DNA) into mononucleotides.
c. Proelastase into elastase. 5. Elastase
d. Procolipase into colipase. Elastase is secreted as inactive proelas­
v. Trypsin also activates collagenase,
tase and is activated into active elastase by
phospholipase A and phospholipase B.
trypsin. It digests the elastic fibers.
vi. Autocatalytic action: Once formed
trypsin itself converts trypsinogen into
6. Collagenase
Collagenase is secreted as inactive pro­
2. Chymotrypsin collagenase and is activated into active
Chymotrypsin is a polypeptide with a mole­ collagenase by trypsin. It digests collagen.
cular weight of 25,700 and 246 amino acids.
It is secreted as inactive chymotrypsinogen „„ DIGESTION OF LIPIDS
and activated into chymotrypsin by trypsin. The lipolytic enzymes present in pancreatic
juice are pancreatic lipase, cholesterol ester
Actions of chymotrypsin
hydrolase, phospholipase A, phospholipase
i. Digestion of proteins: Chymotrypsin is B and a coenzyme called colipase.
also an endopeptidase and it breaks
the proteins into polypeptides. 1. Pancreatic lipase
ii. Digestion of milk: Chymotrypsin digests
casein faster than trypsin. The combi­ Pancreatic lipase is a powerful lipolytic
nation of both enzymes causes more enzyme. It digests the triglycerides into
rapid digestion of milk. mono­glycerides and fatty acids. The activity
iii. On blood clotting: No action. of pancreatic lipase is accelerated in the
presence of bile. The optimum pH required
3. Carboxypeptidases for activity of this enzyme is 7 to 9.
Digestion of fat by pancreatic lipase
The two carboxypeptidases are carboxy- requires two more factors:
peptidase A and carboxypeptidase B. These i. Bile salts which are responsible for
are secreted as procarboxypeptidase A the emulsification of fat prior to their
and procarboxypeptidase B. The inactive digestion.
procarboxypeptidases are activated into ii. Colipase which is a coenzyme neces­
carboxypeptidases by trypsin. sary for the pancreatic lipase to hydro­
lyze the dietary lipids. Colipase is secre­
Actions of carboxypeptidases
ted as an inactive procolipase which
Carboxypeptidases are exopeptidases and activated into colipase by trypsin.
split the polypeptides and other proteins About 80% of fat is digested by pan­
into amino acids. creatic lipase. The deficiency or absence
188 Section 4 ê Digestive System

of this hormone leads to excretion of undi­ of bicarbonate is released into intestine.

gested fat in feces (see below). Presence of large quantity of bicarbonate
ions makes the pancreatic juice highly alka­
2. Cholesterol Ester Hydrolase line. This alkaline pancreatic juice neutra­
lizes acidity of chyme in the intestine.
Cholesterol ester hydrolase or cholesterol
Neutralizing action is an important func­
esterase converts cholesterol ester into
tion of pancreatic juice, because it protects
free cholesterol and fatty acid by hydrolysis.
the intestine from the destructive action of
acid in the chyme.
3. Phospholipase A
It is activated by trypsin. Phospholipase A „„ REGULATION OF
digests phospholipids namely lecithin and PANCREATIC SECRETION
cephalin and converts them into lysolecithin
and lysocephalin. The pancreatic secretion occurs in three
4. Phospholipase B 1. Cephalic phase.
2. Gastric phase.
Phospholipase B is also activated by trypsin. 3. Intestinal phase.
This enzyme converts lysolecithin and lyso­ Each phase is regulated by nervous
cephalin into phosphoryl choline and free mechanism or hormonal mechanism or both.
fatty acids.
5. Colipase
As in case of gastric secretion, the cephalic
Colipase is a small coenzyme, which faci­
phase of pancreatic secretion is regulated by
litates the hydrolysis of fats by pancreatic
nervous mechanism through reflex action.
During this phase, 20% of total amount
pancreatic juice is secreted. Two types of
6. Bile Salt-activated Lipase
reflexes occur:
This enzyme has a weak lipolytic action. It i. Unconditioned reflex.
digests a variety of lipids like phospholipids, ii. Conditioned reflex.
cholesterol esters and triglycerides. Since it
is activated bile salt it is known as bile salt- Unconditioned Reflex
activated lipase (Table 33.1).
Unconditioned reflex is the inborn reflex.
When food is placed in the mouth, it induces
salivary secretion (refer Chapter 31), gastric
Pancreatic amylase is the amylolytic enzyme secretion (refer Chapter 32). Simultaneously
present in pancreatic juice. Like to salivary it induces pancreatic secretion also.
amylase, the pancreatic amylase also con­
verts starch into dextrin and maltose. Conditioned Reflex
Conditioned reflex is the reflex response
acquired by previous experience (refer
Chapter 107). Presence of food in the mouth
When acid chyme enters intestine from is not necessary to elicit this reflex. The
stomach, pancreatic juice with large quantity sight, smell, hearing or thought of food which
Chapter 33 ê Pancreatic Secretion 189
TABLE 33.1: Digestive enzymes of pancreatic juice

Enzyme Activator Acts on End products

Enterokinase Proteoses and
1. Trypsin Proteins
Trypsin polypeptides
2. Chymotrypsin Trypsin Proteins Polypeptides
3. Carboxypeptidases Trypsin Polypeptides Amino acids
4. Nucleases Trypsin RNA and DNA Mononucleotides
5. Elastase Trypsin Elastin Amino acids
6. Collagenase Trypsin Collagen Amino acids
Monoglycerides and fatty
7. Pancreatic lipase Alkaline medium Triglycerides
8. Cholesterol ester Cholesterol and fatty
Alkaline medium Cholesterol ester
hydrolase acids
9. Phospholipase A Trypsin Phospholipids Lysophospholipids
Phosphoryl choline and
10. Phospholipase B Trypsin Lysophospholipids
free fatty acids
Facilitates action of
11. Colipase Trypsin –
Phospholipids Lysophospholipids
Cholesterol and fatty
12. Bile salt-activated Cholesterol esters
Trypsin acids
Monoglycerides and fatty
13. Pancreatic amylase – Starch Dextrin and maltose

induce salivary secretion and gastric sec­ phase. This phase of pancreatic secretion
retion also induces pancreatic secretion is under hormonal control. The hormone
(Fig. 33.2). involved is gastrin.
The impulses from mouth (during uncon­ When food enters stomach, gastrin is
di­tioned reflex) or from the cerebral cortex secreted from stomach (refer Chapter 32).
(during conditioned reflex) reach the dorsal
When gastrin is transported to pancreas
nucleus of vagus. From the dorsal nucleus
of vagus, the efferent impulses reach through blood, it stimulates the pancreatic
the pancreas via efferent fibers of vagus secretion. The pancreatic juice secreted
nerve. The vagal nerve endings release during gastric phase is rich in enzymes.
acetylcholine which stimulates the acinar During gastric phase, only 10% of pan­
cells to release the enzymes. creatic juice is secreted.


Secretion of pancreatic juice when food Intestinal phase is the secretion of pan­
enters the stomach is known as gastric creatic juice when the chyme enters the
190 Section 4 ê Digestive System

FIGURE 33.2: Schematic diagram showing the regulation of pancreatic secretion

intestine. This phase is also under hormonal Action of secretin

control. In this phase, 70% of total amount Secretin stimulates the secretion of watery
of pancreatic juice is secreted. pancreatic juice which contains high
When chyme enters the intestine many concentration of bicarbonate ion.
hormones are released. Some hormones
stimulate the pancreatic secretion and some Cholecystokinin
hormones inhibit the pancreatic secretion. Cholecystokinin (CCK) is also called chole­
cystokinin-pancreozymin (CCK-PZ). It is
Hormones Stimulating secreted by I cells in duodenal and jejunal
Pancreatic Secretion mucosa. The stimulant for the release of
this hormone is the chyme containing
i. Secretin.
digestive products such as fatty acids,
ii. Cholecystokinin.
peptides and amino acids.
Secretin Action of cholecystokinin

Secretin is produced by S cells of mucous Cholecystokinin stimulates the secretion of

membrane in duodenum and jejunum. It is pancreatic juice rich in enzyme and less in
produced in an inactive prosecretin which is volume.
activated into secretin by acid chyme.
Hormones Inhibiting
The stimulant for the release and acti­
Pancreatic Secretion
vation of prosecretin is the acid chyme
entering intestine. The products of protein i. Pancreatic polypeptide secreted by
diges­tion also stimulate the hormonal secre­ PP cells in islets of Langerhans of
tion. pancreas.
Chapter 33 ê Pancreatic Secretion 191
ii. Somatostatin secreted by D cells in Features of Pancreatitis
islets of Langerhans of pancreas. 1. Absence of pancreatic enzymes.
iii. Peptide YY secreted by intestinal 2. Steatorrhea.
mucosa. 3. Severe abdominal pain.
iv. Peptides like ghrelin and leptin. 4. Nausea and vomiting.
5. Loss of appetite and weight.
7. Shock.
Pancreatitis is the inflammation of pan­ „„ STEATORRHEA
creatic acini.
Steatorrhea is the formation of bulky, foul
smelling, frothy and clay colored stools with
Causes of Pancreatitis
large quantity of undigested fat because of
1. Long-time consumption of low alcohol. impaired digestion and absorption of fat.
2. Congenital abnormalities of pancreatic
duct. Causes of Steatorrhea
3. Malnutrition (poor nutrition; mal = bad). 1. Lack of pancreatic lipase.
4. Heavy alcohol intake. 2. Liver disease affecting secretion of bile.
5. Gallstones. 3. Atrophy of intestinal villi.
Chapter 34

Liver and Biliary System



„„ FUNCTIONAL ANATOMY OF structure and it is made up of liver cells called

LIVER AND BILIARY SYSTEM hepatocytes. Hepatocytes are arranged in
hepatic plates. Each plate is made up of
Liver is a dual organ having both secretory two columns of cells. In between the two
and excretory functions. It is the largest columns of each plate lies a bile canali­
gland in the body weighing about 1.5 kg culus (Fig. 34.2).
in man. It is located in the upper and right In between the neighboring plates, a
side of the abdominal cavity immediately blood space called sinusoid is present.
beneath diaphragm. Sinu­soid is lined by the endothelial cells.
In between the endothelial cells some spe­
cial macrophages called Kupffer cells are
„„ LIVER present.
Liver is made up of many lobes called
hepatic lobes (Fig. 34.1). Each lobe consists Portal Triads
of many lobules called hepatic lobules. Each lobule is surrounded by many portal
The hepatic lobule is the structural and triads. Each portal triad consists of three
functional unit of liver. It is a honeycomb-like vessels:
Chapter 34 ê Liver and Biliary System 193
The branches of hepatic artery and portal
vein open into the sinusoid. Sinusoid opens
into the central vein. Central vein empties
into hepatic vein.
Bile is secreted by hepatic cells and emp­
tied into bile canaliculus. From canaliculus,
the bile enters the tributary of bile duct. The
tributaries of bile duct from canaliculi of
neighboring lobules unite to form small bile
ducts. These small bile ducts join together
and finally form left and right hepatic ducts
which emerge out of liver.
FIGURE 34.1: Posterior surface of liver
Biliary system is also known as extrahepatic
biliary apparatus. It is formed by gallbladder
and the extrahepatic bile ducts (bile ducts
outside the liver). The right and left hepatic
bile ducts which come out of liver join to
form common hepatic duct. It unites with
the cystic duct from gallbladder to form
common bile duct (Fig. 34.3).
The common bile duct unites with pan­
creatic duct to form the common hepato­
pancreatic duct or ampulla of Vater which
opens into the duodenum.
There is a sphincter called sphincter
of Oddi at the lower part of common bile
duct, before it joins the pancreatic duct.
It is formed by smooth muscle fibers of
common bile duct. It is normally kept closed;
so the bile secreted from liver enters gall­
bladder where it is stored. Upon appro­
priate stimulation the sphincter opens and
allows flow of bile from gallbladder into the


FIGURE 34.2: Hepatic lobule Liver receives the maximum blood supply of
1. A branch of hepatic artery. about 1,500 mL/min. It receives blood from
2. A branch of portal vein. two sources, namely the hepatic artery and
3. A tributary of bile duct. portal vein (Fig. 34.4).
194 Section 4 ê Digestive System

The portal vein is formed by superior mesen­
teric vein and splenic vein. It brings deoxy­
genated blood from stomach, intestine,
spleen and pancreas. The portal blood is
rich in monosaccharides and amino acids.
It also contains bile salts, bilirubin, urobi­
linogen and GI hormones. However, the
oxygen content is less in portal blood.
The flow of blood from intestine to liver
FIGURE 34.3: Biliary system through portal vein is known as entero­
hepatic circulation (Fig. 34.5).
The blood from hepatic artery mixes
with blood from portal vein in the hepatic
sinusoids. The hepatic cells obtain oxygen
and nutrients from the sinusoid.

The substances synthesized by hepatic cells,
the waste products and carbon dioxide are
discharged into sinusoids. The sinusoids
drain them into the central vein of the lobule.

FIGURE 34.4: Schematic diagram of blood flow

through liver

The hepatic artery arises directly from aorta
and supplies oxygenated blood to liver.
After entering the liver, the hepatic artery
divides into many branches. Each branch
enters a portal triad. FIGURE 34.5: Enterohepatic circulation
Chapter 34 ê Liver and Biliary System 195
The central veins from many lobules unite
to form bigger veins which ultimately form
hepatic veins (right and left) which open
into inferior vena cava.

Bile is a golden yellow or greenish fluid. It
enters the digestive tract along with pan­
creatic juice through the common opening
called ampulla of Vater.
FIGURE 34.6: Composition of bile
Properties of Bile
whenever it is required. When bile is stored
Volume : 800 to 1,200 mL/day in gallbladder, it undergoes many changes
Reaction : Alkaline both in quality and quantity such as:
pH : 8 to 8.6 1. Volume is reduced because of absorption
Specific gravity : 1.010 to 1.011 of large amount of water and electrolytes
(except calcium and potassium).
Composition of Bile 2. Concentration of bile salts, bile pigments,
Bile contains 97.6% of water and 2.4% of cholesterol, fatty acids and leci­thin is
solids. Solids include organic and inorganic increased because of absorp­ tion of
substances. Refer Fig. 34.6 for details. water.
3. The pH is slightly decreased.
„„ SECRETION OF BILE 4. Specific gravity is increased.
5. Mucin is added (Table 34.1).
Bile is secreted by hepatocytes. The initial
bile secreted by hepatocytes contains large „„ BILE SALTS
quantity of bile acids, bile pigments, choles­
Bile salts are the sodium and potassium
terol, lecithin and fatty acids. From hepato­
salts of bile acids, which are conjugated
cytes, bile passes through canaliculi and
with glycine or taurine. Bile salts are formed
hepatic ducts to reach common hepatic
in liver.
duct. From here it may enter the intestine
or gallbladder (Fig. 34.7). „„ FORMATION OF BILE SALTS
Sodium, bicarbonate and water are added
to bile when it passes through the ducts. Bile salts are formed from the primary bile
acids, namely cholic acid and chenodeoxy­
These substances are secreted by the epi­
cholic acid which are formed in liver and
thelial cells of the ducts. The addition of
enter the intestine through bile. Due to the
sodium, bicarbonate and water increases
bacterial action in the intestine, these pri­
the total quantity of bile (Fig. 34.8). mary bile acids are converted into secon­
dary bile acids:
„„ STORAGE OF BILE Cholic acid Deoxycholic
Most of the bile from liver enters the acid
bladder where it is stored. It is rele­ Chenodeoxycholic acid Lithocholic
ased from gallbladder into the intestine acid
196 Section 4 ê Digestive System

TABLE 34.1: Differences between liver bile and to liver through enterohepatic circulation.
gallbladder bile The remaining 5 to 10% of the bile salts
enter large intestine. Here, the bile salts
Types of Gallbladder are converted into deoxycholate and litho­
Liver bile
entities bile cholate and excreted in feces.
pH 8 to 8.6 7 to 7.6
1,010 to 1,011 1,026 to 1,032
gravity The bile salts are required for digestion and
Water absorption of fats in the intestine. The func­
97.6% 89%
content tions of bile salts are given below.
Solids 2.4% 11%
Organic substances 1. Emulsification of Fats
Bile salts 0.5 g/dL 6.0 g/dL Emulsification is the process by which the
Bile fat globules are broken down into minute
0.05 g/dL 0.3 g/dL droplets and made in the form of a milky fluid
Cholesterol 0.1 g/dL 0.5 g/dL
called emulsion. Emulsification of fats occurs
in small intestine by the action of bile salts.
Fatty acids 0.2 g/dL 1.2 g/dL Fats cannot be digested directly by lipo­
Lecithin 0.05 g/dL 0.4 g/dL lytic enzymes of GI tract, because the fats are
Mucin Absent Present insoluble in water due to the surface tension.
The bile salts reduce the surface tension of the
Inorganic substances
fats due to their detergent action. Because of
Sodium 150 mEq/L 135 mEq/L this, the lipid granules are broken into minute
Calcium 4 mEq/L 22 mEq/L particles which can be easily digested by
Potassium 5 mEq/L 12 mEq/L lipolytic enzymes. The emulsification of fats
by bile salts needs the presence of lecithin
Chloride 100 mEq/L 10 mEq/L
from bile.
Bicarbonate 30 mEq/L 10 mEq/L
2. Absorption of Fats
Secondary bile acids from intestine are
transported back to liver through entero­ Bile salts help in the absorption of digested
hepatic circulation. In the liver the secon­ fats from intestine into blood. The bile salts
dary bile acids are conjugated with glycine combine with fats and make complexes of
or taurine and form conjugated bile acids fats called micelles. The fats in the form of
namely glycocholic acid and taurocholic micelles can be absorbed easily.
acids. These bile acids combine with sodium
or potassium ions to form the salts, sodium 3. Choleretic Action
or potassium glycocholate and sodium or
potassium taurocholate. Bile salts stimulate the secretion of bile from
liver. This action is called choleretic action.
BILE SALTS 4. Cholagogue Action
Enterohepatic circulation is the transport Cholagogue is an agent, which causes
of substances from small intestine to liver con­traction of gallbladder and release
through portal vein. About 90 to 95% of of bile into the intestine. Bile salts act as
bile salts from intestine are transported chola­­gogues indirectly by stimulating the
Chapter 34 ê Liver and Biliary System 197

FIGURE 34.7: Formation and circulation of bile pigments

secretion of hormone cholecystokinin. This The bile pigments are formed during the
hormone causes contraction of gall­blad­ breakdown of hemoglobin, which is rele­
der resulting in release of bile. ased from the destroyed RBCs in the reti­
culoendothelial system (refer Fig. 34.7).
5. Laxative Action
Laxative is an agent which induces defe­ „„ FORMATION AND EXCRETION OF
cation. Bile salts act as laxatives by stimu­ BILE PIGMENTS
lating peristaltic movements of the intestine. Stages of formation and circulation of bile
6. Prevention of Gallstone Formation 1. Senile erythrocytes are destroyed in
Bile salts prevent the formation of gallstone reticuloendothelial system and hemo­
by keeping the cholesterol and lecithin globin is released from them.
in solution. In the absence of bile salts, 2. Hemoglobin is broken into globin and
cholesterol precipitates along with lecithin heme.
and forms gallstone. 3. Heme is split into iron and the pigment
„„ BILE PIGMENTS 4. Iron goes to iron pool and is reused.
Bile pigments are the excretory products 5. First formed pigment biliverdin is redu­
in bile. Bilirubin and biliverdin are the two ced to bilirubin.
bile pigments and bilirubin is the major bile 6. Bilirubin is released into blood from
pigment in human being. reti­culoendothelial cells.
198 Section 4 ê Digestive System

