Introduction To Human Physiology: August 2016

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Introduction to Human Physiology
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Introduction to Human Physiology
Dr. Azza Sajid Alkinany
(Assist. Prof.)
I
Preface
While teaching physiology to the medical, pharmacology and health

science students I was introduced to the basic students , needs in physiology to
widen their knowledge in physiology for graduate and to act as a base for
further higher education in physiology and health science.
In the recent time the physiological components are widely available by

internet search in different forms of books, power point presentation, sessions
and animations make most of students lost and face difficulties with these
wide materials. So this book is to meet the basic students , needs. An
experience was based on a summary work for more than ten years in
teaching physiology in Basra University, Pharmacy College and Sultan
Qaboos University, College of Science.
The book is come out inform of simplified accessible notes about each
topic. Each system begins with anatomical considerations notes before the
functional and mechanisms notes .Furthermore each system is supported by
common clinical notes and pharmacology notes.
Alhamdulillah to achieve this book which I hope it would be workable

and helpful to the students by acting a gate to guide and direct them for
further readings and knowledge and not to dispense with the textbooks.
Dr.Azza Sajid Alkinany
II
Chapter One
Introduction to Physiology 1
General concepts
Physiology is the scientific investigation of functions and processes of
living things. Humans have many characteristics of living things such as
organization, metabolism, responsiveness, growth, development and reproduction.
Structural and functional organization

Overview
 There are basic chemical characteristics that are responsible for the structure
and function of the life:
- Cells are the basic structural and functional units of organisms.
- Organelles are the smallest structures within the cell that perform specific
functions.
- Tissues are groups of cells of similar structures, functions and the material
surrounded them. The four primary tissue types are: epithelial, connective
muscles and nervous tissues.
- Organs are structures composed of two or more tissues that perform
specific functions.
- Organs are arranged into eleven organ systems of the human body.
- Organ systems interact to form a whole functioning organism.
 Although many cells of the body differ from each other in their functions, all
of them have certain basic characteristics:
1- Oxygen combines with breakdown products of fats, carbohydrates or
proteins to release energy that is required for normal function.
2- Most cells have the ability to reproduce and whenever the cells are
destroyed, the remaining cells generate new cells until the appropriate
number is restored.
3- Cells are bathed in extracellular fluid (ECF), the constituents of which
are precisely controlled.
 The constancy of ECF is necessary for the maintenance of the cells by
homeostasis mechanism that monitor, regulate its temperature, osmotic
pressure, PH, and composition.
Homeostasis
 Homeostasis is the condition in which the body functions.The body fluids and
other factors of internal environment are maintained at levels suitable to
support life.
 Homeostasis mechanisms are triggered by the alteration in some physiological
properties and act to produce a compensating change to return the system to
the normal situation.
1
 All homeostatic mechanisms consist of receptors, control center and
effectors. The receptors are the sensing component that monitors and
responds to change in the environment. When the receptor senses a stimulus,
it sends information to the control center (brain).
 The brain determines an appropriate response to the stimulus. Then it sends
signals to the effectors, which can be muscles, organs or other structures.
 After receiving the signals, a change occurs to correct the deviation by either
enhancing it with positive feedback or inhibiting it with negative feedback.
Positive feedback
 Positive feedback is a mechanism by which an output is enhanced such as

protein levels.
 A positive feedback mechanism is rarely used by the body due to risks of the
acceleration becoming uncontrollable.
 An example of positive feedback in the body is blood platelet accumulation,
which in turn causes blood clotting in response to a tear in the lining of the
blood vessels.
Negative feedback
 Negative feedback is a mechanism by which the output activity of any organ

and system is reduced back to its normal range of functioning.
 An example of this mechanism is regulating blood pressure:
- Blood vessels can resist blood flow against the walls when blood pressure
increases.
- The blood vessels act as the receptors to relay this message to the brain.
The brain then sends a message to the heart and blood vessels (the
effectors.)
- The heart rate decreases as the blood vessels diameter increases
(vasodilation), causing the blood pressure to fall back to its normal range.
Homeostatic imbalance
Overview
 When positive and negative feedback loops are affected in any way,
complications may occur, leading to homeostatic imbalance.
Many diseases result from of homeostatic imbalance include diabetes,
dehydration, hypoglycemia, hyperglycemia, gout and any disease result
from bloodstream toxins.
- Diabetes occurs when the control mechanism for insulin becomes
imbalance either because deficient insulin or the cells have become resistant
to insulin.
 Aging is a source of homeostatic imbalance as the control mechanisms of the
feedback loops lose their efficiency.
 Homeostasis is the property of a system that regulates its internal
environment, maintaining stable, relatively constant set of properties e.g.,
2
temperature or PH in which the body’s internal environment is kept stable
and functional.
Regulation of body functions

1- Nervous system:
This directs the activity of the muscular thereby providing locomotion .It also
controls the functions of many internal organs through the automatic nervous
system.
 It consists of afferent nerve fibers: linking receptors to coordinating system
in the brain and spinal cord, and efferent nerve fibers that carry information
from the coordinating system to the effecter organs.
 There are two major subdivisions of the efferent system: the somatic nervous
system uses skeletal muscles as effectors for purposive behavior and reflex
actions; the autonomic nervous system sends its efferent to gland, heart,
smooth muscles in hollow organs and blood vessels.
2- Endocrine system:
 This comprises glands which secret hormones into the blood to affect the
function of target cells throughout the body.
 Hormonal actions are generally slower and less sharply localized than those of
nervous system.
 Hormonal actions are under the control of nervous system through
neurohormones produced in the brain (hypothalamus and pituitary gland), that
influence other endocrine glands.
The importance of water in the body:
 Water constitutes about 60%of the body weight.It has special properties
which are suited to life .About 67%of this fluid in the cells ,the intercellular
fluid (ICF),and 33%is extracellular fluid (ECF).
 The ICF is high in K+, the positive charge of which balances the negative
charge of organic solutes .The ECF is high Na+ and Cl- .
 In a man about 60%of the body weight is due to water. In a woman about
55%of the body weight is water (relatively greater percentage of body weight
contributed by fat cells).
 A 70 Kg man has 28Lof intercellular water and 14L of extracellular water.3 L
of extracellular water is in the blood plasma. The remaining 11L constitutes
the interstitial fluid (lymph) that provides an aquatic habitat surrounding the
cells.
Exchange between capillaries and interstitial fluid

 The heart and blood vessels comprises a circulatory system that carries
water and solutes including hormones and gases through the body.
 In the tissues, capillaries bring the blood within 5-10µm of the most cells,
and the solutes like glucose and O2 must:
3
1- Cross the capillary walls.
2- Cross the layer of interstitial fluid between the capillary and the cell.
3- Cross the plasma membrane which separates ICF from ECF.
Cell structure and function
Overview
 Cells are the basic structural and functional unit of the body.
 Most cells contain nucleus to direct the activities of the cells.
 The nucleus surrounded cytoplasm.
 The cytoplasm contain cytosol within which sit various types of organelles.
 The cytoplasm is enveloped by cell membrane (plasma membrane).
 Functions of the cells:
1- Cells metabolize and release energy
2- Cells synthesize molecules.
3- Cells provide means of communications.
4- Cells reproduce and provide for inheritance.
The cell membrane

 Cell membrane is a lipid bilayer separates the internal cellular environment
from ECF.
 The lipid bilayer is composed of phospholipids arranged as hydrophilic
glycerol backbone and two hydrophobic fatty acid tails. Plasma membrane
serves as selectively permeable protective barriers
1- Fat soluble (hydrophobic) substance, e.g., steroid hormones can dissolve
in the hydrophobic bilayer, therefore can freely cross the membrane.
2- Water soluble (hydrophilic) substances, e.g., Na+ and glucose cannot
dissolve in this bilayer and must pass through pores or use carrier proteins.
 Proteins, carbohydrates and cholesterol are embedded in the lipid bilayer.
 Membrane proteins function as signaling, cell-cell recognition (marker
molecules), attachment proteins, transport proteins (include channel proteins,
carrier proteins and ATP powered pump) and enzymes.
 There are two major classes of membrane proteins:
1- Integral, which are permanently bound to lipid bilayer. Most integral
proteins are transmembrane proteins which can function as transporters,
receptors, structural proteins or mediated cell adhesion, (figure1.1).
2- Peripheral which are temporarily associated with lipid bilayer or with

integral protein, Peripheral proteins regulate cell signaling through
assembly into multi-protein complexes or activation of their biological
activity upon membrane binding.
 The cell membrane is commonly described as fluid mosaic model, because
proteins can freely move within the phospholipids bilayer. (Figure1.1).
 The nuclear envelope, endoplasmic reticulum, Golgi apparatus,
lysosomes, and the plasma membrane comprise the endomembrane system
4
Glycolipid
s
Hydrophgilic heads
Channel
Integral protein
Hydrophobic tail Peripheral protein
Figure (1.1): Structure of cell membrane.(Scanlon V.C. and Sanders T. Essential of Anatomy and
Physiology . Philadelphia, E.A. Davis Company, 2007).
The nucleus
 The nucleus averages about 5 microns in diameter.It is centrally located
within the cell and surrounded by two-layer nuclear envelope, which
separate the cytoplasm from the nucleoplasm ( figure1. 2 ). Each layer of the
envelope is a lipid bilayer.
- The double membranes are fused to form a pore that allows large
macromolecules and particles to pass through. The nuclear side of the
envelope is lined by the nuclear lamina, a network of intermediate
filaments that maintain the shape of the nucleus.
 The nucleus contains most of the genes in cell. Within the nucleus, the DNA
and associated proteins are organized into fibrous material, chromatin. In a
normal cell they appear as diffuse mass.
 However when the cell prepares to divide, the chromatin fibers coil up to be
seen as separate structures, chromosomes.
 A typical human cell has 46 chromosomes, but sex cells (eggs and sperm)
have only 23 chromosomes. In the nucleus is a region of densely stained fibers
and granules adjoining chromatin, the nucleolus.
 In the nucleolus, ribosomal RNA (rRNA) is synthesized and assembled with
proteins from the cytoplasm to form ribosomal subunits.
 The subunits pass from the nuclear pores to the cytoplasm where they
combine to form ribosomes.
 The nucleus directs protein synthesis by synthesizing messenger RNA
(mRNA).
5
 The mRNA travels to the cytoplasm and combines with ribosomes to translate
its genetic message into the primary structure of a specific polypeptide chains.
Figure (1.2): Structure of the nucleus.( Reece J.B., Urry L.A., Cain M.L., Wasserman
S.A., Minorsky P.V. and Jackson R.B. Campbell Biology.San Francisco, Benjamin
Cummings,2014).
Ribosomes
 Ribosomes contain rRNA and protein.
 A ribosome is composed of two subunits that combine to carry out protein
synthesis.(Figure 1.3).
 Cell types that synthesize large quantities of proteins (e.g., pancreas) have
large numbers of ribosomes and prominent nuclei.
 Some ribosomes are free ribosomes suspended in the cytosol and
synthesize proteins that function within the cytosol.
 Other ribosomes are bound ribosomes attached to the outside of the
endoplasmic reticulum. These synthesize proteins that are either included
into membranes or for export from the cell.
6
Figure (1.3): The ribosome.(Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A.,
Minorsky P.V. and Jackson R.B. Campbell Biology.San Francisco, Benjamin
Cummings,2014)
Endoplasmic reticulum
 The endoplasmic reticulum (ER) accounts for half the membranes of the
cell.
 The ER includes membranous tubules and internal fluid-filled spaces (
the cisternae).
 The ER membrane is continuous with the nuclear envelope and the cisternal
space of the ER is continuous with the space between the two membranes of
the nuclear envelope. Figure (1.4).
 There are two connected regions of ER that differ in structure and function:
1- Smooth ER looks smooth because it lacks ribosomes.

 Enzymes of smooth ER synthesize lipids, including oils, phospholipids,
and steroids.
 The smooth ER catalyzes a key step in the mobilization of glucose from
stored glycogen in the liver.
 An enzyme removes the phosphate group from glucose phosphate, a
product of glycogen hydrolysis, permitting glucose to exit the cell.
 Other enzymes in the smooth ER of the liver help detoxify drugs and
poisons. These include alcohol and barbiturates.
 Frequent exposure leads to proliferation of smooth ER, increasing
tolerance to the target and other drugs.
 Muscle cells are rich in enzymes that pump calcium ions from the
cytosol to the cisternae. When nerve impulse stimulates a muscle cell,
calcium rushes from the ER into the cytosol, triggering contraction.
2- Rough ER looks rough because bound ribosomes are attached to the

outside, including the outside of the nuclear envelope.
 Rough ER is abundant in the cells that secrete proteins.
 As a polypeptide is synthesized by the ribosome, it is threaded into the
cisternal space through a pore formed in the ER membrane. Many of
these polypeptides are glycoproteins (polypeptides to which the
oligosaccharides are attached).
 These secretory proteins are packaged in transport vesicles that carry
them to their next stage.
 Rough ER is also a membrane factory. Membrane bound proteins are
synthesized directly into the membrane.
 Rough ER enzymes synthesize phospholipids from precursors in the
cytosol.
7
Figure (1.4): Smooth and rough endoplasmic reticulum. (Reece J.B., Urry L.A., Cain
M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco,
Benjamin Cummings,2014).
Golgi apparatus
 The Golgi apparatus is a series of closely modified cisternae that functions
to modify, package and distribute lipid and proteins produced by the ER.
 The Golgi apparatus consists of flattened membranous sacs - cisternae.
- The membrane of each cisterna separates its internal space from the
cytosol
- One side of the Golgi, the cis side, receives material by fusing with
vesicles, while the other side, the trans side, buds off vesicles that move
to other sites. Figure (1.5). During this, products from the ER are
modified (modifications of the oligosaccharide portion of
glycoproteins).
 The Golgi can synthesize its own macromolecules, including pectin and
other noncellulose polysaccharides.
 Finally, the Golgi tags, sorts, and packages materials into transport vesicles.
8
Figure (1.5): Golgi apparatus.( Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A.,
Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco, Benjamin Cummings,
2014).
Lysosomes
 The lysosome is a membrane-bounded sac of hydrolytic enzymes that

digests macromolecules.
 Lysosomal enzymes can hydrolyze proteins, fats, polysaccharides, and
nucleic acids.These enzymes work best at pH 5.
 While rupturing one or few lysosomes has little impact on a cell, but
massive leakage from lysosomes can destroy the cell by autodigestion.
 The lysosomes create a space where the cell can digest macromolecules.
 At least some lysosomes bud from the trans face of the Golgi.
 Lysosomes can fuse with food vacuoles formed when a food item is brought
into the cell by phagocytosis. As the polymers are digested, their monomers
pass out to the cytosol to become nutrients of the cell.
 Lysosomes can also fuse with another organelle or part of the cytosol. This
process of autophagy renews the cell.(Figure1.6).
Clinical note: Several inherited diseases affect lysosomal metabolism.These individuals

lack a functioning version of a normal hydrolytic enzyme. Lysosomes are engorged with
indigestible substrates. These diseases include Pompe’s disease in the liver and Tay-
Sachs disease in the brain.
Clinical note: When mitochondrial dysfunction is inherited through mitochondrial

DNA, all offsprings are equally affected, but only female offspring pass on the
disorder.However the other type of mitochondrial dysfunction result from defects in
specific proteins that are coded by nuclear DNA but function in mitochondria such as
Leber hereditary optic neuropathy (LHON), which is characterized by loss of vision in
the center visual field.
9
Figure (1.6): Function of the lysosomes. Figure (1.7): Structure of mitochondria
(Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell
Biology. San Francisco, Benjamin Cummings,2014).
Mitochondria
 Mitochondrion is the site of cellular respiration, generating ATP from the
catabolism of sugars, fats, and other fuels in the presence of oxygen.
 The proteins of the mitochondria come primarily from free ribosomes in the
cytosol and a few from their own ribosomes. They have small quantities of
DNA that direct the synthesis of the polypeptides produced by these internal
ribosomes.
 The number of mitochondria is correlated with aerobic metabolic activity.
 A typical mitochondrion is 1-10 microns long. Figure (1.7).
 Mitochondria are quite dynamic: moving, changing shape, and dividing.
 Mitochondria have a smooth outer membrane and a highly folded inner
membrane, the cristae. This creates a fluid-filled space between them. The
cristae present ample surface area for the enzymes that synthesize ATP.
 The inner membrane encloses the mitochondrial matrix, a fluid-filled
space with DNA, ribosomes, and enzymes.
 Mitochondria and their DNA are inherited maternally (mitochondria are
received only from the egg, not from sperm).
10
Peroxisomes
 They are membrane bound sacs containing enzymes that transfer hydrogen
from various substrates to oxygen. An intermediate product of this process is
hydrogen peroxide (H2O2), a poison, but the peroxisome has another enzyme
that converts H2O2 to water.
 Some peroxisomes break fatty acids down to smaller molecules that are
transported to mitochondria for fuel.
 Others detoxify alcohol and other harmful compounds.
The Cytoskeleton
Overview
 The cytoskeleton is a network of fibers extending throughout the cytoplasm.
 It Provides mechanical support, cell flexibility and cell motility and aids in
cell division.
 There are three main types of fibers in the cytoskeleton: microtubules,
microfilaments, and intermediate filaments .(Table 1.1)
Table (1.1): The structures and function of the cytoskeleton. (Reece J.B. ,Urry L.A., Cain
Benjamin Cummings,2014).
11
1- Microtubules
 The thickest fibers are hollow rods about 25 microns in diameter.
Microtubule fibers are constructed of the globular protein, tubulin.
 They move chromosomes during cell division.
 Another function is as tracks that guide motor proteins carrying organelles
to their destination.
 Microtubules are the central structural supports in cilia and flagella.
2- Microfilaments
 They are the thinnest class of the cytoskeletal fibers, solid rods of the
globular protein actin.
 An actin microfilament consists of a twisted double chain of actin subunits.
 Microfilaments are designed to resist tension.
 In muscle cells, thousands of actin filaments are arranged parallel to one
another.
 The thicker filaments are composed of a motor protein, myosin, interdigitate
with the thinner actin fibers.
3- Intermediate filaments
 They are intermediate in size at 8 - 12 nanometers, specialized for bearing
tension.
 Intermediate filaments are built from a diverse class of subunits from a
family of proteins called keratins.
 Intermediate filaments are more permanent fixtures of the cytoskeleton than
are the other two classes.
 They reinforce cell shape and fix organelle location.
Extra non-membranous-enclosed organelles
1- Microvilli
 They are small fingerlike projections of the plasma membrane.
 Function to increase surface area for absorption of extracellular substance.
 Examples of cells type with microvilli are the brush borders of the
intestinal epithelium and the proximal convoluted tubule (PCT) of the
nephron.
2- Centrioles
 They are bundles of microtubules linked by other proteins.
 At least two are present in the centrosome of each cell capable of cellular
division. Figure (1.8).
 They are function in the cell division by forming spindle fibers that separate
homologous chromosomes.
12
Figure (1.8): Centrioles. Figure (1.9): Movement of flagella
Biology. San Francisco, Benjamin Cummings, 2014).
3- Cilia
 Long fingerlike projections of plasma membrane, differ from microvilli in
that they are supported by microtubules.
 They are two types motile and non-motile cilia.
 Motile cilia function to move fluid and/or secretions along the cell surface,
whereas the non-motile cilia play a sensory role.
4- Flagella
 They are Similar in shape to cilia but longer.
 Like cilia they supported by microtubules.
 Function in the movement of cells in the medium.
 The sperm cell is only human cell with flagellum.
 A flagellum has an undulating movement. Figure(1.9 )
Transport across membranes

Overview
 Fat soluble molecules pass through the plasma membrane by dissolving in
the bilayer.
 Small molecules pass through membrane channels .Most channels are
positively charged allowing negatively charge ions and neutral molecules to
pass.
 Large polar substances e.g., glucose, amino acids transport through the
membrane by carrier molecules.
 Large pieces of material enter cells in vesicles.
13
1- Simple Diffusion
 The process whereby a substance moves down its concentration gradients
across a semipermeable membrane.
 This tends to equalize the concentration of substance on both side of the
membrane.
 No metabolic energy or carrier protein is required.
a- Diffusion of uncharged substances

 The rate of diffusion (J) is dependent on the concentration gradient
(ΔC), the surface area to diffuse (A) and the membrane permeability
(P).
J=PA (ΔC)
 Permeability (P) is directly proportional to the lipid solubility of the

substance and inversely proportional to the size of molecules and
thickness of the membrane.
 Small hydrophobic molecules have the highest permeability in the lipid
bilayer.
b- Diffusion of charged substances

 The net rate of diffusion (J) depends on the electrical potential
differences across the membrane.
 Positively charge ions (cations) tend to diffuse into the cell, whereas
negatively charged ions (anions) tend to diffuse out of the cells, because
at rest the inside of the cell is negatively charged.
c- Diffusion of polar and non polar substances

 Non polar substances e.g., O2, CO2 gases diffuse across the membrane more
rapidly than the polar substances do e.g., water, due to the relative solubility in
the lipid.
d- Diffusion of gases
 Gases have great area to diffuse across the entire surface area of the cell.
 The diffusion rate of a gas (Vg) depends on the pressure differences
across the membrane (ΔP), surface area of the cell (A), the diffusion
coefficient (d) and thickness of the membrane (T).
Vg= ΔP ˟ A ˟ d
T
14
Clinical note: Gas exchange in lung normally occurs efficiently across thin lipid –
rich pulmonary capillary and alveolar walls. However, in pathologic state such as
pneumonia, gas exchange becomes less efficient because the accumulation of
fluid increases the distance over which O2 must diffuse.
2- Osmosis
 Osmosis is the movement of water (not dissolved solutes) across a
semipermeable membrane.
 A difference in solute concentration across the membrane generates osmotic
pressure which causes the movement of water from area of low solute
concentration (hypotonic solution) to that of high solute concentration
(hypertonic solution), (figure 1.10).
 Osmotic pressure depends on the following :
1. The concentration of osmotically active particles (osmotic pressure
increases with increase solute concentration).
2. The ability of the particles to cross the membrane, which depends on
particles size and charge.
 If the solution on either sides of membrane has equal osmotic pressure,
they are said to be (isotonic solution).
 If cells placed in an isotonic solution neither swell nor shrink. While in a
hypertonic solutionthey the cells shrink. In a hypotonic solution, they swell
and may burst (lyse).
Figure (1.10): Osmosis, the movement of water from thehypotonic solution to the
hypertonic solution. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology.
New York, McGraw –Hill Companies, 2008).
15
3- Carrier- mediated transport
 Mediated transport is the movement of a substance across a membrane by
means of transport protein.
 The substances transported tend to be large, water soluble molecules.
 Characteristics of carrier mediated transport:
1. Stereospecifity of carrier: Only one isomer of a substance is
recognized by the carrier protein.
2. Competition for carrier binding sites. Substances with similar
structure can compete for binding to the carrier proteins.
3. Saturation of carrier proteins: when all transport binding sites for a
particular substance are occupied, the transport maximum (Tm) has
been reached; the substance has no longer bind to its carrier and
therefore cannot pass through the membrane.
 There are three kinds of mediated transport:
1- Facilitated diffusion :
 Movement of substances down their electrochemical gradient and
does not require energy (ATP).
 Stops if the concentration of the substance inside the cell reaches the
extracellular concentration or if carrier molecules become saturated.
 The molecules that are transported via facilitated diffusion are not
permeable to plasma membrane .Thy include ions and nonpolar
molecules that are poorly soluble in water.
2- Active transport :
 Uphill transport of a substance against its electrochemical gradient.
 Energy from hydrolysis of adenosine tri-phosphate (ATP) is required.
 Nerve cells and muscle cells have“sodium pumps” to move sodium ions
(Na+) out of the cells,inspit that Na+ are more abundant outside the cells.
Without the sodium pumps the incoming sodium ions would bring about an
unwanted nerve impulse or muscle contraction. Nerve and muscle cells
constantly produce ATP to keep their sodium pumps (and similar
potassium pumps) working and prevent spontaneous impulses.
Pharmacology note: Proton pump inhibitors such as omeprazole are used to

treat peptic ulcer diseas.These drugs directly inhibit the H+,K+-ATPase (proton)
pump of gastric parietal cells .This reduces the acidic content of the stomach
and allows for healing of the damaged mucosa.
16
Figure (1.11): Sodium potassium pump in the verve cell. ( Randall D., Burggren W.
and French K. Eckert Animal Physiology . New York, W.H. Freeman and Company, 2002).
a- Primary active transport:

 The transport of a substance across the plasma membrane directly coupled
to ATP hydrolysis.
 Examples include the the Na+,K+-ATPase (sodium) pump in the plasma of
all cells, the H+,K+-ATPase(proton) pump of gastric parietal cells, and the
Ca+-ATPase pump in muscle cells.
b- Secondary active transport:

 The simultaneous movement of two substances across the plasma membrane
indirectly coupled to ATP hydrolysis. One substance moves down its
concentration gradient, and this drives the uphill transport of other substance
against its concentration gradient.
- Cotransport (symport): both substances move in the same direction,
e.g., Na+-glucose cotransport in the epithelial cells of the brush border of
the small intestine.
- Countertransport (antiport): the substances move in opposite
directions,e.g.,Na+-Ca+countertransport of the heart muscle cell moves Ca+
against its concentration gradient as Na+ moves down its concentration
gradient.
17
Figure (1.12): Cotransport: Two substances move in the same direction. ( Randall D.,
Burggren W. and French K. Eckert Animal Physiology . New York, W.H. Freeman and
Company, 2002).
Pharmacology note: Cardiac glycosides such as ouabain and digitalis inhibit the
Na+, K+-ATPase (sodium pump in the myocardium) .This increases the amount of
sodium inside the cell, triggering the Ca+-Na+ countertransport .More calcium is
brought into the cell, which increases the contraction of atrial and ventricular
myocardium and increases cardiac output.
4- Vesicular transport
 Large molecules, such as polysaccharides and proteins cross the
membrane via vesicles.
 During exocytosis, a transport vesicle budded from the Golgi apparatus is
moved by the cytoskeleton to the plasma membrane.
 When the two membranes come in contact, the bilayers fuse and spill the
contents to the outside.
 During endocytosis, a cell brings in macromolecules and particulate matter
by forming new vesicles from the plasma membrane.
 Endocytosis is a reversal of exocytosis.
 A small area of the plasma membrane sinks inward to form a pocket
 As the pocket into the plasma membrane deepens, it pinches in, forming a
vesicle containing the material that had been outside the cell
 One type of endocytosis is phagocytosis, “cellular eating”.(Figure1.13,a)
 In phagocytosis, the cell engulfs a particle by extending pseudopodia
around it and packaging it in a large vacuole.
18
 The contents of the vacuole are digested when the vacuole fuses with a
lysosome.
 In pinocytosis, “cellular drinking”, a cell creates a vesicle around a droplet
of extracellular fluid. This is a non-specific process.(Figure 1.12,b)
Clinical note: In chronic granulomatous disease (CGD), mutations in the proteins of

NADH oxidase system result in a reduced ability of phagocytic cells to produce the
super oxide radical (O2-) and its products the hydroxyl radical (OH-) and hydrogen
peroxide (H202).The enzyme catalase breaks down the hydrogen peroxide produced
by the phagocytic cell and further decreases the cell’s ability to destroy the offending
microbe. Microbial killing is severely impaired in these patients and phagocytic cells
accumulate forming granulomas in area of infection such as skin, lungs, liver, spleen
and lymph nodes.
accumulate forming granulomas
Figure (1.13): a: phagocytosis (cellular eating), b: pinocytosis (cellular drinking).

(Marieb E.N .Essential of Human Anatomy and Physiology .San Francisco, Pearson Education,
2012).
 Receptor-mediated endocytosis is very specific in what substances are

being transported.
- This process is triggered when extracellular substances bind to special
receptors, ligands, on the membrane surface, especially near coated pits.
- This triggers the formation of a vesicle receptor-mediated endocytosis
which enables a cell to acquire bulk quantities of specific materials that
may be in low concentrations in the environment.(1.14).
- Human cells use this process to absorb cholesterol.
- Cholesterol travels in the blood in low-density lipoproteins (LDL),
complexes of protein and lipid.
19
- These lipoproteins bind to LDL receptors and enter the cell by
endocytosis.
Clinical note: Familial hypercholesterolemia, an inherited disease, the LDL receptors

are defective, leading to an accumulation of LDL and cholesterol in the blood. This
contributes to early atherosclerosis.
Figure (1.14): Receptor-mediated endocytosis. (Marieb E.N .Essential of Human Anatomy

and Physiology .San Francisco, Pearson Education, 2012).
Junctions between cells

1- Tight junctions :( zonula occludens)
 They are attachments between the cells (epithelial cells)
 Intercellular pathway for solutes depending on size, charge and
characteristic of the junction.
 They may be tight (in renal distal tubule) or leaky as in renal proximal
tubule.
2- Gap junctions:
 They are the attachments between cells that permit intercellular
communication.
 They permit current flow and electrical coupling between myocardial cells.
3- Desmosomes (macula adherence):

 They are cell to cell spot adhesion present on the lateral membrane of cells,
resist shearing force in the squamous epithelium.(Figure 1.15).
4- Hemidesmosomes:
 They anchor cells to the extracellular matrix (ECM).
 They composed of integrin cell adhesion proteins, which play important
roles in cellular attachment and in signal transduction.
20
Figure (1.15): A hypothetical cell shows different types of junctions. (Randall D.,
Burggren W.and French K. Eckert Animal Physiology. New York, W.H. Freeman and
Company, 2002).
References
1. Brown T.A. Rapid Review of Physiology.2nded.Philadelphia, Mosby, 2012.
2. Marieb E.N .Essential of Human Anatomy and Physiology .10th ed. San Francisco,
Pearson Education, Inc.,2012.
3. Peterson O.H.(ed).Lecture notes :Human Physiology.5thed .Massachusetts, USA
,Blackwell Publishing,2007.
4. Randall D. ,Burggren W. and French K. Eckert Animal Physiology .5th ed. New York,
W.H. Freeman and Company, 2002.
5. Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B.
Campbell Biology.9th ed. San Francisco, Benjamin Cummings,2014.
6. Scanlon V.C. and Sanders T. Essential of Anatomy and Physiology .5th ed.
Philadelphia, E.A. Davis Company, 2007.
7. Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . 8 th ed. New York,
McGraw –Hill Companies, 2008.
21
Chapter Two
The Cell Cycle and Genes 2
Control of Protein Synthesis
Organization of the genetic material within the cell

Overview
 Cell division is a complex process requiring precise replication the genetic
material (DNA).
 The entire DNA in a cell is called the cell‟s genome.
 The DNA is divided into many genes, each of which contains one piece of
information necessary for cell function. These structures called
chromosomes.
 Chromosomes consist of long strands of DNA associated with proteins.
 Chromosome is composed of Chromatin which is made up of DNA and
associated proteins. Figure (2.1).
 The chromatin shape changes depending on the cell cycle stage. When the
cell is not dividing the chromatin is stretched out into long thin strands and
is barely visible. After DNA replication and when the cell gets ready to
divide, the chromatin condenses to form tightly coiled, highly visible, dark
bodies, called chromosomes, which are visible under the microscope.
 In sexually reproducing organisms, these chromosomes are in pairs .One
number of each pair is derived from each parent
 Chromosomes numbers are specific to specific type. Most cells are body
cells (somatic cells).In human somatic cells contain 46 chromosomes,
divided into 23 pairs.
 Human gametes (sperm or eggs) have 23 chromosomes, half the number in
a somatic cell.
 When an egg and sperm combine during reproduction, somatic cell
chromosome number will be restored.
Figure (2.1): Chromosome structure.(Reece J.B., Urry L.A., Cain M.L., Wasserman
S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco, Benjamin
Cummings, 2014).
22
Cell Cycle
Overview
 The cell cycle includes all the events that occur from the cell’s formation
until it divides to produce two new cells.
 Cell cycle has two stages: An interphase and a cell division (mitotic phase
(M)).Figure (2.2 ).
Figure (2.2): Cell cycle. (Marieb E.N .Essential of Human Anatomy and Physiology. San
Francisco, Pearson Education, Inc., 2012).
1. Interphase
 Interphase is the phase between cell divisions.
 It represents 90% of the cell cycle.
 During this time ,the cell carries out the metabolic activities necessary for life
and perform its specialized functions ,e.g.,secreting digestive enzymes
 It prepares the cell to divide, e.g.an increase in cell size because many cell
components double in quantity and replication of cell’s DNA.
 The centerioles within the centrosome are also duplicated.
 Consequently when the cell divides, each new cell receives organelles and
DNA necessary for continued functioning.
 It has three phases:
1- The G1 phase (first gap) is for growth.
2- The S phase(synthesis) when the chromosomes are copied (DNA
synthesis)
3- The G2 phase (second gap): the cell completes preparations for division.
23
DNA replication
 DNA replication is the process by which two new strands of DNA are made
using the two existing strands as template.
 During interphase DNA and its associated proteins appear as dispersed
chromatin threads within the nucleus.
 When DNA replication begins the two strands of each DNA molecule
separate from each other .Each strand work as a template for production of
new complementary strand of DNA, which is formed as complementary
nucleotides pair with the existing nucleotides of each strand of the
separated DNA molecule.
 The replication of a DNA molecule begins at special sites, origins of
replication. There may be hundreds or thousands of origin sites per
chromosome .At the origin sites, the DNA strands separate forming a
replication “bubble” with replication forks at each end.
 The production of new nucleotides strands is catalyzed by DNA
polymerase, an enzyme that adds new nucleotides at a replication fork.
 The rate of elongation is about 50 per second in human cells.
 The strands are formed differently because the antiparallel orientation of the
strands.
 Each DNA strand has a 3‟ end with a free hydroxyl group attached to
deoxyribose and a 5‟ end with a free phosphate group attached to
deoxyribose.Figure (2.3).
 The 5’ -> 3’ direction of one strand runs counter to the 3’ -> 5’ direction of
the other strand.
 DNA polymerases can only add nucleotides to the free 3’ end of a growing
DNA strand.
 At the replication fork, one parental strand (3’-> 5’ into the fork), the
leading strand, can be used by polymerases as a template for a continuous
complimentary strand.
 The other parental strand (5’->3’ into the fork), the lagging strand, is
copied away from the fork in short segments (Okazaki fragments). Figure
(2.4).
 Okazaki fragments, each about 100-200 nucleotides, are joined by DNA
ligase to form the sugar-phosphate backbone of a single DNA strand.
 As a result of DNA replication, two identical DNA molecules are produced.
.Each of theseDNA molecules has one strand of nucleotides derived from
the original DNA molecule and one newly synthesized strand.
24
Figure (2.3): Each DNA strand has a Figure (2.4): Leading strand, lagging
3’ end with a free hydroxyl group strand and Okazaki fragment.
attached to deoxyribose and a 5’ end
with a free phosphate group attached
to deoxyribose.
(Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B.
Campbell Biology. San Francisco, Benjamin Cummings,2014).
2. Cell Division
Overview
 A single cell reproduces by cell division, where the cell and its genetic
material are copied and passed along to its offspring.
 The cell division is responsible for carrying out three essential functions:
1- Reproduction: In many single cell organisms, simple cell division is
the major form of reproduction, in which the cell replicates itself
precisely,
2- Growth and development: Sexually producing organism, e.g., a single
fertilized egg or zygote of human exposes to series of divisions to
produce trillions of cells.
3- Repair and replacement of cells: The cells continually wear out due to
injury and diseases and they must be replaced by other cells.
 Cell division involves two major events: the division of the nucleus, by
mitosis, to form two nuclei and then division of cytoplasm (cytokinesis) to
form two new cells.
25
1-Mitosis
 Mitosis is the division of the nucleus into two nuclei, each of which has the
same amount and type of DNA as the original nucleus.
 Mitosis is divided into five phases: prophase, prometaphase, metaphase,
anaphase, and telophase.(Figure2.5).
 By late interphase, the chromosomes have been duplicated but are loosely
packed.
 The centrosomes have been duplicated and begin to organize microtubules
into an aster (star).
1. In prophase
 The chromosomes are tightly coiled, with sister chromatids joined together.
 The nucleoli disappear.
 The mitotic spindle begins to form and appears to push the centrosomes
away from each other toward opposite ends (poles) of the cell.
2. Prometaphase
 The nuclear envelope fragments and microtubules from the spindle interact
with the chromosomes.
 Microtubules from one pole attach to one of two kinetochores, special
regions of the centromere, while microtubules from the other pole attach to
the other kinetochore.
3. Metaphase
 The spindle fibers push the sister chromatids until they are all arranged at
the metaphase plate, an imaginary plane equidistant between the poles,
defining metaphase.
4. Anaphase
 The centromeres divide, separating the sister chromatids.
 Each is now pulled toward the pole to which it is attached by spindle fibers.
 By the end, the two poles have equivalent collections of chromosomes.
5. Telophase
 The cell continues to elongate as free spindle fibers from each centrosome
push off each other.
 Two nuclei begin for form, surrounded by the fragments of the parent’s
nuclear envelope.
 Chromatin becomes less tightly coiled.
 Cytokinesis, division of the cytoplasm, begins.
26
Figure (2.5): Diagramatic and overall view of mitosis phases.( Reece J.B. ,Urry L.A.,
Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San
Francisco, Benjamin Cummings,2014).
2- Cytokinesis
 Cytokinesis is the division of cytoplasm to produce two new cells.
 Cytokinesis begins in anaphase, continues through telophase and end in the
following interphase.
 The first sign is the formation of cleavage furrow, which form midway
between the centrioles.
 A contractile ring composed of actin filaments pulls the plasma membrane
inward, dividing the cell into halves. (Figure 2.7).
27
 Cytokinesis is completed when the membranes of the halves separate at the
cleavage furrow to form two separated cells.
Figure (2.6): Formation of contractile ring. Figure (2.7): Control system.during

cytokinesis. (Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson
R.B. Campbell Biology. San Francisco, Benjamin Cummings,2014).
Regulation of the Cell Cycle
Overview
 The timing and rates of cell division, in different parts the body, are crucial for
normal growth, development, and maintenance.
 The frequency of cell division varies with cell type. Some human cells divide
frequently throughout life (skin cells), others have the ability to divide, but
keep it in reserve (liver cells), and mature nerve and muscle cells do not
divide after maturity.
 The cell cycle events are directed by a cell cycle control system. (Figure
2.7).This triggers and coordinates key events in the cell cycle.
 The control cycle has a built-in clock, but it is also regulated by
external adjustments and internal controls.
 A checkpoint in the cell cycle is a critical control point where stop or go
signals to regulate the cycle.
 Three major checkpoints are found, the G1, G2, and M phases.
 For many cells, the G1 checkpoint, the restriction point in mammalian cells, is
the most important.
 If the cell receives a go-ahead signal, it usually completes the cell cycle and
divides. If it does not receive a go-ahead signal, the cell exits the cycle and
28
switches to a non-dividing state, the G0 phase. Most human cells are in this
phase.
 Liver cells can be “called back” to the cell cycle by external factor (growth
factors), but highly specialized nerve and muscle cells never divide.
 Some control molecules such as protein kinases activate and deactivate
other protein . The levels of these kinases are present in constant amounts,
but these kinases require a second protein, a cyclin,which fluctuate
cyclically,to become activated.
 The complex of kinases and cyclin forms cyclin-dependent kinases (Cdks).
 Cyclin levels rise sharply throughout interphase, then fall abruptly during
mitosis. Figure (2.8).
Figure (2.8): Peaks in the activity of Cdk complex, MPF, correspond to peaks in
cyclin concentration. (Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V.
and Jackson R.B. Campbell Biology. San Francisco, Benjamin Cummings,2014.)
 Peaks in the activity of one Cdk complex, MPF (maturation-promoting

factor), correspond to peaks in cyclin concentration; trigger the cell’s passage
past the G2 checkpoint to the M phase.
 MPF promotes mitosis by phosphorylating a variety of other protein kinases.
 The key G1 checkpoint is regulated by three Cdk proteins and several cyclins.
External adjustments
 A variety of external chemical and physical factors can influence cell division.
 growth factors, proteins released by one group of cells that stimulate other
cells to divide,e.g., platelet-derived growth factors (PDGF), produced by
platelet, in the injuried area resulting in proliferation of fibroblasts to help
heal the wound.
 Each cell type probably responds specifically to a certain growth factor or
combination of factors.
 The Growth factors appear to be a key in density-dependent inhibition of
cell division.
 Most animal cells also exhibit anchorage dependence for cell division.
29
Cell cycle controls in cancer cells.
 Cancer cells divide excessively and invade other tissues because they are free
of the body’s control mechanisms.
 Cancer cells do not stop dividing when growth factors are depleted either
because they manufacture their own, , or problem in the cell cycle control
system.
 If the cancer cells stop dividing, they do it at random points, not at the normal
checkpoints in the cell cycle.
 Cancer cell may divide indefinitely if they have a continual supply of
nutrients. In contrast, mammalian cells divide 20 to 50 times under culture
conditions before they stop, age, and die.
 The abnormal behavior of cancer cells begins when a single cell in a tissue
undergoes a transformation that converts it from a normal cell to a cancer
cell.
 Normally, the immune system recognizes and destroys transformed cells.
However, cells that evade destruction proliferate to form a tumor, a mass of
abnormal cells.
 If the abnormal cells remain at the originating site, the lump is called a benign
tumor (most do not cause serious problems and can be removed by
surgery),but when cells leave the origin site to impair the functions of an
organ or more, this results in a malignant tumor.
 In addition to chromosomal and metabolic abnormalities, cancer cells often
lose attachment to nearby cells, are carried by the blood and lymph system to
other tissues, and start more tumors in a event called metastasis. Figure (2.9).
 The causes of cancer are diverse. However, cellular transformation always
involves the alteration of genes that influence the cell cycle control system.
Figure (2.9): Breast malignancy and its metastasis.(Reece J.B. ,Urry L.A., Cain M.L.,
Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco,
Benjamin Cummings, 2014).
30
Meiosis
 Meiosis is a form of cell division that happens in sexually reproducing

organisms by which two nuclear divisions (meiosis I and meiosis II) occur
without the chromosomal replication in between, This leads to produce four
haploid gametes (sex cells), each containing one of every pair of
homologous chromosomes (that is, with the maternal and paternal
chromosomes being distributed randomly between the cells).
 Homologous chromosomes are pairs of chromosomes, each pair with the
same length, centromere position, and staining pattern, and carry genes that
control the same inherited characters.
 Each final produced cell has only half as many chromosomes as the parent
cell.
 Meiosis reduces chromosomes number by copying the chromosome once,
but dividing twice. Figure (2.10).
 The first division, meiosis I, separates homologous chromosomes and the
second, meiosis II, separates sister chromatids.
 Mitosis and meiosis have several differences, summarized in table(2.1 )
Figure (2.10): The two consecutive cell divisions, meiosis I meiosis II, (Reece
J.B. ,Urry L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B.
Campbell Biology. San Francisco, Benjamin Cummings, 2014).
31
Table (2.1): The differences in the events that occur during mitosis and meiosis.
Genes and Proteins synthesis

Overview
 The DNA contains information in the form of specific sequences of
nucleotides along the DNA strands.
 The DNA inherited by an organism leads to specific traits by dictating the
synthesis of proteins.
 Proteins are the links between genotype and phenotype.
 The study of metabolic defects provided evidence that genes specify
proteins.
 Transcription and translation are the two main processes linking gene to
protein
The Transcription and Translation processes

Overview
 Genes provide the instructions for making specific proteins.
 The bridge between DNA and protein synthesis is RNA
 The RNA molecule consists of a single strand.
 RNA is chemically similar to DNA, except that it contains ribose as its
sugar and substitutes the nitrogenous base uracil for thymine.
 In DNA or RNA, the four nucleotide monomers act like the letters of the
alphabet to communicate information.
 The specific sequence of hundreds or thousands of nucleotides in each gene
carries the information for the primary structure of a protein, the linear order
of the 20 possible amino acids.
32
 During transcription, a DNA strand provides a template for the synthesis
of a complementary RNA strand. This process is used to synthesize any type
of RNA from a DNA template.
 Transcription of a gene produces a messenger RNA (mRNA) molecule.
 During translation, the information contained in the order of nucleotides in
mRNA is used to determine the amino acid sequence of a polypeptide..
 Almost all transcription occurs in the nucleus and translation occurs mainly
at ribosomes in the cytoplasm. (Figure 2.11).
 In summary: genes program protein synthesis via genetic messenger RNA.
 The molecular chain of command in a cell is:[ DNA →RNA → protein ].
Figure (2.11): RNA processing. Figure (2.12): Transcription and translation.

 In the genetic code, nucleotide triplets specify amino acids.

 Triplets of nucleotide bases are the smallest units of uniform length that can
code for all the amino acids.
 In the triplet code, three consecutive bases specify an amino acid, creating
43 (64) possible code words.
 The genetic instructions for a polypeptide chain are written in DNA as a
series of three-nucleotide words
 During transcription, one DNA strand, the template strand, provides a
template for ordering the sequence of nucleotides in an RNA transcript.
Figure( 2.12 )
 The complementary RNA molecule is synthesized according to base-pairing
rules, except that uracil is the complementary base to adenine.
33
 During translation, blocks of three nucleotides, codons, are decoded into a
sequence of amino acids. Figure (2.13).
 The codons are read in the 5‟→3‟ direction along the mRNA.
 Each codon specifies which one of the 20 amino acids will be incorporated
at the corresponding position along a polypeptide.
 Because the base triplets, the number of nucleotides making up a genetic
message must be three times the number of amino acids making up the
protein product. It would take at least 300 nucleotides to code for a
polypeptide that is 100 amino acids long. (Figure 2.13).
 61 of 64 triplets code for amino acids.
 The codon AUG codes for the amino acid methionine
and indicates the start of translation.
 Three codons do not indicate amino acids but signal the termination
of translation.
Figure (2.13):64 triplets, 61 for amino acids, AUG codes for aminoacid methionine and
to start translation, three codons UAA, UAG, UGA to stop translation. (Reece J.B. ,Urry
L.A., Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San
Francisco, Benjamin Cummings, 2014).
 There are several different codons that would indicate a specific amino acid.
However, one codon indicates only one amino acid. But, a specific amino
acid may be decoded by several possible codons.
 Both GAA and GAG specify glutamate, but no other amino acid. Codons
synonymous for the same amino acid often differ only in the third codon
position.
34
 To extract the message from the genetic code requires specifying the correct
starting point. This establishes the reading frame and subsequent codons
are read in groups of three nucleotides.
 The cell’s protein-synthesizing machinery reads the message as a series of
nonoverlapping three-letter words.
 In summary, genetic information is encoded as a sequence of
nonoverlapping base triplets, or codons, each of which is translated into a
specific amino acid during protein synthesis.
Production of proteins
Translation
 In the process of translation, the cell interprets a series of codons along the
mRNA molecule.
 Transfer RNA (tRNA) transfers amino acids from the cytoplasm’s pool to
a ribosome.
 The ribosome adds each amino acid carried by tRNA to the growing end of
the polypeptide chain.
 During translation, each type of tRNA links a mRNA codon with the
appropriate amino acid.(Figure 2.14).
 Each tRNA arriving at the ribosome carries a specific amino acid at one end
and a specific nucleotide triplet, an anticodon, at the other.
 Codon by codon, tRNAs deposit amino acids in the prescribed order and the
ribosome joins them into a polypeptide chain.
Figure (2.14 ):Translation of mRNA to produce a protein.(Reece J.B. ,Urry L.A.,

Cain M.L., Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San
Francisco, Benjamin Cummings, 2014).
35
 There are three stages: initiation, elongation and termination.
1- Initiation brings together mRNA, a tRNA with the first amino acid, and
the two ribosomal subunits.(Figure 2.15).
Figure (2.15): The initiation stage. (Reece J.B., Urry L.A., Cain M.L., Wasserman S.A.,
2014).
2- Elongation consists of a series of three steps cycles, as each amino acid

is added to the proceeding one. Figure (2.16 )
 Codon recognition:an elongation factor assists hydrogen bonding
between the mRNA codon under the A site with the corresonding
anticodon of tRNA carrying the appropriate amino acid.
 Peptide bond formation:rRNA molecule catalyzes the formation of a
peptide bond between the polypeptide in the P site with the new amino
acid in the A site.
 Translocation,: the ribosome moves the tRNA with the attached
polypeptide from the A site to the P site.
 The three steps of elongation continue codon by codon to add amino acids
until the polypeptide chain is completed.
Figure (2.16 ): steps of elongation. (Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A.,
2014).
36
3- Termination occurs when one of the three stop codons reaches the A site. A
release factor binds to the stop codon and hydrolyzes the bond between the
polypeptide and its tRNA in the P site. This frees the polypeptide and the
translation complex disassembles. Figure (2.17).
Figure (2.17): Termination stage. (Reece J.B. ,Urry L.A., Cain M.L., Wasserman S.A.,
2014).
 Typically a single mRNA is used to make many copies of a polypeptide

simultaneously. Multiple ribosomes, polyribosomes, may trail along the
same mRNA.
 A ribosome requires less than a minute to translate an average-sized mRNA
into a polypeptide.
 During and after synthesis, a polypeptide coils and folds to its three-
dimensional shape spontaneously. The primary structure, the order of amino
acids, determines the secondary and tertiary structure.
 Proteins may require posttranslational modifications before doing their
particular job. This may require:
 Additions like sugars, lipids, or phosphate groups to amino acids.

