MSA

University

PHYSIOLOGY
For Dental Students, SGS 235

By
Prof. Dr. Maher Naguib Ibrahim
Professor of Medical Physiology

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 INDEX

1. Autonomic nervous system…………………….. 3

2. Blood …………………………………....……… 19
3. Cardiovascular system ………………………...53
4. Endocrine ……………………………….……...72
5. Renal physiology ……………………………… 73

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 Autonomic Nervous System

All body functions could be regulated by either by nervous system

(rapid, short period) or by chemical regulation (hormones, enzymes
which is slow in onset with prolonged long lasting effect).
8-The nervous system can be classified into:-
1-Central nervous system: which is protected by bone (skull-
vertebral column), and includes, the brain (cerebral cortex - brain
stem "medulla, pons, midbrain"- cerebellum) and the spinal cord
which is formed of 31 segments: 8 cervical (C) ,12 thoracic, 5 lumbar
(L) , 5 sacral (S), 1 coccygeal.

2-Peripheral nervous system: which is divided into somatic (motor

nerves and sensory nerves) and autonomic nervous system.
-The somatic nervous system that controls the voluntary skeletal
muscles contraction.(formed of 12 pairs of cranial nerves, and 31
pairs of spinal nerves)
-The autonomic nervous system which controls the involuntary
activities of the heart, exocrine glands and the smooth muscles all
over the body.
-The functions of the A.N.S :-
1- Preparation of the body to face emergencies (stresses).
2- Regulation of food digestion, body temperature, heart rate, blood
pressure , hormonal secretion and excretory processes.
*The efferent autonomic nervous system:
The A.N.S reaches its target organs via the autonomic nerve.Each
autonomic nerve is an efferent axon of two nerve cells:
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*The first one lies inside either the brain or the spinal cord (C.N.S)
and it's axon is called the pre-ganglionic fiber.
*The second cell lies outside C.N.S (in what is called the autonomic
ganglia) and it's axon which reaches the organ is called the post-
ganglionic fiber.
- The mother cell of the pre-ganglionic autonomic nerve fiber lies in
the lateral horn of the spinal cord.
- Unlike the autonomic nerve, the somatic nerve moves to the
voluntary or skeletal muscles from anterior horn and reach the
muscle directly without passing through any ganglia.
• The differences between somatic and autonomic nerve
Somatic nerve Autonomic nerve

Drawing ,see fig ee

origin(cell) AHC( ant. horn cell LHC( lateral horn cell)

No of fibers Only one i.e on efferent 2 nerves

-One preganglionic inside CNS
-The other is posganglionic, outside CNS

Function Voluntary, Involuntary

operator regulator

Chemical transmitter Only acetyl choline Both acetyl choline & & catecholamines

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 Autonomic ganglia
*Definition: A ganglion is a collection of nerve cells outside the
C.N.S surrounded by connective tissue capsule. It contains
the nerve fibre of the pre-ganglionic neurons and cells of
the post-ganglionic neurons.
*Function of autonomic ganglia:
1- Relay stations as the preganglionic fibers branch and gives
impulses onto several post-ganglionic neurons.
2- Site of action of autonomic drugs.
3- Distributing centers as the ratio of pre to postganglionic fibers is
1:8. In this way, postganglionic impulses are expanded into several
postganglionic neurons. Postganglionic nerves arise in the ganglia
and are distributed to various organs.
*Types of autonomic ganglia:
1-Lateral (=Paravertebral ): Which form the sympathetic chains
lying on both sides of the vertebral column. Each chain is formed of
23 ganglia i.e. 3 cervical (superior, middle and inferior), 12 thoracic,
4 lumbar and 4 sacral ganglia. Lateral ganglia are only sympathetic.
2-Collateral (=Prevertebral): These are the coeliac, the renal, the
superior and inferior mesenteric ganglia and otic , ciliary,
sphenopalatine and submandibular ganglia. All collateral ganglia are
sympathetic ganglia
3-Terminal (Peripheral) : They are present near or in the wall of the
autonomic organ, e.g. the eye, the heart, the stomach and the urinary
bladder. Terminal ganglia are only parasympathetic.
*Divisions of autonomic N.S.

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1- Sympathetic nervous system: Arising from the lateral horn cells
of all the thoracic segments and the upper two lumbar segments. So it
is called the thoraco-lumbar outflow.
2- Parasympathetic nervous system: Arising from 2 distant parts:
(a) From some cranial nervous, i.e. III.VII.IX&X.
(b) From the lateral horn cells of the 2nd , 3rd and 4th sacral
segments of the spinal cord. So, it is called the cranio-sacral outflow.
*Differences between sympathetic and parasympathetic nervous
systems

Sympathetic nerv. system Parasympathetic nerv. system

origin -Thoracolumbar i.e from all -Craniosacral i.e from cranial nerves 3,
thoracic segments and L1,2 7,9,&10 and S2,3,4

ganglia -Lateral and collateral gan. -terminal gang.

distribution -wider - narrower ,no parasympathetic supply

to,skinstructures,limbs,abdominal
wall,ventricles of heart and adrenal
medulla

General actions -generalized, catabolic, acts only-localized ,anabolic, acts only in normal
and function in abnormal conditions .In resting conditions, it increases secretions
normal condition it it causes VC and motility of gut and decreases heart

Effect on blood -VC except in -VD except ,coronary blood vessels

vessels
*Skeletal m. blood vessels
*Coronary blood vessels

Effect on heart -Increases all activity and -Decreases all activity and properties of
properties of heart heart

Effect on bronchus-broncho dilatation -broncho constriction

Effect on glands Viscid secretion and small in Watery secretion and large in amount
amount called trophic sec. called true sec.

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Skin structures -Increase sweating - ve ( no parasympathetic supply)
-VC of skin bl.vessels
-Erection of hairs due to
contraction of erector pilae
muscle

Effect on liver -glycogenolysis - increases bile secretion

Effect on spleen Contraction of splenic capsule -ve ( no parasympathetic supply )

and release of 250 ml of blood

Metabolic effects -Increases glucose -Glycogenesis

-Decrease insulin -lipogenesis
-Lipolysis
-glycogenolysis

Effect on hollow -contraction of sphincter and - contraction of wall and relaxation of

organs e.g gall relaxation of wall leading to sphincter leading to evacuation and
bladder and filling and retention of the empting od the content
urinary bladder content

Effect on sex -ejaculation of semen - erection of male sex organ ( penis)

organ (male sex
organ)

Effects on eye -elevation of upper eye lid due

to cont. of tarsal muscle
myosis, due to cont. of constrictor
-mydriasis due to contraction pupillae m
of dilator pupillae m
-relaxation of ciliary m,helping
in far vision -contraction of cilliary m. helping in
near vision
-VC of blood vessels
-exophthalmos, due to cont. of
Muller m -VD of blood vessels
-increases lacrimation

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 CHEMICAL TRANSMISSION
*Definition : Chemical substance that can transmit stimulation of a
nerve to another nerve or to the organ through a synapse
*Definition of the synapse: It is the junctional area between 2
neurons, or between a neuron and an effector organ,
muscle or gland.( see fig )
Chemical Transmitters
-There are many types of chemical transmitters such as
acetylcholine (Ach), noradrenaline, adrenaline, dopamine, serotonin,
gamma-aminobuteric acid (GABA), glutamate, aspartate, substance
P, endorphins, enkephalins. The commonest are Ach and
catecholamines,noradrenaline and adrenaline
-The nerve that secretes acetylcholine is called a cholinergic nerve
and that which secretes noradrenaline is called an adrenergic nerve.
-Likewise, the receptors, which are activated by acetylcholine, are
called cholinergic receptors and those activated by noradrenaline are
called adrenergic receptors.
Acetyl choline
*Synthesis, transport & storage:
- Acetyl choline is synthesized in the cholinergic nerve fiber by
acetylation of choline base as follows:

Acetyl CoA + choline Acetyl choline + CoA

-Choline is transported from ECF actively to inside the axon
terminals. In the cytoplasm, the enzyme (choline acetyle transferase)
transforms choline into Ach in the presence of acetyle-CoA, ATP and
glucose.
-It is stored in small membrane-bound vesicles called clear vesicles.
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*Release of Ach: ( like release of any chemical transmitter )see fig
- Arrival of the nerve impulse to the nerve terminal which stores
acetyl choline leads to opening of Ca++ channels and Ca++ influx
occurs which destabilizes the stored vesicles causing them to fuse
with the membrane and then released by exocytosis.
- Ach cross the synaptic cleft to bind with its specific receptors on the
postsynaptic membrane producing its action.
Some drugs promote acetyl choline release as "carbachol". Some
drugs interfere with acetyl choline release as Mg++, phosphate and
EDTA through interfering with Ca++ function.
*Sites at which Ach is released (=cholinergic fibers),see fig:
A) central cholinergic fibres
1-Inside C.N.S.
2-At all the autonomic ganglia (all the preganglionic nerve endings)
3- At suprarenal medulla.
4-At the motor end plate (junction between somatic nerve and muscle
fibers).
B) peripheral cholinergic fibres
5-At all post-ganglionic parasympathetic nerve fibres.
6-At some sympathetic post-ganglionic nerve endings to sweat glands
and blood vessels of skeletal muscle
*Cholinergic receptors and types of acetyl choline
ctions(see fig )
A-Nicotinic receptors and actions:
- They are so called nicotinic because small dose of nicotine can
produce the same effects of acetyle choline at these certain sites:
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 1-Inside the CNS.
2-At all the autonomic ganglia.
3-At the motor end plates.
4-At the supra renal medulla.
-The nicotinic actions of Ach at these sites are blocked by large doses
of nicotine.
B-Muscarinic receptors and actions:
-They are so called muscurinic because the drug "muscurine" can
produce all the actions (slow but of long duration) of Ach at these
sites.
-Atropine or hyosine blocks muscurinic actions of acetyl choline.
-Muscurinic actions of acetyl choline are found in all the
postganglionic parasympathetic nerve fibers and at some
postganglionic sympathetic nerve fibers (sweat glands, skeletal
muscles):
1-Cardiovascular system. 2-Gastrointestinal tract (G.I.T).
3-Respiratory system. 4-Exocrine glands.
5-Genitourinary system. 6- C.N.S. 7- Eye.
Nicotinic receptors Muscarinic receptors