FIGURE 34.8: Diagram showing the formation of bile from liver and changes taking place in the
composition of gallbladder bile

7. Bilirubin circulating in the blood is free bilirubin which is later reduced

called free bilirubin or unconjugated into urobilinogen.
bilirubin. 2. Remaining 50% of conjugated bilirubin
8. Within few hours the free bilirubin is from intestine enters the liver through
taken up by the liver cells. enterohepatic circulation. From liver, it
9. In the liver, it is conjugated with glu­ is re-excreted in bile.
curonic acid to form conjugated bili­ 3. Most of the urobilinogen from intes­tine
rubin. enters liver via enterohepatic circu­
10. Conjugated bilirubin is then excreted lation. Later, it is re-excreted through
into intestine through bile. bile.
4. About 5% of urobilinogen is excreted
„„ FATE OF CONJUGATED BILIRUBIN by kidney through urine. In urine, due
Stages of excretion of conjugated bilirubin: to the exposure to air, the urobilinogen
1. In the intestine, 50% of the conjugated is converted into urobilin by oxidation.
bilirubin is converted into urobilinogen 5. Some of the urobilinogen is excreted in
by intestinal bacteria. First the conju­ feces as stercobilinogen. In feces, ster­
gated bilirubin is deconjugated into cobilinogen is oxidized to stercobilin.
Chapter 34 ê Liver and Biliary System 199
The normal bilirubin (total bilirubin) con­ As the bile is highly alkaline, it neutralizes
tent in plasma is 0.5 to 1.5 mg/dL. When acid chyme which enters the intestine from
it exceeds 1 mg/dL, the condition is called stomach. Thus, an optimum pH is main­
hyper­bilirubinemia. When it exceeds 2 mg/ tained for the action of digestive enzymes.
dL, jaundice occurs.
Refer function of bile salts.
Most of the functions of bile are due to the
bile salts. „„ 9. LUBRICATION FUNCTION
The mucin in bile acts as a lubricant for the
chyme in intestine.
Refer functions of bile salts
„„ 2. ABSORPTIVE FUNCTIONS Bile salts act as cholagogues (see above).
Refer functions of bile salts
„„ 3. EXCRETORY FUNCTIONS Liver is the largest gland and one of the
vital organs of the body. It performs many
Bile pigments are the major excretory pro­ vital metabolic and homeostatic functions,
ducts of the bile. The other substances which are summarized below.
excreted in bile are:
i. Heavy metals like copper and iron. „„ 1. METABOLIC FUNCTION
ii. Some bacteria like typhoid bacteria.
Liver is the organ where maximum meta­
iii. Some toxins.
bolic reactions are carried out such as
iv. Cholesterol.
meta­ bolism of carbohydrates, proteins,
v. Lecithin.
fats, vitamins and many hormones.
vi. Alkaline phosphatase.
Many substances like glycogen, amino
Bile salts act as laxatives (see above). acids, iron, folic acid and vitamins A, B12,
and D are stored in liver.
Bile inhibits the growth of certain bacteria
in the lumen of intestine by its natural Liver produces glucose by gluconeogenesis.
detergent action. It synthesizes all the plasma proteins and
other proteins (except immunoglobulins)
such as clotting factors, complement factors
and hormone-binding proteins. It also
Bile salts have the choleretic action (see synthesizes steroids, somatomedin and
above). heparin.
200 Section 4 ê Digestive System

„„ 4. SECRETION OF BILE drugs. The fat-soluble drugs are con­verted

into water-soluble substances, which are
Liver secretes bile, which contains bile
excreted through bile or urine.
salts, bile pigments, cholesterol, fatty acids
and lecithin. „„ 10. DEFENSIVE AND
The functions of bile are mainly due to DETOXIFICATION FUNCTIONS
the bile salts. The bile salts are required
The reticuloendothelial cells (Kupffer cells)
for digestion and absorption of fats in the of the liver play an important role in the
intestine. Bile helps to carry away waste defense of the body. Liver is also involved
products and breakdown fats, which are in the detoxification of the foreign bodies:
excreted through feces or urine. i. Foreign bodies such as bacteria or
antigens are swallowed and digested
„„ 5. EXCRETORY FUNCTION by reticuloendothelial cells of liver by
Liver excretes cholesterol, bile pigments, means of phagocytosis.
heavy metals (like lead, arsenic and bismuth), ii. Reticuloendothelial cells of liver are
also involved in production of some
toxins, bacteria and virus (like that of yellow
substances like interleukins and tumor
fever) through bile.
necrosis factors, which activate the
immune system of the body (refer
Chapter 15).
Liver is the organ where maximum heat is iii. Liver cells are involved in removal of
produced because of the metabolic reac­ toxic property of various harmful sub­
tions. stances. The removal of toxic property
of the harmful agent is known as deto­
„„ 7. HEMOPOIETIC FUNCTION xification.

In fetus (hepatic stage), liver produces the „„ GALLBLADDER

blood cells (refer Chapter 10). It stores
The bile secreted from liver is stored in gall­
vitamin B12 necessary for erythropoiesis
bladder. The capacity of gallbladder is
and iron necessary for synthesis of hemo­
approximately 50 mL. The gallbladder is not
globin. Liver produces thrombopoietin that
essential for life. The removal of gallbladder
promotes production of thrombocytes. (cholecystectomy) is often done in patients
suffering from gallbladder dysfunction. After
„„ 8. HEMOLYTIC FUNCTION cholecystectomy, patients do not suffer from
The senile RBCs after the lifespan of 120 any major disadvantage. In some species,
days are destroyed by reticuloendothelial gallbladder is absent.
cells (Kupffer cells) of liver.
„„ 9. INACTIVATION OF HORMONES The major functions of gallbladder are the
AND DRUGS storage and concentration of bile.
Liver catabolizes the hormones such as
1. Storage of Bile
growth hormone, parathormone, cortisol,
insulin, glucagon and estrogen. It also inacti­ Bile is continuously secreted from liver. But
vates the drugs particularly the fat soluble it is released into intestine only intermittently
Chapter 34 ê Liver and Biliary System 201
and most of the bile is stored in gallbladder 1. Choleretics
till it is required.
Substances, which increase the secretion
of bile from liver, are known as choleretics.
2. Concentration of Bile The effective choleretic agents are:
Bile is concentrated while it is stored in i. Acetylcholine.
gallbladder. The mucosa of gallbladder rapidly ii. Secretin.
reabsorbs water and electrolytes except iii. Cholecystokinin.
calcium and potassium. But the bile salts, iv. Acid chyme in intestine.
bile pigments, cholesterol and lecithin are v. Bile salts.
not reabsorbed. So, the concentration of
these substances in bile increases 5 to 10 2. Cholagogues
times (refer Fig. 34.8).
Cholagogue is an agent, which increases
the release of bile from gallbladder into the
3. Alteration of pH of Bile intestine by contracting the gallbladder. The
The pH of bile decreases from 8–8.6 to common cholagogues are:
7–7.6 and it becomes less alkaline when it i. Bile salts.
is stored in gallbladder. ii. Calcium.
iii. Fatty acids.
iv. Amino acids.
4. Secretion of Mucin
v. Inorganic acids.
Gallbladder secretes mucin into the bile. All these substances stimulate the secre­
Mucin acts as a lubricant for movement of tion of cholecystokinin, which in turn causes
chyme in the intestine. contraction of gallbladder and flow of bile
into intestine.
5. Maintenance of Pressure in
Biliary System 3. Hydrocholeretic Agents
Due to the concentrating capacity, gall­ Hydrocholeretic agent is a substance, which
bladder maintains a pressure of about 7 cm causes secretion of bile from liver with
H2O in biliary system. This pressure in the large amount of water and less amount of
biliary system is essential for the release of solids. Hydrochloric acid is a hydrocholeretic
bile into the intestine. agent.


Bile secretion is a continuous process
though the amount may be less during fas­ Jaundice or icterus is the condition charac­
ting. It starts increasing 3 hours after the terized by yellow coloration of the skin,
meals. Secretion of bile from the liver and mucous membrane and deeper tissues due
release of bile from the gallbladder are to increased bilirubin level in blood. The word
influ­enced by some chemical factors which jaundice is derived from the French word
are categorized into three groups: ‘jaune’ meaning yellow.
1. Choleretics. The normal serum bilirubin level is 0.5 to
2. Cholagogue. 1.5 mg/dL. Jaundice occurs when bilirubin
3. Hydrocholeretic agents. level exceeds 2 mg/dL.
202 Section 4 ê Digestive System

Types of Jaundice 3. Posthepatic or Obstructive or

Extrahepatic Jaundice
Jaundice is classified into three types:
1. Prehepatic or hemolytic jaundice. This type of jaundice occurs because of the
2. Hepatic or hepatocellular jaundice. obstruction of bile flow at any level of the
3. Posthepatic or obstructive jaundice. biliary system. The bile cannot be excre­ted
into small intestine. So, bile salts and bile
1. Prehepatic or Hemolytic Jaundice pigments enter the circulation. The blood
contains more amount of conjugated bili­
Hemolytic jaundice is the type of jaundice
rubin (Table 34.2).
that occurs because of excessive destruc­
tion of RBCs resulting in increased blood Causes
level of free (unconjugated) bilirubin. The
i. Gallstones.
function of liver is normal. Since the quantity
ii. Cancer of biliary system or pancreas.
of bilirubin increases enormously, the liver
cells cannot excrete that much bilirubin „„ HEPATITIS
rapidly. So, it accumulates in the blood
resulting in jaundice. Hepatitis is the liver damage characterized
by swelling and inadequate functioning of
Causes liver. It is caused by several factors such as
Any condition that causes hemolytic anemia viral infection, bacterial infection and excess
can lead to hemolytic jaundice. The com­ alcohol.
mon causes of hemolytic jaundice are: Common features of hepatitis are fever,
i. Liver failure. nausea, vomiting, diarrhea, loss of appetite,
ii. Renal disorder. jaundice. Liver failure and death occur in
iii. Hypersplenism. severe conditions.
iv. Burns.
v. Infections such as malaria.
vi. Hemoglobin abnormalities such as Cirrhosis of liver refers to inflammation and
sickle cell anemia or thalassemia. damage of parenchyma of liver resulting in
vii. Drugs or chemical substances causing degeneration of hepatic cells and dysfunc­
red cell damage. tion of liver. It is caused by infection, obstruc­
viii. Autoimmune diseases. tion of biliary system and liver enlargement
due to intoxication.
2. Hepatic or Hepatocellular or Features of cirrhosis of liver are fever,
Cholestatic Jaundice nausea and vomiting, jaundice, portal hyper­
tension, muscular weakness and wasting of
This is the type of jaundice that occurs due
muscles. Coma occurs in advanced stages.
to the damage of hepatic cells. Because of
the damage, the conjugated bilirubin from „„ GALLSTONES
liver cannot be excreted and it returns to
blood. Definitions

Causes Gallstone is a solid crystal deposit that is

formed by cholesterol, calcium ions and bile
i. Hepatitis or cirrhosis of liver. pigments in the gallbladder or bile duct.
ii. Alcoholism. Cholelithiasis is the presence of gallstones
iii. Exposure to toxic materials. in gallbladder.
Chapter 34 ê Liver and Biliary System 203
TABLE 34.2: Features of different types of jaundice

Prehepatic jaundice Hepatic jaundice Posthepatic jaundice

(hemolytic) (hepatocellular) (obstructive)

Excess breakdown of
Cause Liver damage Obstruction of bile ducts
Type of bilirubin in Conjugated and
Unconjugated Conjugated
blood unconjugated
Urinary excretion of
Increases Decreases Absent in severe
Fecal excretion of Decreases (pale Absent (clay colored
stercobilinogen feces) feces)
van den Bergh
Indirect – positive Biphasic Direct – positive
Liver functions Normal Abnormal Exaggerated
Blood picture Reticulocytosis Normal Normal
Abnormal RBC
Albumin – increases
Plasma albumin Globulin – increases
Normal Normal
and globulin A : G ratio –
Hemorrhagic Present due to lack Present due to lack of
tendency of vitamin K vitamin K

Formation of Gallstones 3. Excess of calcium ions due to incre­

ased concentration of bile.
Normally, cholesterol is water soluble. Under
4. Damage or infection of gallbladder
some abnormal conditions, it precipitates epithelium.
resulting in the formation of crystals in the 5. Obstruction of bile flow from the gall­
mucosa of gallbladder. Bile pigments and bladder.
calcium are attached to these crystals
resulting in formation of gallstones. Features

Causes for Gallstone Formation The common feature of gallstone is the pain
in stomach area or in upper right part of the
1. Reduction in bile salts. belly under the ribs. Other features include
2. Excess of cholesterol or disturbed nausea, vomiting, abdominal bloating and
choles­terol metabolism. indigestion.
Chapter 35

Functions and Secretions of

Small Intestine


„„ FUNCTIONAL ANATOMY The villi are lined by columnar cells, which

are called enterocytes. Each enterocyte
Small intestine is the part of GI tract exten­
gives rise to hair-like projections called micro­
ding between the pyloric sphincter of
stomach and ileocecal valve, which opens villi. Within each villus, there is a central
into large intestine. It is called small intestine channel called lacteal. The lacteal opens
because of its small diameter compared to into lymphatic vessels, It contains blood
that of large intestine. But it is longer than vessels.
large intestine. Its length is about 6 meters.
The functional importance of small intes­ „„ CRYPTS OF LIEBERKÜHN OR
tine is absorption. Maximum absorption of INTESTINAL GLANDS
digested food products takes place in small
The crypts of Lieberkühn or intestinal glands
Small intestine consists of three portions: are simple tubular glands of intestine. These
1. Proximal part known as duodenum. glands open into lumen of intestine between
2. Middle part known as jejunum. the villi. The intestinal glands are lined by
3. Distal part known as ileum. columnar cells. The lining of each gland is
continuous with epithelial lining of the villi
OF SMALL INTESTINE Epithelial cells lining the intestinal glands
undergo division by mitosis at a faster rate.
„„ INTESTINAL VILLI The newly formed cells push the older cells
The mucous membrane of small intestine upward over the lining of villi. The cells
is covered by minute projections called villi. which move to villi are called enterocytes.
Chapter 35 ê Functions and Secretions of Small Intestine 205
Secretion from small intestine is called suc­
cus entericus.

Properties of Succus Entericus

Volume : 1,800 mL/day
Reaction : Alkaline
pH : 8.3

Composition of Succus Entericus

The succus entericus contains water (99.5%)
and solids (0.5%). Solids include organic
and inorganic substances (Fig. 35.2). The
bicarbonate concentration is slightly high in
succus entericus.

FIGURE 35.1: Intestinal gland and villus SUCCUS ENTERICUS

The enterocytes secrete the enzymes. The „„ 1. DIGESTIVE FUNCTION

old enterocytes are continuously shed into The enzymes of succus entericus act on
lumen along with enzymes. the partially digested food and convert them
Three types of cells are interposed into final digestive products.
between columnar cells of the glands:
1. Argentaffin cells which are otherwise Proteolytic Enzymes
known as enterochromaffin cells. These
The proteolytic enzymes in succus enteri­
cells secrete intrinsic factor that is essen­
cus are the peptidases which convert pep­
tial for the absorption of vitamin B12.
tides into amino acids (Fig. 35.2).
2. Goblet cells which secrete mucus.
3. Paneth cells which secrete the cyto­ Amylolytic Enzymes
kines called defensins.
The carbohydrate splitting enzymes of suc­
„„ BRUNNER’S GLANDS cus entericus are listed in Fig. 35.2. Lactase,
sucrase and maltase convert the disac­
In addition to intestinal glands, the first charides (lactose, sucrose and maltose)
part of duodenum contains some mucus into two molecules of monosaccharides
glands, which are called Brunner’s glands. (Table 35.1).
Brunner’s glands secrete mucus and traces Dextrinase converts dextrin, maltose
of enzymes. and maltotriose into glucose. Trehalase or
206 Section 4 ê Digestive System

FIGURE 35.2: Composition of succus entericus

TABLE 35.1: Digestive enzymes of succus entericus

Enzyme Substrate End products

1. Peptidases Peptides Amino acids

2. Sucrase Sucrose Fructose and glucose
3. Maltase Maltose and maltotriose Glucose
4. Lactase Lactose Galactose and glucose
5. Dextrinase Dextrin, maltose and maltotriose Glucose
6. Trehalase Trehalose Glucose
7. Intestinal lipase Triglycerides Fatty acids

tre­halose glucohydrolase causes hydrolysis „„ 2. PROTECTIVE FUNCTION

of trehalose (carbohydrate present in mush­ i. The mucus present in the succus ente­
rooms and yeast) and converts it into ricus protects intestinal wall from the
glucose. acid chyme, which enters the intestine
from stomach; thereby it prevents the
Lipolytic Enzyme intestinal ulcer.
ii. Paneth cells of intestinal glands secrete
Intestinal lipase acts on triglycerides and defensins which are the antimicrobial
converts them into fatty acids. peptides.
Chapter 35 ê Functions and Secretions of Small Intestine 207
The enterokinase present in intestinal juice Refer functions of succus entericus.
activates trypsinogen into trypsin. Trypsin
which in turn activates other enzymes (refer „„ 7. HYDROLYTIC FUNCTION
Chapter 33).
Refer functions of succus entericus.
The intrinsic factor of Castle, which is pre­
sent in the intestine, plays an important role The presence of villi and microvilli in small
in erythropoiesis (refer Chapter 9). intestinal mucosa increases the surface
area of the mucosa. This facilitates the
„„ 5. HYDROLYTIC PROCESS absorptive function of intestine.
The digested products of foodstuffs, pro­
Intestinal juice helps in all the enzymatic
teins, carbohydrates, fats and other nutri­
reactions of digestion.
tive substances such as vitamins, mine­rals
and water are absorbed mostly in small
„„ FUNCTIONS OF intestine. From the lumen of intestine,
SMALL INTESTINE these substances pass through lacteal of
„„ 1. MECHANICAL FUNCTION villi, cross the mucosa and enter the blood
directly or through lymphatics.
The mixing movements of small intestine
help in the thorough mixing of chyme with
the digestive juices like succus entericus,
pancreatic juice and bile. OF SUCCUS ENTERICUS
The secretion of succus entericus is regu­
„„ 2. SECRETORY FUNCTION lated by both the nervous and hormonal
Small intestine secretes succus entericus,
enterokinase and the GI hormones.
„„ 3. HORMONAL FUNCTION Stimulation of parasympathetic nerves
causes vasodilatation and increases the
Small intestine secretes many GI hormo­
secretion of succus entericus. Stimulation
nes such as secretin, cholecystokinin, etc.
of sympathetic nerves causes vasocons­
These hormones regulate the movement
triction and decreases the secretion of
of GI tract and secretory activities of small
succus entericus. But, the role of these
intestine and pancreas.
nerves in the regulation of intestinal
secretion in physiological conditions is
„„ 4. DIGESTIVE FUNCTION uncertain.
Refer functions of succus entericus. However, the local nervous reflexes play
an important role in increasing the secretion
of intestinal juice. When chyme enters the
small intestine, the mucosa is stimulated
Refer functions of succus entericus. by tactile stimuli or irritation. It causes
208 Section 4 ê Digestive System

development of local nervous reflexes, which „„ APPLIED PHYSIOLOGY –

stimulate the glands of intestine. MALABSORPTION

„„ HORMONAL REGULATION Malabsorption is difficulty in the digestion or

absorption of nutrients from small intestine. It
When the chyme enters the small intestine, may be the failure to absorb either the specific
the intestinal mucosa secretes enterocrinin, substances such as proteins, carbohydrates,
secretin and cholecystokinin which promote fats and vitamins or some general nonspeci­
the secretion of succus entericus by stimu­ fic substances of food. Malabsorption affects
lating the intestinal glands. growth and development of the body.
Chapter 36