 Enzymes may remove some amino acids or cleave whole polypeptide
chains.
 Two or more polypeptides may join to form a protein.
Regulation of Genetic Expression

 Cells become specialized because of inactivation of certain parts of the
DNA molecule and activation of other parts.
 The level of DNA activity and protein production can be controlled
internally by regulatory substances secreted by other cells.
37
Genetic Disorders
 A genetic disorder is a failure of structure, function or both as a result of
abnormalities in a person’s genetic makeup.
 Genetic disorders involve either a single gene or an entire chromosome, as
in the case of aneuploidy, (see below).
 A mutation is a change in a gene that usually involves a change in the
number or kinds of nucleotide composing the DNA.
 Mutations are known to occur randomly without known cause, but they can
be caused by chemicals, radiation and viruses. Agents that cause mutations
are called mutagens.
 Once a mutation has occurred, however the abnormal trait can be passed
from one generation to the next.
 A point mutation is a mutation involving a single nucleotide change. For
example, sickle-cell disease is caused by a mutation of a single base pair in
the gene that codes for one of the polypeptides of hemoglobin. Figure (2.18)
 A change in a single nucleotide from T to A in the DNA template leads to
an abnormal protein.
Figure (2.18): A mutation of a single base pair in the gene. (Reece J.B. ,Urry L.A., Cain
 Structural mutations are the mutations that change the sequence or number
of nucleotides involves changes in chromosome structure.
 Segregation errors that may occur during meiosis cause changes in the
chromosome number in the gametes. As the chromosomes separate during
meiosis, the two members of homologous pair may become stick and not
segregate normally .As a result the one of the new daughter cell receives both
chromosomes and the other daughter cell receives none .This is called
nondisjunction. When the gametes are fertilized, the resulting zygote has
either 47 chromosomes or 45 chromosomes rather than normal 46, a condition
called aneuploidy, which are usually lethal. Down syndrome is an example of
an aneuploidy that is not always lethal.
38
References
2. Marieb E.N. and Hoehn K. Human Anatomy and Physiology .8th ed. San Francisco,
Pearson Education Inc., 2010.
5. Tortora G. and Derrickson B. Principle of Anatomy and Physiology .13th ed.
Hoboken ,NJ, John Wiley & Sons,Inc.,2012.
39
Chapter
Chapter
ThreeThree
Nervous
Nervoussystem
System 3 3
Nervous system
Overview
 The nervous system is unique in that it affects every other system of the
body.
 Functions of nervous system :
1. Nervous system detects external and internal stimuli(sensory input )
2. It Processes and responds to sensory input (integration)
3. It Controls body movements through skeletal muscles.
4. It maintains homeostasis by regulation other system.
5. It is the center for mental activities.
Organization of the nervous system

 The nervous system is anatomically divided into two divisions:
1- The central nervous system (CNS) is responsible for analyzing data
received from sense organs and making decisions. It consists of the
brain and the spinal cord. Division of nervous system is illustrated in
figure (3.1).
2- The peripheral nervous system (PNS) is the nerves around the body. It
consists of sensory receptors, nerves, ganglia and plexuses. The PNS has
two divisions:
- The sensory system (afferent fibers):transmits action potential from
sex organs to the CNS, and usually consists of single neurons that
have their cell bodies in ganglia
- The motor system (efferent nerves): transmit action potential from
CNS to glands, muscles. This can be subdivided into:
 The somatic system controls contraction of skeletal muscle.
 The autonomic system (ANS) controls the cardiac muscle,
smooth muscle and glands. This further subdivided into:
1. Sympathetic division, which is active during physical
activity.
2. Parasympathetic division regulates functions at rest and
enteric nervous system, which control the digestive system.
40
Nervous
system
PNS CNS
Sensory Spinal
Motor system Brain
system cord
Autonomic Somatic
NS NS Cerebrum Cerebellum Diencephalon Brainstem
Parasympathetic
Sympathetic NS
NS
Figure (3. 1): Nervous system divisions.
Cells of the nervous system

 The nervous system is made up of neurons (nerve cells) and neuroglia to
support cells. (Figure3.2).
1-Neurons: This is made up of:

 The cell body is the primary site of protein synthesis. It contains the nucleus
and cell organelles.
 Dendrites are a mass of very short and branched filaments receive impulses
from other neurons.
 The axon is a very thin tube surrounded by neuroglia and may be >1m long.
It transports the impulse around the body. The axon connects to the cell
body by an axon hillock. This where an impulse (action potential) starts.
 Synaptic knobs at the end of the axon pass on the impulse usually use
chemical neurotransmitters, to the next neuron.
Type of neurons
1- Multipolar neurons have several dendrites and single axon ,e.g.,
Interneurons and motor neurons
2- Bipolar neurons have a single axon and dendrite, they are found as
components of sensory organs.
3- Unipolar neurons have a single axon .Most sensory neurons are unipolar.
41
Figure (3.2): Neurons. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and
Physiology . New York, McGraw –Hill Companies, 2008).
2- Neuroglia.
a- Neuroglia of CNS ,(figure 3.3:a,b,c,d,e )
1. Astrocytes provide structural support for neurons and blood vessels.
Astrocytes influence the functioning of the blood brain barrier and process
substances that pass through it.Astrocytes isolate damaged tissue and limit
the spread of inflammation.
2. Ependymal cells secrete and circulate using cilia the cerebrospinal fluid
surrounding the CNS. The fluid forms a reservoir and transport system for
nutrients (water, salts, and sugars) as well as being a shock absorber
against physical damage. They line the ventricle of the brain and the
central canal of the spinal cord.
3. Microglia are amoeboid phagocytic cells that destroy bacteria and dead
cells.
4. An oligodendrocyte forms myelin sheaths around the axon of several
CNS neurons.
42
a b
d
c
Figure (3.3): Types of Neuroglia, (a): Astrocytes (b): Ependymal cells, (c): Microglia
(d): A Schwann cells, (e): An oligodendrocyte. (Seeley R.R., Stephens T.D. and Tate P.
Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
b- Neuroglia of PNS
1. A Schwann cells form myelin sheath of the axon of the PNS neurons.
The cell wraps itself concentrically around the axon to produce a thick
myelin sheath. Myelin is a fatty substance forming an insulator, which
prevents the impulse from escaping
2. Satellite cells support and nourish neuron cell bodies within ganglia.
43
Myelinated and unmyelinated axon
a. Myelinated axons are wrapped by several layers of plasma membrane from

Shwann cells or oligodendrocytes .Space between the wrappings are the
node of Ranvier. Figure (3 .4).Myelinated axons conduct action potential
rapidly.
b. Unmyelinated axons rest in invaginations of Schwann cells or
oligodendrocyte. They conduct action potential slowly.
Figure (3.4): Node of Ranvier. (Randall D., Burggren W. and French K. Eckert Animal
Physiology . New York, W.H. Freeman and Company, 2002).
Organization of Nervous Tissue

 Nervous tissue can be grouped into white and gray matter
 Whit matter consists of myelinated axons, it propagates action
potential.White matter forms nerve tracts in the CNS and nerves in the PNS.
 Gray matter consists of collections of neurons cell bodies or unmyelinated
axons. Gray matter forms cortex and nuclei in the CNS and ganglia in PNS.
Membrane potential, Action Potential

and Nerve Transmission
Overview
 Plasma membrane of the neurons is the site of electrical signaling, and it
plays crucial role in cell to cell interactions that occur during the
development.
 Neurons are highly irritable or excitable (responsive to stimuli).
 When a neuron is adequately stimulated, an electrical impulse is generated
and conducted along the axon .This response is called action potential or
nerve impulse.
 Action potentials are important means by which cells transfer information
from one part of the body to another.
 Electrical properties of the cells result from the ionic concentration
differences across the plasma membrane.
44
 There are concentration differences for positively charged ions (cations) and
negatively charged ions (anions) between the intercellular and extracellular
fluids. These difference result primary from :
1. The Na+ - K+ pump
2. The permeability characteristic of the plasma membrane.
Concentration Differences Across

The Plasma Membrane
 The Na+ - K+ pump moves ions by active transport .K+ move into the cell,
and Na+ move out of it.
 The concentration of K+ and negatively charged proteins is higher inside,
and the concentrations of Na+ and Cl- are higher outside the cell.
 Negative charged proteins and other negative charge ions are synthesized
inside the cell and cannot diffuse out of it .They repel Cl- .
 The permeability of the plasma membrane to ions is determined by leak
channels and gated ion channels :
- Potassium ions leak channels are more numerous than Na+ leak
channels, thus the plasma membrane is more permeable to K+ than to
Na+ at rest.
- Membrane channels are large proteins with several subunits of amino
acids chains across the membrane. Membrane ions channels may be
leakage channels (non gated), and they are always open, or gated
channels. Gated ion channels include:
1- Ligand gated channels, open when appropriate
chemicals”neurotransmitters” bind.
2- Voltage gated channels open and close in response to change in
membrane potential.
3- Mechanically gated channels open in response to physical
deformation of the receptors.
Resting potential
 A potential difference across the plasma membrane is known as membrane
potential or voltage.
 In the resting state all body cells(not just neurons) a resting potential of
about -70mv, so the inside of the cell is negatively charged compared with
the fluid surrounding the cell. This results from several factors:-
- The plasma membrane contains ionic pumps (using ATP to pump

against the concentration gradient), which pump sodium ions out and
potassium ions in to the cell. But, 3 Na+ are pumped out for each 2 K+
pumped in (making the outside of the cell more positive).Figure (3.5).
- Although gradients are set up by the Na/K pump, the ions cannot diffuse
back through the plasma membrane. However, the membrane contains
specific Na+ channels and K+ channels, but the Na+ channels are shut.
Thus the Na+ pumped out cannot diffuse back in. However, the K+
45
pumped in, will be able to diffuse back out of the cell (but more slowly
than being pumped in), because some of the K+ channels are open.
Thus inside the cell is most of the K+, but outside contains almost all the
Na+ and some of the K+, giving more positive ions outside than in.
- Inside the cell are large anions, too big to escape. The attraction of
their negative charge slows down the escaping K+ until equilibrium
is set up at a potential difference of -70mv.
Nl
Figure (3.5): Events that involved in the resting membrane potential. (Seeley R.R.,
Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –Hill Companies,
2008).
 It is more correct to say that ions diffusion occurs according to the

electrochemical gradients, recording the effect of both electrical charge
and concentration of ions.
 Membrane potential acts as signals .Neurons use changes in their membrane
potential as communication signals for receiving, integrating and sending
information.
 A change in membrane potential is produced by :
- Anything that alters ion concentrations on the two sides of plasma
membrane.
- Changes in membrane permeability to any ions.
 The change in membrane potential produces two types of signals:
46
1- Graded potentials
 A graded potential is a small change in the resting membrane potential that
is confined to a small area of the plasma membrane.
 An increase in membrane permeability to Na+ can cause graded
depolarization, and an increase in membrane permeability to K+ or Cl- can
result in graded hyperpolarization.(Figure3.6 : ,a,b).
- Depolarization and repolarization: are terms describing membrane

potential changes related to resting membrane potential.
- Depolarization : Reduction in membrane potential (inside the membrane
becomes less negative than resting potential.)It can result from decrease
in K+ concentration gradient, a decrease in membrane permeability to K+,
an increase in the membrane permeability to Na+, and an increase in the
permeability to Ca2+ or decrease in extracellular Ca2+ concentration.
- Hyperpolarization occurs when membrane potential increases ,becoming
more negative than resting potential (-70 to -75mv).It can result from an
increase in the K + concentration gradient, an increase in membrane
permeability to K+ ,an increase in membrane permeability to Cl- ,a
decrease in membrane permeability to Na+ or an increase in extracellular
Ca2+ concentration.
 The term graded potential is used because a stronger stimulus produces a

greater potential change than a weaker stimulus .
 Graded potentials can summate or added together.
 A graded potential decreases in magnitude as the distance increases from the
stimulation.
2- Action potential(AP)
 Action potential is a larger change in the resting membrane potential that
spread over the entire surface of the cell.
 Neurons have the ability to suddenly raise the potential difference in the
axon to +20mv (an action potential), (figure3.7) then reduce back down to
-70mv. This is known as an impulse. It is mainly controlled by movement
of Na+ and K+ across the plasma membrane of the axon.
 A rapid change in membrane potential is action potential , which varies in
response to variety of stimuli.
47
Figure (3. 6): Graded potential, a: Depolarization, b: Hyperpolarization.
(Randall D., Burggren W. and French K. Eckert Animal Physiology . New York, W.H.
Freeman and Company, 2002).
Figure (3.7): Action potential Figure (3.8): Action potential stages

(Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –Hill
Companies, 2008).
48
Stages of action potential, (Figure3.8):
1- The resting state. Closed voltage-gated K+ channels open slowly in

response to depolarization.
2- Threshold. Some sodium ions diffuse along the axon from an action
potential to the adjacent resting potential. In addition, the Na+ are pulled into
the resting section by its negative charge. This small number of ions is
sufficient to raise the potential from -70 to -55mv. At -55mv, the sodium
channels open. (-55mv is a threshold), if the number of Na+ is insufficient
to raise the potential to -55mv, no action potential will result, because the
Na+ gates will not open.
3- Depolarization.The open Na+ channels allow Na+ to diffuse down its

gradient into the axon. The flood of Na+ makes the inside of the axon rise to
+20mv, at which the Na+ channels shut and the remaining K+ channels open
(a few were already open). This is the action potential.(Figure 3.9:a ).
4- Repolarisation.With the Na+ channels shut, no more Na+ enters the axon,
but the Na+/K+ pump is still removing Na+ from the axon (the pump does
not stop, but is irrelevant when the channels are wide open). At the same
time K+ is diffusing out through its open channels. Thus both ions are
leaving the axon, which becomes progressively more negative. (Figure 3.9:
b ).
5- Hyperpolarization or undershoot .It is a brief period following

repolarization. Some K+ channels still open. K+ efflux outside the cell .Na+
channels reset.
 All events involved in action potential are summarized in figure (3.10).
a b
Figure(3.9): a:Depolarization ,b: Repolarization. (Seeley R.R., Stephens T.D. and
Tate P. Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
49
Figure (3.10): Events of action potential.( Randall D. ,Burggren W. and French K. Eckert
Animal Physiology . New York, W.H. Freeman and Company, 2002).
Properties of Action Potential
1- All or none phenomenon

 Generation of action potential is determined by the ability of stimulus to
cause the cell to reach threshold.
 If the threshold potential is reached, an action potential is generated, if it is
not reached, no action potential is generated.
 Regardless of stimulus intensity, the action potential will have the same
amplitude.
2-Frequency
 Increased stimulus intensity lead to high frequency of AP generation.That is
how can CNS determine whether a particular stimulus intense or weak.
 The strong stimuli cause nerve impulse to be generated more often in a
given time interval than do weak stimuli. That is stimulation intensity is
coded for by the number of impulse per second rather than by increase the
strength (amplitude) of the individual AP.
50
3- Refractory period.
 During refractory period the cells are unable to generate AP .Refractory
period is important property of excitable cells to prevent overly rapid
generation of action potential, which may cause continual contraction
(tetany).
 Absolute Refractory period: AP cannot be generated regardless of
stimulation intensity, during the depolarization phase of AP and is due to
closure Na+ channels inactivation gate.
 Relative Refractory period: Stimulation with much greater intensity than
threshold can stimulate another AP. During the repolarization phase K+
conductance is higher than in resting state, the membrane potential is more
negative.
4- Accommodation.
 Cells are held in depolarization phase or depolarized very slowly,
inactivation gates on Na+ channels automatically close so no Na+ current.
Even if the cell has reached its normal threshold potential, it’s impossible
for the cell to generate another AP because few Na+ channels open.
Clinical note: In hyperkalemia, the extracellular potassium concentration is

higher than normal, so there is less of driving force for K+ to leave the cell and
keep the membrane potential at -70mv .Thee cell depolarizes enough to trigger
the closure of sodium inactivation gates. This depolarization brings the
membrane closer to threshold but no action potential is generated.
Propagation of Action Potential
 Action potential is generated by Na+ influx through a given area of the

membrane. This influx establishes local currents that depolarize the adjacent
membrane area in the forward direction, away from origin of the nerve
impulse.
 Because the area of originated action potential just generate AP, the Na+
channels in that area inactivated and no new AP generated, AP propagates
away from its point of origin.
 If isolated axon is stimulated by electrode, nerve impulse will move away
from the point of stimulation in all directions along the membrane .But in
the body AP initiated at one end conducted away from that point toward the
axons terminals.
 Once AP is initiated, it is self propagating and continues along the axon at a
constant velocity like domino effect .This propagation process occurs on
unmyelinated axon.
 Propagation process along the myelinated axon is called Saltatory
conduction.
51
Transmission of the impulse.
 As an action potential travels along the axon, it raises the potential
difference of the resting axon adjacent to it until the threshold has been
reached. This is done by diffusion of Na+ along the axon and results from
two factors:-
1. The section of axon with an action potential has a very high

concentration of Na+ (which have entered the axon through their open
channels), while the resting section of axon has a low concentration (due
to the Na/K pump and shut channels). This produces a large gradient
inside the axon and thus diffusion of Na+ into the resting section of
axon.
2. The resting section of axon has a negative charge, which attracts the Na+
from the action section of axon. (Figure3.11).
Figure (3.11): Transmission of the impulse (Randall D. ,Burggren W. and French K.

Eckert Animal Physiology . New York, W.H. Freeman and Company, 2002)
 Small nerves made up of only a few axons are often unmyelinated -

although the axon is surrounded by Schwann cells, (Figure3.12: a), these are
not wrapped around the axon in many layers of myelin. Such nerves
transmit an impulse by continuous conduction .This is slow conduction.
Clinical note: Multiple sclerosis is autoimmune disease characterized by

inflammation and destruction of the myelin resulting in demyelinated fiber in
CNS .It manifested in many different forms:patients have cognitive changes ,
paresis and optic neuritis.
52
Figure (3.12): a-Small nerve with few unmyelinated axon. b-myelinated axon.
(Randall D. ,Burggren W. and French K. Eckert Animal Physiology . New York, W.H. Freeman
and Company, 2002).
 Most nerves are made up of hundreds or thousands of axons and are

myelinated. (Figure3.12:b).The myelin prevents the movement of ions
through the plasma membrane. Na+ and K+ channels are thus only found in
the nodes of Ranvier, between the Schwann cells. The impulse thus jumps
from node to node, which is saltatory conduction. (Figure 3.13 ) There
are no ionic movements between the nodes. This (compared with
continuous conduction) is:-
 Very fast (up to 120m/sec compared with 15m/sec).
 Has a very fast recovery (very short refractory period), because only a
small number of ions enter the axon and have to be pumped out again.
 The impulses can have a higher frequency.
53
Figure (3.13): Saltatory conduction.( Seeley R.R., Stephens T.D. and Tate P. Anatomy and
Transmission of AP between the cells:
1- Electrical transmission: rare form of action potential transmission, current

travels through openings between the cells “gap junctions” in cardiac and
muscles cells, where there is cytoplasmic continuity between the cells
constituents.
2- Chemical transmission: primary form by which action potential are
transmitted.
The synapse
 Synapse :( clasp or join) ,is a junction that mediate information transfer from
one neuron to the next or from a neuron to an effectors cells –its where the
action is .
 The impulse reaching the end of the axon and enters the synaptic knobs
(presynaptic terminals). These do not directly connect with the next
neuron, but have a narrow gap the (synaptic cleft) in between. The post-
synaptic membrane (PSM) of the next neuron may be either its dendrites
or its cell body (synapses connect with both). (Figure 3.14).
54
Figure (3.14): Chemical transmission at a Figure(3.15): presynaptic terminals
synapse. at rest.
(Marieb E.N.and Hoehn K.Anatomy and physiology. San Francisco, Pearson Education Inc.,
2011).
 The impulse diffuses across this gap as a chemical neurotransmitter, such

as acetylcholine. A resting synapse has the neurotransmitter stored inside
vesicles in the knob(figure 3.15). The impulse arriving in the synaptic knob
results in,(figure3.16):
 Ca2+ channels open to allow Ca2+ to diffuse into the knob.
 This causes the vesicles to empty the neurotransmitter into the
synaptic cleft.
 The neurotransmitter diffuses across to the post-synaptic membrane
of the next neuron, where it combines with its receptors.
 Attachment of the neurotransmitter to its receptor opens or closes
ionic channels.
55
a b
c d
Figure (3.16): The events that occur when impulse arrives the synaptic
 This
knob binding,
.( Seeley R.R., on the postsynaptic
Stephens T.D. and Tate cell causesand
P. Anatomy either excitatory
Physiology . New York,
McGraw –Hill Companies, 2008).
 Postsynaptic potential (EPSP) or an inhibitory postsynaptic potential

(IPSP).EPSPs are a result of localized depolarization caused by increased
conductance to Na+. IPSP are a result of localized hyperpolarization
caused by increased conductance to Cl- or K+ .
 If summation of IPSP and EPSP at the axon hillock brings the membrane
potential to threshold, generation of action potential occurs by opening
of voltage- gated sodium channels.
 After use, the neurotransmitter attached to the receptor is broken down by

an enzyme, e.g. acetylcholine is destroyed by cholinesterase, while
neurotransmitter still in the cleft is pumped back in to vesicles in the knob.
This ends the impulse and so prepares the synapse for the next impulse.
56
 Each neurotransmitter has its own specific receptor attached to a particular
type of channel.
 The same neurotransmitter can produce different effects on different types
of cells.
Types of neurotransmitters
1- Acetylcholine: cholineregic transmission
 Acetylcholine (ACh) is used by all motor axons, autonomic
preganglionic neurons and postganglionic parasympathetic nerves.
 Depending on the postsynaptic, ACh can be either excitatory (at the
neuromuscular junction by motor neurons) or inhibitory (in
parasympathetic postganglionic fibers to cardiac muscle).
 Pathophysiology of cholinergic transmission: myasthenia gravis,
Parkinson disease, Alzheimer dementia.
Clinical note: In the autoimmune disease myasthenia gravis, antibodies are made
against ACh receptors of the neuromuscular junction in skeletal muscle. These
antibodies bind to the ACh receptors on the postsynaptic membrane and block
ACh binding resulting in muscles weakness and easy fatigability .Treatment
includes administration of acetylcholinesterase inhibitors such as neostigmine
to increase the amount of ACh in the synaptic cleft.
2- Amino acids
 Glutamate :glutamatergic transmission
- Glutamate is the primary stimulatory neurotransmitter of the brain.
- It binds to both stimulatory and modulator receptors.
- Excess glutamatergic activity is associated with excitation and
seizures.
 Gamma aminobutyric acid (GABA)
- GABA is the primary inhibitory neurotransmitter in the brain.
- It is abundant within the basal ganglia and cerebellum.
- It is derived from the amino acid glutamate by action of glutamate
decarboxylase.
- Deficient GABA activity may result in movement abnormalities,
anxiety disorders, and seizure and muscles spasm.
Clinical note:In Huntington disease ,there is progressive deterioration of the

caudate nucleus and frontal cortex .Clinical symptoms do not appear until the
fourth or fifth decade ,by which many patients have already passed on the
mutated autosomal dominant gene to their children. Loss of GABA secreting
neurons is one factor responsible for the abnormal movement.
57
Pharmacology note: Because GABA is an inhibitory neurotransmitter, GABA
agonists such as benzodiazepines, alcohol and barbiturates are frequently used
as antianxiety agents (anxiolytics), suppressing cortical function.
 Glycine
- Glycine is the primary inhibitory neurotransmitter of the spinal cord .
- It increases chloride conductance in the postsynaptic membrane.
- This results in hyperpolarization of the postsynaptic membrane and
inhibition of action potential generation.
Clinical note: Glycine secretion in the spinal cord is inhibited by the tetanus toxin,
exposure to which results in excessive stimulation of the lower motor neurons,
producing spasmic muscle contraction(i.e., spastic paralysis).
3- Monoamines
 These neurotransmitters contain a single amine group in their chemical
structure, and include norepinephrine, serotonin and dopamine.
Clinical note: The monoamine deficiency theory of depression links depression to

a deficiency in at least one of the three monoamine transmitters norepinephrine,
serotonin and dopamine. Extensive pharmacologic support for this theory has
been obtained for over the years, as evidenced by the efficacy of monoamine
oxidase inhibitor and tri cyclic antidepressant, which increase levels of
monoamine neurotransmitters in the brain .However, these drugs affect levels of
other neurotransmitters and have numerous side effects. Serotonin-specific
reuptake inhibitors (SSRIs) and non-serotonin-specific reuptake inhibitors
(NSRIs) have been shown to be extremely effective in the treatment of depression
with minimal side effects.
 Norepinephrine: adrenergic transmission

- It is derived from amino acid tyrosine.
- It is synthesized and released by the sympathetic nervous system, adrenal
medulla, and locus ceruleus of central nervous system.
58
 Serotonin
- Serotonin is derived from the amino acid tryptophan
- Most of the body’s serotonin is found in the enteric nervous system of
the gut.
- The serotonin in the brain plays an important role in control of mood.
 Dopamine: dopaminergic transmission
- Dopamine is derived from the amino acid tyrosine.
- Dopamine is an important neurotransmitter in the brain .It affects sleep,
mood, attention, and learning.
- A lack of dopamine in the brain is associated with Parkinson‟s disease.
Excessive dopamine is linked to schizophrenia.
Pharmacology note: Dopamine agonist such as bromocriptine are used

clinically to treat prolactinomas, the most common type secreting pituitary
tumor, they are mainstay of treatment of Parkinson’s disease.
4- Neuropeptides
- These have longer duration of action than the smaller molecular
neurotransmitters, partly because they act by altering gene expression, so
their effect may continue after they are degraded.
- Neuropeptides may be secreted at the same time as a small –molecule
neurotransmitter .This results in an immediate ,rapid response (because
of smaller neurotransmitters ) and delayed but prolonged response
caused by neuropeptide.e.g.,glutamate and neuropeptide substance P
are cotransmitted in the pain pathway ;glutamate causes immediate
inhibition of neurotransmission of pain ,whereas substance P causes
change in the gene expression to produce a lasting effect .
- Neuropeptide Y, enkephalins, endophrins and nitric oxide are other
examples of neuropeptides.
Spatial and Temporal Summation

 Presynaptic action potentials through neurotransmitters produce graded
potentials in postsynaptic neurons .The graded potential can summate to
produce an action potential at the trigger zone.
 Spatial summation occurs when two or more presynaptic terminals
simultaneously stimulate a postsynaptic neuron. (Figure 3.17).
 Temporal summation occurs when two or more action potentials arrive in
succession at a single presynaptic terminal.
59
 Inhibitory and excitatory presynaptic neurons can converge on a
postsynaptic neuron .The activity of the postsynaptic neuron is determined
by the integration of the EPSPs and IPSPs in the postsynaptic neuron.
Figure (3.17): Spatial and Temporal Summation. (Marieb E.N .Essential of Human
Anatomy and Physiology. San Francisco, Pearson Education,Inc.,2012).
The Spinal cord
Overview
 Spinal cord is extremely important to overall function of the nervous
system.
 It is the major communication link between the brain and the PNS, inferior
to the head; it participates in the integration of incoming information and
produces responses through reflex mechanism.
 The spinal cord gives rise to 31 pairs of spinal nerves .The spinal cord has
cervical and lumbosacral enlargements where nerves of the limbs enter and
leave.
 The spinal cord is shorter than the vertebral column .Nerves from the end
of the spinal cord form the cauda equina .
 Meninges of the Spinal Cord: Three meningeal layers surround the spinal
cord: the dura mater, arachnoid mater and pia mater.
 Cross section of the spinal cord: The spinal cord consists of peripheral
white matter and central gray matter. (Figure3.18).
 White matter is organized into funiculi, which are subdivided into fasciculi
or nerve tracts, which carry action potentials to and from the brain.
60
Figure (3.18): Cross section of the spinal cord. (Seeley R.R., Stephens T.D. and Tate P.
 Gray matter is divided into horns. (Figure3.19).

- The dorsal horns contain sensory axons that synapse with interneurons.
- The ventral horns contain the neuron cell bodies of somatic motor
neurons
- The lateral horns contain the neuron cell bodies of autonomic neurons.
 The gray and white commissures connect each half of the spinal cord.
 The dorsal root conveys sensory input into the spinal cord and the ventral
root conveys the motor output away from the spinal cord.
Figure (3.19): Gray matter is divided into horns .(Seeley R.R., Stephens T.D. and Tate P.
61
Reflexes
Overview
 The reflex arc has five basic components,(Figure 3.20 ):
1- A sensory receptor
2- A sensory neuron
3- An interneuron
4- A motor neuron
5- An effector organ
 The reflex arc is the functional unit of the nervous system.
- Sensory receptors respond to stimuli and produce action potentials in
the sensory neurons.
- Sensory neurons propagate action potential to the CNS.
- Interneurons in the CNS synapse with sensory neurons and with motor
neurons.
- Motor neurons carry action potentials from CNS to effector organs.
- Effector organs such as muscles or glands respond to the action
potentials.
 Reflexes do not require conscious thought and they produce a consistent

and predictable result. (e.g., same response every time the individual
touches something hot).Information will at the same time be sent to the
brain, but this involves thousands of neurons and so takes much longer (the
individual will already remove the hand before the realizing of touching
something hot).
 Reflexes are homeostatic.
 Many reflexes are integrated within the spinal cord and others are integrated
within the brain.
 Some reflexes involve excitatory neurons and result in a response .Other
reflexes involve inhibitory neurons and result in the inhibition of a
response. Higher brain centers can suppress or exaggerate reflexes.
62
Figure (3.20): Reflex arc components. (Seeley R.R., Stephens T.D. and Tate P. Anatomy
and Physiology . New York, McGraw –Hill Companies, 2008).
 Individual reflexes vary in their complexity:

 Monosynaptic reflexes involve simple neural pathways in which
sensory neurons synapse directly with motor neurons.
 Polysynaptic reflexes involve more complex pathways and integrative
center with one or more interneurons between the sensory and motor
neurons.
Stretch Reflexes:
 A reflex in which muscles contract in response to a stretching force applied
to them.
 The sensory receptor of this reflex is the muscle spindle, which consist of 3-
10 small specialized skeletal muscle cells.
 The cells are contractile only at their ends and innervated by specific motor
neurons called gamma motor neurons, originating from the spinal cord and
control the sensitivity of the muscle spindle cells.
 Sensory neurons innervate the contractile centers of the muscle spindle cells.
Axon of these sensory neurons extends to the spindle cord and synapse
directly with motor neurons in the spinal cord called alpha motor neurons.
 The stretch reflex is monosynaptic reflex because there is no interneuron
between the sensory neuron and the alpha motor neuron.
Knee-Jerk reflex or patellar reflex is a classic example of the stretch reflex.

Clinicians use this reflex to determine whether the higher CNS centers that are
normally influence this reflex are functional.
63
Golgi Tendon Reflex
 The Golgi tendon reflex prevents contracting muscles from applying
excessive tension to tendon, so protects muscles and tendon from damage.
 Intense stretch of skeletal muscle results in :
1- Golgi tendon organs detect tension applied to a tendon.
2- Sensory neurons conduct action potential to the spinal cord.
3- Sensory neurons synapse with inhibitory interneurons that synapse with
the alpha motor neurons.
4- Inhibition of the alpha motor neurons causes muscle relaxation, relieving
the tension applied to the tendon.
Withdrawal Reflex
 The function of withdrawal or flexor reflex is to remove a limb or another
body part from a painful stimulus.
 The sensory receptors are pain receptors. Stimulation of pain receptors
results in:
1- Pain receptors detect a painful stimulus.
2- Sensory neurons conduct action potential to the spinal cord
3- Sensory neurons synapse with the excitatory interneurons that synapse
with alpha motor neurons.
4- Excitation of the alpha motor neurons results in contraction of the flexor
muscles and withdrawal the limb from the painful stimulus.
 Reciprocal innervations: is associated with the withdrawal reflex and

reinforce its efficiency. It causes relaxation of muscles that would oppose
the withdrawal movement.
 Crossed extensor reflex: is another reflex associated with the withdrawal
reflex .In this reflex, during flexion of one limb caused by the withdrawal
reflex, the opposite limb is stimulated to extend.
The Brain
Overview
 The brain is that part of the CNS contained within the cranial cavity.
 It is the control center for many of the body’s functions.
 The brain is divided into 4 main regions,(figure 3.21 ):
- the brainstem is at the top of the spinal cord; includes medulla, Pons,
midbrain and reticular formation.
64
- The diencephalon is the part of the brain located between the
brainstem and the cerebrum; includes the thalamus, epithalamus and
hypothalamus.
- The cerebrum makes up most of the brain. Conscious perception,
thought and conscious motor activity; can override most other system.
- Cerebellum is at the posterior part of the brain. Control of muscle
movement and tone; balance; regulates extent of intentional movement
and involved in learning motor skills.
Figure ( 3.21 ): A median section of the brain. (Seeley R.R., Stephens T.D. and Tate
P. Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
 Damage to small brainstem areas often causes death because many reflexes
essential for survival are integrated in the brainstem, whereas relatively
large areas of the cerebrum or cerebellum may be damaged without life-
threatening consequences.
1- Brainstem
 Medulla Oblongata.
- This is the top of the spinal cord (so many neurons pass through it
going to the rest of the brain).
- It contains sensory and motor tracts; cranial nerve nuclei; other
related nuclei and part of the reticular formation.
- It has centers controlling blood circulation, respiration, swallowing,
coughing.
65
 Medbrain
- It located superior to the pons.
- It contains the nuclei of cranial nerves III, VI(trochlear),and
V(trigeminal)
- It is involved in visual reflexes, such as looking towards a loud
sound or bright light, altering the pupil of the eye, depending on the
amount of light, and focusing the lens.
 Pons
- The part of the brainstem just superior to the medulla is the pons.
- It contains ascending and descending tract and several nuclei.
- The pontine nuclei located in the anterior portion of the pons, relay
information from the cerebrum to the cerebellum.
- Pontine nuclei regulate sleep and respiration. The nuclei of cranial
nerves V-XI are in the pons.
 Reticular formation
- This is a diffused system consisting of several loosely packed nuclei
scattered throughout the length of the brainstem.
- It receives axon from a large number of sources and especially from
nerves that innervate the face.
- It is involved in “cycle” of activity such as sleep –wake cycle.
2- The diencephalon
 Thalamus
- It is the largest part of the diencephalon, constituting about four –
fifth of its weight. (Figure 3.22).
- It consists of two lobes connected by a small stalk called the
interthalamic adhesion or intermediate mass.
- The thalamus functions as an integration center.
- Most sensory input synapse in the thalamus .Pain is registered in the
thalamus.
- It influences mood, and action associated with strong emotions such
as fear and rage.
- It has some motor functions.
 Subthalamus
- It is a small area immediately inferior to the thalamus that contains
several ascending and descending tracts and the subthalamic nuclei.
- It is involved in the motor functions.
 Hypothalamus
- The hypothalamus is the most inferior portion of the diencephalon.It
contains several small nuclei and tracts. (Figure3.22) .The most
conspicuous nuclei called mammillary bodies; they are involved in
olfactory reflexes and emotional response to odor. They also
involved in memory.
66
- A funnel –shape stalk, the infundibulum extends from the floor of the
hypothalamus and connects it to the posterior pituitary gland.
- The hypothalamus play an important role in controlling endocrine
system because it regulates the pituitary gland‟s secretion of hormones
which influence many functions such as metabolism, reproduction
,response to stressful stimuli and urine production.
- Sensory neurons that terminate in the hypothalamus provide input from:
1- Internal organs
2- Taste receptors in the tongue
3- The limbic system which is involved in response to smell
4- Specific cutaneous area ,and the eye
5- Prefrontal cortex of the cerebrum carrying information relative to
mood through the thalamus.
- Hypothalamic nuclei directly control temperature by stimulating
sweating and shivering.
- Other hypothalamic nuclei are involved in the control of thirst, hunger
and sex drive.
- The hypothalamus is also very important in a number of functions
related to mood, motivation, and emotion. This is one reason that strong
emotional experience may affect the person’s desire or ability to eat and
drink.
Figure (3.22): General overview of the right half of diencephalon. (Seeley R.R.,
Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –Hill
Companies, 2008).
3- Cerebrum
 It is the largest portion of the total brain weight, which is 1200g in
females and 1400 g in males.
 The most conspicuous features on the surface are numerous folds called
gyri .These are to increase surface area of the cortex. The grooves
between the gyri are called sulci.
67
 Central sulcus, which extends the lateral surface of the cerebrum from
superior to inferior, is located about midway along length of the brain,
(figure3.23).
 Cerebrum is divided into left and right hemispheres by longitudinal
fissure. Each hemispheres have lobes:
1- The frontal lobes are involved in smell, voluntary motor function
motivation, aggression and mood.
2- The parietal lobes contain the major sensory areas receiving
general sensory input, taste and balance.
3- The occipital lobes contain the visual centers.
4- The temporal lobes receive olfactory and auditory input and are
involved in memory, abstract thought and judgment.
 Tracts connect areas of the cortex within the same hemisphere are
association fibers, between hemispheres are commissural fibers and
with other parts of the brain and spinal cord are projection fibers.
 More complex activities, such as speech and language, and thinking,
may involve several different parts of the brain.
Figure (3.23): Lateral view of the left cerebral hemisphere. (Marieb E.N.and Hoehn
K. Anatomy and physiology. San Francisco, Pearson Education Inc., 2011).
4- Cerebellum
 The term cerebellum means little brain.
 The cerebellum is attached to the brainstem posterior to the pons.
 It communicates with other regions of the CNS through three large tracts:
1- The superior cerebellar peduncles connect the cerebellum to the
midbrain.
2- The middle cerebellar peduncles connect the cerebellum to the pons.
3- The inferior cerebellar peduncles connect the cerebellum to the
medulla oblongata.
68
 The cerebellar cortex contains several cell types: stellate cells, basket
cells, granule cells, Golgi cells and Purkinje cells.
 The cerebellum consists of three parts,(figure 3.23) :
1- A small inferior part the flocculonodular lobe: control balance and
eye movement.
2- A narrow central vermis: vermis with the medial portion of the lateral
hemispheres are involved in the control of posture, locomotion and
fine motor coordination.
3- Two large lateral hemispheres: The major portions functions in the
concert with the frontal lobe of cerebral cortex participate and learn
complex movements.
Clinical note: Lateral cerebellar lesion causes a defect known as decomposition

of movement. The result is a disruption in the timing of the components of a
movement, which appear to take place sequentially rather than being
coordinated smoothly.
Basal Nuclei
 The basal nuclei are the largest nuclei of the brain and occupy a large part of
the cerebrum.
 They are a group of functionally related nuclei located bilaterally in the
inferior cerebrum, diencephalon and midbrain.
 They are important in the initiation of voluntary movements.
 They include the putamen and caudate nucleus, which collectively termed
the striatum, globus pallidus, substantia nigra and subthalamic nucleus.
 Output of the basal nuclei is to the motor thalamus, which in turn projects
to the motor cortex.
 Basal nuclei output is always inhibitory in nature.
 The basal nuclei influence movement through one of two pathways, the :
1- The direct pathways: is activated by binding of dopamine to D1
receptors in the striatum. This results in direct inhibition of basal
nuclei output to the motor thalamus.
2- The indirect pathway: inhibited by binding of dopamine to D2 in the
striatum. The indirect stimulation through the subthalamic of basal
ganglia output to the motor thalamus.
Limbic system
 Limbic system is parts of the cerebrum and diencephalon which are
grouped together.
 Limbic system includes part of the cerebral cortex, basal nuclei, the
thalamus, the hypothalamus and the olfactory cortex.
69
 It plays a role in the basic functions such as: memory, reproduction and
nutrients.
 It is also involved in emotional interpretation of sensory input and emotions
in general.
 One of the major sources of sensory input into the limbic system is the
olfactory neurons.The smell or thought of food stimulates the sense of
hunger in the hypothalamus.
Higher functions of the cerebral cortex

 The human brain is capable of many functions besides awareness of sensory
input and the control of skeletal muscles.
 Speech, mathematical and artistic ability, sleep, memory, emotions and
judgment are functions of brain.
Language
 The major area for language comprehension is Werinke area, located
behind the primary auditory cortex in the posterior part of the superior gyrus
of the temporal lobe.
 The major area for expressing language is Broca area in the prefrontal and
premotor facial region of the cortex.
 Language center presents in the left hemisphere in 95% of people, even if
left handed.
 The right hemisphere is dominant with respect to facial expression,
intonation, spatial tasks and body language.
Clinical note: Werinke area lesions cause receptive aphasia which consists of
the inability to comprehend spoken language.
Broca area lesions cause expressive aphasia which reflects difficulty piecing
together words to produce speech. Patients can understand written and spoken
language but unable to express themselves verbally.
Memory
 Memories are caused by changes in the sensitivity of synaptic transmission
between neurons as a result of previous neural activity.
 These changes result in memory tracts, (the facilitated pathways developed
for the transmission of signals through the neural circuits of the brain,
providing for memory).
 Memory is divided into three major types:
1- Short –term memories last for seconds or minutes unless they are
converted to long term memories .The basis of short term memory
involves synaptic changes.
70
2- Intermediate long term memories last for days to weeks, then
forgotten. They result from temporary chemical or structural changes.
3- Long term memories can be recalled years later. Formation of long
term memories involves structural changes in the nervous system and
the formation of stable memory tracts. Two types of long-term memory
exist:
 Declarative or explicit memory involves the retention of facts such
as names, dates and places. This is accessed by part of the temporal
lobe called the hippocampus and amygdale or ammygdaloid.
 Procedural or implicit involves the development of skills like
riding a bicycle or playing piano. Implicit memory is stored in the
cerebellum and the premotor area of the cerebrum.
Brain waves
 Waves of electrical activity are large enough to be detected from the outer
surface of the head by an electroencephalogram (EEG).
 EEG records the electrical activity when millions of neurons fire
synchronously.
 Both intensity and pattern of electrical activity are determined by the level
of excitation of the brain during sleep and wakefulness or in disease states
such as epilepsy
 There are different types of brain waves,(figure3.24 ). Characteristics of
each of these brain waves are illustrated in table (3, 1).
1. Alpha wave (8 – 13 Hz).
2. Beta wave (>13 Hz).
3. Theta wave (4 – 7.5 Hz).
4. Delta waves (1 – 3.5 Hz).
Figure (3, 24): Different brain waves,

( Retrieved from http://www.studyblue.com)
71
Table (3, 1): Characteristics of the brain waves.
Rhythm Frequency Amplitude (uV) Recording Location

(Hz)
Alpha(α) 8 – 13 50 – 100 Adults, awake rest Occipital

quiet region
Beta(β) 14 – 30 20 Adult, mental activity Frontal region
Theta(θ) 5–7 Above 50 Children, drowsy Occipital

adult, emotional region
distress
Delta(δ) 2–4 Above 50 Infants , deep sleep,

patient with serious
organic brain disease
M
Sleep
 The sleep –wake cycle is a circadian rhythm .This cycle is driven by the
suprachiasmatic nucleus of the hypothalamus.
 Sleep is divided into two types: non-rapid eye movement (NREM) sleep
and rapid eye movement (REM) sleep occur in alternating cycle.
 Most dreaming occurs during REM sleep.
 Aging, alcohol, and benzodiazepines decrease the duration of REM sleep.
 Most sleep time is spent in NREM.
 NREM sleep can be divided into four stages, on the basis of changes in EEG
waves.
- Stage 1: consists of very light sleep and low voltage EEG waves.
- Stage 2: is the primary sleep stage during normal night’s sleep.EEG
characterized by sleep spindles.
- Stage 3: is a deeper sleep pattern with decrease EEG activity and
muscles tone.
- Stage 4: is a deeper sleep with delta waves on EEG recording and
further decreasing in muscles tone.
72
Meninges, Ventricles and cerebrospinal fluid
Meninges
 There are three connective tissue membranes. These are: the dura,
arachnoid and pia mater.(Figure3.25 ).
 The meninge surrounds and protects the brain and spinal cord.
 The dura mater is the most superficial and thickest membrane .It is
composed of dense irregular connective tissue.
 The dura mater attached to the skull and has two layers: the outer layer is
called the periosteal dura and the inner layer is meningeal dura.The
meningeal dura is separated from periosteal dura in various regions to form
dural venous sinuses.
 Meningeal dura is continuous with the dura of spinal cord.
 Arachnoid mater is very thin wispy .The space between this membrane and
dura is subdural space, which contains a small amount of serous fluid.
 The pia mater is bound tightly to the surface of the brain. The space
between arachnoid and pia mater is the subarachnoid space.It contains
weblike strands of arachnoid mater and the blood vessels supplying the
brain and is filled with cerebrospinal fluid (CSF).
Figure (3.25): Meningeal membranes. Modified from (Marieb E.N .Essential of

Human Anatomy and Physiology. San Francisco, Pearson Education,Inc.,2012).
73
Ventricles
 Ventricles are within each hemisphere of the brain, they secrete and
circulate the CSF. (Figure 3.26).
 These ventricles :
 The lateral ventricles is separated from each othe by thin septa
pellucid
 The third ventricle is located in the diencephalon between the two
halves of the thalamus. The lateral ventricles connected to the third
ventricle through the interventricular foramen. (Figure 3.26).
 The fourth ventricle is in the inferior part of the of the potine region.
The third ventricle communicates with the fourth ventricle through the
cerebral aqueduct.
 The central canal of the spinal cord is connected to the fourth ventricle.
Figure (3.26): Brain ventricles.(Marieb E.N .Essential of Human

Anatomy and Physiology. San Francisco, Pearson
Education,Inc.,2012).
Cerebrospinal Fluid
 Cerebrospinal fluid (CSF) is a fluid similar to the blood serum with most
of protein removal.
 It bathes the brain and spinal cord and provides a protective cushion around
the CNS.
 CSF allows the brain to float within the cranial cavity, so it does not rest
directly on the surface of skull or dura .In addition it protects the brain
against the shock of rapid movement of the head.
 It provides some nutrients to CNS tissues.
 About 80-90% of CSF is produced by specialized ependymal cells within
the lateral ventricles. The remainder produced by similar cells in the third
and fourth ventricles. These specialized cells, their support tissues and the
associated blood are collectively called choroid plexuses.
 CSF is formed through a variety of mechanisms. The majority of the fluid
enters the ventricles by following Na+ concentration gradient.
74
 Ependymal cells of the choroid plexus actively transport Na+ into ventricles
and water passively follows. Large molecules are transported by
pinocytosis.
 Endothelial cells of the blood vessels in the choroid plexus, which are joined
by tight junctions form the blood brain barrier or blood cerebrospinal
barrier .So the substances do not pass between the cells but pass through
the cells.
 CSF fills the ventricles, the subarachnoid space of the brain and spinal cord
and the central canal of the spinal cord.
Cerebrospinal fluid flow
 The cerebrospinal fluid flows through eight steps:

1- Choroid plexus in the lateral ventricles produces CSF.
2- CSF flows through interventricular foramina into third ventricle.
3- Choroid plexus in the third ventricle adds more CSF.
4- CSF flows down cerebral aqueduct to fourth ventricle.
5- Choroid plexus in the fourth ventricle adds more CSF.
6- CSF flows out two lateral apertures and one medial aperture.
7- CSF fills subarachnoid space and bathes external surfaces of brain and
spinal cord.
8- At arachnoids villi, CSF reabsorbed into venous blood of dural venous
sinuses and it becomes part of the blood flow that is drained by the internal
jugular veins. The flow of CSF is illustrated in figure ( 3.27 ).
Figure (3.27): Flow of CSF. (Marieb E.N .Essential of Human Anatomy and Physiology. San
Francisco, Pearson Education,Inc.,2012).
75
Blood Supply to the Brain
Overview
 The brain requires a tremendous and constant amount of blood to maintain
its normal functions and to meet the demands for glucose and oxygen. This
is because:
- The brain has a very high metabolic rate.
- Brain cells are not capable of storing high energy molecules for long
time.
- Brain cells depend entirely on glucose as the energy source.
 Even though the brain account for only 2% of the total weight of the body, it
receives approximately 15-20% of blood pumped by the heart.
 Interruption of the brain’s blood supply for only seconds can cause
unconsciousness and interruption of the blood supply for minutes can cause
irreversible brain damage.
 Blood reaches the brain through :
1- The internal carotid arteries, which enter the cranial cavity through
the carotid canals.
2- The vertebral arteries which enter through the foramen magnum.
 The vertebral arteries join together to form the basilar artery which lies on
the ventral surface of the pons.
 The basal artery and internal carotid contribute to the cerebral arterial
circle (circle of Willis).
 Branches from this circle and from the basilar artery supply blood to the
brain.
Blood brain barrier

 The arteries within the brain divide into capillaries, which their epithelial
cells are surrounded by processes of astrocytes .The astrocytes, promote
the formation of tight junctions between epithelial cells.
 The epithelial cells with their tight junctions form the blood brain barrier.
 Blood brain barrier regulates the movements of materials from the blood
into the brain. .Most materials cannot pass through the blood brain barrier.
 The materials that enter the brain pass through the epithelial cells.
 Lipid soluble substances, e.g., nicotine, ethanol, and heroin can diffuse
through the plasma membrane of epithelial cell and enter the brain.
 Water soluble molecules, e.g, amino acids and glucose pass the plasma
membrane of the epithelial cells by mediated transport.
Pharmacology note: The permeability of the blood brain barriers must be

considered when developing drugs that affect the CNS. ,e.g,, Parkinson
disease is caused by a lack of the neurotransmitter dopamine( produced by
neurons of the brain). Administering dopamine is not helpful because
dopamine cannot pass the blood brain barrier. Levodopa a precursor to
dopamine,is administered instead because it can cross the blood brain
barrier.CNS neurons then convert levodopa to dopamine ,which helps reduce
the symptoms of Parkinson disease.
76
Cranial nerves
Overview
 The cranial nerves are composed of twelve pairs of nerves that arise from
the nervous tissue of the brain. They are called cranial nerves because they
either enter or exit the cranium through openings in the skull to reach their
targets.
 Like spinal nerves, cranial nerves are bundles of sensory or motor fibers, or
show a combination of these fiber types.
 Motor components of the cranial nerves are derived from the cells that
located in the brain. These cells send their axons outside the brain, where
they will control muscles and glandular tissues.
 The sensory components of cranial nerves originate from collections of
cells that are located outside the brain (sensory ganglia).
 These 12 pairs of cranial nerves perform sensory, somatic, motor
proprioceptive and parasympathetic functions. Here is a brief description for
each of these nerves and its function.(Table3, 2 )
1- Olfactory (I)
- This type of sensory nerve contributes in the sense of smell.
- It carries the information from nasal epithelium to the olfactory center
in brain, in frontal lobe.
2- Optic nerve(I)
- This sensory nerve transforms information about vision to the brain.
- This supplies information to the retina in the form of ganglion cells.
3- Oculomoter nerve(III)
- This is a form of motor nerve that supplies to different centers along
midbrain.
- Its functions include superiorly uplifting eyelid, superiorly rotating
eyeball, construction of pupil on the exposure to light and operating
several eye muscles.
4- Trochlear nerve(IV)
- This motor nerve supplies to the midbrain and performs the function
of handling the eye muscles and turning the eye.
5- Trigeminal nerve (v)
- This is a largest cranial nerve.
- It performs many sensory functions related to nose, eyes, tongue and
teeth.
- It is divided in three branches that are ophthalmic, maxillary and
mandibular nerve.
- This is a type of mixed nerve that performs sensory and motor
functions in brain.
6- Abducent nerve (VI)
- This is a motor nerve that supplies to the pons and perform function of
turning eye laterally.
77
7- Facial nerve(VII)
- This motor nerve is responsible for different types of facial
expressions, presents over brain stem.
- This also performs some functions of sensory nerve by supplying
information about touch on face and senses of tongue in mouth.
8- Vestibulocochlear nerve (VIII)
- This is a motor nerve. It is involved in the sense of hearing and
balance.
9- Glossopharyngeal nerve(XI)
- This sensory nerve carries sensory information from pharynx (initial
portion of throat) and posterior portion of tongue and palate.
- The information sent is about temperature, pressure. It also covers
some portion of taste buds and salivary glands.
- The nerve also carries some motor functions such as helping in
swallowing food.
10- Vagus nerve(X)
- This is a type of mixed nerve that carries both motor and sensory
functions.
- It innervates the muscles of pharynx, palate and larynx .It is involved
in the sense of taste.
- The vagus nerve is sensory for the pharynx and larynx and for
receptors that monitor blood pressure and gas levels in the blood.
- The vagus nerve provides sensory and parasympathetic innervations
to the thoracic and abdominal organs.
11- Spinal accessory nerve(XI)
- This nerve has only a spinal component.It is a motor nerve, supplies
the sternocleidomastoid and trapezius muscles.
12- The hypoglossal nerve(XII)
- It supplies the intrinsic tongue muscles, three of four extrinsic tongue
muscles and two throat muscles.
78
Table (3, 2): Cranial nerves.
Nerves Type Function
I
sensory olfaction (smell)
Olfactory
II
Sensory Vision
Optic
III
Motor eyelid and eyeball muscles
Oculomotor
IV
Motor eyeball muscles
Trochlear
Sensory: facial and mouth

V
Mixed sensation
Trigeminal
Motor: chewing
VI
Motor eyeball movement
Abducens
Sensory: taste
VII
Mixed Motor: facial muscles and
Facial
salivary glands
VIII
sensory hearing and balance
Vestibulocochlear
IX Sensory: taste
Mixed
Glossopharyngeal Motor: swallowing
Sensory for the pharynx and

X larynx
Mixed
Vagus parasympathetic nervous
system (PNS)
XI
Motor moving head and shoulder
Accessory
XII
Motor tongue muscles
Hypoglossal
79
Peripheral Nervous System
Overview
 The peripheral nervous system (PNS) consists of all parts of the nervous
system, except the brain and spinal cord.
 The PNS connects the CNS to the reminder of the body. Through which the
neural signal transmitted to and from the CNS. (Figure 3.28).
 Sensory neurons transmit impulses to the CNS from sensory receptors.
 Motor neurons transmit neural signals from the CNS to the effectors
(glands, organs, muscles).
 The PNS is divided into two subsystems:
1- The sensory somatic nervous system.
2- The autonomic nervous system.
 Sensory nervous system comprises 12 pairs of cranial nerves and 31 pairs of
spinal cord nerves.
- Some pairs are exclusively sensory neurons (involved in smell, vision,
hearing and balance).
- Other pairs are made up of motor neurons (included in taste and
swallowing).
- Spinal cord nerves are mixed of sensory and motor neurons .This allows
to spinal cord neurons to function as conduit of transmission of the
signals of the stimuli and subsequent response.
Figure (3.28): Peripheral Nervous System. (Reece J.B. ,Urry L.A., Cain M.L.,
Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco,
80
Sensation
 The sense includes general sense and special sense.(Figure 3.29 ).
 The somatic sense includes touch, pressure, temperature, proprioception and
pain.
 Sensation or perception is the conscious awareness of stimuli received by
sensory receptors.
 Sensation requires a stimulus, a receptor, and conduction of action potential
to CNS, translation of action potential and processing of the action potential
in CNS.
SENSES
Receptors distributed over a Receptors localized within

large part of the body specific organs
General senses Special senses
Located in Located in
skin, muscle internal organs
joints
Balance
Smell
Tast Heari
Somatic Visceral e ng
Sight
Touch Pain
Pain Pressure
Pressur Temp.
e
Proprioception
Figure (3.29): Classification of senses.

81
Sensory receptors
 Sensory receptors are specialized nerves cells that detect environmental

stimuli and transducer them through neural signals.
 Receptors include mechanoreceptors, chemoreceptors,
thermoreceptors, photoreceptors and nociceptors.
 A stimulus produces action potential in a focal area of sensory surface
(e.g., skin), the receptive field.
 The receptive fields allow the body to be topographically mapped
throughout the whole nervous system from the skin to the brain.
 Primary receptors have axons that transmit action potential toward CNS.
 Secondary receptors have no axons but release neurotransmitters.
 Some signals need to be transmitted to the CNS rapidly, whereas others
can be transmitted more slowly, so different types of sensory fibers have
different size and velocities.
Sensory transduction
 A process, in which a stimulus is detected, amplified and conducted to CNS.

 This occurs through changes in membrane potential, this change is called a
receptor potential, which achieved by opening ion channels allowing
current to flow.
 If membrane potential reaches threshold, action potential occurs.
 The signal intensity (e.g., intensity of pain) can be conveyed by recruiting
increased membranes of parallel fibers or by increasing the frequency of
action potential.
Adaptation
 Adaptation a special characteristic of all sensory receptors.
 Sensory receptors is adapt after period of time to any stimulus. This is either
partially or completely.
- Slowly adapting (tonic): receptors continue to transmit impulse to the
brain as long as the stimulus is present, such as muscle spindle, pressure
receptor slow pain receptors.
- Rapidly adapting (phasic): receptors rapidly adapt to constant stimulus
by decreasing their action potential frequently over time, such as light
touch receptors, Meissner corpuscles and deep pressure (pacinian
corpuscles).
82
Sensory pathways
 Sensory pathway is a group of neurons linked synaptically, share common
function and course:
1- The receptors potential is created.
2- Receiving of the signal from the receptors by first order neurons (cells in
the dorsal root ganglia)
3- Second order neurons (in the spinal or brainstem) receive signals from
the first order neurons and transmitted them to the thalamus.
4- The third order neurons are located in the relay nuclei of the thalamus,
the ventral posterior nucleus and project to the cerebral cortex.
5- The fourth order neurons (in the cortical cortex) confer conscious
perception of the stimulus.
6- The orientation of these neurons in the cortex creates a sensory
homunuclu, which is a map of the body in the brain.(Figure3.30).
Figure (3.30):The sensory map of the body in the brain.( Barrett K.E.,Barman S.M.
Boitano S. and Brooks H.L. Ganong, s Review of Medical Physiology . Singapore, McGraw-
Hill Companies,2012).
83
Pain perception
 Pain is a sensation characterized by a group of unpleasant and complex

perceptual and emotional experience that trigger autonomic, psychologic
and somatic motor response.
 Pain components:
1- Rapidly conducted action potential by large diameter myelinated axons,
resulting in sharp, well localized, pricking or cutting pain.
2- More slowly propagated action potential carried by smaller myelinated
axons causing poorly localized diffuse burning or aching pain.
 Pain receptors:
- Free nerve endings that are located in the skin, muscle and viscera are
responsible for detecting and perception of pain (nociception).
- The pain receptors adapt very little and sometime not at all.
- The pain receptors have very uniform sensitivity, which does not change
dramatically from one instant to another.
 Variation in pain result from :
1- The mechanism by which pain receptors are stimulated.
2- Differences in the integration of action potential from the pain
receptors and complex interactions in the cerebral cortex, cingulated
gyrus and thalamus where the emotional components of pain is
registered.
Motor tracts
 Motor tracts are descending pathways containing axons that carry action
potential from cerebrum or cerebellum to the brainstem or spinal cord.
 The descending motor fibers are divided into two groups,(Figure 3.31) :
1- The direct pathways: maintain muscle tone and control fine skilled
movement in the face and distal limbs.
2- The indirect pathways control conscious and unconscious muscle
movements in the trunk and proximal limbs.
 The corticospinal tracts control muscles movements below the head.
- About 75%-85% of the upper motor neurons of the corticospinal tracts
cross over in the medulla to form the lateral corticospinal tracts in the
spinal cord.
- The remaining upper motor neurons pass through the medulla to form
the anterior corticospinal tracts, which cross over in the spinal cord.
- The upper motor neurons of both tracts synapse with interneurons that
synapse with lower motor neurons in the spinal cord.
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Figure (3,31): Descending motor pathways.Modified from: (Marieb E.N.and Hoehn
K.Anatomy and physiology. San Francisco, Pearson Education Inc., 2011).
 The corticobulbar tracts innervate the head muscles. Upper motor neurons
synapse with interneurons in the reticular formation, which inturn synapse
with lower motor neurons in the cranial nerve nuclei.
 The indirect pathways include the rubrospinal, vestibulospinal and
reticulospinal tracts and fibers from the basal nuclei.
Autonomic nervous system

Overview
 Autonomic nervous system (ANS) is the part of nervous system that is
responsible for homeostasis.It consists of three subsystems :
1- The sympathetic nervous system.
2- The parasympathetic nervous system.
3- The enteric (ENS) nervous system.
 The ANS regulates the activities of smooth muscles, cardiac muscles,
endocrine glands and exocrine glands. (Figure 3.32).
 These functions are regulated by brain centers in the hypothalamus and
brainstem.
 Some target organs are innervated by both sympathetic and parasympathetic
nervous system .Others are controlled by one.
 The ENS controls the activity of gastrointestinal tract.
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 The ANS functions involuntarily (reflexively) in an automatic manner
without conscious control. The ANS operates through visceral reflexes.
(e.g., response to cold).
Figure (3.32): Autonomic Nervous system.( Seeley R.R., Stephens T.D. and Tate P.
 Peripheral motor portion of ANS are made up of two neurons:

1) Periganglionic neurons 2) Postganglionic neurons.
 The cell bodies of periganglionic neurons are located in the
intermediolateral (IML) column of the spinal cord and motor nuclei of
some cranial nerves.
 Periganglionic axons are small diameter myelinated, relatively slowly
conducted.
 Autonomic output diffuse by diverging periganglionic axon to average 8-9
postganglionic neurons.
 Postganglionic axons are unmyelinated and terminate on the visceral
effectors.
 Periganglionic neurons release acetylcholine (ACh) at their nerve terminals.
86
1- Sympathetic nervous system
 The sympathetic nervous system is called “fight or flight system” because
it is most active in times of stress ,fear or excitement
 The system originates in the spinal cord as pre-ganglionic neurons, which
connect with post-ganglionic neurons going to the organ they act upon.
 This prepares for physical activity by:
- Increasing ventilation and expanding the respiratory passages.
- Increasing the cardiac output, blood pressure (so the blood is pumped
faster) and blood distribution through vasoconstriction (blood to the
muscles at the expense of the gut).
- Increasing the concentration of blood glucose above normal, by
releasing glucose from the liver.
- Increasing sweating (to cool the body during activity)
- Inhibiting digestion.
2- The parasympathetic nervous system.