Other name Central Peripheral

In front of Central cholinergic fibers Peripheral cholinergic fibers

Present in Post ganglionic nerves suppling All postganglionic nerves suppling

,skeletal muscle and adrenal autonomic organs
medulla

Stimulated by A.cholin or small dose of nicotine A.cholin or muscarine

Blocked by Large dose of nicotine, ganglion Atropine or hyoscine

blockers or neuromuscular blocker

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• Inactivation of Ach see fig:
1- ACh is rapidly hydrolyzed within few seconds into choline base
and acetate by the help of cholinesterase enzyme.
2-Diffusion from site of release to the blood or to other site.
3-Re-uptake by the synaptic vesicles.
• Drugs that are related to the Parasympathetic system:
A-Parasympathomimetics " cholinergic receptor stimulants".:
They produce or stimulate the same actions of the parasympathetic
system in the body. e.g:
1-Choline esters:
.They are resemble Ach in structure, but synthetic and not
hydrolyzed by esterase enzyme.
.They stimulate muscarinic receptors much more than the nicotinic
receptors e.g. Carbacol and methacholine.
.They are used in treatment of :-
a) Postoperative paralytic ileus.
b) Urine retention.
2-Naturally occurring alkaloides:
.They are plant in origin.
.Stimulate directly muscurinic receptors.e.g muscurine and
pilocarpine Both drugs act mainly on the eye and on the secretory
glands.
.Uses: Pilocarpine is used as eye drops to cause myosis in the
treatment of simple glucoma to lower the intraoccular pressure.
3-Anti choline esterases (choline esterase inhibitors):

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 .These drugs act indirectly by inhibiting cholinesterase enzyme thus
allowing accumulation of endogenously secreted Ach.
.These drugs have both muscarinic and nicotinic actions.
. These drugs are classified into two big groups:
A) Reversible anticholine esterases:
-Their inhibitory effect on the enzyme persists only for few hours,
then the enzyme resumes again it's activity because these drugs binds
loosely by the enzyme.e.g
* Eserine (pheostigmine) which is used mainly as eye drops to lower
intraoccular pressure in glucoma. Also it is used to antagonize
mydriatic effect of atropine.
*Prostigmine (neostigmine) this drug beside its reversible
anticholine esterase effect has also direct nicotinic stimulant effect.
Thus the most important uses are:
1-To stimulate intestinal motility after abdominal surgical operations
to avoid paralytic ileus which is caused by over sympathetic activity.
2-To stimulate smooth muscles of the urinary bladder in urine
retention.
3-In treatment of Myathenia gravis: that is a hereditary disease
more common in females characterized by marked skeletal muscle
weakness and extreme easy fatigability.
B) Irreversible anticholine esterases:=(Organophosphorus
poisoning): used as war gases or insecticides
-These are highly toxic drugs and have no medical uses. They
undergo intial and permenant binding to the choline esterase enzyme
- e.g DFP (dilsopropyl flurophosphate one of the war gases which
must not be used), Parathion (used as insecticide to kill insects),and
the most serious member soman which is used as nerve gas in wars.

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- The danger of these compounds is that they can be absorbed from
even the intact healthy skin beside the stomach and they reach the
brain very easy (can cross blood brain barrier) leading to sever
stimulation of all cholinergic receptors.
B-Parasympatholytics (Drugs blocking A.ch effects):
-These are drugs which when given it antagonize the actions of
parasympathetic nervous system or they block the cholinergic
receptors.
I- Muscurinic receptor blockers:
- These drugs block the muscarinic receptors and antagonize actions
of acetyl choline on organs.
- The most important drugs are atropine and hyoscine. Atropine is
natural alkaloid found in Atropa belladonna and Datura stramonium.
It causes reversible competitive blockage of ACh actions at the
muscarinic receptors.
- Most important uses are:
1-Mydriasis for fundus examination.
2-In pre-anathetatic medication (before surgical operations) to block
vagal tone for protecting the heart from bradycardia and to abolish
bronchial secretion (atropine inhibits all exocrine secretions except
milk).
3-Diminshing gastric secretions in hyperacidity and peptic ulcers.
4-Releifing intestinal and renal colic.
5-Inhibiting excessive sweating.
N.B: Atropine has 3 famous signs (side effects): Tachycardia, dry
mouth and flushed face (due to inhibition of sweating that increase
body temperature causing V.D).
II- Nicotinic receptor blockers: - divided in to
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a. ganglionic blockers
-These drugs block the actions of Ach at all the nicotinic receptors
i.e at all the autonomic ganglia, C.N.S and in the motor end plate.This
group of drugs are not used nowadays .
b. Neuromuscular blockers:
- These drugs block the action of Ach at the motor end plate causing
muscle relaxation "skeletal muscle relaxant ".
- They are mainly used before surgical operation to facilitate
abdominal exposure , in the treatment of convulsions in some cases of
epilepsy and decreases muscle tone and heat production.
- Postsynaptic blockers which are medically used are divided into:
1-Competitive neuromuscular blocker e.g curare which combine
with Ach receptors at motor end plate and it's action is reversible.
2-Depolarizing blockers which causes maintained depolarization as
succinyl choline and it is also reversible.
-Curare and succinyl choline are use in a) treatment of convulsions
and b) in anesthesia
Catecholamines
-The chief chemical transmitters in the sympathetic N.S, are mainly
noradrenaline (Norepinephrine) and adrenaline (epinephrine)
- In the body Noradrenaline, adrenaline and dopamine are naturally
formed and they are called "catecholamines" because they contain
catechol ring.
- Another important synthetic catecholamine called "isoprenaline" are
not present in our body but has important medical value.
• Synthesis and transport: see fig

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They are formed from the amino acid "tyrosine" and phenylalanine
and are transported and stored inside the synaptic vesicles.

Tyrosine Dopa dopamine

Adrenaline noradrenaline
*Storage: stored in nerve terminals as:
1) Free not bound with ATP and released by nerve impulse.
2) Cytoplasmic (bound with ATP but not vesicular) and released by
exogenous drugs.
3) Vesicular (dark vesicle): combined with ATP and protein
*Sites of release of catecholamines also called adrenergic fibers :
1-At all adrenergic nerve fibers (form mainly noradrenaline 80%).
2-At the chromaffin cells of the suprarenal medulla (modified
sympathetic ganglia). Where adrenaline is formed more (about 80%)
while noradrenaline (only 20%).
3-Also, dopamine in some areas in the brain as basal ganglia is more
concentrated and acting as the chief chemical transmitter.
*Release:
- By exocytosis (Nearly like mechanism of release of Ach)
*Inactivation of catecholamines: see fig
-After their release catecholamines must be removed from the
circulation to avoid prolonged undesirable effects (tachycardia and
elevation of the blood pressure).The main methods of inactivation
are:
1-Active re-uptake: (about 85%).
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 -This uptake may be neural into neural cytoplasm, granular into
storage vesicles or non-neural into glial cells, muscles.
2-Methylation by catechol ortho-methyl transferase "COMT" which
is found in liver and kidney not in the nerve endings.
3-Oxidation_by mono-amino-oxidaze enzyme “MAO” that is
mitochondrial enzyme widely distributed in liver, kidney, gut and in
the noradrenergic neurons
4-Small amounts are excreted in urine
N.B:- Adrenaline differs from Noradrenaline in that :-
Adrenaline Noradrenaline
(norepinephrine)
(epinephrine)

- Structure noradrenaline+ methyl group

- Secretion -in suprarenal medulla -In postganglionic

- Receptors -Beta > alpha -alpha > beta receptors

- Effect -mainly metabolic (bl. glucose, - mainly vascular (VC)

lipolysis)

*Adrenergic receptors:
-Types of adrenergic receptors:
-There are 2 types of adrenergic receptors, which explain the
antagonizing effects of the sympathetic stimulation in different
organs: 1-Alpha receptors, which is further subdivided into alpha-l,
and alpha-2 2-Beta receptors, which is also, subdivided into Beta- l,
and Beta-2.
-Alpha-1 adrenoceptors:
- stimulation of them cause vasoconstriction of blood vessels, cardiac
acceleration, contraction of the plain muscles of the sphincters of the

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G.I.T , contraction of the smooth muscles of the vas deference and
seminal vesicles, also mydriasis.
-Alpha-2 adrenoceptors:
. stimulation of alpha-2 receptors causes platelets aggregation,
inhibition of both lipolysis and insulin secretion and relaxation of
small intestine.
-Beta-1 adrenoceptors:
-located in the heart and stimulation of them increase all the cardiac
properties, also lipolysis in the fat cells and increase renin release.
-Beta-2 adrenoceptors:
- They are present in uterus, lung and other sites. Stimulation of them
causes: coronary dilatation; relaxation of the bronchial, uterine and
bladder smooth muscles; inhibition of platelets aggregation; stimulate
insulin secretion and glycogenolysis in the liver.
Alpha adrenergic receptors Beta adrenergic receptors

Action& Mostly excitatory except in small

Mostly inhibitory except in
general rule intestine heart

Subtypes Alpha one and alpha two Beta one and beta two

Examples Alpha 1,excitatory Beta 2, inhibitory

-contraction of dilator pupillae -bronchodilatation
causing mydriasis
-relaxation of wall of
-vasoconstriction of blood vessels
urinary bladder
-contraction of all sphincters -Relaxation of wall of of
small intestine
-contraction of splenic capsule
-contraction of seminal vesicles
causing ejaculation of semen

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 Alpha 2, inhibitory Beta 1 excitatory
Relaxation of smooth muscle of
-Heart
small intestine
-Metabolic actions, as
lipolysis,glycogenolysis
&increase renin secretion

Drugs acting
-Stimulants -Noradrenaline and adrenaline -Adrenaline and isoprenaline
(agonists)
-salbutamoul(ventoline)is a B 2
-Blockers ( agonist
(antagonists)

-indral(=propranolol),oratenolol

Drugs acting on sympathetic nervous system(see figure )

-Sympathomimetic drugs , they are used to1) increase blood pressure
for hypotensives,2)to dilate bronchus for asthmatics, 3) to reduce
weight for obese
-Sympatholytic drugs, more used than sympathomimetic drugs. Most
of them are used as hypotensive drugs for hypertensive patients,

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 Blood
Blood is a connective tissue with fluid matrix present inside the
cardiovascular system and plays an important role in homeostasis.
Composition of blood:
- 55% clear yellowish fluid called plasma.
- 45% cellular elements [red blood cells (RBCs), white blood cells
(WBCs) and platelets].
Physical properties:
(1) Colour: red due to presence of hemoglobin in RBCs.
(2) pH: 7.4 (7.35-7.45) ( the venous blood is slightly acidic as it
contains more Co2 and metabolites from tissue)
(3) Specific gravity:
-It equals to 1.060 [of plasma = 1.030 & of RBCs = 1.090].
(4) Viscosity:
-It is about 5 times as water, due to presence of fibrinogen + albumin,
and RBC. It increases in polycythemia and decreases in anemia.
(5) Osmotic pressure:
-Due to presence of crystalloids (electrolytes, ) mainly.
-It is equal to 5000-5500 mmHg ( like osmotic pressure of 0.9% gm
NaCl or a solution having 300 milliosmol/ liter). Plasma proteins
have only 28 mmHg (called plasma colloid osmotic pressure) but it is
more important as it cannot pass the capillary membrane.
(6 ) Volume of blood : 5-6 litres =7-8% of body weight
Functions of the blood:

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(1)Transport medium for:
- O2, CO2 -Digestive absorbed food.
- Waste products (urea, creatinine…..).
- Vital substances as hormones & vitamins.
- Heat liberated by the body metabolism to skin to be lost.
(2) Defensive function:
-WBCs attack the organism by phagocytosis or antibodies formation.
-Prevention of blood loss from injured vessels by formation of blood
clot (hemostasis).
(3)Homeostatic function:(regulation of internal composition of the
body):
a- Regulation of water content: by exchange of
fluidbetween plasma and interstitial fluids also by
removal of excess fluids via kidneys.
b- Regulation of pH: by plasma and RBCs buffer systems.
c- Regulation of metabolism: by transport of hormones and vitamins.
d- Regulation of body temperature: by transport of heat to skin and to
heat regulating center to regulate the body temp.
e- Regulation of arterial bl. pressure by its viscosity which regulate
the peripheral resistance.