Functions and Secretions of

Large Intestine


The large intestine is also known as colon.
It extends from ileocecal valve up to anus
(refer Fig. 30.1). It consists of seven portions:
1. Cecum with appendix.
2. Ascending colon.
3. Transverse colon.
4. Descending colon.
5. Sigmoid colon or pelvic colon.
6. Rectum.
7. Anal canal.
The wall of large intestine is formed by
four layers of structures like any other part FIGURE 36.1: Composition of large
of the gut. intestinal juice

Digestive enzymes are absent and con­

„„ SECRETIONS OF LARGE centration of bicarbonate is high in large
INTESTINE intestinal juice.
The large intestinal juice is a watery fluid
with pH of 8.0.
„„ COMPOSITION OF LARGE Neutralization of Acids
Strong acids formed by bacterial action in
The large intestinal juice contains 99.5% large intestine are neutralized by the alkaline
of water and 0.5% of solids (Fig. 36.1). nature of large intestinal juice. The alkalinity
210 Section 4 ê Digestive System

of this juice is mainly due to the presence of By this function, large intestine contributes
large quantity of bicarbonate. in erythropoietic activity and blood clotting
Lubrication Activity
The mucin present in secretion of large
intes­tine lubricates the mucosa of large „„ DIARRHEA
intes­tine and the bowel contents, so that
Diarrhea is the frequent and profuse dis­
the movement of bowel is facilitated.
The mucin also protects the mucous charge of intestinal contents in loose and
membrane of large intestine by preventing fluid form. It occurs due to the increased
the damage caused by mechanical injury or movement of intestine. It may be acute or
chemical substances. chronic.

INTESTINE 1. Intake of contaminated water or food,
artificial sweeteners found in food, spicy
„„ 1. ABSORPTIVE FUNCTION food, etc.
Large intestine plays an important role in 2. Indigestion.
the absorption of various substances such 3. Infections by bacteria, viruses and para­
as water, electrolytes and organic sub­ sites.
stances like glucose, alcohol and drugs like 4. Reaction to medicines like antibiotics,
anesthetic agents, sedatives and steroids. laxatives.
5. Intestinal diseases.
After the absorption of nutrients, water and
other substances, the unwanted substances Severe diarrhea results in loss of excess
in the large intestine form feces. This is water and electrolytes leading to dehydration
excreted out. and electrolyte imbalance. Chronic diarrhea
results in hypokalemia and metabolic acidosis.
„„ 3. EXCRETORY FUNCTION Other features of diarrhea are abdominal
pain, nausea and bloating (a condition in
Large intestine excretes heavy metals like which the subject feels the abdomen full and
mercury, lead, bismuth and arsenic through
tight due to excess intestinal gas).
Failure of voiding of feces, which produces
Large intestine secretes mucin and inorga­ discomfort, is known as constipation. It is
nic substances like chlorides and bicarbo­ due to the lack of movements necessary for
defecation (refer Chapter 37). Due to the
absence of mass movement in colon, feces
remain in the large intestine for a longtime
The bacterial flora of large intestine synthe­ resulting in absorption of fluid. So the feces
sizes folic acid, vitamin B12 and vitamin K. become hard and dry.
Chapter 36 ê Functions and Secretions of Large Intestine 211
1. Lack of fiber or lack of liquids in diet. Appendix is a small, finger-like pouch pro­
2. Irregular bowel habit. jecting from cecum of ascending colon.
3. Spasm of sigmoid colon. The inflammation of appendix is known as
4. Many types of diseases. appendicitis. The cause for appendicitis is
5. Drugs such as diuretics, pain relie­ not known. It may occur by viral infection
vers, antihypertensive drugs antipar­ of the gastrointestinal (GI) tract or if the
kinson drugs, antidepressants and anti­ con­nection between appendix and large
convulsants. intestine is blocked.
6. Dysfunction of myenteric plexus in The main symptom of appendicitis is the
large intestine called megacolon. pain, which starts around the umbilicus and
Megacolon is the condition characterized then spreads to the lower right side of the
by distension and hypertrophy of colon abdomen. The pain becomes severe within
associated with constipation. It is caused by 6 to 12 hours. Other features are nausea,
the absence or damage of ganglionic cells in vomiting, constipation, diarrhea and abdo­
myenteric plexus, which causes dysfunction minal swelling.
of myenteric plexus. It leads to accumulation If not treated immediately, the appendix
of large quantity of feces in colon. The colon may rupture and the inflammation will spread
is distended to a diameter of 4–5 inches. It to the whole body leading to severe compli­
also results in hypertrophy of colon. cations, sometimes even death.
Chapter 37

Movements of Gastrointestinal Tract


„„ MASTICATION 3. Pterygoid muscles.

4. Buccinator muscle.
Mastication or chewing is the first mechani­
Movements involved in mastication:
cal process in the GI tract by which the
1. Opening and closure of mouth.
food substances are torn or cut into small
particles and crushed or ground into a soft 2. Rotational movements of jaw.
bolus. 3. Protraction and retraction of jaw.
The significances of mastication:
1. Breakdown of foodstuffs into smaller „„ CONTROL OF MASTICATION
particles. Action of mastication is mostly a reflex pro­
2. Mixing of saliva with food substances cess. It is carried out voluntarily also. The
thoroughly. center for mastication is situated in medulla
3. Lubrication and moistening of dry food and cerebral cortex. The muscles of masti­
by saliva so that, the bolus can be cation are supplied by mandibular division
easily swallowed. of V cranial (trigeminal) nerve.
4. Appreciation of taste of the food.
Muscles of mastication: Deglutition or swallowing is the process
1. Masseter muscle. by which food passes from mouth into
2. Temporal muscle. stomach.
Chapter 37 ê Movements of Gastrointestinal Tract 213
Stages of Deglutition „„ PHARYNGEAL STAGE OR
Deglutition occurs in three stages:
1. Oral stage, when food moves from Pharyngeal stage is an involuntary stage.
mouth to pharynx. In this stage, the bolus is pushed from
2. Pharyngeal stage, when food moves pharynx into the esophagus. The pharynx
from pharynx to esophagus. is a common passage for food and air. It
3. Esophageal stage, when food moves divides into larynx and esophagus. Larynx
from esophagus to stomach. lies anteriorly and continues as respiratory
passage. Esophagus lies behind the larynx
„„ ORAL STAGE OR FIRST STAGE and continues as GI tract. Since pharynx
Oral stage is a voluntary stage. In this stage communicates with mouth, nose, larynx and
of swallowing, the bolus from oral cavity esophagus, during this stage of deglutition,
passes into the pharynx by means of series the bolus from the pharynx can enter into
of actions such as: four paths:
1. Bolus is placed over posterodorsal 1. It can come back into mouth.
sur­face of the tongue. It is called the 2. It can go upwards into nasopharynx.
pre­paratory position. 3. It can move forwards into larynx.
2. Anterior part of tongue is retracted and 4. It can move downwards into eso­
depressed. phagus.
3. Posterior part of tongue is elevated However, due to various coordinated
and retracted against hard palate. This movements, bolus is made to enter only
pushes the bolus backwards into the into the esophagus. The entrance of bolus
pharynx. through other paths is prevented as
4. Forceful contraction of tongue against follows.
the palate produces a positive pres­
sure in the posterior part of oral 1. Back into Mouth
cavity. This pressure in the oral cavity
also pushes the food into pharynx Return of bolus back into the mouth is
(Fig. 37.1). prevented by:

FIGURE 37.1: Stages of deglutition. A. Preparatory stage; B. Oral stage; C. Pharyngeal stage;
D. Esophageal stage.
214 Section 4 ê Digestive System

i. Position of tongue against the soft iii. At the same time, the peristaltic con­
palate (roof of the mouth). tractions start in the pharynx due to the
ii. High intraoral pressure developed by contraction of pharyngeal muscles.
the movement of tongue. iv. Elevation of larynx also lifts the glottis
away from the food passage.
2. Upward into Nasopharynx All the factors mentioned above act
together so that, the bolus moves easily into
The movement of bolus into the nasopharynx the esophagus. The whole process takes
from pharynx is prevented by elevation of place within 1 to 2 seconds. And this pro­
soft palate along with its extension called cess is purely involuntary.
3. Forward into Larynx THIRD STAGE

The movement of bolus into the larynx is It is also an involuntary stage. In esophageal
prevented by the following actions: stage food from stomach enters esophagus.
i. Approximation of the vocal cords. It the function of esophagus is to transport
ii. Forward and upward movement of the bolus from the pharynx to the stomach.
larynx. The movements of esophagus are speci­
fically organized for this function and the
iii. The backward movement of epiglot­
movements are called peristaltic waves.
tis to seal the opening of the larynx
Peristalsis means a wave of contraction
followed by the wave of relaxation of muscle
iv. All these movements arrest respiration
fibers of GI tract, which travel in aboral
for a few seconds. It is called deglutition
direction (away from mouth). By this type
apnea. of movement, the contents are propelled
Deglutition apnea down along the GI tract.

Apnea refers to temporary arrest of breath­ Role of Lower Esophageal Sphincter

ing. Deglutition apnea or swallowing apnea
is the arrest of breathing during deglutition. The distal 2 to 5 cm of esophagus acts like a
sphincter and it is called lower esophageal
sphincter. It is constricted always. When
4. Entrance of Bolus into Esophagus
bolus enters this part of the esophagus,
Since the other three paths are closed for this sphincter relaxes so that the contents
the bolus, it has to pass only through the enter the stomach. After the entry of bolus
esophagus. It occurs by the combined effects into the stomach, the sphincter constricts
of various factors: and closes the lower end of esophagus.
i. Upward movement of the larynx stret­ The relaxation and constriction of sphincter
ches the opening of the esophagus. occur in sequence with the arrival of peris­
ii. Simultaneously, the upper 3 to 4 cm taltic contractions of esophagus.
of esophagus relaxes. This part of the
esophagus is formed by the crico­
pharyn­geal muscle and it is called upper Though the beginning of swallowing is a
esophageal sphincter or pharyngo­eso­ voluntary act, later it becomes involuntary
phageal sphincter. and is carried out by a reflex action called
Chapter 37 ê Movements of Gastrointestinal Tract 215
deglutition reflex. It occurs during the pharyn­ „„ HUNGER CONTRACTIONS
geal and esophageal stages.
Hunger contractions are the movements
of empty stomach. These contractions are
related to the sensations of hunger.
When the bolus enters the oropharyngeal Hunger contractions are the peristaltic
region, the receptors present in this region waves superimposed over the contractions
are stimulated. of gastric smooth muscle as a whole. This
type of peristaltic waves is different from
Afferent Fibers the digestive peristaltic contractions. The
digestive peristaltic contractions usually
Afferent impulses from the oropharyngeal occur in body and pyloric parts of the
receptors pass via the glossopharyngeal stomach. But the peristaltic contractions of
nerve fibers to the deglutition center. empty stomach involve the entire stomach.

The deglutition center is at the floor of the
Receptive relaxation is the relaxation of the
fourth ventricle in medulla oblongata of
upper portion of the stomach when bolus
enters the stomach from esophagus. It invol­
ves the fundus and upper part of the body of
Efferent Fibers stomach. Its significance is to accom­modate
The impulses from deglutition center travel the food easily without much increase in
through glossopharyngeal and vagus ner­ pressure inside the stomach. This process is
ves (parasympathetic motor fibers) and called accommodation of stomach.
reach soft palate, pharynx and esophagus.
The glossopharyngeal nerve is concerned „„ PERISTALSIS OF STOMACH
with pharyngeal stage of swallowing. The When the food enters the stomach, the
vagus nerve is concerned with esophageal peristaltic contraction or peristaltic wave
stage. appears with a frequency of 3/min. It starts
from the lower part of the body of stomach,
Response passes through the pylorus till the pyloric
The reflex causes upward movement sphincter.
of soft palate to close nasopharynx and Initially, the contraction appears as a
upward movement of larynx to close respi­ slight indentation on the greater and lesser
ratory passage so that bolus enters the curvatures and travels towards pylorus. The
esophagus. Now the peristalsis occurs in contraction becomes deeper while trave­
esophagus pushing the bolus into stomach. ling. Finally, it ends with the constriction of
pyloric sphincter. Some of the waves disap­
pear before reaching the sphincter. Each
peristaltic wave takes about one minute to
The movements of the stomach area: travel from the point of origin to the point of
1. Hunger contractions. ending.
2. Receptive relaxation. This type of peristaltic contraction is called
3. Peristalsis of stomach. digestive peristalsis because it is respon­sible
216 Section 4 ê Digestive System

for the grinding of food particles and The gastric emptying is influenced by
mixing them with gastric juice for digestive various factors of the gastric content and
activities. food. The factors which affect gastric emp­
tying are given below.
„„ FILLING AND EMPTYING OF 1. Volume of gastric content
Gastric emptying is directly proportional to
„„ FILLING OF STOMACH the volume. If the content of stomach is
While taking food, the food arranges itself more, a large amount is emptied into the
in the stomach in different layers. The first intestine rapidly.
eaten food is placed against the greater
2. Consistency of gastric content
curvature in the fundus and body of the
stomach. The successive layers of food parti­ Emptying of the stomach depends upon
cles lie nearer the lesser curvature until the consistency (degree of density) of the
the last portion of food eaten lies near the contents. Liquids, particularly the inert liquids
upper end of lesser curvature, adjacent to like water (which do not stimulate the
cardiac sphincter. stomach) leave the stomach rapidly. Solids
move out of stomach only after being con­
„„ EMPTYING OF STOMACH verted into fluid or semifluid. Undigested
Gastric emptying is the process by which solid particles are not easily emptied.
the chyme from stomach is emptied into 3. Chemical composition
intestine. The food that is swallowed enters
the stomach and remains there for about 3 The chemical composition of the food also
hours. During this period, digestion takes plays an important role in the emptying of
place. The partly digested food becomes the stomach. Carbohydrates are emptied
the chyme. rapidly than the proteins. Proteins are
emptied rapidly than the fats.
4. pH of the gastric content
Chyme is the semisolid mass of partially
Gastric emptying is directly proportional to
digested food that is formed in the stomach.
pH of the chyme.
It is acidic in nature. The acid chyme is
emptied from stomach into the intes­tine 5. Osmolar concentration of gastric
slowly with the help of peristaltic contrac­ content
tions. It takes about 3 to 4 hours for emp­ The gastric content, which is isotonic to
tying of the chyme. This slow emptying is blood, leaves the stomach rapidly than the
necessary to facilitate the final digestion hypotonic or hypertonic content.
and maximum (about 80%) absorption
of the digested food materials from small
intestine. Gastric emptying occurs due to
the peristaltic waves in the body and pyloric Vomiting or emesis is the abnormal emp­
part of the stomach and simultaneous rela­ tying of stomach and upper part of intestine
xation of pyloric sphincter. through esophagus and mouth.
Chapter 37 ê Movements of Gastrointestinal Tract 217
„„ CAUSES OF VOMITING Sequence of events
1. The presence of irritating contents in 1. Beginning of antiperistalsis which runs
GI tract. from ileum towards the mouth through
2. Mechanical stimulation of pharynx. the intestine pushing the intestinal
3. Pregnancy. contents into the stomach within few
4. Excess intake of alcohol. minutes.
5. Nauseating sight, odor or taste. 2. Deep inspiration followed by temporary
6. Unusual stimulation of labyrinthine cessation of breathing.
appa­ratus as in the case of sea sick­ 3. Closure of glottis.
ness, air sickness, car sickness or 4. Upward and forward movement of
swinging. larynx and hyoid bone.
7. Abnormal stimulation of sensory recep­ 5. Elevation of soft palate.
tors in other organs like kidney, heart, 6. Contraction of diaphragm and abdomi­
semicircular canals or uterus. nal muscles with a characteristic jerk
8. Drugs like antibiotics, opiates, etc. resulting in elevation of intra-abdomi­
9. Any GI disorder. nal pressure.
10. Acute infection like urinary tract infec­ 7. Compression of the stomach between
diaphragm and abdominal wall leading
tion, influenza, etc.
to rise in intragastric pressure.
11. Metabolic disturbances like carbohy­
8. Simultaneous relaxation of lower
drate starvation and ketosis (pregnancy),
esophageal sphincter, esophagus and
uremia, ketoacidosis (diabetes) and
upper esophageal sphincter.
9. Forceful expulsion of gastric contents
(vomitus) through esophagus, pharynx
and mouth.
Nausea All the movements during the act of
vomiting throw the vomitus (materials ejec­
Vomiting is always preceded by nausea.
ted during vomiting) to the exterior through
Nausea is unpleasant sensation which
mouth. Some of the movements play impor­
induces the desire for vomiting. It is charac­
tant roles by preventing the entry of vomitus
terized by secretion of large amount of through other routes and thereby prevent
saliva containing more amount of mucus. the adverse effect of the vomitus on many
Retching Such movements are:
Strong involuntary movements in the GI 1. Closure of glottis and cessation of
tract start even before actual vomiting and breathing prevent entry of vomitus into
intensify the feeling of vomiting. This condi­ the lungs.
tion is called retching (try to vomit). And, 2. Elevation of soft palate prevents entry
vomiting occurs few minutes after this. of vomitus into the nasopharynx.
3. Larynx and hyoid bone move upward
Act of Vomiting and forward and are placed in this
position rigidly. This causes the dila­
Act of vomiting involves series of move­ tation of throat which allows free exit of
ments that takes place in GI tract. vomitus.
218 Section 4 ê Digestive System

„„ VOMITING REFLEX which occur regularly or irregularly but in

a rhythmic fashion. So, these movements
Vomiting is a reflex act. The sensory impul­
are also called rhythmic segmentation con­
ses for vomiting arise from the irritated or
distended part of GI tract or other organs The contractions occur at regularly
and are transmitted to the vomiting center spaced intervals along a section of intestine.
through vagus and sympathetic fibers. The segment of the intestine involved in
The vomiting center is situated bilaterally each contraction is about 1 to 5 cm long.
in medulla oblongata near the nucleus The segments of intestine in between the
tractus solitarius. contracted segments are relaxed. The length
Motor impulses from the vomiting center of the relaxed segments is same as that of
are transmitted through V, VII, IX, X and XII the contracted segments. These alternate
cranial nerves to the upper part of GI tract; segments of contraction and relaxation give
and through spinal nerves to diaphragm appearance of rings resembling the chain
and abdominal muscles. of sausages.
After sometime, the contracted segments
„„ MOVEMENTS OF are relaxed and the relaxed segments are
SMALL INTESTINE contracted (Fig. 37.2). Therefore, the seg­
mentation contractions chop the chyme
The movements of small intestine are essen­ many times. This helps in mixing of chyme
tial for mixing the chyme with digestive with digestive juices.
juices, propulsion of food and absorption.
Four types of movements occur in small Pendular Movement
1. Mixing movements: Pendular movement is the sweeping move­
i. Segmentation movements. ment of small intestine resembling the
ii. Pendular movements.
2. Propulsive movements:
i. Peristaltic movements.
ii Peristaltic rush.
3. Peristalsis in fasting – migrating motor
4. Movements of villi.