 The parasympathetic nervous system is called the “rest and digest system”
because it is most active in times of rest and relaxation.
 Parasympathetic pathways are composed preganglionic and postganglionic
neurons.
 The perganglionic nerve fibers originate in the cranial nerve nuclei in the
brainstem and in lower spinal cord.
 This system prepares for resting activities by
- Promoting digestion, defecation and urination.
- Slowing respiration.
- Slowing the heart beat.
3- The enteric nervous system

 This system comprises submucosal and myenteric plexuses; entirely
contained within the gut wall.
 Stimulation of the myenteric plexus increases the intestinal motility by
stimulation peristalsis and inhibiting contraction of sphincter muscles
throughout the intestinal tract.
 The ANS influences functioning of the enteric nervous system :
- The sympathetic stimulation inhibits peristalsis and increases sphincter
tone, thereby inhibiting digestion.
- The parasympathetic stimulation promotes peristalsis and relaxes the
sphincters, thereby enhancing digestion.
87
Chemical transmission
 Transmission at the synaptic junction between preganglionic and
postganglionic neurons, and between postganglionic neurons and autonomic
effectors are chemically mediated.
 The principle transmitter agents involved are: acetylcholine (ACh) and
norepinephrine.
 The autonomic neurons that are cholinergic(release ACh)are:
- All periganglionic neurons
- All parasympathetic postganglionic neurons
- Sympathetic postganglionic neurons that innervate sweat glands.
- Sympathetic postganglionic neurons that end on blood vessels in some
skeletal muscles and produce vasodilatation when stimulated.
 The remaining sympathetic postganglionic neurons are noradrenergic
(release norepinephrine).
 Transmission in autonomic ganglia is mediated by the action of ACh on
nicotinic cholinergic receptors that are blocked by hexamethonium (Nn
receptors) to distinguish them from the nicotinic cholinergic receptors
(Mm) located at the neuromuscular junction and blocked by D-tubocurane.
 Noradrenergic neurotransmission :
- Norepineprine spreads farther and has more prolonged action than ACh
- Norepinephrine, epinephrine and dopamine are all found in plasma.
- The epinephrine and some of dopamine come from the adrenal
medulla, but most of the norepinephrine diffuses into the blood stream
from sympathetic nerve endings.
Autonomic dysfunction
 Drugs, neurodegenerative diseases, trauma, inflammatory processes and
neoplasia are factors that can lead to dysfunction of the ANS.
 The types of dysfunction may range from complete autonomic failure to
autonomic hyperactivity.
 Among disorders associated with autonomic failure are orthostatic
hypotension, neurogenic syncope, impotence, neurogenic bladder,
gastrointestinal dysmotility and Horner,s syndrome .
 Autonomic hyperactivity can be basic for neurogenic hypertension, cardiac
arrhythmias, neurogenic pulmonary edema, and myocardial injury.
88
References
1. Barrett K.E.,Barman S.M. Boitano S. and Brooks H.L. Ganong, s Review of Medical
Physiology .24th ed. Singapore, McGraw-Hill Companies,2012.
3. Costanzo L.S. Physiology .4thed,Philadelphia ,Saunders,2012.
4. Guyton A.C. and Hall J.E., Textbook of Medical Physiology .13th ed. Philadelphia,
Saunders, 2015.
5. http://www.studyblue.com
6. https://WWW.boundless.com /physiology.
8. Marieb E.N.and Hoehn K. Anatomy and physiology.4thed, San Francisco, Pearson
Education Inc., 2011.
9. Randall D. ,Burggren W. and French K. Eckert Animal Physiology .5th ed. New York,
10. Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology. 8th ed. New York,
89
Chapter Four
Special Senses 4
Special Senses
Overview
 Special senses are senses with highly localized receptors to provide specific
information about the environment.
 They comprise olfaction, taste, vision, hearing and equilibrium (the
vestibular system).
1- Olfaction
 Olfaction is the sense of smell.
 Smell is detected by olfactory receptors cells in the mucus-coated olfactory
epithelium that lines the posterodorsal parts of the nasal cavities.
 Olfactory glands secrete a fluid to bath the cilia of the receptors and acts as a
solvent for odorant molecules.
 Olfactory receptors cells are stimulated by binding of odor molecules to
their cilia.
 Axon of olfactory receptor cell form the first cranial nerve (CN I).
 Axon of the mitral cells of the olfactory bulb: form the olfactory tract and
lateral olfactory stria,(figure4.1 ), which project to olfactory cortex and
amygdala .
 Olfactory receptor cells: only regenerative neurons in adult human.
Figure (4.1 ): Olfactory region, olfactory tract and olfactory bulb. (Seeley R.R., Stephens
T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill Companies, 2008).
90
 Olfactory transduction: Binding of odoriferous molecules to cilia on
olfactory cells: results in action potential generation and transduction of
signal to olfactory cortex.
2- Taste
 Taste is detected by taste receptor cells which are located on specialized
papillae of the taste bud, (figure4.2.b) and are stimulated by taste
chemicals.
 Each bud contains about 40 taste cells, each ending in an exposed hair-like
projection, to which chemicals attach.
 The taste cells are a mixture of 5 types: sweet, salt, umami (savory), sour
and bitter, but 1 type will be dominant. Thus the tip of the tongue mainly
detects sweet, the front sides detect salt, back sides detect sour and the back
of the tongue mainly detects bitter.(Figure 4.2.a).
 Taste transduction:
- The binding of taste chemicals to the taste receptors causes a
depolarization of the receptors membrane.
- The depolarization results in action potential that is propagated
centrally until the taste sensation is perceived.
a b
Figure(4.2 ):a ;Surface of the tongue ,b:A taste bud . (Seeley R.R., Stephens T.D. and Tate
P. Anatomy and Physiology .New York, McGraw –Hill Companies, 2008).
91
3- Vision
Structure of the eye
 The eye is a spherical structure filled with liquid vitreous humor (aqueous
humor )in front of the lens, which is enclosed by 3 layers,(figure4.3):
1. Sclera
 Sclera is the outer thick layer.It is white connective tissue that
protects the eye from physical damage and helps maintain the
spherical shape.
 There are 6 skeletal muscles, the (extrinsic eye muscles) attached to
the outside of the sclera, which move the eye ball.
 At the front of the eye, the white sclera is replaced by a transparent
cornea, which not only allows the light to enter the eye, but also
helps to focus the light on to the retina.
2. Choroid
 Choroid is a middle thin vascular layer (provide oxygen to the eye)
and black pigment cells (stop internal reflections by absorbing stray
light).
 At the front of the eye, the choroid becomes ciliary body, which
contains the ciliary muscles that focus the lens, by changing its
shape.
 The ciliary body continues interiorly into the iris, which controls the
amount of light entering the eye.
3. Retina
 Retina is the inner layer which has an outer black layer (like the
choroid) and an inner sensory layer, which contains 2 types of
receptors: rods and cones, and 5 types of association neurons.
Figure (4.3): The layers of eyeball (sagittal section). (Marieb E.N.and Hoehn
92
Detection of light
In order to see, the eye must solve the following problems:-
1. Control the amount of light entering the eye.
This is due to the iris, which is made up of 2 concentric areas of smooth muscle.
 In bright light, parasympathetic stimulation of the central circular
muscle contracts it to reduce the size of the central pupil (hole through
which the light enters).(Figure 4.4.a).
 In low light levels, sympathetic contraction of the outer radial muscle
decreases the size of the iris to increase the pupil. (Figure 4.4.b).
Pupil
Figure(4.4):Controlling the amount of the light entering the eye. (Seeley R.R.,
Stephens T.D. and Tate P. Anatomy and Physiology .New York, McGraw –Hill
Companies, 2008).
2. Focus the light on to the retina.

 When looking at an object, the light from that object must be focused on the
retina in order to get a sharp picture. Although most focusing is done by the
cornea, focusing must change for a near object compared with a distant
object. This change in focus is done by the lens, whose shape can be changed
by the ciliary muscle of the ciliary body. (Figure 4.5).
Figure (4.5): The lens and ciliary body. (Seeley R.R., Stephens T.D. and
93
- In distant vision, the muscles are relaxed. Thus suspensory ligaments
around the lens stretch it into a flattened shape.
- For a near object, the muscles contraction and being circular reduce the
central area (like in the iris) to shorten the ligaments. The ligaments are
thus relaxed and the lens becomes more rounded as it relaxes. This
focusing process is known as accommodation. When an object is in
focus, it will appear on a small area of the retina known as the fovea (in
the rest of the retina, the objects are out of focus). (Figure 4.6).
Figure (4.6): Focus and accommodation by the eye,(a): The lens is flattened and the
image is focused on the retina,(b): Accommodation for near vision ,the lens is more
rounded and the image is focus on the retina.( Seeley R.R., Stephens T.D. and Tate P.
Anatomy and Physiology .New York, McGraw –Hill Companies, 2008).
3. Detect the light in the retina.

 The receptors detect light using the visual pigment, rhodopsin. They are of
two types:-
1- Rods, (figure 4.8.b) are the most abundant (about 125 m) and are
distributed throughout the retina. Because they contain a large amount of
rhodopsin, they are very sensitive to light. They work in low light levels
such as at night, but are inactive during the day (when all the rods will
be highly stimulated, and so cannot produce a picture of light and dark).
2- Cones are less abundant (only 6.5 m), (figure 4.8.a) but are
concentrated at the fovea, where the object you are looking at will be
focused. The cones will therefore give a detailed picture of the object
you are staring at, but all the peripheral vision will be very blurred (few
cones are in the peripheral retina). (Figure 4.7) .Although cones also
use a rhodopsin-like pigment; the opsin component of the rhodopsin can
be of 3 types, each of which is sensitive to a different color: which are
red, green and blue. Detection of a color depends on the relative
stimulation of the 3 types (thus red will strongly stimulate the red cones,
but orange will give less stimulation and yellow give even less). Cones
only work in daylight (so, the colors cannot be seen at night, when only
the rods are working).
94
Figure (4.7): Section through the retina with its major layers.( Seeley R.R., Stephens T.D.
and Tate P. Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
 The rhodopsin is found in the outer part of each receptor, which is made up
of parallel discs. (Figure4.8.c). Rhodopsin consists of the pigment retinal
combined with the protein opsin.
 When hit by a photon of light, the retinal changes shape, breaking away
from the opsin and releasing energy, which results in the depolarization of
the neuron attached to the receptor. ATP is then used to change the retinal
back to its original shape and reattach it to the opsin. This rhodopsin cycle
is illustrated in figure (4.9).
a b c d
Figure ( 4.8 ): Sensory receptor cells of the retina. a: Cone cell, b:Rod cell,
c:An enlargement of the discs in the outer segment d: An enlargement of one of the
discs.( Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –
Hill Companies, 2008).
95
Figure (4.9): The rhodopsin cycle. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and
 The five types of interneurons connected to the rods and cones are
responsible for integration of the data. By combining the data from the
6,500,000 cones, they make the picture sharper by looking for patterns, such
as boundaries between 1 color and another, while at the same time reducing
the information down to the 100,000 neurons in the optic nerve. Further
integration will then occur in the thalamus and in the occipital lobe of the
cerebrum, where to put final picture together.
 Note that the light must 1st pass through the interneurons before it is detected
by a rod or cone and finally absorbed by the black pigment.
Clinical note: Myopia is the ability to see close objects clearly but distant objects
appear blurry .It is a defect of the eye in which the focusing system, the cornea and
lens is optically too powerful or the eye ball is too long .As r result the focal point is
too near the lens and the image is focused in front of the retina. Myopia is
corrected by a concave lens that counters the refractive power of the eye.
Hyperopia is the ability to see distant objects clearly but close objects appear
blurry. It is a disorder in which the cornea and lens system is optically too weak or
the eye ball is too short .The image is focused behind the retina .Hyperopia can be
corrected by convex lenses that cause light rays to converge as they approach the
eye.
Presbyopia is the normal unavoidable degeneration of the accommodation power
of the eye that occurs as a consequence of aging .It occurs because the lens
becomes sclerotic and less flexible. It can be corrected by using of reading glasses.
Astigmatism is a type of refractive error in which the quality of focus is affected If
the cornea or lens is not uniformly curved the light rays do not focus at a single
point but fall as a blurred circle. Regular astigmatism can be corrected by glasses
that are formed with the opposite curvature gradation.
96
2. The ear - Hearing.
Structure of the ear
1- The outer ear
 It consists of pinna and the external acoustic meatus which lined with
hair and glands that secrete wax (cerumen).
2- The middle ear
 It is air filled.
 It contains the "tympanic membrane" a three layered membrane
between the middle ear and the inner, and three small bones (auditory
ossicles): malleus, incus and stapes.
 The stapes inserts into the oval window,
 Sound waves cause the tympanic membrane to vibrate. In turn, the
ossicles vibrate, pushing the stapes into the oval window and displacing
fluid in the inner ear.
 Sound is amplified by the lever action of ossicles and the concentration
of sound waves from the large tympanic membrane onto the smaller oval
window.
3- The inner ear
 It is fluid –filled
 It consists of a bony labyrinth (semicircular canals, cochlea and
vestibule) and a series of ducts called the membranous labyrinth.
 The fluid outside the ducts is perilymph. The fluid inside the ducts is
endolymph. (Figure 4.10).
Figure (4.10): Structure of the ear. (Scanlon V.C. and Sanders T. Essential of Anatomy and
Physiology . Philadelphia, E.A. Davis Company, 2007).
97
 The cochlea consists of three tubular canals:(Figure4.11)
- The scala vestibuli and scala tympanic contain perilymph ,which
has a high Na+
- The scala media contains endolymph ,which has a high K+ .
 The cochlea is bordered by the "basilar membrane" which houses the
organ of Corti .
 Organ of Corti contains inner and outer hair cells needed for audition.
These cells have cilia embeded in tectorial membrane.
 The spiral ganglion contains the cell bodies of the auditory nerve(cranial
nerveVIII),which synapse on the hair cells.
Figure ( 4.11 ):Structure of the cochlea. (Seeley R.R., Stephens T.D. and Tate P. Anatomy
Auditory transduction
 Sounds waves cause vibration of the organ of Corti.Because the basilar
membrane is more elastic than the tectorial membrane ,vibration of the
basilar membrane causes the hair cells to bend by a shearing force as they
push against the tectorial membrane.
 Bending of the cilia causes changes in the K+ conductance of the hair cell
membrane.Bending in one direction causes depolarization ;bending in the
other direction causes hyperpolarization.The oscillating potential that results
is the cochlear microphonic potential.
 The oscillating potential of the hair cells causes intermittent firing of the
cochlear nerves.
Sound encoding
 The frequency that activates a particular hair cell depends on the location of
the hair cell along the basilar membrane.
- The base of the basilar membrane (near the oval and round window)is
narrow and stiff .It responds best to high frequencies.
98
- The apex of the basilar membrane (near the helicoterma) is wide and
compliant .It responds best to low frequencies.
Neural pathways of hearing

 Axons from the vestibulocochlear nerve synapse in the medulla.
 Axons from the medulla project to the inferior colliculli to synapse .
 Neurons from the inferior colliculli project to the thalamus.
 Thalamic neurons extend to the auditory cortex.
 Discrimination of complex features e.g.,recognizing a patterned sequence ,is
a property of the cerebral cortex.
Clinical not: The term hearing-impaired refers to any type or degree of

hearing loss. The hearing loss can be conductive, sensorineural, or a
combination of both. Conduction deafness involves a mechanical deficiency
in the transmission of sound waves from the external ear to the spiral organ.
The spiral organ and neural pathways function normally. Sensorineural
deafness involves the spiral organ or neural pathways. Sound waves are
transmitted normally to the spiral organ, but nervous system’s ability to
respond to the sound waves is impaired.
3. Body
. equilibrium.
 Apart from the cochlea, two other sense organs make up the ear:
- The vestibule detects static equilibrium (position of the head).
- The semicircular canals detect kinetic equilibrium (movement of
the head).
Static equilibrium
 The saccule (at the base of the cochlea) and the utricle (at the base of the
semicircular canals) both contain hair cells in which the microvilli are
enclosed in a gelatinous layer containing otoliths.
 The hair cells and gelatinous layer are together known as the macula.
Otoliths are small stones of protein and calcium carbonate, which press
down on the microvilli. (Figure 4.12).
 The hair cells thus form a gravity receptor, in which tilting of the head
results in bending of the microvilli: the amount of microvilli bending
being proportional to the amount of head tilting.
Kinetic equilibrium
 The semicircular canals are at right angles to each other, so that each is in a
different plane: 1) horizontal and 2) vertical. Each canal has at its base a
swelling, the ampulla, which contains hair cells with their microvilli
embedded in a mass of jelly, the cupula (similar to the macula, but without
otoliths).
99
 The canals are filled with endolymph. When the head moves in one plane,
e.g. horizontally, the endolymph in the horizontal canal swirls around the
circular canal and pushes over the cupula filling the base of the canal. Thus
the microvilli inside it are bent. Note that the endolymph appears to move in
the opposite direction to the head movement, because the liquid gets left
behind as the head starts to move. (Figure 4.13).
Figure ( 4.12 ):Structure of macula. a:utricle and saccule in the vestibule.b: Part of
macula ,showing hair cells and otoliths. (Marieb E.N.and Hoehn K.Anatomy and
physiology.San Francisco, Pearson Education Inc., 2011).
Figure (4.13): Semicircular canals .a: ampullae in the semicircular canal. b: cupula and
hair cells. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New
York, McGraw –Hill Companies, 2008).
The canals measure four factors:

 The plane of movement (which of the 3 canals is affected).
 The direction of movement (clockwise/ anticlockwise).
 The velocity of movement (how far over the cupula is pushed).
 Acceleration/deceleration (the rate at which the cupula is pushed over and
recovers).
100
References
101
Chapter Five
Skeleton and Muscular system 5
Skeletal system
Overview
 The skeleton is made up of: bone, cartilage and attachment structures
(tendons & ligaments).
1. Bone. Bone matrix consists of calcium phosphate (hydroxyapatite) around a
framework of collagen fibers (which make the bone flexible and less
brittle).
Bone functions:
 Support the body by providing a rigid framework.
 Protection from damage by enclosing vital parts e.g. the ribs and scapula
(shoulder blade) enclose the thorax (heart & lungs); the vertebrae and skull
enclose the central nervous system.
 Movement. Bones provide a rigid attachment against which muscles
contract. Joints between bones control body movements.
 Mineral storage. Stores minerals such as calcium ions, so that their blood
concentration can be kept constant by releasing from storage as needed. The
bone marrow also stores fat.
 Blood cell formation. All blood cells (both erythrocytes and leucocytes) are
produced by the bone marrow.
2. Cartilage. The matrix of the cartilage is made up of collagen which gives

strength and flexibility and proteoglycan: a polysaccharide storing water
(giving smoothness).
Cartilage functions:
 Model for bone growth. During growth, cartilage is produced first and
gradually replaced by bone.
 Reduce friction at joints. At joints, the bone is covered by a layer of
cartilage, which provides a smooth plastic-like surface, with a low friction
and acts as a shock absorber.
 Flexible support. For the nose, ears and trachea.
102
Bone structure
Bone cells
 Osteoblasts produce bone matrix and become osteocytes.
- Osteoblasts connect to each other through cell processes and surround
themselves with bone matrix to become osteocytes.
- Osteocytes are located in lacunae and are connected to each other
through canaliculi.
 Osteoclasts are large cells responsible for the resorption of bone.
 Osteoblasts originate from osteochondral progenitor cells. Osteoclasts
originate from stem cells in red bone marrow.
 Ossification is the formation of bone by osteoblasts, occurs through the
appositional growth.
Compact and Cancellous Bone

1- Compact bone
 Compact bone is dense with few spaces.
 It comprises the outer layer of large bones, but the whole of smaller bones,
is made up of lamellae (each is a layer of matrix: hydroxyapatite and
collagen) arranged concentrically around Haversian canals (blood vessels).
 Osteocytes (bone cells) lie in between the lamellae and are connected
together by canaliculi (threads of cytoplasm for food and oxygen transport
between cells), which also connect to the Haversian canal
 Diaphysis of a long bone is composed of compact bone and it can also
contain some cancellous bone.
 The medullary cavity fills the center of the large bones. It contains bone
marrow, producing the blood cells.
 The periosteum is a layer of connective tissue and blood vessels around the
outside of all bones and contains osteoblasts.
 Endosteum is a single layer of cells that lines the internal surface of all
cavities within bones. (Figure 5.1).
103
a
c
Figure (5.1):Compact bone . a: Long bone .b: Compact bone consists of

concentric lamellae(Osteon ) surrounding blood vessels within central canals.
c:Osteon.Modified from: (Seeley R.R., Stephens T.D. and Tate P. Anatomy and
Physiology.New York, McGraw –Hill Companies, 2008).
104
2- Cancellous bone
 Cancellous bone has many spaces.
 It forms the inner layer of large bones. It forms a network of bone
(trabeculae) enclosing spaces filled with bone marrow.
 Compared with compact bone, it is still strong but much lighter and so
reduces the overall weight of the bone.
 Most trabeculae are thin( 50-400µm )and consist of several lamellae within
osteocytes located in the lacunae between the lamellae.(Figure5.2).
Figure (5.2): Cancellous Bone. a: Trabeculae surround spaces in the bone.

b:Transverse section of the trabeculae. .(Seeley R.R., Stephens T.D. and Tate P.
105
Bone shape
 Individual bones are classified according to their shape as long, short, flat or
irregular.
 Long bones are longer than they are wide, e.g., most of the upper and lower
limbs.
 Short bones are about as broad as they are long., e.g., carpal and wrist
bones.
 Flat bones have thin flattened shape and are usually curved, e.g., ribs,
sternum and shoulder blades (scapulae).
 Irregular bones have shape that do not fit readily into the other three
categories,e.g., vertebrae and facial bones.
 Flat, short and irregular bones have an outer covering of compact bone
surrounding cancellous bone.
Bone growth
 Most bones develop from a cartilage model.
 The cartilage matrix is calcified and chondrocytes die .Osteoblasts form
bone on the calcified cartilage, producing cancellous bone.
 Osteoblasts build an outer surface of compact bone beneath the periosteum.
 Primary ossification centers form in the diaphysis during fetal
development.
 Secondary ossification centers form in the epiphyses.
 Articular cartilage on the ends of bones and epiphysial plate is cartilage
that does not ossify.
 Bones increase in size only by appositional growth, the adding of new
bone on the surface of older bone or cartilage.
 Trabeculae grow by appositional growth.
Bone remodeling
 Bone remodeling is a process by which the old bone is replaced with new
bone. In this process the osteoclasts remove old bone and osteoblasts deposit
new bone.
 This process converts the woven bone to lamellar bone.
 It involves in bone growth, bone shape, adjustment of bone to stress, bone
repair and calcium regulation in the body.
 The relative thickness of compact bone is maintained by removal bone on
the inside by osteoclasts and addition of bone to the outside by osteoblasts.
Factors affecting bone growth

1- Genetic factors determine bone shape and size.
2- Factors that alter the mineralization process or production of organic matrix,
such as deficiencies in vitamins D and C can affect bone growth.
3- Growth hormone, thyroid hormone, estrogen and testosterone stimulate
bone growth.
4- Estrogen and testosterone cause increased bone growth and closure of the
epiphyseal plate.
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Clinical note: Giantism is a condition of abnormal increased height that usually
results from excessive cartilage and bone formation at the epiphyseal plates of
long bones.
Dwarfism: the condition in which a person is abnormally short.
Osteomyelitis is bone inflammation; results from bacterial infection .It can lead to
complete destruction of the bone.
Osteomalacia: the softening of bones, results from calcium depletion from bones.
Osteoporosis: results from a reduction in the overall quantity of bone tissues. It
occurs when the rate of bone resorption exceeds the rate bone formation. The
loss of bone mass makes the bones so porous and weakened that they become
deformed and prone to fracture. It increases with age.
Joints
 Bones connected to each other by joints, to allow movement. These are:
1- Synovial joints (have a capsule enclosing synovial fluid as a lubricant).
2- Fibrous joints hold two parallel bones together (e.g. lower arm and
lower leg).
3- Cartilaginous joints connect the ribs to the sternum.
 Synovial joints have a number of problems to solve:-
 Friction.
- The ends of the bones are covered by a layer of cartilage. This is
smooth and plastic-like, reducing friction, thus preventing one bone
damaging the other by rubbing it away.
- Synovial fluid between the bones acts as a lubricant. The fluid is
held in place by being enclosed in the joint capsule, made of
connective tissue.
 Controlling movement. The bones are held together by ligaments of
collagen fibers. The distribution of these and the shape of the ends of the
bones control the amount of movement that is possible at the joint.
- Hinge joints only allow movement in one plane e.g. the fingers and
the knee. These are very strong joints, so few muscles are needed.
- Ball & socket joints allow movement in almost any direction e.g.
the shoulder and leg/hip joints. These are more flexible but weaker,
so a ring of muscles is needed to control movement.
Clinical note: Damage to the cartilage results in two diseases:-

Osteoarthritis in old people is where the cartilage has been worn away, so the
bones (especially the hip and knee joints) rub and damage each other.
Rheumatoid arthritis is an auto-immune disease, in which the leucocytes attack
and destroy the cartilage, especially in the fingers and toes, so the joints become
deformed and fused together.
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Muscular system
Overview
 There are three types of muscle tissues: Skeletal muscles, cardiac muscles
and smooth muscles.
 Skeletal muscle cells and smooth muscle cells are elongated so called
muscle fibers.
1- Skeletal muscle
- Skeletal muscle fibers are longest muscle cells, multinucleated and
striated.
- Skeletal muscle is voluntary muscle, responsible for overall mobility.
- It contracts rapidly, tires easily and must rest after short period of
activity.
2- Smooth muscle
- It is arranged in circular layers around hollow visceral organs such as
stomach, urinary bladder and respiratory passages.
- It is spindle shape ,not striated
- It contracts involuntary.
3- Cardiac muscle
- It occurs only in the heart.
- It is involuntary, without conscious control.
- It can contract without nervous system stimulation, by the heart
pacemaker, but neural control allows the heart to speed up for brief
period.
Characteristics of muscle tissues

1- Excitability or irritability is the ability to receive and respond to a
stimulus. The stimulus may be a chemical (neurotransmitters released by
nerve cells) or local change in PH.
2- Contractility is the ability to shorten when adequately stimulated.
3- Extensibility is the ability to be stretched or extended.
4- Elasticity is the ability of muscle cell to recoil after being stretched.
Muscles functions
 Body movement. Skeletal muscles responsible for all locomotion and
manipulation
 Posture. Skeletal muscles, by contracting continuously, maintain our body
position, e.g. standing or sitting.
 Respiration. Skeletal muscles raise and lower the ribs during ventilation of
the lungs.
 Body heat. The body is homoeothermic, with a constant temperature of 37.5
o
C. This requires production of heat by skeletal muscles, either as a by-
product of contraction or by special contractions known as shivering.
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 Communication. Speaking, writing and facial expressions all depend on
skeletal muscles.
 Heart beat. Cardiac muscles contract to pump blood around your body.
 Contraction of internal organs. Smooth muscles transport materials by
peristaltic contractions (a wave of contraction pushes the material along the
tube) in the gut, reproductive system, blood vessels, glands, etc. Smooth
muscles also mix food in the stomach.
Skeletal muscle structure

 The skeletal muscle is made up of many fasciculi (bundles), each of which
is made up of many fiber cells.
 The skeletal muscle cells are unusual because:-
- The cells lie parallel to each other, so each cell stretches from one end
of the muscle to the other end.
- Each cell has many nuclei. This is because the cells are so huge (maybe
30cm long), that 1 nucleus cannot control the cell. The nuclei are found
around the edge of the cell, just under the sarcolemma (cell membrane).
- Cells contain a network of membrane invaginations (T-Tubules): to
connect sarcolemma and ER (sarcoplasmic reticulum in muscle cell),
which is filled with calcium at rest.
- Each cell has inside it thousands of myofibrils, lying parallel to each
other. Each myofibril is divided into a long chain of thousands of
sarcomeres.
- Each sarcomere is separated from the next by a Z-disk, which appears
as a dark line. Since all the cells have their Z-disk lined up with adjacent
cells, dark lines run across the muscle and the cells are said to be
“striated”.(Figure 5.3).
109
b
a
Figure (5.3): Parts of muscle, a:part of muscle attached by tendon to a bone.

b:Enelargement of one muscle fiber. c: Myofibril extended out the end of the muscle
fiber. : (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology .New York, McGraw
–Hill Companies, 2008).
 Each sarcomere contains four types of proteins:-

1- Actin. These are spherical molecules attached to each other in a row
(Figure5.4.a). Two rows are twisted around each other in a helix to form a
myofilament. Myofilaments are attached on either side of the Z-disk in
parallel rows.
a b
Figure (5.4): Structure of actin and myosin, a: Actin myofilament.b:Myosin
myofilament. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York,
2- Myosin. Each molecule is a long rod ending in a head (like a golf club).
(Figure5.4.b) .The molecules are arranged in bundles to form a
myofilament. These are arranged parallel to each other, lying in between the
actin filaments (and so lying in the middle of the sarcomere attached to an
M-line). (Figure 5.5).The heads of the molecules stick out of the
myofilament and attach to the actin, during a muscle contraction.
110
3- Troponin. These are attached to the actin and have Ca2+ receptors.
4- Tropomyosin. This is attached to the troponin and forms long threads
covering the attachment sites on the actin. They prevent myosin attachment,
when the muscle is resting. (Figure5.4.a).
Myofibril
Figure (5.5): Composition of a single sarcomere of a myofibril.Modified from (Marieb

E.N .Essential of Human Anatomy and Physiology .San Francisco, Pearson
Muscle contraction
Sliding Filament Model
 Muscle contraction is explained by the sliding filament mechanism, in
which the actin filaments slide over the myosin filaments.
 Since the actin filaments are attached to the Z-discs, the sarcomere becomes
shorter as the two Z-discs come towards each other, but there is no change
in the length of either the actin or myosin filaments.
 As all the sarcomeres shorten on all the myofibrils, then the whole muscle
fiber cell becomes shorter.
 Sliding the actin over the myosin is due to the myosin heads repeatedly
attaching to and detaching from the actin. (Figure 5.6).
Motor units
 For a skeletal muscle cell to contract, it must first be stimulated by impulses
from a neuron, the motor neuron (in the anterior horn of spinal cord).
 Neuron and all muscle fibers are supplied by it is the motor unit.
 A single neuron innervates multiple muscle fibers (axon branches to nerve
terminals and each nerve terminal supplies one muscle fiber.
 The neuron branches connect with muscle cells by a neuromuscular
junction.
 When motor neuron transmits action potential all muscle fibers which it
innervates, contract.
111
Figure (5.6): Sarcomere shortening.( Marieb E.N .Essential of Human Anatomy and
Physiology . San Francisco, Pearson Education,Inc.,2012).
Excitation –contraction coupling and cross –bridge movement

 Because of the huge size of the muscle cells, the impulse is further
transported inside the cell by transverse (T) tubules, to each sarcomere on
each myofibril.
 The arrival of an impulse through the T-tubules causes the sarcoplasmic
reticulum to release calcium ions in to the sarcomeres.
 Calcium ions attach to receptors on the troponin and push it and thus the
tropomyosin to one side. This uncovers the actin attachment sites.
The attachment of the myosin head to the actin requires a constant ATP
supply.
 ATP attaches to the myosin head and breaks down in 3 stages:
112
1- The ATP on the myosin head breaks down into ADP + PO4, causing the
myosin head to attach to the binding site on an actin molecule
2- A Release of the ADP and PO4 molecule from the head, releasing the
energy .The energy is used to bend back the myosin head. Since this is
attached to the actin filament, the bending movement slides the actin
filament over the myosin filament.
3- Attachment of a new ATP to the myosin head releases it from the actin, so
that the head can bend forwards in to its resting position (so its lies beside
a new actin molecule). (Figure5.7).
Figure (5.7): Breakdown of ATP and Cross bridge movement. (Marieb E.N.and
Hoehn K .Anatomy and Physiology .San Francisco, Pearson Education Inc., 2011).
113
 As long as there is a constant supply of ATP, the actin will continue to
progressively slide over the myosin, causing the sarcomere to shorten.
 The contraction will end when there are no more impulses arriving from
the neuron. This causes the calcium ions to be pumped back in to the
sarcoplasmic reticulum, so that the tropomyosin covers up the binding sites
on the actin and pushes the myosin away from the actin.
 When there is no contraction between the actin and myosin, the actin will
slide back into its resting position (due to elastic elements in the muscle that
were stretched during the contraction), causing the sarcomeres to expand.
The muscle twitch

 When an impulse travels down the neuron, all of its muscle cells will
contract and then relax.
 This is investigated by using apparatus that produce a myogram, the line it
records is called tracing.
 Every twitch myogram has three phases: (Figure5.8).
1. Latent period: is the first few milliseconds between application of a
stimulus to the motor neuron and the beginning of contraction.
2. Contraction phase: is the time which the contraction occurs.
3. Relaxation phase: is the time during which the relaxation occurs
initiated by reentry of Ca2+into sarcoplasmic reticulum.
Figure (5.8): The phases of muscle twitch. (Randall D. ,Burggren W. and French K. Eckert
Animal Physiology .5th ed. New York, W.H. Freeman and Company, 2002).
114
Types of contraction
1- Graded: the strength of contraction depends primarily on the number of
muscle fibers recruited rather than the strength of muscle fibers.
2- Twitch: an electrical stimulation of muscle cell above the threshold results
in a limited efflux of Ca2+ from the sarcoplasmic reticulum into the
cytoplasm stimulating a single contraction.
3- Summation and tetanus: if muscle is stimulated at a high enough
frequency, individual muscle twitches combine (summate) to produce
sustained contraction (tetanus) (Figure 5.9).
 Incomplete tetanus: as the frequency of action potential in skeletal
muscle fiber increases, the frequency of contraction also increases,
muscle fibers partially relax between the contractions.
 Complete tetanus: action potentials are produced so rapidly in muscle
fibers that no relaxation occurs between them.
4- Isotonic muscle contraction
 A constant force is produced while muscle length is changing.
 As the muscle tension increases, the muscle shortens and lifts the load. (
e. g, biceps curls in weight lifting).
5- Isometric muscle contraction: causes a change in muscle tension but no
change in muscle length (e.g., pushing against immovable objects such as a
wall).
Figure (5.9): Multiple summations.

1-5: are stimuli of increasing frequency.
Up arrow: the start of stimulation .Down Arrow: the end of stimulation.
Stimulus frequency 1 produces successive muscle twitches with complete
relaxation.
Stimuli frequencies 2-4: without complete relaxation.
Stimulus frequency 5: causes tetanus –no relaxation between stimuli.
(Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology .New York, McGraw –Hill
Companies, 2008).
115
Regulation of contraction
 Muscle contraction is regulated by the somatic nervous system (under
voluntary control).
 The fewer muscle fibers innervated by a given motor neuron the greater
precision of control of contraction.
 The strength of skeletal muscle contraction is determined by four factors:
1- Metabolic condition
2- Amount of load
3- Recruitment of motor units
4- Initial length of muscle fibers.
 The amount of tension that can be generated is determined by the length –
tension relationship (the extent of actin –myosin myofilament overlap).
- If the sarcomeres is shortened, the actin –myosin have less room to
overlap and develop tension.
- If the muscle is stretched to a point at which actin and myosin no longer
overlap, no cross-bridge can be formed and no tension can develop.
Energy source for muscle contraction

 Energy required for muscle contraction comes from ATP.
 ATP for crossbridge movement and detachment is generated by:
1- Direct phosphorylation of ADP by creatine phosphate .This converts
ADP back to ATP (by donating a PO4 + energy). There is only enough
creatine phosphate to keep the muscle contracting for a few seconds.
2- Glycolysis (anaerobic pathway): ATP is produced by the breakdown

of glucose .This does not use O2, but is very inefficient (2 ATP/ glucose
molecule). To compensate, the cell usually has large stores of glycogen
that can be broken down into glucose. The cell can only work
anearobically for 2-3 minutes before it runs out of ATP and the buildup
of lactic acid inhibits the muscle contraction resulting in fatigue.
3- Aerobic respiration: This uses O2 to break down glucose to 36ATP +

CO2 + H2O. It is very efficient and there is no lactic acid, so it can
continue contracting for long periods. But the cell requires:
a. Large numbers of mitochondria in the cell to carry out aerobic
respiration using Kreb’s cycle.
b. A good oxygen supply, so large numbers of capillaries enter the
muscle.
c. Myoglobin inside the muscle cell picks up O2 from the capillaries
and transport around the muscle cell. Myoglobin also stores O2
when the cell is resting.
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Fatigue: is the decreased ability to do work .It can develop at three sites:
1-Psychological fatigue: is common type involving CNS. The muscles are
capable of functioning but the individual perceive that an additional work is not
possible.
2-Muscular fatigue: results from ATP depletion.
3-Synaptic fatigue: results from depletion of ACh in the muscular synapse.
Rigor motis: development of rigid muscles several hours after death, that is ATP
production stops shortly after death.
Types of skeletal muscle fibers

1- Fast twitch fibers
 They use glycogen and anaerobic metabolism, fatigue easily but good
for explosive high intensity activity of short duration.
 They are whitish in color due to small amount of myoglobin.
2- Slow twitch fibers
 They use aerobic metabolism so do not fatigue easily.
 They are rich in myoglobin, red appearance.
 Common in muscle controlling posture.
Clinical note: Muscle disorders are caused disruption of normal innervations,

degeneration and replacement of muscle cells injury, lack of use and diseases.
Atrophy: is a decrease in the size of muscles.
Fibrosis: is replacement of muscle tissues by connective tissues.
Fibrositis : is an inflammation of fibrous connective tissues causing stiffness
,pain and soreness.
Cramps: are painful spastic contractions of muscle that usually result from an
irritation within a muscle that causes a reflex contraction.
Smooth muscle
Overview
 Smooth muscle is arranged in a circular layer around hollow organs
(esophagus, respiratory airways) and blood vessels .Contraction of these
muscles reduces the size of the organs.
 The cells are spindle shape .Actin-myosin myofilaments are not arranged
into sarcomeres, so the cells are nonstriated in appearance.
 The absence of sarcomeres enable smooth muscle to contract even when the
cells are enormously stretched.(smooth muscle contraction is not limited by
the length –tension relationship).
117
 The sarcoplasmic reticulum is loosely arranged within the cells, and there
are no T-tubules.
 The cells contain dense bodies, structures analogous to the Z disks found in
skeletal muscles.
Types of smooth muscles

1- Single unit(unitary or vesiral ) smooth muscle
 Predominant type located in GIT, bladder, uterus and ureters.
 There are gap junctions to transmit nerves impulses causing the
contraction of many cells at once.
 They are characterized by the rhythmic fluctuation of membrane
potential (slow waves) that gives rise to spike potential which can cause
muscle contraction.
 The slow waves are the primary regulator of single –unit smooth muscle,
but the activity may be modified through the autonomic nervous system.
2- Multi smooth muscle

 They are located in the iris, ciliary muscles of the lens and vas
deferens.
 They are similar to the skeletal muscle in that each fiber is innervated,
therefore functions separately.
 Gap junctions are absent. (Figure5.10.a).
 Regulated by autonomic nervous system.
Figure (5.10): Types of smooth muscle.( Reece J.B. ,Urry L.A., Cain M.L., Wasserman
S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San Francisco, Benjamin
Cummings,2014).
118
Mechanism of contraction
 Slow waves give rise to spike potentials, which stimulate cell contraction.
 The initial phase of contraction is triggered by an increased releasing of
cytoplasmic calcium from the sarcoplasmic reticulum.
 Sustained contraction is mediated by continued influx of Ca2+ into the
cytoplasm from interstitium through voltage-gated calcium channels.
 Calcium combines with the protein calmodulin to form (calcium-
calmodulin complex) and activates myosin light chain kinase (MLCK).
 MLCK phosphorylates the myosin cross bridge.
 Actin and myosin form cross-bridge that contract the muscle cell.
 Relaxation occurs when Ca2+ has been pumped back into the sarcoplasmic
reticulum.
 Smooth muscle is innervated by autonomic nervous system.
 Sympathetic and parasympathetic nerves are distributed to all organ
systems in the body and stimulate smooth muscle activity in many organs at
once.
 Parasympathetic stimulation has opposite effects to that of sympathetic
stimulation.
 Hormones are important in the regulation smooth muscles. Some hormones
can increase the Ca2+ permeability of the smooth muscle membrane
therefore cause contraction without change in resting membrane potential.
Cardiac muscle
Overview
 Cardiac muscle is found in the heart only.
 Cardiac muscle tissue is striated; each muscle contains one nucleus located
near the center.
 Adjacent cells join together to form branching fibers by specialized
attachment (intercalated disk), which have gap junctions allowing the
action potential to pass from cell to cell.
 Some cardiac muscle cells are autorhythmic .One part of the heart acts as
the pacemaker.
 Action potentials of cardiac muscle are similar to those of nerve and skeletal
muscle, but have much longer duration and refractory period. That is the
extracellular Ca2+ plays a substantial role in triggering contraction.
119
 Cardiac cells have an unstable resting membrane potential that allows them
to generate their own electrical pacemaker activity.
 Strength and rate of contraction are regulated by autonomic nervous system.
 Sympathetic stimulation has a positive effect through binding of
norepinephrin and epinephrine to adrenergic receptors.
 Parasympathetic stimulation has negative effect through binding of ACh to
muscarinic receptors.
 The comparison of the three muscle types are summarized in table (5.1).
Pharmacology note: The fact that extracellular calcium plays such an important
role in stimulating cardiac muscle contraction is exploited by calcium channel
blocking drug such as diltiazm and verapamil. Calcium channel blocker reduce
heart rate and contractility without adversely affecting skeletal muscle functioning
and are therefore useful for treating hypertension and a myriad of cardiac
condition.
Table (5.1): Comparison among the three muscle types. (Seeley R.R., Stephens T.D. and
120
References
3. Costanzo L.S. Physiology .4thed, Philadelphia, Saunders,2012.
Pearson Education, Inc., 2012.
5. Randall D., Burgggren W. and French K .Eckert Animal Physiology: Mechanisms
and Adaptations.4th ed. New York, W.H. Freeman and Company, 2000.
121
Chapter Six
Cardiovascular system 6
Cardiovascular system
Overview
 Humans have a closed circulatory system, in which blood is confined to
vessels and is distinct from the interstitial fluid.
 The heart pumps blood into large vessels that branch into smaller ones leading
into the organs.
 Materials are exchanged by diffusion between the blood and the interstitial
fluid bathing the cells.
I. Heart
Overview
 The heart consists of 2 pumps lying side by side.
 Each pump has an atrium, which collects blood from the veins, and a
ventricle, which pumps out the blood.
 The right side of the heart receives blood from the body and pumps blood
through the pulmonary circulation which carries the blood to the lung and
returns it to the left side of the heart.
 The left side of the heart pumps blood through systemic circulation which
delivers oxygen (O2) and nutrients to all remaining tissues of the body .then
carries the blood to the right side of the heart.
 The heart of 70 Kg healthy person pumps 7200 L of blood each day, at a
rate 5L/min.
Systemic and pulmonary circulation

 The right ventricle pumps the blood to the lungs through the pulmonary
artery. The blood returns via the pulmonary vein into the left atrium. This
is the pulmonary circulation.
 The left ventricle pumps the blood around the body via the aorta. Because
of the greater distances, this ventricle is larger than the right ventricle; so
that it creates a higher pressure (a higher pressure to the lungs would destroy
the delicate capillaries). The blood return via the vena cava into the right
atrium. This is the systemic circulation. (Figure 6.1).
- The blood thus has a double circulation, so that all the blood going to
the tissues is oxygenated (because it earlier went to the lungs) and
under high pressure and thus traveling at high velocity.
 There is actually a 3rd circulation: the coronary circulation: This provides a

separate blood supply to the heart muscles.
122
- The coronary artery branches from the aorta; the blood from the
capillaries is then collected by the cardiac vein and returned to the vena
cava.
- The coronary artery is small for the size of the heart, but gives up 75% of
its oxygen to the cardiac muscle. In contrast, a typical artery in the rest of
the body is much larger but gives up 25% of its O2 to the body tissues,
when the body is at rest (so that a vein contain blood that is still 75%
oxygenated), but has the option to increase this when the muscles
become active.
 The heart muscle is never resting and so has a more constant O2 demand.
Figure (6.1): Systemic and pulmonary circulation.( Marieb E.N.and Hoehn K.Anatomy
and physiology. San Francisco, Pearson Education Inc., 2011).
Functions of the Heart

1- Generating blood pressure: This is due to the contraction of the heart.
2- Routing blood: The heart separates the pulmonary and systemic circulation
3- To Ensuring one-way blood flow: Heart valves ensure one-way flow
4- Regulating blood supply: Changes in contraction rate and force match blood
delivery to the changing metabolic needs of the tissues.
123
Heart anatomy
 Shape: The adult heart is shaped like a blunt cone. The rounded point of the
cone is the apex .The larger flat part is the base.
 Size:
- It is the size of closed fist.
- It is larger in physically active person than in other healthy adults.
- The size decreases with age after 65 years, but not in physically active.
 Location:
- The heart lies obliquely in the mediastinum .(Figure 6.2 )
- It is located in the thoracic cavity between the lungs.
- The base of the heart is directed posteriorly and slightly superiorly.
- The apex is directed anteriorly and slightly inferiorly.
- The location is of a clinical importance for positioning the stethoscope
to hear the heart sounds and positioning the electrodes to record
electrocardiogram (ECG) from the chest leads.
Figure (6.2): Location of the heart. Retrieved from : www.rci.rutgers.edu).
 More anatomical considerations :

- Pericardium: is the sac that surrounds the heart and consists of 2 types
of pericardium: (Figure 6.3).
1. Fiberous pericardium: helps hold the heart in the place.
2. Serous pericardium: reduces friction as the heart beats.It consists
of :
 Parietal pericardium:lines fibrous pericardium
 Vesiral pericardium: lines exterior surface of the heart.
 Pericardial cavity between parietal and vesiral
124
Figure (6.3): Pericardium. (Marieb E.N.and Hoehn K.Anatomy and physiology.
San Francisco, Pearson Education Inc., 2011).
- Heart Wall: The heart wall is composed of 3 layers :( Figure 6.4).

1. Epicardium: This serous membrane of smooth outer surface of heart,
provides protection against the friction of the rubbing organs
2. Myocardium: Middle layer composed of cardiac muscle cell and
responsible for heart contraction.
3. Endocardium: Smooth inner surface of heart chambers composed of
simple squamous epithelium over a layer of connective tissues .It
reduces the friction resulting from the blood passing through the heart.
Figure (6.4): Heart wall. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and
External Anatomy
 The heart is composed of :
- Four chambers :2 atria and 2 ventricles
- Major veins :Superior vena cava and pulmonary veins
- Major arteries : Aorta and pulmonary trunk.
 Each atrium has a flap the auricle.
125
 The coronary sulcus separates the atria from the ventricles.
 The inferior and superior venae cava and the coronary sinus enter the right
atrium .The pulmonary veins enter the left atrium.
 The pulmonary trunk exits the right ventricle and the aorta exits left
ventricle.(Figure 6.5).
 Coronary arteries branch off aorta to supply the heart.
 Blood returns from the heart tissues to the right atrium through the coronary
sinus and cardiac veins.
Figure ( 6.5): Anterior view of the heart. (Marieb E.N .Essential of Human Anatomy
and Physiology . San Francisco, Pearson Education,Inc.,2012).
Internal anatomy: Heart chambers and valves

 Interaterial septum: separates the atria from each other.
 Interventricular septum: separates the ventricles.(Figure 6.6).
 Tricuspid valve: separates right atrium and ventricle
 Bicuspid valve: separates left atrium and ventricle
 The chordae tendineae : attach the papillary muscles
 Semilunar valve: separates aorta and pulmonary trunk from the ventricles.
Figure (6.6): Internal anatomy of the heart.( Seeley R.R., Stephens T.D. and Tate P. Anatomy
126
Blood flow through the Heart
 The 2 atria collect the blood from the veins and pump the blood into the
ventricles. When the ventricles have filled with blood, they contract
together, pushing the blood out through the arteries.
 The 2 ventricles are separated by a septum. The left ventricle has much
thicker muscle than the right because it produces a much higher blood
pressure around the body (around 120 mm Hg, compared with 24 mm Hg
from the right ventricle to the lungs).
 The direction of blood flow is controlled by 4 valves :
- During atrial contraction:

 The 2 atrial-ventricular (AV) valves between the atria and
ventricles (tricuspid for the right ventricle; bicuspid: mitral valve
for the left ventricle) are both open, so blood is pumped into the
ventricles.
 The pulmonary valve (at the base of the pulmonary artery) and the
aortic valve (base of aorta) are closed, to prevent arterial blood
flowing back into the relaxed ventricles. (Figure 6.7.a).
- During the ventricular contraction:
 Tricuspid and bicuspid valves are closed, due to contraction of
papillary muscles attached to the corners of the valve by long
tendons (chordae tendinae), to prevent the blood being pumped
back in to the atria.
 The pulmonary and aortic valves are open to allow the ventricular
blood to be pumped out in to the arteries. (Figure 6.7 .b).
Figure (6.7): Function of the heart valve .a: atrial contraction, b: ventricular
contraction. ( Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York,
127
 There is thus a double contraction of the heart:
- First a small contraction of the 2 atria.
- Larger contraction of the 2 ventricles after 0.1 sec later. The left
ventricle forces a pressure wave (pulse) through the aorta, which
spreads through the other arteries and into the veins. This pressure
wave is known as systole, while the relaxation of the ventricle gives
diastole (the resting pressure of the artery).
 Blood from the body flows through the right atrium into right ventricle
as the ventricle relaxes, and then to the lung, where gas exchange occurs.
(The blood flows from an area of higher pressure in the systemic
circulation to area of a lower pressure, the right atrium).
 Oxygenated blood returns from the lungs to the left atrium, enters the
left ventricle and is pumped back to the body. (Blood flowing through
the aorta is distributed to all parts of the body, except to the parts of the
lungs which supplied by the pulmonary blood vessels). Blood flow
through the heart is depicted in figure (6.8).
Figure (6.8): Blood flow through the heart. (Seeley R.R., Stephens T.D. and Tate P.
Pathology note: The aortic valve in some individual is congenitally bicuspid.