The Plasma
Volume: 5% of body wt. – 3.5 liter in adult 70 kg.
Composition:- It is yellowish in colour as it contains bilirubin.
- Water = 90%
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- Organic constituents:
. Plasma proteins = 7.1-7.4 gm.% the most important
. Nutrients, hormones, waste products & enzymes = 2%
- Inorganic constituents = 0.9% e.g
. NaCl, NaHCO3, KCl, CaCl2
*Plasma proteins:
* Types:
Albumin Globulin Fibrinogen Prothrombin

- Value 4.2 gm% 2.4 gm% 400mg % 10 mg %

- M.W 70.000 150.000 350.000 69.000

-Synthesis Liver Liver for alpha &B Liver Liver

but gamma type in ,

RES

- Main -Transporter -Carrier -Viscosity Act as clotting

function -Osmotic pressure

-Defensive (see
-Bl. Clotting &,and
factor II
regulation &carrier below),&carrier viscosity of blood

* Functions of plasma proteins:

1) Blood clotting (haemostasis): Fibrinogen, prothrombin and
some clotting factors are plasma proteins required for clot formation.
2) Defense (immunity): by gamma globulin, which secreted by
the reticuloendothelial system (bone marrow, spleen, liver, lymph
nodes) 5 types of immunoglobulins (IgM, IgA, IgG, IgE, IgD) to
attack bacteria & viruses.
3) Transport function: most of minerals and hormones are
combined to plasma proteins preventing its loss in urine.

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4) Regulation of body fluids: plasma proteins can attract fluids
from tissue spaces to plasma regulation of bl. volume, tissue fluid and
prevent oedema. Also, it controls urine volume by limitation of
filtration by renal glomeruli. (albumin is responsible for this function
as it has highest concentration and lowest molecular weight)
5) Regulation of plasma viscosity: which regulate the peripheral
resistance of blood flow regulation of diastolic bl. Pressure and
velocity of blood.
6) Control of capillary permeability as the pores of capillary
wall are partially blocked by protein .
7) Buffer functions: plasma proteins are present as proteinic acid
to buffer alkali and as Na proteinate to buffer acids.
8) Nutritional functions: plasma protein can be used by the tissue
in prolonged starvation.
9) CO2 carriage: as carbamino compounds.
10) Specific functions: some hormones, clotting factors and some
enzymes (esterase & phosphatase) are plasma proteins in nature.
* Albumin/globulin ratio (A/G ratio):
- It is about 1.2-1.7 - It is decreased in:
(1) Liver diseases (cirrhosis,hepatitis,bilharziasis)due to decrease
albumin synthesis.However,globulin is formed and increased by RES.
(2) Kidney failure or nephrosis : due to loss of albumin in urine
as it is the smallest molecular weight.
(3) Infections: due to increase gamma globulin as a defense
mechanism.

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 Red blood cells
(Erythrocytes -RBCs)
* Shape: small, circular, biconcave, non-nucleated discs.
* Size: 90 cubic microns in volume, 7.5 microns in diameter, 2.5
microns thickness in edges & 1 in center (So, the center
appears paler than periphery due to the biconcavity).
* Structure: (see fig.)
1) Red cell membrane:
- Composed of lipid bilayer.
- Proteins traverse the lipid bilayer and responsible for:
- Antigenic property of red cells. e.g blood grouping.
- Ion channels e.g. Na+, K+, Cl-
- Binding of submembranous cytoskeleton.It is a flexible
plastic to allow RBCs passage in narrow capillaries.
2) Submembranous cytoskeleton:
-It is a protein network of two types of proteins
spectrin and actin) under the cell membrane to give
RBC its shape and its ability of deformation.
3) Contents of RBCs:
a-Haemoglobin: red pigments give the RBCs its eosinophilic
appearance and carry oxygen.
b-Cytoplasmic enzymes: asglucose-6-phosphate dehydrogenase &
pyruvate kinase required for cell metabolism and carbonic anhydrase
which is necessary for CO2 transport
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d- Ions: K+, Na+, Mg++, Cl-, HCO3- & phosphate.
e-RBCs don’t contain some normal cellular organelles as
mitochondria , nucleus ,endoplasmic reticulum and centriole.
* Functions of RBCs:
1) Function related to cell membrane:
a- The great surface area of the biconcave discs facilitate:
- Gas exchange - deformation in narrow capillaries
- For giving the RBC its characteristic shape and in case of hydration
the cell swell without rupture.
b-Through the ion channels the normal ionic composition, osmotic
pressure, Cl—shift phenomenon occurs.
c- It contains blood groups antigens.
d- It keeps Hb and enzymes inside RBCs to prevent the bad effects of
escape of HB in the plasma..

2) Functions related to contents:

- O2 carriage: 1 molecule of Hb carries 4 O2 molecule and each gram
of Hb carries 1.33 ml of oxygen.
- CO2 carriage: by Hb in form of carbamino Hb.
- carbonic anhydrase enzyme is important for CO2 carriage
- Acid – base buffer: by Hemoglobin
- RBCs & plasma proteins are responsible for bl. viscosity and blood
pressure regulation.

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* Formation of RBCs (Erythropoiesis):
(A) Sites of formation:
1- In the foetus:-Yolk sac: in the first few weeks of pregnancy
till 6 weeks
-Liver & spleen: from 6 wks to 6 months.
-Bone marrow: from the 6th month till puberty.
2- In infancy & childhood:
- From red bone marrow of all bones.
3- In adult life:
-From red bone marrow present in central skeleton (flat bones as
skull, vertebrae, ribs, sternum, pelvic bones) also proximal ends of
long bones as humerus, femur & tibia.
-The yellow bone marrow can change to active red marrow to
produce RBCs as in case of severe anemia (extramedullary
hemopiosis).
(B) Factors affecting erythropoiesis:
[I]- Oxygen supply to tissue: (hypoxia):
-As the main function of RBCs is O2 supply to tissue, so hypoxia (as
in anemia, high altitude, heart or lung diseases) is the main stimulus
for RBCs.
-Hypoxia stimulates the secretion of erythropoitin hormone. It is
secreted from the kidney (85%) and the remaining from the liver. It
stimulates red bone marrow to form new RBC ( see fig )

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-Erythropoitin formation is stimulated by alkalosis in high altitude,
catecholamines, prostaglandins, androgens & cobalt.
-If hypoxia is corrected there is negative feed back inhibition of
erythropoitin secretion.
-In severe hemorrhage, the level of erythropoitin increases to activate
the yellow bone marrow and liver and spleen (extramedullary sites) to
form RBCs.
[II] - Dietary factors:
a-Proteins: of high biological value as animal proteins (contain
essential amino acid) to form globin part of Hb.
b- Metal ions:
1- Iron:
* Importance: - for synthesis of haem part of Hb.
- for synthesis of myoglobin and enzymes as
cytochrome oxidase, peroxidase & catalase.
* Sources: meat, liver, green vegetables & molasses (it must be
added to infant diet as the mother milk is not sufficient
in iron).
* Requirements: - adult male require 10 mg/day.
- adult female require 15 mg/d.
- pregnant require 20 mg/d.
- infant require 10 mg/d
* Loss: - In faeces, sweat, exfoliated skin (about 1mg/day) and very
little amount in urine and in lactating milk.

26
 - Women loss in menstruation= 0.5 mg/d (3.5 mg/period)
* Importance – Fe is important in formation of haem
*Absorption of iron: about 10% of dietary intake. ( see .fig)
1- Iron is fed in diet as ferric state

2- Ferric state of iron ferrous state.

3-Fe is absorbed only in the form of ferrous and this ferrous enters the
cells of the duodenum by help of a transporter called divalent metal
transporter ( DMT1 ) . Some of the iron is stored in the form of
ferritin. Iron absorbed will be carried on on a plasma protein called
transferrin to be given to the bone marrow and rest will be stored in
the liver in the form of ferritin . It is to be noted that vitamin C and
HCl increase absorption of iron but alkalies , some cereals , its ferric
form decrease its absorption ( see fig )
N.B.: Factors affecting iron absorption:
1- Body need of iron: increase need as in pregnancy lead to increase
absorption directly from intestinal lumen to plasma.
2- pH of stomach: acidic pH change of ferric to ferrous with increase absorption.(so, patient
with gastrectomy demonstrate impaired iron absorption with iron deficiency anemia).

3-Contents of food:

- Oxalates, phytate & phosphate absorption.

- Ascrobate, lactate & succinate absorption.

4-Hypoxia and anemia increase iron absorption

5-Some foods: some cereals, phytate and alkalies decreases its absorption .

2-Copper: carried by plasma protein (ceruloplasmin) to catalyse and

oxidyse ferrous into ferric state to be carried as transferrin.

27
3-Cobalt: stimulate erythropoitin release from the kidney, so increase
cobalt may lead to polycythemia.
c- Vitamins: (= Erythrocytic Maturation factors)
1- Vitamin B12: (=Extrinsic factor=Antipernicious anemia factor)
(= Maturation factor )
Importance:
- It is very important for maturation of RBCs, biosynthesis of purine,
pyramidines, nucleic acids and DNA synthesis and cell division.
Absorption: see fig
-Vit B12 present in diet as protein bound complex.
-It is fred by HCl & proteolytic enzymes.
-Then it combines with glycoprotein secreted from parietal cells of
gastric glands called the intrinsic factor to prevent its digestion by
enzymes till it reaches the terminal ileum.
-In the terminal ileum, absorption of B12 occurs by pinocytosis into
intestinal cells then to blood.
- In the blood vit. B12 carried by transcobalamin to bone marrow.
-Storage: in liver. Normal liver can store amount of vitamin B12
enough to supply the body for 5-7 years
-Requirement:
- 1-2 g/day - storage in liver is very high = 1-5 mg.
So, intake or absorption of vit.B12 is not manifested till 5 years.