The mixing movements of small intestine are
responsible for proper mixing of chyme with
digestive juices like pancreatic juice, bile
and intestinal juice. The mixing movements
of small intestine are segmentation con­
tractions and pendular movements.

Segmentation Contractions
The segmentation contractions are the com­
mon type of movements of small intestine, FIGURE 37.2: Movements of small intestine
Chapter 37 ê Movements of Gastrointestinal Tract 219
movements of pendulum of clock. Small por­ „„ PERISTALSIS IN FASTING –
tions of intestine (loops) sweep forward and MIGRATING MOTOR COMPLEX
backward or upward and downward. It is a It is a type of peristaltic contraction, which
type of mixing movement noticed only by occurs in stomach and small intestine during
close observation. the periods of fasting for several hours.
It helps in mixing of chyme with digestive It is different from the regular peristalsis
juices. because, a large portion of stomach or
intestine is involved in the contraction. The
„„ PROPULSIVE MOVEMENTS contraction extends to about 20 to 30 cm
Propulsive movements are the movements of the stomach or intestine. This type of
movement occurs once in every 1½ to 2
of small intestine which push the chyme
in the aboral direction through intestine.
It starts as a moderately active peris­
The propulsive movements are peristaltic talsis in the body of stomach and runs
movements and peristaltic rush. through the entire length of small intestine.
It travels at a velocity of 6 to 12 cm/min.
Peristaltic Movements Thus, it takes about 10 minutes to reach the
Peristalsis is defined as the wave of colon after taking origin from stomach.
contraction followed by wave of relaxation,
which travels in aboral direction. The stimu­ Significance of Peristalsis in Fasting
lation of smooth muscles of intestine initia­ The migrating motor complex sweeps the
tes the peristalsis. It travels from point of excess digestive secretions into the colon
stimulation in both directions. But under and prevents the accumulation of the
normal conditions, the progress of contrac­ secre­tions in stomach and intestine. It also
tion in an oral direction is inhibited quickly sweeps the residual undigested materials
and the contractions disappear. Only the into colon.
contraction that travels in an aboral direc­
tion persists. „„ MOVEMENTS OF VILLI
The Intestinal villi also show movements
Peristaltic Rush simultaneously along with intestinal move­
Sometimes, the small intestine shows a ments. It is because of the extension of
powerful peristaltic contraction. It is caused smooth muscle fibers of the intestinal wall
by excessive irritation of intestinal mucosa into the villi.
The movements of villi are shortening
or extreme distention of the intestine.
and elongation, which occur alternatively
This type of powerful contraction begins
and help in emptying lymph from the
in duode­num and passes through entire central lacteal into the lymphatic system.
length of small intestine and reaches the The surface area of villi is increased dur­
ileocecal valve within few minutes. This is ing elongation. This helps absorption of
called peristaltic rush or rush waves. diges­ted food particles from the lumen of
The peristaltic rush sweeps the contents intestine.
of intestine into the colon. Thus, it relieves Movements of villi are caused by local
the small intestine off either irritants or nervous reflexes, which are initiated by the
excessive distention. presence of chyme in small intestine.
220 Section 4 ê Digestive System


LARGE INTESTINE Mass movement drives the feces into sig­
Large intestine shows sluggish movements. moid or pelvic colon. In the sigmoid colon,
Still, these movements are important for the feces is stored. The desire for defecation
occurs when some feces enters rectum due
mixing, propulsive and absorptive functions.
to the mass movement. Usually, the desire
Large intestine shows two types of move­ for defecation is elicited by an increase
ments: in the intrarectal pressure to about 20 to
1. Mixing Segmentation 25 cm H2O.
: The usual stimulus for defecation is
movements contractions.
intake of liquid like coffee or tea or water.
2. Propulsive
: Mass peristalsis. But it differs from person to person.
Act of Defecation
SEGMENTATION CONTRACTIONS The act of defecation is preceded by volun­
tary efforts like assuming an appropriate
Large circular constrictions, which appear posture, voluntary relaxation of external
in the colon, are called mixing segmenta­ sphincter and the compression of abdominal
tion contractions. The contractions occur at
regular distance in colon. The length of the
portion of colon involved in each contraction
is nearly about 2.5 cm.

Mass peristalsis or mass movement propels
the feces from colon towards anus. Usually,
this movement occurs only a few times every
day. The duration of the mass movement is
about 10 minutes in the morning before or
after breakfast. This is because of the neuro­
genic factors like gastrocolic reflex (see below)
and parasympathetic stimulation.

Voiding of feces is known as defecation.
Feces is formed in the large intestine and
stored in sigmoid colon. By the influence FIGURE 37.3: Defecation reflex. Afferent and
of an appropriate stimulus, it is expelled efferent fibers of the reflex pass through pelvic
(parasympathetic) nerve. Voluntary control of
out through the anus. This is prevented by
defe­cation is by pudendal (somatic) nerve. Defe­
tonic constriction of anal sphincters, in the cation center is in the sacral segments of spinal
absence of the stimulus. cord.
Chapter 37 ê Movements of Gastrointestinal Tract 221
contents by voluntary contraction of abdo­ This reflex causes only a weak con­
minal muscles. traction of rectum. But, it initiates defecation
Usually, the rectum is empty. During reflex.
the development of mass movement, the
feces is pushed into rectum and the defe­ „„ PATHWAY FOR
cation reflex is initiated. The process of DEFECATION REFLEX
defecation involves the contraction of When rectum is distended due to the entry
rectum and relaxation of internal and exter­ of feces by mass movement, sensory nerve
nal anal sphincters. endings are stimulated. The impulses from
The internal anal sphincter is made the nerve endings are transmitted via
up of smooth muscle and it is innervated afferent fibers of pelvic nerve to the defe­
by parasympathetic nerve fibers via pelvic cation center, situated in sacral segments
nerve. The external anal sphincter is com­ (center) of spinal cord.
posed of skeletal muscle and it is controlled The center, in turn sends motor impul­
by somatic nerve fibers, which pass through ses to the descending colon, sigmoid
pudendal nerve. The pudendal nerve always colon and rectum via efferent nerve fibers
keeps the external sphincter constricted of pelvic nerve. The motor impulses cause
and the sphincter can relax only when the strong contraction of descending colon,
pudendal nerve is inhibited. sigmoid colon and rectum and relaxation
of internal sphincter.
Gastrocolic Reflex Simultaneously, voluntary relaxation of
external sphincter occurs. It is due to the
Gastrocolic reflex is the contraction of rectum inhibition of pudendal nerve by impulses
followed by desire for defecation caused by arising from cerebral cortex (Fig. 37.3).
distention of stomach by food. It is mediated Failure of voiding of feces is called con­
by intrinsic nerve fibers of GI tract. stipation (refer Chapter 36).
222 Questions in Digestive System


„„ LONG QUESTIONS 12. Gastrin.

13. Peptic ulcer.
1. What are the different types of salivary 14. Properties and composition of pan­
glands? Describe the composition, creatic juice.
functions and regulation of secretion 15. Functions of pancreatic juice.
of saliva. 16. Regulation of exocrine function of pan­
2. Describe the different phases of gastric creas.
secretion with experimental evidences. 17. Steatorrhea.
3. Explain the composition, functions and 18. Secretin.
regulation of secretion of pancreatic 19. Cholecystokinin.
juice. 20. Composition of bile.
4. Describe the composition, functions and 21. Functions of bile.
regulation of secretion of bile. Enume­ 22. Bile salts/bile pigments.
rate the differences between the liver 23. Enterohepatic circulation.
bile and gallbladder bile. Add a note on 24. Functions of liver.
enterohepatic circulation. 25. Differences between liver bile and gall­
bladder bile.
„„ SHORT QUESTIONS 26. Functions of gallbladder.
27. Jaundice.
1. Properties and composition of saliva. 28. Succus entericus.
2. Functions of saliva. 29. Functions of small intestine.
3. Nerve supply to salivary glands. 30. Functions of large intestine.
4. Glands of stomach. 31. Mastication.
5. Functions of stomach. 32. Swallowing.
6. Properties and composition of gastric 33. Movements of stomach.
juice. 34. Filling and emptying of stomach.
7. Functions of gastric juice. 35. Vomiting.
8. Mechanism of secretion of hydrochloric 36. Movements of small intestine.
acid in stomach. 37. Movements of large intestine.
9. Pavlov’s pouch. 38. Defecation.
10. Sham feeding. 39. Constipation.
11. Cephalic phase of gastric secretion. 40. Diarrhea.
Section 5
Renal Physiology and Skin

38. Overview of Kidney.................................................................. 225
39. Nephron................................................................................... 228
40. Juxtaglomerular Apparatus...................................................... 234
41. Renal Circulation...................................................................... 238
42. Urine Formation....................................................................... 241
43. Concentration of Urine............................................................. 250
44. Acidification of Urine and Role of
Kidney in Acid-base Balance.................................................... 256
45. Renal Function Tests................................................................ 260
46. Micturition................................................................................. 263
47. Skin.......................................................................................... 268
48. Body Temperature.................................................................... 273
Chapter 38

Overview of Kidney


„„ INTRODUCTION homeostasis. Thus, the functions of kidneys

are detailed below.
Excretion is the process by which the unwan­
ted substances and metabolic wastes are
eliminated from the body.
Although various organs such as GI tract, The primary function of kidneys is homeo­
liver, skin and lungs are involved in removal stasis. It is accomplished by the formation of
of wastes from the body, their excre­ tory urine. During the formation of urine, kidneys
capacity is limited. But, the renal system regulate various activities in the body, which
or urinary system has maximum capacity of are concerned with homeostasis as detailed
excretory function. below.
Renal system includes:
1. A pair of kidneys. i. Excretion of Waste Products
2. Ureters.
3. Urinary bladder. Kidneys excrete the unwanted waste pro­
4. Urethra. ducts which are formed during metabolic
Kidneys produce the urine. Ureters trans­ activities:
port the urine to urinary bladder. Urinary a. Urea: End product of amino acid meta­
bladder stores urine until it is voided (emptied). bolism.
Urine is voided from bladder through urethra b. Uric acid: End product of nucleic acid
(Fig. 38.1). metabolism.
c. Creatinine: End product of metabolism
in muscles.
d. Bilirubin: End product of hemoglobin
Kidneys perform several vital functions degradation.
besides formation of urine. By excreting e. Products of metabolism of other sub­
urine, kidneys play the principal role in stances.
226 Section 5 ê Renal Physiology and Skin

these organs, kidneys play major role in

preventing acidosis.

Kidneys stimulate the production of erythro­
cytes by secreting erythropoietin. Erythro­
poietin is the important stimulating factor
for erythropoiesis (refer Chapter 9). Kidney
also secretes another factor called thrombo­
poietin, which stimulates the production of
thrombocytes (refer Chapter 16).

Kidneys secrete many hormonal substan­
FIGURE 38.1: Urinary system ces in addition to erythropoietin and thrombo­
poietin (refer Chapter 56). The hormones
f. Harmful foreign chemical substances: secreted by kidneys are:
Toxins, drugs, heavy metals, pesti­ i. Erythropoietin.
cides, etc. ii. Thrombopoietin.
iii. Renin.
ii. Maintenance of Water Balance iv. 1,25-dihydroxycholecalciferol (calcitriol).
v. Prostaglandins.
Kidneys maintain the water balance in the
body by conserving water when it is decre­
ased and excreting water when it is excess
in the body (refer Chapter 4 for details).
Kidneys play an important role in long-term
iii. Maintenance of Electrolyte Balance regulation of arterial blood pressure (refer
Chapter 71) by two ways by regulating
Maintenance of electrolyte balance, espe­
ECF volume and through renin-angiotensin
cially sodium is in relation to water balance.
Kidneys retain sodium if the osmolarity of
body water decreases and eliminate sodium
when osmolarity increases. „„ 5. REGULATION OF BLOOD
iv. Maintenance of Acid-base Balance Kidneys play a role in the regulation of blood
calcium level by activating 1,25-dihydro­
The pH of the blood and body fluids should
xycholecalciferol into vitamin D. Vitamin D
be maintained within narrow range for
is necessary for the absorption of calcium
healthy living. It is achieved by the func­
from intestine (refer Chapter 52).
tion of kidneys (refer Chapter 44). Body is
under constant threat to develop acidosis,
because of production of lot of acids
during metabolic activities. However, it is KIDNEY
prevented by kidneys, lungs and blood Kidney is a compound tubular gland
buffers, which eliminate these acids. Among covered by a connective tissue capsule.
Chapter 38 ê Overview of Kidney 227
There is a depression on the medial border
of kidney called hilum, through which renal
artery, renal veins, nerves and ureter pass.


The components of kidney are arranged in
three layers (Fig. 38.2):
1. Outer cortex.
2. Inner medulla.
3. Renal sinus.

1. Outer Cortex
Cortex is dark and granular in appearance.
It contains renal corpuscles and convoluted
FIGURE 38.2: Longitudinal section of kidney
tubules. At intervals, cortical tissue pene­
trates medulla in the form of columns, iii. Branches of nerves and arteries and
which are called renal columns or columns tributaries of veins.
of Bertin. iv. Loose connective tissues and fat.

2. Inner Medulla „„ PARENCHYMA OF KIDNEY

Medulla contains tubular and vascular Parenchyma of kidney is made up of tubular

structures arranged in parallel radial lines. structures called uriniferous tubules. The
It is divided into 8 to 18 medullary or uriniferous tubules are of two types:
Malpighian pyramids. 1. Terminal or secretary tubules called
nephrons, which are concerned with
formation of urine.
3. Renal Sinus
2. Collecting ducts or tubules which are
Renal sinus consists of the following struc­ concerned with transport of urine from
tures: nephrons to pelvis of ureter.
i. Upper expanded part of ureter called The collecting ducts unite to form ducts
renal pelvis. of Bellini, which open into minor calyces
ii. Subdivisions of pelvis, 2 or 3 major through papilla. Other details are given in
calyces and about 8 minor calyces. Chapter 39.
Chapter 39




Nephron is defined as the structural and
functional unit of kidney. Each kidney con­ Renal corpuscle is situated in the cortex of
sists of 1 to 1.3 million of nephrons. The the kidney either near the periphery or near
number of nephrons decreases in old age. the medulla. Based on the situation of renal
Each nephron is formed by two parts corpuscle, the nephrons are classified into
(Fig. 39.1): two types:
1. A blind end called renal corpuscle or
1. Cortical nephrons or superficial neph­
Malpighian corpuscle.
2. A tubular portion called renal tubule.
2. Juxtamedullary nephrons.

1. Cortical Nephrons
The renal corpuscle is also known as Mal­
pighian corpuscle. It is a spheroidal and Cortical nephrons are the nephrons, which
slightly flattened structure with a diameter have their corpuscles in the outer cortex of
of about 200 µ. The function of the renal the kidney near the periphery (Fig. 39.2). In
corpuscle is the filtration of blood which human kidneys 85% nephrons are cortical
forms the first phase of urine formation. nephrons.
Chapter 39 ê Nephron 229

FIGURE 39.1: Structure of nephron

2. Juxtamedullary Nephrons
Juxtamedullary nephrons are the nephrons
which have their corpuscles in the inner cortex
near medulla or corticomedullary junction.
The features of the two types of neph­
rons are given in Table 39.1.

The renal corpuscle is formed by two portions:
1. Glomerulus.
2. Bowman’s capsule.
FIGURE 39.2: Types of nephron
Glomerulus divides into many small capillaries. These small
Glomerulus is a tuft of capillaries enclosed capillaries are arranged in irregular loops and
by Bowman’s capsule. These capillaries are form anastomosis. All the smaller capil­laries
disposed between afferent arteriole efferent finally reunite to form the efferent arteriole
arteriole. Thus, the vascular system in the which leaves the Bowman’s capsule.
glomerulus is purely arterial (Fig. 39.3). The diameter of the efferent arteriole
The glomerular capillaries arise from is less than that of afferent arteriole. This
the afferent arteriole. After entering the difference in diameter has functional signi­
Bowman’s capsule, the afferent arteriole ficance.
230 Section 5 ê Renal Physiology and Skin

TABLE 39.1: Features of two types of nephron

Features Cortical nephron Juxtamedullary nephrons

Situation of renal corpuscle Outer cortex near the periphery Inner cortex near medulla
Short Long
Loop of Henle Hairpin bend penetrates only up Hairpin bend penetrates up to
to outer zone of medulla the tip of papilla
Blood supply to tubule Peritubular capillaries Vasa recta
Mainly the concentration of
Function Formation of urine
urine and formation of urine

Visceral layer covers the glomerular capil­

laries. It is continued as the parietal layer at
the visceral pole. The parietal layer is conti­
nued with the wall of the tubular portion of
nephron. The cleft-like space between the
visceral and parietal layers is continued as
the lumen of the tubular portion.

Functional Histology
Both the layers of Bowman’s capsule are
composed of a single layer of flattened
epithelial cells resting on a basement mem­
brane. The basement membrane of the
visceral layer fuses with the basement mem­
FIGURE 39.3: Renal corpuscle brane of glomerular capillaries on which
the capillary endothelial cells are arranged.
The capillaries are made up of single Thus, the basement membranes, which are
layer of endothelial cells which are attached fused together, form the sepa­ration between
to a basement membrane. The endothelium the glomerular capillary endothelium and
has many pores called fenestra or filtration the epithelium of visceral layer of Bowman’s
pores. The diameter of each pore is 0.1 µ. capsule.
The presence of the fenestra is evidence of The epithelial cells of the visceral layer
the filtration function of the glomerulus. fuse with the basement membrane but the
fusion is not complete. Each cell is con­
Bowman’s Capsule
nected with the basement membrane by
Bowman’s capsule encloses the glome­ cytoplasmic extensions of epithelial cells
rulus. The structure of Bowman’s capsule called pedicles or feet. These pedicles are
is similar to a funnel with filter paper. Its arranged in an interdigitating manner
diameter is 200 µ. leaving small cleft-like spaces in between.
It is formed by two layers: The cleft-like space is called slit pore. The
1. The inner visceral layer. epithelial cells with pedicles are called
2. The outer parietal layer. podocytes (Fig. 39.4).
Chapter 39 ê Nephron 231
Loop of Henle consists of:
i. Descending limb.
ii. Hairpin bend.
iii. Ascending limb.

