Physiology-1

Chapter 1: Autonomic Nervous System

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:
 Relay stations
 Site of action of autonomic drugs.
 Distributing centers
Types of autonomic ganglia:
 Lateral (=Paravertebral ): Only sympathetic
 Collateral (=Prevertebral): Sympathetic ganglia
 Terminal (Peripheral) : Only parasympathetic
Divisions of autonomic N.S.
 Sympathetic nervous system
 Parasympathetic nervous system
 Acetyl choline
Sites at which Ach is released (=cholinergic fibers):
A) central cholinergic fibres

 Inside C.N.S.
 At all the autonomic ganglia (all the preganglionic nerve endings)
  At suprarenal medulla.
 At the motor end plate (junction between somatic nerve and
muscle fibers).
B) peripheral cholinergic fibres
 At all post-ganglionic parasympathetic nerve fibres.
 At some sympathetic post-ganglionic nerve endings to sweat
glands and blood vessels of skeletal muscle.

Inactivation of Ach:
 Cholinesterase enzyme.
Drugs that are related to the Parasympathetic system:
1)Parasympathomimetics " cholinergic receptor stimulants":
A-Choline esters: e.g. Carbacol
They are used in treatment of :-
 Postoperative paralytic ileus.
 Urine retention.
B-Naturally occurring alkaloides:
Uses: Pilocarpine is used as eye drops to cause myosis in the
treatment of simple glaucoma.
C-Anti choline esterases (choline esterase inhibitors):
  Reversible anticholine esterases:
*Prostigmine: In treatment of Myathenia gravis
 Irreversible anticholine esterases:=(Organophosphorus poisoning):
used as war gases or insecticides
e.g: DFP used as war gases & Parathion used as insecticide
2)Parasympatholytics (Drugs blocking A.ch effects):
I- Muscurinic receptor blockers:
Atropine & hyoscine
Most important uses are:
 Mydriasis for fundus examination.
 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).
 Diminshing gastric secretions in hyperacidity and peptic ulcers.
 Releifing intestinal and renal colic.
 Inhibiting excessive sweating.
II- Nicotinic receptor blockers:
Ganglionic blockers & Neuromuscular blockers: "Skeletal muscle
relaxant".
E.g curare & succinyl choline
Uses
 treatment of convulsions
 in anesthesia
Catecholamines
Chief chemical transmitters : noradrenaline (norepinephrine) &
adrenaline (epinephrine)

Natural ones in the body: adrenaline, noradrenaline & dopamine (they

are called catecholamines bec. they contain catechol ring)

Synthetic catecholamine: isoprenaline (not present in our body but has

medical value)
Sites of release of catecholamines also called adrenergic fibers :

 At all adrenergic nerve fibers

 At the chromaffin cells of the suprarenal medulla
Inactivation of catecholamines:
 Methylation: by catechol ortho-methyl transferase "COMT"
 Oxidation: by mono-amino-oxidaze enzyme “MAO”
Drugs acting on sympathetic nervous system
 Sympathomimetic drugs:
-Amphetamine
-Ephedrine
-Noradrenaline
-Adrenaline
-Phenylephrine (alpha1 agonist)
-Clonidine (alpha2 agonist)
-Isoprenaline
-Dobutamine (beta1 agonist)
-Salbutamol (beta2 agonist)
 Sympatholytic drugs:
-Quanithidine
-Reserpine
-CH3 dopa
-Phentolamine
-Ergotamine
-Prazocine (alpha1 blocker)
-Yohimbine (alpha2 blocker)
-Atenolol (beta1 blocker)
-Butoxamine (beta2 blocker)
 Chapter 2: Blood
Blood
It 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:

 Colour: red due to presence of hemoglobin in RBCs.

 pH: 7.4 (7.35-7.45) ( the venous blood is slightly acidic as it
contains more Co2 and metabolites from tissue)
 Specific gravity: It equals to 1.060 [of plasma = 1.030 & of RBCs =
1.090].
 Viscosity: It is about 5 times as water, due to presence of
fibrinogen + albumin, and RBC. It increases in polycythemia and
decreases in anemia.
 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.
 Volume of blood : 5-6 litres =7-8% of body weight
Functions of the blood:
 Transport medium
 Defensive function
 Homeostatic function
a- Regulation of water content
b- Regulation of pH
c- Regulation of metabolism
d- Regulation of body temperature
e- Regulation of arterial bl. pressure
Functions of plasma proteins:
 Blood clotting (haemostasis)
 Defense (immunity)
 Transport function
 Regulation of body fluids
 Regulation of plasma viscosity
 Control of capillary permeability
 Buffer functions
 Nutritional functions
 CO2 carriage
 Specific functions
Functions of RBCs:
 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..
  Functions related to contents:
a)O2 carriage: 1 molecule of Hb carries 4 O2 molecule and each
gram of Hb carries 1.33 ml of oxygen.
b)CO2 carriage: by Hb in form of carbamino Hb.
c)carbonic anhydrase enzyme is important for CO2 carriage
d)Acid – base buffer: by Hemoglobin
e)RBCs & plasma proteins are responsible for bl. viscosity and
blood pressure regulation.
Formation of RBCs (Erythropoiesis):
(A) Sites of formation:
 In the foetus:-Yolk sac: in the first few weeks of pregnancy till 6
weeks
-Liver & spleen: from 6 weeks to 6 months.
-Bone marrow: from the 6th month till puberty.
 In infancy & childhood: From red bone marrow of all bones.
 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
 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:
Proteins: of high biological value as animal proteins (contain
essential amino acid) to form globin part of Hb.
Metal ions:

 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.
- 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.
-Iron is fed in diet as ferric state
-Ferric state of iron ferrous state.
-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.
Factors affecting iron absorption:
- Body need of iron: increase need as in pregnancy lead to
increase absorption directly from intestinal lumen to plasma.
- 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).
-Contents of food: - Oxalates, phytate & phosphate decrease
absorption. Ascrobate, lactate & succinate increase absorption.
-Hypoxia and anemia increase iron absorption
-Some foods: some cereals, phytate and alkalies decreases its
absorption .
 Copper: carried by plasma protein (ceruloplasmin) to catalyse and
oxidyse ferrous into ferric state to be carried as transferrin.
 Cobalt: stimulate erythropoitin release from the kidney, so
increase cobalt may lead to polycythemia.
Vitamins: (= Erythrocytic Maturation factors)
 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: -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.
Deficiency: - Due to malabsorption resulting in an anemia called
megaloblastic ,pernicious anemia and B12 deficiency anemia
 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.
Both vitb12& folic acid are necessary for maturation of RBC
 Vitamin C: is required for reduction of ferric to ferrous and help
maturation of red blood cells
  Vitamin 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:
-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.
Structure: It is made of 4 subunits each of them is formed from one
haem and one polypeptide chain.
Functions: - Carriage of O2 & CO2 - Strong buffer system.
Reactions of Hb and all forms of carriage:

 Oxyhemoglobin: O2
 Met Hb: strong oxidation
 Carboxy Hb: carbon monoxide
  Carbamino Hb: CO2
Types of Hb:
A) Normal Hb :
 Adult ( HbA): contain 2 chains alpha and 2 beta
 HbA2: contain 2 chains alpha and 2 delta
 Fetal Hb (HbF): contain 2 chains alpha and 2 gamma
 Glycosylated Hb( Hb a1C ): contain 2 chains alpha and 2 beta and
one glucose
B) Abnormal Hb

 Abnormal chain (HbS) : contain 2 alpha and 2 S. It causes sickle cell

anaemia.
 Abnormal arrangement of chains (HbB) : contain 4 B. It causes
Thalassemia.
Anaemia
Definition: Anaemia is the decrease in red cell count or hemoglobin
content leading to decrease O2 supply to tissues with symptoms of
hypoxia.
Classification:
(A) Etiological
(B) Morphological: Very important in diagnosis: According to the size
and hemoglobin content of the red cells:
Normocytic (normal MCV) normochromic (normal MCH) anaemia:
 Acute haemorrhagic
 Hemolytic
 Aplastic
 Decreased erythropoietin production as renal and liver failure.
Microcytic (decreased MCV) hypochromic (decreased MCH) anemia:
 Iron deficiency anaemia.
 Chronic blood loss
 Disorders of globin.
 Disorders of porphyrin.
Macrocytic (increased MCV) hyperchromic (increased MCH) or
normochromic

 Vitamin B12 deficiency anaemia.

 Folic acid deficiency anaemia.
Polycythemia
Definition: It is abnormal increase in RBCs number above 6 millions
/cmm and it might reach 101 millions/ cmm
Types:
 Secondary polycythaemia: Increased erythropoietin
a)Chronic lung diseases (hypoxia).
b)Cigarette smoking(hypoxia).
c)Kidney diseases
 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).
Hemostasis
Steps of hemostasis , chronologically
 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.
c)The reduced blood flow help contact activation of platelet and
clotting factors.
 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:
a)It stops blood loss from small punctures.
b)It closes the minute ruptures of very small vessels, which occur
hundreds of times daily.
c)The chemicals released from the plug help other mechanisms of
haemostasis as the following: as serotonin and throboxane A2
 Blood coagulation
It is the formation of blood clot (= a network of insoluble fibrin
entangling blood cells)
It needs the following clotting factors:
 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
Steps of blood clotting
[1] Formation of Prothrombin activator:

 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.
 Intrinsic pathway:
1)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.
2)Also, subendothelial collagen or the wettable surface activate
the platelet to release platelets phospholipids .
3)Then factor XIIa activates factor XI in presence of high molecular
weight kininogen (HMWK).
4)Then factor XIa activates factor IX .
5)Then factor IXa + Factor VIII + platelet phospholipids in presence
of calcium ions activate factor X.
6)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:

 Conversion of fibrinogen to fibrin threads.