28
Deficiency: - Due to malabsorption resulting in an anemia called
megaloblastic ,pernicious anemia and B12 deficiency anemia
2- Folic acid:
- It is water soluble vitamin.
- It is present in green vegetables, some fruits, liver and meat.
- Folic acid is essential for DNA formation and cell maturation.
- Its deficiency leads also to megaloblastic anaemia.
N.B: Both vitb12& folic acid are necessary for maturation of RBC
3- Vit. C: is required for reduction of ferric to ferrous and help
maturation of red blood cells
4- Vit B complex: needed for normal erythropoiesis.
[III]- Hormonal factors:
- Androgens stimulate erythropoitin production from the kidney and
its effect on bone marrow causing increase RBCs (so in male RBCs
count more than in female).
- Thyroid hormone stimulates the bone marrow cells and general
metabolism & increase O2 consumption and decrease O2 supply
hypoxia which stimulates erythropoiesis. So, increase in thyroid
hormone lead to polycythemia and its decrease leads to anemia
- Growth hormone from pituitary gland
-Glucocorticoids: stimulate the general metabolism and also
stimulate bone marrow to produce more RBCs.
[IV] State of liver, bone marrow and kidney and endocrinal glands:
- Liver:
29
-It is site for storage of iron, vit B12, folic acid & copper.
-It shares in formation of erythropoietin hormone.
-It is responsible for formation of globin part of hemoglobin.
-It is responsible for synthesis of RBCs in the fetal life.
-It is responsible for destruction of old RBCs.
- Bone marrow: is site of erythropoiesis so any disease(atomic
irradiation, deep x-ray, drugs) aplastic anaemia.
- Kidney: is the site of formation of erythropiotin protein. So, its
failure lead to decrease erythropoitin and retention of toxic substances
as urea lead to depression of bone marrow.

Haemoglobin
• Definition: It is the principal constitute (33% ) of RBCs . It is a
red pigment which gives the blood its red colour.
• Normal levels:
-Infant at birth 20 gm/dl (as the newborn has more RBCs due to
relative intrauterine ischemia).
-Infant after one week 15.5gm/dl
- Adult male 13-18 gm/dl - Adult female 12-16 gm/dl.
• Structure: ( see fig )
It is made of 4 subunits each of them is formed from one haem and
one polypeptide chain.
• Functions:
- Carriage of O2 & CO2

30
 - Strong buffer system.
• Reactions of Hb and all forms of carriage:
* Oxyhemoglobin: O2 just carries iron in ferrous state forming
oxyhemoglobin,which is not an oxidation
* Met Hb: strong oxidation by certain drugs or oxidizing agents
ferric state which not carry O2 dusky colouration of skin like
cyanosis (normally, MetHb doesn’t exceed 0.5% due to the activity of
NADH-MetHb-reductase enzyme in the RBCs which converts it back
to normal Hb).Deficiency of this enzyme causes a disease called
favism
* Carboxy Hb: carbon monoxide is a toxic gas and attached to Fe++
in high affinity (210 times as O2). This part attached to CO doesn’t
carry O2 and the remaining part of Hb, which carries O2 doesn’t give
its O2 to the tissue.
*Carbamino Hb: normally CO2 is attached to the globin part of Hb.
• Types of Hb: ( see fig. )
A) Normal Hb :
1-Adult ( HbA): contain 2 chain (each is consisted of 141 amino
acids) and 2 chain (146 amino acids).(97.5% of adult Hb.)
2-HbA2: contain 2 chains and 2 delta (146 amino acids) chains which
differ from -chains in the terminal 10 A.A.
3-Fetal Hb (HbF):
-It is the type of Hb in the human fetus then it is usually replaced by
adult Hb after birth.
-It contains 2 and 2 gamma(146 amino acid )
31
-It has high affinity for O2 and less to 2,3 diphosphoglycerate .So this
facilitates movement of O2 from maternal circulation to the fetus.
4-Glycosylated Hb( Hb a1C ): (3-7% of Hb) glucose is attached to
terminal valine amino acid in -chain. This value increases in cases of
uncontrolled diabetes mellitus.
B) Abnorma Hb
a. Abnormal chain e.g HbS : It is abnormal type of Hb due to
congenital abnormality of -globin in which valine amino acid present
instead of normal glutamic acid at position 6 of -chain hemoglobin-S
which causes sickle cell anaemia (see later).
b.Abnormal arrangement of chains : as in Thalassemia, A and B
- In thalassemia A globin is formed of 4 B chains,called Hb H.
* Destruction of RBCs:
-The life span of RBCs is 120 days , old RBCs destroyed in bone
narrow capillaries and spleen . Hb is released and splitted by the cells
of the reticuloendothelial system into globin & haem.
- Globin used in protein metabolism.
-Haem loses its iron to be stored as ferritin.
-The protoporphyrin part of haem yellow bile pigments .
* RBCs laboratory tests: RBC count, PCV, Hb concentration ,
blood indices, ESR , see practical course

Anaemia
* Definition: Anaemia is the decrease in red cell count or
hemoglobin content leading to decrease O2 supply to tissues

32
with symptoms of hypoxia.
* Classification:
(A) Etiological: Not so important
(B) Morphological: Very important in diagnosis: According to the
size and hemoglobin content of the red cells:
1)Normocytic (normal MCV) normochromic (normal MCH)
anaemia:
- acute haemorrhagic - Hemolytic - Aplastic
-Decreased erythropoietin production as renal and liver failure.
2) Microcytic (MCV) hypochromic ( MCH) anemia:
- Iron deficiency anaemia. - Chronic blood loss
- Disorders of globin. - Disorders of porphyrin.
3) Macrocytic (MCV) hyper or normo chromic (MCH)
- Vitamin B12 deficiency anaemia.
- Folic acid deficiency anaemia.
N.B.: General effects of anaemia
-Anaemia decreases the blood viscosity decreases resistance to
blood flow cardiac output (see CVS) .It also leads to easy
fatigability and loss of concentration.
-Anaemia causes decrease O2 supply to tissue and metabolite
accumulation leading to vasodilatation of tissue vessels with
increase venous return to the heart and increase cardiac output.

33
-If the patient increases his activity, this may lead to heart failure
due to heart load.
-Also, heart failure may occur due to severe decrease in oxygen
supply to cardiac muscle itself.
Polycythemia
Definition: It is abnormal increase in RBCs number above 6 millions
/cmm and it might reach 101 millions/ cmm
Types:
1- Secondary polycythaemia: Increased erythropoietin
a.At high attitude for several weeks hypoxia release of
renal erythropoietic factor erythropoietin stimulate
RBCs formation from bone marrow (Physiologic type).
b.Congenital cyanotic heart disease with hypoxia.
c.Chronic lung diseases (hypoxia).
d.Cigarette smoking(hypoxia).
e.Kidney diseases associated with erythropoietin
secretion.
2-Primary polycythaemia (polycythaemia vera): normal
eythropoietin concentration:The bone marrow produces
excessive amount of red blood cells (8-9 million). The cause is
unknown (may be tumor).
Effects:
-Increase in blood cells and bl. volume causes increase in viscosity
and total peripheral resistance ABP.

34
-The increased bl. volume causes increase in cardiac output &
ABP and increased load on heart which might to heart failure.
-Sluggish blood flow with prolonged circulating time and
reduction of oxygen supply to tissue (stagnant hypoxia) So, the
colour of skin is bluish (cyanosed).
-The capillaries may be plugged with the viscous blood and
haemorrhage may occur.
Treatment:
-Repeated venosection to reduce blood viscosity.
-Chemotherapy to suppress the overactivity of the bone marrow.
-Treatment of the cause of the secondary type.
Blood Groups and blood transfusion : see practical
Platelets
(=Thrombocytes)
Shape: Minute round or oval discs (2-4 ) non-nucleated.
Number: 150.000 – 400.000/mm3.[It decreases during menstruation
and increases during exercise, pregnancy, high altitude,
surgical trauma especially spleenectomy]
Formation: Thy are formed in the bone marrow as buds on the
surface of megakaryocytes and released into the blood under
stimulation of thrombopoietin reledased from the kidney.
Life span: 8-12 days, then removed by tissue macrophage as spleen
so, the number increases after spleenectomy.
Platelet structure: ( see fig )
35
1.The platelets have a mucopolysaccharide surface coat,
which is important in adhesion and aggregation of
platelets. Glycoproteins bind with the Von Willebrand
factor which are necessary for platelet adhesion to the
damaged endothelial cells. Also, glycoproteins act as
fibrinogen receptors.
2.The plasma membrane is formed of 3 layers. This
membrane is the basic structure of platelet factor 3 (PF3).
3- Beneath the membrane there are:
a-Microfilaments: formed of actin, myosin and thrombasthenin
b-Microtubules: which maintains the disc shape of the platelets.
4-The platelets contain 3 types of granules:
a-Dense granules: contain nucleotides (ADP) serotonin and
calcium.
b-Specific (Alpha) granules: contain platelet growth factor, beta
thromboglobulin, fibrinogen and other clotting factors as V, XIII also
platelet factor 4 (PF4) which is heparin antagonist factor.
c- Dense tubular system which contains calcium and may be site of
synthesis of prostaglandin and thromboxane A2.
5-The platelets also contain mitochondria, glycogen and
lysosomes which contain hydrolytic enzymes.
*Von Willebrand factor (VWF): is an adhesive protein formed by
the vascular endothelial cells and secreted in the plasma. It is
also formed by megakaryocytes and stored in the platelets.
Blood clotting factor VIII circulated in plasma bound to
VWF.

36
 Hemostasis
It is the stoppage of bleeding in case of small vascular injury. It
depends on the vascular wall, platelets and the clotting factors.
Mechanism:
(1) Extravascular:
-Physical effects of skin and elastic tissue in closing the bl. vs.
-Biochemical effects of released substances from tissue in activation
of clotting.
(2) Vascular factors
(3) Intravascular a. platelet plug
b. Blood coagulation
Steps of hemostasis , chronologically
(1). Vasoconstriction of the injured blood vessel
Causes:
a-Direct effect of serotonin and thromboxane A2 released from
platelets will cause V.C. (chemical role )
b-Injury of endothelium will release EDRF which causes VC
c-Pain produces nervous VC reflex.( nervous role )
d-Local myogenicVC of injured vessel.
Significance:
a- It helps in stoppage of bleeding.
b- It allows time for haemostatic mechanisms to occur.
37
c- The reduced blood flow help contact activation of platelet and
clotting factors.
(II)Formation of platelet plug: (Platelet function):
The main function of platelets is the formation of mechanical plug to
close the vascular injury in the following steps: It is done in steps
1. Platelet adhesion : due to glycoprotein present in platelet wall
2. ,, aggregation ,, ,, ADP and thromboxane A2 released from
broken platelets
3. ,, activation and release ,, ,, exposure of collagen fibres of
the injured area
4. platelet plug and fusion: due to ADP released from broken platelets
- This plug is temporary and fast but it is weak as it can stop bleeding
from small puncture only. It cannot stop bleeding if the puncture is
large or if the blood flow is rapid
Importance of the plug:
1.It stops blood loss from small punctures.
2.It closes the minute ruptures of very small vessels, which occur
hundreds of times daily.
3.The chemicals released from the plug help other mechanisms of
haemostasis as the following: as serotonin and throboxane A2
[III] Blood coagulation
It is the formation of blood clot (= a network of insoluble fibrin
entangling blood cells)
It needs the following clotting factors:

38
 -I(Fibrinogen) - II ( prothrombin -III (thromboplastic)
- IV (Calcium) -V (Labile factor) - VII (stable factor)
-VIII (antihaemophilia globulin)- IX (christmas factor)
-X (Stuart prower factor) -XI -XII (Hageman factor)
- XIII(fibrin stabilizing factor)-Platelet factor-3(phospholipid)&VWF
• The clotting factors are formed in:
The liver,megakariocytes,macrophages and endothelial cells:
*Mechanism of blood coagulation: ( enzyme cascade hypothesis):
Through 2 pathways intrinsic & extrinsic pathways see figure
*Steps of blood clotting ( see fig )
[1] Formation of Prothrombin activator:
A- Extrinsic pathway:
1-Injury of the blood vessels and surrounding tissue causes release of
tissue thromboplastin (lipoprotein mixture) which activate factor VII
which stimulate factor X in the presence of Ca++.[It is called extrinsic
because it depends on external factors from the tissue]
2-Activated factor X with factor Va and tissue phospholipids and
calcium form enzyme complex called prothrombin activators.
3-The extrinsic mechanism takes few seconds and depends on the
degree of tissue injury and quantities of factor VII, V and X.
B- Intrinsic pathway:
-When the blood comes in contact with subendothelial collagen in
injured bl.vs. or with wettable surface as test tube, factor XII is
activated to active XII (XIIa) which aided by kallikrein.
39
- Also, subendothelial collagen or the wettable surface activate the
platelet to release platelets phospholipids .
-Then factor XIIa activates factor XI in presence of high molecular
weight kininogen (HMWK).
-Then factor XIa activates factor IX .
-Then factor IXa + Factor VIII + platelet phospholipids in
presence of calcium ions activate factor X.
-Activated factor X with factor V and platelet phospholipids to
form enzyme complex called prothrombin activator.
[2] Conversion of Prothrombin to thrombin:
By the prothrombin activators the prothrombin changed into thrombin
in the presence of calcium and then thrombin acts on prothrombin
itself producing more thrombin (positive feed back effect) Then
thrombin acts as proteolysis enzyme and has the following actions:
1-Conversion of fibrinogen to fibrin threads.
2-Thrombin activates some of the clotting factors (V,VII,VIII) which
are required for its formation in a positive feed back.
3-Thrombin increases platelet adhesion and aggregation.
[3] Conversion of fibrinogen to fibrin (formation of fibrin clot):
-Thrombin acts as an enzyme and splits small negatively
charged peptide fragments from the fibrinogen molecules
(removing the repulsive forces from the molecules) and
allowing the remainder to polymerize to form fibrin
polymers or threads. These threads adhere to the injured

40
blood vessel wall forming loose net like meshwork that
traps the blood cells forming red soft bl clot.
(IV) Clot retraction: this
1.Makes clot firm and attached to the nearby tissue
2.Stimulates healing of the wound
-This is done by help of certain proteins coming from
adherent platelets
*Causes of fluidity of blood inside the cardiovascular system
A)[Factors against intravascular clotting]( = factor preventing
formation of a clot): These factors prevent blood clotting in
normal state
1) Smoothness of endothelium in prevention of clotting:This
prevents contact activation of XII.
2) Anticoagulant in the blood itself:
a- Blood flow: this helps removal of activated coagulation factors by
the rapid circulating blood and their inactivation in the liver, spleen
and the bone marrow.
b- Antithrombin action of fibrin and antithrombin III:
Fibrin: adsorb about 90% of thrombin formed during this process
preventing its spread into the blood causing more coagulation.
Antithrombin III (alpha globulin) Combine and inhibit the
remaining thrombin and factor Xa.
c- Protein C & protein S: (Both are natural anticoagulants are
formed in the liver in presence of vit.K)

41
d-Heparin :
- It is the most powerful anticoagulant
- It is negatively charged mucopolysaccharide.
- It is secreted by mast cells and basophile cells in minute amounts.
- Mechanism of its action:
1. It combines with antithrombin III aiding its inhibition of thrombin
Also, it inhibits the activated factors IX,X and XI
2.It inhibits platelet aggregation and stimulate fibrinolysis.
3.Lipaemia clearing effect occurs by activation of lipase enzyme to
hydrolyse lipids and prevents its deposition in blood vessels so
prevents the development of atherosclerosis.
2. Breakdown of the clot if formed
If clot is formed it is brocken down by a system called
fibrinolytic system , What is fibrinolytic system?
Fibrinolytic System
* Definition: see fig- Fibrinolysis means lysis and removal of
blood clot after stoppage of bleeding and healing of the vascular
wall.
-This is produced by enzyme called plasmin (fibrinolysin) which
present in plasma as inactive plasminogen (profibrinolysin).
* Mechanism:
-After the blood clotting stops the bleeding, tissue plasminogen
activator (t-PA) converts plasminogen into plasmin which lyses the
blood clot into fibrin degradation products(FDP).
-After lysis of the blood clot, plasmin, t-PA and FDP are removed
by the phagocytic cells.
-Then the inhibitor to t-PA limit its effect to site of blood clot only.
42
*Activation of plasminogen & fibrinolysis:
(1) Tissue plasminogen activator: (t-PA)
Released from injured tissue & endothelium but the plasma
contains a physiological inhibitor to the t-PA to balance its effect.
(2) Factor XII, Kallikrein & thrombin.
(3) Other physiological activators as:
a-Urokinase enzyme in the urine to lyse blood clots in the urine.
b- Enzymes in pleural, peritoneal & uterine cavities to prevent
blood clot in these sites and passage of uterine blood to outside.
(4) Exogenous activators: as streptokinase enzyme from bacteria to
treat acute myocardial infarction to dissolve clot.
* Significance and importance of fibrinolysis:
1-Lysis of blood clots & reopening the blood vessels and prevent
closure of capillaries by sluggish circulation.
2-Cleaning of the tissue from the blood clots formed outside the
blood vessels
3-Removal & prevent bl. clots in the urinary tract (to prevent
blocking of renal tubules), pleural, uterine & peritoneal cavities.
4-Treatment of early stages of myocardial infarction by:
- Injection of tissue plasminogen activator.
- Streptokinase & urokinase injection [direct on the clot].
ANTICOAGULANTS
*Prevention of blood clotting outside the body [ Invitro
anticoagulants]
(1)Blood is collected in silicon or paraffin coated test tube to
prevent aggregation and activation of factor XII.
(2)Cooling of the blood delay clotting.
(3 Removal of Ca++ ions: by
-Precipitation of ionized calcium by addition of Na oxalate , Ca++
oxalate (toxic) or by EDTA.
Adding of Na citrate ® Chelation of Ca++ and formation of non-
ionized Ca++ (Ca++ citrate) This compound is not toxic, and is
rapidly removed from the blood so citrate is used in blood
transfusion.

43
-EDTA(Ethelyne diamine tetraacetic acid) causes chelation of Ca++
(4) Defibrination of blood by a glass rod.
(5) Addition of heparin as in artificial kidney machine.
*Prevention of blood clotting inside the body [In vivo
anticoagulants]These drugs are used for prevention and treatment
of thrombosis as in:
1- Deep venous thrombosis or pulmonary thrombosis.
2- Myocardial infarction.
3- After cardiac surgery.
4- Rheumatic valve disease complicated with embolism.
- There are two types of invivo anticoagulants drugs:
Heparin Coumarin
· Origin: - Animal origin from - Plant origin as warfarin
mast cells and basophils and Dicumarol
· Mode of action: - Anti-thrombin - Competitive inhibition with
- Inhibits platelet aggregation vit K in liver. So prevent
- Prevent activation of IX, X, XI formation of factors II, VII, IX
- - Lipaemia clearing effect & X and protein C & S.
· Site of action: -In vivo and in vitro -In vivo only
· Onset: -Rapid -Delayed onset (1-3 days)
· Duration: -Short duration (4-6 h.) then -Long duration (3 days)
hydrolysed by heparinase
enzyme.
· Mode of -Intravenous or intra-muscular -Orally
administration: (as it is digested by the
stomach)
· Antidote: -Protamine sulphate 1% (It has -Vitamin K or blood
strong positive charges to transfusion
neutralize the negative charges
of heparin)
* Tests of hemostatic function: see practical work , include
1) Platelets count: 2) Bleeding time:
3) Tests for blood coagulation:
a- Clotting time:
b- Prothrombin time:
- Is a test of extrinsic pathway.
c- The activated partial thromboplastin time (APTT):
- Is a test of intrinsic pathway.
44
*Disorders of hemostasis:
[A] Bleeding tendencies:
(1) Vitamin K deficiency:
Causes: (a) decrese intake of vit.K
(b)decrease absorption as in decrease fat absorption in
cases of obstructive jaundice or steatorrhea (fatty
diarrhea).
(c) Vit. K antagonist as Dicumarol.
(d) Intestinal antibiotics to kill intestinal bacteria even
that facilitate the synthesis of vit.K.
Effect: decrease synthesis of clotting factors II & VII & IX &X
by the liver ® bleeding tendency.
(2) Purpura:
· Purpura is a hemorrhagic disease in the skin and the mucous
membrane with small purplish blotches giving the disease its
name ”purpura”.
· Causes and types of purpura:
A-Thrombocytopenic purpura:
Due to: decrease platelets count below 60.000/mm3
Causes:
1-Idiopathic or 1ry: may due to autoimmune disease leading to
destruction of the platelets.
2-2ndry: -Platelet production due to bone marrow lesion as
radiation, infiltration by tumor cells or due to decrease of
vitamine B12 or folic acid.
- Platelet destruction by drugs or repeated thrombosis or
hypersplenism.
B-Non-Thrombocytopenic purpura:
Due to: Abnormal vascular or platelets function even their count
is normal.
Causes:
1-Platelet abnormality:
. Inherited weakness of the platelets (thrombasthenia) due to
deficiency of plasma membrane.

45
. Acquired due to the effect of some drugs as Aspirin blockage of
thromboxane A2 which is required for platelet aggregation.
2- Vascular abnormality:
As in vit.C deficiency,allergic purpura or due to infectious
diseases.
Clinical picture: bleeding tendency in the form of subcutaneous
petechiae (small spots of blood) or ecchymosis.
Characters of purpura:
- Decrease Platelet count (in thrombocytopenic type).
- Prolonged bleeding time.
- Normal clotting time.
(3) Hemophilia:
-It is a hereditary disease characterized by severe bleeding
tendency. It is sex-linked, Mendelian recessive disease
transmitted by females (abnormal x- chromosome) to males but
females themselves rarely suffer.
There are 3 types of hemophilia:
- Haemophilia (A) (85%) due to deficiency of factor VIII.
- Haemophilia (B) (10%) due to deficiency of factor IX
which is called Christmas disease.
- Haemophilia (C) (5%) due to absence of factor XI. It
affects both male and female and most common in jews.
·Hemophilia is characterized by:
All tests are which are related to the intrinsic pathway are
affected:
- Normal bleeding time.
- Prolonged clotting time.
[B] Intravascular thrombosis:
- It is the formation of blood clot inside the blood vessel.
- It is promoted by:
(1) Rough endothelium as in atherosclerosis and in injury
of blood vessels by trauma.
(2)Slow blood flow as in prolonged lying in bed.
(3)Increase blood viscosity.