Descending Limb
Descending limb of loop of Henle is made
up of thick descending segment and thin
descending segment. The thick descending
segment is the direct continuation of the
proximal convoluted tubule. It descends
down into medulla. It has a length of 6
FIGURE 39.4: Filtering membrane in renal mm and a diameter of 55 µ. The thick des­
corpuscle. It is formed by capillary endothelium
cending segment of Henle’s loop is conti­
on one side (red) and visceral layer of Bowman’s
capsule (yellow) on the other side.
nued as thin descending segment (Fig.


The thin descending segment is continued
The tubular portion of nephron is the conti­ as hairpin bend of the loop. The hairpin bend
nuation of Bowman’s capsule. It is made up is continued as the ascending segment of
of three parts: loop of Henle.
1. The proximal convoluted tubule.
2. Loop of Henle. Ascending Limb
3. The distal convoluted tubule.
Ascending limb of Henle’s loop has two
parts, thin ascending segment and thick
ascending segment. Thin ascending seg­
It is the coiled portion arising from Bowman’s ment is the continuation of hairpin bend.
capsule. It is situated in the cortex. It is The total length of thin descending
continued as descending limb of loop of segment, hairpin bend and thin ascending
Henle. Length of proximal convoluted segment of Henle’s loop 10 to 15 mm and
tubule is 14 mm and the diameter is 55 µ. the diameter is 15 µ.
The thin ascending segment is conti­
Functional Histology nued as thick ascending segment. It is
about 9 mm long with a diameter of 30 µ.
Proximal convoluted tubule is formed by
Thick ascending segment ascends to the
single layer of cuboidal epithelial cells.
cortex and continues as distal convoluted
The special feature of these cells is the
pre­sence of hair-like projections directed
towards the lumen of the tubule. Because
Length and Extent of Loop of Henle
of the presence of these projections, the
epithelial cells are called brush-bordered The length and the extent of the loop of
cells. Henle vary in different nephrons:
232 Section 5 ê Renal Physiology and Skin

FIGURE 39.5: Parts of nephron

1. In cortical nephrons, it is short and the „„ DISTAL CONVOLUTED TUBULE

hairpin bend penetrates only up to
It is the continuation of thick ascending
outer medulla.
2. In juxtamedullary nephrons, this is segment and occupies the cortex of kidney.
long and the hairpin bend extends It is continued as collecting duct. The
deep into the inner medulla. In some length of the distal convoluted tubule is
nephrons it even runs up to the papilla. 14.5 to 15 mm. It has a diameter of 22 to
50 µ.
Functional Histology
Functional Histology
Thick descending segment is formed by
brush-bordered cuboidal epithelial cells. Distal convoluted tubule is lined by single
Thin descending segment, hairpin bend layer of cuboidal epithelial cells without
and thin ascending segment are lined by brush border. The epithelial cells in distal
flattened epithelial cells without brush border. convoluted tubule are called intercalated
Thick ascending segment is lined by cuboidal cells (I cells).
epithelial cells without brush border.
The terminal portion of thick ascending „„ COLLECTING DUCT
segment which runs between the afferent
and efferent arterioles of the same nephrons The distal convoluted tubule continues as
forms the macula densa. Macula densa is the initial or arched collecting duct, which
the part of juxtaglomerular apparatus. is in cortex. The lower part of the collecting
Chapter 39 ê Nephron 233
duct lies in medulla. 7 to 10 initial collecting Passage of Urine
ducts unite to form the straight collecting At the inner zone of medulla, the straight
duct, which passes through medulla. collecting ducts from each medullary pyra­
The length of the collecting duct is 20 mid unite to form papillary ducts or ducts of
to 22 mm. The diameter of collecting duct Bellini, which open into the papilla. Papilla
varies between 40 and 200 µ. collects the urine from each medullary pyra­
mid and drains into a minor calyx. Three or
Functional Histology four minor calyces unite to form one major
calyx. Each kidney has got about 8 minor
The collecting duct is formed by cuboidal calyces and 2 to 3 major calyces. The major
or columnar epithelial cells. The epithelial calyces open into the pelvis of the ureter.
cells of collecting duct are of two types: The pelvis is the expanded portion of ureter
1. The principal or P cells. present in the renal sinus. Through ureter,
2. Intercalated or I cells. urine enters the urinary bladder.
Chapter 40

Juxtaglomerular Apparatus


Juxtaglomerular apparatus is a specialized
organ situated near the glomerulus of each These cells are situated in the triangular region
nephron (juxta = near). bound by afferent arteriole, efferent arte­riole
and macula densa. These cells are also called
„„ STRUCTURE OF agranular cells, lacis cells.
JUXTAGLOMERULAR Extraglomerular mesangial cells secrete
APPARATUS prostaglandin and cytokines.

The juxtaglomerular apparatus is formed by Glomerular Mesangial Cells

three different structures (Fig. 40.1):
1. Macula densa. Glomerular mesangial cells or intraglome­
2. Extraglomerular mesangial cells. rular mesangial cells are situated in bet­
3. Juxtaglomerular cells. ween the glomerular capillaries and form a
cellular network which supports the capillary
„„ 1. MACULA DENSA loops. These cells are contractile in nature
and play an important role in regulating the
Macula densa is the terminal portion of thick glomerular filtration.
ascending segment that runs in between The glomerular mesangial cells are also
afferent and efferent arterioles of the same phagocytic and secrete matrix of glomerular
nephron. Actually, it is very close to afferent interstitium, prostaglandins and cytokines.
arteriole. In this part of thick ascending seg­
ment, the cuboidal epithelial cells are tightly „„ 3. JUXTAGLOMERULAR CELLS
Macula densa plays an important role in Juxtaglomerular cells are situated in the
tubuloglomerular feedback mechanism. It wall of afferent arteriole just before it enters
also secretes thromboxane A2. the Bowman’s capsule. This part of the
Chapter 40 ê Juxtaglomerular Apparatus 235

FIGURE 40.1: Juxtaglomerular apparatus

afferent arteriole is thickened like a cuff Stimulants for Renin Secretion

and it is called polar cushion or polkissen. Secretion of renin is stimulated by four
Juxtaglomerular cells which are the special­ factors:
ized type of smooth muscle cells derived 1. Fall in arterial blood pressure.
from the tunica media and tunica adventitia 2. Reduction in the ECF volume.
of wall of the afferent arteriole. Because of 3. Increased sympathetic activity.
the presence of secretary granules in their 4. Decreased load of sodium and chloride
cytoplasm, the juxtaglomerular cells are in macula densa.
also called granular cells.
Renin-angiotensin System
„„ FUNCTIONS OF When renin is released into the blood, it acts
JUXTAGLOMERULAR on a specific plasma protein called angio­
APPARATUS tensinogen or renin substrate. It is the α2
globulin. By the activity of renin, the angio­
The primary function of juxtaglomerular appa­ tensinogen is converted into a deca­ pep­
ratus is the secretion of hormonal substan­ tide called angiotensin I. Angiotensin I is
ces. It also regulates the glomerular blood converted into angiotensin II which is an
flow and glomerular filtration rate. octapeptide by the activity of angiotensin-
converting enzyme (ACE) secreted from
„„ SECRETION OF RENIN lungs. Most of the conversion of angiotensin
I into angiotensin II takes place in lungs.
The juxtaglomerular cells secrete renin. Angiotensin II has a short half-life of about
Renin is a peptide with 340 amino acids. 1 to 2 minutes. Then it is rapidly degraded
Along with angiotensins, renin forms the into a heptapeptide called angiotensin III by
renin-angiotensin system which is a hor­ angiotensinases which are present in RBCs
mone system that plays an important role and vascular beds in many tissues. Angio­
in the maintenance of blood pressure (refer tensin III is converted into angiotensin IV
Chapter 71). which is a hexapeptide (Fig. 40.2).
236 Section 5 ê Renal Physiology and Skin

Actions of Angiotensins is a general vasocons­trictor (refer

Angiotensin I Chapter 71).
2. On adrenal cortex:
It is physiologically inactive and serves only It stimulates zona glomerulosa of
as the precursor of angiotensin II. adre­nal cortex to secrete aldosterone.
Angiotensin II Aldosterone acts on renal tubules and
increases retention of sodium which is
Angiotensin II is the most active form. Its also responsible for elevation of blood
actions are given below:
1. On blood vessels:
3. On kidney:
i. Angiotensin II increases arterial
i. Angiotensin II regulates glomerular
blood pressure by directly acting
on the blood vessels and causing filtration rate by two ways:
vasoconstriction. It is a potent con­ a. It constricts the efferent arteriole
strictor of arterioles. Earlier, when which causes decrease in filtra­
its other actions were not found it tion after an initial increase (refer
was called hypertension. Chapter 42).
ii. It increases blood pressure indirectly b. It contracts the glomerular mes­
also by increasing the release of an­gial cells leading to decre­ase
noradrenaline from post­gang­lionic in surface area of glome­ rular
sympathetic fibers. Noradrenaline capillaries and filtration.

FIGURE 40.2: Renin-angiotensin system

Chapter 40 ê Juxtaglomerular Apparatus 237
ii. It increases sodium reabsorption adrenal cortex. It has 100% adrenal cortical-
from renal tubules. This action is more stimulating activity and 40% vasopressor
predominant on proximal tubules. activity of angiotensin II.
4. On brain:
i. Angiotensin II inhibits the baro­ Angiotensin IV
receptor reflex and thereby indi­
It also has adrenal cortical stimulating and
rectly increases the blood pressure.
vasopressor activities.
Baroreceptor reflex is responsible
for decreasing the blood pressure
(refer Chapter 71). „„ SECRETION OF
ii. It increases water intake by stimu­ OTHER SUBSTANCES
lating the thirst center.
The extraglomerular mesangial cells of
iii. It increases the secretion of corti­
glomerular apparatus secrete prosta­
cotropin-releasing hormone (CRH)
from hypothalamus. CRH in turn glandin (refer Chapter 56). In vitro secre­
increases secretion of adrenocorti­ tion of cytokines like IL-2 and TNF (refer
cotropic hormone (ACTH) from Chapter 15) by the mesangial cells is obser­
pituitary. ved recently. Macula densa secretes throm­
iv. It increases secretion of antidiu­ boxane A2.
retic hormone (ADH) from hypo­
Angiotensin II acts as a growth factor FILTRATION RATE
in heart and it is thought to cause mus­
cular hypertrophy and cardiac enlarge­ Macula densa of juxtaglomerular apparatus
ment. plays an important role in the feedback
mechanism called tubuloglomerular feed­
Angiotensin III back mechanism, which regulates the renal
Angiotensin III increases the blood pressure blood flow and glomerular filtration rate
and stimulates aldosterone secretion from (refer Chapter 42 for details).
Chapter 41

Renal Circulation


„„ INTRODUCTION pyramid, it turns and runs parallel to the

base of pyramid forming arcuate artery.
Blood vessels of kidneys are highly speciali­
zed to facilitate the functions of the neph­ Each arcuate artery gives rise to interlo­
rons in the formation of urine. Renal arteries bular arteries. The interlobular arteries run
supply the blood to the kidneys. through the renal cortex perpendi­cular to
In the adults, during resting condi­ arcuate artery. From each interlobular artery,
tions both the kidneys receive 1,300 mL numerous afferent arterioles arise.
of blood per minute or about 26% of the The afferent arteriole enters the Bowman’s
cardiac output. Kidneys are the second capsule and forms glomerular capillary
organs to receive maximum blood flow, the tuft. The afferent arteriole divides into 4
first organ being the liver which receives or 5 large capillaries. Each large capillary
1,500 mL per minute. The maximum blood divides into small capillaries, which form
supply to kidneys has got the functional


Renal artery arises directly from abdominal
aorta and enters the kidney through the
hilus. While passing through renal sinus, the
renal artery divides into many segmental
arteries, which subdivide into interlobar
arteries (Fig. 41.1).
Each interlobar artery passes in between
the medullary pyramids. At the base of the FIGURE 41.1: Renal blood vessels
Chapter 41 ê Renal Circulation 239
the loops. And, the capillary loops unite to
form the efferent arteriole, which leaves the
Bowman’s capsule.
The efferent arterioles form a second
capillary network called peritubular capil­
laries which surround the tubular portions
of the nephrons. Thus, the renal circulation
forms a portal system by the presence of
two sets of capillaries – glomerular capil­
laries and peritubular capillaries.
The peritubular capillaries are found
around the tubular portion of cortical neph­
rons only. The tubular portion of juxta­
medullary nephrons are supplied by some
specialized capillaries called vasa recta.
Vasa recta arise directly from the efferent
arteriole of the juxtamedullary nephrons
and run parallel to the renal tubule into the
medulla and ascend up towards the cortex
(Fig. 41.2).
The peritubular capillaries and vasa
recta drain into the venous system. Venous
system starts with peritubular venules and
continues as interlobular veins, arcuate veins,
interlobar veins, segmental veins and finally
the renal vein (Fig. 41.3).

FIGURE 41.3: Schematic diagram showing

renal blood flow

Renal vein leaves the kidney through

the hilus and joins inferior vena cava.

The blood flow to kidneys is measured by
using plasma clearance of para-aminohip­
puric acid (refer Chapter 45).

The regulation of renal blood flow is mostly
FIGURE 41.2: Renal capillaries by autoregulation. The nerves innervating
240 Section 5 ê Renal Physiology and Skin

renal blood vessels have no significant „„ SPECIAL FEATURES OF RENAL

role in this. CIRCULATION

„„ AUTOREGULATION The renal circulation has some special featu­

res to cope up with the functions of the
The intrinsic ability of an organ to regulate kidneys. Such special features are:
its own blood flow is called autoregulation 1. The renal arteries arise directly from
(refer Chapter 102). Autoregulation is pre­ the aorta. So the pressure in aorta is
sent in some vital organs in the body such very high and it facilitates a high blood
as brain, heart and kidneys. It is highly flow to the renal parenchyma.
2. Kidneys receive about 1,300 mL of blood
significant and more efficient in kidneys.
per minute, i.e. about 26% of car­diac
output. Kidneys are the second organs
Renal Autoregulation
to receive maximum blood flow, the first
Renal autoregulation is important to main­ organ being the liver which receives
tain the glomerular filtration rate (GFR). 1,500 mL per minute, i.e. about 30% of
Blood flow to kidneys remains normal even cardiac output.
when the mean arterial blood pressure vary 3. Whole amount of blood which flows to
kidney has to pass through the glome­
widely between 60 and 180 mm Hg. This
rular capillaries before entering the
helps to maintain normal GFR. venous system. Because of this, the
Two mechanisms are involved in renal blood is completely filtered at the renal
autoregulation: glomeruli.
1. Myogenic response. 4. Renal circulation has a portal system,
2. Tubuloglomerular feedback. i.e. a double network of capillaries namely
glomerular capillaries and peritubular
1. Myogenic Response capillaries.
5. Renal glomerular capillaries form high
Whenever the blood flow to kidneys incre­
pressure bed with a pressure of 60 to
ases, it stretches the elastic wall of the 70 mm Hg. It is much greater than the
afferent arteriole. Stretch of the vessel wall capillary pressure elsewhere in the
increases the flow of calcium ions from body, which is only about 25 to 30 mm
extracellular fluid into the cells. The influx Hg. High pressure is maintained in
of calcium ions leads to the contraction of the glomerular capillaries because the
smooth muscles in afferent arteriole which diameter of afferent arteriole is more
causes constriction of afferent arteriole. So, than that of efferent arteriole. The high
the blood flow is decreased. capillary pressure augments glome­
rular filtration.
2. Tubuloglomerular Feedback 6. The peritubular capillaries form a low
pressure bed with a pressure of 8 to 10
Macula densa plays an important role in mm Hg. This low pressure helps tubu­
tubu­loglomerular feedback which controls lar reabsorption.
the renal blood flow and GFR (refer Chapter 7. The autoregulation of renal blood flow
42 for details). is well established.
Chapter 42

Urine Formation


„„ INTRODUCTION The mechanism of urine formation inclu­

des three processes:
Urine formation is a blood-cleansing func­ 1. Glomerular filtration.
tion. Normally, about 26% of cardiac output 2. Tubular reabsorption.
enters the kidneys to get rid of unwanted 3. Tubular secretion.
substances. Kidneys excrete the unwanted Among these three processes, filtration
substances in urine. is the function of the glomerulus. Reab­
Normally, about 1 to 1.5 L of urine is for­ sorp­tion and secretion are the functions of
med every day. tubular portion of the nephron (Fig. 42.1).
242 Section 5 ê Renal Physiology and Skin

„„ GLOMERULAR FILTRATION 2. Basement Membrane

„„ INTRODUCTION The basement membrane of glomerular capil­

laries fuses with the basement mem­brane
Glomerular filtration is the process by which of visceral layer of Bowman’s capsule.
the blood that passes through glome­rular The basement membrane separates the
capillaries is filtered through the filtration endo­thelium of glomerular capillary and the
membrane. It is the first process of urine for­ epi­thelium of visceral layer of Bowman’s
mation. The structure of filtration membrane capsule.
is well suited for this.
3. Visceral Layer of
Filtration Membrane Bowman’s Capsule

It is formed by three layers: This is composed of a single layer of flatte­

1. Glomerular capillary membrane. ned epithelial cells resting on a basement
2. Basement membrane. mem­ brane. Each cell is connected with
3. Visceral layer of Bowman’s capsule. the basement membrane by cytoplasmic
extensions called pedicles or feet. The
pedicles are arranged in an interdigitating
1. Glomerular Capillary Membrane
manner leaving small cleft-like spaces in
The glomerular capillary membrane is formed between. The cleft-like space is called slit
by single layer of endothelial cells which are pore. Filtration takes place through these
attached to the basement membrane. The slit pores. The epithelial cells with pedicles
capillary membrane has many pores called are called podocytes (refer Fig. 39.4).
fenestra or filtration pores with a diameter
of 0.1 µ. Process of Glomerular Filtration
When the blood passes through the glome­
rular capillaries, the plasma is filtered into
the Bowman’s capsule. All the substances
of plasma are filtered, except the plasma
proteins. The filtered fluid is called glome­
rular filtrate.