These bicuspid valves are predisposed to early calcification and stenosis, often
causing aortic stenosis in individuals in their late 40 S or early 50 S. Common
cause of the aortic stenosis is the calcification of the normal tricuspid valve
(senile calcific aortic stenosis).Another cause of aortic stenosis is rheumatic
fever .Aortic stenosis increases the rate of blood flow through the aortic valve
producing turbulent flow and consequently systolic ejection murmur.
128
Pathology note: Mitral Stenosis: the mitral valve becomes stenotic due to
abnormal structural changes. The most common is the rheumatic fever.
Symptoms of mitral stenosis are dyspnea and exercise intolerance.
In Mitral regurgitation, the mitral valve does not form good seal causing
blood flow into the left atrium during early systole.
Heart Skeleton ,( Figure 6.9):

 Consists of plate of fibrous connective tissue between atria and ventricles
 Fibrous rings around valves to support them.
 Serves as electrical insulation between atria and ventricles
 Provides site for muscle attachment
Figure (6.9 ): Skeleton of the heart. (Marieb E.N .Essential of

Human Anatomy and Physiology . San Francisco, Pearson
Cardiac muscle,(Figure 6.10):

 Cardiac muscle is similar to skeletal muscle in having actin and myosin
arranged in sarcomeres (so the cells are striated) forming many myofibrils.
Thus contraction takes place in the same way (sliding-filament mechanism)
 Cardiac muscle differs from skeletal muscle in that:
- The cells contract spontaneously, and most cells have no nerves
connected to them.
- It has short cells (only 1 nucleus in the center of each cell), which are
branched and connected to other cells by intercalated discs.
- The intercalated discs have a large surface area between 1 cell and the
next and many gap-junctions, allowing the impulse to travel directly
from 1 cell to the next.
- The branching cells results in all the cells being connected together, so
that the impulse will travel throughout the whole muscle. Thus cardiac
muscle cells function as a unit.
 Cardiac muscle cells have slow onset of contraction and a prolonged
contraction time caused by the long time required for calcium to move.
129
 Cardiac muscle is well supplied with blood vessels that support aerobic
respiration.
Figure (6.10): Cardiac muscle cells. (Reece J.B. ,Urry L.A., Cain M.L.,
Wasserman S.A., Minorsky P.V. and Jackson R.B. Campbell Biology. San
Francisco, Benjamin Cummings,2014).
Conducting system of the heart

 Conducting system of the heart consists of modified cardiac muscle cells.
 Modified cardiac muscle cells form : two nodes and conducting bundles
 Two nodes within the walls of right atrium ,named according to the
position in the atrium:
- SA node: Sinoatrial node is medial to the opening of the superior vena
cava.
- AV node: Atrioventicular node is medial to the right atrioventicular
valve.
 AV gives rise to conducting bundle of the heart (bundle of His).
 This bundle passes through a small opening in the fibrous skeleton to reach
interventicular septum, where divided to form right and left bundle
branches.
 Bundle branches extend beneath the endocardium on each side of the
interventicular septum to the apices of the right and left ventricles
respectively.
 The inferior terminal branches of the bundle branches are called Purkinje
fibers.
 Purkinje fibers are larger diameter than cardiac muscle fibers. They have
fewer myofibrils than most cardiac muscle cells and DO NOT contract as
forcefully.
 Intercalated disk are well developed between Purkinje fibers and contain
numerous gap junctions, so: These structural modifications make action
potential travels along Purkinje fibers much more rapidly than other
cardiac muscle tissues.
 AS node generates spontaneous action potential at a greater frequency. This
AS node is called the Pacemaker.
 The SA node is made up of specialized small diameter cardiac muscle cells
that merge with other cardiac muscle cells of the right atrium, thus: The
heart contract spontaneously and rhythmically.
130
 Once action potentials are produced, they spread from the SA node to the
adjacent cardiac muscle fibers.
 The conducting system of the heart which shows how action potential
originates and travels through the heart is depicted in figure (6.11).
Electrical properties
Overview
 Cardiac muscles have resting membrane potential (RMP).
 RMP depends on low permeability of plasma membrane to Na+ ,Ca+2 and
high permeability to K+
 When cardiac cells are depolarized to threshold level action potentials result.
 Action potentials exhibit depolarization and then repolarization.
 Alterations in membrane channels are responsible for the change in
membrane permeability, that produces the action potential.
 Action potential in cardiac muscles last longer than in skeletal muscle .In
muscles ,action potentials take less than 2millisecond (ms) to complete ,but
in cardiac muscle take 200-500 ms to complete.
Figure ( 6.11):The conducting system of the heart. (Seeley R.R., Stephens T.D. and Tate P.
Action potential in cardiac muscles
 Action potential in cardiac muscle consists of :

- Voltage gated Na+ channels open causing Na+ to diffuse into the cell.
Rapid depolarization occurs until the cells are polarized to (+20 mv).
- Voltage gated K+ channels closed. Movement of K+ is responsible for
establishing RMP in cardiac cells. If voltage gated K+ channels close,
membrane permeability to K+ decreases.
131
- Voltage gated Ca2+ channels begin to open .This channels open and
close slowly as compare to that of Na+.
1- Early repolarization and plateau phase
 Voltage gated Na+ channels close.
 Voltage gated K+ channels open causing early polarization.
 Voltage gated Ca2+ channels open producing plateau and slowing
repolarization. (Figure 6.12.b).
2- Final repolarization phase
 Voltage gated Ca2+ channels close.
 Many voltage-gated K+ channels open.
 Action potentials in cardiac muscle are conducted from cell to cell,
whereas action potentials in skeletal muscle fibers are conducted along the
length of a single muscle fiber, not from fiber to fiber.
 The rate of action potential propagation is slower in the cardiac muscle
because cardiac muscle cells are smaller in diameter and shorter than
skeletal muscle fibers. The comparison of action potentials in skeletal and
cardiac muscle is illustrated in figure (6.12).
 Although the gap junctions of intercalated disk allow the transfer action
potential between cardiac muscle cells, they do slow the rate of action
potential conduction between the cardiac muscle cells.
Figure (6.12): Comparison of action potential between skeletal and cardiac muscle.
a:Action potential in skeletal muscle. b:Action potential in cardiac muscle . (Seeley
R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –Hill
Companies, 2008).
132
Autorhythmicity of cardiac muscle
 The heart is autorhythmic because it stimulates itself to contract

at regular intervals (rhythmic).
 If the heart is removed from the body and put under normal
physiological condition it will continue to beat autorhythmically
for long time.
 SA generates action potential spontaneously at regular intervals.
Action potentials spread through the conducting system to other
cardiac muscle cells causing voltage gated Na+ channels to open.
As a result action potential is produced and cardiac muscle cells
contract.
 The production of action potential by SA node is responsible for
autorhythmicity of the heart (Figure 6.13).
Figure ( 6.13):Action potential in SA

node.
Permeability changes in pacemaker
include:
1-Prepotential phase:
-Voltage gated Na+ channels open
-Volltage gated K+ channels close
-Voltage gated Ca+ channels begin to
open
2-Deploarization phase:
-Voltage gated Ca2+ channels open
-Voltage gated K+ channels close
3-Repolarization phase:
- Voltage gated Ca2+ channels close.
-Voltage gated K+ channels open.
Pharmacology note: Calcium channels blockers e.g., diltiazem , verapamil block

voltage Ca2+ channels preventing the influx extracellular Ca2+ during cardiac
action potential and causing less Ca2+enter the cardiac cells to activate
contractile mechanism .Therefore, these drugs are widely used in treatment of
tachycardia ,arrhythmia .
The drug atropine blocks the muscarinic receptors in the heart and increases
heart rate .It is therefore useful in treating patients with acute bradycardia
133
Refractory period
 Cardiac muscle cells cannot be excited again immediately after
depolarization.
 Absolute refractory period: Cardiac muscle cell are completely insensitive
to further stimulation
 Relative refractory period: Cell exhibits reduced sensitivity to additional
stimulation.
 The presence of plateau phase delays repolarization and prolongs the
refractory period. The long refractory period ensures that contraction and
relaxation are completed before another action potential can be initiated.
This prevents occurring of tetani.
The Electrocardiogram
 The electrocardiogram (ECG) monitors the electrical activities in the
heart by recording the electrical changes at the surface of the body.
 Electrodes are placed on the surface of the body and attached to an
appropriate recording device that can detect a small voltage change resulting
from action potential in the cardiac muscle.
 Electrodes detect a summation of all the action potentials that are
transmitted by the cardiac muscle cells through the heart at a given time.
 ECG is valuable diagnostic tool in identifying a number of abnormal cardiac
rhythms e.g., abnormal heart rate, abnormal conduction pathways,
hypertrophy or atrophy of portions of heart and the approximate location of
damaged cardiac muscle can be detected from analysis of ECG.
 The normal ECG consists of(Figure6.14 ) :
1- P wave represents atrial depolarization.
2- QRS complex composed of 3 individual waves Q,R,S result from
ventricular depolarization.
3- T wave represents repolarization of the ventricles. (Repolarization of
atria cannot be seen because it occurs during the QRS complex.)
a. PQ interval is the time between the beginning of P wave and the
beginning of the QRS complex .During this time the atria contract
and begins to relax. (0.16 second).
b. QT interval extends from the beginning of QRS to the end of T
wave, represents the time required for ventricles to contract then
relax.(0.36 second).
Figure (6.14): The normal Electrocardiogram (Brown T.A.

Rapid Review of Physiology. Philadelphia, Mosby, 2012).
134
Pathology note: Alteration in ECG: (Figure 6.15 )
1-Elongation of PQ interval can result from:
-A delay in action potential conduction through the atrial muscle because of
damage e.g. caused by ischemia.
-A delay in action potential conduction through the atrial muscle because of
dilated atria
-A delay in action potential conduction through AV node and bundle because
of ischemia or necrosis of AV node.
2-Unusual long QT interval reflects the abnormal conduction of AP through
the ventricles which may result from:
-Myocardial infarction (MI)
-Abnormal enlarged left or right ventricles.
Figure (6.15): Alterations in ECG. (Seeley R.R., Stephens T.D. and Tate P.
Common cardiac arrhythmias
1- Tachycardia
 It means fast heart rate(HR). In adult person, HR is faster than100
beats/min.
 ECG is normal except that HR as determined from the time intervals
between QRS complex is 150 beats /min instead of 72beats/min.
 Some causes of tachycardia include increased body temperature, stimulation
of sympathetic nerves and simple weakness of the myocardial which
increases the HR because this elicits sympathetic reflexes.
2- Bradycardia
 It means slow HR. Usually HR is fewer than 60beats/min.
135
 Stimulation of vagus verves causes release of Ach in the heart giving a
parasympathetic effect.
 The athlete‟s heart is larger and stronger than normal person, which
allows the heart to pump a large stroke volume output causing excessive
quantities of blood pumped into the arterial tree with each beat initiating
feedback circulatory reflexes or other effect to cause bradycardia.
Pathology note: In patients with carotid sinus syndrome, the baroreceptors

in the carotid artery walls are excessively sensitive to even mild pressure .This
elicits a strong baroreceptors reflexes and causing intense Ach effect on the
heart including extreme Bradycardia.
3- Sinus arrhythmia
 Heart rate varies between 5% during the respiratory cycle and up to 30%
during deep respiration.
 Sinus arrhythmia can result from any circulatory condition that alters the
strength of sympathetic and parasympathetic nerve signals to the heart
sinus node.
4- A premature contraction
 It is shortened intervals between one contraction and the succeeding one.
 Most of premature contractions result from ectopic foci in the heart which
emits abnormal impulses at odd time during the cardiac rhythm.
Cardiac cycle
 Cardiac cycle is the repeating series of contraction and relaxation that

move the blood through the heart (Figure 6.16).
 It is composed of systole and diastole.
1- Systole
a. Period of isovolumic contraction
 The atria are relaxed causing blood flow into them from the veins.
 Ventricular contraction leads to ↑ ventricular pressure and AV valves
to close.
 Semilunar valves remain closed.
b. Period of ejection
 Ventricular contraction lead to greater increased in ventricular
pressure causing push out the blood and opening the semilunar
valve.
136
2- Diastole
a. Period of isovolumic relaxation
 As ventricles begin to relax at the beginning of the ventricular
diastole, the blood flow back from the aorta and pulmonary trunk
toward the relaxing ventricles causing the semilunar valves to close.
b. Passive ventricular filling
 As ventricular relaxation continues AV valves open causing blood
flow from atria into the relaxing ventricles.
c. Active ventricular filling
 Atria contract leading to ↑ arterial pressure and completing
ventricular filling while the ventricles are relaxed.
 The events that occur during the cardiac cycle are depicted in figure (6.17).
.
Figure (6.16): Cardiac cycle.( Marieb E.N .Essential of Human Anatomy and Physiology .
San Francisco, Pearson Education,Inc.,2012).
Heart sounds
1. First heart sound or “lubb”
Atrioventricular valves and surrounding fluid vibrations as valves close at
beginning of ventricular systole
2. Second heart sound or “dupp”
Results from closure of aortic and pulmonary semilunar valves at beginning
of ventricular diastole, lasts longer
Pathological note: Blood flow through the cardiovascular system is laminar and
silent .In certain circumstances, flow velocity is increased or viscosity is decreased
and turbulent flow occurs that can produce noise (murmurs or bruits).
137
Figure (6.17): Events occurring during the cardiac cycle.
The cardiac cycle is divided into 5 periods (top).From top to
bottom: The electrocardiogram; pressure changes for the left
atrium (blue line), left ventricle (black line) and aorta (red line);
left ventricular volume curve; and heart sounds.
Marieb E.N.and Hoehn K.Anatomy and physiology. San Francisco, Pearson

Aortic pressure curve

 Blood is ejected into the aorta by contraction of the ventricles, raising the
aortic pressure and producing peak systolic pressure till to 120 mmHg.
 The elastic recoil of the aorta maintains the aortic pressure and producing
dicrotic notch or incisura, a double pulse can be felt.
 Aortic pressure then gradually falls throughout the rest of ventricular
diastole as blood flows through the peripheral vessels .This produces a
diastolic pressure (80mmHg).
 When aortic pressure reaches 80 mmHg the ventricles contract again
forcing the blood into the aorta.
138
Mean Arterial Blood pressure
 Mean arterial pressure (MAP) is the average blood pressure in the aorta.
 MAP is proportional to the cardiac output (CO) times peripheral
resistance (PR).
MAP=CO X PR
- Cardiac output (CO) is the amount of blood pumped by the heart per
minute.
- Peripheral resistance PR is the total resistance against which the
blood must be pumped.
CO= HR X SV
- Heart rate (HR) is the number of times the heart beats (contracts) per
minutes. It is 72 bpm.
- Stroke volume (SV) is the blood volume pumped during each heart
beat. It is equal to the end diastolic volume minus end systolic volume.
SV= EDV-ESV
- End diastolic volume (EDV) is the blood volume in the ventricles at

the end of diastolic, just before the cardiac contraction. It is increased
during exercise because the increased venous return (amount of
blood returning to the heart from the peripheral circulation).
- End systolic volume (ESV) is the small quantity of blood remaining
in the ventricles at the end of systole. It is decreased during exercise
because the heat contracts forcefully.
 At rest , the value of HR is 72 bpm ,SV is 70 ml/beat ,therefore CO is
about 5L/min (CO=72 X 70 ).
 During exercise, the value of HR is 190 bpm, SV is 115, and therefore
CO is about 22L/min.
 The difference between CO when person at rest and maximum CO is
called cardiac reserve .The greater person’s cardiac reserve is the greater
person’s capacity for doing exercise.
 Lack of exercise and cardiovascular diseases reduce cardiac reserve
.Exercise training increases cardiac reserve by increasing CO.
139
Regulation of MAP
1- Short term:
 Baroreceptors are sensory receptors sensitive to stretch.
- Baroreceptors are located in the carotid sinuses and the aortic arch.
- The baroreceptor reflex changes peripheral resistance, heart rate, and
stroke volume in response to changes in blood pressure.
 Chemoreceptors are sensory receptors sensitive to oxygen, carbon
dioxide and PH level in the blood.
 Epinephrine and norepinephrine are released from adrenal medulla as
a result of sympathetic stimulation .They increase heart rate, stroke
volume and vasoconstriction.
2- Long term:
 Renin –angiotensin –aldosterone mechanism .Renin is released by the
kidney in response to low blood pressure .Renin promotes the
production of angiotensin II,which causes vasoconstriction and an
increase in aldosterone secretion.
 Antidiuretic Hormone is released from the posterior pituitary in
response decrease blood pressure resulting vasoconstriction.
 Aterial natriuretic hormone is released from the cardiac muscle cells
when arterial blood pressure increases resulting in an increase in urinary
production, a decrease in blood volume and blood pressure.
Regulation of the Heart
1- Intrinsic regulation
 An increased venous return cause increased EDV, which lead to
increase the stretch of the ventricular walls, the preload.
 The relationship between the preload and SV is the Starling‟s law .An
increased preload causes cardiac muscle fiber to contract forcefully
and produce greater SV.
2- Extrinsic regulation: Includes neural and hormonal control.
 Neural regulation: The cardioregulatory center in the medulla
oblongata regulates the parasympathetic and sympathetic nervous
control of the heart.
 Parasympathetic stimulation is supplied by the vagus nerve.
- Parasympathetic stimulation decreases HR.
- Postganglionic neurons secrete Ach which increases K+ membrane
permeability producing hyperpolarization.
 Sympathetic stimulation is supplied by cardiac nerves.
- Sympathetic stimulation increases the HR and SV.
- Postganglionic neurons secrete norepinephrine which increases
membrane permeability to Na+ and Ca2+ producing membrane
depolarization.
140
 Hormonal regulation: Epinephrine and norepinephrine are released
in the blood from the adrenal medulla causing long lasting effect
compared with the neural effect. They increase HR and SV.
Heart homeostasis
 Effect of blood pressure

- Baroreceptors monitor blood pressure: By baroreceptor reflexes, the
decrease in pressure (and thus cardiac output) cause increased
sympathetic stimulation and decreased parasympathetic stimulation .An
increase in pressure has the reverse effect.(Figure 6.18 )
 Effect of pH, carbon dioxide, oxygen.
- Chemoreceptors monitor blood CO2, PH, and O2 level.
- Increased CO2 and PH cause the medullary chemoreceptor reflexes to
increase sympathetic stimulation and decrease parasympathetic
stimulation of the heart. (Figure 6.19).
- Carotid body chemoreceptors stimulated by low O2 level result in a
decreased HR and vasoconstriction.
 Effect of extracellular ion concentration
- Increase or decrease in extracellular K+ decreases heart rate.
 Effect of body temperature
- Heart rate increases when body temperature increases, HR decreases
when body temperature decreases.
Clinical note: Heat failure is the result of progressive weakening of the heart muscle
and the cardiac output is inadequate to meet the body’s metabolic demands.
-Systolic heat failure: is pump failure (impaired contractility, increased afterload).
-Diastolic heart failure: impaired ventricular filling during diastole, due to stiff
ventricle or obstruction ventricular filling (mitral stenosis).
Hypertension results in heart failure due to increase afterload on the heart.
Many other factors e.g., advanced age, malnutrition, chronic infection, severe
anemia and hyperthyroidism can cause degeneration of heart muscle resulting in
heart failure. Hereditary factors can be responsible for increased susceptibility to
heart failure.
Angina pectoris is a pain that results from a reduction in blood supply to
cardiac muscle. Angina pectoris is characterized by chest discomfort deep to the
sternum described as heaviness, pressure or moderately severe pain .Angina
pectoris results from narrowed and hardened coronary arterial walls .The reduced
blood flow results in reduced oxygen supply to the cardiac muscle cell.
Low oxygen level leads to limited anaerobic metabolism of the cardiac
muscle results in reduced PH in the affected area. The decreased PH stimulates pain
receptors.
141
Figure ( 6.18 ):The baroreceptors reflexes :Homeostasis in response to changes in
blood pressure .( Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology .New York,
Figure (6.19): Chemoreceptors reflexes: Homeostasis in response to changes in CO2

and H+ pressure .( Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology .New
York, McGraw –Hill Companies, 2008).
142
II. Blood vessels
1- The arteries
- They are the strongest of the blood vessels.
- They carry the blood under a high pressure away from the heart.
- They have strong vascular walls (figure 6.20) and rapid blood flow.
2- The arterioles
- They are the last branches of the arterial system.
- They have strong vascular walls that can be constricted or dilated in
order to alter blood flow to the capillaries in response to changing tissue
needs.
3- The capillaries
- The capillaries allow exchange of gases, nutrients and wastes between
blood and tissues
- Overall large surface area and low blood flow.
- Two main types:
1. Continuous capillaries: narrow space between cells  permeable
to small or lipid soluble molecules
2. Fenestrated capillaries: large pores between cells large
molecules can pass.
4- The Venules
- They collect the blood from the capillaries.
- Gradually coalesce into large veins.
5- The veins
- They work as conduits to transport blood from the tissue back to the
heart.
- They serve as reservoirs for blood.
- They have thin walls, low pressure and rapid blood flow. (Figure
6.20).
Dynamic of blood circulation

The interrelationships among pressure, flow, resistance and the control
mechanisms that regulate blood pressure and blood flow through the vessels
play critical roles in the in the function of the circulatory system.
Blood flow
 It’s the volume of blood flowing through a vessel, an organ or the entire
circulation in a given period (ml/min).
 Blood flow through the vessels is streamlined or laminar.
 Turbulent flow unusual blood flow occurs when the rate of flow exceeds a
critical velocity or when the blood passes a constriction, a sharp turn or a
rough surface.
143
Figure ( 6.20 ): Overview of vasculature. (Marieb E.N .Essential
of Human Anatomy and Physiology . San Francisco, Pearson Education,
Inc.,2012).
Blood pressure
 Blood pressure is the pressure the blood exerts against the inner walls of the
blood vessels, and it is the force that keeps blood circulating continuously
even between heartbeats.
 Blood pressure is high in the arteries, lower in the capillaries and lowest in
the veins. Blood is forced along descending pressure gradients.
 Measuring of blood pressure:
Continuous contraction and relaxation of the heart cause the off and on
blood flow ,therefore the blood pressure rises and falls during each beat,
thus two arterial blood pressure measurements are made :
 Systolic pressure: is the pressure in the arteries at the peak of
ventricular contraction.
 Diastolic pressure: is the pressure when the ventricles are relaxing.
 Blood pressures are reported in millimeters of mercury (mmHg), with the
systolic pressure written first120 over 80 translated to 120mmHg and a
diastolic pressure of 80 mmHg.
 Systolic arterial blood pressure is measured indirectly by the auscultatory
method, which is used to measure blood pressure in the brachial artery of the
arm.
 Because the arterial pressure is the product of the cardiac output and
peripheral resistance, it is affected by any condition that affects either or both
of these factors.
 Many factors may influence blood pressure including the activity of the
sympathetic nerves, kidneys, drugs and diet.
144
Clinical note: Hypertension is a sustained elevation of the systemic arterial
pressure .It is most commonly due to increased peripheral resistance .It is
common and dangerous disease affects 30% of the people over than 50 years
of age . mmHg . Hypertension can be caused by many conditions include a
decrease in functional kidneys mass, excess aldosterone or angiotensin
production and increase resistance to blood flow in the renal arteries .All
these conditions cause an increase in total blood volume and cardiac output.
Although these conditions may result in hypertension, 90% of the diagnostic
cases are called idiopathic or essential hypertension which means the cause
of the condition is unknown.
Hypotension or low blood pressure, the systolic pressure is less than
100mmHg. It may reflect individual variations and is no cause for concern.
Pharmacology note: Diuretics (drugs that increase the rate of urine production,
vasodilator drugs and drugs that cause decrease cardiac output normally used
to treat essential hypertension.
Angiotensin –converting enzyme (ACE) inhibitors are effective in lowering
blood pressure in many people who suffer from hypertension. ACE inhibitors
are class of drugs that inhibit angiotensin –converting enzyme which converts
angiotensin I to angiotensin II.
Pharmacology note: Daily taking an aspirin reduces the chance of heart

attack.Aspirin inhibits the synthesis of prostaglandins in the platelets and
prevents clot formation.
Resistance
 It is the sum of all the factors that inhibit blood flow.
 There are three important sources of resistance :
1- Viscosity :
- It is a measurement of the resistance of a liquid to flow.
- As the viscosity increases, the pressure required for the liquid to
flow increases.
- The viscosity is influenced by the hematocrit (it increases when the
hematocrit increases).
2- Total blood vessels length
The longer vessels are the greater resistance.
3- Blood vessel diameter
- Changes in blood vessel diameter alter peripheral resistance .Blood
in direct contact with blood vessel walls flows relatively slowly
because the friction between the blood and the lining of the vessel,
while the fluid in center flows more freely.
145
- Laplace’s law states that the force acting on the wall of blood vessel
is proportional to the diameter of the vessel times blood pressure.
F= D X P {F: force, D: diameter, P: pressure.}
The effect of blood pressure and vessel resistance on blood flow

 Poiseuille,s equation describes the relationship between pressure ,vessel
radius ,viscosity and vessel length on blood flow. A small variation in vessel
radius translated into large change in blood flow.
πΔPr4
Blood flow (ΔQ) = _______
8ƞl
{ΔP: The pressure difference between two ends of the of the vessel
ƞ: viscosity, l: blood vessel length, r4: The fourth power of vessel radius} .
Vascular compliance
 It is the tendency of blood vessels volume to increase as blood pressure
increases.
 The compliance depends on the stretch ability of the blood vessel walls.
 Compliance is expressed by the following formula :
Increase in volume (ml)

Compliance=__________________________________
Increase in pressure (mmHg)
 The venous system has a larger compliance, and acts as a blood reservoir.
Most of volume is in the veins (64%).
 Smaller blood volumes are in the arteries (15%) and capillaries (15%).
Pathological note: Arteriosclerosis is the hardening of the arteries .It consists

of degenerative changes in the arteries making them less elastic and increase
resistance to blood flow .It becomes more sever with advancing age.
Advanced arteriosclerosis reduces blood circulation and increases the heart
work.
Atherosclerosis is a common type of arteriosclerosis caused by deposition of
cholesterol on the wall of the arteries to form a plaque. It affects medium
and large arteries including coronary arteries.
146
Capillary blood pressure
 Capillary blood pressure is low .It is about 35 mmHg by the time the blood
reaches the capillaries, and falls to 15 mmHg at the end of the capillary bed.
 The low capillary blood pressure is important because :
- The capillaries are fragile and the high pressure would rupture them.
- Most capillaries are permeable thus even the low pressure force solute
containing fluid out of the blood stream into the interstitial space.
Capillary exchange and interstitial fluid volume regulation.

 Capillary exchange is the movement of substances into and out of
capillaries.
 It is the process by which the cells receive everything they need to survive
and eliminate metabolic products.
 Small molecules and lipid soluble molecules move by diffusion through the
cell membrane. (Figure 6.21).
 Larger molecules, charged molecules must pass through membrane
channels, by exocytosis or in between 2 cells.
 Water movement is controlled by the capillary hydrostatic and osmotic
pressures.
Figure ( 6.21): Material exchange across the capillary membrane. Retrieved from
(www.studyblue.com).
 Arterial side of the capillary:

- High capillary hydrostatic pressure (BHP), lower capillary osmotic
pressure (BOP, due to proteins and other molecules in the blood)  Net
filtration pressure pushes fluid from the blood toward the tissue (but
the proteins remain in the capillary).(Figure 6.22 ).
 Venous side of the capillary:
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- Lower hydrostatic pressure (due to resistance) and higher capillary
osmotic pressure  Net filtration pressure moves fluid back toward the
capillary. (Figure 6.22 ).
 Interstitial fluid hydrostatic (IFHP) and osmotic pressures (IFOP) remain
identical.
 Fluid moves toward the tissues at the arteriole side and reenters the capillary
at the venous side.
 For every 1 liter of fluid entering the tissues, only 0.85 L reenter the
capillary. The remaining 0.15 L is reabsorbed as lymph by lymphatic
capillaries and eventually returned back to blood circulation
 Alterations in the forces affecting fluid movement across the capillary
membrane are responsible for edema.
Figure ( 6.22): Fluid exchange at the arterial and venous ends according to the
total pressure differences. (Marieb E.N.and Hoehn K.Anatomy and physiology. San
Francisco, Pearson Education Inc., 2011).
Clinical note: Edema is the result of increased permeability of the capillary walls
allowing the plasma proteins to move from capillaries into the interstitial fluid.
This causes an increase in the colloid osmotic pressure of the interstitial fluid
leading to a net increase in the amount of fluid moving from capillary into the
interstitial space.
148
Local control of blood flow by the tissue
 Blood flow through the tissue is proportional to the metabolic needs of the
tissue.
 Control of blood flow by metarterioles (no sphincters) and precapillary
sphincters(on the arteriole and beginning of capillaries) can be regulated
by vasodilators substances and lack of nutrients.
 Because of autoregulation which is the same mechanism to that of
vasomotion (periodic contraction and relaxation of the capillary sphincters
resulting in cyclic blood flow through the capillary.
Circulatory insufficiency or shock

 Shock is a state of inadequate tissue perfusion which often occurs in
hypotensive state.
 This inadequate tissue perfusion invokes compensatory responses from
sympathetic nervous system through diversely located barareceptors and
chemoreceptors.
 Signs and symptoms include cold and clammy skin, rapid and weak pulse,
confusion and reduced urinary output.
Types of shock
1- Circulatory shock
 The heart fails as a pump, it is unable to maintain a cardiac output
sufficient to meet the body’s metabolic demands in the presence of an
adequate intravascular volume.
 The most common cause is sever left ventricular dysfunction .Other
causes include valvular diseases.
2- Distributive shock
 Vasodilatation decreases the peripheral resistance thereby lowering
blood pressure to an inadequate level.
 There are several causes of the distributive shock :
- Neurogenic shock: sympathetic tone to the vasculature is removed
(severing the spinal cord in the cervical region).
- Septic shock: cytokines released in response to the toxins cause
vasodilatation.
- Anaphylactic shock: histamine and prostaglandins are released in
response to allergens cause vasodilatation and increased
permeability resulting in fluid loss into the interstitium.
3- Hypovolemic shock
 An effective circulatory volume due to not enough fluid within the
vascular compartment.
 It occurs mainly as a result of hemorrhage.
 It may occur in conditions such as dehydration.
149
References
2. Hall J.E. Pocket Companion to Guyton and Hall: Textbook of Medical Physiology.
11th ed. Philadelphia, Elsevier.2007.
3. http//:www.rci.rutgers.edu
4. http//:www.studyblue.com
9. Widmair E.P., Vander,s Human Physiology:The Mechanism of Body Function.11th
ed. New York, McGraw –Hill Companies.2011.
150
Chapter seven
Blood 7
Blood
Overview
 Blood is a type of connective tissue consisting of cells and cell fragments
surrounded by a liquid matrix.
 It is only the fluid tissue in the body.
 Blood performs many essential functions to life and uncontrolled loss of it
can result in death.
Functions of blood
 Transport function
- Transport of gases, nutrients and waste products.
- Transport of processed molecules (transport of the precursor to vitamin
D from skin to the liver, then to the kidney for processing into active
form.
- Transport of hormones and enzymes.
 Regulation of PH and osmosis.
 Maintenance of body temperature.
 Protection against foreign substances by the cells and chemical of the blood,
which make up important part of the immune system.
 Clot formation .Blood clotting protects against excessive blood loss when
blood vessels are damaged.
Blood components
1- Plasma
 Plasma is the fluid portion of the blood .It is a pale yellow fluid that contains
of about 91% water and 9% other substances (proteins, ions, organic and
inorganic molecules.)
 Normal plasma volume is 5% of the body weight.
 It is colloid liquid containing proteins :
- Albumin:
 It is about 58% of the plasma proteins .It maintains osmotic pressure
that pulls the water into the blood.
 It transports substances in the blood: thyroid hormones, and fatty
acids.
- Fibrinogen: It is about 40% of plasma proteins .It is responsible for the
formation of blood clots.
- Globulins
 It is about 38% of plasma proteins. They are divided into α, β and γ
globulins .They transport substances in the blood.
 Globulins provide protection against microorganisms, as part of
immunity.
151
 Serum: is the plasma without the clotting factors.
 All plasma proteins are produced by the liver or blood cells.
 Plasma volume remains relatively constant because water intake through the
gastrointestinal tract matches water loss through the kidney, lung and skin.
Clinical note: Hypoproteinemia: when the plasma proteins levels are low. Plasma
proteins decrease in prolonged starvation, malabsorption syndrome. They are also
low in liver diseases due to depression of hepatic proteins synthesis and low in
nephrosis due to losing of large amounts of albumin in the urine. Plasma protein
depletion causes a decrease in the plasma oncotic pressure and edema tends to
develop.
2- Formed elements
Red blood cells

Overview
 Red blood cells (RBCs) or erythrocytes constitute 95% of the formed
elements.
 Normal erythrocytes are biconcave discs with a diameter is 7.5micrometers
at the thickest point and 1 micrometers at the center. (Figure 7.1).
 They are flexible; their shape can change as the cells squeeze through the
capillaries due to the stretchability of their membrane.
 The average number of the erythrocytes is 5.2 millions/mm3 in man and
4.7millions/mm3 in woman.
 They have no nucleus and their life span is about 120 days.
Figure (7.1): Shape and dimension of red blood cell.(Seeley R.R., Stephens
T.D. and Tate P. Anatomy and Physiology .New York, McGraw –Hill
Companies, 2008).
152
Function of red blood cells
 The major function of red blood cells is to contain hemoglobin (Hb), which
carries the oxygen from the lungs to the tissues.
 The contain a large quantity of carbonic anhydrase :an enzyme that
catalyzes the reversible reaction between carbon dioxide (CO2)and water to
form H2CO3 .This to increase the efficiency of CO2 transport ,in form of
bicarbonate from the tissue to the lungs ,where it converted to CO2 and
expelled into the atmosphere.
[carbonic anhydrase]
CO2 + H2O H2CO3 H+ + HCO3-
 Hemoglobin in the red blood cells is an acid –base buffer, so the red blood
cells are responsible for the acid base buffering power of whole blood.
Formation of blood cells

Overview
 The process of blood cells production is called hematopoiesis.
 In the embryo and fetus, hematopoiesis occurs in tissues such as the yolk
sac, liver, thymus, spleen, lymph nodes and bone marrow.
 At birth, hematopoiesis is confined to red bone marrow with some
lymphoid tissues helping to produce lymphocytes.
 In young children, they are produced in the marrow of all bones.
 In adults, they are produced in the bone marrow of the ribs, sternum,
vertebrates, pelvis and proximal femur and hummers.
Stages of the hematopoiesis

 All the formed elements of blood cells are produced derived from a single
population of stem cells called hemocytoblasts in the red bone marrow.
 Hemopoitic stem cells are precursor cells capable of dividing to produce
daughter cells that can differentiate into various types of
cells:proerythroblast
 Proerythroblasts give rise to late erythroblasts, which lose their nuclei and
released to the blood as reticulocytes. Reticulocytes form red blood cells.
Formation of red blood cells is called erythropoisis.(Figure 7.2)
Figure( 7.2): Erythropoiesis.(Marieb E.N.and Hoehn K.Anatomy and physiology. San

Francisco, Pearson Education Inc., 2011).
153
 Myoblasts originated from hemopoietic stem cells form basophils,
eosinophils and neutophils.
 Lymphoblasts give rise to lymphocytes, monoblasts form the monocytes
and megakaryocytes form the platelets. (Figure 7.3).
 The development of cell lines is regulated by different growth factors.
Figure ( 7.3 ): Development of blood cells. (Marieb E.N.and Hoehn K.Anatomy and
physiology. San Francisco, Pearson Education Inc., 2011).
Regulation of red blood cells production

 Tissue oxygenation: The condition that causes the quantity of O2
transported to the tissues to decrease increases the rate of red blood cells
production. Many factors can decrease tissues oxygenation(figure7.4) :
- Anemia: extreme anemia induces the bone marrow to produce large
quantity of red blood cells.
- High altitude: at a high altitude the quantity of O2 in the air is greatly
decreased causing insufficient O2 transported to the tissues (hypoxia),
the red blood cells production is greatly increased.
154
Figure (7.4): Factors affecting on the tissue oxygenation and RBC formation.
Guyton A.C. and Hall J.E., Textbook of Medical Physiology. Philadelphia,
Saunders, 2015).
- Various diseases of circulation that cause decreased blood flow can also
increase the rate of red blood cells production e.g., prolonged heart
failure and lungs diseases ,because the cause tissue hypoxia .
 Erythropoietin : is a circulating hormone stimulates red blood cells

production in low oxygenation state .It is formed in the kidney in about
90% and the reminder in the liver .
 In the absence of erythropoietin, hypoxia has no effect on stimulation of
red blood cells production .But when erythropoietin is functional, hypoxia
causes a marked increase in erythropoietin production and then enhances red
blood cells production until the hypoxia is relieved.
 When both kidneys are destroyed by renal disease, the person becomes
invariably anemic because the normal erythropoietin formed in the liver is
sufficient to cause 1/3-1/2 of red blood cells formation needed by the body.
 An adequate amount of folic acid, vitamin B12 and iron are necessary for
normal red blood cells production.
Fate of red blood cells

 Red blood cells stay in the circulation for about 120 days .As their
components degenerate, the cells become less able to transport O2 and their
plasma membranes become more fragile and rupture as they squeeze
through a tight spot in the circulation and Hb is released.
 The released Hb is taken up by the macrophages which are located in the
spleen, liver, and other lymphatic tissues.
 Lysosomal enzymes of the macrophages digest the Hb to yield amino acids,
iron and bilirubin.
 Amino acids are reused in the production of other proteins, iron atoms are
carried by the blood to the bone marrow, while the non iron part of the heme
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group is converted to biliverdin and then to bilirubin, which is released to
plasma.
 Bilirubin binds to albumin and is transported to liver cells, which is
converted to conjugated bilirubin, the part of the bile (fluid secreted from
the liver into the small intestine).
Hemoglobin
 Hemoglobin (Hb) is the oxygen carrying pigment in the red blood cells.
 Hb consists of four polypeptides chains:2 α globin chains & 2 β globin
chains .Each polypeptide chain is bound to one heme .Each heme contains
one iron atom. (Figure 7.5).
 Iron atom is necessary for normal function of Hb; each O2 that is transported
is associated with an iron atom.
 Dietary iron is absorbed into the circulation from the upper part of the
intestinal tract. Stomach acids and vitamin C in the food increase
absorption of iron by converting ferric iron (Fe3+) to ferrous iron (Fe2+)
which is more absorbed.
 There are three kinds of Hb with different affinity for binding with O2 :
1- Embryonic Hb: is the first type of Hb provided during the
development.
2- Fetal Hb: This replaces the embryonic Hb at the third month of
development.
3- Adult Hb: At birth 60-90% of the Hb is adult Hb .At 2-4 years of age;
fetal Hb is less than 2% .At adulthood only trace of fetal Hb may be
found.
Figure ( 7.5 ): Hemoglobin structure. (Marieb E.N. Human Anatomy and

Physiology. San Francisco Benjamin Cummings; Addison Wesley Longman.2001)
Hemoglobin functions
 Transport O2: When Hb exposed to O2, one oxygen molecule associates
with each heme to form oxyhemoglobin. Hb containing no O2 is called
deoxyhemglobin .
 Transport CO2: Hb transport CO2 by attachement to amino groups of
globin molecule .This form of Hb is called carbaminohemoglobin.
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 Hb transports nitric oxide produced by the endothelial cells lining the blood
vessels.
Clinical note: Jaundice is a yellowish staining of the skin caused by a buildup of a bile
pigment in the circulation and intestinal space due to increased destruction of red
blood cells.
White blood cells

Overview
 White blood cells (WBCs) or leukocytes are about 4.000-11.000/mm3.
 They are complete cells contain nuclei and usual organelles.
 White blood cells protect the body against microorganisms and remove dead
cells and debris.
 White blood cells have some special characteristics :
- They are motile exhibiting (amoeboid movement)by forming
cytoplasmic projections.
- The leave the circulation and enter the tissues by slipping between the
cells of blood vessels wall. This process is called diapedesis .
- They attract to the foreign materials by chemotaxis ,at the site of
infection. They accumulate and engulf bacteria and dead cells
(phagocytosis), then die.
- Accumulation of dead WBCs, bacteria along with fluid and cells debris
is called pus.
 Leukocytosis: is when total WBCs count above 11.000cells/mm3 .This
indicates for bacterial or viral infection in the body.
 Leukopenia:is abnormal low WBCs count ,caused by drugs such as
corticoids and anticancer agents.
Clinical note: Leukemia is abnormal huge production of one or more of WBSc

types because of cancerous bone marrow .The new formed WBCs are immature
and lack their protective function and the patients become very susceptible to
infection. The excess production of WBCs in bone marrow interfere RBCs and
platelets formation resulting in anemia and bleeding.
White blood cells classification

 White blood cells are classified into two major groups (granulocytes and
agranulocytes) depending on the presence of visible granules in the
cytoplasm.(Figure7.6 ) .
i. Granulocytes
1- Neutrophils
- They comprise 60-70% of WBCs.
- They have small cytoplasmic granules that stain with both acidic and
basic dyes.
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- Their nuclei are multilobed (2-5lobes) so they are called
polymorphonuclear neutrophils (PMNs).
- PMNs have very strong phagocytic activity. They stay for10-12hours in
the circulation before leaving to the tissues to do their phagocytic
function, to engulf bacteria, fungi and antigen –antibodies complex
which are destroyed during the respiratory burst (a phase of elevated
O2 consumption that occurs in the neutrophils monocytes and
macrophages shortly after phagocytosing materials).
- They secret an enzyme called lysozyme which destroys certain bacteria.
2- Eosinophils
- Eosinophils comprise 2-4% of WBCs.
- They contain cytoplasmic granules that stain red with acidic stain
(eosin), with blue red nucleus that resembles an old fashioned
telephone.
- They have weak phagocytic activity .Their number increases during
parasitic infection.
- They are most common in tissues undergoing an allergic response and
their numbers are elevated in blood of people with allergies.
3- Basophils
- Basophils comprise 0.5-1% of WBCs.
- They contain large histamine containing granules that stain blue with
basic dyes .
- Their numbers increase in both allergic and inflammatory reactions.
- They release histamine that makes the blood vessels leaky and attract
other WBCs to the inflammatory sites.
ii. Agranulocytes
1- Lymphocytes
- Lymphocytes comprise 20-25% 0f WBCs.
- They are the smallest WBCs, have large dark purple nucleus that
occupies most of the cell volume. (Figure 7.7).
- Lymphocytes tend to take up residence in the lymphatic tissues where
the play an important role in the immune response.
2- Monocytes
- Monocytes comprise 3-8% of WBCs.
- They are the largest cells of the WBCs with kidney shape nucleus.
- They remain in the circulation for 3 days then leave the circulation and
become transported into macrophages and migrate through different
tissues.
- They have a capability to phagocytize large quantities of bacteria,
viruses, necrotic tissues or other foreign particles.
- An increase in the number of monocytes is associated with chronic
infection.
158
Figure (7.7): Different types of leukocytes. (Marieb E.N .Essential of Human Anatomy and
Physiology . San Francisco, Pearson Education,Inc.,2012).
Platelets
 Platelets or thrombocytes are fragments of bizarre multinucleated cells
called megakaryocytes, produced in bone marrow.
 The normal platelets count is about 300.000cells/mm3.
 Life expectancy of platelets is 5-9days.
 Platelets play an important role in controlling blood loss by:
- Forming platelets plugs to seal holes in small blood vessels.
- They promote the formation of clots to seal off larger wounds in the
vessels.
Hemostasis
 A number of events occur to prevent excessive blood loss when a blood
vessel is damaged.
 There are three major events that cause the hemostasis :
1- Vascular spasm
- Immediate and temporary vasoconstriction of a damaged vessel,
decreasing blood loss (Figure 7.8 ). Vasoconstriction causes the vessel
to go into spasm. This is result from the following:
1. Nerve reflexes
2. Local myogenic spasm
3. Releasing of serotonin by anchored platelets.
Figure (7.8 ):Vascular spasm. Figure (7.9): Platelets plug formation.

(Marieb E.N .Essential of Human Anatomy and Physiology . San Francisco, Pearson
159
2- Platelets plug formation
- A platelet plug is an accumulation of platelets forming a mass that
can seal up small breaks in blood vessel.(Figure 7.9 ).
- An injury to the lining vessels exposes collagen fibers causing
platelets to adhere to the damaged site forming a small mass (a
platelets plug).
- Mechanism of platelets plug formation :
 When platelets come in contact with damaged vascular surface
such as collagen fibers in the vascular wall or damaged
endothelial cells, they change their characteristics; begin to
swell forming numerous pseudopodes, their contractile proteins
contract causing the release of granules that contain multiple
active factors. They become sticky and stick to collagen fibers.
 They secret ADP and their enzymes form thromboxane A2 into
the blood acting on additional platelets and causing them to
adhere to the original present platelets.
3- Coagulation
- Coagulation or blood clotting results in formation of clot which is a
network of threadlike protein fibers called fibrin that traps blood
cells and fluid. .(Figure 7.10 ).
- A blood clot formation depends on number of proteins called
coagulation factors in the plasma which normally found in an
inactive state but after injury these they are activated to produce a
clot.
- Activation of clotting factors is a complex process involving many
chemical reactions some of which require calcium ion,
phospholipids and clotting factor V.
Figure (7.10): Coagulation. (Marieb E.N .Essential of Human

Anatomy and Physiology. San Francisco, Pearson Education, Inc.,
2012).
- Blood clots within 3-6minutes and the mechanism of clotting takes

place in three steps:
1. A complex cascade of chemical reactions occur in blood involving
more than dozen coagulation factors leading to form prothrombin
activator.
2. Conversion of prothrimbin to thrombin by the act of prothrombin
activator.
160
3. Conversion of soluble fibrinogen into insoluble fibrin by the action
of thrombin.
 The first stage of coagulation occurs through extrinsic or
intrinsic pathway (figure 7.11) to produce factor X.
 The extrinsic pathway begins with the release of thromboplastin
from the damaged tissues.
 The intrinsic pathway begins with the activation of factor XII.
 Prothrombin activator is formed at the end of this stage.
 Prothrombin activator goes through the second stage to activate
formation of thrombinIIa, which stimulates formation of fibrin
at the end of third stage. (Figure 7.12).
Figure (7.11): A sequence of chemical reactions of clot formation through the

extrinsic and intrinsic pathway.( Marieb E.N. and Hoehn K. Human Anatomy and
Physiology . San Francisco, Pearson Education Inc., 2010).
- Calcium ions are required for promotion of all the blood clotting
(except the first two), therefore in the absence of calcium ions blood
clotting does not occur.
- Many of factors involved in clot formation require vitamin K for their
production .About half comes from the diet and half comes from
bacteria within large intestine.
161
Figure (7.12): Stage2, 3 of the coagulation.( Marieb E.N. and Hoehn K. Human
Anatomy and Physiology . San Francisco, Pearson Education Inc., 2010).
Disorders of hemostasis
1- Unwanted clot
 Unwanted clot sometimes formed in intact blood vessels (in the legs).
 A clot that develops and persists in an unbroken blood vessel is called
thrombus. If the thrombus is large enough it may prevent the blood from
flowing to the ells beyond the blockage.
 If a thrombus breaks away from the vessel wall and float freely in the blood
it becomes embolus, which causes problem when it lodge in a too narrow
vessels to pass through, e.g., cerebral embolus which may cause a stroke.
 Unwanted clot may be caused by anything that roughens the endothelium of
blood vessels e.g., severe burns, accumulation of fatty materials).
 A number of anticoagulants e.g., aspirin, heparin and dicumarol are used
for thrombus –prone patients.
2- Thrombocytopenia
 Thrombocytopenia is a condition in which the number of platelets is greatly
reduced resulting in chronic bleeding through small vessels and capillaries.
 It has several causes including: increased platelets destruction, infection,
and decrease in production caused by pernicious anemia, drugs therapy,
radiation therapy or leukemia.
3- Hemophilia
 Hemophilia is a term applied to several different hereditary bleeding
disorders that result from a lack of any of the factors needed for clotting.
Even minor tissue trauma may result in prolonged bleeding and can be life
threatening.
Blood grouping
 Blood groups are classified on the basis of presence a protein on the surface
of RBCs (antigen) called agglutinogens the, best known of these are A and
B.
 There are four major blood types on the basis of agglutinogens present in
their red cells .These are A,B,AB and O.
162
 Antibodies are recognizers present in the plasma that attach to RBCs bearing
agglutinogens differ from those on the patients (blood recipients) .Those
antibodies called agglutinins.
 Antibodies can bind to RBCs antigens resulting in agglutination or
hemolysis.
Transfusion
 Transfusion is transfer of blood or blood components from one individual to
another.
 The interaction between the agglutinogens and agglutinins cause a
transfusion reaction, which include clotting in blood vessels, kidney
damage and death.
 An infusion: is the introduction of a fluid other than blood such as saline or
glucose solution into the blood.
1- ABO Blood groups

1- Individual with type A blood: have aggulinogen A on their red cells and
antibodies against aggulinogens B called anti-B-agglutinin. [If their plasma
is mixed with type B cells ,the agglutinins and B-cell agglutinogens react
causing type B cells to be clumped (agglutinated ) and hemolyzed].
2- Individual with type B blood have anti -A agglutinins. (Figure 7.13).
3- Individual with type O –blood have both anti -A and anti -B agglutinins.
This is an universal donor because there are no regular anti-O agglutinins
so this type can be given to anyone of the other type ,but this does not mean
that the blood should ever be transfused without being cross matched except
in the extreme emergencies.
4- Individual with type -AB blood.This is un universal recipient because
there are no circulating agglutinins and can be given blood from any type
without developing transfusion.
2- Rh group
 The Rh group is so named because it was first studied in the rhesus
monkeys.
 Rh-positive (Rh+): blood individual has certain Rh-antigens (D-antigens),
whereas Rh –negative: blood has no D antigen.
 If an Rh- person receives mismatched blood (Rh+) after transfusion the
immune system becomes sensitized and produces anti-Rh+ antibodies
against foreign blood type .Hemolysis does not occur with the first
transfusion because it takes time for the body to react and make antibodies
But ,the second time of transfusion ,a typical transfusion occurs.
 Hemolytic disease of the newborn (erythroblastosis fatalis) occurs when
Rh- mother carries a Rh+ fetus .A first pregnancy ,the baby is healthy .But
the mother will form anti-Rh+ antibodies ,the mother’s antibodies will pass
cross the placenta and destroy the baby’s RBCs.
163
 It has been possible to prevent hemolytic disease of the newborn by
administering a therapeutic injection of Rh antibodies into the Rh- maternal
circulation within 72 hours after delivery of an Rh+ infant.
Figure (7.13): ABO Blood groups.(Randall D. ,Burggren W. and French K. Eckert Animal
Physiology . New York, W.H. Freeman and Company, 2002).
Disorders of the blood

Anemia
 Anemia means deficient of hemoglobin in blood, which can be caused by
either too few blood cells, or too little hemoglobin in the cells.
 Types of anemia :
1- Blood loss anemia. After rapid hemorrhag the RBCs concentration can
return to normal level within 3 – 6weeks.
2- Iron deficient anemia: In chronic blood loss, a person cannot absorb
enough Fe from intestine to form hemoglobin as rapidly as it is loss. The
RBCs are then produced are much smaller than normal in sizes and have too
little hemoglobin inside, this giving rise to microcytic hypochromic
anemia.
3- Aplastic anemia: Bone marrow aplasia means lack of functioning bone
marrow.This occurs when person exposed to gamma radiation from
explosion of atomic bomb, that can sustain complete destruction of bone
marrow followed in few weeks by lethal anemia. Also excessive X-rays
treatment a certain industrial chemical and even drugs can cause some effect
( benzene, and arsenic compound).
4- Megaloblastic anemia: It is slow production of erythroblast in the bone
marrow, due to lack of vitamin B12, folic acid and intrinsic factor from
stomach mucosa. As result red cells grow to large in size with odd shape
(peculiar shape) called megaloblast, also resulted if patient have intestinal
164
sprue, in which folic acid and B12 and other vitamins B compounds are
poorly absorbed, often developed Megaloblastic anemia (pernicious
anemia). In these cases erythroblast cannot proliferated rapidly enough to
form normal number of RBCs. These cells have fragile membrane and are
easily ruptured, leaving person in dire need of an adequate number of cells.
5- Hemolytic anemia: different abnormalities of RBCs, many of which are

hereditary acquired, make cells more fragile, so that they are ruptured easily
as they pass through capillaries especially in spleen. The number of red cells
is normal and some time is greater than normal produced in some hemolytic
disease. The life span is shorter, that the cells destroyed faster than they
produced leading to serious anemia , some of these are:
 Sickle cell anemia: is present in western Africa and American black.

The cells have abnormal type of Hb (Hbs), containing faulty β-chain in
Hb molecule, that, glutamic at the position 6 in beta chain is substituted
by valine amino acid. When this Hb is exposed to low concentration of
oxygen, it precipitates into long crystals inside RBCs. These crystals
elongate the cell, so that the cells appear in sickle shape, rather than
biconcave disc(figure7.14) . The crystals damage the cell membrane, so
that the cells become highly fragile causing to serous anemia. If person
who has sickle disease and exposed to low oxygen tension for long time
may lead to death, because of hemolysis of RBCs.
Figure ( 7.14): Sickle cell anemia. ( Marieb E.N. and Hoehn K. Human Anatomy and
 Erythroblastosis fetalis :( See hemolytic diseases of newborn).

 Thalassemia: in which both of alpha and beta chain of Hb are
changed. The red cells become more fragile, it is either beta
thalassemia or alpha thalassemia.
 Spherocytic anemia: the red cells are spherical in shape rather than
biconcave disc; and hemolyzed more rapidly than the normal cells in
hypotonic sodium chloride solution, leading to a reduction in the
number of RBCs. This disease is congenital hemolytic. The spherocyte
165
cells also removed by spleen. The reason for spherocytosis is due
abnormalities of protein network that maintain the shape and
flexibility of red cell membrane.
 Enzyme glucose 6-phosphate dehydrogenase deficiency. This enzyme
catalyzes the initial step in oxidation of glucose via the hexose
phosphate pathway. In this pathway generates ADPH, which needed
in some way for the maintenance of red cell fragility.
Effect of anemia on function of circulatory system

 The viscosity of blood mostly depended on blood concentration of RBCs.
 In anemia the viscosity may decrease to less than 1.5 normal value. This
decreases the resistance, leading to greater blood flow to the tissues and
return to the heart.
 Increased cardiac output and pumping workload on the heart.
Polycythemia
 It means an increase in the number of the RBCs, there are 2 types of
polycythemia:
1- Secondary polycythemia: In case of tissues hypoxia, when O2 level
decreases in the air, such as high altitude, or failure of oxygen delivery to
the tissues such in cardiac failure; the blood forming organ automatically
produced large amount of blood cells. Red cells count increases up the 7
million/ mm3.
2- Primary polycythemia (polycythemia vera or Erythremia).This is a
pathological condition in which red cells account increases to 7.000.000 –
8.000.000 Cells / mm3and hematocrit may be 60-70%.
 Polycythemia Vera is caused by a genetic aberration in hemocytoblast
cells that produced the blood cells. The blast cells no longer stop
producing red cells in addition to increase of white blood cells and
platelets.
Effect of polycythemia on circulatory system.