46
 - It may lead to:
(1) Arterial obstruction and ischemia
(2) Venous obstruction and edema
(3) Emboli formation to affect other organs or may reach the heart
then to the lung producing fatal pulmonary embolism.
- It may be treated by: anticoagulants.
White Blood Cells
(=Leucocytes) (=WBCs)
*Number: 4.000-11.000/mm3 in adult man (increased in children
due to increased non-granulocytes count).
*Origin : *Life span* Types and Functions: see table
*Comparison between different types of leucocytes
granular Non granular
Neutrophil eosinoph basophil lymphocyte Monocyte
il
% 60-70 1-4 0-1 20-30 2-8
Shape+nuc multilobed bilobed Band like rounded Kidney- shaped
leus

granules neutrophili acidophi basophilic - -

c lic
origin Bone Bone Bone marrow Bone Bone marrow and
marrow marrow marrow and lymphoid tissue
lymphoid
tissue
life spane 12hs 12hs 12hs Few days to Few weeks
100 days
function 1.phagocyt Increase Forms Acquired Phagocytosis,macr
osis, s in heparin,brad immunity ovage
microcyte 1.allergy ykinin and 1.B
2.diapedisis 2.parasiti histamine lymphocyte
3.chemotax c 2.T
ix infestati lymphocyte
on s

47
(*) Chemotaxis:
-Some substances released at site of infection (degenerative
products, bacterial toxins & complement system) lead to attraction
of leucocytes from near capillary (<100 m distance) to migrate
towards the inflamed area (positive chemotaxis).
N.B.: Some bacterial toxins repel the neutrophils (-ve chemotaxis).
(*) Diapedesis:
-WBCs can squeeze themselves through the pores of the healthy
capillaries to outside. In infected area these pores increase in size
to facilitate diapedesis.
(5) Phagocytosis:
-This is the power of leucocytes to engulf foreign materials as
bacteria, toxins and dead cells. Then ingest these material via
proteolytic enzymes of lysosomes. Also bactericidal agent as
hydrogen peroxide (H2O2) can kill bacteria. A neutrophil can
phagocytize 5-20 bacteria before the neutrophils die and form pus.
. Defensive Mechanisms[Immunity]
-It is the ability of the body to protect itself against foreign agents
as bacteria, virus or foreign bodies. It is classified into:
[I] Natural immunity: - It is the immunity resulted from general
processes rather than from specific ones directed to certain disease
It includes the following:
1)Intact skin which resists the invasion by bacteria.
2)The presence of certain chemical structures as:
a.Lysozymes which are mucolytic enzyme that attack
the invaders.
b.Complement complex of 20 proteins which
activated to destroy bacteria.
c.Basic polypeptides which react with certain types of
bacteria.
[II] Acquired immunity:-It is the ability to develop specific
immune response against certain type of bacteria and virus.
-It includes two types:

48
 1-Humoral immunity: by circulating antibodies formed by
Blymphocytes. 2-Cell-mediated immunity: by activated
Tlymphocytes
-The foreign agents are either antigens or haptens.
Antigens:
-These are foreign agents which produce an immune response.
-They are mostly protein or glycoprotein e.g bacteria, viruses and
foreign cells.
Haptens:
These are substances with low molecular weight (<8000) as
drugs (penicillin) which combine with a protein in the body
and then behaves as a foreign protein and initiates immune
response.
- Development of the immune system: see figure
*Primary immune response: due to first exposure to antigen ,Ig M
is increased and the response is of short time
*Secondary immune response: due to exposure to the
antigen for the second time, Ig G is responsible , and it
takes a longer time or may be life long
Humoral immunity
· It is produced by B-lymphocytes.
· It is the major defense against bacterial infections.
· When bacterial or other foreign antigens enter the body they
stimulate proliferation and transformation of specific B-
lymphocytes into plasma cells and memory B-cells. The plasma
cells secrete large amount of specific antibodies called
immunoglobulins, which circulate with the globulin, and attacks
the foreign antigens.

49
Immunoglobulins: see tabl
IgG IgM IgA IgE IgD
Concentration,i 750-1500 150-250 100-200 0.3 30
n mg/dl highest lowest
% 85% 10% 5%
M.W smallest largest In between
Crossing + • - - -
placenta
Presence in - - + - -
secretions
Fixation to - - - + -
mast cells
Functions 1.Sec.respons 1.Anti AB Present Increasin Of unknown
e antigens in g in fun , or may
2.Passive 2.prim.respons secretion allergy help in
immunity e s and on identificatio
3. anti bac, surfaces n of antigen
fung&virus to B cell
4.antiRh

-Mechanism of action of antibodies=antigen antibody reactions

(1) Direct: interaction neutralizes the dangerous effect of the
antigen by:
- Agglutination: of the antigen by agglutinin antibody.
- Precipitation: of the antigen by precipitin antibody.
- Lysis: of the antigen by lysin antibody.
- Antitoxication: of the antigen by antitoxin antibody.
- Opsonization: of the antigen by opsonins antibody.
( opsonins make bacteria more easily phagocytized )
(2) Complement system: see bacteriology for more details
- It is a system of 20 plasma proteins in inactive enzyme
Precursors that are activated by presence of antigens &antibodies
Cellular immunity (cell-mediated)
-Produced by cytotoxic T-lymphocytes.
-Major defense against virus, fungi, some bacteria, tumors and
responsible for rejection of foreign tissue transplanted.
-Exposure to the proper antigen will lead to formation and
activation of large number of lymphocytes which released into the
lymph blood , tissue spaces , and lymph& blood stream again.
50
 -Types and functions of T-lymphocytes:
(1) Cytotoxic T8 lymphocytes:
- Directly attack and destroy the cells that contain the antigen by
releasing of cytotoxic substances as lysosomal enzymes with lysis
of the target cells (killer cells).
- Also secrete lymphokins and responsible for tissue rejection.
(2) Helper-T4 cells (75%)
-They increase the activation of T & B cells
-The causative virus of AIDS, destroy these cells causing cell
immune deficiency.
(3) Suppressor or regulatoryT8 cells:
-They suppress the function of B and other T cells so called
regulatory T cells.
(4) Memory T cells:
- They are responsible for the second response of the same antigen,
which occur more rapidly and powerful than the first response.
N.B.: Natural killer cells (non-T non B-cells):
- A third type of lymphocytes are activated by interferon and have
the following functions:
(1) They kill cells without Ag-Ab reaction.
(2) They destroy malignant cells.
(3) They have antiviral effect.
Differences between B and T lymphocytes
B lymphocyte T lymphocyte
% 25 70
Life spane Shorter longer
Responsible for -Humoral immunity -Cellular immunity
( =function ) -Does not help T lymphocytes -Can help B lymphocytes
Prim lymphoid Bursa in birds , but peyer s patches, Thymus gland
tissue liver and spleen in human
Sec. lymphoid Cortex of lymph node Paracortical area of lymph
tissue node
types One type 4 types ,killer , helper , sup.
And memory

51
Sometimes immunity is classified into
Active immunity : in which the body is forming the immune
response as in cases of intake of
(1) Detoxicated organism e.g tetanus.
(2) Attenuated living organism e.g poliomyelitis.
Passive immunity is temporary immunity done by intake of
already made antibodies, activated -T cells or both.

52
 Cardiovasular System
INTRODUCTION
-The circulatory system is a closed system (i.e. blood does not get
into direct contact with the tissues except in sinuses of liver, spleen
and bone marrow).
-The function of the circulatory system is to maintain homeostasis
(i.e. to supply the cells with nutrient materials, hormones and
blood gases, and remove waste products away from the tissues).
The functional parts of the circulatory system:
A. The heart: Formed of 2 pumps
1. Left side of heart: It functions as a pressure pump.
It pump blood into the arteries at sufficient pressure energy to
drive the blood through the body.
2. Right side of heart: It functions as volume pump.
It delivers blood to the pulmonary circulation at low pressure.
B. The vascular system:
1-Arteries (Distributing system):
(a)Elastic arteries (= as aorta): it is elastic because its wall
contains a lot of elastic fibers. It acts as a second pump, it pushes
blood during diastole
(c) Arterioles: They function as resistance vessels to maintain
ABP (especially diastolic pressure) and regulates the blood flow
(into the capillary bed) to each tissue according to its activity. They
contain a thick layer of plain muscles so, they also called muscular
or narrow arterioles.
2- Capillary networks (Diffusion system) : -They function as
exchange vessels for nutrients, blood gases and waste products
between blood and the tissues as their wall is thin and porous.
3- Veins (Collecting system): -They function as capacitance
vessels and volume reservoir (contain 65% of blood volume).They

53
can accommodate a large volume of blood with minimal change in
pressure (= high compliance).
4- Pulmonary vessels :They function as gas exchange.
5- Lymphatic vessels :They function as drain system
THE HEART
- Adult heart has the size of a man's fist and weight about 300 gm.
- It is divided into: right and left sides and each side is formed of
two chambers, an atrium and a ventricle.
-The heart is composed actually of two pumps. See fig
1.The right heart pump : that pumps the blood to the lung.
2.The left heart pump: that pumps the blood to the peripheral
circulation.
*The main tissues of the heart:
1.The connective tissues: represent the septa of the heart and the
fibrous valves in addition to its chordae tendinae fibrous tendons
by which the papillary muscles attached to the vanes of the atrio-
ventricular valve (AV valve).

2.The muscular tissues:

·The atrial muscles: are thin . The right atrial wall is thinner than
the left atrial wall.
· The ventricular muscles: formed of three layers:
· The specialized cardiac muscles for initiation and propagation of
excitation waves. They are modified cardiac muscle fibers which
have the ability to conduct the nerve impulses throughout heart
They are present in:
A. Nodal fibers (or automatic pace maker fibers):
1. Sino-atrial node (S.A. node)
Characters:
- The pace maker of the heart (initiate rhythmicity of the heart).