The glomerular filtration is called ultrafil­
tration because even the minute particles
are filtered. But, the plasma proteins are
not filtered due to their large molecular
size. The protein molecules are larger than
the slit pores present in the endothelium of
capillaries. Thus, the glomerular filtrate con­
tains all the substances of plasma except
FIGURE 42.1: Events of urine formation the plasma proteins.
Chapter 42 ê Urine Formation 243
„„ GLOMERULAR FILTRATION RATE 2. Colloidal Osmotic Pressure
Glomerular filtration rate (GFR) is defined It is exerted by plasma proteins in the glome­
as the total quantity of filtrate formed in all ruli. The plasma proteins are not filtered
the nephrons of both the kidneys in the through the glomerular capillaries and remain
given unit of time. in the glomerular capillaries. These proteins
The normal GFR is 125 mL per minute develop the colloidal osmotic pressure which
or about 180 L per day. is about 25 mm Hg. It opposes glome­rular
3. Hydrostatic Pressure in
Filtration fraction is the fraction (portion) of Bowman’s Capsule
the renal plasma which becomes the filtrate.
It is the ratio between renal plasma flow and It is the pressure exerted by the filtrate in
Bowman’s capsule. It is also called cap­
glomerular filtration rate. It is expressed in
sular pressure. It is about 15 mm Hg. It also
opposes glomerular filtration.
The normal filtration fraction varies from
15 to 20%.
Net Filtration Pressure
Filtration GFR
= × 100 Net filtration pressure is the balance between
fraction Renal plasma flow
pressure favoring filtration and pres­sures
125 mL/min opposing filtration. It is otherwise known
= × 100
650 mL/min as effective filtration pressure or essential
= 19.2%. filtration pressure.
The net filtration pressure is given by:
The pressures, which determine the GFR,
1. Glomerular capillary pressure. = 60 – (25 + 15) = 20 mm Hg.
2. Colloidal osmotic pressure in the Normal net filtration pressure is about
glomeruli. 20 mm Hg, and it varies between 15 and
3. Hydrostatic pressure in the Bowman’s 20 mm Hg.
1. Glomerular Capillary Pressure
1. Renal Blood Flow
It is the pressure exerted by the blood in
glomerular capillaries. It is about 60 mm It is the most important factor that is necessary
Hg, and varies between 45 and 70 mm Hg. for glomerular filtration. GFR is directly propor­
Glomerular capillary pressure is the highest tional to renal blood flow. The renal blood flow
capillary pressure in the body. This pressure itself is controlled by autoregulation (refer
favors glomerular filtration. previous Chapter for details).
244 Section 5 ê Renal Physiology and Skin

2. Tubuloglomerular Feedback
Tubuloglomerular feedback is the mecha­
nism that regulates GFR through renal tubule
and macula densa (Fig. 42.2). Macula
densa of juxtaglomerular apparatus in the
terminal portion of thick ascending limb
is sensitive to the sodium chloride in the
tubular fluid.
When glomerular filtrate passes through
the terminal portion of thick ascending seg­
ment, macula densa acts like a sensor. It
detects the concentration of sodium chlo­
ride in the tubular fluid and accordingly
alters the glomerular blood flow and GFR.

When the concentration of sodium

chloride increases in the filtrate FIGURE 42.2: Tubuloglomerular feedback. GFR =
Glomerular filtration rate, NaCl = Sodium
When the concentration of sodium chlo­ chloride.
ride increases in the filtrate, macula densa
rele­ases adenosine from ATP. Adenosine
4. Colloidal Osmotic Pressure
causes constriction of afferent arteriole. So
the blood flow through glomerulus decre­ The GFR is inversely proportional to colloidal
ases leading to decrease in GFR. osmotic pressure which is exerted by plasma
proteins in the glomerular capillary blood.
When the concentration of sodium When colloidal osmotic pressure incre­
chloride decreases in the filtrate ases as in case of dehydration or increa­
When the concentration of sodium chloride sed plasma protein level, GFR decreases.
decreases in the filtrate, macula densa During hypoproteinemia, colloidal osmotic
secretes prostaglandin (PGE2), bradykinin pressure is low and GFR increases.
and renin.
PGE2 and bradykinin cause dilatation 5. Hydrostatic Pressure in
of afferent arteriole. Renin induces the Bowman’s Capsule
mation of angiotensin II which causes
GFR is inversely proportional to this. The
constriction of efferent arteriole. The dilata­
tion of afferent arteriole and constriction hydrostatic pressure in Bowman’s capsule
of efferent arteriole leads to increase in increases in conditions like obstruction of
glomerular blood flow and GFR. urethra and edema of kidney beneath renal
3. Glomerular Capillary Pressure
6. Constriction of Afferent Arteriole
The GFR is directly proportional to glome­
rular capillary pressure. The capillary pres­ The constriction of afferent arteriole reduces
sure, in turn depends upon the renal blood the blood flow to the glomerular capillaries
flow and arterial blood pressure. which in turn reduces GFR.
Chapter 42 ê Urine Formation 245
7. Constriction of Efferent Arteriole If the glomerular capillary membrane
is affected as in the cases of some renal
If efferent arteriole is constricted, initially
diseases, the surface area for filtration decre­
the GFR increases because of stagnation
ases. So there is reduction in GFR.
of blood in the capillaries. Later when all
the substances are filtered from this blood,
11. Permeability of Capillary Membrane
further filtration does not occur, because
the efferent arteriolar constriction prevents GFR is directly proportional to the perme­
outflow of blood from glomerulus and ability of glomerular capillary membrane.
no fresh blood enters the glomerulus for In many abnormal conditions like hypoxia,
filtration. lack of blood supply, presence of toxic
agents, etc. the permeability of the capillary
8. Systemic Arterial Pressure membrane increases. In such conditions,
even plasma proteins are filtered and excr­
Renal blood flow or GFR are not affected eted in urine.
till the mean arterial blood pressure is bet­
ween 60 and 180 mm Hg. It is due to the 12. Contraction of Glomerular
autoregulatory mechanism (refer Chapter Mesangial Cells
41). Variation in pressure above 180 mm
Glomerular mesangial cells are situated in
Hg or below 60 mm Hg affects the renal
between the glomerular capillaries. Contrac­
blood flow and GFR accordingly, because
tion of these cells decreases surface area
the autoregulatory mechanism fails beyond of capillaries resulting in reduction in GFR
this range. (refer Chapter 51 for details).

9. Sympathetic Stimulation 13. Hormonal and Other Factors

Afferent and efferent arterioles are supplied Many hormones and other secretory fac­
by sympathetic nerves. The mild or mode­ tors alter GFR by affecting the blood flow
rate stimulation of sympathetic nerves does through glomerulus.
not cause any significant change either in
renal blood flow or GFR. Factors increasing GFR by
Strong sympathetic stimulation causes
severe constriction of the blood vessels by i. Atrial natriuretic peptide.
releasing the neurotransmitter substance, ii. Brain natriuretic peptide.
noradrenaline. The effect is more severe on iii. cAMP.
the efferent arterioles than on the afferent iv. Dopamine.
arterioles. So, initially there is increase in v. Endothelium-derived nitric oxide.
filtration, but later it decreases. However, vi. Prostaglandin E2 (PGE2).
if the stimulation is continued for more Factors decreasing GFR by
than 30 minutes, there is recovery of both vasoconstriction
renal blood flow and GFR. It is because of
reduction in sympathetic neurotransmitter. i. Angiotensin II.
ii. Endothelin.
iii. Noradrenaline.
10. Surface Area of Capillary Membrane
iv. Platelet-activating factor.
GFR is directly proportional to the surface v. Platelet-derived growth factor.
area of the capillary membrane. vi. Prostaglandin F2 (PGF2).
246 Section 5 ê Renal Physiology and Skin

„„ TUBULAR REABSORPTION Substances reabsorbed actively

„„ INTRODUCTION The substances reabsorbed actively from the
renal tubule are sodium, calcium, potassium,
Tubular reabsorption is the process by which phosphates, sulfates, bicarbonates, glucose,
water and other substances are trans­ amino acids, ascorbic acid, uric acid and
ported from renal tubules back to the ketone bodies.
blood. When the glomerular filtrate flows
through the tubular portion of nephron, both 2. Passive Reabsorption
quantitative and qualitative changes occur.
Passive reabsorption is the movement
Large quantity of water (more than 99%),
of molecules along the electrochemical
electrolytes and other substances are (downhill) gradient. This process does not
reabsorbed by the tubular epithelial cells. need energy.
The reabsorbed substances move into the
interstitial fluid of renal medulla. And, from Substances reabsorbed passively
here, the substances move into the blood in The substances reabsorbed passively are
peritubular capillaries. chloride, urea and water.
Since the substances are taken back
into the blood from the glomerular filtrate, „„ SITE OF REABSORPTION
the entire process is called tubular reab­
The reabsorption of the substances occurs
in almost all the segments of tubular portion
of nephron.
Tubular reabsorption is known as selective 1. Substances Reabsorbed from
reabsorption because the tubular cells Proximal Convoluted Tubule
reabsorb only the substances necessary
About 7/8 of the filtrate (about 88%) is
for the body. Essential substances such
reabsorbed in proximal convoluted tubule.
as glucose, amino acids and vitamins are
The brush border of the epithelial cell in
completely reabsorbed from renal tubule. proximal convoluted tubule increases the
Whereas the unwanted substances like surface area and facilitates reabsorption.
metabolic waste products are excreted Substances reabsorbed from proximal
through urine. convoluted tubule are glucose, amino acids,
sodium, potassium, calcium, bicarbonates,
„„ MECHANISM OF REABSORPTION chlorides, phosphates, uric acid and water.
The basic transport mechanisms involved
in tubular reabsorption are of two types: 2. Substances Reabsorbed from
1. Active reabsorption. Loop of Henle
2. Passive reabsorption. The substances reabsorbed from loop of
Henle are sodium and chloride.
1. Active Reabsorption
Active reabsorption is the movement of 3. Substances Reabsorbed from
Distal Convoluted Tubule
molecules against the electrochemical
(uphill) gradient. It needs liberation of Sodium, calcium, bicarbonate and water are
energy which is derived from ATP. reabsorbed from distal convoluted tubule.
Chapter 42 ê Urine Formation 247
„„ REGULATION OF TUBULAR increases in the blood by the time it reaches
REABSORPTION efferent arteriole and peritubular capil­laries.
Tubular reabsorption is regulated by three The elevated osmotic pressure in the peri­
factors: tubular capillaries increases reabsorption
1. Glomerulotubular balance. of sodium and water from the tubule into
2. Hormonal factors. the capillary blood.
3. Nervous factors.
2. Hormonal Factors
1. Glomerulotubular Balance The hormones which regulate GFR are
Glomerulotubular balance is the balance listed in Table 42.1.
between the filtration and reabsorption of
3. Nervous Factor
solutes and water in kidney. When GFR
increases, the tubular load of solutes and Activation of sympathetic nervous system
water in the proximal convoluted tubule is increases the tubular reabsorption (parti­
increased. It is followed by increase in the cularly of sodium) from renal tubules. It also
reabsorption of solutes and water. This pro­ increases the tubular reabsorption indi­
cess helps in the constant reabsorption of rectly by stimulating secretion of renin from
solute, particularly sodium and water from juxtaglomerular cell. Renin causes forma­
renal tubule. tion of angiotensin II which increases the
sodium reabsorption (refer Chapter 40).
Mechanism of
glomerulotubular balance „„ TRANSPORT MAXIMUM – Tm
Glomerulotubular balance occurs because VALUE
of osmotic pressure in the peritubular capil­ Tubular transport maximum or Tm is the
laries. When GFR increases, more amount rate at which a substance is reabsorbed
of plasma proteins accumulate in the glome­ from the renal tubule. For example, the
rulus. Consequently, the osmotic pressure trans­port maximum for glucose (TmG), is

TABLE 42.1: Hormones regulating tubular reabsorption

Hormone Action
Increases sodium reabsorption in ascending limb, distal convoluted
tubule and collecting duct
Increases sodium reabsorption in proximal tubule, thick ascending
Angiotensin II limb, distal tubule and collecting duct (mainly in proximal
convoluted tubule)
Increases water reabsorption in distal convoluted tubule and collecting
Antidiuretic hormone
Atrial natriuretic factor Decreases sodium reabsorption
Brain natriuretic factor Decreases sodium reabsorption
Increases reabsorption of calcium, magnesium and hydrogen
Decreases phosphate reabsorption
Calcitonin Decreases calcium reabsorption
248 Section 5 ê Renal Physiology and Skin

375 mg/minute in adult males and about Reabsorption of water from proximal
300 mg/minute in adult females. convoluted tubule – obligatory water
Obligatory reabsorption is the type of water
Renal threshold is the plasma concentration reabsorption in proximal convoluted tubule,
at which a substance appears first in urine. which is secondary to sodium reabsorption.
Every substance has a threshold level in When sodium is reabsorbed from the
plasma or blood. Below that threshold level, tubule, the osmotic pressure decreases. It
the substance is completely reabsorbed causes osmosis of water from renal tubule.
and does not appear in urine. When the
con­centration of that substance reaches Reabsorption of water from distal
the threshold, the excess amount is not convoluted tubule and collecting duct –
reabsorbed and, so it appears in urine. This facultative water reabsorption
level is called the renal threshold of that
substance. Facultative reabsorption is the type of water
For example, the renal threshold for glu­ reabsorption in distal convoluted tubule and
cose is 180 mg/dL. That is, glucose is com­ collecting duct that occurs by the activity of
pletely reabsorbed from tubular fluid, if its antidiuretic hormone (ADH). Normally, the
concentration in blood is below 180 mg/dL. distal convoluted tubule and the collecting
So, the glucose does not appear in urine. duct are not permeable to water. But in the
When the blood level of glucose reaches presence of antidiuretic hormone (ADH),
180 mg/dL, it is not reabsorbed completely
these segments become permeable to water
and appears in urine.
and so it is reabsorbed.
„„ REABSORPTION OF Mechanism of action of
IMPORTANT SUBSTANCES antidiuretic hormone
Reabsorption of Sodium ADH combines with V2 receptors in the
From the glomerular filtrate, 99% of sodium tubular epithelial membrane and activates
is reabsorbed. Two thirds of sodium is reabsor­ adenyl cyclase, to form cyclic AMP. This
bed in proximal convoluted tubule and remai­ cyclic AMP increases the permeability of the
ning one third in other segments (except tubules for water by activating aquaporins
descending limb) and collecting duct. which form the water channels.
Sodium reabsorption occurs:
i. In exchange for hydrogen ion by antiport Aquaporins
(sodium countertransport protein) – in Aquaporins (AQP) are the membrane pro­
proximal convoluted tubules.
teins which function as water channels.
ii. Along with other substances like glu­
ADH increases water reabsorption in distal
cose and amino acids by symport
(sodium cotransport protein) – in other convoluted tubules and collecting ducts by
segments and collecting duct. regulating the aquaporins.

Reabsorption of Water Reabsorption of Glucose

Reabsorption of water occurs from proxi­ Glucose is completely reabsorbed in the
mal and distal convoluted tubules and in proximal convoluted tubule. It is tran­spor­
collecting duct. ted by secondary active transport (sodium
Chapter 42 ê Urine Formation 249
cotransport) mechanism. Glucose and sodium „„ TUBULAR SECRETION
bind to a common carrier protein in the
luminal membrane of tubular epithe­lium and
enter the cell. The carrier protein is called Tubular secretion is the process by which
sodium-dependent glucose transporter 2 the substances are transported from blood
into renal tubules. It is also called tubular
(SGLT2). From tubular cell glucose is trans­
ported into medullary interstitium by another
carrier protein called glucose transporter 2 „„ SUBSTANCES SECRETED IN
Renal threshold for glucose RENAL TUBULES

Renal threshold for glucose is 180 mg/dL in 1. Potassium is secreted actively by

sodium-potassium pump in proximal
venous blood. When the blood level reaches
and distal convoluted tubules and collec­
180 mg/dL glucose is not reabsorbed com­ ting ducts.
pletely and appears in urine. 2. Ammonia is secreted in the proximal
Tubular maximum for glucose (TmG) convoluted tubule.
3. Hydrogen ions are secreted in the
In adult male, TmG is 375 mg/minute and proxi­mal and distal convoluted tubules.
in adult females, it is about 300 mg/minute Maximum hydrogen ion secretion
(see above). occurs in proximal tubule.
Thus, urine is formed in the nephron by
Reabsorption of Bicarbonates the processes of glomerular filtration, selec­
tive reabsorption and tubular secretion.
Bicarbonate is reabsorbed actively, mostly
in proximal tubule (refer Chapter 54). It is „„ SUMMARY OF URINE
reabsorbed in the form of carbon dioxide. FORMATION
Bicarbonate is mostly present as sodium
Urine formation takes place in three pro­
bicarbonate in the filtrate. Sodium bicarbo­
nate dissociates into sodium and bicarbo­
nate ions in the tubular lumen.
Glomerular Filtration
Sodium diffuses into tubular cell in
exch­ange of hydrogen. Bicarbonate com­ Plasma is filtered in glomeruli and the sub­
bines with hydrogen to form carbonic acid. stances reach the renal tubules along with
Carbonic acid dissociates into carbon water as filtrate.
dioxide and water in the presence of carbo­
Tubular Reabsorption
nic anhydrase. Carbon dioxide and water
enter the tubular cell. 99% of filtrate is reabsorbed in different
In the tubular cells, carbon dioxide com­ seg­ments of renal tubules.
bines with water to form carbonic acid. It
immediately dissociates into hydrogen and Tubular Secretion
bicarbonate. Bicarbonate from the tubu­lar Some substances are secreted from blood
cell enters the interstitium. There it combi­ into the renal tubule.
nes with sodium to form sodium bicar­bo­ With all these changes filtrate becomes
nate (refer Fig. 44.1). urine.
Chapter 43

Concentration of Urine


„„ INTRODUCTION If water content in body is more, kidney

excretes excess water making the urine
Osmolarity of glomerular filtrate is same
dilute. It is achieved by the inhibition of ADH
as that of plasma and it is 300 mOsm/L.
But, normally urine is concentrated and its
ADH is secreted by posterior pituitary
osmolarity is four times more than that of
(refer Chapter 66). The stimulus for its secre­
plasma, i.e. 1,200 mOsm/L. Osmolarity of
tion is the decreased body fluid volume
urine depends upon two factors:
and/or increased sodium concentration
1. Water content in the body.
(hyper­osmolarity). ADH increases the water
2. Antidiuretic hormone.
reabsorption from distal convoluted tubule
and collecting duct resulting in concen­
tration of urine.
Mechanism of urine formation is the same But when, the volume of body fluid
for dilute urine and concentrated urine till the incre­ases or the osmolarity of body fluid
fluid reaches the distal convoluted tubule. decreases, ADH secretion stops. So water
Whether it has to be excreted as dilute reabsorption from renal tubules does not
urine or concentrated urine depends upon take place. This leads to excretion of large
the water content of the body. amount of water in urine making the urine
Chapter 43 ê Concentration of Urine 251
dilute. It brings back the normalcy of water
content and osmolarity of body fluids.

When the water content in body decreases,
kidney retains water and excretes concen­
trated urine. Formation of concentrated
urine is not as simple as that of dilute urine.
It involves two important processes:
1. Medullary gradient.
2. Secretion of ADH.