 Increased viscosity leading to sluggish blood flow through the peripheral
blood vessels.
 Increased blood viscosity causes a decrease in venous blood return to the
heart.
 Blood volume is greatly increased in polycythemia.
 The arterial pressure mostly normal in most people with polycythemia, but
1/3 of them arterial pressure is elevated.
 Persons with polycythemia, their skin has ruddy complexion with a bluish
tint, because of hypoxic occurs in blood capillaries of skin at venous plexus,
which might be related to sluggish movement.
166
References
Saunders, 2015.
4. Marieb E.N. Human anatomy and physiology.5th.ed. San Francisco Benjamin
Cummings;Addison Wesley Longman.2001.
6. Randall D., Burggren W. and French K. Eckert Animal Physiology .5th ed. New York,
167
Chapter eight
Lymphatic system and Immunity 8
I. Lymphatic system
Overview
 Lymphatic system consists of lymph, lymphatic vessels, lymphatic tissues,
lymphatic nodes and nodules and lymphatic organs.
 Functions:
1- It maintains fluid balance in tissues.
2- It absorbs fats from the small intestine
3- Defense functions.
 The innate defenses hinder pathogen entry, prevent the spread of
diseases causing microorganisms, and strengthen the immune
response.
 The adaptive defenses protect against disease by destroying foreign
cells and inactivating toxins with antibodies.
Lymphatic vessels
 Lymphatic capillaries carry lymph away from tissues.
 Lymphatic capillaries join to form lymphatic vessels.
- Lymphatic vessels have valves to control one way flow of lymph.
- Contraction of lymphatic vessels smooth muscle, skeletal muscle action
and thoracic pressure changes move the lymph.
 Lymphatic nodes are along the lymphatic vessels. After passing through
lymphatic nodes ,lymphatic vessels form lymphatic trunks and lymphatic
ducts.
 Lymphatic trunks and ducts empty into the blood at thoracic veins (junctions
of the internal jugular and subclavian veins).
 Thoracic duct is the largest lymphatic vessel.
 The jugular, subcalavian and bronchomediastinal trunks may unite to form
the right lymphatic duct.
Lymphatic tissues and organs

 Lymphatic tissues are reticular connective tissue that contains lymphocytes
and other cells.
 Lymphatic tissues can be surrounded by capsule (e.g., lymph nodes,
spleen) or they are non capsulated (e.g., lymphatic nodules, tonsil).
 Although all lymphoid organs have roles in protecting the body, only lymph
nodes filter lymph.
 Lymphatic nodules are small aggregates of lymphatic tissues (e.g., Peyer‟s
patches in the small intestine)
168
 Tonsils: are large groups of lymphatic nodules in the oral cavity and
nasopharynx. Their job is to trap and remove any bacteria and foreign
pathogens entering the throat. They are three groups:
1. Palatine tonsils are on the each sides of the junction between the oral
cavity and the pharynx.
2. Pharyngeal tonsils are near the junction between the nasal cavity and
pharynx.
3. Lingual tonsils are on the posterior surface of the tongue.
 Sometimes the palatine or pharyngeal tonsils become chronically infected
and must be removed, while lingual becomes infected less often than the
others and is difficult to remove.
 Lymphatic nodes: lymphatic tissues in the nodes are organized into cortex
and medulla. Sinuses extend through the lymphatic tissue. (Figure 8.1).
- They protect the body by removing bacteria and other a foreign
materials from lymphatic stream and by producing lymphocytes, that
function in the immune response.
- They filter the lymph which is transported toward the heart through
thousands of nodes that cluster along the lymphatic vessels.
- Macrophages are present within the lymph nodes ,which engulf and
destroy bacteria ,virus and foreign substances in the lymph .
 The spleen: is soft blood rich organ that filters the blood.
- It is located in the left side of the abdominal cavity beneath the
diaphragm.
- It filters and cleanses the blood of bacteria, virus and other debris.
- It destroys worn out RBSc and returns some of their broke down
products to the liver.
- It stores of platelets and acts as reservoir.
 Thymus:
- Lymphoid mass found in the throat overlying the heart.
- It produces hormone (thymosin) which function in programming of
certain lymphocytes, so they can carry out their protective functions.
Figure ( 8.1 ): Structure of a lymph node. (Seeley R.R., Stephens T.D. and Tate P.
169
Lymphatic circulation
Overview
 Normally fluid efflux exceeds influx across the capillary walls, but the extra
fluid enters the lymphatic channels and drain through them back to the
blood. This prevents the interstitial fluid from rising.
 The normal 24hours lymph flow is 2-4L.
 Lymphatic vessels can be divided into two types :
1. Initial lymphatic vessels
- They lack valves and have no smooth muscles in their walls.
- They are found in organ like intestine, skeletal muscles.
- Lymph (tissue fluid) enters the initial lymphatic vessels through a loose
junction between the endothelial cells in their walls.
- The lymph in these channels moves by muscles contraction of the organs
and by contraction s of the arterioles and venules which is often associated
with them.
2. The collecting lymphatic vessels
- The initial lymphatic vessels drain into collection lymphatic vessels which
have valves, smooth muscles in their walls and peristaltic, propelling the
lymph along these channels.(Figure 8.2).
- The flow of lymph in the collecting vessels is further added by skeletal
muscles contraction, the negative intrathoracic pressure during inspiration
and the suction effect of blood flow of the veins in which the lymphatic
terminate.
Figure ( 8.2): Lymphatic vessels. (Marieb E.N .Essential of

Human Anatomy and Physiology. San Francisco, Pearson
170
II.Body defense and immune mechanism
 Immunity is the ability of the body to resist almost all types of organisms
and toxin that tend to damage the tissues and organs.
 Immunity may be: Innate immunity or acquired (adaptive) immunity.
1- Innate immunity
Overview
 Innate immunity is nonspecific defense .It responds immediately to
protect the body from all foreign substances.
 The first line of defense against the diseases- causing microorganisms is the
skin and mucus membrane lining the digestive, respiratory, urinary and
reproductive tracts.
 The acidity of the stomach secretion, urine and female reproductive canal
have a protective effect by inhibiting bacterial growth.
 Phagocytosis process: the cellular ingestion of the offending agents.
 Presence of certain chemical compounds in the blood that destroy the
foreign microorganisms and toxins ,these are:
1- Lysozyme
2- Complement complex
3- Natural killer lymphocytes for infected cells, tumor cells and foreign
cells.
Internal defenses: cells and chemicals

 It is a second line of defense, includes natural killer cells, phagocytes,
inflammatory response and a variety of chemical substances that kill
pathogens and help repair.
1- Natural killer cells

 A unique group of lymphocytes that can lyse and kill cancer cells, viruses
infected body cells.
 Natural killer cells (NK) are not phagocytic but they attack the target cells
and release lytic chemicals.
 Natural killer cells release powerful inflammatory chemicals.
2- Inflammatory response
 Inflammatory response is non -specific response that is triggered wherever
body tissues are injured by: physical trauma, heat, infection by bacteria and
viruses.
 The most common indicators of acute inflammation are pain, redness, heat
and swelling.
The events of the inflammatory process

 The injured cells release inflammatory chemicals (histamine and kinins )that
cause :
1- Dilatation of blood vessels in the inflamed area and become more leaky
171
- Dilatation of the blood vessels increases blood flow to the area
accounting for the redness and heat. Increased permeability of
the capillaries allows plasma to leak from the blood into the
tissues space causing the swelling.
2- They activate pain receptors.
3- They attract phagocytes and WBCs to the area.
 Migration of large number of granulocytes into the tissue

 Monocytes follow the neutrophils into the inflamed area, which become
macrophages and exhibit great capability to ingest bacteria.
 Clotting proteins leaked from the blood into the inflamed area are activated
and begin to wall off the damaged area within fibrin to prevent spread of
pathogens to the neighboring tissues.
 The adaptive response mediated by lymphocytes (the third line of defense)
is activated when the damaged area contains the invading pathogens.
Pathological note: In sever infected area creamy yellow pus may form in the
wound .Pus is a mixture of dead neutrophils, breakdown cells and living and dead
pathogens. If the inflammatory mechanism fails to clear the infected area, a sac of
pus may become walled off forming an abscess.
3- Phagocytes
 Phagocytes (macrophages, neutrophils) engulf foreign particles by process
called phagocytosis.
 Phagocytosis is a selective process by which the phagocytes ingest only the
foreign particles by forming a cytoplasmic extension around these particles,
forming a phagocytic vesicle or phagosome inside the cytoplasm.
 The vesicle is then fuses with the proteolytic enzymes of the lysosome,
which digest the contents of the vesicle.
 Monocytes turn to macrophages when entering the tissues .They become
activated and much more powerful than neutrophils .These macrophages can
engulf 100 bacteria and also have the ability to engulf malaria parasite,
even whole blood cell, while the neutrophils phagocytize 5-10 bacteria
before they die.
 Neutrophils and macrophages have oxidizing agents which are powerful
bactericidal agents include: superoxide (O2-), hydrogen peroxide (H2O2) and
hydroxyl ion (OH).
Life span of the phagocytes

 The life span of the neutrophils is 4-8 hours in the blood and 3-5days in the
tissue. The life span may shorten to few hours in serious infection.
 Monocytes have transit time 12 hours in the blood .they are transformed into
macrophages in the tissue, and stay there for months or even years unless
they are destroyed by phagocytic action.
172
4- Basophils, Mast cells and Eosinophils
 Basophils are motile white blood cells derived from red bone marrow .They
can leave the blood and enter infected tissues.
 Mast cells are non-motile cells in connective tissues .They located in the
skin, lung, gastrointestinal tract and urogenital tract.
 Basophil and mast cells can be activated through innate immunity (e.g.,
complement) or through adaptive immunity.
 They release chemicals e.g., histamine and leukotrienes which produce an
inflammatory response and activate other mechanisms such as smooth
muscle contraction in the lungs.
 Eosiophils are produced in bone marrow, enter the blood and leave to the
tissues within few minutes. They release enzymes which break down the
chemicals produced by basophils and mast cells. They secrete effective
enzymes to kill some parasites. Their number greatly increases in parasitic
infection and allergic reactions.
5- Antimicrobial proteins
 Antimicrobial proteins enhance the innate defense either by attacking
microorganisms directly or by hindering to produce.
 The most important of these are :the complement system and interferon
1- Complement system
 Complement system is a group of at least 20 plasma proteins that circulate
in the blood in an inactive state. These proteins are named C1-C9 and
factors B, D and P (properdin).
 It is nonspecific defense mechanism enhance the effectiveness of both
innate and adaptive defense.
 When complement becomes attached to foreign cells such as bacteria, fungi,
it is activated and becomes the major factor in the fight against the foreign
cells. This is the complement fixation.
 Complement fixation leads to form membrane attack complex (MAC) that
causes lesions in the foreign cell’s surface.
 The lesions make the water to move inside the cell causing it to burst.
 Activated complement amplifies the inflammatory response by :
1. Releasing of vasodilators and chemotaxis chemicals which attract
neutrophils and macrophages into the region.
2. Opsonization : the complement causes the cell membrane of the
foreign cells to become sticky so they are easy to phagocytize.
 Complement can be activated by either the alternative or classical
pathway.
173
Antigen-antibody complex
Opsonization of bacteria
C1 C1
Activate of mast cells &basophiles
C4+C2 C42+C4a
C3 C3b+C3a
C5 C5b+C5a Chemotaxis of WBCs
C6+C7 C5b67
Microorganism+
C8+C9 C5b6789
B and D
Lysis of cells
Figure (8.3): Cascade of reactions during activation of the classic pathway of complement.
(Guyton A.C. and Hall J.E., Textbook of Medical Physiology . Philadelphia, Saunders, 2015).
1- Alternative pathway: is part of innate immunity initiated when

complement proteins C3 becomes activate. Activated C3 can combine
with some foreign substances and activate the complement cascade.
2- Classical pathway: is part of the adaptive immunity, (figure 8.3).
2- Interferon
 Interferon is a small protein that protects the body against viral infection
and some forms of cancer.
 Interferon molecules diffuse to nearby cells to bind to their membrane
receptors. This binding stimulates the synthesis of protein that interferes
with the ability of the viruses to multiply within these still healthy cells.
Pharmacology note: Interferon may play a role in controlling some cancers that
are induced by viruses. Interferons activate macrophages and natural killer cells
which attack tumor cells. Interferons are produced through genetic engineering
in sufficient quantities for clinical uses .They are effective in treating certain viral
infections and cancers e.g., hepatitis c ,viral disorder that can cause cirrhosis and
liver cancer and treat of genital warts caused by herpes virus.
Fever
 Fever or high body temperature is a systemic response to invading
microorganism.
 Body temperature is regulated by a part of hypothalamus.
 Temperature is set at 37C◦ (98.6 F◦) but it can be reset upward in response to
pyrogens (a chemical secreted by WBCs and macrophages when exposed to
foreign cells or substances).
 High fever is dangerous because an excess heat scrambles enzymes and
other body proteins.
174
 Mild and moderate temperature fever seems to benefit the body by
increasing the metabolic rate of the tissue cells, specially speeding up repair
process.
2- Adaptive immunity
Overview
 Adaptive immunity is a specific defense system and functional system that
recognizes foreign substances (antigen) and acts to destroy.
 It protects the body from a wide variety of pathogens and abnormal body
cells.
 When it fails, some of devastating diseases such as cancer, rheumatoid
arthritis, and AID may result.
 There are three important aspects of the adaptive immunity :
1- It is antigen specific: It recognizes and acts against particular pathogens
or foreign substances.
2- It is a systemic: the immunity is not restricted to initial infection site.
3- It has memory: It recognizes even stronger attacks on previously
encountered pathogens.
 Adaptive immunity may be :
1- Humerol immunity:
- It is due to circulating antibodies (Ab) in the body’s fluid.
- It is major defense against bacterial infections.
2- Cellular immunity:
- This is mediated by lymphocytes products of high molecular weight
called: Lymphokins
- It is responsible for delayed allergic reaction and rejection of
transplants of foreign tissues.
- It constitutes a major defense against infections by viruses, fungi and
few bacteria like: tubercle bacilli.
Antigens
 Antigens (Ag) are large complex molecules recognized by the body as a
foreign.
 Variety of substances can act as antigens including: all foreign proteins,
nucleic acids, many large carbohydrates and some lipids. Proteins are the
strongest antigens.
 Pollen grains, bacteria, fungi and viruses particles are antigenic because
their surfaces bear such foreign molecules.
 Complete antigens provoke an immune response and bind with the
products of that response (antibodies and sensitized lymphocytes).
 Incomplete antigens or hatpins are small molecules that are unable to
cause immune response by themselves, but do when they bind to body
proteins forming complexes which are recognized as a foreign.
175
Cells of adaptive immune system
1- Lymphocytes
 Lymphocytes arise from hematoblast of red bone marrow.
 They exist in two major types :
1. T-cells arise from lymphocytes that migrate to the thymus, where they
undergo a maturation process of 2-3 days. They are responsible for
cellular immunity.
2. B-cells develop immune-competence in bone marrow and provide
humeral immunity.
 T-cells and B-cells migrate to the lymph nodes, spleen and loose connective
tissues, where their encounter with antigens.
 T-cells and B-cells are morphologically indistinguishable and can be
identified with special technique.
2- Antigen presenting cells

 Antigens presenting cells (APCs) present the antigens to the cells that will
deal with these antigens.
 The major types of cells acting as APC are: dendritic cells in connective
tissues and epidermis, macrophages and B-lymphocytes.
Macrophages
 Macrophages arise from the monocytes produced in the bone marrow.
 They are widely distributed throughout the lymphoid organs and connective
tissues, where they act as phagocytic in the innate defense system.
 Macrophages and other APCs phagocytize pathogens and present part of the
antigens on their surface for recognition by T-cells.
Humeral (antibody-mediated) immune response

 Clonal selection of B-cells occurs when antigens bind to their receptors
causing them to proliferate.
 The resulting family of identical cells descended from the same ancestor cell
is called a clone.
 The clone formation is the primary humeral response to antigen.
 Most clone members become plasma cells, which secrete antibodies.
 Other clone members that do not become plasma cells; become memory
cells, which are capable of responding to the same antigens at later meeting
with them. They are responsible for the immunological memory.
 This later immune response is the secondary humeral response.
 B-cells proliferation is clarified in details in figure (8.4).
176
Figure (8.4): Proliferation of B-cells. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and
Active and passive humeral immunity

 Active humeral immunity is when B cells encounter antigens and produce
antibodies against them.
- Naturally acquired: during bacterial and viral infection the person may
develop the signs and symptoms of the disease.
- Artificially acquired: by receiving vaccines which contain dead or
attenuated pathogens .The vaccine provides immunological memory.
 Passive immunity: It is when the person receives antibodies from an

outside source without having manufactured them. Some examples are:
- The fetus receives antibodies from the mother, because it does not
have a working immune system. Antibodies (being small proteins) can
cross in to the fetus.
- After birth, while the baby’s immune system is continuing to be set up,
the baby continues to receive the mother’s antibodies in her milk.
177
Antibodies
 Antibodies are gamma globulins (immunoglobulin (Ig). They are made up
of 4 polypeptides (2 long “heavy” chains and 2 short “light” chains)
arranged in a “Y‟ shape. (Figure 8.5.a).
 The two arms have “variable regions”, because there are the 2 receptors
into which a correctly shaped antigen can fit. The rest are “constant
regions” which have binding sites for the receptors that activate
complement proteins and leucocytes, such as phagocytes and basophiles.
(a) (b)
Figure (8.5): a: Structure of an antibody, b: Structure of IgM.( Seeley R.R., Stephens T.D.
 There are 5 types of antibodies:

1- IgM is the first antibody in the blood produced to fight an infection. Unlike
others, it has a star shape from 5 “Y” molecules joined together, giving 10
receptors (figure 8.5.b).Thus it can attack many parasites simultaneously -
useful when there is a high pathogen concentration. It does not directly kill
pathogens, but:
- It activates complement proteins e.g. perforin to kill bacteria.
- It attracts phagocytes and stimulates them to attack the pathogen.
- It clumps (joins) together many pathogens, so they are unable to attack
the cells.
- It blocks the pathogen receptors that it uses to enter the cells.
2- IgG replaces IgM during the latter part of an infection (when the
concentration of parasites is reduced), because it has a more stable long-
lasting molecule. It acts in the same way as IgM.
3- IgA is found in tears and saliva. It prevents parasites from attaching to and
entering mucous membranes.
4- IgE stimulates mast cells and basophiles to secrete histamine, starting
inflammation.
5- IgD is involved in activating B-lymphocytes.
178
Primary and secondary responses
1-Primary response
 Primary response is a slow response of the body immunity to a particular
pathogen at the first time exposure to this pathogen.
 The immune system is unprepared and activation of B-lymphocytes takes
time and clonal selection takes even longer. The pathogen thus has up to 2
weeks, in which to multiply and during this period, the body will be ill or
even die. Once antibody production starts up by plasma cells, there will be
such a large population of pathogens that they will be very difficult to
control.
2-Secondary response
 Secondary response is when the body is next infected by the pathogen
(maybe years later), the immune system is prepared.
 The memory cells detecting the pathogen arrival will rapidly divide to form
normal plasma cells and start antibody production within a few hours.
 The pathogen is thus eliminated before it has time to establish itself and
before the body shows any symptoms of the disease.
 Many diseases, e.g. yellow fever, measles and polio, the person can only
get once in the life, because he will have immunity against future infection.
Cellular (cell mediated) immune response

 Immunocompetent T cells are activated to form a clone by binding with a
recognized antigen.
 T cells are not able to bind with free antigen, but the antigen must be
presented by macrophages and APCs.
 Clonal selection occurs and clone members differentiate into effector T
cells or memory cells.
 There are several different classes of T-cells:
1- Cytotoxic(killer)Tcells are specialized in killing virus infected cell, cancer
cell or foreign graft cells .They do their function by binding tightly to the
foreign cells and release toxic chemicals called perforins which kill the
cells.
2- Helper T cells interact with the B cells bound to the antigens. They
liberate chemicals (cytokines) that enhance the killing activity of the
macrophages.
3- Regulatory (suppressor) Tcells release chemicals that suppress the
activity of both T and B cells to terminate the immune response after
an antigen has been destroyed in order to control immune system
activity.
179
Disorders of immunity
 The most important disorders of the immune system are:
1-Autoimmune diseases
2-Allergies
3-Immunodefeciencies
1- Autoimmune diseases
 Autoimmune diseases occur when the body’s self tolerance breaks down
and antibodies or T cells attacks the body’s own tissues.
 Most forms of autoimmune diseases result from the appearance of hidden
self antigens or changes in structure of self antigens and antibodies formed
against foreign antigens that resemble self antigens.
 The most autoimmune diseases include:
1- Rheumatoid arthritis which is chronic inflammatory disorder and
systematically destroy the joints.
2- Multiple sclerosis (MS) which destroy the white matter (myeline
sheaths of the brain and spinal cord).
3- Myasthenia gravis which impairs communications between nerves and
skeletal muscles.
4- Graves, disease in which the thyroid gland produces excessive amount
of thyroxin.
5- Type I diabetes mellitus which destroys pancreatic beta cells resulting
in deficient production of insulin.
6- Systemic lupus erythematosus (SLE) a systemic disease that occurs
mainly in young women affect kidneys, heart, lungs and skin.
7- Glomerulonephritis: is a sever impairment of the kidney function.
2- Allergy or hypersensitivity
 The immune system overreacts to even harmless antigens causing tissues
destruction.
 In hyperreactivity reactions, the antigen is called allergen. The process that
eliminates the allergen also produce undesirable side effect such as very
strong inflammatory reaction.
 Hypersensitivity reactions are categorized as :
1- Immediate reaction such as hay fever and anaphylaxis due to IgE. The
symptoms occur within few minutes of exposure to the allergens.
2- Delayed reaction is mediated by T cells .The symptoms take several
hours and days to develop such as contact dermatitis, poison ivy
cosmetics and drugs. This type reflects the activity of T cells,
macrophages and cytokines.
Pharmacology note: Penicillin is a hapten of a clinical importance. It does not

evoke the immune system response. It can breakdown and bind to serum proteins
to form a combined molecule that can produce an allergic reaction which
commonly produces a rash and fever.
180
3-Immunodeficiency
 Immunodeficiency is a failure of part of the immune system to function
properly.
 Immunodeficiency disorders include many diseases.
 It may be acquired due to inadequate proteins in the diets which inhibit
proteins synthesis thereby decreasing antibodies. Stress may also depress
immune system.
- AID is acquired immunodeficiency disease by viruses that attack and
destroy the T-helper cells.
 Congenital immunodeficiency can involve inadequate B cells formation,
inadequate T cells or both as in severe combined immunodeficiency disease
(SCID).
Transplantation
 Genes that code for the production of MHC molecules are called major
histocompatibility complex genes.
 Histocompatibility is the tissues’ ability to get along when tissues are
transplanted from one individual to another.
 There are four types of grafts:
1. Autografts are tissue grafts transplanted from one site to another in the
same person.
2. Isografts are tissue grafts donated by genetically identical persons
(identical twin).
3. Allografts are tissue grafts taken from a person other than an identical
twin.
4. Xenografts are tissue grafts harvested from a different animal species.
 Tissue matching tests are done to ensure the best match possible.
 Organ transplantation is followed by immunosuppressive therapy.
 The rejection of the transplanted organ is a real problem. The rejection may
be:
- Acute rejection of a graft occurs several weeks after transplantation. It
results from a delayed hypersensitivity reaction and cell lysis.
- Chronic rejection may occur at a late time .Immune complexes form in
the arteries supplying the graft, blood supply fails and the graft is
rejected.
181
References
2. Brown T.A. Rapid Review of Physiology.2nded.Philadelphia, Mosby, 2012
Saunders, 2015.
182
Chapter nine
Respiratory system 9
Respiratory system
Overview
 Respiratory system is the system responsible for equipment of air to the
body tissues.
 Respiration is a complex process by which living organisms exchange O2
and CO2 between the organism and the environment.
 Respiration is important in obtaining energy by oxidation of food
substances. The obtained energy is stored in form of high energy phosphate
compounds like ATP.
 Respiration includes many processes:
1- External respiration: exchange of air between the external
environment and pulmonary alveoli.
2- Exchange of gases between the alveolar air and the blood flowing along
the pulmonary capillaries.
3- Transport of gases by the blood.
4- Exchange of gases between the tissue cells and blood in the tissue
capillaries.
5- Internal respiration: consumption of O2 by the cells and production of
CO2.
Functions of respiratory system:
 In addition to the main function of the respiratory system which is the gas
exchange between the organism and the environment, the respiratory can
perform other non respiratory functions include the following:
1- Protective function: respiratory system provides a protection against
some microorganisms by preventing them from entering the body or by
removing them from the respiratory surface. These are done by:
 Ciliary activity moves the superficial liquid lining layer continuously
toward the pharynx.
 Neutrophils, lymphocytes and alveolar macrophages are present in
the alveoli defense against bacteria and viruses.
 Lungs synthesize immunoglobulin IgA for its own defense.
2- Acid –Base balance: respiratory system can alter blood PH by changing
blood CO2 level so as to keep the blood PH at a level 7.4.This is done
through the chemoreceptors and respiratory center integrations.
183
3- Olfaction: the sensation of smell occurs when air born molecules are
drawn into the nasal cavity.
4- Metabolic functions of the lungs: these functions include:
 Regulation of blood pressure: endothelial cells of the pulmonary
capillary secrete an enzyme called angiotensin converting enzyme
(ACE), which converts angiotensin I to active angiotensin II, a potent
vasoconstrictor.
 Lungs synthesize hormones like serotonin, histamine,
prostaglandin E2, F2 and G2 and release them to the circulation
under various circumstances such as histamine, bradykinin and
prostaglandins are released during asthma attack .Heparin
histamine, serotonin and prostaglandinsE2and F2 are released
during anaphylactic shock.
 Bradykinin , norepinephrine ,serotonin and prostaglandins are
degraded and removed by the lungs.
Structural considerations
Respiratory system is composed of the followings:
1- Respiratory airways.
2- Two lungs
3- Chest walls which consist of muscles of respiration such as the diaphragm,
external inter costal muscles, internal intercostal muscles and abdominal
muscles and the rib cage.
4- Part CNS concerned with the control of respiratory muscles.
Respiratory airways
1- Upper respiratory airways
 Upper respiratory airways have several physiological functions in addition
to air conduction, such as swallowing, conditioning of air (warming and
humidification) before its passage to the trachea and defense mechanism.
 Upper respiratory airways include many parts: the external nose, nasal
cavity and pharynx.
- Nose: Mucous membrane of the nose is lined by ciliated columnar
epithelium containing scattered goblet cells.
- Pharynx is lined by ciliated columnar epithelium with goblet cells.
Oropharynx is lined by stratified squamous epithelium.
184
Figure (9.1): Structure of respiratory system. Retrieved
from: www.thinglink.com
2- Lower reparatory airways

 The lower respiratory tract consists of larynx, trachea, bronchi and
bronchioles, alveolar ducts and alveoli in the lungs. (Figure9.1).
 Larynx: upper part of the larynx and vocal cords are lined by stratified
squamous epithelium. Lower part is lined by ciliated columnar epithelium.
 Trachea is a tube extends from the larynx to the bifurcation in the
mediastinum.
- It is lined with „C‟ shaped rings of cartilage, which prevent the
collapse of the tube when the air pressure is reduced during inspiration
(otherwise breathing would be impossible).
- The dorsal surface of the trachea has no cartilage, but instead has
smooth muscles, which contract to reduce the size of the trachea, (e.g.
during coughing or an asthma attack).Smooth muscles relax during
swallowing (food passing down the esophagus )and also to expand the
trachea during exercise (so air breathed in faster).(Figure 9.2).
185
Figure (9.2): Structure of trachea. a: longitudinal section, b: cross section.( Marieb
E.N. and Hoehn K. Human Anatomy and Physiology . San Francisco, Pearson Education
Inc., 2010).
Tracheobronchial Tree
 Trachea the first generation respiratory passageway is divided into right
and left main bronchi, which are the second generation respiratory
passageway.
 Bronchus in turn is divided into small branches: the bronchioles inside the
lung.(Figure 9.3).
 Bronchioles are further divided into very small bronchioles: the respiratory
bronchioles.
 There are 20- 25 generations before reaching finally to the alveolar duct
and alveoli.
 The inner surface of the trachea (bronchi and bronchioles) is lined with mucus
secreting goblet cells (the mucus traps foreign particles, e.g. dust and
parasites) and ciliated cells carrying the mucus to the nose
 Conducting zone extend from the trachea to terminal bronchioles which are
ciliated for removal of debris. It is anatomically incapable of gas exchange
but they work as a passageway for air movement. It constitutes the
anatomical dead space.
 Respiratory zone extends from the respiratory bronchioles to the alveoli. It
is a site for gas exchange. (Figure 9.4).
186
Figure (9.3): Tracheobronchial Tree.(Seeley R.R., Stephens T.D. and Tate P. Anatomy and
Figure (9.4): Conducting zone and respiratory

zone.(LevitzkyM.G.PulmonaryPhysiology.Singapore,
McGraw-Hill,Inc.,1995).
187
The lungs
 Lungs are principle organs of the respiratory system. Each lung is conical
shape resting on the diaphragm.
 The right lung is larger than the left lung. The right lung has three lobes
while the left lung has two lobes .Each lobe is supplied by a lobar bronchus.
The lobes are divided into bronchopulmonary segments which are
supplied by the segmental bronchi (Figure 9.5).
- Nine bronchopulmonary segments are present in the left lung.
- Ten bronchopulmonary segments are present in the right lung.
 The lung is surrounded by a double layered serous membrane called
pleura:
- Parietal pleura is the outer layer of the pleura
- Visceral pleura are the inner layer, directly connected to the lung.
- Pleural cavity – slit-like potential space filled with 2 ml mucoid pleural
fluid, which is secreted by parietal pleura.
 Function of the pleural fluid:
1- It keeps the two pleura layers together.
2- It acts as a lubricant to help the sliding movement between the two
layers.
3- It is essential for the proper expansion and contraction of the lungs.
Pathology note: Pleural effusion: an accumulation of significant quantity of

fluid in the pleural cavity .It results from blockage of lymphatics ,increased
pulmonary capillary pressure which leads to excessive transudation of fluid into
the pleural cavity as in cardiac failure, reduced plasma colloid osmotic pressure
in the hyperproteinemia ,and infection or inflammation of the pleura lead to
damage the capillary membrane.
Figure (9.5): Bronchopulmonary segments. Retrieved from www.slideshare.net
188
Pulmonary ventilation
Overview
 Pulmonary ventilation means inflow and outflow of air between the
atmosphere and the lung alveoli.
 Air moves from the region of a high pressure to one of a lower pressure.
 A pressure difference is established by the mechanics of pulmonary
ventilation: inspiration and expiration.
 The muscles cause the lungs to expand and contract.
 Lungs can be expanded and contracted in two ways:
- Downward and upward movement of the diaphragm to lengthen or
shorten the chest cavity.
- Elevation and depression of the ribs to increase and decrease the
anterior-posterior diameter of the chest cavity.
 Normal quiet breathing is accomplished by the movement of the diaphragm.
Inspiration
 Inspiration is an active process.
 The dome shaped diaphragm flattens as it contracts. This increases the
height of the thoracic cavity.(Figure 9.6).
 The external intercostal muscles contract to raise the ribs .This increases
the circumference of the thoracic cavity
 During deep or forced inspiration, additional muscles are recruited: scalene,
sternocleidomastoid and pectoralis minor.
 Intrapleural pressure becomes more negative (-2.5 − -6)mmHg ,due to
increase thoracic volume ,as compare to the atmospheric pressure, therefore
air flows into the lung.
Expiration
 Quiet expiration in healthy people is a passive process(no muscle
contraction)
 Inspiratory muscles relax
 Relaxing diaphragm moves superiorly (up). (Figure9.6).
 Elastic fibers in lung recoil
 Volumes of thorax and lungs decrease simultaneously, increasing the
pressure to slightly positive so the air flows out of the lungs.
 Expiration during the exercise or lung diseases becomes active process
requiring use of accessory muscles like internal intercostal muscles and
abdominal muscles.
189
Figure (9.6): Respiratory muscles action during inspiration and expiration. (Seeley R.R.,
Stephens T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill Companies,
2008).
Basic concepts of air movement and pressure

Pulmonary pressure
 The lungs have tendency to collapse due to their elastic structures, therefore
they collapse like a balloon to expel the air through the trachea when there is
no force to keep it inflated.
 The lung floats in the thoracic cavity surrounded by pleural fluid that
lubricates movement of the lung in the thoracic cavity.
 Pleural pressure is the pressure of the fluid in the thin space between the
lung and the chest wall .This is slightly negative, and becomes more
negative at the beginning of the inspiration, reaching to about -6 cm of H2O
or even -7.5cm of H2O by increasing the force that expands the lung.
- During inspiration: pleural pressure decreases because thoracic
volume increases according to the Boyle’s law. (Table 9.1).
- During expiration: pleural pressure increases because thoracic
volume decreases. (Figure 9.7).
 Atmospheric pressure is the pressure exerted by the weight of the air in the
atmosphere (760 mmHg at sea level)
190
 Alveolar pressure: is the pressure of the air inside the alveoli.
- If the glottis is open, no air moves into or out of the lungs .The pressure
in all parts of the respiratory tree and all the ways to the alveoli is equal
to the atmospheric pressure (0 cm of H2O).
- During inspiration the alveolar pressure falls to (-1cm of H2O) as
compare to the atmospheric pressure. (Figure 9.7 ).
- During expiration, alveolar pressure slightly increases to +1cm of H2O
to force 0.5 litter of inspired air out of the lung during 2-3 seconds of
expiration.
 Transpulmonary pressure is the differences between the alveolar pressure

and pleural pressure.
- Pressure differences between the alveoli and the pressure on the outer
surface of the lung measures the elastic force of the lung that tends to
collapse the lung, which is known as recoil pressure.
 Pulmonary pressures and volumes changes during respiratory cycle

(inspiration and expiration) are illustrated in figure (9.8).
Table( 9.1 ):Gas laws

Description Importance
Boyle‟s law: The pressure of a When alveolar volume increases, pleural
gas is inversely proportional to pressure decreases below atmospheric
its volume at a given volume. pressures causing airflow into the lungs ,and
vice versa when alveolar volume decreases
Dalton‟s law: The partial The greater the difference in partial pressure
pressure of a gas in a mixture of between 2 points, the greater the rate of gas
gases is the percentage of the gas movement.
in the mixture times the total
pressure of the mixture of gas.
Henry‟s law: The concentration A small amount of the gases in air dissolves
of a gas dissolved in a liquid is in the fluid lining the alveoli (CO2 is
equal to the partial pressure of 24times more soluble than O2, therefore
the gas over the liquid times the CO2exits through the respiratory membrane
solubility coefficient of the gas. more readily than O2 enters).
191
Figure (9.7): Alveolar pressure during inspiration and expiration. (Seeley R.R., Stephens
T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill Companies, 2008).
1-Pleural pressure 4- Pleural pressure

↓because thoracic ↑because thoracic
volume ↑ volume ↓.
2- As inspiration 5-As expiration

begins alveolar begins alveolar
pressure ↓below the pressure ↑below the
atmospheric atmospheric pressure
pressure because the because the
decreased pleural increased pleural
pressure causes pressure causes
alveolar volume to ↑ alveolar volume to ↓
3-Air flows into the 6-Air flows out of the

lungs because the lungs because the
alveolar pressure is alveolar pressure is
lower than greater than
atmospheric atmospheric
pressure. pressure.
Figure (9.8): Pressures and volumes changes during the respiratory cycle. (Seeley R.R.,
2008).
192
Work of breathing
 Work of breathing is pressure volume work performed in moving air into
and out of the lungs. Most of this work is performed during inspiration.
 Work of breathing must overcome three sources of resistance encountered
during inspiration :
1- Airway resistance is generated between air molecules and the walls of
conducting airways.
 Most of the total airway resistance comes from the large conducting
airways, because they are arranged in series and airflow resistances
are additive.
R total =R1+R2+R3+-----R n
=
 Small airways provide little resistance because they arranged in
parallel and airflow resistance in parallel are added reciprocally.
1/R =1/R1+1/R2+1/R3+-----1/R n
Pathophysiology note: Airway diameter can be reduced(and increased

airway resistance)by number of cases e.g., airway diameters are reduced by
smooth muscle contraction and excess inflammatory secretions in
obstructive airway diseases such as asthma and chronic bronchitis .As a
result work caused by airway resistance increases
Pharmacology note :Many classes of drugs affect large airway diameter by

affecting bronchial smooth muscles tone .For example β2 –adrenergic
agonists such as albuterol which stimulates bronchodilation .Other classes of
drugs prevent bronchoconstriction or inhibit inflammation e.g., steroids
anticholinergics ,leukotriene receptors antagonists and lipoxygenase
inhibitors .
2- Compliance work: is the work performed to overcome elastic recoil of

the lungs. It accounts for the largest proportion of the total work of
breathing.
Pathology note: In emphysema compliance work is reduced because the

destruction of lung tissues and loss of elastic tissues of the lung, but in
pulmonary fibrosis, compliance work is increased because the fibrotic
tissues require more work to expand.
193
3- Tissues resistance: is generated as the pleural surfaces slide over each
other during respiratory cycle .It accounts for a small portion (5%) of the
total work of breathing.
Pulmonary compliance
 Pulmonary compliance is a measure of lung dispensability.
 It is defined as the extent to which the lung will expand for each unit
increase in transpulmonary pressure. Compliant lungs are easy to distend.
ΔV
C= −−−−
ΔP
 Total lung compliance of both lungs and thorax is 200ml/cm.H2O, every

time transpulmonary pressure increases 1 cm.H2O lung volume will expand
200 ml.
 The diagram which shows the relation between lung volume change and
change in transpulmonary pressure refers to compliance diagram. (Figure
9.9).
 Compliance diagram shows two curves for expiration and inspiration.
Figure (9. 9): Total lung compliance, TLC: total lung capacity, FRC: functional
residual capacity, RV: residual volume.(Brown T.A. Rapid Review of Physiology.
Philadelphia, Mosby, 2012).
194
 Compliance is determined by:
- Elastic force which is caused by elastic tissues of the lungs (elastin and
collagen fibers).It represents one third of the total lung elasticity.
- Elastic force caused by surface tension of the fluid that lines the inside
wall of the alveoli (caused by air fluid interface).It represents two thirds
of the total lung elasticity.
Pulmonary surfactant
 Surfactant is a surface tension lowering agent present in the alveolus
between the alveolar fluid and air.
 It is a complex mixture of phospholipids (dipalmitoyl phosphocholine),
proteins and Ca2+.
 It is secreted by type II alveolar epithelial cells which are 10% of the
surface area of the alveoli.
 Role of surfactant :
- Surfactant reduces surface tension. The surface tension of normal fluid
lining the alveoli without surfactant is 50 dynes/cm, while that for fluid
lining the alveoli with normal surfactant is about 5-30dynes/cm.
- It reduces compliance resistance of the lungs.
- It maintains alveolar stability .It prevents over distention or collapse
(atelectasis) of the alveoli. When there is increase in the diameter of
the alveoli, during inspiration, the number of surfactant molecules per
unit area decreases and the surface tension increases.
 Surfactant production is decreased by the effect of smoking, histamine and
hypoxia while its production increases by hormonal effect (insulin, thyroid
hormone and glucocorticoid hormone).
Clinical note: Absence of surfactant from the fluid lining the alveoli especially in
some newborn babies known as respiratory distress syndrome of newborn babies
(hyaline membrane disease), which is fetal if it is not treated .That is why the
premature babies may be at risk if they are born before the 6-7 months of
gestation.
Alveolar ventilation
 Volume of air moves in and out of the lungs with each normal breath .This
represents the tidal volume (VT).The typical VT is about 500ml.
 There are 12-15 breathes per minute ,therefore the total air volume leaving
the lung per minute (minute ventilation ) ,which is measured as in the
following equation :
Minute ventilation= respiratory rate X VT

= 12 breathes /min X 500 ml
= 6000ml/min
195
 Not all the air that passes the lips reaches the alveolar gas compartment
,where the gas exchange occurs, but about 150 ml remains behind in the
anatomical dead space .So the alveolar ventilation (air volume entering g
the respiratory zone ) is calculated as in the following equation :
Alveolar ventilation (AV) =12 breathes /min X( 500 ml – 150 ml )

= 4.2 Lit/minute
 Alveolar ventilation represents the fresh inspired air for gas exchange.
Lung volume and capacities

Overview
 The way to study the pulmonary ventilation is known spirometry, which is
done by recording the volume of air moved into and out of the lungs. The
device which is used to study the lung volumes is the spirometer, while the
record is the spirogram.
 Lung volumes and capacities are divided into two types
1. Static lung volumes and capacities
2. Dynamic lung volumes and capacities.
 There are normal physiological differences in lung volumes and capacities,
e .g; they are less in women than those in men in about 20-25%.They are
greater in large and athletic people than in small asthenic people.
Clinical note: Lung volumes tend to decease in restrictive lung diseases (e.g.,
pulmonary fibrosis) because of limitations of pulmonary expansion and they tend
to increase in obstructive lung diseases (e.g., emphysema) as a result of
increased compliance.
Static lung volumes and capacities (figure 9.10)

 Static lung volumes are not changed with time. They include the following :
1- The tidal volume (TV): The volume of air inspired or expired with each
normal breath (500ml).
2- The Inspiratory Reserve Volume (IRV): The extra air volume that can
be inspired forcefully after inspiration of normal tidal volume.(3000 ml).
3- The Expiratory Reserve Volume (ERV): The extra amount of air that
can be expired forcefully after the end of normal tidal
expiration.(1100ml).
4- The Residual Volume (RV): Air volume remaining in the lungs after
the most forceful expiration. (1200ml).
196
Figure (9.10): Static lungs volumes and capacities. (Seeley R.R., Stephens T.D. and
Tate P. Anatomy and Physiology. New York, McGraw –Hill Companies, 2008).
 Two or more of these volumes together are called: pulmonary capacities.

1- The Inspiratory Capacity(IC): amount of air that can be breathed
beginning at the normal expiratory level and distending the lung to the
maximum amount (3500ml).
IC=TV+IRV
2- The functional Residual Capacity (FRC): amount of air remaining in

the lungs at the end of normal expiration. (2300ml).
FRC=RV+ERV
3- Vital Capacity (VC): maximum amount of air that can be expelled from
the lung after first filling the lungs to their maximum extent then expiring
to the maximum extent. (4600ml).
VC=TV+IRV+ERV
4- The Total Lung Capacity (TLC):The maximum volume which lungs can
be expanded with the greatest possible inspiratory effort.(5800 ml).
TLC=TV+IRV+ERV+RV
TLC=VC+RV
197
Clinical note: There are two major categories of respiratory diseases, which
can alter the dynamic lung volumes:
Chronic Obstructive Pulmonary Diseases (COPD): the diseases that interfere
with airflow. They are characterized by increased airway resistance to air flow
caused by excessive secretion or increased contraction of bronchial smooth
muscle.
Asthma: is a disease characterized by increased constriction of the bronchi
and bronchioles in response to various stimuli causing air narrowing and
decrease ventilation efficiency. The symptoms include rapid shallow breathing
wheezing, cough and shortness of breath.
Chronic bronchitis: is the inflammation of the bronchioles causing swelling of
the walls of the bronchioles and bronchi and reducing air passage through
them.
Emphysema results in damage to the alveoli, so that the walls become less
elastic (taking longer to inflate and deflate).
Chronic Restrictive Pulmonary Disease (CRPD): is a chronic disorder that
causes a decrease in lung’s ability to expand. It is characterized by reduced
lung volume. The most common restrictive lung diseases are interstitial lung
fibrosis including sarcoidosis granulomatous disorder and extrapulmonary
restrictive lung diseases including scoiliosis.
Dynamic lung volumes

 Dynamic lung volumes quantify the time rate of gas flow along the airways.
 They are of a clinical importance in the assessment of airways resistance,
specifically during expiration, therefore they are of interest in patients with
COPD like :asthma ,emphysema ,chronic bronchitis .These are:
1- Forced Vital Capacity (FVC): The maximum air volume which can be
expired forcefully after maximum inspiration.(Figure 9.11 ).
2- Forced Expiratory Volume at the first second of expiration (FEV1):
Maximum air volume which can be expired forcefully at the first second
of expiration after maximal inspiration.
3- FEV1%: Is the ratio of air expired forcefully at the first second related
as a percentage of total amounts of air expired during FVC.
FEV1%=FEV1/FVC X 100
4- Peak Expiratory Flow (PEF): is the maximal flow rate which is

achieved during force expiration. (Figure 9.11).
5- Maximum Voluntary Ventilation (MVV): is the maximal air volume
which can be expired by breathing deeply and rapidly with maximal
voluntary effort for a short time.
6- Forced Expiratory Time (FET): is the time required to expire all air in
the lung by using the force.
7- Estimated Lung Age: is the age when the person pulmonary function is
normal.
198
Figure (9.11):a: Expiratory flow curve showingPEF
,b:expiratory volume to showing FEV1and FVC.( Levitzky M.G.
Pulmonary Physiology . Singapore,McGraw-Hill,Inc.,1995)
Pathology note: FEV1 and FVC are reduced in lung diseases and the degree of
reduction depends on the nature of the diseases. In obstructive diseases the
expiratory volumes are reduced because of airway narrowing, therefore FEV1
is reduced more than is FVC and FEV1% is reduced. In restrictive diseases,
inspiration is limited by noncompliance of the lung leading to limited
expiratory volumes. FVC is reduced more than is FEV1 resulting normal FEV1%
or even increased, because the elastic recoil of the lung is preserved.
Gas exchange
Overview
 Gas exchange across the respiratory membrane occurs by diffusion.
 Respiratory gases diffuse from area of high partial pressure to area of low
pressure.
 Partial pressure: is the pressure of each gas alone, which is used to express
the concentration of the gas.
- Partial pressure of O2 and CO2 are designed as PO2 and PCO2
respectively
- Partial pressure of a gas is calculated by multiplying its fractional
concentration by the total pressure, for example the percentage of O2
199
is 21% of the total pressure 760 mmHg (atmospheric pressure), therefore
thePO2 is 160 mmHg
 Atmospheric air ,alveolar air and expired air have different concentrations of
gases because:
1- Air is humidified before it reaches the alveoli.
2- A constant diffusion of O2 from the alveoli into the blood, while CO2 is
constantly diffusing from the pulmonary blood to the alveoli.
3- The alveolar air is only partially replaced by atmospheric air.
Diffusion of gases through the respiratory membrane

 There are about 300 millions alveoli in the two lungs.
 The alveolar walls are thin ,within them is a solid network of
interconnecting capillaries, and blood flows in the alveolar walls as a sheet
 Gas exchange occurs through the membrane of all the terminal portions of
the lungs (not only the alveoli).These membranes are known the
respiratory membrane or the pulmonary membrane.
Respiratory membrane
 The respiratory membrane is composed of the following layers(figure9.12):
1- A layer of fluid lining the alveoli that contains surfactant.
2- The alveolar epithelium
3- An epithelial basement membrane.
4- A thin interstitial space between the alveolar epithelium and the
capillary membrane.
5- A capillary basement membrane that, in many places, fuses with
epithelial basement membrane.
6- The capillary endothelial membrane.
 The membrane is very thin, about 0.6 µm as average, and total surface area
is70 m2 in normal adult .The total amount of blood in the lung capillaries is
60-140 ml, therefore the gas exchange is very rapid.
 The diameter of pulmonary capillaries is 5 µm, so the RBCs must squeeze
through them (RBC touches the membrane) and O2, CO2 dot need to pass
through the plasma.
 Factors affecting the rate of diffusion through the respiratory

membrane
1- The thickness of the membrane.
2- The surface area of the membrane.
3- The diffusion coefficient of the gas in the substance of the membrane.
4- The pressure differences between the two sides of the membrane.
200
Figure (9.12): The respiratory membrane. (Seeley R.R., Stephens T.D. and Tate P. Anatomy
and Physiology. New York, McGraw –Hill Companies, 2008).
Diffusing capacity of the respiratory membrane

 Diffusing capacity is the volume of gas that is able to diffuse across the
respiratory membrane in 1 minute with pressure gradient across the
membrane of 1 mmHg.
 Exchange of O2 is normally so efficient that is perfusion limited (the
amount of O2 that enters the arterial circulation is limited only by the
amount of blood flow to the lung).
 The diffusing capacity of the lung for CO2 is 20 times greater than that for
O2.At rest the diffusing capacity for O2 is 21ml/min/mmHg, while its 440ml
/min/mmHg for CO2.
 All factors that affect diffusion through the respiratory membrane can affect
the diffusing capacity.
 The diffusing capacity for O2 increases during exercise.
Perfusion -limited and diffusion-limited gas exchange

 Perfusion -limited gas exchange: diffusion can be increased only if blood
flow increases, e.g., O2 uptake under normal condition.
 Diffusion- limited exchange: diffusion continues as long as pressure
differences exist across the respiratory membrane, e.g., O2 diffusion during
heavy exercise at high altitude.
Pulmonary blood flow

 The pressures in the pulmonary circulation are low compared with those of
systemic circulation.
 In the upright position ,perfusion in the apices of the lung is different from
that of the bases because the effects of gravity, therefore there are three
zones of pulmonary blood flow:
1- Zone 1(top of the lung)
 It has no blood flow because alveolar pressure is greater than artery
pressure.
 It can occur when pulmonary artery pressure is decreased
(hemorrhage) and when alveolar pressure is increased.
201
2- Zone 2(middle of the lung)
 It has an intermittent blood flow that occurs during systole (the
artery pressure is greater than the alveolar pressure) while during
diastole (the artery pressure is less than the alveolar pressure).
3- Zone 3( base of the lung )
 It has a continuous blood flow because pulmonary capillary pressure
remains greater than alveolar pressure during the cardiac cycle.
 In the lying position, blood flow in normal person blood flow is continuous
because all areas of the lung at the same level to the heart.
Alveolar ventilation and pulmonary circulation perfusion

 In normal conditions there is match between the alveolar ventilation and
alveolar blood flow .This maintained the effective gas exchange between the
air and the blood. This concept is called ventilation –perfusion ratio
(AV/Q)
 Increased alveolar ventilation or increased pulmonary circulation leads to
increase gas exchange.
 The balance between the alveolar ventilation(AV) and blood flow(Q) can be
disrupted in 2 ways:
1- Alveolar ventilation exceeds the body’s ability to pick up oxygen .This
occurs because of inadequate cardiac output due to heart attack.
2- Alveolar ventilation may be not great enough to provide O2, e.g.
bronchial asthma.
 Shunted blood: The blood which is not completely oxygenated.
 There are two types of shunts: anatomic and physiologic shunt.
 Anatomic shunt: occurs when the blood would normally go to the lung is
diverted elsewhere, such as fetal blood flow.
 Physiologic shunt: when the blood supplying the lung is not involved in gas
exchange such as bronchial arterial circulation and in pathologic state, the
pneumonia and pulmonary edema.
Oxygen and carbon dioxide transport in the blood

Overview
 Oxygen diffuses through the respiratory membrane into the blood.
 In the blood O2 combines reversibly with hemoglobin (98.5%) and smaller
amount dissolves in the plasma (1.5%).
 Oxygen is transported by Hb from pulmonary capillary to the tissues
capillaries where some O2 is released.
 The released O2 diffuses from the blood to the tissue cells to be used in
aerobic respiration.
 Carbon dioxide is produced during aerobic metabolism and diffuses from
the cells into the tissue capillaries.
 In the blood CO2 is transported in three ways:
1- Dissolved in plasma.
2- In combination with Hb.
3- In form of bicarbonate.
202
Partial pressure gradient of oxygen and carbon dioxide
1- Oxygen partial pressure gradient
 Oxygen moves from the alveoli, where PO2 is 104mmHg into the blood
where PO2 is 40 mmHg.
 In the blood the PO2 decreases to 95mmHg due to the mixing with
deoxygenated blood.
 Oxygen moves from the tissue capillaries (PO2=95mmHg) into the tissue
where PO2 is 40 mmHg.(Figure 9.13 ).
2- Carbon dioxide partial pressure
 Carbon dioxide of the tissue (PCO2 is 45 mmHg) moves into the tissue
capillaries (PCO2 is 40 mmHg). (Figure 9.13).
 Carbon dioxide moves from the capillaries (PCO2 is 45mmHg) to the alveoli
(PCO2 is 40mmHg).
Figure (9.13): Gas exchange according partial pressure gradient of O2 and CO2. (Seeley
R.R., Stephens T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill
Companies, 2008).
203
Oxygen-Hemoglobin dissociation curve
 Oxygen-Hb dissociation curve is to describe the saturation percentage of
Hb in the blood at different blood level PO2 values.
 Hemoglobin is 100% saturated with O2 if four O2 molecules are bound to
each Hb molecule. Hb is 50% saturated with O2 if two O2 molecules are
bound to each Hb molecule.
 Hemoglobin is 98% saturated when PO2 in blood leaving pulmonary
capillaries is 104mmHg.Decrease in PO2 in pulmonary capillaries have
small effect on Hb saturation .Even if PO2 decreases to 60mmHg, the Hb is
still 90% saturated. Hb is very effective in picking up the O2 in the lungs.
 Hemoglobin saturation is 75% when the PO2 of blood leaving the tissue
capillaries is 40 mmHg, because 23% of O2 picked up in the lung is released
and diffuse into the tissues.(Figure9.14 ).In the tissues , a small change in
PO2 results in large change in Hb saturation
Figure (9.14): Oxygen-Hb dissociation curve. (Seeley R.R., Stephens

T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill
Companies, 2008).
The Bohr effect