54
Site: in the posterior wall of the right atrium, below and medial to
the opening of the superior vena cava.
Size : 1 cm long, 3 mm thick.
Supplied by: right vagus nerve and sympathetic nervous system.
Rhythm:90-110 impulses/min (highest rhythm-so called
pacemaker)
2. Atrioventricular node (A. V. Node)
Conducts the impulses from the atria to the ventricles.
Site: on the right side of the inter-atrial septum, at the junction of
atria and ventricles
Size: 0.5 cm long and 3 mm thick.
Supplied by: the left vagus N. and sympathetic N.S.
Rhythm: 60/min (has lower rhythm.)
Comparison between SAN &AVN
SAN AVN
site Below and medial to the opening of In lower part of right side of inte
SVCin post.wall of right atrium ratrial septum
size 1cm long x 3mm thick 0.5cm long x3mm thick
Nerve -right vagus ( parasym) -left vagus(parasym)
supply -sympathetic -sympathetic

rhythm Higher rhythm Lower rhythm

90-110 beats/min 60 beats/min
B.The specialized conducting fibers:
- They are specialized for propagation of cardiac impulse.
- They are present in Bundle of His and its branches, and Purkinje
fibers. See conductivity.
The bundle of His:
- It is continuous with the A.V.N. It enters the septum between the
two ventricles. It is the only electrical connection between atria
and ventricles
*The heart valves:
-There are two types of the valves in the heart:
{A}The atrio-ventricular valves (A.V. valves) located between
the atria and the ventricles.

55
 (1) The tricuspid valve, at the right side of the heart, it has 3 cusps
(or flaps).
(2) The mitral valve, at the left side of the heart. It has 2 cusps
(bicuspid).
{B} The semilunar valves:
(1) The aortic valve : It has 3 cusps. It is present between left
ventricle and aorta
(2) The pulmonary valve: it has 3 cusps .It is present between right
ventricle and pulmonary blood vessel
-Function of the valves:They allow blood flow in one direction
-Functional histology of cardiac muscle:
- The heart is composed of two functional syncytia (atrial
syncytium and ventricular syncytium).
- There is one capillary for each muscle fiber.
- The ends of muscle fibers are attached via intercalated discs. The
side of the muscle fibers fuse by tight junctions.
- Both intercalated discs and tight junctions have low electric
resistance, so the excitation from fiber to fiber can be easily and
rapidly pass through the cardiac muscle.
* The pericardium:
-It is a double wall sac that surrounds the heart, its inner layer is
called “visceral” and outer layer is called “parietal pericardium”.
-In between the two layers a serous fluid is present to allow easy
movement of the heart.
PROPERTIES OF CARDIAC MUSCLE
1-Excitability
· Definition : It is the ability of the cardiac muscle to respond to
an adequate stimulus by generation of action potential followed
by mechanical contraction.
2. Rhythmicity (Automaticity)
· Definition :- It is the ability of the heart to initiate its own beat
continuously and regularly independent of nervous connection
but can be modified by nervous and hormonal factors.This
56
 property is a myogenic produced by the intrinsic activity of
specialized myocardial fibers, not neurogenic (from nerve
supply). This beating will continue even if the heart is removed
from the body. The heart obeys the highest rhythm of SAN.
N.B. :
* SA node has rapid slope and so rapid rate 90/mm. AV node has
slow slope and so, slow rate 60/min.
* Although SA nodal rhythm is more than 90 beat/min. yet the
heart rate is only 70 beat/min. This is due to the effect of vagus
nerve on rhythmicity of SA node decreasing it to about 70 beat/min
(called vagal tone).
3. Conductivity:
·Definition: It is the ability of the cardiac muscle to conduct the
excitation wave from S.A.N to all parts of the heart.
·The conducting system of the heart: see figure, it is formed of :
1-S.A.N .
2-Bachman’s bundle :
3-3 nternodal pathways ( ant, middle and posterior ):
4-AVN (Atrio-ventricular node):It delays impulse till end of atrial
contraction
-The purkinje system:Has high rate of conduction
4. Contractility
·Definition :
.It is the ability of the heart to contract and pump the blood against
the peripheral resistance with special characters. It contracts both
isotonically (with decrease in its length) and isometrically (with
increase in its tone). Some special contractile properties
(1) All or non rule (law) :
-It states that “Stimuli causes the cardiac muscle contracts
maximally or does not contract at all, provided that all factors
affecting contraction are kept constant”.
(2) The cardiac muscle cannot be tetanized:

57
(3) Length - tension relationship (Starling law) :- Starling law
states that “The force of contraction of the cardiac muscle is
directly proportional to the initial length of the cardiac muscle fiber
within limit”(i.e. the greater the initial length of the cardiac muscle
fiber, the stronger will be the force of its contraction, however,
over stretch decrease its power of contraction (as in heart failure).
(4) Force - velocity relationship :
-The velocity of contraction is inversely proportional to after load
and directly proportional with preload.
N.B Changes in pressures during the cardiac cycle:
Rt.V. Lt. V. Pul. A. Aorta
Systolic pressure 25 120 25 120 mmHg
Diastolic pressure 0 0 10 80 mmHg
CARDIAC OUTPUT (COP)
* Definitions:
·Cardiac output:Cardiac output )COP( is the volume of blood
(in liters) pumped by each ventricle per minute.
Cardiac output(COP) = stroke volume (SV) x heart rate (HR)
COP = SV x HR
·Stroke volume(SV): is the volume of blood pumped by each
ventricle per beat. It equals to the end diastolic volume (EDV)
minus the end systolic volume (ESV). It is about 70 ml/beat.
SV = EDV –ESV
·End diastolic volume(EDV):End diastolic volume (EDV) is the
volume of blood in the ventricle at the end of diastole. It is
about 135 -140 ml.
·End systolic volume(ESV):End systolic volume (ESV) is the
volume of blood in the ventricle at the end of systole. It is
about 70 ml (from 65 -70 ml).
SV = 140 -70 = 70 ml/beat.
·Heart rate(HR):Heart rate is the number of heart beats per
minute. It is about 70 beats/minute.
So COP = 70 x 70 = about 5000 ml/minute (5 liters/minutes).

58
·Cardiac index (CI): is the cardiac output per square meter
surface area. So,
CI = COP/m2 = 5L/1.73m = 3.2 L/min/m2. If we consider
the surface area of adult male weighted 70 Kg = 1.73 m2.
· Ejection fraction:
-It is the percent between the SV and the end diastolic volume.
-It ranges between 50-65%.It increases in increased contractility
and decreases in increased aortic resistance and in heart failure.
* Cardiac output in various conditions:
A- Cardiac output is not changed during:
- Sleep
- Moderate changes in environmental temperature.
B-Cardiac output is increased in:
1-Excitement: increase COP by about 50 -100% due to
sympathetic stimulation.
2-Exposure to extremes of temperature: as in high temperature due
to skin vasodilatation.
3-Eating: in the first few hours after eating due to increase GIT
blood flow.
4-Exercise: exercise can increase COP up to 700% in trained
athletes
5-Pregnancy: due to increase uterine blood flow and placental
arterio-venous shunt
C- Cardiac output is decreased in:
1-Sitting or standing from lying down decrease COP by 20 -30%.
2-Marked arrhythmia (tachycardia or bradycardia).
3-In all conditions which destroy the cardiac muscle fibers.
REGULATION OF CARDIAC OUTPUT
This is carried out through the modification of either the SV
or heart rate or both . It should be noted that in normal heart
VR = CO = SV X HR
So factors regulating CO include:
59
1. Stroke volume ( SV ) :
- Stroke volume is directly proportional with CO provided that HR
is constant
- SV is increased by one of two ways
a.by increasingEDV, called heterometric autoregulation of CO
b. by decreasing ESV , called homometric autoregulation of CO,
THUS, any factor that increases contractility , can decrease ESV,
as in, sympathetic stimulation , cases of increased catecholamines ,
thyroxin , xanthine’s, glucagon hormone and digitalis….ect, and
vise versa, any substance that decreases contractility as hypoxia
parasympathetic stimulation anemia or ischemia , will increase
ESV and decease CO
2 . Heart Rate ( HR ) :
- Heart rate is directly proportional to CO provided that SV is
constant,
- Moreover , HR is inversely proportional with SV provided that
CO is kept constant
3. Venous return ( also called cardiac input = CI )
- Normal heart can eject any amount of blood it receives , If heart
pumps blood less than the amount it receives , this condition is
called heart failure
- Venous return is also called preload
Vascular System
Blood flow in arteries are regulated from the following equation
P = F X R where
P : pressure of the blood inside blood vessels unit is mmHg
F : Flow , means amount of blood passing per unit time ,unit is
mL/min
R : resistance , that blood faces in blood vessels, unit is
mL/min/mmHg
It is to be noted that resistance is directly proportional with
a pressure provided that flow is constant
b length of blood vessel
c viscosity of blood , which is affected by no of blood cells and

60
 diameter of arterioles
and inversely proportional with
a fourth power of of radius o0f blood vessel
b flow provided that pressure is constant
Arterioles
Arterioles are the terminal branches of the arterial system
· Characters of arterioles:
1) Loss of elastic elements and increase smooth ms. layer.
2) They are responsible for the peripheral resistance (so the blood
pressure drops from 80 to 30 mmHg) .
3)The only site at which arterioles can be seen is the retina.
·Functions of arterioles:
1.Determination of the peripheral resistance : They are called the
resistance vessels.
2.They control the blood flow to the tissues : by changing their
diameter through producing V.D. or V.C.
3.They are responsible for regulation of body temperature
·Factors regulate arteriolar diameter:
Factors causing vasodilatation of arterioles and thus
decreasing blood pressure :
1. hypoxia , except in pulmonary blood vessels
2. Other metabolites as K lactic acid and pyruvic acids , and
hyperthermia
3. Prostacycline ,
4. Endothline Drived Relaxing Factor ( EDRF =NO=VIAGRA )
5 Histamine , released from mast cell
6 Bradykinin released in inflammation
7. ANP ( atrial natriuretic peptide )
Factors causing vasoconstriction of arterioles and thus causing
increase in blood pressure :
1. O2 except in pulmonary blood vessels
2. ThroboxaneA2

61
 3. Endothelines: intake of low dose of aspirin will increase
prostacycline and decrease throboxane A2 , this protects adults
from hypertension and thrombus formation
4. serotonin ( 5HT ) released from platelets
5. ADH (= antidiuretic hormone )
6.Angiotensin II
ARTERIAL BLOOD PRESSURE
*Definitions:
-Arterial blood pressure (ABP): it is the pressure of the blood on
the arterial wall.
-The systolic blood pressure: the maximum pressure is reached
during ventricular systole ranges from 90 - 140 mmHg with
average 120 mmHg.
-The diastolic blood pressure: the minimal pressure reaches just
before the ventricular contraction ranges from 60 - 90 mmHg with
an average value of 80 mmHg.
-Pulse pressure:
- It is the difference between the systolic and diastolic blood
pressure i.e. pulse pressure = systolic BP - diastolic BP = 120 - 80
= 40 mmHg
-It increased in cases of hyperdynamic circulation (aortic
regurgitation, arteriosclerosis, sever anemia, hyperthyroidism and
pregnancy).
-It decreased in hypodynamic circulation( hemorrhage, aortic
stenosis).
-Mean aortic (=arterial ) blood pressure:
-It is the average pressure in the systemic arteries throughout the
cardiac cycle.
-Mean systemic ABP = diastolic P + 1/3 pulse pressure
= 80+1/3 ( 40) = 93.3 mmHg
*Measurement of ABP:
1. Direct Method:-By cardiac catheter cannulated through a large
artery under local anesthesia. It transmits the blood pressure to
manometer. Used only in experimental animals

62
2. Indirect Method:- using sphygmomanometer and stethoscope ,
see practical course
*Physiological variations of ABP :
1. Age:
- In newly - born infants the blood pressure is 80/40.
- Then it increases gradually where
● at 4 years old it is 100/65.
● at 20 years it is 120/80.
- It increases gradually after the age of 20 years to reach 150/90 at
the age of 60 years due to decrease the elasticity of arteries.
2. Sex:
-The blood pressure in adult male is higher than in adult female,
but after the menopause( about 50 years ) it becomes higher in
females this may be due to hormonal changes during this period.
3. Body built:
-The blood pressure usually higher in obese persons.
4. Race:
-The blood pressure in Orientals is less than that in europeans
and americans may be due to:
(a) Genetic factors (b) Environmental ,,
(c) less cholesterol in diet (d) less stress in life.
5. Sleep:
-During quiet sleep the ABP is decreased due to parasympathetic
activity. But it is increased in REM sleep
6. Emotions:
-In different emotional state (e.g. anger) the ABP is elevated due to
sympathetic over activity.
7. Meals:
-After meals the ABP increases
8. Gravity:
-During standing, the blood pressure increases in all vessels below
the heart and decreases in vessels above the heart level.