The osmolarity of the cortical interstitial
fluid is isotonic, i.e. similar to that of plasma
and it is 300 mOsm/L.
The osmolarity of medullary interstitial
fluid near the cortex also is 300 mOsm/L.
However, while proceeding from outer part
towards the inner part of medulla, it
increases gradually and, reaches the maxi­
mum at the inner most part of medulla FIGURE 43.1: Countercurrent multiplier.
Numerical indicate osmolarity (mOsm/L).
near renal sinus. Here, it is 1,200 mOsm/L
(Fig. 43.1).
This type of gradual increase in the „„ COUNTERCURRENT
osmolarity of the medullary interstitial fluid MECHANISM
is called the medullary gradient. It plays „„ COUNTERCURRENT FLOW
an important role in the concentration of
urine. A countercurrent system is a system of ‘U’
shaped tubules (tubes) in which, the flow of
„„ DEVELOPMENT AND fluid is in opposite direction in two limbs of
MAINTENANCE OF the U-shaped tubules.
MEDULLARY GRADIENT In kidney, the structures, which form the
counter current system, are the loop of Henle
Kidney has some unique anatomical arran­ and the vasa recta. In both, the direction of
ments called countercurrent system, flow of fluid in the descending limb is just
which are responsible for the develop­ment opposite to that in the ascending limb.
and maintenance of medullary gradient and The loop of Henle forms the counter­
hyperosmolarity of interstitial fluid in the current multiplier and, the vasa recta form
inner medulla. the countercurrent exchanger.
252 Section 5 ê Renal Physiology and Skin

„„ COUNTERCURRENT MULTIPLIER Other Factors Responsible for

Hyperosmolarity of Medullary
Loop of Henle
Interstitial Fluid
Loop of Henle functions as countercurrent
In addition to countercurrent multiplier action
multiplier. It is responsible for the develop­
ment of hyperosmolarity of medullary inter­ provided by the loop of Henle, two more
stitial fluid and medullary gradient. factors are involved in hyperosmolarity of
medullary interstitial fluid:
Role of Loop of Henle in 1. Reabsorption of sodium from medul­
Development of Medullary Gradient lary part of collecting duct into the
medullary interstitium, which adds to
The loop of Henle of juxtamedullary neph­ the osmolarity.
rons plays a major role as countercurrent 2. Urea recirculation: Urea is completely
multiplier. It is because the loop of juxta­ filtered in the glomeruli. As it is a waste
medullary nephrons is long and extends up product, it is not reabsorbed from the
to the deeper parts of medulla. renal tubule. So, all the filtered urea
The major cause for the hyperosmolarity reach collecting duct. Now, due to con­­
of medullary interstitial fluid is the active centration gradient, urea diffuses from
reabsorption of sodium, chloride and other the collecting duct into the inner medul­
solutes from ascending limb of Henle’s loop lary interstitium. So, the osmolarity
into the medullary interstitium. These solutes increases in the inner medulla.
accumulate in the medullary interstitium Due to the continuous diffusion, the
and increase the osmolarity. concentration of urea increases in the
Now, due to the concentration gradient, medullary interstitium. Again, by concentra­
the sodium and chloride ions diffuse from tion gradient, urea enters the ascending
medullary interstitium into the descending limb. From here, it passes through distal
limb of Henle’s loop and reach the ascen­ convoluted tubule and reaches the collecting
ding limb again via hairpin bend. duct. From here, urea enters the medullary
Thus, the sodium and chloride ions are interstitium and the cycle repeats. By this
repeatedly recirculated between the des­ way urea recirculates repeatedly, and helps
cen­ding limb and ascending limb of Henle’s to maintain the hyperosmolarity in the inner
loop through medullary interstitial fluid medullary interstitium. Only a small amount
leaving a small portion to be excreted in the of urea is excreted in urine.
Apart from this there is regular addition „„ COUNTERCURRENT EXCHANGER
of more and more new sodium and chloride
Vasa Recta
ions into descending limb by constant filtra­
tion. Thus, the reabsorption of sodium chlo­ Vasa recta functions as countercurrent
ride from ascending limb and addition of exchanger. It is responsible for the main­
new sodium chloride ions into the filtrate tenance of the hyperosmolarity of medullary
increase or multiply the osmolarity of medul­ interstitial fluid and the medullary gradi­
lary interstitial fluid and medullary gradient. ent developed by countercurrent multiplier
Hence, it is called countercurrent multiplier. (Fig. 43.2).
Chapter 43 ê Concentration of Urine 253
descending limb of vasa recta. Simultane­
ously water diffuses from descen­ding limb of
vasa recta into medullary interstitium.
The blood flows very slowly through
vasa recta. So, a large quantity of sodium
chloride accumulates in descending limb of
vasa recta and flows slowly towards ascen­
ding limb. By the time the blood reaches
the ascending limb of vasa recta, the con­
centration of sodium chloride increases
very much. This causes diffusion of sodium
chloride into the medullary interstitium. Water
from medullary interstitium enters the ascen­
ding limb of vasa recta. And the cycle is
Thus, vasa recta retain sodium chloride
in the medullary interstitium and removes
water from it. So, the hyperosmolarity of
medullary interstitium is maintained.
Recycling of urea also occurs through
vasa recta. From medullary interstitium, along
with sodium chloride, urea also enters the
descending limb of vasa recta. When blood
passes through ascending limb of vasa
recta, urea diffuses back into the medullary
interstitium along with sodium chloride.
Thus, sodium chloride and urea are
FIGURE 43.2: Countercurrent exchanger. exchanged for water between the ascend­
Numerical indicate osmolarity (mOsm/L). ing and descending limbs of vasa recta,
hence this system is called countercurrent
Role of Vasa Recta in the exchanger.
Maintenance of Medullary Gradient
Vasa recta act like countercurrent exchanger „„ ROLE OF ADH
because of its position. It is also ‘U’ shaped The final concentration of urine is achie­­ved
tubule with a descending limb, hairpin bend by ADH. Normally, the distal convoluted
and an ascending limb. A vasa recta runs tubule and the collecting duct are not
parallel to loop of Henle. Its descending limb perme­ able to water. In the presence of
runs along the ascending limb of Henle’s ADH, distal convoluted tubule and collec­
loop and its ascending limb runs along with ting duct become permeable to water
descending limb of Henle’s loop. resulting in water reabsorption. The water
The sodium chloride reabsorbed from reabsorption induced by ADH is called
ascending limb of Henle’s loop enters the facultative reabsorption of water (refer
medullary interstitium. From here it enters the Chapter 52 for details).
254 Section 5 ê Renal Physiology and Skin

This is because it contains all the substances

of plasma except proteins. The osmolarity
of the filtrate at Bowman’s capsule is 300

When the filtrate flows through proximal
convoluted tubule, there is active reabsor­
ption of sodium and chloride followed by
obligatory reabsorption of water. So, the
osmolarity of fluid remains the same as
in the case of Bowman’s capsule, i.e. 300
mOsm/L. Thus, in proximal convoluted
tubules, the fluid is isotonic to plasma.

FIGURE 43.3: Role of ADH in the formation

of concentrated urine. ADH increases the
permeability for water in distal convoluted tubule
and collecting duct.

A large quantity of water is removed

from the fluid while passing through distal
convoluted tubule and collecting duct. So,
the urine becomes hypertonic with an osmo­
larity of 1,200 mOsm/L (Fig. 43.3).

When the glomerular filtrate passes through
renal tubule, its osmolarity is altered in
ferent segments as described below
(Fig. 43.4).

FIGURE 43.4: Mechanism for the formation
The glomerular filtrate collected at the of dilute urine. Numerical indicate osmolarity
Bowman’s capsule is isotonic to plasma. (mOsm/L).
Chapter 43 ê Concentration of Urine 255
ADH increases the permeability for mOsm/L. Thus in this segment the fluid is
water in distal convoluted tubule and col­ hypertonic to plasma.
lecting duct.
When the fluid passes from proximal con­ When the thin ascending segment of the
voluted tubule into the thick descending loop ascends upwards through the medullary
segment, water is reabsorbed from the region, osmolarity decreases gradually.
tubule into outer medullary interstitium by Due to concentration gradient, sodium
means of osmosis. It is due to the increased chloride diffuses out of tubular fluid and
osmolarity in the medullary interstitium, i.e. osmolarity decreases to 400 mOsm/L. The
fluid in this segment is slightly hypertonic to
outside the thick descending tubule. The
osmolarity of the fluid inside this segment
is between 450 and 600 mOsm/L. That „„ 6. THICK ASCENDING SEGMENT
means the fluid is slightly hypertonic to
plasma. This segment is impermeable to water. But
there is active reabsorption of sodium and
„„ 4. THIN DESCENDING SEGMENT chloride from this. Reabsorption of sodium
OF HENLE’S LOOP decreases the osmolarity of tubular fluid to
a greater extent. The osmolarity is between
As the thin descending segment of Henle’s 150 and 200 mOsm/L. The fluid inside
loop passes through the inner medul­ lary becomes hypotonic to plasma.
interstitium (which is increasingly hyper­
tonic) more water is reabsorbed. „„ 7. DISTAL CONVOLUTED TUBULE
This segment is highly permeable to AND COLLECTING DUCT
water, and so the osmolarity of tubular fluid In the presence of ADH, distal convoluted
becomes equal to that of the surrounding tubule and collecting duct become permeable
medullary interstitium. to water resulting in water reabsorption and
In the short loops of cortical nephrons, final concentration of urine.
the osmolarity of fluid at the hairpin bend Reabsorption of large quantity of water
of loop becomes 600 mOsm/L. And, in the increases the osmolarity to 1,200 mOsm/L
long loops of juxtamedullary nephrons, at (refer Fig. 43.3). The urine becomes hyper­
the hairpin bend, the osmolarity is 1,200 tonic to plasma.
Chapter 44

Acidification of Urine and Role of

Kidney in Acid-base Balance


„„ INTRODUCTION in urine. Out of 4,380 mEq, about 4,280 to

4,330 mEq of H+ is utilized for the reab­
Kidney plays an important role in mainte­
sorption of filtered HCO3–. Only the remai­
nance of acid-base balance by excreting
ning 50 to 100 mEq is excreted. It results in
hydrogen ions and retaining bicarbonate
the acidification of urine.
Normally, urine is acidic in nature with
a pH of 4.5 to 6. The metabolic activities
in the body produce lot of acids (with lot of HYDROGEN IONS
hydrogen ions) which threaten to push the H+ is secreted in proximal convoluted tubule,
body towards acidosis. However, kidneys distal convoluted tubule and collecting
prevent this by excreting hydrogen ions (H+) duct. Secretion of H+ into the renal tubules
and conserving bicarbonate ions (HCO3–). occurs by the formation of carbonic acid.
About 4,320 mEq of HCO3– is filtered by Carbon dioxide formed in the tubular cells
the glomeruli every day. It is called filtered combines with water to form carbonic acid.
load of HCO3–. Excretion of this much HCO3– Carbon dioxide enters the cells from tubu­
through urine will affect the acid-base lar fluid also. Carbonic anhydrase is essen­
balance of body fluids. So, HCO3– must be tial for the formation of carbonic acid. This
taken back from the renal tubule by reab­ enzyme is available in large quantities
sorp­tion. in the epithelial cells of the renal tubules.
The reabsorption of filtered HCO3– occurs The carbonic acid immediately dissociates
by the secretion of H+ in the renal tubules. into H+ and HCO3– (Fig. 44.1). H+ from the
About 4,380 mEq of H+ appear every day tubular cells is secreted into proximal con­
in the renal tubule by means of filtration voluted tubule, distal convoluted tubule and
and secretion. Not all the H+ are excreted collecting duct.
Chapter 44 ê Acidification of Urine and Role of Kidney in Acid-base Balance 257
Role of Kidney in Preventing
Metabolic Acidosis
Kidney plays an important role in preven­
ting metabolic acidosis by excreting H+.
The excretion of H+ occurs by three mecha­
1. Bicarbonate mechanism.
2. Phosphate mechanism.
3. Ammonia mechanism.

FIGURE 44.1: Reabsorption of bicarbonate „„ BICARBONATE MECHANISM

ions by secretion of hydrogen ions in renal
All the HCO3– filtered into the renal tubules
tubule. P = Sodium-hydrogen antiport pump.
is reabsorbed. About 80% of it is reabsor­
bed in proximal convoluted tubule; 15% in
The distal convoluted tubule and collec­ Henle’s loop and 5% in distal convoluted
ting duct have a special type of cells called tubule and collecting duct. The reabsorption
intercalated cells (I cells) that are involved of HCO3– utilizes the H+ secreted into the
in handling hydrogen and bicarbonate ions. renal tubules.
There are two mechanisms for the sec­ The H+ secreted into the renal tubule,
retion of H+: combines with filtered HCO3– forming car­
1. Sodium-hydrogen antiport pump. bonic acid. Carbonic acid dissociates into
2. ATP-driven proton pump. carbon dioxide and water in the presence
of carbonic anhydrase. Carbon dioxide and
„„ SODIUM-HYDROGEN water enter the tubular cell.
ANTIPORT PUMP TABLE 44.1: Secretion and removal of
hydrogen ions in renal tubule
When sodium ion (Na ) is reabsorbed from

the tubular fluid into the tubular cell, H+ is Mechanism Segment of renal tubule
secreted from the cell into the tubular fluid
in exchange for Na+. The sodium-hydrogen Sodium-hydrogen
Distal convoluted tubule
antiport pump present in the tubular cells pump
is responsible for the exchange of Na+ and ATP-driven Distal convoluted tubule
H+. This type of sodium-hydrogen counter proton pump Collecting duct
transport occurs predominantly in distal Proximal convoluted
convoluted tubule (Table 44.1). Bicarbonate tubule
mechanism Henle’s loop
„„ ATP-DRIVEN PROTON PUMP Distal convoluted tubule
Phosphate Distal convoluted tubule
This is an additional mechanism of H+ sec­ mechanism Collecting duct
re­tion in distal convoluted tubule and col­
Ammonia Proximal convoluted
lec­ ting duct. This pump is operated by
mechanism tubule
obtaining energy from ATP.
258 Section 5 ê Renal Physiology and Skin

In the tubular cells, carbon dioxide com­ urine acidic. In the tubular epithelial cells,
bines with water to form carbonic acid. It ammonia is formed when the amino acid
immediately dissociates into H+ and HCO3–. glutamine is converted into glutamic acid in
HCO3– from the tubular cell enters the the presence of the enzyme glutaminase.
interstitium. Simultaneously Na+ is reab­ Ammonia is also formed by the deamination
sorbed from the renal tubule under the of some of the amino acids such as glycine
influence of aldosterone. HCO3– combines and alanine (Fig. 44.3).
with Na+ to form NaHCO3. Now, the H+ is
secreted into the tubular lumen from the
cell in exchange for Na+ (refer Fig. 44.1).
Thus, for every hydrogen ion secreted
into lumen of tubule, one bicarbonate ion
is reabsorbed from the tubule. In this way,
kidneys conserve the HCO3–. The reabsorp­
tion of filtered HCO3– is an important factor in
maintaining pH of the body fluids.

In the tubular cells, carbon dioxide combi­
nes with water to form carbonic acid. It
imme­diately dissociates into H+ and HCO3–.
HCO3– from the tubular cell enters the
interstitium. Simultaneously, Na+ is reab­
FIGURE 44.2: Excretion of hydrogen ions in
sorbed from renal tubule under the influ­ combination with phosphate ions
ence of aldosterone. Na+ enters the inter­
stitium and combines with HCO3–. The H+
is secreted into the tubular lumen from the
cell in exchange for Na+ (Fig. 44.2).
The H+, which is secreted into renal tubu­
les, reacts with phosphate buffer system.
It combines with sodium-hydrogen phos­
phate to form sodium-dihydrogen phos­phate.
Sodium-dihydrogen phosphate is excreted
in urine. The H+, which is added to urine,
makes it acidic. It happens mainly in distal
tubule and collecting duct because of the
presence of large quantity of sodium-hydro­
gen phosphate in these segments.

This is the most important mechanism by FIGURE 44.3: Excretion of hydrogen in
which kidneys excrete H+ and make the combination with ammonia
Chapter 44 ê Acidification of Urine and Role of Kidney in Acid-base Balance 259
The ammonia (NH3) formed in tubular urine in the form of ammonium compounds
cells is secreted into tubular lumen in resulting in acidification of urine.
exchange for sodium ion. Here, it com­ This process takes place mostly in the
bines with H+ to form ammonium (NH4). proximal convoluted tubule because gluta­
The tubular cell membrane is not perme­ mine is converted into ammonia in the cells
able to ammonium. Therefore, it remains of this segment.
in the lumen and combines with sodium Thus, by excreting H+ and conserving
acetoacetate to form ammonium aceto­ HCO3–, kidneys produce acidic urine and
acetate. Ammonium acetoacetate is excre­ help to maintain the acid-base balance of
ted through urine. Thus, H+ is added to body fluids.
Chapter 45

Renal Function Tests



„„ PROPERTIES AND of kidney. The renal function tests are of

COMPOSITION OF three types:
NORMAL URINE 1. Examination of urine alone.
2. Examination of blood alone.
„„ PROPERTIES OF URINE 3. Examination of blood and urine.
Volume : 1,000 to 1,500 mL/day
Reaction : Slightly acidic with pH of „„ EXAMINATION OF
Specific gravity : 1.010 to 1.025 Routine Examination of Urine
Color : Normally, urine is straw
colored During the routine examination of urine, the
Odor : Fresh urine has light following are determined:
aro­matic odor. If stored i. Specific gravity: Normally it is 1.010 to
for some time, the odor 1.025. But, in some conditions like
becomes stronger due to chronic nephritis, it is decreased.
bacterial decomposition ii. Presence of normal constituents of
urine in abnormal quantity: Normally,
„„ COMPOSITION OF URINE substances like water, salt, amino acids
Urine consists of water and solids. Solids and creatinine are excreted in urine
include organic and inorganic substances either in greater or lesser amount. But,
(Fig. 45.1). if abnormally large amount is excre­
ted, it suggests some abnormal func­
tional status of kidney. If 4 to 5 liters
of water is excreted consistently
Renal function tests are the group of tests per day, it is suggestive of diabetes
that are performed to assess the functions insipidus. Abnormally low amount of
Chapter 45 ê Renal Function Tests 261
To determine the plasma clearance of a
particular substance, measurement of the
following factors is required:
1. Volume of urine excreted.
2. Concentration of the substance in
3. The concentration of the substance in
The formula to calculate clearance
value is:
FIGURE 45.1: Quantity of solids excreted in
urine (mMol/day) UV
water excretion indicates nephritis. P
Abnormal amount of salts or nutritive Where,
substances like amino acids appear in C = Clearance
urine during congenital tubular defects. U = Concentration of the substance in
Abnormal albumin excretion occurs urine
in defective filtration. Abnormal amount V = Volume of urine flow
of glucose is excreted in diabetes P = Concentration of the substance in
mellitus. plasma
iii. Microscopic examination: This reveals
the presence of red blood cells, pus 1. Measurement of
cells, epithelial cells, casts and crystals Glomerular Filtration Rate
which suggests the renal pathology.
A substance that is completely filtered but
neither reabsorbed nor secreted should be
used to measure glomerular filtration rate
The level of plasma proteins, urea, uric acid (GFR). Inulin is a substance that is com­
and creatinine are determined in blood. The pletely filtered. And, it is neither reabsorbed
blood level of these substances is altered in nor secreted. So, inulin is the ideal sub­
renal failure. stance used to measure GFR.
Inulin clearance
BLOOD AND URINE A known amount of inulin is injected into the
body. After sometime, the concentration of
Plasma Clearance
inulin in plasma and urine and the volume
Plasma clearance is defined as the amount of urine excreted are estimated.
of plasma that is cleared off a substance in For example,
a given unit of time. It is also known as renal Concentration of
clearance. It is based on Fick’s principle. inulin in urine = 125 mg/dL
The determination of clearance value Plasma concentration = 1 mg/dL
for certain substances helps in assessing Volume of urine output = 1 mL/min
the following renal functions: Thus,
1. Glomerular filtration rate.
2. Renal plasma flow. Glomerular filtration rate =
3. Renal blood flow. P
262 Section 5 ê Renal Physiology and Skin

i. Renal plasma flow.