 The effect of of PH on the oxygen-Hb dissociation curve is called the Bohr
effect.
 Based on the fact that when O2 binds to Hb, certain amino acids in the Hb
molecule release H+ ions [ Hb + O2 ↔ HbO2 + H+ ]
 An increase in H+ (a decrease in pH) pushes the reaction to the left, causing
O2 to dissociate from Hb
 Hb affinity for O2 is decreased when H+ ions bind to Hb, therefore O2 is
released from Hb
 H+ concentration increases in active tissues, which facilitates O2 unloading
from Hb so that it may be utilized by the active tissues
204
 In the tissues, factors such as a decreased PH (Bohr effect) ,increased PCO2
and increased temperature cause the O2-Hb dissociation curve shifts to the
right (an increased release of O2),(Figure9.15.a ).
 In the lungs ,an increased PH, a decreased PCO2 and decreased temperature
cause the O2-Hb dissociation curve shifts to the left(an increase in Hb ability
to pick up O2),(Figure 9.15.b).
 The substance 2, 3-biphosphoglycerate binds to Hb and reducing its affinity
for O2.
 Fetal Hb has a greater affinity for O2 than does maternal Hb.
Figure (9.15): Factors affecting O2-Hb dissociation curve to (a): shift to right in
the tissues and (b): shift to left in the lungs. (Seeley R.R., Stephens T.D. and Tate P.
Anatomy and Physiology. New York, McGraw –Hill Companies, 2008).
Transport of Carbon dioxide

 Carbon dioxide is byproduct of cellular respiration .It diffuses across the cell
and capillary membranes into the blood and enters the RBCs.
1- In the RBCs, CO2 is combine with water to form H2CO3,in the presence
of carbonic anhydrase .70% of CO2 is transported as HCO3-
 The H2CO3 dissociates to form bicarbonate HCO3- and H+.
 Chloride shift : Cl- enters the RBCs in exchange for HCO3- ,which
travels freely in blood to the lung.
 In the pulmonary capillary HCO3- enters RBCs in exchange for Cl-
and converted to CO2 to expire. (Figure 9.16).
2- Approximately 20% of CO2 is transported in the blood as
carbaminohemoglobin, by binging to amino groups of Hb. This causes a
right –shifting of O2-Hb dissociation curve.
3- Approximately 10% of CO2 is transported as dissolved CO2.
205
Halden effect :
 Halden effect illustrates the role of O2-Hb reaction in CO2 transport .
 Deoxygenated Hb binds more CO2 than oxyhemoglobin and form
carbaminohemoglobin .Whenever the Hb is oxygenated it diplaces CO2 from
its combination.
 Halden effect occurs because (deoxygenated Hb has more affinity for CO2
and so there is an increased pickup of CO2 from the tissues,while
oxyhemoglobin has less affinity for CO2 )and ,so CO2 is released from the
blood to the alveoli.
 The importance of Halden effect is to doublicat the CO2 amount released
from the blood into the lungs and to doublicate the CO2 pick up from the
tissues.
Figure (9.16): Carbone dioxide exchange, a: in the tissues, b: in the lung. (Seeley R.R.,
2008).
Regulation of respiration
 The basic rhythm of respiration is controlled by two groups of neurons
located in the in the medulla oblongata :
1- Two dorsal respiratory groups:
 They are located bilaterally in the dorsal part of the medulla oblongata.
 They control the basic rhythm of respiration which is accomplished by
neurons that spontaneously generate action potential which stimulate
respiratory muscles.
206
2- Two ventral respiratory groups :
 They are located bilaterally in the ventral part of the medulla oblongata.
 They stimulate the expiratory muscles which are important in the forced
expiration.
 Pneumotaxis center :
- Groups of neurons located in the pone.
- It inhibits inspiration, limiting the size of TV.
 Controlling of respiratory muscles is voluntary and made by the neural
communications between higher brain center and brain stem as in holding
of breath, emotional upset and irritant that alter normal breathing pattern.
 Chemoreceptors
1- Peripheral receptors
 They are located in the carotid artery and aortic bodies.
 They detect the chemical concentration of blood and cerebrospinal fluid
(changing level of CO2, O2 and PH).
- They are sensitive to low arterial O2 concentration.
- Low arterial PH (↑H+) occurs when CO2 level increases.
- Decreased O2 causes increase in ventilation (hyperventilation).
2- Central chemoreceptors
 They are located on the ventral surface of the medulla.
 They keep the PCO2 within normal by having indirect response to the
amount of CO2 dissolved in cerebrospinal fluid.
 High PCO2 (hypercapnia) and ↓PH stimulate hyperventilation.
Chemoreceptors reflexes
 Chemoreceptors maintain normal level of arterial CO2 through
chemoreceptors reflexes.
 Increased CO2 lead to increase H+ (↓PH) resulting in stimulation of
chemoreceptors.
 Decreased PH is caused by exercise, breath holding and other metabolic
causes.
 Herring-Breuer reflex: the reflex that limits the degree of inspiration and
prevents over inflation of the lung.
Hypoxia
 Hypoxia refers to insufficient O2 supply to the tissues, while hypoxemia
refers to insufficient O2 in the blood which may be caused by high altitude,
anemia, CO poisoning pulmonary edema and fibrosis.
 As a response to hypoxemia :chemoreceptors increase their firing ,control
breathing centers regulate the respiratory rate (tachypnea)and heart rate
(tachycardia) and cause large TV .All these events result in increased
oxygenation at the pulmonary membrane and increase delivery of O2 to the
tissues.
207
References
2. Geetha N. Textbook of Medical Physiology.3rd ed. Hyderabad, New Delhi, Paras
Medical Publisher, 2014.
Saunders, 2015.
4. http//: www.thinglink.com
5. http//:www.slideshare.net
6. Levitzky M.G. Pulmonary Physiology .4th ed.Singapore,McGraw Hill,Inc.,1995.
208
Chapter 10
Urinary system 10
Urinary system
Overview
 The urinary system consists of two kidneys , a single midline urinary
bladder, two ureters which carry the urine from the kidney to the urinary
bladder and a single urethra which carries the urine from the bladder to the
outside of the body(figure 10.1).
 The kidneys make up the main purification system of the body. They control
the composition of the blood by removing the waste products and conserving
the useful substances.
 The kidneys are the major excretory organ among other excretory organs of
the body: skin, liver, lungs and intestine.
Figure (10.1): Structure of the urinary system. (Marieb E.N. and Hoehn K. Human
Functions of the kidneys

1. Excretory functions
 Kidneys filter blood producing large volume of large molecules (proteins ,
RBCs)are retained in the blood ,small molecules and ions enter the filtrate.
 Most of filtrate volume is reabsorbed back into the blood.
 Metabolic waste, toxic materials and excess ions remain in a small volume
of filtrate.
 Additional waste products are secreted into the filtrate resulting urine
formation.
209
2. Regulatory function
 Regulation of blood volume and pressure by controlling the extracellular
fluid volume (ECF) in the body by producing either a large volume of
diluted urine or small a small volume of concentrated urine.
 Regulation of concentration of solutes in the blood by regulation of
concentration of major ions (Na+,Cl-,HCO3-,HPO42- ).
 Regulation of PH of ECF by secreting variable amounts of H+ .
 Regulation the synthesis of RBCs by secreting of erythropoietin hormone.
 Vitamin D synthesis therefore regulates Ca2+ blood level.
 The kidneys are paired of bean shaped organs that lie behind peritoneal
lining of the abdominal cavity.
 Each kidney is surrounded by a thin capsule to resist stretch and limit the
swelling.
 The renal artery, renal vein, renal lymphatic and ureter enter and leave the
kidney through a helium on the midline concave surface of the kidney.
Internal structure of the kidneys

 There are two distinguished layers inside the longitudinal section of the
kidney .The outer layer the cortex and the inner layer the medulla.
 The medulla is made up of series of cone shape pyramids which project to
the minor calyces. (Figure 10.2).
 Minor calyces open into major calyces which open into renal pelvis.
 The renal pelvis leads to the ureter which drains into the bladder.
Figure (10.2): Longitudinal section of the kidney.( Marieb E.N .Essential of Human
Anatomy and Physiology . San Francisco, Pearson Education,Inc.,2012).
210
Structure of the nephron
Overview
 The functional unit of the kidney is the nephron (where the blood is
filtrated)
 Nepheron is blind end tubules running from the Bowman‟s capsule into the
renal pelvis.(Figure 10.3).
 There are about one million nephrons in each kidney.
 The nephron begins at the glomerulus (comprises a tuft of glomerular
capillaries with the Bowman’s capsule). (Figure 10.5 .a).
 The capillaries are derived from the afferent arterioles and drain into the
efferent arterioles.
 Many branches of capillaries of capillaries form cluster that invaginates into
the Bowman’s capsule (Figure 10.5.a).
 The glomerulus and the Bowman’s capsule form the renal corpuscle.
 The materials leave the blood in the glomerulus and enter the Bowman’s
capsule through the filtration membrane.
 Fluid from Bowman’s capsule flows into the coiled segment (proximal
convoluted tubule), then into loop of Henle, down into the medulla.
Figure (10.3): The nephron. . (Seeley R.R., Stephens T.D. and Tate P. Anatomy
211
 There are two types of nephrons:
1- Cortical nephrons :
- The glomeruli are in the two thirds of the cortex.
- Short loop of Henle, that dips into the outer medulla.
2- Juxtamedullary nephrons
- Glomeruli are in the inner cortex.
- Long loop of Henle extends deeply into the medulla
 Proximal convoluted tubule is about 14 mm long ,60 µm in diameter .It is

composed of simple cuboidal epithelial cells ,made up the wall.
 Loops of Henle are continuous of proximal convoluted tubule .Each loop has
two limbs: descending and ascending. (Figure 10.3).
- The ascending limb of loop of Henle leads into a second coil section: the
distal convoluted tubule.
 Distal convoluted tubule begins at a special structure: the juxtaglomerular
apparatus. Figure 10.5.b ).
 Collecting duct: The cells of collecting duct have some microvilli and
numerous mitochondria. The absorb Na+, K+ and Cl- actively.
Juxtaglomerular apparatus (Figure 10.5. b)

 The tubule passes between the afferent arteriole that supplies blood to the
glomerulus and the efferent arteriole that drains it. This short section of the
tubular cells is known as macula densa
 Juxtaglomeruler apparatus secretes enzyme rennin , and play an important
role in the regulation of filtrate formation and blood pressure.
 The distal tubules of several nephrons join to form a collecting duct that
passes through the medulla to the papilla.
 The overall structure of the nephron is summarized in a diagram (figure10.4).
Glomerulu
s
Renal corpuscle
Bowman,s capsule
Nephron
Proximal tubule
Thick segment of descending
limb
Renal tubules Thin segment of descending
Loop of Henle limb
Thin segment of ascending
limb
Thick segment of ascending
Distal tubule
limb
Figure ( 10.4 ): Overall structure of nephron.
212
a b
Figure (10.5):a: The renal corpuscle consists of Bowman’s capsule and glomerulus,
b:Bowman,s capsule covers the glomerular capillaries. Juxtaglomerular apparatus
consists of cells from the wall of the afferent arteriole and the distal convoluted tubule.
Companies, 2008).
Structure of the glomerulus

 Glomerulus is composed of fenestrated capillaries (Figure 10.6).
 The filtrated fluid passes from the capillaries into the Bowman,s capsule
through the filtration membrane.
 The filtration membrane consists of(figure 10.7 ) :
1. Fenestrated glomerular capillary endothelium.
2. Basement membrane.
3. Podocytes processes
Figure(10.6):Fenesterated capillaries Figure(10.7):Filtration membrane.

of the glomerulus.
(Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology. New York, McGraw –Hill
Companies, 2008).
213
Renal blood flow
Overview
 The renal artery enters the kidneys at the hilum (figure10.2).
 The renal artery branches to form interlobar arteries, which radiate out
towards the cortex.(Figure 10.8.a).
 Interlobar arteries diverge near the base of the pyramid to form arcuate.
 Interlobular arteries project from the arcuate.
 Interlobular arteries give rise to the afferent arterioles that supply the
glomerular capillaries.(Figure10.8.b).
 Efferent arterioles arise from the glomerular capillaries to carry the blood
away from the glomeruli.
 When the efferent arteriole exists the glomerulus, it gives rise to plexus of
capillaries, peritubular capillaries around the proximal and distal tubules.
 Vasa recta is a specialized part of the peritubular capillaries course into the
medulla along the loop of Henele of the juxtamedullary nephrons, then back
toward the cortex.
 Veins form from peritubular capillaries are: interlobular veins to arcuate
vein to interlobar vein to renal vein .
3-interlobar artery
2-segmental artery
1-renal artery
11-renal vein
(a)
Figure (10.8):a: Blood flow to the kidney ,b:blood flow to the nephron. (Seeley R.R.,
Stephens T.D. and Tate P. Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
214
Renal nerve supply
 The kidney has rich sympathetic noradrenergic innervations which supply
renal artery and its branches, juxtaglomerular apparatus and renal tubules.
Urine formation
 Three major processes are essential for urine formation: Filtration , tubular
reabsorption and tubular secretion
1- Filtration
 Filtration is the movement of water and small solutes from blood flowing
through the glomerulus across the filtration membrane as a result of pressure
differences into the Bowman’s capsule forming the filtrate.
 Most substances in the plasma (except for proteins) are freely filtrated, so
their concentrations in the glomerular filtrate in the Bowman’s capsule are
the same in the plasma.
Glomerular blood flow

 The part of the total cardiac output that passes through the kidney is called
renal fraction.
 The normal cardiac output is 5600ml/min, while the renal fraction is 1200
ml/min which represents 21% and varies from 12-30%.
Glomerular filtrate
 Glomerular filtrate is the fluid filtrated through the glomerular membrane
into Bowman’s capsule.
 Filtration membrane is composed of three layers (mentioned previously)
each of these layer is several hundred times as permeable as the capillary
membrane ,which accounts for the volume of the glomerular filtrate formed
each minute ,but still of high degree of selectivity for the size of passing
molecules.
The permeability of the G. membrane to substances of different molecular weights =
Concentration of dissolved substance on the filtrate side of the membrane

Its concentration on the plasma side
 The reasons for the high selectivity of the glomerular membrane are :
1. Size of the pores in the glomerular membrane is large enough to pass
molecules with diameter 8 nanometers.
2. Electrical charges of the molecules .The pores are lined by glycosylated
proteins which have strong negative electrical charges.
 Glomerular filtrate has the same components of the plasma except it has no
significant amount of proteins.
215
The glomerular filtration rate (GFR)
 The glomerular filtration rate (GFR) is the quantity of glomerular filtrate
formed each minute in all nephrons of both kidneys. It is 125ml/min in
normal person.
 Glomerular filtrate formed each day is 180 Lit/day; over 99% of the
glomerular filtrate is reabsorbed in the tubules, while remaining is passing
into the urine.
 Normal plasma flow through the kidney is 650 ml /min and GFR of both
kidneys is 125ml/min, so the average filtration fraction is 19%.
Factors that affect the GFR
GFR= Filtration pressure x Kf
 The factors that determine the filtration pressure (glomerular pressure,

plasma colloid osmotic pressure and Bowman’s capsule pressure) will
determine the GFR.
 The conditions that affect these pressures and therefore affect the GFR are:
1- Renal blood flow: an increase in the rate of blood flow through the
nephrons increases the GFR by increasing the glomerular pressure which
enhances the filtration process.
2- Afferent arteriolar constriction decreases the rate of blood flow into the
glomerulus and also decreases the glomerular pressure causing a decrease
in the filtration rate.
3- Efferent arteriolar constriction causes an increase in the resistance to
outflow from the glomeruli .This increases the glomerular pressure and
increase in efferent resistance causes slight increase in the GFR.
4- Sympathetic stimulation of the kidneys causes the afferent arterioles to
constrict, thereby decreasing the GFR.
 With strong sympathetic stimulation, glomerular blood flow and
glomerular pressure are reduced so that glomerular filtration
decreases to only a few percent of normal and the urinary output
can fall to zero for as long as 5 to 10 minutes.
5- Arterial pressure
 When the arterial pressure rises, afferent arteriolar constriction
occurs automatically .This prevents a significant rise in glomerular
pressure despite the rise in the arterial pressure. Therefore, the GFR
increases only few percent even when the mean arterial pressure
rises to 150 mmHg. This phenomenon is called autoregulation.
 An increase in arterial pressure can greatly increase the urinary
output even though it affects GFR slightly.
216
Pathological note: glomerular nephritis results from inflammation of the
filtration membrane within the renal corpuscle. The inflammation leads to
increased membrane permeability and accumulation of WBCs in the area
,resulting in high concentration of plasma proteins that enter the filtrate along
with WBSc. Glomerular nephritis may be acute when occurs within 1-3 weeks
after bacterial infection ,or chronic which is long term and progressive .The
filtration membrane becomes thick and replaced by connective tissues .
Reabsorption and secretion in the tubules

Overview
 The filtrate entering the nephrons flows through the following tubules:
1- The proximal tubule
2- The loop of Henele
3- The distal tubule
4- The collecting tubule
5- The collecting duct.
 Substances are selectively reabsorbed or secreted by the tubular epithelium.
 Reabsorption plays greater role than does secretion in the formation of urine,
but secretion is important in the determining the amounts of K+ and H+.
 The resulting fluid entering the pelvis is urine
 The tubules separate the substances that are to be conserved in the body from
those be eliminated in the urine.
 Water in the glomerular filtrate is reabsorbed in about 99% as it passes
through the tubules.
 Glucose and amino acids are entirely reabsorbed.
Renal transport mechanism

Overview
 Substances are reabsorbed or secreted by:
1- Trancellular transport: Transport across tubular epithelial cells from
the tubular lumen into tubular epithelial cells across the luminal
membrane, (figure 10.9) and from inside the epithelial cell into the
interstitium and peritubular capillaries across the basolateral membrane.
 It involves active transport and passive transport.
 Active transport is responsible for transport of Na+
 Secondary Active Transport utilizing Na+ gradient (Sodium
Symport).It is used for transporting glucose, amino acids, ions,
metabolites.
217
Figure (10.9): Trancelluar transport. Retrieved from: www.studyblue.com
Figure (10.10):Na+ is pumped into the interstitial fluid ,K+ is pumped into the tubular
cell. Retrieved from : www.studyblue.com
2- Paracellular transport done via tight junction and lateral intercellular

space
 It is important for electrolytes K+, Ca+2 and varies in the permeability in
different tubules.
 It allows to leak amount of solute and fluid in the proximal tubule,
while in collecting tubule is more limited.
Tubular transport maximum

 Transport maximum(Tm) is a limit for the amount of transported substances
per unit time.
 It exists for substances that are actively reabsorbed, because the carriers
responsible for transport become saturated.
 When the carriers are saturated, excess of substances is excreted.
 The renal threshold for a substance is the plasma concentration at which this
substance first occurs in the urine.
218
Renal clearance
 Clearance is the plasma volume from which a substance has been
completely cleared per the kidney per unit of time.
 A substance which is freely filtered across the glomerulus and neither
reabsorbed nor secreted into the tubule (e.g., insulin) its rate of clearance is
equivalent to GFR. The concept of clearance is to estimate GFR.
 A substance has a clearance greater than that of insulin; it must have been
secreted into the tubular fluid.
 A substance has lower clearance than that of insulin; it must have been
reabsorbed from the tubular fluid.
 Clearance can be calculated by the following equation :
Clearance =Amount excreted in urine in 1 minute/ Plasma concentration
1-The proximal tubule

 About 2/3 of the glomerular filtrate is reabsorbed from the proximal tubule.
 About 60-70% of Na+, water and urea is reabsorbed.
 Complete reabsorption of Cl- ,HCO3- ,HPO3-K,glucose,aminoacids and
proteins
 H+, ammonia and organic acids are secreted into the tubule.
1- Sodium reabsorption
 Sodium reabsorption in the proximal tubule is important because it conserves
total body Na+ and the reabsorption of Cl- , H2O, glucose and amino acids
depends upon it.
 Sodium is pumped out of cells into the interstitial fluid by Na+/K+ ATPase
pump on the basolateral membrane of the proximal tubule cells. This makes
the intercellular concentration of Na+ lower relative to the lumen ,so the Na+
diffuse passively from the lumen into the cells down electrochemical gradient
and are actively pumped out of the cells in exchange with K+ at the
basolateral membrane. (Figure 10.10 )
 Three Na+ leave for 2 K+ enter the cell.
 Potassium ions entering the cell ,leave the via K+ channels on the basolateral
membrane therefore intercellular concentration of K+ in the body is not
changed by Na+/K+ pump.
2- Chloride
 Sodium reabsorption is accompanied by water reabsorption ,leading to
increase Cl- concentration in the tubular lumen along the length of the
proximal tubule.Therefore Cl- move passively into the cell and then into the
interstitial fluid.
 The increased negativity of the intestinal fluid causes some Na+ to move
passively into the intestinal fluid from the lumen.
219
3- Water reabsorption
 Transport of Na+ and Cl- into the lateral intercellular space causes osmotic
flow of water from the lumen into the same space.
 Water and solutes transport from the lateral intercellular space into the
peritubular capillaries by osmotic and hydrostatic pressure gradients.
 Some water and solutes may leak back into the tubular lumen.
 The volume of reabsprbed water depends partly on the filtration fraction :
 If the filtration fraction increases then more water will be filtrated at the
glomerulus leaving high protein concentration in the glomerular
capillaries and raising the oncotic pressure in the peritubular capillaries
causing an increase in reabsorption from the lateral space.
 If the filtration fraction decreases, the opposite happens.
4- Glucose reabsorption
 All glucose in the filtrate is reabsorbed in the proximal tubule at a normal
level of plasma glucose.
 Glucose is cotransported with Na+ at the luminal membrane .When Na+
moves down its electrochemical gradient, glucose diffuses from the cell into
interstitial fluid and then to the peritubular capillaries.
 The normal plasma concentration of glucose is (0.6-1 mg/ml).
 The transport maximum for glucose is about 375mg/ml in man350 mg/ml for
woman).The renal threshold for glucose (the plasma concentration at which
glucose first appears in urine is 375mg/ml divided by GFR (125ml/min),
which is 0.3 mg/ml for man).
 When plasma glucose is high, in diabetes mellitus, glucose appears in urea
(glycosuria).
5- Bicarbonate reabsorption
 Hydrogen ions enter the lumen in exchange with Na+ or they are secreted by
H+ ATpase .
 Hydrogen ions combine with HCO3- filtrated at the glomerulus to form
H2CO3.
 H2CO3 dissociate to H2O and CO2, raising the luminal PCO2.This reaction is
catalyzed by carbonic anhydrase.
 Carbone dioxide diffuse into the cells, by reverse reaction H+ and HCO3- are
formed. H+ replaces those that enter the lumen.HCO3- diffuse across the
basolateral cell membrane with Na+ into the interstitial space, then absorbed
into peritubular capillaries.
6- Amino acids
 Amino acids are freely filtered at the glomerulus ,so they occur in the filtrate
at the same concentration in plasma(3 mmol/lit).
 They are reabsorbed by cotransport with Na+ at the luminal membrane.
220
7- Phosphate
 Phosphate is a breakdown product of protein metabolism .Its concentration in
plasma is 1 mmol/Lit.
 It is freely filtered at the glomerulus and cotransport with Na+ at luminal
border of the proximal tubule.
 An increase in phosphate concentration in plasma causes an increase in
phosphate excretion.
 Its reabsorption is regulated by hormone PTH and increased by calcitriol.
8- Potassium
 Potassium is filtered freely at the glomerulus and present in the filtrate at the
concentration equal to that in the plasma (4-5 mmol/Lit).
 It is reabsorbed passively into the cells of proximal tubule through the
paracellular pathway and active transport at the luminal border (figure10.11).
9- Calcium
 Plasma Ca2+ level is 2.5 mmol/Lit. About 40-50% of calcium is bound to
protein and cannot be filtrated by the glomerulus.
 The ionized form Ca2+ is freely filtered by glomerulus.
 Calcium is reabsorbed from the proximal tubule in parallel with Na+ and
water, so Ca2+ enters the cells passively down its electrochemical gradients
and leaves the cells by Ca2+/Na+ countertransport or by Ca2+ ATPase
mechanism.
Figure (10.11): Reabsorption of different ions and substances by proximal cells (Marieb
E.N. and Hoehn K. Human Anatomy and Physiology . San Francisco, Pearson Education Inc.,
2006).
10- Urea
 Urea is the product of protein metabolism .Its concentration in plasma is 2.5-
7 mmol/Lit.
 It is freely filtered .About 50% of it is reabsorbed by the end of proximal
tubule.And ions reabsorption increases urea concentration in the lumen of
tubule; therefore it diffuses out of tubule down its concentration gradient.
221
11- Organic cations and anions
 Proximal tubule secrets organic cations and anions ,some of which are the
end products of metabolism that circulate in plasma ,e.g., bile salt ,oxalate,
urate, prostaglandins and creatinine.
 The proximal tubule secrets exogenous organic compounds e.g.,(polycyclic
aromatic hydrocarbon)( PAH), which is used to determine renal plasma flow
and drugs such as penicillin, aspirin, morphine and quinine.
 Most of them are bound to plasma protein and cannot be filtered so
eliminated by secretion into the lumen.
2- Loop of Henle, distal tubule and collecting duct

Overview
 The part of the nephron after the proximal tubule can be divided into: the
thin descending and ascending limbs of loop of Henle, the thick
ascending limb, the early and late part of distal lobule and the collecting
duct.(Figure10.3).
 These tubules have different functional have different functional
characteristics but they have a common role (concentrating the urine).
 The descending limb has a high permeability to water and low solute
permeability (water moves across the descending limb into the interstitium
until osmotic equilibrium).
 The thin and thick ascending limbs have low permeability to water. The thick
ascending limb reabsorbs Na+ from the tubular fluid. It plays a major role in
the diluting the tubular fluid.
 The distal tubule and collecting duct reabsorb Na+ :
- In the presence of ADH , the late part of distal tubule and collecting duct
become very permeable to water. This allows water to move out until
reaching to the osmotic equilibrium.
 Urea plays an important role in concentrating process.
- The highest urea permeability is found in the inner medullary part of the
collecting duct.
- The thick ascending limb, distal tubule and cortical parts of collecting
duct have no permeability to urea but the thin limb of ascending and
descending of the loop of Henle are permeable to urea.
- Urea moves passively down its concentration gradients.
 The distal tubule and the collecting duct are important in the secreting K+, H+
and in reabsorption of Cl- and HCO3- .
Loop of Henle
 The descending loop has a high permeability to water and low permeability
to solutes.
- As the filtrate descends, the higher osmotic pressure causes the water to
suck out, but small quantities of NaCl can diffuse in.
222
- By the bottom of the loop the osmotic pressure of filtrate increases to
1200 mOsm.15% of the water is reabsorbed in the descending loop
of Henle, so the volume of filtrate is now only 20% of the original.
- In the thin segment of the ascending loop, the walls are not permeable to
water, so as it moves up through progressively lower salt concentrations,
some salt will diffuse out, to reduce its osmotic pressure. (Figure10.12.a)
- In the thick segment of the ascending loop, there are Na+ pumps (like in
the proximal tubule). Na+ is pumped out, while Cl- follows passively;
K+ also moves out by cotransport. This progressively dilutes the
filtrate (water will not be removed because the walls throughout the
ascending loop are not permeable). By the top of the loop (as the tubule
re-enters the cortex), the filtrate will be hypotonic (100 mOsm).
(Figure10.12.b).
a b
Figure (10.12): Reabsorption in the loop of Henle,a: reabsorption in the thin segment
of the ascending limb ,b:reabsorption in the thick segment of the ascending limb.
Companies, 2008).
 The descending loop thus loses water (and thus reduces its volume); the
ascending loop loses salt (no further change in volume).
223
Distal tubule
 Osmotic pressure of the filtrate is less than the surrounding plasma .Some
water diffuse out and some salt diffuse in to return osmotic pressure to 300
mOsm.
 Aldosterone acts in this section by activating Na+/K+ pump (Na+ moves
out, K+ moves in unlike loop of Henle).
Collecting duct
 There are two types of cells :
1- The principle cells reabsorb Na+ and secret K+ in the presence of ADH,
also reabsorb water.
2- The intercalated cells secret H+ and reabsorb HCO3-.
 As the collecting duct passes through the deepest layer of the medulla
(which have very high concentration of NaCl) the maximum reabsorption of
water occurs (by osmosis), raising the osmotic pressure of the filtrate to over
1200mOsm. (Figure10.13).
 In the presence of ADH, water passes through the cells from the lumen to
the interstitial fluid down the osmotic gradient.
Figure (10.13): Urine concentration mechanism along the nephron parts.( Seeley R.R.,
2008).
The countercurrent mechanism

 The kidney’s ability to establish an osmotic gradient rest primarily in the
loop of Henle, which folds back on itself to form countercurrent system .
 The salt removed from the ascending limb and used to concentrate the fluid
within the descending limb by creating hyper osmolar interstitium.
224
 Active transport of NaCl from the ascending limb of loop of Henle and
urea trapping within medullary interstitium are other factors that
countercurrent system depends on.
Urea trapping
 Urea contributes to the medullary concentrating gradients. It is freely
filtrated in the glomerulus and partially reabsorbed in the proximal tubule.
 The cortical and medullary portions of the collecting tubule are
impermeable to urea, whereas the inner medullary collecting tubules are
variably permeable to urea.
 In the presence of ADH ,urea concentration in the collecting tubules
becomes high due to removing of water through open channels.ADH
increases the permeability of inner medullary collecting tubule to urea
allowing more urea to diffuse into the medullary interstitium causing more
hypertonic medulla which enable further concentration of the urine.
Vasa recta
 Vasa recat is a capillary network that supplies the nephron.
 It has a hairpin configuration that prevents these vessels from dissipating the
concentration gradient.
 The vessels are efficient in exchange O2 and CO2 with the cells in then
deeper medulla.
 Large change in blood flow in the vasa recta can reduce or increase the
medullary interstitial osmolality beyond its normal value.
Potassium excretion
 Most potassium is intercellular (140mmol/Lit), while extracellular plasma
concentration is kept low (4 mmol/Lit) to maintain the resting potential of
the body cells.
 The distribution of Na+ and K+ between the intercellular and extracellular
compartments is maintained by Na+/ K+ ATPase pump which moves Na+ out
and K+ into the cells.
 The kidney plays a major role in the regulating K+ excretion in about 90%.
About 5-10% is lost in the faeces and sweat.
 Acute renal failure results in hyper kalmia due to decrease ability of the
kidney to excrete K+ due to decrease ability of the kidney to excrete K+.
 Proximal tubule reabsorbs 80% of K+.
 Distal tubule and collecting tubule secret K+, and aldosterone increases the
activity of Na+/ K+ pump ,increasing the intercellular concentration of K+
and pumping Na+ out of the cells .
 Potassium is also regulated by flow rate of tubular fluid and changes in acid-
base balance.
225
Pharmacology note: Several drugs can affect K+ distribution, e.g., digitalis
which is used in the treatment of congestive heart failure and overdose impairs
the Na+,K+ ATPase and may cause sever hyperkalemia (due to inability of K+ to
be moved intercellularly. Insulin and albuterol (a β2-receptor agonist ),used to
treat sever hyperkalemia .They can shift K+ to intercellular location.
Renal regulation
1. The sympathetic nonadrenergic fibers supply the afferent ,efferent
arterioles and tubules
 A strong increase in the renal sympathetic causes vasoconcentraction to the
arterioles by the baroreceptors reflex and renal blood flow decreases.
Although the GFR is autoregulated but it may fall.
 An increase in the renal sympathetic activity results in direct increase
reabsorption of Na+ by the proximal tubule.
 An increase in sympathetic activity stimulates rennin secretion and
angiotensin II production.
 A reduced renal sympathetic stimulation results in an opposite effect.
2. Renin-angiotensin system
 Renin is an enzyme that is synthesized, stored and secreted in a specialized
region (the juxtaglomerular apparatus).(Figure10. 5. b).
 Renin is stimulated by 3 factors:
1- Increased renal sympathetic activity
2- Reduced renal perfusion pressure.
3- Decreased NaCl delivery to the macula densa (distinct cells of the
distal tubule that are close to the afferent, efferent arterioles and
Bowman’s capsule) .These cells respond to change in the composition
of the tubular fluid.
 Renin cleaves the angiotensin I from angiotensinogen .Angiotensin I is
then converted to angiotensin II by angiotensin converting enzyme
(ACE) in the vascular endothelium.
 Angiotensin II has the following effects:
1- I t causes vasoconcentraction
 In the systemic circulation, it increases arterial blood pressure.
 In the kidneys, it constricts the efferent arterioles raising the
pressure in glomerular capillaries and help in GFR.
2- It stimulates Na+ reabsorption by the proximal tubule the Cl- and water.
3- It stimulates the aldosterone secretion by the adrenal cortex.
4- It stimulates ADH secretion from the posterior pituitary gland.
5- It stimulates thirst by an action on the brain.
 Angiotensin II has a negative feedback effect on rennin secretion.
226
3. Prostaglandins
 Prostaglandins are localized hormone .Their synthesis is increased by renal
sympathetic activity, when angiotensin II levels are high and when rennin
release is stimulated.
 Renal prostaglandins are vasodilator help to prevent excessive reduction in
renal blood flow.
4. Aldosterone
 Aldosterone is a hormone synthesized and secreted by the adrenal cortex.
 It is stimulated to release when the concentration of angiotensin II and
plasma K+ increase.
 It acts within the kidney to stimulate Na+ absorption and K+ secretion by the
distal tubule and collecting duct.
5. Atrial Natriuretic Peptide

 Atrial natriuretic peptide (ANP) is a polypeptide hormone synthesized
and released by the myocardial cells of the atrium.
 ANP tends to oppose the rennin-angiotensin system action:
1- Vasodilatation within the kidney.
2- Inhibition of aldosterone secretion.
3- Inhibition of ADH.
6. Antidiuretic Hormone(ADH)
 ADH is released from the posterior pituitary gland.
 Its secretion is stimulated by an increase in plasma osmolality and decrease
in the arterial blood pressure.
 ADH has the following effects:
1- Vasoconstriction of arterioles of the systemic circulation (including the
kidney) by acting on vasopressin V1 receptors.
2- It increases water reabsorption by the kidney (↑water permeability of the
collecting duct).
3- It increases the urea permeability of the medullary portion of the
collecting duct.
7. Parathyroid Hormone(PTH)
 Parathyroid hormone (PTH) is secreted by the parathyroid gland.
 It secretion is stimulated by decrease in the concentration of plasma Ca2+ .
 PTH stimulates the production of calcitriol which increases Ca2+, phosphate
absorption from the gastrointestinal tract and stimulates bone reabsorption.
 In the kidney, PTH stimulates Ca2+ reabsorption by the thick ascending limb
of loop of Henele and distal tubule, raising the Ca2+ plasma level.
227
Urine collection and Micturition
Passage of urine from kidney to bladder
Overview
 Urine moves from the collecting ducts of the renal tubules to the renal
pelvis by hydrostatic pressure.
 Urine moves from the pelvis into the ureter by the smooth muscles
contraction.
 The peristaltic wave which propagates along the ureters length propels
urine into the bladder to store the urine.
Micturition
 The flow of urine to the urinary bladder is relatively continuous.
 The urinary bladder acts as a reservoir for urine until it can be eliminated at
appropriate time.
 The bladder can distend to accommodate the large volume of fluid .The
maximum volume it can contain is 1L, and discomfort begins when urine
volume exceeds 500ml.
 The capacity of the urinary bladder to distend is due to the following factors:
1- The walls of the bladder contain large folds, which unfold to enlarge the
lumine of the urinary bladder.
2- The lining of urinary bladder is stretchable transitional epithelium.
3- Smooth muscle wall of the urinary bladder stretch to accommodate the
fluid volume.
 The bladder expands as the urine flows into it , but the internal pressure does
not increase(because its structure) until the bladder volume becomes large.
Micturition reflex
 Micturition reflex is activated when the bladder wall is stretched resulting in
elimination of urine from the urinary bladder (micturition).
 Integration of the micturition reflex occurs in the sacral region of the spinal
cord and modified in the pons of cerebrum.(Figure 10.14).
 When urine fills the bladder stimulates stretch receptors which produce
action potential.
 Action potential is carried by sensory neurons to spinal cord through the
pelvic nerves.
 Action potential is carried to the bladder through parasympathetic fibers
- Parasympathetic stimulation causes contraction of smooth muscles of
the bladder and decrease somatic motor action potentials causing the
external urinary sphincter to relax.
 Urine flows from the bladder to the urethra by increase the pressure.
 The micturition reflex produces a series of contractions of the urinary
bladder.
228
Figure (10.14): Control of micturition. (Marieb E.N. and Hoehn K. Human Anatomy and
Regulation of micturition
 Ascending pathways carry an increased action potential up the spinal cord
to the pons and cerebrum when the bladder becomes stretched .This
increases the conscious urge to urinate.
 Descending pathways carry the action potential to the sacral region of the
spinal cord to inhibit micturition reflex to prevent automatic urination when
bladder is full.
Pathology note: Renal failure results from any condition that interferes with
kidneys function. Acute renal failure is an extensive kidney damage lead to
accumulate urea in the blood and acidosis. It results from acute glomerular
nephritis, damage of tubules and some poisons. In complete renal failure death
occurs in 1-2 weeks. Chronic renal failure is when many nephrons are
permanently damaged and the remaining functional nephrons cannot
compensate. It results from chronic glomerular nephritis, trauma to the kidney,
congenital abnormalities or tumor and kidney stones. Chronic renal failure
causes the GFR to decrease and the kidneys lose their ability to excrete the
metabolic waste products and accumulation the solute in the body fluids
resulting in water retention and edema.
229
Anatomical considerations of the ureters, urinary bladder
 Ureters are tubes extend from the kidney to the urinary bladder .They extend
inferiolrly and medially from the renal pelvis at the renal hilum of each
kidney to reach the urinary bladder.
 Urinary bladder is a hallow muscular container that lies in the pelvic cavity,
posterior to the symphysis pubis.
 The ureters enter on its posterolateral surface.
 The urethra transports urine to the outside of the body .It exists the bladder
inferiorly.
 The triangular area of bladder’s wall between the two ureters posteriorly is
called trigone which is histologically distinct from other
region.(Figure10.15.b).
 The walls of ureters and the bladder are lined with:
- Transitional epithelial mucosa.
- Smooth muscle muscularis (stimulated to contract by parasympathetic
fiber)
- Fibrous connective tissue adventitia.
 The outlet of the bladder into the urethra is graduated by two sphincters:
1. Internal sphincter involuntary sphincter of smooth muscle.
2. External sphincter is skeletal muscle surrounds the urethra as it extends
through the pelvic floor. It acts as a valve that controls the flow of urine
through the urethra.
Figure (10.15): Basic structures of urinary bladder and urethra. (Marieb E.N. and Hoehn
K. Human Anatomy and Physiology . San Francisco, Pearson Education Inc., 2006).
230
- In male, the urethra has three regions (Figure 10.15.a):
1. Prostatic urethra: runs within the prostate gland
2. Membranous urethra : runs through the urogenital diaphragm
3. Spongy urethra: passes through the penis and opens via the external
urethral orifice.
- In female, it is shorter than in male and opens into the vestibule anterior
to the vaginal opening.
Diuretics
 Diuretics are agents that increase the rate of urine formation.
 Diuresis is an increase in urine volume with loss of water and solutes.
 Mechanism of action:
- Diuretics are ions transport inhibitors that decrease the reabsorption of
Na+ at different site of nephron.
- Sodium and other ions (Cl-) enter in greater amounts than normal along
with water to maintain osmotic equilibrium.
 Diuretics are used to treat different disorders such as hypertension, several
types of edema and liver cirrhosis.
 The use of diuretics may cause complications such as electrolytes imbalance
and dehydration.
 There are different classes of diuretics act at different sites of nephron
(table10.1), because each class interacts with luminal sodium transport.
Table ( 10.1 ):Different classes of diuretics. (Brown T.A. Rapid Review of Physiology.
Philadelphia, Mosby, 2012).
Class of diuretics Site of action Mechanism Clinical uses
Carbonic anhydrase Proximal convoluted ↑bicarbonate High altitude
inhibitors tubule excretion sickness
,glaucoma
Thiazide diuretics Distal convoluted ↓activity of Na+,Cl- Hypertension,
(HCTZ metolazone) tubule cotransporter diabetes
insipidus
K+ sparing diuretics Collecting tubule ↓NO.of open Na+ Liver cirrhosis
channels in the tubular
cells
Loop diuretics Loop of Henle ↓Na+-K+-2Cl- in the Pulmonary
(furosemide) thick ascending loop of edema
Henle associated with
congestive
heart failure
Osmotic Osmotic diuresis Cerebral

diuretics(mannitol) edema
231
Body fluid regulation
Overview
 Water balance is regulated by mechanisms that prevent the large change in
plasma osmolality.
 Plasma osmolality (concentration of body fluid) is measured in terms of the
amount of dissolved substances per unit mass of water (it is given in unit
mol/kg).
 Plasma osmolality is determined by plasma Na+ concentration.
 Na+ balance is regulated by mechanism that prevents large change in
extracellular fluid volume (ECV).
 Change in Na+ balance leads to changes in the ECV not in osmolality.
 Plasma osmolality is regulated by changes in water intake and excretion,
whereas Na+ balance is regulated by changes in Na+ excretion.
Regulation of body fluid osmolality

 Water is lost from the body by :
 Breathing
 Sweating
 In faeces
 Via the kidney, the most important to keep plasma osmolality constant.
 Water is provided for the body by drinking and by water content in the food.
- The fluid ingested by drinking is regulated by sensation of thirst.
- Osmoreceptors play a major role in the regulation of water by kidneys
and thirst.
- ADH regulates water excretion and osmolality.
- Osmoreceptors respond to change in plasma osmolality by shrinking or
swelling, resulting in change in ADH output from the posterior pituitary
gland.
 An excessive loss of water from the body leads to increase plasma osmolatity
and the osmoreceptors stimulate secretion of ADH(which conserves water)
and cause sensation of thirst.
Regulation of extracellular fluid volume

 An increase in ECF volume results in an increase in ANH secretion and
decreases in aldosterone, ADH and sympathetic stimulation of afferent
arterioles.
Regulation of intracellular fluid composition

 Large molecules e.g., proteins are synthesized within the cells and influence
the concentration of solutes inside the cells.
 Electrolytes’ concentrations are determined by transport mechanism and
electrical charges.
 Water movement across the plasma membrane is controlled by osmosis,
which is affected by the changes of concentration of solutes in the
extracellular and intracellular fluids.
232
Regulation of acid –base balance
 The maintenance of H+ concentration within narrow range is essential for
normal metabolic reactions, because H+ affect the activity of many enzymes
and chemical reactions within the body.
 The mechanisms that regulate the H+ concentration are: buffer systems,
respiratory system and the kidneys
Acids and bases

 Acids are substances that release H+ into a solution, while base binds to H+
and removes them from the solution.
 Acids and bases are either strong or weak .Strong acids dissociate
completely to form ions in the solution. Weak acids dissociate partially.
Equilibrium is established between that acid and the forms ions.
 Weak acids are common in living system because they play an important role
in the preventing significant changes in the body fluid PH.
 Buffer systems resist changes in the PH of solution .Buffer within the body
fluids regulate PH by binding to excess H+ or by releasing H+ when H+
concentration decreases.
 There are several buffer systems function together to resist PH changes of
body fluids :
1- Carbonic acid /Bicarbonate buffer system

 Carbonic acid H2CO3 is weak acid dissolved in water :
H2CO3 HCO3- + H+
The carbonic acid /bicarbonate buffer system depends on the equilibrium
that is established between H2CO3 and (H+, HCO3-).
 Adding of H+ to the solution leads to a large portion of H+ binds to HCO3-
to form H2CO3 .On the other hand if H+ are removed from a solution
containing H2CO3, more H2CO3 dissolves to form HCO3- and H+. Thus
the large PH change is resisted.
2- Protein molecules buffer system

 They provide three fourths of the buffer capacity.
 Hemoglobin is one of the most important intracellular proteins.
 The capacity of these proteins is due to the functional groups of amino
acids e.g., carboxyl and amino groups ,which act as weak acids and base:
- AS the H+ concentration increases, more H+ ions bind to the
functional groups. When H+ decreases, more H+ ions are released
from the functional group.
3- Phosphate buffer system

 Phosphate containing molecules e.g., DNA, RNA, ATP and HPO4-2 in
solution act as buffers.
 Phosphate ions act as weak acids can bind to H+ to form H2PO4 when H+
increase and release H+ when these ions decrease.
233
Respiratory regulation of acid- base balance
 Carbon dioxide reacts with H2O to form H2CO3.This reaction is catalyzed by
carbonic anhydrase in the RBCs.
 Many H2CO3 dissocite to form H+ and HCO3-.
 Increased CO2 leads to decrease PH and decreased CO2 leads to increase PH.
 Deceased PH in the body fluid stimulates respiratory center to increase the
rate and the depth of ventilation (hyperventilation) in order to eliminate the
excess CO2 from the body and reducing H+ resulting from dissociation of
H2CO3.
 Increased PH in the body fluid causes hypoventilation to increase the level
of CO2 and H+.
Clinical note: Respiratory Acidosis: when PH value of the body fluid is less than
7.35, while respiratory alkalosis when PH of body fluid is more than 7.45. Both
respiratory acidosis and alkalosis are due to respiratory abnormalities.
Metabolic acidosis or metabolic alkalosis is caused by cases other than respiratory
abnormalities. Metabolic acidosis characterized by abnormal low HCO3- in
systemic arterial blood .Loss of HCO3- results from severe diarrhea or renal
dysfunction.
Metabolic alkalosis is characterized by abnormal high HCO3- in systemic arterial
blood. It is caused by non-respiratory loss of acid, vomiting of acidic stomach
contents, gastric suctioning, excessive intake of alkaline drugs (antacids), use of
certain diuretics and severe dehydration.
Renal regulation of acid- base balance

 Renal tubules regulate acid base balance by increasing or decreasing the H+
into the filtrate and HCO3- reabsorption.
 Carbonic anhyrase in the nephron cells catalyzes the formation of H2CO3
from CO2 and H2O.
 Secretion of H+ into the filtrate by antiport mechanism in exchange for Na+
causing to decrease PH of the filtrate.
 Bicarbonate ions move into the interstitial fluid and then diffuse into the
capillaries.
 In the capillaries HCO3- combine with H+ causing to decrease the H+
concentration and increase blood PH.
234
References
2. Davies A., Blakeley A.G.H. and Kidd C. Human Physiology. International edition,
London, Churchill Livingstone, 2001.
3. http//:www.studyblue.com
Pearson Education Inc., 2006
235
Chapter eleven
Digestive system 11
Digestive system
Overview
 The digestive system also called gastrointestinal system consists of an
alimentary canal and accessory organs (salivary glands, tongue, teeth,
liver, gallbladder and pancreas).
 The system is responsible for mechanical and chemical breakdown of food to
smaller molecules to be absorbed into the circulation and used by the body
cells.
Functions of digestive system

1- Ingestion is taking the food into the stomach.
2- Mastication: food is chewed by the teeth to break the large food particles
into smaller with larger surface area for the enzymes to work.
3- Propulsion is the movement of food from one part to other of the digestive
tract, by peristaltic waves. Peristalsis is done by muscles contractions.
4- Mixing is mixing the food particles with digestive secretion to break them
into smaller pieces.
5- Secretion is to lubricate, liquefy and digest the food.
 Mucus is secreted along the entire tract to protect the epithelial cells of
the tract from the damaging effect of acid stomach and digestive
enzymes.
 Water secretion is to liquefy the food and make it easier to digest.
 Liver secretions break the large fat droplets into smaller droplets to
facilitate the digestion and absorption of fat.
 Enzymes secreted by the oral cavity, stomach intestine and pancreas
break the large particles of food into smaller particles to be absorbed by
the intestinal walls.
6- Digestion
 Mechanical digestion: is breakdown the large food particles into smaller
ones.
 Chemical Digestion: is the breakdown of covalent chemical bonds in
organic molecules by digestive enzymes.
7- Absorption is the passage of food from the digestive tract into the
circulation. This requires diffusion, facilitated diffusion, active transport and
endocytosis.
8- Defecation is elimination of waste products of digestion from the body in
form of semi solid (feces).
236
Regions of digestive system. (Figure 11.1).
 Mouth has salivary glands, teeth and tongue.
 Pharynx with tubular mucus glands.
 Esophagus with tubular mucus glands.
 Stomach which contains glands and mucous cells.
 Small intestine consists of duodenum, jejunum and ileum with accessory
organs (liver, gallbladder and pancreas).
 Large intestine includes the, colon, rectum and anal canal with mucous
glands.
 Anus
Figure (11.1): Digestive system regions. (Marieb E.N .Essential of Human

Oral cavity
 Oral cavity is called buccal cavity. It involves in the ingestion process.
 The digestive function is associated with its accessory organs e.g., teeth,
salivary glands and tongue.
 It has a propulsive process to push the food through the pharynx and
esophagus into the stomach.
Teeth
 Teeth are special structures in the mouth that break down food physically by
chewing and grinding (mastication).
 There are 32 teeth on 2 jaws in adults, in which each jaw consists from the
front of: 2 pairs of incisors, 1 pair of canines, 2 pairs of premolars and 3
pairs of molar teeth.
 Incisors are designed to cut the food, while premolars and molars having a
flattened surface are used to grind the food.
237
Tongue
 Tongue is a muscular organ that contains receptors called taste bud.
 The taste buds help in taste sweet, salt, sour and bitter sensations.
 The tongue is involved in speech, mastication and moving the food around
the mouth and swallows it.
 It has intrinsic and extrinsic skeletal muscle fibers. The intrinsic one is to
change the shape of the tongue while the extrinsic is to move the tongue.
 The interior two thirds is covered with different papillae :
1- Filiform papillae give the rough surface to licking semisolid food and
provide friction to manipulate it.
2- Fungi form papillae, vallvate papillae and foliate papillae which house
taste buds. (Figure 11.2 ).
Figure (11.2): Different types of papillae on the tongue

surface. Retrieved from :www.authorstream.com
The palate
 The palate forms the roof of the mouth .It has 2 distinct parts :
1- Hard palate is bony structure separate the mouth from the nasal cavity.
2- Soft palate is a mobile fold formed of skeletal muscle that rises
reflexively to close the nasopharynx during swallowing.
 The muscular structure that projects downward from the free edge of
the soft palate is the uvula which prevents food from entering the
nasopharynx during swallowing.
Salivary glands
 There are three pairs of glands that secret saliva.
1- Parotid gland lies anterior to the ear.
2- Sublingual gland lies beneath the tongue.
3- Submandibular gland lies underneath the chin.
 Saliva has several functions:
1- It cleans the mouth.
238
2- It dissolves food chemicals to be tasted.
3- It moistens food to compact it in a bolus.
4- It contains enzymes for chemical breakdown of starchy food.
 Saliva has high watery content (97-99%).It is hypotonic and PH is 6.7-7.
 Its solute includes:
 Electrolytes Na+, K+, Cl- and HCO3-
 Organic components such as:
1- LgA antibodies to give a protection against bacteria
2- Lysozymes
3- Salivary amylase digests the starch (polysaccharides to disaccharides).
4- Mucoprotein is to lubricate the oral cavity and hydrate foodstuff.
 Food is chewed and mixed with saliva to form a bolus (lump of food) which
is easier to swallow and pass the pharynx.
 Pharynx is the tube that carries the food to the esophagus.
 When bolus is swallowed, muscle action causes epiglottis to close over
larynx.
Regulation of salivation
 Salivary secretion is under control of parasympathetic and sympathetic
nervous system.
1- Parasympathetic stimulation increases watery output and enzyme-rich
saliva.
2- Sympathetic division causes release of mucin rich saliva.
 Strong stimulation inhibits saliva release (dry mouth).
 Fear and fatigue reduce nerve activity and secretion.
Esophagus
 Esophagus is the muscular tube that extends from the pharynx to the
stomach.
 It is about 2.5 cm long, lies in the mediastinum, posterior to the trachea.
 It transports food from the pharynx to the stomach.
 The movement of the materials is regulated by the upper esophageal
sphincter (at the upper end) and lower esophageal sphincter (at the lower
end).
 The esophagus consists of an adventitia, muscular layer, submucosal layer
(with mucous glands) and stratified squamous epithelium.
Steps of swallowing
1- Buccal phase: Tongue pushes the bolus against soft palate backing the
mouth and triggering swallowing reflex.
2- Pharyngeal phase: Relaxing the upper esophageal sphincter, epiglottis
closes to prevent swallowed material from entering the airways.
3- Esophageal phase: Food moves downward into the esophagus by peristaltic
movement and by gravity help (figure 11.3).
239
Figure ( 11.3 ): Steps of swallowing .Modified from : (Marieb E.N. and Hoehn K. Human
Stomach
Anatomical and histological considerations
 Stomach is the enlarged part of the digestive tract that receives the food from
the esophagus.
 It lies in the left superior part of the abdomen.
 The opening between the esophagus and the stomach is esophageal or
cardiac opening which surrounded by cardiac sphincter.
 The part to the left of the cardiac part is the fundus (figure 11.4.a).
 The largest part of the stomach is the body which turns to the right to form a
greater curvature and lesser curvature to the left.
 The narrow part of the body is the pyloric part. The wide part of the pyloric
part is the pyloric antrum while the narrow part is the pyloric canal which
opens into the small intestine through the pyloric orifice, which surrounded
by pyloric sphincter.
 The wall of the stomach consists of the following:
1- An external serosa.
2- A muscle layer (longitudinal, circular and oblique) (Figure11.4.b)
3- Simple columnar epithelium (surface mucous cells),which function as:
 Protection the stomach walls from being damaged by acidic secretion
and digestive enzymes.
 Producing an alkaline mucous to neutralize the acidity and as a
barrier to the digestive enzymes.
 The mucous membrane that lining the stomach contains rugae which
disappear when the stomach fills with food.
240
 The epithelium forms numerous gastric pits, which are opening to the
gastric glands.
 Gastric glands contain:
1- Mucous neck cells produce mucus.
2- Parietal cells produce hydrochloric acid and intrinsic factor.
3- Chief cells produce pepsinogen.
4- Endocrine cells produce regulatory hormones.
Figure (11.4): a-anatomy of the stomach, b-Stomach wall.( Seeley R.R., Stephens T.D.
241
Function of the stomach
 Store food: Food is temporarily stored in the stomach, and then released
gradually into the duodenum, because presence of rugae makes it able to
expand.
 Mixing the food with enzyme: Food is mixed with stomach secretion to
form the chyme (semi liquid material).
 Secretion: Such as mucus, HCl, gastrin, histamine, intrinsic factor and
pepsinogen.
- Intrinsic factor: is a glycoprotein that binds to vitamin B12 to make it
ready to be absorbed by the ileum.B12 is required in production of RBCs.
- Hydrochloric acid: results in low PH (1-3), which kills microorganisms
and activates pepsin.
 Hydrogen formed from O2 and H2O enters the parietal cells.
 Carbonic anhydrase inside the cells catalyzes reaction between the
CO2 and H2O to form H2CO3, which dissociate to form H+ and HCO3-
 H+ transported actively by proton pump (H+- K+ pump) into the lumen
of the stomach.
 Chloride ions diffuse with H+ from the cells (to reduce the energy
required to transport H+ against the concentration gradient).
 HCO3- is exchanged for Cl- down the concentration gradient and Cl-
enters the cells.(Figure 11.5).
Figure (11.5): Production of HCl by the parietal cell. Retrieved from:

tube.medchrome.com
242
 Pepsinogen is secreted by the chief cells and split by HCl into smaller active
molecules (pepsin). Pepsin starts protein digestion by cleavage of some
covalent bonds in the protein to break them into polypeptides chains.
 Endocrine cells secret gastrin and histamine.
Regulation of secretion function