63
-The rise or decrease in BP is equal to the weight of blood column
from the vessel to the heart i.e. 0.77 mmHg per cm.
9. Exercise:
The systolic blood pressure increases sharply, while the diastolic
blood pressure remains constant or even decreases .
10. Respiration: see fig
-The changes in the blood pressure during each respiratory cycle
are called "respiratory pressure waves".
-"The ABP increases during the late part of inspiration and the
early dart of expiration, while it falls during the remainder of the
respiratory cycle".
*Factors determining and maintaining the arterial blood
pressure:
Pr essure gradient
Flow = resis tan ce
ABP = COP x TPR= SV x HR x TPR
SO,Arterial blood pressure =
heart rate X stroke volume X peripheral resistance
REGULATION OF ARTERIAL BLOOD PRESSURE
1. Rapidly acting mechanism: Acts within sec or minutes ,rapid
.They has weak effect :called nervous regulation as there cardiac
centers and vascular centers in medulla oblongata that can regulate
activity of heart and blood vessels after receiving impulses from
different parts of the body and respond to theses impulses by doing
VC or VD.
2. Intermediately acting mechanism: Acts within minutes
,hours or even few days, They are a little pit stronger: They act
through shift of body fluids from arteries to veins in cases of
hypertension and vise versa in cases of hemorrhage, called
capillary fluid shift mechanism.
3. Slowly acting mechanism(role of the kidney): Acts within
days or weeks , by help of kidney, This mechanism is powerful but
slow. That is why , in renal failure there is hypertension

64
 The Heart Rate (HR)
Its value: depends on the effect of the vagal tone on the
heart. So HR changes according to:
·Age: - in newborn 90-120/min (no vagal tone)
- in adult 65-90 (75/min)
· Sex:- in females the HR > in male (weak vagal tone)
· Muscular exercise: emotion & pregnancy & after meals lowers
HR
· Athelets: during rest have low HR (more vagal tone)
· Sleep: strong vagal tone lowers ¯HRbut in REM sleep HR
increases

Measurement: - from radial artery pulsation.

- heart sounds listening.
60
- from ECG HR = Time between 2R waves
- from arterial pulsation curve.

Regulation of heart rate: similar to regulation of arterial blood

pressure .
In addition to previous regulation

*The respiratory center has direct effect on the heart rate

called:- The respiratory sinus arrhythmia:
-The heart rate normally increases during inspiration and decreases
during expiration.
*Thyroxine: it produces tachycardia due to:
-Direct stimulation of S.A. node.
- Increases SAN sensitivity to catecholamines.
-Increases the metabolic rate all over the body
*The blood temperature:
-A rise in the blood temperature by 1°C increases the heart rate
about 10 beats/minute. This is due to:

65
 Hemorrhage and shock
I- Hemorrhage
*Definition: hemorrhage is the loss of blood from the vascular
system.
*Types: - According to site: to outside the body (external), into the
body cavity (internal) or into the tissue spaces
(interstitial).
- According to onset: It may be acute (sudden loss of
blood after trauma which is fatal with rapid loss of
blood) or chronic (small and gradual loss e.g
peptic ulcer or piles which causes severe anemia
and hypoxia).
- According to prognosis: If the amount of blood loss less
than 20% of total blood volume it can be
compensated and the Bl. pressure may return to
normal level spontaneously, but if more than 20%
rapid blood transfusion must be occurred to avoid
the refractory shock.
*The Compensatory homeostatic mechanism:
[I] Immediate compensatory mechanisms:
These mechanisms are very rapid within minutes and aim to
restore the blood pressure and blood supply to the vital organs.
(A)Nervous control: Stimulation of the pressor area of
cardiovscular centre( this center is present in medulla oblongata
and responsible for increase in blood pressure and heart rate )
(B) Hormonal secretion :
1) Secretion of more catecholamins:
2) Secretion of renin-angiotensin system:
3) Secretion of antidiuretic hormone
4) Cortisol hormone secretion:
(C)Intense thirst sensation:
(D) Acceleration of respiration:
66
N.B.:Clinical picture after haemorrhage: progressive decrease in
ABP, rapid weak pulse (= called thready pulse),increase in
respiration, cold pale sweaty skin ( due to sympathetic VC),
intense thirst and nervous irritability(brain ischemia) and in severe
cases coma may occur.
(II) Delayed (long-term) compensatory mechanisms:
This mechanism becomes effective after 30 minutes and takes
longer time:
1- Restoration of plasma volume: (12-72 hours):
2- Restoration of plasma proteins: (3-4 days)
3- Restoration of cellular elements : (4-8 weeks)
II- Shock
*Definition: Circulatory shock means inadequate tissue perfusion
with blood due to decreased CO & ABP.
*Types and causes of shock: see fig
(I)Low-resistance shock: (= primary shock)(=Normovolumic
shock):
-It is caused by acute severe VD ( but bl. volume is normal) as in:
(1) Neurogenic shock:
- Sever emotions ( as in vago-vagal syncope)will cause vaso&
venodilatation of skeletal blood vessels & bradycardia leads to
severe decrease in ABP and shock.
(2) Psychogenic shock : due to severe psychic trauma. This
sometimes leads to severe hypotension.
(2) Anaphylactic shock:
- Due to exaggerated antigen-antibody reaction with release of
histamine or kinin causing severe vasodilation with drop in blood
pressure.
(3) Septic shock:
-Severe infection will release bacterial endotoxin and depress the
vasomotor center of medulla oblongata. This will with result in

67
VD of arterioles and capillaries , increase in capillary
permeability, decrease in blood pressure and shock.
(II) Hypovolemic shock: (Secondary shock) (Cold shock)
Caused by loss of blood or plasma or extracellular fluid as in
(1)Post hemorrhagic shock with failure of compensatory
mechanisms.
(2) Burn shock: loss of plasma & VD.
(3)Traumatic shock: Hemorrhage, pain, loss of plasma to tissue &
toxic substance.
(4) Dehydration: severe vomiting, diarrhea or sweating.
(III) Cardiogenic shock: ( low CO shock )
-As in myocardial infarction, heart failure or severe arrhythmia
Cardiac output will be severely decreased leading to shock.
(IV) Obstructive shock:
- due to obstruction of the blood flow as in cases of pulmonary
embolism and thrombosis
* Clinical picture of shock :
1.there is increase in HR, some hormones as ADH , renin
,catecholamines, ACTH , cortisol and T3 & T4 ., sweating ,
irritability and thirst
2.there is decrease in blood pressure , urine output and PH
*Prognosis of shock:
- Its severity depends largely on the degree and rate of blood
pressure drop and resistance of the patient, it may be either:
(A) Reversible (compensated) shock:
-The compensatory mechanisms (immediate and delayed) tries
gradually to restore the ABP up to normal level in negative feed
back manner
(B) Irreversible (Refractory) shock:
-This occurs in severe causes of shock and the patient is not treated
for about 3-5 hours with progressive decrease in cardiac output and
ABP in a +ve feed back manner .

68
 Edema
*Introduction : Methods of transport of substances through
capillary wall: see fig.
• Diffusion : passively, all substances are diffused except cells
And plasma proteins except albumin
• Filtration : passively, for fluids through capillary pores
• Cytopempesis active, or vesicular transport for big particles
• Diabedisis : movement of neutrophil outside capillary wall
*Definition:
-Edema is the presence of excess fluid in the body tissues spaces.
*Types :
-1. Extra or intra cellular :It may be extracellular (most common) or
intracellular (less common).
-2. Localized or generalized :It may be localized (in one fingers as in
inflammation) or generalized (all over the body).
-3. Pitting or non pitting : pitting if the collected fluid is water , non
pitting if the collected fluid is not water e.g lymph, fat .etc
[I] Causes of extracellular edema: see fig
* Causes & types:
(1) Increased capillary and venous pressures as in:
a)Hypertension
b)High venous pressure as in:
- Heart failure generalized edema, called cardiac edema
- Venous obstruction (thrombotic edema), as in deep venous
69
 Thrombosis (=DVT )
- Pregnancy (lower limb edema), called pregnancy edema
- Failure of muscular pump to venous return as in muscle paralysis.
(2) Decreased plasma proteins: see fig
-When plasma proteins fall to an abnormally low value will lead to
marked decrease in plasma colloid pressure and marked ↓ in the
suction power of fluid into the capillaries as in the following cases:
a) Nutritional edema: as in lactating infants without protein diet
support. Due to lack of intake of protein as in kowashirkor
b) Hepatic edema: protein synthesis as in liver diseases.
c) Renal edema: albumin loss in urine as in nephrotic disease.
d) Burn edema: due to loss of plasma protein .
(3) Increased capillary permeability:
-The capillary membrane has become so permeable that even protein
molecules pass from the plasma into the interstitial spaces with ease
as in:a) Immune reaction by released histamine. b) Toxins, bacterial
infection. c) Burn and vit. C deficiency.
(4) Blockage of lymph return:
-If the lymphatic drainage becomes blocked, more and more protein
and fluids collect in the local tissue spaces ,resulting in edema
-Lymphatic obstruction may be caused by:
•Filariasis : the larva of this worm lives in lymphatics causing their
obstruction with edema
•Following removal of lymph nodes in cancer e.g as in radical
mastectomy.

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B-Intracellular Edema: (a non pitting edema):
Cellular edema results from two conditions:
1-Depression of cellular metabolism: This decreases the ATP
formation depression of the Na-K pump Na influx into the cell
water follows Na cellular edema.
2-Inflammations: these increase the membrane permiability to Na and
other ions which diffuse into the cells water following ions cellular
edema.

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 ENDOCRINES AND HORMONES
• See attached synopsis

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 RENAL PHYSIOLOGY
• See attached synopsis

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