125 × 1
= ii. Percentage of plasma volume in the
1 blood.
= 125 mL/min
i. Renal plasma flow
2. Measurement of Renal Plasma Flow Renal plasma flow is measured by using
PAH clearance.
To measure renal plasma flow, a sub­
stance, which is filtered and secreted but ii. Percentage of plasma volume in the
not reabsorbed, should be used. Such a blood
substance is para-aminohippuric acid (PAH).
The percentage of plasma volume is indi­
PAH clearance indicates the amount of
rectly determined by using PCV. For example,
plasma passed through kidneys.
if PCV is 45%, the plasma volume in
A known amount of PAH is injected into
the blood is 100 – 45 = 55%, i.e. 55 mL
the body. After sometime, the concentration
of plasma is present in every 100 mL of
of PAH in plasma and urine and the volume
of urine excreted are estimated.
Renal blood flow is calculated with the
For example,
values of renal plasma flow and % of
Concentration of PAH
plasma in blood by using a formula given
in urine = 66 mg/dL
Plasma concentration = 0.1 mg/dL
Volume of urine output = 1 mL/min Renal plasma flow
Renal blood flow =
Thus, % of plasma in blood
UV For example,
Renal plasma flow =
P Renal plasma flow = 660 mL/min
Amount of plasma
66 × 1 in blood = 55%
0.1 660
Renal blood flow =
= 660 mL/min 55/100

3. Measurement of Renal Blood Flow 660 × 100

To determine renal blood flow value of two 55
factors is necessary: = 1,200 mL/min
Chapter 46



„„ INTRODUCTION The lower part of the bladder is narrow

and forms the neck. The distal end of the
Micturition is a process by which urine is
bladder is guarded by internal urethral
voided from the urinary bladder. It is a reflex
process. However, in grown up children and sphinc­ter. This sphincter is made up of detru­
adults, it can be controlled voluntarily to sor muscle. It opens towards urethra. At
some extent. The functional anatomy and the distal end of urethra, there is external
nerve supply of urinary bladder are essen­ urethral sphincter. It is made up of skeletal
tial for the process of micturition. muscle fibers. Therefore, it is responsible
for voluntary control of micturition.
Urinary bladder consists of the body, neck
and internal urethral sphincter. The smooth Urinary bladder and the internal sphincter
muscle forming the body of bladder is called are supplied by sympathetic and para­
detrusor muscle. At the posterior surface of sympathetic divisions of autonomic nerv­
the bladder wall, there is a triangular area ous system whereas, the external sphincter
called trigone. At the upper angles of this is supplied by the somatic nerve fibers
trigone, two ureters enter the bladder. (Fig. 46.1).
264 Section 5 ê Renal Physiology and Skin

filling of urinary bladder and so, the sym­

pathetic nerve is called nerve of filling.

The preganglionic fibers of parasympathe­
tic nerve form the pelvic nerve or nervous
erigens. Pelvic nerve fibers arise from
second, third and fourth sacral segments
(S2, S3 and S4) of spinal cord. These
fibers run through hypogastric ganglion and
synapse with postganglionic neurons situ­
ated in close relation to urinary bladder and
internal sphincter (Table 46.1).
FIGURE 46.1: Nerve supply to urinary bladder
and urethra Function of Parasympathetic Nerve
The stimulation of pelvic (parasympathetic)
„„ SYMPATHETIC NERVE SUPPLY nerve causes contraction of detrusor muscle
Preganglionic fibers of sympathetic nerve and relaxation of the internal sphinc­ter
arise from first two lumbar segments leading to emptying of urinary bladder. So,
(L1 and L2) of spinal cord. After leaving the parasympathetic nerve is called the
spinal cord, the fibers pass through lateral nerve of emptying or nerve of micturition.
sympathetic chain without any synapse in The pelvic nerve has also the sensory
the sympathetic ganglia and finally termi­ fibers which carry impulses from stretch
nate in hypogastric ganglion. The postgang­ receptors present on the wall of the urinary
lionic fibers arising from this ganglion form bladder and urethra to the central nervous
the hypogastric nerve, which supplies the system.
detrusor muscle and internal sphincter.
Function of Sympathetic Nerve The external sphincter is innervated by the
The stimulation of sympathetic nerve causes somatic nerve called the pudendal nerve.
relaxation of detrusor muscle and cons­ It arises from second, third and fourth sacral
triction of the internal sphincter. It results in segments of the spinal cord.

TABLE 46.1: Functions of nerves supplying urinary bladder and sphincters

On detrusor On internal On external

Nerve Function
muscle sphincter sphincter
Relaxation Constriction Not supplied Filling of urinary bladder
Contraction Relaxation Not supplied Emptying of urinary bladder
Somatic nerve Not supplied Not supplied Constriction Voluntary control of micturition
Chapter 46 ê Micturition 265
Function of Pudendal Nerve changes by connecting it to a suitable
recording instrument.
It maintains the tonic contraction of the
skeletal muscle fibers of the external First, the bladder is emptied completely.
sphincter and keeps the external sphincter Then, a known quantity of fluid is introduced
constricted always. into the bladder at regular intervals. The
During micturition, this nerve is inhibited. intravesical pressure developed by the fluid
It causes relaxation of external sphincter is recorded continuously. A graph is obtai­
leading to voiding of urine. Thus, the puden­ ned by plotting all the values of volume
dal nerve is responsible for voluntary con­ and the pressure. This graph is the cysto­
trol of micturition. metrogram (Fig. 46.2).

„„ FILLING OF URINARY BLADDER Description of Cystometrogram

„„ PROCESS OF FILLING Cystometrogram shows three segments.
Urine is continuously formed in the neph­
rons and it is transported drop by drop Segment I
through the ureters into the urinary bladder. Initially, when the urinary bladder is empty,
When urine collects in the pelvis of ureter, the intravesical pressure is 0. When about
the contraction sets up in pelvis. The con­
100 mL of fluid is collected, the pressure
traction is transmitted through rest of the
ureter in the form of peristaltic wave up to rises sharply to about 10 cm H2O.
trigone of the urinary bladder. The peristaltic
wave moves the urine into the bladder. Segment II
A reasonable volume of urine can be This segment shows the plateau, i.e. the
stored in urinary bladder without any dis­
intra­vesical pressure remains more or less
comfort and without much increase in
at 10 cm H2O (level of segment I) without any
pressure inside the bladder (intravesical
change even after introducing 300 to 400 mL
pres­sure). It is due to the adaptation of
detru­sor muscle. The relationship between
the volume of urine and pressure in urinary
bladder is studied by cystometrogram.

Cystometrogram is the graphical registra­
tion (recording) of pressure changes in
urinary bladder in relation to volume of
urine collected in it.

Method of Recording Cystometrogram

A double lumen catheter is introduced into
the urinary bladder. One of the lumen is
used to infuse fluid into the bladder and the FIGURE 46.2: Cystometrogram. Dotted
other one is used to record the pressure lines = Contraction of detrusor muscle.
266 Section 5 ê Renal Physiology and Skin

of fluid. It is because of adaptation of urinary „„ MICTURITION REFLEX

bladder by relaxation. It is in accordance
It is the reflex by which micturition occurs.
with law of Laplace.
This reflex is elicited by the stimulation of
Law of Laplace stretch receptors situated on the wall of
urinary bladder and urethra. When about
According to this law, the pressure in a 300 to 400 mL of urine is collected in the
spherical organ is inversely proportional to bladder, the pressure inside the bladder
its radius, the tone remaining constant. That increases. This stretches the wall of bladder
is, if radius is more, the pressure is less resulting in stimulation of stretch receptors
and if radius is less the pressure is more, and generation of sensory impulses.
provided the tone remains constant. The sensory (afferent) impulses from
Urinary bladder obeys Laplace law. In the receptors reach the sacral segments
the bladder, the tension increases as the of spinal cord via the sensory fibers of
urine is filled. At the same time, the radius pelvic (parasympathetic) nerve. The motor
also increases due to relaxation of detrusor (efferent) impulses produced in spinal cord,
muscle. Because of this, the pressure rise travel through motor fibers of pelvic nerve
is almost zero. towards bladder and internal sphincter.
When about 100 mL of urine is collected, The motor impulses cause contraction of
the pressure rises to about 10 cm H2O and
detrusor muscle and relaxation of internal
now, the desire for micturition occurs. The
sphincter so that, urine enters the urethra
desire for micturition is associated with a
from the bladder (Fig. 46.3).
vague feeling in the perineum. An additional
Once urine enters urethra, the stretch
volume of about 200 to 300 mL of urine
receptors in the urethra are stimulated and
can be collected in bladder without much
send afferent impulses to spinal cord via
increase in pressure. However, when total
pelvic nerve fibers. These impulses inhibit
volume rises beyond 400 mL, the pressure
pudendal nerve. So, the external sphincter
rises sharply and the urge for micturition
starts. Still voluntary control of micturition relaxes and micturition occurs.
is possible. And, beyond 600 to 700 mL of Once a micturition reflex begins, it is
urine, voluntary control starts failing. self-regenerative, i.e. the initial contraction
of bladder further activates the receptors to
Segment III cause still further increase in sensory impul­
ses from the bladder and urethra. These
As the pressure increases with collection impulses, in turn cause further increase
of 300 to 400 mL of fluid, the contraction in reflex contraction of bladder. The cycle
of detrusor muscle becomes intense, increa­ continues repeatedly until the force of con­
sing the consciousness and the urge traction of bladder reaches the maximum
for micturition. Still, voluntary control is and the urine is voided out completely.
possible. The voluntary control is possible During micturition, the flow of urine is
up to volume of 600 to 700 mL at which the facilitated by the increase in the abdominal
pressure rises to about 35 to 40 cm H2O. pressure due to the voluntary contraction of
When the intravesical pressure rises abdominal muscles.
above 40 cm water, the contraction of detru­
sor muscle becomes still more intense.
Higher Centers for Micturition
And, voluntary control of micturition is not
pos­sible. Now, pain sensation develops and Spinal centers for micturition are present in
micturition should take place. sacral and lumbar segments. These spinal
Chapter 46 ê Micturition 267
centers are regulated by higher centers
which are of two types:
1. Inhibitory centers which are situated in
midbrain and cerebral cortex.
2. Facilitatory centers which are situated
in pons and cerebral cortex.

Atonic bladder is the urinary bladder with
loss of tone in detrusor muscle. It is caused
by destruction of sensory (pelvic) nerve
fibers of urinary bladder.
Due to the destruction of sensory nerve
fibers, the bladder is filled up without any
stretch signals to spinal cord. Detrusor
muscle loses the tone and becomes flaccid.
So, bladder is completely filled with urine.
Later, overflow occurs in drops as and when
urine enters the bladder. It is called over­
flow incontinence or overflow dribbling. It
occurs in spinal injury and syphilis.

Automatic bladder refers loss of voluntary
control of micturition. So, even with small
amount of urine collected in the urinary FIGURE 46.3: Micturition reflex
bladder, micturition reflex occurs resulting
in emptying of urine. This occurs in tran­ urine collected in bladder will elicit the
saction of spinal cord above the sacral micturition reflex.
„„ 3. THE UNINHIBITED Nocturnal micturition is the involuntary
NEUROGENIC BLADDER voiding of urine during night. It is otherwise
known as enuresis or bedwetting. It occurs
It is the urinary bladder with frequent and due to the absence of voluntary control
uncontrollable micturition caused by lesion of micturition. It is a common and normal
in midbrain. process in infants and children below 3 years.
The lesion in midbrain causes conti­ It is because of incomplete myelination of
nuous excitation of spinal micturition motor nerve fibers of the bladder. When
cen­ters resulting in frequent and uncontroll­ myelination is complete, voluntary control of
able micturition. Even a small quantity of micturition develops and bedwetting stops.
Chapter 47



„„ STRUCTURE OF SKIN 1. Stratum corneum.

2. Stratum lucidum.
3. Stratum granulosum.
Skin is the largest organ of the body. It is 4. Stratum spinosum.
not uniformly thick. At some places, it is 5. Stratum germinativum.
thick and in some places, it is thin. The The important feature of epidermis is that,
average thickness of the skin is about 1 to it does not have blood vessels (Fig. 47.1).
2 mm. In the sole of the foot, palm of the The nutrition is provided to epidermis by the
hand and in the interscapular region, it is capillaries of dermis.
considerably thick, measuring about 5 mm.
In other areas of the body, the skin is thin. „„ DERMIS
It is thinnest over eyelids and penis measu­ Dermis is the inner layer of the skin. It is a
ring about 0.5 mm only. connective tissue layer made up of dense
Skin is made up of two layers: and stout collagen fibers, fibroblasts and
1. Outer epidermis. histiocytes. Dermis is made up of 2 layers:
2. Inner dermis. 1. Superficial papillary layer.
2. Deeper reticular layer.
The epidermis is the outer layer of skin. „„ APPENDAGES OF SKIN
It is formed by stratified epithelium, which The hair follicles with hairs, nails, sweat
consists of 5 layers: glands, sebaceous glands and mammary
Chapter 47 ê Skin 269

FIGURE 47.1: Structure of skin

glands are considered as appendages of Melanin

the skin.
Melanin is the skin pigment and it forms
the major color determinant of human skin.
Skin becomes dark when melanin content
The color of the skin depends upon two increases. It is protein in nature and it is
important factors: synthesized from the amino acid tyrosine
1. Pigmentation of skin. via dihydroxyphenylalanine (DOPA).
2. Hemoglobin in the blood.
2. Hemoglobin in Blood
1. Pigmentation of the Skin
The amount and the nature of hemoglobin
Cells of the skin contain a brown pigment that circulates in the cutaneous blood ves­
called melanin. Melanin is synthesized by sels play an important role in the coloration
melanocytes which are present mainly in the of the skin.
stratum germinativum and stratum spinosum Skin becomes:
of epidermis. After synthesis, this pigment i. Pale when hemoglobin content decre­
spreads to the cells of the other layers. ases.
270 Section 5 ê Renal Physiology and Skin

ii. Pink when blood rushes to skin due to Activation of Sebaceous

cutaneous vasodilatation (blushing). Glands at Puberty
iii. Bluish during cyanosis which is caused
Sebaceous glands are inactive till puberty.
by excess amount of reduced hemo­
At the time of puberty these glands are acti­
vated by sex hormones in both males and
At the time of puberty particularly in
The skin contains two types of glands, seba­ males, due to the increased secretion of
ceous glands and the sweat glands. sex hormones especially dehydroepiandro­
sterone, the sebaceous glands are stimu­
„„ SEBACEOUS GLANDS lated suddenly. It leads to the development
Sebaceous glands are simple or branched of acne on the face.
alveolar glands situated in the dermis of the
skin. Acne
These glands are ovoid or spherical in Acne is the localized inflammatory condition
shape and open into the neck of the hair of the skin characterized by pimples on face,
follicle through a duct. In some areas like face, chest and back. It occurs because of over
lips, nipple, glans penis and labia minora activity of sebaceous glands. Acne vulgaris
the sebaceous glands open directly into the is the common type of acne that is developed
exterior. during adolescence. Acne disappears within
The sebaceous glands secrete an oily few years when the sebaceous glands
substance called sebum. become adapted to the sex hormones.

Composition of Sebum „„ SWEAT GLANDS

Sebum contains: Sweat glands are of two types:
1. Free fatty acids. 1. Eccrine glands.
2. Triglycerides. 2. Apocrine glands.
3. Squalene.
4. Sterols. Eccrine Glands
5. Waxes.
The eccrine glands are tubular glands dis­
6. Paraffin.
tributed throughout the body (Table 47.1).
These glands open out through the sweat
Functions of Sebum
1. The free fatty acid content of the sebum
Secretory activity of eccrine glands
has antibacterial and antifungal actions.
Thus, it prevents the infection of skin Eccrine glands function throughout life since
by bacteria or fungi. birth. These glands secrete a clear watery
2. The lipid nature of sebum keeps the sweat. The secretion increases during incre­­
skin smooth and oily. It protects the ase in temperature and emotional condi­
skin from unnecessary desquamation tions.
and injury caused by dryness. Eccrine glands play important role in
3. The lipids of the sebum prevent heat regulating the body temperature by secre­
loss from the body. It is particularly ting sweat. Sweat contains water, sodium
useful in cold climate. chloride, urea and lactic acid.
Chapter 47 ê Skin 271
TABLE 47.1: Differences between eccrine and apocrine sweat glands

Features Eccrine glands Apocrine glands

Only in limited areas like axilla,
1. Distribution Throughout the body
pubis, areola and umbilicus
2. Opening Exterior through sweat pore Into hair follicle
3. Period of functioning Function throughout life Start functioning only at puberty
4. Secretion Clear and watery Thick and milky
5. Regulation of body Play important role in Do not play any role in
temperature temperature regulation temperature regulation
6. Conditions when During increased temperature
Only during emotional conditions
secretion increases and emotional conditions
7. Control of secretory
Under nervous control Under hormonal control
8. Nerve supply Sympathetic cholinergic fibers Sympathetic adrenergic fibers

Control of eccrine glands The apocrine glands do not play any

role in temperature regulation like eccrine
Eccrine glands are under nervous control
and are supplied by sympathetic post­
ganglionic cholinergic nerve fibers, which Control of apocrine glands
secrete acetylcholine. Stimulation of these
The apocrine glands are innervated by sym­
nerves causes secretion of sweat.
pathetic adrenergic nerve fibers. But, the
secretory activity is not under nervous control.
Apocrine Glands
However, adrenaline from adrenal medulla
Apocrine glands are situated only in cer­ causes secretion by apocrine glands.
tain areas of the body like axilla, pubis, Glands of eyelids, glands of external audi­
areola and umbilicus. These glands are tory meatus and mammary glands are the
also tubular in nature but open into the hair modified apocrine glands.
Secretory activity of apocrine glands „„ FUNCTIONS OF THE SKIN

Apocrine sweat glands are nonfunctional The primary function of skin is the protec­
till puberty and start functioning only at the tion of organs. However, it has many other
time of puberty. In old age, the function of important functions also.
these glands gradually declines.
The secretion of the apocrine glands is