Regulation of stomach secretion is divided into three phases:
1- Cephalic phase, (figure 11.6)
 The tastes, smell, thinking of foods activate the hunger center in the
medulla oblongata.
 Action potentials are sent from medulla oblongata along the
parasympathetic neurons within vagus nerves to the stomach to activate
enteric plexus neuron.
 Postganglionic neurons stimulate parietal cells, chief cell and endocrine
cells.
 Gastrin is carried through the circulation to the stomach again to
stimulate secretion of HCl and pepsinogen.
Figure (11.6): Cephalic phase Figure (11.7): Gastric phase

Companies, 2008).
2- Gastric phase
 Distention of the stomach walls stimulates the stretch receptors and
parasympathetic reflex. Action potentials are carried by vagus nerve to the
medulla oblongata.
 Medulla oblongata increases action potential to stimulate parietal cells,
chief cells and endocrine cells.
 Activation the local reflexes to increase stomach secretion.
 Gastrin travels through the circulation backing to the stomach to stimulate
additional secretion. (Figure11.7).
243
3- Intestinal phase
 Small quantities of chyme are released into the duodenum, at intervals,
through the pyloric sphincter valve.
 Acidic chyme in the duodenum (PH<2)or lipid content inhibits gastric
secretion by several mechanisms:
 Stimulation the chemoreceptors by increased H+ concentration or
lipid. Chemoreceptors generate action potentials which travel to the
medulla oblongata where they inhibit parasympathetic stimulation to
decrease gastric secretion.
 H+ or lipids activate local reflexes to inhibit gastric secretion.
 Secretin secretion inhibits gastric secretion by inactivation parietal
cell and chief cells. Cholecystokinin (CCK) inhibits gastric
secretion. (Figure 11.8).
Figure (11.8): Intestinal phase. (Seeley R.R., Stephens T.D. and Tate P.
Pharmacology note: Gastric acid secretion Inhibitors: there are H2 receptors

(histamine receptors on the parietal cells different from H1 receptors involved in
allergic reactions). Drugs that affect allergic reaction do not affect stomach acid
secretion. Cimetidine (Tagamet) and ranitidine (zantac) are histamine receptors
antagonists that prevent the binding of histamine to the receptors on parietal
cells.These drugs are effective inhibitors of gastric acids secretion .Cimetidine is
used to treat increased gastric acid secretion resulting from gastritis and gastric
ulcer.
Gastric motility
1- Gastric filling
 Relaxation of the proximal segment of the stomach (fundus and the
proximal portion of the body) to receive the food bolus.
 Swallowing a bolus of food triggers a vasovagal reflexes which causes
the lower esophageal sphincter to open and proximal segment to dilate
(receptive relaxation).
244
2- Mixing of stomach contents is accomplished by:
 Mixing wave to break the food into smaller pieces and mix it with the
gastric secretion. Wave contraction occurs every 20 seconds proceeding
from the body of the stomach toward the pyloric sphincter. It is 80% of
the contraction.
 Peristaltic waves are more powerful than mixing wave and less
frequently. They force the chyme toward the pyloric sphincter. It is 20%
of the contraction.
 Gastric contraction is increased by parasympathetic stimulation and
hormones (gasterin and motlin).While sympathetic stimulation and
hormones secretin and gastric inhibitory peptides (GIP) decrease the
contraction.
3- Emptying of stomach
 Stomach is empty within 3-4 hours after the meal.
 The pyloric sphincter remains partially closed. The peristaltic
contractions are able to push a small amount of chyme through the
pyloric opening and duodenum by pyloric pump.
 Emptying of stomach is regulated by hormones and nervous mechanisms:
1- Hormones: Fats in the duodenum stimulate the releasing of GIP
which decreases peristaltic contraction and slowing the passage of the
chyme into the duodenum.CCK is the major inhibitory hormone of
the gastric motility.
2- Nervous mechanism: The receptors in the duodenal mucosa are
sensitive to the distention and acidity; therefore the impulses along
sensory and motor fibers in the vagal nerves cause reflex inhibition to
the peristaltic contraction.
Pharmacology note: Metoclopramide is a D2 receptor antagonist and 5-HT3

antagonist which is prokinetic agent used in treatment of nausea and vomiting in
patients who have delayed gastric emptying (gastroparesis).
Clinical note: Patients with long uncontrolled diabetes mellitus may develop sever
dysfunction of gastric motility (gastroparesis) which occurs as a result of damage
to the autonomic nerves that supply the stomach.This makes the patients suffer
from nausea and vomiting.In this case, Metoclopramide can relief the symptoms.
Small intestine
 Small intestine is a convoluted tube extends from the pyloric sphincter to
the ileocecal valve where it joins the large intestine.
 It is where the greatest amount of digestion and absorption occur.
 It consists of three parts: Duodenum is about 25 cm long ,jejunum (2 m
long)and ileum(3.5 m).(Figure 11.9).
245
 There are two major accessory glands associated with duodenum: liver and
pancreas.
Figure (11.9): Parts of small intestine. (Marieb E.N. and Hoehn K. Human Anatomy
and Physiology . San Francisco, Pearson Education Inc., 2010).
Duodenum
 Duodenum is the first part of the small intestine, curves around the pancreas.
 The bile duct (that deliver the bile from the liver) and pancreatic duct (that
carries the pancreatic juice) unit in the hepatopancreatic ampulla.
 The hepatopancreatic ampulla opens in to the duodenum via the major
duodenal papillae.(Figure 11.11).
 The entry of bile and pancreatic juice is controlled by the hepatopancreatic
sphincter.
 The mucosa and submucosa in the surface of the duodenum form structural
modifications to increase the efficiency of digestion and
absorption(figure11.10 ):
1- Circular folds (plicae): permanent folds of the mucosa and submucosa,
about 1cm long .These structures force the chyme to spiral through the
lumen and slow the movement to allow more time for absorption.
2- Villi: finger like projections of mucosa, about 0.5-1.5 mm in length. Each
villus is covered by simple columnar epithelium and contains blood
capillary network and lymphatic capillary called lacteal. (Figure11.10).
3- Microvilli: cytoplasmic extensions from the cells that make up the villi
surface. These are for further increase the surface area. These microvilli
on the entire epithelial surface form the brush border.
 There are four types of cells in the mucosa of the duodenum:
1- Absorptive cells: produce digestive enzymes.
2- Goblet cells: produce protective mucus.
3- Granular cells: protect the intestinal epithelium from bacteria.
4- Endocrine cells: produce regulatory hormones.
 The epithelial cells are produced within the invaginations of the mucosa,
called (crypst of Lieberkuhn) at the base of the villi.
 The tubular mucous glands in the submucosa are called Brunner gland.
246
Figure (11.10): Histological modifications in the small intestine. (Marieb E.N.and Hoehn
Jejunum and ileum

 Jejunum and ileum show decreasing in the diameter, wall thickness, number
of folds and villi.
 They hang in the central and lower part of the abdominal cavity suspended
from the posterior abdominal wall(mesentery)
 These two parts are the major site for absorption.
 There are numerous lymphatic nodules called Peyer‟s patches which have
immune function against microorganisms entering the mucosa.
Small intestine secretions

 The secretion produced by the mucosa of the small intestine contains:
mucus, electrolytes (HCO3- neutralize the PH) and water.
 The intestinal secretions lubricate and protect the walls of small intestine
from the digestive enzymes and acidic chyme. They also keep the intestinal
contents in a liquid form.
 Secretions from the intestinal mucosa, liver and pancreas enter the small
intestine to do their digestive functions. Most digestive enzymes are
produced by the pancreas.
 Intestinal mucosa release secretin and CCK to hepatic and pancreatic
secretion.
 Enzymes of the intestinal mucosa are surface bond enzymes attached to
microvilli. These enzymes are:
1- Disaccharidase: breaks down the disaccharides to produce
monosaccharides.
2- Peptidase: hydrolyzes the peptide bonds between the amino acids in
polypeptide chains.
247
 Break down products of digestion are absorbed through the microvilli and
enter the circulation.
 Vagus nerves, secretin and chemicals or tactile sensation of the duodenal
mucosa stimulate the duodenal glands and goblet cells.
 The chyme takes 3-4hours to move from the pyloric region to the ileocecal
junction.
Intestinal motility
 There are two kinds of movement of the intestine:
1- Segmental contraction: is accomplished by smooth muscle in the walls
of the small intestine. It is propagated for short distance .It mixes the
intestinal contents.
2- Peristaltic contraction: propel the contents along the digestive tract.
They are continuations of peristaltic contraction in the stomach.
Clinical note: Duodenal glands secretion is inhibited by the sympathetic stimulation,

resulting in reducing the protective mucous layer on the duodenal wall.Therefore
the person who is highly stressed and has an elevated sympathetic activity may
illustrate more susceptibility to duodenal ulcer.
Regulation of the intestinal motility

 Local mechanical and chemical stimuli are important in the regulating the
intestinal movement.
 Smooth muscle contraction due to distention of intestinal walls, acidic
solution and presence of amino acids or peptides stimulate intestinal
contraction.
 Local reflex and parasympathetic stimulate contraction.
Pharmacology note: The antibiotic erythromycin is sometime used as a laxative in

constipated adults because its common side effects (nausea, diarrhea).It produces
these effects by stimulating the motilin receptors
Liver
 Liver is the largest organ in the body, about 1.36 Kg weight.
 It is located in the right upper quadrant of the abdomen.
 It consists of two major lobes: left and right and two minor lobes: caudate
and quadrate. (Figure 11.12 , a).
 A porta is the site where the vessels, ducts and nerves enter and exit the
liver.
 The bile is transported out of the liver by the hepatic duct.
 The right and left hepatic ducts unit to form common hepatic duct.
248
Pancreatic duct
Hepatopancreatic ampulla
Figure( 11.11):Anatomical structures of the liver and ducts system . (Marieb E.N. and Hoehn
K. Human Anatomy and Physiology . San Francisco, Pearson Education Inc., 2010).
Central vein
Figure(11.12):a:Lobes of the liver,b:Liver histology. (Seeley R.R., Stephens T.D. and Tate
P. Anatomy and Physiology . New York, McGraw –Hill Companies, 2008).
249
 Common hepatic duct joins the cystic duct (from gallbladder) to form
common bile duct which joins the pancreatic duct at the hepatopancreatic
ampulla.
 Hepatopancreartic ampulla empties into the duodenum at the major
duodenal papillae. (Figure 11.11).
 The liver is made up of millions lobules,each with a centarl vein and portal
triad at the corner (composed of hepatic duct,hepatic porta; vein and hepatic
artery ).(Figure 11.12 . b ).
 Hepatic cords radiate out from the central vein.
 Hepatic cord is composed of hepatocytes.The spaces between the hepatic
cords are the hepatic sinusoids which empty into the central vein.
Functions of the liver

1- Bile production :Liver produces and secrets the bile which play a role in
digestion by:
 Neutrilze and dilute the acidic chyme.
 Bile salts emulsify the fats.
 Bile contains bile pigment(bilurubin)from hemoglobin destruction.
 Bile contains cholesterol,fat and fat soluble hormones.
 Control of bile secretion and release is summerized in figure( 11.13).
2- Storage
 Storage of excess glucose in the blood in form of glycogen.Hepatocytes
control blood sugar by preventing hyperglycemia when the blood passes
from the intestine to the liver through the hepatic vein,and secret glucose
again to the circulation when needed.
 Storage of fats ,vitamins( A,B12,D,E and K),copper and ions.
3- Interconversion of the nutrients
 The liver converts some nutrients into other form (fructose into glucose).
 Ingested fats are combined with choline and phosphorus in the liver to
form phospholipids.
4- Detoxification
 Some ingested food produce harmful by-products when metabolized. The
liver detoxify these by-products by altering their structures to less
toxic,or eliminated easily e.g.,ammonia (by-product of amino acids
metabolism)into urea which is less toxic and secreted into the circulation
then eliminated by the kidney.
5- Phagocytic activity
 Phagocytic cells of the liver (kupffer cells) have the ability to
phagocyteize dying RBCs,WBCs and some bacteria entering the
circulation.
6- Synthesis of blood components
 Liver produces many blood proteins such as: albumins, fibrinogen,
globulins, heparin and clotting factors.
250
Clinical note: Hepatitis is the inflammation of the liver that results from alcohol
consumption or infection (viral infection).Hepatitis A is called infectious hepatitis,
hepatitis B is called serum hepatitis ,is more chronic infection and hepatitis C.It is
caused by one or more virus types which is spread by the blood transfusion and sexual
intercourse. If it is not treated ,liver cells die leading to loss of liver function and liver
failure.
1-Duodenum secrets
secretin which is carried
to the liver to stimulate
-
HCO3 into the bile.
2-CCK produced by the

duodenum is carried to
the gallbladder to
contract and release bile
into the duodenum.
3- Vagus nerve
stimulation to contract
and release bile into the
duodenum.
4-Bile salt stimulate bile

secretion
Circulation
Figure( 11.13): Bile secretion regulation.(Seeley R.R., Stephens T.D. and Tate P. Anatomy
Gallbladder
 Gallbladder is a small sac on the inferior surface of the liver.It stores the bile.
 Bile is secreted by the liver and flows to the gallbladder to store in about40-
70ml.
 Water and electrolytes are absorbed while salt and pigment become
concentrated.
 After a meal ,the gallbladder contracts in response to CCK and vagal
stimulation and secrets the bile into the small intestine.
Clinical note: Gallstone results from excess cholesterol in the bile due to high
cholesterol diet or high concentration of cholesterol in the gallbladder. Gallstones
may pass out of gallbladder and enter the cystic duct, blocking the release of bile.In
some cases they move down and block the pancreatic duct resulting in pancreatitis.
They must be removed surgically.
251
Pancreas
Anatomical considerations
 The pancreas is composed of both endocrine and exocrine tissues.
 It consists of a head in the curvature of the duodenum ,body and tail which
extends to the spleen.(Figure 11.14. a ).
 Endocrine part consists of ilets of Langerhans .The ilets cells produce:
1- Insuline which regulates blood glucose level.
2- Glucagon which is important in contrilling glucose and amino acids
levelin the blood.
3- Somatostatin hormone which regulates insulin and glucagon.
 Exocrine tissues composed of lobules that contain acini. (Figure11.14.b).
 The acini connect to a duct system that leads to pancreatic duct.
Figure (11. 14): a: Structure of the pancreas, b: histology of the pancreas. (Seeley R.R.,
2008).
252
Pancreatic secretion
 The exocrine secretions are called pancreatic juice, which delivered to the
duodenum through the pancreatic duct.
 The pancreatic juice is composed of :
- An aqueous component. This contains Na+, K+ and HCO3- that
neutralizes the acidic chyme entering the small intestine and activates
pancreatic enzyme.
- Enzymatic components:
1- Proteolytic enzymes: digest tyrosine, chymotrypsin and
carboxypeptides. They are secreted in inactive form to prevent digestion
of the tissues that producing them.
 Enterokinase is an intestinal enzyme produced in active form to
activate the trypsinogen to trypsin which activates more
trypsinogen and chymotrypsinogen.
2- Pancreatic amylase: digests polysaccharides.
3- Pancreatic lipases break down lipids into monoglycerides, free fatty
acids and cholesterol.
4- Deoxyribonucleases and ribonucleases break down DNA and RNA.
Regulation of pancreatic secretion.

 The pancreatic secretion is regulated by hormonal and neural mechanisms.
 An acidic chyme in the duodenum stimulates the release of secretin.
 Secretin stimulates the watery secretion of the pancreas which contains
HCO3- to increase PH of the chyme in the duodenum.
 Cholecystokinin released from the duodenum stimulates bile release from
the gallbladder and secretion of enzymatic components of the pancreas.
 Parasympathetic stimulation through vagus nerves stimulates the pancreatic
juice secretion, while sympathetic stimulation inhibits the secretion.
Clinical note:Pancreatitis is the inflammation of the pancreas that involves the

release of pancreatic enzymes within the pancreas which digest pancreatic tissues.It
may result from alcoholism,certain drugs viral infection and cancer.Its symptoms
range from mild abdominal pain to systemic shock.
Large intestine
Anatomical considerations
 Large intestine is the portion of the digestive tract that extends from ileocecal
junction to the anus.
 It consists of cecum, colon, rectum and anal canal. (Figure11.15).
 The chyme in the colon is converted to feces where it stored until eliminated
by defecation
253
Cecum
 Cecum is the first portion of the large intestine where the large intestine
meets the small intestine at ileocecal junction.
 It is attached to a small blind tube, about 9 cm long called vermiform
appendix, which its walls contain lymphatic nodules.
Figure (11. 15): Large intestine. (Seeley R.R., Stephens T.D. and Tate P.
Colon
 Colon is the second portion of the large intestine.
 It consists of ascending colon, transverse colon, descending colon and
sigmoid colon which ends at the rectum.
 The longitudinal muscle layer is incomplete and form three bands called
teniae coli that cause pouches called haustra when it contracts.
 The mucosa of the large intestine is simple columnar epithelium with tubular
glands called crypts.
Rectum
 The rectum is a muscular expandable tube begins at end of the sigmoid colon
and ends at the anal canal.
 Movement of fecal material into rectum triggers defecation urge.
Anal canal
 Anal canal is the last portion of the digestive tract that ends at the anus.
 It is surrounded by the internal sphincter (composed of smooth muscles) at
the superior end and external sphincter (composed of skeletal muscles) at
the end of the anal canal.
Large intestine motility

 Segmental movement is to mix the contents of the colon.
 Mass movement is to a strong contraction responsible for propel the colon
contents toward the anus.
254
 Local reflexes (gastro and duodenocolic reflexes) integrate mass reflexes,
which are mediated by :
1- Parasympathetic stimulation.
2- Hormones (CCK, gastrin).
3- Thoughts or smell of food; movement of the chyme into the duodenum
stimulate large intestine movement.
Defecation
 Defecation is the elimination of feces by reflexes activity.
 It requires relaxation of the internal and external sphincters.
 Movement of the feces from the colon into the rectum stimulates the
defecation reflexes.
 Feces is formed by water and salt reabsorption, secretion of mucus and action
of the microorganisms.
 About 1500 ml of the chyme enters the cecum each day and 90% is
reabsorbed.
Defecation reflexes
 The feces in the rectum stimulate local reflexes.
 Action potential is produced and propagated to the defecation center in the
spinal cord.
 Action potential stimulates colon and rectum contraction and relaxation of
internal anal sphincter.
 Action potential is propagated to the brain through the ascending nerve.
 The descending nerves from the brain regulate the defecation reflex center.
 Action potential from the brain controls the external anal sphincter.
 The voluntary action regulates the movement through the external sphincter.
Secretion of the large intestine

 Mucus is the major secretion of the large intestine. It lubricates the walls of
the colon and causes the fecal material to hold together.
 Tactile and parasympathetic stimulations increase the mucous secretion.
 The epithelial cells secrete HCO3- to neutralize the decreased PH by the
bacterial actions.
 Sodium ions are absorbed by active transport and water move by osmosis.
The feces consists of water, solid undigested food, microorganisms and
sloughed off epithelial cells.
 Microorganisms constitute 30% of the dry feces. They are responsible for
vitamin K production and gas production.
Digestion and absorption

 Digestion is the break down the organic materials into their main
components parts.
 Absorption and transport are means by which the molecules are moved out
of the digestive tract and distributed throughout the body.
 Transport is done by two routs:
255
1- Water soluble materials, water and ions are transported to the liver
through the hepatic portal vein.
2- Lipid soluble products are transported to the circulatory system through
the lymphatic system.
 There are three types of food: carbohydrates, proteins and lipids which are
digested and absorbed in the small intestine.
Carbohydrates
 Carbohydrates are first exposed to digestion in the mouth by the effect of
salivary amylase to produce maltose, maltotrios and dextrin.
 In the duodenum:
- More amylase is secreted from the pancreas.
- Maltase, sucrase and α-dextrinase hydrolyze the oligosaccharides to
glucose.
- Lactase degrades lactose to galactose and glucose.
- Sucrase degrades sucrose to fructose and glucose.
 Monosaccharides (glucose and galactose) are taken into the intestinal
epithelial cells by symport depending on Na+ - K+ pump.(Figure11.16).
 Monosacchrides move out the epithelial cells by facilitated diffusion to the
intestinal villi capillaries, and then they are carried to the liver by the hepatic
portal vein.
 In the liver, non-glucose sugar is converted to glucose.
 Glucose enters the cells by facilitated diffusion which is regulated by
insulin.
Clinical note: Lactose intolerance results from the absence of lactase and thus
inability to hydrolyze lactose (in milk and dairy products) to glucose and galactose
to absorb .Therefore non absorbed lactose and water remain in the lumen of
digestive tract resulting in osmotic diarrhea.
Pharmacology note: Carbohydrates digestion can be impaired in diabetic patients

by α-glucosidase inhibitors (acarbose).These drugs inhibit the intestinal enzymes
sucrose,maltase and amylase leading to impairing carbohydrates digestion and
glucose absorption.This facilitates glucose control in diabetic patients,but the
carbohydrates remain in the gut causing adverse effects (nausea and diarrhea).
256
Figure (11.16): Monosaccharides transport.( Seeley R.R., Stephens T.D. and Tate P. Anatomy
Proteins
 Proteins are made of long chains of amino acids.
 Proteins are broken down into shorter chains of polypeptides chains by
protein digesting enzyme (pepsin) which is secreted in inactive form and
activated by HCl.
 In the small intestine polypeptides chains expose to digestion by
proteolytic enzymes of pancreas and intestinal mucosa:
1- Endopeptidases act at anterior peptides bonds, e.g., trypsin,
chymotrypsin and elastase.
2- Exopeptidases act at the carboxyl and amino ends of the polypeptide
chains, such as carboxypeptidase.
 Digestive products of the proteins can be absorbed as amino acids,
dipeptides and tripeptides.
1- Transport of free amino acids:
 Amino acids absorbed by Na+ dependent amino cotransport that
occurs in the luminal membrane.
 Amino acids are transported then from cells to the blood by
facilitated diffusion. (Figure11.17).
2- Transport of dipeptides and tripeptides
 They are absorbed by H+ dependent cotransport that occurs in the
luminal membrane.
 They are hydrolyzed by peptidase to amino acids in the intestinal
cells.
 Amino acids are carried to the liver through the hepatic portal vein
where to be modified and distributed throughout the body.
257
Figure (11.17): Transport of protein.( Marieb E.N. and Hoehn K. Human Anatomy and
Physiology.San Francisco, Pearson Education Inc., 2010.Retrieved from
:www.studyblue.com).
Lipids
 Lipids are insoluble in water. They include: triglycerides, phospholipids,
cholesterol, steroids and fat soluble vitamins.
 Digestion of the lipids :
1- In the stomach
 The first step of lipids digestion is emulsification .Emulsification is
break down the large lump of fat into much smaller droplets to
increase the surface area for attack by lipase.
 Lingual lipase digests the triglycerides into monoglycerides and free
fatty acids.
2- In the small intestine
 Emulsification of lipids by bile acids for further increase in the
surface area for digestion.
 Pancreatic lipase hydrolyzes lipids into fatty acids, monoglycerides,
cholesterol and lysolecithin.
 Formation of micelles: Fatty acids and monoglycerides are enclosed
by bile salt to form micelles. Fatty acids and monoglycerides at the
center of the micelles and the hydrophilic ends are directed
outward.
 Lipids absorption
1- Micelles make the products of the lipid digestion in contact with the
epithelial cells of the small intestine. Fatty acids, monoglycerides and
cholesterol pass by simple diffusion through the plasma membrane into
the cells.
258
2- In the intestinal cells, lipids digestion products are converted into
triglycerides, cholesterol ester and phospholipids.Proteins coat the
triglycerides to form chylomicrons.
3- Chylomicrons are transported out of the intestinal cells by
exocytosis.They enter the lacteals of the intestinal villi and carried
through the lymphatic system to the general circulation. (Figure11.18).
Lipids transport
 Lipids are transported through the blood in combination with proteins.
 Lipids combined with proteins are called lipoproteoins.Lipoproteins are two
types:
1- Low density lipoprotein (LDL): its components are (99 % lipids and 1%
proteins).It is considered to be bad, because when excess it deposits
cholesterol on the arterial walls.
2- High density lipoprotein (HDL): its components are (55% lipids and
45% proteins).It is good because it transports cholesterol from the tissues
via blood to the liver to be removed from the body in the bile.
Figure (11.18): Digestion and absorption of lipids. (Marieb E.N. and Hoehn K. Human
Anatomy and Physiology . San Francisco, Pearson Education Inc., 2010.Retrieved from
:www.studyblue.com).
Absorption of water
 Water is transported through the intestinal membrane by osmosis (Isosmotic
absorption ):
- When chyme is diluted, water is absorbed into the blood of the villi,
through the intestinal mucosa.
- Water is transported from the plasma to the chyme when hyperosmotic
solution is discharged from the stomach into the duodenum.
259
 About 9 L of water enter the digestive tract each day,92% is reabsorbed in
the small intestine ,6-7% is reabsprbed in the large intestine and 1% is
secreted in the feces, (figure 11.19 ).
Absorption of electrolytes
1- Apsorption of NaCl
 Na+ is actively absorbed in the jejunum and ileum.
 Na+ moves into the intestinal cells down its electrochemical gradient across
the luminal membrane by :
1. Passive diffusion
2. Na+ -glucose and Na+ - amino acid cotransport.
3. Na+ - Cl cotransport
4. Na+ - H+ exchange.
 Na+ pump out of cell against its electrochemical gradient by the Na+ - K+
pump in the basolateral membrane.
 Absorption of Cl- accompanies the absorption of Na+ by:

1. Passive diffusion
2. Na+ - Cl- cotransport.
3. Cl- -HCO3- exchange.
Figure (11.19): Water volume along the digestive tract.(Seeley R.R., Stephens T.D.
260
2- Absorption of K+
 Dietary K+ is absorbed passively in the small intestine via paracellular route.
 K+ is actively secreted in the colon and is regulated by aldosterone.
 K+ secretion by the colon is elevated in diarrhea.An excessive loss of K+
causes hypokalemia.
3- Absorption of Ca2+
 Calcium is absorbed actively by the blood of the duodenum.
 Its absorption is controlled by parathyroid hormone and active form of
vitamin D (1, 25-dihydroxycholecalciferol) produced in kidney.
Clinical note: Renal failure or vitamin D deficiency results in a decrease in Ca2+

absorption causing rickets in children and osteomalacia in adults.
Absorption of vitamins
 Fat soluble vitamins (A, D, E and K) are absorbed along with other fats.
 Water soluble vitamins are absorbed by Na+ dependent cotransport
mechanism.
 Vitamin B12 requires intrinsic factor for absorption.
Clinical note: Gastroectomy results in loss of gastric parietal cells which produce
intrinsic factor, therefore administration of vitamin B12 is important to avoid
pernicious anemia.
Absorption of iron
 Iron is essential for oxidative metabolism and DNA synthesis.
 Iron is contained in the RBCs .It is present as heme iron (iron bond to
hemoglobin and myoglobin) and non heme iron (Fe3+) which reduced to
Fe2+ prior to absorption.
 Iron absorption occurs mainly in the duodenum and upper jejunum.
- In the intestinal cells heme iron is degraded and free Fe2+ is released.
- Free Fe2+ binds to (apoferritin) and transported to the blood.
- Free Fe2+ circulates in the blood bound to transferrin which transported
from small intestine to the liver, then to the bone marrow for hemoglobin
synthesis.
 Iron deficiency is the most common cause of anemia.
261
References

2. Costanzo L.S. Board Review Series(BRS): physiology.5th ed. Philadelphia, Lippincott
Williams & Wilkins, 2011.
3. http//: tube.medchrome.com
4. http//: www.authorstream.com
5. http//: www.studyblue.com
262
Chapter Twelve
Endocrine system 12
Endocrine system
Overview
 Endocrine system is a coordination and communication system, regulates
the activities of all other body structures by releasing of chemical
substances: hormones.
 Hormones are secreted from endocrine glands and carried to all part of the
body by the circulatory system.
 The cells that are able to recognize the hormones and respond to them are
target cells.
 The target cells must have specific receptors for specific hormone.
 Some hormones travel free as soluble compounds .Whereas others travel
mainly bound, associated with specific binding proteins.
 The effectiveness of specific hormone depends on :
1. Concentration of free hormone.
2. Concentration of hormone receptors.
3. Effectiveness of the transduction mechanism.
 All endocrine diseases are due to a quantitative or qualitative in hormone
synthesis or altered tissue sensitivity to the hormone.
Function of endocrine system

1- Metabolism and tissues maturation.
2- Ions regulation ,it helps regulate blood PH
3- Water balance by controlling the solutes in the blood.
4- Immune system regulation, control production of immune cells.
5- Heart rate and blood pressure regulation.
6- Control blood glucose and other nutrients.
7- Control the reproductive functions.
8- Uterine contraction during delivery and milk release in the lacting female.
Mechanism of hormones action

 All hormones must interact with a cellular receptor, which then transduces a
signal and generate a cellular response.
263
 The receptors may be :
- Intracellular receptors. These are usually found in the nucleus, but
may be in the cytoplasm. (Figure 12.1 ) The hormone thus must first
pass through the plasma membrane, and so must be fat soluble. On
combining with the receptor, it triggers the production of mRNA, which
directs ribosomes in the cell to secrete proteins. Production of proteins
may take several hours, so this type of hormone known as steroids, is
slow acting. (Figure 12.2).
Figure (12.1): Intracellular receptors. (Seeley R.R., Stephens T.D. and Tate P.
Figure (12.2): Intracellular receptors work. (Seeley R.R., Stephens T.D. and Tate P.
264
- On the plasma membrane. Hormones that are water soluble cannot
cross the plasma membrane, but attach to receptors on the outside of the
membrane. This triggers a response inside the cell. The response may
be:
 Opening ion channels to allow ions move in or out of the cell
(neurotransmitter).
 Activate a G-protein (which then usually activates an enzyme). The
receptor has a G protein attached to it, which is activated when the
hormone attaches to the receptor. The G protein produces an
intracellular activator, such as cyclic adenosine monophosphate
(cAMP), cyclic guanosine monophosphate (cGMP), inositol
triphosphate (IP3) and diacylglycerol (DAG). These may activate an
enzyme.(Figure 12.3.a ).
 Directly activate an enzyme attached to the receptor.
(Figure12.3.b).
Figure (12.3.a): Membrane –bound receptors that activate G protein.
Figure (12.3.b): Membrane bound receptors directly activate an enzyme.( Seeley R.R.,
2008).
265
Types of hormones
1- Protein, peptide, amino acid
 They are hydrophilic, stored in a vesicle and released on demand.
 They bind to membrane bound receptors on the target cells.
 Ex: growth hormone(GH)
2- Thyroid hormones
 They are unique that they derived from amino acid tyrosine.
 They diffuse into the cell, bind to a receptor and alter gene expression.
 Ex: thyroid hormones(T3,T4)
3- Steroid hormones
 They are lipid soluble compounds derived from cholesterol that are able
to enter all cells of the body and diffuse through lipid rich membrane.
 They cannot be stored, but produced continually, synthesis and secretion
increase on demand.
 Ex: sex steroid (like testosterone, progesterone, and estrogen);
adrenal steroid (cortisol, aldosterone).
Regulation of hormone secretion

1- Negative feedback.
 The most common applied for hormone regulation.
 It is self limiting.
 A hormone has biological actions that directly or indirectly inhibit
further secretion of the hormone.
 Ex: insulin is secreted by pancreatic β cells in response to an increase
in blood glucose, in turn causes increase intake of glucose into the cells,
causing decreased blood glucose. Decreased blood glucose
concentration decreases insulin secretion.
2- Positive feedback
 This is rare, an explosive and self reinforcing.
 A hormone has biological actions, directly or indirectly cause more
secretion of the hormone.
 Ex: the surge of luteinizing hormone (LH),that occurs just before
ovulation is a result of positive feedback of estrogen on the anterior
pituitary .LH then acts on the ovaries and cause more secretion of
estrogen.
266
Pituitary gland and Hypothalamus
Overview
 The pituitary gland or hypophysis secrets nine major hormones that
regulate numerous body functions and secretory activity of several other
endocrine glands.
 The hypothalamus of the brain and the pituitary gland are major sites where
the nervous and endocrine systems interact.
 The posterior pituitary is an extension of the hypothalamus.
 Hormones, sensory information that enters the CNS and emotions in turn
influence the activity of the hypothalamus.
Structure of the pituitary gland

 The pituitary gland is 1cm in diameter and 0.5-1.0 gm weight.
 It rests in the sella turcica of the sphenoid bone.
 It is located inferior to the hypothalamus and connected to it by a stalk of
tissue called infundibulum.
 The pituitary gland is divided functionally into two parts:(Figure 12.5).
1- The posterior pituitary gland

 The posterior pituitary is called neurohypophysis because it’s continuous
with the brain.
 Secretions of the posterior pituitary are neurohormones because the
posterior pituitary is an extension of the nervous system.
2- The anterior pituitary gland

 The anterior pituitary is subdivided into three areas with indistinct
boundaries.
1- The pars tuberalis
2- The pars distalis: enlarged distal portion of the anterior pituitary.
3- The pars intermedia: is adjacent to the posterior pituitary.
 Hormones secreted by the anterior pituitary are not neurohormones,
because the anterior pituitary is not derived from neural tissue.
Figure (12.5): The 2 functional

parts of the Pituitary gland
,anterior part and posterior which
is an extensionof the
hypothalamus. Retrieved from:
www.slideshare.net
267
Relationship of the pituitary to the brain
 The hypothalamohypophysial portal system connects the hypothalamus
and the anterior pituitary. (Figure 12.6).
 Hypothalamus neurons produce and secret neurohormones.
 These neurohormones leave the blood and act on the cells of anterior
pituitary.
 Neurohormones are:
1- Releasing hormones: increase the secretion of anterior pituitary.
2- Inhibitory hormones: decrease the secretion of the anterior pituitary.
 In response to the releasing hormones, the anterior pituitary secrets
hormones that enter the secondary capillaries and carried by general
circulation to their target tissues.
 Hypothalamohypophysial system provides means by which the
hypothalamus using neurohormones as chemical signals to regulate the
secretory activity of the anterior pituitary.
Figure (12.6): Relationship between the hypothalamus and anterior pituitary. (Seeley
R.R., Stephens T.D. and Tate P. Anatomy and Physiology .New York, McGraw –Hill
Companies, 2008).
268
 Several releasing and inhibiting hormones are produced in the
hypothalamus:
1. TRH(Thyrotropin Releasing Hormone).This hormone will affect the

anterior pituitary which will then affect thyroid gland activity
2. PRH(Prolactin Releasing Hormone ) and PIH(Prolactin Release-Inhibiting
Hormone).These two hormones will affect the secretion of prolactin from
the anterior pituitary
3. CRH (Corticotropin Releasing Hormone).This hormone affects ACTH
release from the anterior pituitary
4. GnRH( Gonadotropin Releasing Hormone).This hormone will affect the
anterior pituitary which will then affect the gonadal release of sex hormones
5. GHRH(Growth Hormone Releasing Hormone )
6. GHIH (Growth Hormone Inhibitory Hormone) or SS (Somatostatin)
Both 6, 7 affect secretion of growth hormone by the anterior pituitary.
 Relationships among the hypothalamus, anterior pituitary and the other

endocrine glands or (target tissues) are illustrated in figure (12.7).
Figure (12.7): Relationship among the hypothalamus, anterior pituitary and the other
endocrine glands or (target tissues). (Marieb E.N.and Hoehn K. Anatomy and physiology.
269
Anterior pituitary Hormones
Overview
 They are protein ,glycoprotein or polypeptides,
 Each hormone is secreted by a separate cell type.
 Theses hormones are:
1- Growth Hormone(GH)
 Growth hormone (GH) or (somatotropin) stimulates growth in most
tissues, play a role in the regulation of growth and determining how tall a
person becomes.
 It regulates metabolism
 It stimulates the uptake of amino acids and conversion into protein;
stimulates the breakdown of fat and synthesis of glucose.
 GH stimulates the production of somatomedins, which both promote bone
and cartilage growth.
 GH is regulated by GHRH and GHIH.
 GH secretion increases in response to an increase in blood amino acids; low
blood glucose or stress.
 High blood glucose level inhibits secretion of GH .
 Rhythm of GH secretion occurs, daily peak level correlated with deep sleep.
Pathological conditions
 Several pathological conditions are associated with abnormal secretion of
GH.
 The cause for hypersecretion or hyposecretion of GH is the result of tumors
in the hypothalamus; pituitary; synthesis of structurally abnormal GH and
the lack functional receptors in target tissues.
Clinical note: Chronic hyposecretion of GH in infants and children leads to

dwarfism (pituitary dwarfism).It results in a short stature due to delayed bone
growth .On the other hand hypersecretion of GH leads to gigantism
(acromegaly)
2- Thyroid Stimulating Hormone (TSH)

 It is called thyrotropin also; glycoprotein in nature consisting of α, β
subunits which bind to membrane bound receptors of the thyroid gland.
 This hormone stimulates thyroid gland to synthesize and secrete of thyroid
hormones (T3, T4).
 TSH increases the activity of phospholipase which activates the mechanism
that opens Ca+2 channels and increases Ca+2 concentrations in the cells of
thyroid gland.
270
 TSH is controlled by TRH from the hypothalamus.
TRH TSH T3,T4

\
3- Adrenocorticotropic Hormone(ACTH)
 ACTH is a peptide hormone.
 It stimulates synthesis of cortisol and androgen from the adrenal cortex.
 It is controlled by CRH from the hypothalamus ( androgen do not feedback
inhibit ACTH)
CRH ACTH CORTISOL
4- Melanocyte Stimulating Hormone(MSH)

 It binds to membrane bound receptors on the skin melanocytes.
 It stimulates melanin secretion and deposition in the skin.
5- Gonadotropin Hormone(GnH)
 It is a glycoprotein hormone.
 The two major important hormones are Luteinizing Hormone (LH) and
Follicle Stimulating Hormone(FSH),which are secreted from anterior
pituitary to the blood and stimulate the production of gametes :sperms in the
testes and oocytes in the ovaries.
 LH and FSH control the production of reproductive hormones (estrogen and
progesterone in the ovaries and testosterone in the testes).
 Releasing LH and FSH is under the influence of hypothalamic releasing
hormone (GnRH).
GnRH GnH Estrogen, progesterone in ♀
Testosterone in ♂
6- Prolactin
 It s a protein hormone.
 It plays an important role in milk production in the mammary gland of
lacting females.
 Prolactin is controlled by Prolactin Releasing Hormone (PRH) and Prolactin
Inhibitory Hormone (PIH) from the hypothalamus.
271
PRH
+
+ PROLACTIN Mammary gland
-
PIH
Relationship among the hypothalamus, posterior pituitary and target

tissue
 Posterior pituitary gland does not produce its own hormones, but stores and
releases hormones that it receives from the hypothalamus.
 The axons of the hypothalamic neurons extend from the hypothalamus
through the infundibulum into the posterior pituitary forming tract called:
hypothalamohypophysial tract.(Figure12.8)
 Neurohormones produced in the hypothalamic neuron pass down the axon
in tiny vesicles and stored in secretory vesicles in the enlarged end of the
axon.
 Action potential in the bodies of hypothalamic neurons propagated along
the axon to the axon terminals in the posterior pituitary.
 Action potential causes the release of neurohormones to the circulatory
system.
Figure (12.8): Relationship among the hypothalamus, posterior pituitary and target
tissues. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology. New York,
McGraw –Hill Companies, 2008)
272
Posterior pituitary Hormones
 Posterior pituitary stores and secrets two polypeptides hormones:
ADH (Anti diuretic Hormone) and oxytocin.
1- ADH (Anti diuretic Hormone)

 It is named antidiuretic hormone because it prevents the output of large
amount of urine (dieresis).
 It is called vasopressin because it constricts blood vessels and raises blood
pressure when large amount are released.
 It is synthesized in the hypothalamus and released by posterior pituitary in
response to action potential from the axon terminal, to the blood and carried
to the primary target tissue (kidney tubules).
 ADH promotes the water retention in the kidney tubules and reduces urine
volume.
 The secretion rate for ADH changes in response to alterations in blood
osmolality and blood volume .Increased osmolality (increased
concentration of solutes in the solution) results in:
- Indirect stimulation of ADH by: increased frequency of action potential
in osmoreceptors (specialized neurons synapse with ADH
neurosecretory cells in the hypothalamus resulting in an increased
action potential in the axon of ADH neurosecretory cells
leading to increase ADH secretion.
- Direct stimulation of ADH neurosecretory cells.
 Decreased osmolality results in less secreted ADH.
2- Oxytocin
 Oxytocin is synthesized by neurocells in the hypothalamus, and then
transported through the axon to the posterior pituitary, where it stored in the
axon terminals.
 Oxytocin stimulates smooth muscles contraction of the uterus so help in the
explosion of the fetus from the uterus during delivery.
 It causes expel the uterine epithelium and small amount of blood during
menses.
 It is responsible for milk ejection in the lacting females.
Classification of Endocrine diseases

 A hormone deficiency or excess can occur as a result of defect anywhere
along the hypothalamic –pituitary –target tissue axis.
 It is important to determine the location of defect to make an accurate
diagnosis.
273
- Primary endocrine diseases: Ex: the defect is in the thyroid gland itself,
makes it unable to produce thyroid hormones effectively .This disease is
known as primary hypothyroidism.
- Secondary endocrine disease: The defect is in the pituitary such as
decrease secretion of TSH from the pituitary can cause secondary
hypothyroidism.
- Tertiary endocrine disease: Ex: decrease hypothalamic TRH secretion,
(rare) causes tertiary hypothyroidism.
Thyroid Gland
Overview
 Thyroid gland is composed of two lobes connected by a narrow band of
thyroid tissue (isthmus).(Figure12.9)
 The lobes are lateral to the upper portion of the trachea, inferior to the
larynx.
 Thyroid gland is one of the largest endocrine gland with a weight of 20 gm.
 It is highly vascularized and appears more red than the surrounding tissues.
 It contains numerous small sphere follicles, (figure12.10) .The center of
each thyroid follicle is filled with proteins called thyroglobulin, which is
synthesized and secreted by the cells of the thyroid follicles.
 Large amount of thyroid hormones are stored in the follicles as part of the
thyroglobulin.
 Between the follicles there is a network of loose connective tissue which
contains capillaries.
 There are scattered parafollicles among the follicles these parafollicles
secrete calcitonin.
 Calcitonin regulates calcium level in the body fluid .It Reduce Ca2+ level in
the body fluid when Ca2+level become elevated.
274
Figure (12. 9): The two lobes of thyroid gland connected by
isthmus.( Marieb E.N Essential of Human Anatomy and Physiology.San
Francisco, Pearson Education,Inc.,2012).
Figure (12.10): Follicles of the thyroid gland. (Marieb E.N .Essential of

Human Anatomy and Physiology . San Francisco, Pearson Education,Inc.,2012).
Thyroid Hormones
 The major secretory products of the thyroid gland are:
1- Triiodothyronine (T3), which constitutes 3-10% of the thyroid
hormones.
2- Tetraiodothyronine or thyroxin (T4) constitutes 90-97% of the thyroid
hormones.
 T3andT4 are of a clinical importance, secreted from the thyroid follicles.
 Calcitonin: is other hormone secreted by the parafollicular cells of thyroid
gland.
275
Synthesis of T3, T4
 TSH from anterior pituitary stimulates thyroid hormones (T3,T4) synthesis
and secretion.
 T3andT4 then stored in the follicles and released to the circulation by the
effect of TSH.
 Because iodine is a component of T3and T4, an adequate amount of iodine
in diet is required for thyroid hormones.
 The steps for synthesis of thyroid hormones include:(Figure 12.11 )
1- Iodide (I-) are taken up by thyroid follicle cells by active transport.
2- Thyroglobulins which contain numerous tyrosine amino acid
molecules are synthesized within the cells of the follicles.
3- I- is oxidized to iodine I by peroxidase .
4- Either one iodine atom is bound to each tyrosine molecules of the
thyroglobulin to form monoiodotyrosine (MIT),
Or two of iodine atoms bound to tyrosine to form diiodotyrosine . This
event occurs close to the time the thyroglobulin molecules are secreted
by exocytosis into the lumen of the follicle.
I+ TYROSINE MIT
Or: 2I + TYROSINE DIT
5- In the lumen two diiodotyrosine molecules combine to form T4,or one

monoiodotyrosine and one doiodotyrosine combine to form T3.Large
amounts of T3andT4 are stored within the thyroid follicles as part of
thyroglobulin .
6- Thyroglobulin is taken into the follicle cells by endocytosis.
7- Thyroglobulin breaks down to amino acids and T3andT4 by
proteolytic enzymes.T3,T4 diffuse out of the follicle cells and enter the
circulation. The remaining amino acids are used again to synthesize
more thyroglobulin.
Pharmacology note: Formation of DIT and MIT is called organification, which is

inhibited by thionamides propylthiouracil (PIU) and methimazole, which are used
to treat hyperthyroidism.
276
Figure (12.11): The steps for synthesis of thyroid hormones. Retrieved from:
www.ruisimeao.com
Transport of T3, T4
 70-75% of circulating T3andT4 are bound to thyroxin binding globulin
(TBG), which is synthesized by the liver.
 20-30% of T3,T4 are bound to other plasma proteins (Albumin).
 30-40% of T4 is converted to T3 in the body tissues.
 T3 is the major hormone that interacts with the target cells and is several
times more potent than T4.
 Much of circulating T4 eliminated by conversion to tetraiodothyroacetic
acid.
Pharmacology note: Amiodarone is an iodine –rich drug (40%by weight) that is

commonly used for rate control of tachyarrhythmias such as atrial fibrillation. On
the other hand amiodarone causes thyroid dysfunction, both hyperthyroidism
(common) and hypothyroidism (rare), necessitating frequent monitoring of
thyroid function.
Physiological effects of T3, T4
 T3andT4 affect every tissues in the body but not in identical response:
1- They regulate the metabolism at a normal metabolic rate:
277
 Thyroid hormones lead to the basal metabolic rate.
 Thyroid hormones level lead to the rate of metabolism of
protein, fat and glucose.
 Metabolic rate produces heat, causing heat intolerance.
2- Blood level of cholesterol decline.
3- Activity of Na+ _ K+ pump which leads to body temperature.
4- They can alter the number and activity of mitochondria to produce more
ATP.
5- They potentiate catecholamine actions.
 Thyroid hormones up regulate expression and stimulate activity of
β-adrenergic receptors in the tissues such as heart and skeletal
muscles causing enhanced sensitivity to circulating catecholamine.
 They act directly on the heart, stimulate contractility and increase
the heart rate, result in high output congestive heart failure.
 In muscles, they contribute to muscle tremors
Pharmacology note: By preventing catecholamine from binding to their

receptors, β-adrenergic antagonists (β-blocker) such as propranolol can
ameliorate many of the symptoms of hyperthyroidism associated with
sympathetic activity (tachycardia, tremors).
Regulation of thyroid hormones (T3, T4)
1. TRH released from the hypothalamus pass through the

hypothalamohypophysial portal system to the anterior pituitary.
2. Anterior pituitary secrete TSH which pass through the general circulation to
the thyroid gland.
3. TSH causes increased release of T3andT4 from thyroid gland into general
circulation.
4. T3and T4 act on target tissues to produce a response.
5. T3 and T4 have an inhibitory effect on the secretion of TRH from the
hypothalamus and TSH from the anterior pituitary. (Figure 12.12).
278
Hypothalamus
-
TRH
Anterior pituitary
+
-
TSH
Thyroid gland
+
T3,T4
Physiological actions
Figure (12.12): Thyroid hormones regulation.
1- Hyperthyroidism
 It refers to a pathological increase in thyroid hormones synthesis.
 Manifestations of hyperthyroidism include:
1- Weight loss with increased appetite.
2- Heat intolerance.
3- Diarrhea
4- Often atrial fibrillation.
 T3andT4 concentrations are elevated in hyperthyroidism .TRH and TSH
vary in concentration depending on the cause of hyperthyroidism.
Clinical note: Thyrotoxicosis: symptoms associated with pathological elevated

level of thyroid hormones irrespective of etiology (gland destruction or increases
synthesis).
Graves’s disease: The most common cause of hyperthyroidism, immunoglobulin G
(IgG) antibodies mimics TSH and stimulates TSH receptors on thyroid gland.
Thyroditis: is caused by viral infection and autoimmune destruction as in
Hashimoto.
279
2- Hypothyroidism
 It refers to decrease synthesis of thyroid hormones.
 Manifestation of hypothyroidism :
1- Weight gain ,constipation
2- Cold intolerance.
3- Bradycardia and atrial fibrillation
4- Dulled mentation.
5- Congenital hypothyroidism may cause mental retardation (cretinism).
 T3, T4 are decreased, TRH, TSH concentration vary with the cause of
hypothyroidism.
3- Euthyroid sick syndrome
 Low to normal T3, T4 in ill patients with no appearance signs of thyroid
dysfunction.
Clinical note: Abnormal enlargement of thyroid gland may result from

conditions that cause hypothyroidism as well as conditions that cause
hyperthyroidism. Iodine deficiency goiter when dietary iodine intake is very
low and there is too little iodine to synthesis T3,T4 as a result blood level of
T3,T4 decrease and the person may exhibit symptom of hypothyroidism.
Calcitonin Hormone
 Calcitonin is secreted by the parafollicular cells of the thyroid gland.
 Increased level of Ca2+ in the blood leads to an increase secretion of
calcitonin.
 The primary target tissue for calcitonin is the bone.
 Calcitonin causes decrease in osteoclast and lengthens the life span of
osteoblast result in decrease in blood Ca2+ level and phosphate.
 Ca2+ level is regulated primarily by another hormone (parathyroid
hormone) that is why complete thyroidectomy does not result in high
blood Ca2+.
Parathyroid Gland
Overview
 Parathyroid glands are embedded in the posterior part of each lobe of the
thyroid gland.(Figure 12.13).
 Parathyroid glands are made up of two cell types :
1- The chief cells :secret parathyroid hormone(PTH)
2- Oxyphils with unknown function.
280
a b
Figure (12.13): a: Position of the parathyroid glands in the thyroid gland.
b: Back view of the thyroid gland. Retrieved from: www.ent-surgery.com.am
Parathyroid hormone (PTH)

 PTH is a polypeptide hormone.
 It regulates the Ca2+ level in the body fluid (normal Ca2+ level is 8-
10mg/dl). (Figure 12.14).
 Bone, intestine and kidney are the major target tissues.
 In the bone, PTH stimulates osteoclast activity, leading to bone
resorption and release of Ca2+ and phosphate, resulting in an increase
blood Ca2+ level.
 In the kidney :
1- PTH induces Ca2+ reabsorption, so less Ca2+ level leaves the body in
the urine.
2- PTH increases the enzymatic formation of active vitamin D.
 In the intestine: Active vitamin D causes increase in the rate of Ca2+ and
phosphate absorption resulting in elevated blood Ca2+ level.
281
--------------------------------------------------------------------------------------------------
Figure (12.14): Regulation of blood Ca2+ level by PTH.( Seeley R.R., Stephens T.D. and
282
Pathological conditions of PTH
1- Hyperparathyroidism
 Primary Hyperparathyroidism( ↑PTH,↑Ca2+)
- It caused by adenoma and hyperplasia
 Secondary Hyperparathyroidism(↑PTH,↓Ca2+)
- It occurs during chronic stimulation of PTH due to decrease serum Ca2+
- Ex: renal failure, vitamin D deficiency, or malabsorption syndromes.
2- Hypoparathyroidism
 Decreased PTH occurs mainly by accidental removal of parathyroid during
thyroid surgery and (or) parathyroid surgery.
Adrenal Gland
Overview
 There are two adrenal glands (Figure 12.15). These glands have a similarity
in anatomical structure, function, secreted hormones.
 The two glands are located above the two kidneys, i.e. one gland above each
kidney; exactly at the position of 12th thoracic vertebra.
 Adrenal glands are also termed suprarenal glands (due to the position).
The term (adrenal) comes from the fact that these glands secrete the
hormone (adrenaline) in cases of stress.
 Adrenal gland consists of two distinct layers; Cortex and Medulla.
 These two layers differ in their anatomical structure and in their functions.
Figure (12.15): Adrenal glands. Retrieved from

www.adrenalfatique.co.nz
283
1- Adrenal medulla
 Adrenal medulla arises from neural crest cells and functions as part of
CNS.
 It is composed of closely packed cells, devoted to synthesis of
catecholamines, which include adrenaline (epinephrine) and noradrenaline
(norepinephrine). Both hormones are secreted in stressful situations.
Physiological effects of catecholamines

 Catecholamines cause general physiological changes that prepare the body
for physical activities. (Figure 12.16).
 In case of ( fight or flight ) , catecholamines cause :
- Elevation of blood pressure .
- Increasing blood sugar.
- Increasing heart rate.
- Increased metabolic rate.
- Affects peripheral nervous system.
Figure (12.16): Actions of adrenal medulla hormones. (Seeley R.R., Stephens T.D. and
 Pheochromocytoma: Is a tumor In the adrenal medulla (very rare ) that
causes hypersecretion of catecholamines which leads to:
1. Hypertension.
2. Very high blood sugar.
3. High rate of heartbeat.
284
2- Adrenal cortex
 It is derived from mesoderm
 Adrenal cortex is devoted to the synthesis of CORTICOSTEROID
HORMONES due to the presence of large amounts of fats specially
cholesterol which is the precursor of these hormones.
 Adrenal cortex exhibits three functional zones:
1. Zona glomerulosa
1. Zona fasciculata
2. Zona reticularis
1. Zona glomerulosa
 The outer most layer of the cortex.
 It is the main site for production of ( Mineralcorticoids )
 The main mineralcorticoid in human is aldosterone while there are some
endogenous hormones which have a mineralcorticoid function
(progesterone & deoxycorticosterone).
 Aldosterone hormone is a derivative of cholesterol.
 Its normal level is about (4-9 Mg /100 ml blood). About 2-18 Mg of
aldosterone is wasted with urine daily.
 Aldosterone acts on kidneys to provide active reabsorption of sodium and
passive absorption of water. (increases the blood pressure)
 It causes secretion of both potassium ions and protons from the collecting
ducts and distal tubules.
 Aldosterone synthesis is regulated by :( Figure12.17).
- Angiotensin II.
- Adrenocrticotropic hormone (ACTH).
- Blood level of Na+ and K+.
Figure (12.17): Aldosterone regulation. (Seeley R.R., Stephens T.D. and Tate P. Anatomy
285
Pathological conditions of aldosterone
1- Natural increase: is due to deficiency of sodium and plenty of potassium in
the diet and heavy sweat.
2- Natural decrease: is due to deficiency of potassium in the diet and having
large amounts of water and drinks.
3- Conn disease
 It occurs due to increased activity of zona glomerulosa.
 It leads to increased secretion of aldosterone which results in a high blood
pressure, low blood potassium and high blood sodium levels.
2- Zona fasciculate
 The central region of the adrenal cortex.
 It is the main site for production of ( Glucocorticoids )
 The primary glucocorticoid in human is (cortisol).
 Cortisol (a stress hormone) secretion is stimulated by hypoglycemia or
stressful conditions, anxiety, and when the sympathetic nervous system is
activated.
 Cortisol has a diurnal pattern of secretion based on daily pattern of ACTH.
 Its primary function is to increase blood sugar and stores of sugar in the
liver as glycogen.
 Zona fasciculata can produce (7-7.5 mg/day) of cortisol hormone.
 Biosynthesis of cortisol is done by conversion of cholesterol to
pregnenolone.
Physiological effects of cortisol

1. Cortisol has anti – insulin effect. It contributes to “hyperglycemia” by
stimulation of hepatic gluconeogenesis and inhibition of peripheral
utilization of glucose.
2. It increases gastric acid secretion.
3. It cooperates with adrenaline to create memories of short – term events.
4. It has an anti – inflammatory action as inhibits secretion of histamine from
basophils and mast cells and it can cause immune suppression
5. It elevates blood pressure by increasing the expression of adrenergic
receptors in various tissues.
6. Cortisol may weaken the bones by inhibiting osteoblasts and stimulating
bone degrading cells (osteoclast).
Regulation of cortisol secretion

 CRH is released by the hypothalamus as response to stress and decreased
blood glucose. (Figure 12.18).
 CRH affects the anterior pituitary to release ACTH.
 ACTH stimulates the secretion of cortisol by the adrenal cortex.
 Cortisol acts on the target tissues to cause its effects.
 Cortisol has negative feedback effect to inhibit CRH releasing from the
hypothalamus and decrease ACTH secretion from anterior pituitary.
286
Figure (12.18): Regulation of cortisol secretion. (Seeley R.R., Stephens T.D. and Tate P.
Pathological conditions of cortisol

1-Hypercortisolism (Cushing syndrome)
 The condition results from increased amount of cortisol hormone in the
blood.
 It may be caused by:
- Tumors in cortisol secreting cells.
- Tumors in ACTH secreting cells.
- Iatrogenic (Taking glucocorticoids drugs).
 Symptoms of Cushing syndrome include :
- Rapid weight gain.
- Increased growth of body and facial hair
- Very high blood sugar which may lead to diabetes mellitus.
- High blood pressure
- Loss of minerals which leads to osteoporosis
2-Hypocortisolism (Addison disease)

 Addisone disease is due to an inadequate secretion of cortisol.
 The causes of Addison disease are:
- Iatrogenic is the most common cause, occurs because of abrupt
cessation of chronically administrated cortisol.
- Primary adrenal insufficiency causing increase level of ACTH.
287
- Secondary adrenal insufficiency or chronic use of steroid, the ACTH is
low.
 Symptoms of Addison include:
- Low blood sugar.
- Low blood pressure.
- High potassium levels in the blood.
- Full body weakness and loss of energy.
3-Zona reticularis
 It is the interior layer of the adrenal cortex.
 It is responsible for production of ( Androgens ) and ( Estrogen)
 The main adrenal androgen is Testosterone, while the main adrenal
estrogen is Estradiol
1- Testosteron
 Testosterone is secreted in both males and females , but in males in a larger
amount so , its effects appear clearly on males and therefore , it is the
“muscularity hormone”
 In males, it is secreted mainly from Leyding cells in the testes, and a small
amount from adrenal reticularis.
 In females, it is secreted from Thecal cells in the ovaries, placenta and a
small amount from adrenal reticularis.
 Its activity is mediated by LH and FSH.
Physiological effects of testosterone

1- Regulation the production of sperms (spermatogenesis)
2- Development and maintenance of male reproductive organs and secondary
sex characteristics.
3- Stimulating protein synthesis (anabolic effect)
2-Estradiol
 Estradiol is the predominant sex hormone in females.
 It is produced primarily by granulosa cells in ovaries, in addition to small
amount from adrenal reticularis.
 During pregnancy, its amount increases due to secretion from placenta also.
 It is present in males but in lower amounts than females.
 Its activity is mediated by LH and FSH.
Physiological effects of estradiol

 Growth of female reproductive organs.
 Maintaining of oocytes in ovaries.
 During pregnancy, it promotes uterine blood flow and stimulates breast
growth.
 Regulation of menstrual cycle.
 It affects liver to synthesize lipoproteins, binding proteins and proteins of
blood clotting.
288
Pancreas
Overview
 Pancreas is an exocrine and endocrine organ.
 Its function as exocrine is the secretion of digestive enzymes and
bicarbonates, into the duodenum ,while its function as endocrine is to
synthesize and release hormones by the cells of the Islet of Langerhans
into the circulation
 It is located horizontally behind the stomach, upper left abdominal quadrant.
 Humans have roughly one million islets. (Figure12.19)
 The islets of Langerhans are clusters of 4 types endocrine cells these are:
1. β cells-secrete insulin and amylin;
2. α cells- secrete glucagon;
3. δ cells-secrete somatostatin
4. γ cells-secrete a polypeptide of unknown function.
 Nerves from both divisions of autonomic nervous system innervate the
pancreatic islets.
 There is well developed capillary network surround each islet.
 Pancreatic hormones play an important role in regulating the concentrations
of nutrients in the circulating especially glucose and amino acids.
 Insulin and glucagon maintain blood sugar at level of 100mg/100ml of
blood.
Figure (12.19): The pancreas. (Marieb E.N. and Hoehn K. Human Anatomy and Physiology .
289
1-Insulin
 Insulin is a rather small protein, with a molecular weight of about 6000
Daltons. It composed of 2 chains held together by disulfide bonds.
 It is continuously produced but production increases when there is a high
blood glucose ,it thus to decrease blood glucose by :
1- Encouraging all cells to take up more glucose out of the blood.
- Insulin molecules binds to membrane bound receptors on the
target cells (the GLUT-4 is the major transporter used for uptake of
glucose which is made available in the plasma membrane through
the action of insulin).Then the receptors cause specific protein in
the membrane to become phospherylated, part of the cells
response to insulin is to increase number of transport proteins in
the membrane of cells for glucose and amino acids .
- Finally insulin and its receptors are taken by endocytosis.
- Insulin molecules are released from receptors and broken down
within the cell. The receptors can again become associated with
plasma membrane.
2- Stimulate the liver to convert glucose to glycogen.
3- Stimulate the adipose tissues to convert glucose to fat.
4- Acts on satiety center of the hypothalamus so that no longer feel hungry
to stop eating more sugar.
Physiological effects of insulin

1- Action of insulin on the liver
 ↑ Glucose uptake when glucose level is high
 ↑ Glucose use to:
- ↑ glycogenesis and ↓glycogenolysis
- ↑ glycolysis , ↓gluconeogenesis
 ↑ Fatty acid synthesis and very low density lipoprotein formation,
↓ ketogenesis
 ↓ Urea cycle activity.
2- Action of insulin on the adipose tissues
 ↑ Glucose uptake by ↑GLUT-4 availability.
- ↑ Glycolysis.
- ↑ production of α-glycerol phosphate
 ↑ Esterification of fats.
 ↓ Lypolysis
3- Action of insulin on the muscle
 ↑ Glucose uptake by ↑ GLUT-4 availability.
- ↑ Glycogenesis and ↓ glycogenolysis
- ↑ Glycolysis.
 ↑ amino acid uptake
 ↑ Protein synthesis, ↓ proteolysis.
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Regulation of insulin secretion (Figure12.20.a,b)
1- The factors that increase insulin secretion are:
 ↑ Blood glucose
 ↑ Amino acids
 ↑Fatty acids
 Glucagon
 Ach
2- The factor that decrease insulin secretion are:
 ↓ Blood glucose
 Somatostatin
 Epinephrine and norepinephrine
Pathophysiology of insulin
 In the absence of insulin the following events occur:
1- Movement of glucose and amino acids into the cells decline.
2- Satiety center cannot detect the presence of glucose in the extracellular
fluid result in intense sensation of hunger inspite of high blood glucose
(polyphagia )
3- These events lead to increase blood glucose level.
4- Increase urine volume (Polyuria): [↑ concentrations of glucose enter
kidney tubules result in water osmosis and increase amount of water in
the urine].
5- Increase sensation of thirst (polydipsia).
6- The patients present initially in diabetic ketoacidosis (DKA) (the
acidity of some ketone bodies (aceton) which formed during the
lipolysis in adipose tissue which metabolize the fatty acids to ketone
bodies).
Figure (12.20. a): Blood glucose homeostasis .Events occurring in case of increased
blood glucose. (Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . New York,
291
Figure (12.20. b): Blood glucose homeostasis .Events occurring in case of
decreased blood glucose.
Clinical note: Diabetes mellitus is due to insulin problems. There are 2 types:
Type 1: insulin dependent. This is a genetically controlled (inherited). Auto-
immune disease in which the pancreas has insufficient  cells (due to destruction
by antibodies) and so produces insufficient insulin. This means that:
• Blood glucose is excessively high and exceeds the kidney threshold resulting in
excretion of glucose in the urine.
• Insulin is required for cells to take up glucose, so cell death occurs and the
satiety center of the hypothalamus cannot record the blood glucose. The
person thus keeps eating sugar, further boosting blood glucose and thus
excretion. As cells switch to fat and protein metabolism as an alternative to
glucose, the body wastes away. Treatment requires insulin injections
throughout life.
Type 2 : Non-insulin dependent. Lack of insulin receptors on target cells means
that although insulin is normal, cells cannot take up glucose and die. This form of
diabetes is associated with extreme overweight (and thus prolonged over-
consumption of glucose and so prolonged excessive insulin production damaging
receptors). In developed countries, it is one of the fastest expanding diseases. It
is easily controlled by dieting.
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Pharmacology note: One way to reduce plasma glucose is to stimulate the β cells
to secrete more insulin. The sulfonylurea drugs (e.g. tolbutamide, glyburide)
stimulate insulin secretion by closing membrane spanning K+ channels on β cells
resulting in depolarization followed by K+ influx that triggers insulin secretion.
This drug is useful in type 2 diabetes. However these drugs cause a significant risk
for hypoglycemia.
2-Glucagon
 Glucagon is the primary hormone of the fasting state
 It is a primary regulator of plasma glucose homeostasis.
 Glucagon function is to increase plasma glucose levels, thereby opposing
the action of insulin.
Regulation of glucagon
 The primary stimulus for glucagon secretion is amino acids
 Glucagon secretion is also stimulated by low blood glucose levels and
inhibited by high levels.
Physiologic effect of glucagon

 In the fasting state glucagon promotes hepatic glycogenolysis and
gluconeogenesis.
 Glucagon stimulates β-oxidation of the fat by the liver which liberates
energy that can be used to support hepatic gluconeogenesis.
 Glucagon has a minimal metabolic action on the adipose tissues and muscle.
These actions include stimulation of lipolysis in adipose tissue and
inhibition of glucose utilization by the peripheral tissues.
3- Somatostatin (SS)
 SS is secreted by a broad range of tissues, including pancreas,
gastrointestinal tract (GIT) and regions of the central nervous system outside
the hypothalamus.
 A majority of the circulating SS appears to come from the pancreas and GI
tract.
 It inhibits the secretion of GH.
Physiologic Effects of SS
 SS acts by both endocrine and paracrine pathways to affect its target cells.
 It affects the anterior pituitary to decrease GH.
 SS appears to act primarily in a paracrine manner to inhibit the secretion of
both insulin and glucagon.
293
 It also has the effect in suppressing pancreatic exocrine secretions, by
inhibiting CCK -stimulated enzyme secretion and Secretin stimulated
bicarbonate secretion.
 It has an inhibitory effect on the secretion of some GIT hormones such as
gastrin, CCK and VIP
 SS is often referred to as having neuromodulatory activity within the central
nervous system, and appears to have a variety of complex effects on neural
transmission.
Hormones of the pineal body

 The pineal gland (pineal body) in the epithalamus of the brain secretes
hormones that act on the hypothalamus or gonads to inhibit the reproductive
functions.
 The secretory products are:
1- Melatonin: can decrease GnRH secretion from the hypothalamus and
may inhibit reproductive functions through this mechanism. It may also
help regulate sleep cycle.
2- Arginine vasotocin: works with melatonin to regulate the reproductive
functions.
The thymus
 The thymus is located in the neck, posterior to the heart in the thorax.
 It secretes hormone called thymosin.
 Both the thymus and thymocin play a role in the immune system
development and maturation.
Hormones of the gastrointestinal tract

 Several hormones are released from GIT .They regulate the digestive
function by influencing the activity of stomach, intestine, liver and pancreas
(they are discussed in chapter 11).
Hormones of the reproductive system

 Reproductive hormones are secreted by ovaries, testes, placenta and
pituitary gland.
1. The main endocrine glands of the male reproductive system are the testes.
 The main hormone secreted by testes is the testosterone.
 The function of the testes depends on the secretion of FSH and LH from
the anterior pituitary.
2. The main endocrine glands of the female reproductive system are the
ovaries
 Functions of the ovaries depend on the secretion of FSH and LH.
 The main hormones secreted by the ovaries are:
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- Estrogen :is a steroid hormone work on most cells to control:
1- Uterine and mammary glands development and function.
2- Secondary sex characteristics and maturation of genitalia.
3- Sexual behavior and menstrual cycle.
- Progesterone :is a steroid hormone responsible for:

1- Uterine and mammary glands development and function.
2- Secondary sex characteristics and maturation of genitalia.
- Inhibin: a hormone secreted by the ovaries to inhibit secretion of

FSH.
- Relaxin: a hormone secreted by the ovaries to increase the flexibility
of the connective tissues of the symphysis pubis and help in dilation
of cervix of the uterus to facilitate the delivery.
3. The placenta: During the first one third of pregnancy placenta secretes LH-
like substance, which is necessary to maintain the pregnancy.
References
1. Basak A.K. Physiology: Made easy .Kolkata, India, New Central Book Agency
(NCBA), 2012.
2. Brown T.A. Rapid Review of Physiology.2nded.Philadelphia, Mosby, 2012
3. http//: www.ent-surgery.com.am
4. http//:www.adrenalfatique.co.nz
5. http//:www.ruisimeao.com
Pearson Education, Inc., 2012.
10. Seeley R.R., Stephens T.D. and Tate P. Anatomy and Physiology . 8th ed. New York,
295
Chapter thirteen
Reproductive system 13
Reproductive system
Overview
 The reproductive system controls the development of the structural and
functional differences between male and female.
 Differences between males and females depend on a single chromosome (Y
chromosome) and single pair of endocrine structures (the gonads): testes in
the male and ovaries in the females.
 The gonads have a dual function :the production of germ cells
(gametogenesis) and secretion of sex hormones .The testes secrete large
amounts of androgen principally testosterone but they also secrete small
amounts of estrogen .The ovaries secret large amount of estrogens and
small amounts of androgen.
 It has profound effects on the behavior.
 Reproduction is an essential characteristic of the living organism. The
functional male and female reproductive systems are necessary for
individual to reproduce.
 The male reproductive system produces sperm cells and can transfer them
to the female.
 The female reproductive system produces oocytes and can receive sperm
cells.
 One sperm cell may unit with an oocyte.
 Both male and female reproductive systems have number of similarities.
Many reproductive organs of males and females are derived from the same
embryologic structures.
 Some hormones are same in both sexes.
The male reproductive system

1- Testes:
 There is a pair of testes enclosed in a scrotal sac.
 The testes are divided by septa into compartments that contain the
seminifrous tubules ,where the sperm cells are produced(spermatogenesis)
 The seminifrous tubules become straight to form (tubulus recti) which lead
to (rete testis),(figure 13.1.a).
 The rete testis opens into the efferent ductules of the epididymis which is a
coiled tubule system located in the testis that is site of sperm cells
maturation.
 Spermatozoa pass through the tail of the epididymis into the vas deferens.
296
 The end of the ductus defernse (ampullae) and the seminal vesicle join to
form ejaculatory duct.
 The ejaculatory ducts pass through the prostate and empty into the urethra
within the prostate.
 The urethra exits from the pelvis and passes through the penis to the outside
of the body.
 Sertoli cells: cells are present in the testis to provide food to the developing sperm.
 Interstitial cells or Leydig cells: clusters of endocrine cells are located
between the seminiferous tubules secrete the hormone testosterone. (Figure
13.1.b).
Figure (13.1):a:Gross anatomy of the testis shows internal structures ,b:Cross section
of a seminiferous tubule. Spermatogonia are near the periphery and mature sperm cells
are near the lumen of the seminiferous tubule. (Seeley R.R., Stephens T.D. and Tate P.
2- Scrotum
 The scrotum contains the testes and is divided into two internal
compartments by incomplete connective tissue septum.
 The outer layer of the scrotum includes the skin, a layer of superficial
fascia consisting of loose connective tissue and a layer of smooth muscle
called: the dartos.
 The dartos and cremaster muscles(extension of abdominal muscles into
scrotum )have a role in temperature regulation of the testes:
- When the scrotum is exposed to cool temperature :
 The dartos muscle contracts so the skin of the scrotum becomes
firm and wrinkled and reducing its overall size.
 The cremaster muscles contract to help pull the testes near the
body to keep them warm.
- When the scrotum is exposed to warm temperature (exercise ,fever):
297
 The dartos and cremaster muscles relax and the skin of scrotum
becomes loose and thin allowing the testes to descend away from
the body to keep the testes cool.
 The regulation of temperature of the testes is important in the
spermatogenesis.
Sperm cells development

 Before puberty, the testes remain simple and unchanged from the time of
their initial development.
 The interstitial cells are not prominent at this period, lumen of the
seminiferous tubule are not functional.
 At 12-14 years of age, the interstitial cells increase in number, a lumen
develops in each seminiferous tubule and sperm cells production begins.
 Sperm cells development (spermatogenesis) occurs in the seminiferous
tubules (the process by which germ cells divide and differentiate to form
sperm cells).
 Interstitial cells and sertoli cells produce a number of hormones such as
androgen, estrogen and inhibin.
 Tight junction between the sertoli cells form blood testis barrier .It isolates
the sperm cells from immune system .As the sperms develop, they form
surface antigens that could stimulate an immune response resulting in their
destruction.
Spermatogenesis steps
 The spermatogonia divide by mitosis on the outer layer of the seminiferous
tubule.One daughter cell remains a spermatogonium (to divide again by
mitosis).Other daughter cell becomes a primary spermatocyte.
(Figure13.2).
 The primary spermatocytes divide by the first meiosis to form secondary
spermatocytes.
 The secondary spermatocytes divide by secondary meiosis to form 2
spermatids .Each spermatid contains one of each of the homologous
chromosome pair.(Each sperm contains 22 of autosom and either x or y
chromosome).
 Spermatids differentiate to form the sperm cells. Each spermatid undergoes
the last phase of spermatogenesis to form a mature sperm (spermatozoa).
 At the end of the spermatogenesis sperm cells gather around the lumen of
the seminiferous tubule (head directed toward the surrounding sertoli cells
and the tail directed to the center of the lumen).
 Finally the sperm cells released into the lumen of the seminiferous tubule.
298
Figure (13.2): Spermatogenesis. (Seeley R.R., Stephens T.D. and Tate P. Anatomy
and Physiology .New York, McGraw –Hill Companies, 2008).
 The mature sperms have:

1. The head: contains chromosome, at leading end has a cap (acrosome)
which contains enzymes necessary to penetrate the female sex cell.
2. Mid piece: has large number of mitochondria to produce ATP necessary
for microtubule movement.
3. Tail or flagellum: the movement of microtubule past one another within
the tail causing the tail to move. (Figure 13.3).
Figure (13.3): Structure of a mature sperm cell. (Seeley R.R., Stephens

T.D. and Tate P. Anatomy and Physiology .New York, McGraw –Hill
Companies, 2008).
299
3- Epididymis
 A long tube (6 cm) located along the superior and posterior margin of the
testis.
 Each epididymis consists of a head, a body and a tail.
 Sperm cells that leave the testis are immature .They complete their
maturation as the pass through the epididymis.
 Mature sperms are stored in the tail of the epididymis.
4- Ductus deferens or vas deferense

 Ductus deferens a fibromuscular tube that emerges from tail of the
epididymis.(Figure13.1 ).
 It ascends along the posterior of the testis medial to the epididymis and
becomes associated with the blood vessels and nerves that supply the testis.
 The end of the ductus deferens enlarges to form ampullae.
 The sperms are stored in the proximal portion of the ductus, near the
epididymis.
5- Spermatic cord: consists of:

1. Proximal ductus deferens
2. Testicular artery and venous plexus
3. Lymphatic vessels and nerves
4. Cremaster muscles and connective tissue.
6- Ejaculatory duct
 Each ductus deferens at the ampullae joins the short duct from the adjacent
seminal vesicle, to form the ejaculatory duct.
 Each ejaculatory duct (2-5 cm ) passes through the prostate gland and ends
by opening in the urethra . (Figure 13.4).
7-Urethra
 The male urethra is about (20 cm long), extends from the urinary bladder to
the distal end of the penis.
 It is a passageway for both urine and male reproductive fluid.
 It is divided into 3 regions:
1. prostatic urethra
2. Membranous urethra
3. Spongy urethra (penile urethra).
8-Penis
 It is located anterior to the scrotum and functions to transfer sperms to the
female reproductive system.
 It consists of 3 columns of erectile tissues that are wrapped in connective
tissue and covered with skin:
- The 2 dorsal columns are the corpora cavernosa
300
- The single midline ventral column surrounds the urethra is the corpus
spongium.
 It is 3 parts: The root attaches it to the pubic arch, the body and the glans.
 The prepuce covers the glans.
Figure (13.4): Male reproductive structures. www.slideshare.net
Accessory glands
1- Seminal vesicles
 The seminal vesicles are sac shape gland located next to the ampullae of the
ductus deferens.
 Each gland is 5 cm long and tapers into short excretory duct that joins the
ampullae to form the ejaculatory duct.
 The seminal vesicles have a capsule containing fibrous connective tissue
and smooth muscle.
2- Prostate gland
 The prostate gland consists of glandular and muscular tissues
 It is about the size (4cmx2cm) and shape of a walnut.
 It is located dorsal to the symphysis pubis at the base of the urinary bladder.
 The muscular parts are covered by a layer of columnar epithelial cells which
form secular dilation into which the columnar cells secrete prostatic fluid.
 Prostatic fluid is carried by prostatic duct into prostatic urethra.
3- Bulbourethral glands
 The bulbourethral glands are pair of small gland located near the
membranous part of the urethra.
 Each gland is a compound mucous gland that emptied into spongy urethra.
301
Semen
 Semen is a mixture of gland secretions and sperm cells :
- 60% of seminal vesicle production: contains fructose and fibrinogen.
- 30%of the prostate fluid: make the seminal fluid more neutral.
- 5% of the bulbourethral secretion: The bulbourethral gland and urethral
mucosa glands produce mucus which neutralizes the acidic PH of the
urethra.
- 5% of the testicular secretion: contains sperm cells.
Regulation of male reproductive function

 Regulation of male reproductive system depends on both hormonal and
neural mechanism :
- Hormones are responsible for development of the reproductive
structures, maintenance the functional capacity and development of
secondary sexual characteristics.
- Neural mechanisms are involved on sexual behavior and control of
sexual act.
Regulation of sex hormones secretion:

 The pituitary gland produces 2 hormones acting on the testes:
1. Follicle stimulating hormone (FSH) stimulates sperm development by
increasing activity of Sertoli cells (to produce food for the sperms).
2. Luteinising hormone (LH) controls secretion of testosterone by the
interstitial cells.
 Testosterone controls the male secondary sexual characters, such as
increasing facial hair, changes in the skeleton, distribution of fat, etc. It also
stimulates sperm development.
Puberty:
 Puberty is the age at which the individuals become capable of sexual
reproduction, which normally begins when a boy is 12-14 years old.
 Before puberty, small amount of testosterone inhibit GnRH release from
the hypothalamus.
 At puberty the hypothalamus becomes much less sensitive to the inhibitory
effect of androgens.
- ↑Secretion of GnRH lead to ↑LH and FSH release.
- ↑LH level causes the interstitial cells to secrete ↑amount of testosterone.
- Testosterone still has negative feedback effect on GnRH secretion, but
not complete suppressing .
Male sexual act

 Testosterone is required to initiate and maintain male sex behavior.
 The male sex act is a complex series of reflexes that results in the erection,
emission and ejaculation.
 Stimulation of the sexual act can be tactile or psychological.
302
 Action potentials are conducted by sensory neurons from the genitals
through the pudendal nerve to the sacral region of the spinal cord, where
the reflexes that result in the male sexual act are integrated.
 Action potentials travel from the spinal cord to the cerebrum to produce
conscious sexual sensation.
 Parasympathetic stimulation is responsible for :
- Erection: is due to vasodilatation of blood vessels that supply the
erectile tissues.
- The glands of the urethra and the bulbourethral produce mucosa.
 Sympathetic stimulation causes erection, emission and ejaculation.
- Emession: is the discharge of secretion of seminal vesicle, prostate
gland, bulbourethral and sperm cell from epididymis into the urethra to
form semen.
- Ejaculation: is the forceful expulsion of semen from urethra by
contraction of urethra in the floor of the pelvis and the muscles at the
base of the penis.
Clinical note: erectile dysfunction or impotence is the inability to achieve or

maintain the erection, may be due psychic causes or due to nerve damage
and exposure to surgery such as prostate surgery.
Pharmacology note: Erection can be achieved in some people by oral

medication such as: sildenafil (Viagra),tadafil(Cialis) or verdenafil (Livitra).
Sildenafil block the activity of the enzyme that converts cGMP to GMP.
Consequently it allows cGMP to accumulate in smooth muscle cells in the
artery of erectile tissues and cause them to relax.
Clinical note: Benign prostatic hypertrophy (BPH): Nonmalignant

enlargement of the prostate gland; common in older men.
Epididymitis: Inflammation of an epididymis; usually starts as an urinary
tract infection.
Prostate cancer: Most common form of cancer in men over 40; risks of
developing it increase with age.
Prostatitis: Inflammation of the prostate gland; may be acute or chronic.
Testicular cancer: Malignant growth in one or both testicles; more common
in males 15–30 years; more aggressive malignancy
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The Famle reproductive system
 Female reproductive system consists of the ovaries, uterus, uterine tube,
vagina, accessory glands, external gentilia (Figure 13. 5) and breast.
 Internal reproductive organs are within the pelvis between the urinary
bladder and the rectum.
 A group of ligaments holds the internal organs in the place.
 The board ligament is an extension of the peritoneum that spread out on
both side of uterus and to which the ovaries and uterine tubes are attached.
1- Ovaries
 The ovaries serve a dual purpose: produce female gametes (ova) and
produce sex hormones (estrogen and progesterone).
 The two ovaries are small organs about 2-3.5 cm long, 1-1.5cm wide.
 The ovaries are hold by a group of ligaments: (Figure 13.5).
1- Mesovarium (mesentery of the ovary) attaches the ovaries to the
posterior surface of the board ligament.
2- Suspensory ligament: extends from the mesovarium to the body wall.
3- Ovarian ligamen: attaches the ovaries to the superior margin of uterus.
 The vesiral peritoneum is made up of simple cuboidal epithelium called
germinal epithelium.
 There is a capsule of dense connective tissue (tunical albuginea) below the
germinal epithelium.
 The denser outer part of the ovary is called the cortex, while the looser inner
part is called the medulla.
 The connective tissue of the ovary is called stroma, through which ovarian
follicles (numerous small vesicles) are distributed.
 Each ovarian follicle contains (an oocyte).
Figure (13.5): Structures of female reproductive system. (Marieb E.N.and

Hoehn K. Anatomy and physiology. San Francisco, Pearson Education Inc., 2011).
304
Oocyte development and fertilization
 Formation of female sex cells begin in the fetus .By the 4th month of
development, the ovaries contain 5 million (oogonia).
 The oocytes develop from oogonia. (Figure13.6).
 Primary oocytes begin at the first meiosis and stop at the prophase I and
remain in this state until there are about 2 million of primary oocytes at
birth.
 From birth to puberty the number decreases to 800-400 thousands.
 Only 400 primary oocytes complete development and give rise to
secondary oocytes and the polar body released from the ovaries.
- Ovulation: release of secondary oocytes from the ovary, the polar body
either degenerates or divides to form 2 polar bodies.
- The secondary oocyte begins the second meiosis and stop in
metaphaseII.
 After ovulation: the secondary oocytes may be fertilized by a sperm cell.
- Fertilization: begins when a sperm cell binds to the plasma membrane
and penetrates into the cytoplasm of the secondary oocyte.
 Secondary oocyte completes the second meiosis to form 2 cells, each with
23 chromosomes.
- One of these cells is small and degenerates .The other large one.
- 23 chromosomes from sperm cell join with 23 chromosomes from the
female cell to form the zygote.
 The zygote has 23pair of chromosomes .All cells of human body contain
23pairs of chromosomes except for the male and female sex cells (23
chromosomes).
 The zygote divides by mitosis to form 2 cells which divide to form 4 cells
and so on.
 The mass cells formed after 7 days after ovulation may implant to the wall
of the uterus.
 The implanted mass of cells continues to develop to form a new individual
after 9 months of pregnancy.
305
Figure (13.6): Oocyte development and fertilization. (Seeley R.R., Stephens T.D.
and Tate P. Anatomy and Physiology .New York, McGraw –Hill Companies, 2008).
Follicle development
 A primordial follicle is a primary oocyte surrounded by a single layer of flat

cells (granulomas cells).
 A primordial follicle becomes a primary follicle as the granulosa cells
become enlarged.
 Primary follicle enlarges .Granulosa cells form more than one layer of cells .A
zona pellucid forms around the primary oocyte.
 The primary follicles become secondary follicles when fluid filled vesicles
develop among the granulose cells and well developed theca becomes
apparent.
 Formation of mature follicle when the fluid filled vesicles form a single
antrum.
 Ovulation occurs when the follicle swells and ruptures and the secondary
oocyte is released from the ovary.
 The mature follicle becomes the corpus luteum.If pregnancy occurs, the
corpus luteum persists .If no pregnancy occurs, it becomes the corpus
albicans. (Figure 13.7).
306
Figure (13.7): Maturation of follicle and oocyte.( Seeley R.R., Stephens T.D. and Tate P.
2- Uterine tube
 There are two uterine tubes (fallopian); each one is on each side of the
uterus associated with an ovary.
 Each tube is located along the superior margin of the broad ligament.
 The uterine tube opens directly into the peritoneal cavity to receive oocyte
from the ovary.
 It expands to form infundibulum and the long thin process is called
fimbriae surrounds the opening of the infundubulum. The inner surface of
the fimbriae consists of a ciliated mucus membrane.
 The part of the uterine tube that is nearest the infundibulum is called the
ampulla.
 The uterine tube consists of an outer serosa, middle muscular layer and an
inner mucosa with simple ciliated columnar epithelium.
 The mucosa provides nutrients for the oocyte or (if fertilization occurs) for
development of embryonic mass.
307
Movement of oocyte
 Cilia move the oocyte over the fimbriae surface into the infundibulum.
 Peristaltic movement and cilia move the oocyte within the uterine tube.
 Fertilization occurs in the ampullae, where the zygote remains for several
days.
3- Uterus
 Uterus is a pear shape muscular organ in the upper female reproductive
tract.
 The fundus is the upper portion of the uterus , where the pregnancy occurs.
 The cervix is the lower portion of the uterus that connects with the vagina
and serves as a sphincter to keep the uterus closed during pregnancy until
the time to deliver a baby.
 The wall of the uterus consists of perimeterum (myometrium: smooth
muscle layer) and the endometerium: the inner lining of vascular and
glandular material.
- The endometerium thicknes during the menstrual cycle to allow
implantation of the fertilized egg.
- If fertilization does not occur, the endometerium sloughs off and
expelled as menses flow.
4- Vagina
 It a muscular ridged sheath connecting the external genitals to the uterus.
 The vagina is folded into longitudinal folds.The hymen covers the vestibular
opening of the vagina. (The vestibule is the space into which the vagina and
urethra open).
5- Memory glands
 The memory glands are the organs of milk production, located within the
breast which is supported by Cooper’s ligaments.
 The memory glands are modified sweat glands.
 The general structure of the breast is similar in both males and females
before puberty.
 The female breast begins to enlarge during the puberty under the influence
of estrogen and progesterone.
 The memory gland consists of glandular lobes and adipose tissue.
 The lobes consist of lobules that are divided into alveoli.
 The lobes connect to the nipple, which is surrounded by areola through the
lactiferous ducts. (Figure13.8).
308
Figure (13.8): Structure of the breast . (Marieb E.N.and Hoehn K. Anatomy and
Puberty
 Puberty begins with the first menstrual bleeding (menarche), between the
ages 11-16 years.
 The reproductive organs begin to enlarge.
 Fat is deposited in the breast and around the hips.
 The ducts of the breast develop, pubic and axillary hair grows.
 GnRH , LH and FSH are secreted in greater quantities.
Menstrual cycle
 The term menstrual cycle refers to the cyclic changes that occurs in
sexually mature non pregnant females and culminate in menses. It is due to
changes in the uterus and cyclic changes in hormone secretion in the ovary
and uterus .It is about 28 days. (Figure 13.9).
 Menses is a period of mild hemorrhage, which occurs once each month,
during which the uterine epithelium is sloughed and expelled from the
uterus.
 The first day of menses is day 1 of the menstrual cycle .Menses lasts 4-
5days.
 Ovulation occurs in the 14 of the 28 days menstrual cycle.
 The time between ovulation and the next menses is typically 14.
 The time between the ending of the menses and the ovulation is called:
follicular phase due to rapid development of ovarian follicle, or
Proliferative phase because of rapid proliferation of the uterine mucosa.
309
 The period after ovulation and before the next menses is called: luteal
phase because of existence of corpus luteum, or Secretory phase because of
secretion of uterine glands.
Figure (13.9): Menstrual cycle.( Marieb E.N.and Hoehn K. Anatomy and

Clinical note: Dysmenorrhea a condition with severe menstrual cramps is the

result of strong myometrial contractions that occur before and during
menstruation. The cramp can result from excessive prostaglandin secretion as
part of inflammatory process.
Amenorrhea: absence of menstrual cycle .If it is due to abnormal pituitary
function and the female will not begin to menstruate at puberty .This is called
primary amenorrhea. If a female has had normal menstrual cycles and later
stops menstruation, this is called secondary amenorrhea .Anorexia is one cause
of this condition.
310
Pharmacology note: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as
aspirin or ibuprofen are effective in treatment of some painful menstruation
because they inhibit prostaglandin biosynthesis.
Ovarian cycle
 Refer to events occurring in a rhythymicity in the ovaries of sexually mature
nonpregnent women during the menstrual cycle.
 The hypothalamus and anterior pituitary release hormones that control
these events.
 FSH from the anterior pituitary is responsible for the initiating and
development of primary follicles.
 Although several follicles begin to mature during each cycle, normally one
is ovulated .The remaining follicles degenerate.
 Early in the menstrual cycle, the release of GnRH from the hypothalamus
increases the release of FSH, LH by anterior pituitary.
 FSH and LH stimulates follicular growth and maturation .FSH exerts the
main effect on the granulose cells. LH exerts its main effect on the theca
interna and later on the granulosa cells.
 LH stimulates the theca interna to produce androgens which diffuse from
the theca interna to granulosa cells.
 FSH stimulates the granulosa cells to convert androgen to estrogen.
 In addition FSH increases LH receptors in the granulosa cells and the
estrogen produced by the granulosa cells increases LH receptors in the theca
interna cells .( theca interna and granulosa cells cooperate to produce
estrogen). Estrogen increases receptors for LH in both theca interna and
granulosa cells.
 After LH receptors in the granulosa cell increase ,LH stimulate granulosa
cells to produce progesterone which diffuse from granulosa cells to the
theca interna cells where it is converted to androgen .
 Thus the production of androgen by theca interna cells increases and
conversion of androgen to estrogen by granulosa is responsible for gradual
increase in the estrogen secretion by these cells throughout the follicular
phase.
 FSH level decrease during the follicular phase because follicle cells produce
inhibin.
 As estrogen level increases during the follicular phase have negative
feedback on the FSH, LH.
311
 The gradual increase in the estrogen in the late follicular phase begins to
have positive feedback on FSH, LH .This leads to great stimulation for LH
and FSH secretion.
 As a result of positive LH, FSH increase rapidly in large amount just before
ovulation. This is called FSH surge and LH surge.LH surge initiates
ovulation and converts ovulated follicles to corpus luteum.
 FSH makes the follicle more sensitive to the LH by synthesis of LH
receptors .Shortly after ovulation the follicles production of estrogen
decreases and corpus luteum cells begin to release progesterone.
 Increased progesterone has negative feedback on the GnRH and as a result
LH and FSH decrease.
 If fertilization of the oocyte occurs, the outer layer of the developing
embryo begins to secret human chorionic gonadotropin (HCG) which
keep the corpus luteum from degeneration as a result blood level of estrogen
and progesterone does not decrease and the menses does not occur .In case
of fertilization does not occur, HCG is not produced and the cells of
corpus luteum begin to atrophy after 25 days of cycle. Blood level of
estrogen and progesterone decrease rapidly which result in menses.
Uterine cycle:
1-Menstrual phase:
 Menses: the functional layer of the endometrium sloughs off as the spiral
arteries remain in a constricted state in response to decrease level of
progesterone and estrogen.
 Functional layer tissue and some blood make up the menstrual fluid .The
basal layer of endothelium remains.
2-Proliferative phase:
 The basal portion of the endometrium is called basal layer.
 The epithelial cells of the basal layer proliferate in response to estrogen as a
result; the epithelial cells and loose connective tissue on which they rest
form the spiral shape uterine gland.
3-Secondary phase:
 The endothelial layer reaches the greater thickness and the spiral artery
remains dilated due to the presence of progesterone. (Figure 13.20).
Clinical note: Endometriosis is a condition in which endometrial tissue is found

in abnormal location, reduces fertility .Generally it results from some
endomertrial cells passing from the uterus through the uterine tubes into pelvic
cavity.
312
Figure (13.20): Phases of menstrual cycle.( Marieb E.N .Essential of Human
Female fertility and pregnancy

 In case of fertilization to occur,intercourse must take place 5 days before
and 1 day after ovulation if
 Sperm cells transport to the ampullae depend on the ability of the sperm s to
swim and on contraction of the uterus and uterine tubes.
 The oocyte can be fertilized for up to 24 hours after ovulation.
 One sperm enters the secondary oocyte and fertilization occurs.
 For the next several days ,a sequence of cell divisions occurs while the
developing embryo passes through the uterine tube to the uterus.(Figure
13.21).
 By 7-8 days after ovulation the endometrium of the uterus has been prepared
for implantation.
 Estrogen and progesterone cause the endometrium to reach to maximum
thickness and secretory activity and embryo begins to implant.
 The outer layer of the developing embryo is the trophoblast(forms
placenta)
 The trophoblast secretes HCG which is transported in the blood to the ovary
and causes the corpus luteum to remain functional.
 Estrogen and progesterone secreted by the corpus luteum are essential for
the maintenance of pregnancy.
 After the first 3 months of pregnancy the placenta has become an endocrine
that secretes sufficient quantities of estrogen and progesterone.
313
Trophoblast
Day 2
Day 5
Day 1
Blastocyst
Implantation day 6
Figure (13.21): Blastocyst (Seeley R.R., Stephens T.D. and Tate P. Anatomy
Menopause
 The cessation of menstrual cycle is called menopause.
 The menstrual cycle of a woman 40-45years old becomes less regular and
evaluation does not occur.
 Menopause is associated with changes in the ovaries, the number of follicles
remaining is small and the remaining follicles become less sensitive to
stimulation by LH and FSH.
 Morphological changes occur in the females in response to reduced amount
of estrogen and progesterone.
 A variety of symptoms occur in some women during this period: hot flashes,
irritability, fatigue, anxiety and emotional disturbance.
Pharmacology note: Symptoms that occur during the climacteric may be

treated by administration small amount of estrogen in combination with
progesterone, then gradually decreasing this treatment .On the other hand
some potential side effects of hormonal therapy are concern such as increase
risk for breast, ovarian and uterine cancer. Some data indicate that risk for
heart attacks, strokes and blood clots is also increased.
Clinical note: Ovarian cyst: fluid filled sacs that grow on or in the ovaries. Most
ovarian cysts are noncancerous and not harmful but may sometimes become
cancerous in women over 40 years.
Pelvic inflammatory disease (PID): Inflammation of female reproductive
organs most often due to sexually transmitted diseases.
Fibroids: Benign tumors in the uterine wall affect 25% of the women between
35-55 years.
314
References
Saunders, 2015.
8. Tortora G. and Derrickson B. Principle of Anatomy and Physiology .13th ed. Hoboken
,NJ, John Wiley & Sons,Inc.,2012.
315
Contents
1- Chapter one: Introduction to Myelinated and unmyelinated axon
Physiology 1 42
General concept 1 Organization of the nervous tissues 43
Structural and functional Membrane potential, Action potential and
organization 1 Nerve transmission 43
Homeostasis 1 Resting potential 44
Homeostatic imbalance 2 Graded potential 45
Regulation of body functions 3 Action potential 46
The importance of water in the Transmission of the impulse 51
body 3 Transmission of action potential between
Exchange between blood the cells 53
capillaries and interstitial fluid 3 The synapse 53
The cell and its functions 4 Types of neurotransmitters 56
Transport across membrane 13 Spatial and temporal summation 58
Simple diffusion 14 The spinal cord 59
Osmosis 15 Reflexes 61
Carrier mediated transport 15 The brain 63
Vesicular transport 18 Basal nuclei 68
Junctions between the cells 20 Limibic system 69
Higher functions of the cerebral cortex 69
2-Chapter Two: The Cell Cycle Language 69
and Genes Control of Protein Memory 70
Synthesis 22 Brain waves 70
Organization of genetic materials Sleep 71
within the cell 22 Meninges Ventricles and cerebrospinal
Cell cycle 23 fluid 71
DNA Replication 24 Cerebrospinal fluid flow 74
Regulation of cell cycle 28 Blood supply to the brain 75
Cell cycle control in cancer cells Blood brain barrier 76
30 Cranial nerves 76
Gene and protein synthesis 32 Peripheral nervous system 79
The transcription and translation Sensation 80
processes 32 Sensory receptors 81
Production of proteins 35 Sensory transduction 81
Regulation of genetic expression Adaptation 81
37 Sensory pathways 82
Genetic disorders 38 Pain receptors 83
Motor tracts 83
3-Chapter Three: Nervous Autonomic nervous system 84
system 39 Sympathetic nervous system 86
Organization of nervous system Parasympathetic nervous system 86
39 The enteric nervous system 86
Cells of nervous system 40 Chemical transmission 87
Autonomic dysfunction 87
316
4-Chapter four: Special senses Regulation of contraction 117
88
Olfaction 88 6-Chapter six: Cardiovascular
Taste 89 system 118
Vision 90 Heart 118
Detection of light 91 Systemic and pulmonary
The ear –Hearing 95 circulation 118
Auditory transduction 96 Functions of the heart 119
Sound encoding 96 Heart anatomy 120
Neural pathways of hearing 97 Blood flow through the heart
Body equilibrium 97 123
Heart skeleton 125
5-Chapter Five: Skeleton and Cardiac muscle 125
Muscular system 99 Conducting system of the heart
Skeletal system 99 126
Bone function 99 Electrical prosperities 127
Cartilage functions 99 Action potential in cardiac
Bone structure 100 muscle 128
Compact and cancellous bone Autorhythmicity of cardiac
100 muscle 129
Bone shape 103 Refractory period 130
Bone growth 103 The electrocardiogram 130
Bone remodeling 103 Common cardiac arrhythmias
Factors affecting bone growth 131
103 Cardiac cycle 132
Joints 104 Heart sounds 133
Muscular system 105 Aortic pressure curve 134
Characteristics of muscle tissues Mean arterial pressure 135
105 Regulation of MAP 136
Muscle functions 105 Regulation of the heart 136
Skeletal muscle structure 106 Heart homeostasis 137
Muscle contraction 108 Blood vessels 139
Sliding filament model 108 Dynamic of blood circulation
Motor units 108 139
The muscle twitch 111 Blood flow 139
Types of contraction 112 Blood pressure 140
Regulation of contraction 113 Capillary blood pressure 143
Energy source for muscle Capillary exchange and
contraction 113 interstitial fluid volume
Types of skeletal muscle fibers regulation 143
114 Local control of blood flow by
Smooth muscle 114 the tissue 145
Types of smooth muscle s 115 Circulatory insufficiency or
Mechanism of contraction 116 shock 145
Regulation of contraction 116 Types of shock 145
Cardiac muscle 116
317
7-Chapter seven : Blood Cells of adaptive immune system
Blood 146 170
Functions of blood 146 Macrophages 170
Red blood cells 147 Humeral immune response 170
Formation of blood cells 148 Active and passive humeral
Regulation of red blood cells immunity 171
production 149 Antibodies 172
Fate of red blood cells 150 Primary and secondary
Hemoglobin 151 response 173
White blood cells 152 Cellular immune response 173
White blood cells classification Disorders of immunity 174
153 Transplantation 175
Platelets 154
Hemostasis 154 9-Chapter nine: Respiratory
Platelets plug formation 155 system 176
Coagulation 155 Functions of respiratory system
Disorders of hemostasis 157 176
Blood grouping 158 Structural considerations 177
Transfusion 185 Respiratory airways 177
ABO blood groups 158 The lung 181
Rh group 158 Pulmonary ventilation 182
Disorders of blood 159 Inspiration 182
Anemia 159 Expiration 182
Polycythemia 161 Basic concepts of air movements
and pressure 183
8-Chapter eight: Lymphatic Work of breathing 186
system and immunity Pulmonary compliance 187
Lymphatic system 162 Pulmonary surfactant 188
Lymphatic vessels 162 Lung volumes and capacities
Lymphatic tissues and organs 189
162 Dynamic lung volumes191
Lymphatic circulation 164 Gas exchange 192
Body defense and immune Diffusion of gases through the
mechanism 165 respiratory membrane 193
Innate immunity 165 Respiratory membrane 193
Innate defense cells and Diffusion capacity of the
chemicals 165 respiratory membrane 194
The events of inflammatory Perfusion limited and diffusion
processes 165 limited gas exchange 194
Life span of phagocytes 166 Pulmonary blood flow 194
Complement system 167 Alveolar ventilation and
Interferon 168 pulmonary circulation perfusion
Fever 168 195
Adaptive immunity 169 Oxygen and carbon dioxide
Antigen 169 transport in the blood 195
318
Partial pressure gradient of O2 Regulation of acid-base balance
and CO2 196 225
Oxygen hemoglobin Respiratory regulation of acid –
dissociation curve 197 base balance 226
The Bohr Effect 197 Renal regulation of acid-base
Transport of CO2 198 balance226
Regulation of respiration 199
Hypoxia 200 11-Chapter eleven: Digestive
system 227
10-Chapter ten : Urinary Functions of digestive system
system201 227
Function of the kidneys 201 Structural considerations 228
Structural considerations 202 Salivary glands 230
Structure of nephron 203 Regulation of salivation 230
Structure of glomerulus 305 Esophagus 230
Renal blood flow 206 Steps of swallowing 230
Renal nerve supply 207 Stomach 231
Urine formation 207 Regulation of secretion function
Glomerular blood flow 207 234
Glomerular filtrate 207 Small intestine 236
The glomerular filtration rate Small intestine secretions 238
208 Intestinal motility 239
Factors that affect GFR 208 Liver 239
Reabsorption and secretion in Functions of the liver 241
the tubules 209 Pancreas 243
Renal transport mechanism Pancreatic secretions 244
209 Large intestine 244
Tubular transport maximum Defecation 246
210 Defecation reflexes 246
Renal clearance 211 Secretion of large intestine 246
The proximal tubule 211 Digestion and absorption 246
Loop of Henle, distal tubule Carbohydrates 247
and collecting duct 214 Proteins 248
Urea trapping 217 Lipids 249
Vasa recta 217 Absorption of water 250
Potassium excretion 217 Absorption of electrolytes 251
Renal regulation 218 Absorption of vitamins 252
Urine collection and Absorption of iron 252
micturition 220
Regulation of micturition 221 12-Chapter twelve: Endocrine
Anatomical considerations of system253
ureters, urinary bladder222 Functions of endocrine system
Diuretics 223 253
Body fluid regulation224 Mechanism of hormones action
Regulation of body fluid 253
osmolality 224 Types of hormones 256
319
Pituitary gland and Glucagon 283
hypothalamus 257 Somatostatin 283
Structure of pituitary gland Hormones of the pineal body
257 284
Relationship f the pituitary to The thymus 284
the brain 258 Hormones of the
Anterior pituitary hormones gastrointestinal tract 284
260 Hormones of the reproductive
Pathological conditions 260 system 284
Relationship among the
hypothalamus, posterior 13-Chapter thirteen:
pituitary and target tissues Reproductive system 286
262 The male reproductive system
Posterior pituitary hormones 286
263 Structural considerations 286
Classification of endocrine Sperm cells development 288
diseases 263 Spermatogenesis steps 288
Thyroid gland 264 Accessory glands 291
Thyroid hormones 265 Semen 292
Regulation of thyroid Regulation of male reproductive
hormones 268 function 292
Pathological conditions 269 Regulation of sex hormones
Parathyroid gland270 secretion 292
Parathyroid hormones 271 Puberty 292
Pathological conditions 273 Male sexual act 293
Adrenal gland 273 The female reproductive system
Pathological conditions 274 294
Pathological conditions of Structural considerations 294
aldosterone 276 Oocyte development and
Physiological effect of cortisol fertilization295
276 Follicle development 296
Regulation of cortisol Movement of oocytes 298
secretion 276 Puberty 299
Pathological conditions of Menstrual cycle 299
cortisol 277 Ovarian cycle 301
Testosterone 278 Uterine cycle 302
Estradiol 278 Female fertility and pregnancy
Pancreas 279 303
Insulin 279 Menopause 304
Regulation of insulin secretion
281
Pathological of insulin 281
320
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Introduction to Human Physiology

Book · August 2016

Azza Sajid Jabbar

Researchers in pulmonary physiology View project

The user has requested enhancement of the downloaded file.

While teaching physiology to the medical, pharmacology and health

In the recent time the physiological components are widely available by

Alhamdulillah to achieve this book which I hope it would be workable

Dr.Azza Sajid Alkinany

Structural and functional organization

 Positive feedback is a mechanism by which an output is enhanced such as

 Negative feedback is a mechanism by which the output activity of any organ

Regulation of body functions

The importance of water in the body:

Exchange between capillaries and interstitial fluid

The cell membrane

2- Peripheral which are temporarily associated with lipid bilayer or with

1- Smooth ER looks smooth because it lacks ribosomes.

2- Rough ER looks rough because bound ribosomes are attached to the

 The lysosome is a membrane-bounded sac of hydrolytic enzymes that

Clinical note: Several inherited diseases affect lysosomal metabolism.These individuals

Clinical note: When mitochondrial dysfunction is inherited through mitochondrial

Extra non-membranous-enclosed organelles

Transport across membranes

a- Diffusion of uncharged substances

 Permeability (P) is directly proportional to the lipid solubility of the

b- Diffusion of charged substances

c- Diffusion of polar and non polar substances

Pharmacology note: Proton pump inhibitors such as omeprazole are used to

a- Primary active transport:

b- Secondary active transport:

Clinical note: In chronic granulomatous disease (CGD), mutations in the proteins of

accumulate forming granulomas

Figure (1.13): a: phagocytosis (cellular eating), b: pinocytosis (cellular drinking).

 Receptor-mediated endocytosis is very specific in what substances are

Clinical note: Familial hypercholesterolemia, an inherited disease, the LDL receptors

Figure (1.14): Receptor-mediated endocytosis. (Marieb E.N .Essential of Human Anatomy

Junctions between cells

3- Desmosomes (macula adherence):

Organization of the genetic material within the cell

Figure (2.6): Formation of contractile ring. Figure (2.7): Control system.during

Regulation of the Cell Cycle

 Peaks in the activity of one Cdk complex, MPF (maturation-promoting

 Meiosis is a form of cell division that happens in sexually reproducing

Genes and Proteins synthesis

The Transcription and Translation processes

Figure (2.11): RNA processing. Figure (2.12): Transcription and translation.

 In the genetic code, nucleotide triplets specify amino acids.

Figure (2.14 ):Translation of mRNA to produce a protein.(Reece J.B. ,Urry L.A.,

2- Elongation consists of a series of three steps cycles, as each amino acid

 Typically a single mRNA is used to make many copies of a polypeptide

 Additions like sugars, lipids, or phosphate groups to amino acids.

Regulation of Genetic Expression

Organization of the nervous system

Figure (3. 1): Nervous system divisions.

Cells of the nervous system

1-Neurons: This is made up of:

a. Myelinated axons are wrapped by several layers of plasma membrane from