 Thrombin activates some of the clotting factors (V,VII,VIII) which
are required for its formation in a positive feed back.
 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 blood
vessel wall forming loose net like meshwork that traps the blood cells
forming red soft blood clot.
[4] Clot retraction:

 Makes clot firm and attached to the nearby tissue

 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
[Factors against intravascular clotting]( = factor preventing
formation of a clot): These factors prevent blood clotting in
normal state

 Smoothness of endothelium in prevention of clotting:This

prevents contact activation of XII.
 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)
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.
Breakdown of the clot if formed: If clot is formed it is broken down by a
system called fibrinolytic system.
Activation of plasminogen & fibrinolysis:
 Tissue plasminogen activator: (t-PA)
 Factor XII, Kallikrein & thrombin.
 Other physiological activators as: Urokinase enzyme
 Exogenous activators: as streptokinase enzyme
Anticoagulants
Prevention of blood clotting outside the body [ Invitro
anticoagulants]
 Blood is collected in silicon or paraffin coated test tube to prevent
aggregation and activation of factor XII.
 Cooling of the blood delay clotting.
 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
nonionized Ca++ (Ca++ citrate) This compound is not toxic, and is
rapidly removed from the blood so citrate is used in blood
transfusion.
-EDTA(Ethelyne diamine tetraacetic acid) causes chelation of Ca++
 Defibrination of blood by a glass rod.
 Addition of heparin as in artificial kidney machine.
Prevention of blood clotting inside the body [In vivo anticoagulants]

Disorders of hemostasis:
[A] Bleeding tendencies:
(1) Vitamin K deficiency:
Causes:
 Decrese intake of vit.K
 Decrease absorption as in decrease fat absorption in cases of
obstructive jaundice or steatorrhea (fatty diarrhea).
 Vit. K antagonist as Dicumarol.
 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.
(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:
 Thrombocytopenic purpura:
Due to: decrease platelets count below 60.000/mm3
Causes:
a)Idiopathic or 1ry: may due to autoimmune disease leading to
destruction of the platelets.
b)2ry: -Platelet production due to bone marrow lesion as
radiation, infiltration by tumor cells or due to decrease of vitamin
B12 or folic acid.
- Platelet destruction by drugs or repeated thrombosis or
hypersplenism.
 Non-Thrombocytopenic purpura:
Due to: Abnormal vascular or platelets function even their count is
normal.
Causes:
a)Platelet abnormality:
. Inherited weakness of the platelets (thrombasthenia) due to
deficiency of plasma membrane.
. Acquired due to the effect of some drugs as Aspirin blockage of
thromboxane A2 which is required for platelet aggregation.
b)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:

 Rough endothelium as in atherosclerosis and in injury of blood

vessels by trauma.
 Slow blood flow as in prolonged lying in bed.
 Increase blood viscosity.
It may lead to:
 Arterial obstruction and ischemia
 Venous obstruction and edema
 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)

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:

 Intact skin which resists the invasion by bacteria.

 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:
 Humoral immunity: by circulating antibodies formed by B-
lymphocytes.
 Cell-mediated immunity: by activated T-lymphocytes
Humoral immunity

Mechanism of action of antibodies=antigen antibody reactions

(1) Direct: interaction neutralizes the dangerous effect of the antigen by:
 Agglutination
 Precipitation
 Lysis
 Antitoxication
 Opsonization
Cellular immunity (cell-mediated)
Types of T-lymphocytes:
 Cytotoxic T8 lymphocytes
 Helper-T4 cells (75%)
 Suppressor or regulatoryT8 cells
 Memory T cells
Chapter 3: Cardiovascular System
The Vascular System
Arteries (Distributing system):

 Elastic arteries (= as aorta): acts as a second pump.

 Arterioles: function as resistance vessels.
Capillary networks (Diffusion system) : function as exchange vessels.
Veins (Collecting system): function as capacitance vessels.
Pulmonary vessels: function as gas exchange.
Lymphatic vessels: function as drain system.

The Heart

Properties:
 Excitability
 Rhythmicity (Automaticity)
 Conductivity: 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:
1)S.A.N .
2)Bachman’s bundle :
3)3 intermodal 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
  Contractility
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).

CARDIAC OUTPUT (COP)

Definitions:
Cardiac output: 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): 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): the volume of blood in the ventricle at the
end of diastole. It is about 135 -140 ml.
End systolic volume(ESV): 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): 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).
Cardiac index (CI): 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: 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:

 Excitement: increase COP by about 50 -100% due to sympathetic

stimulation.
 Exposure to extremes of temperature: as in high temperature due
to skin vasodilatation.
 Eating: in the first few hours after eating due to increase GIT blood
flow.
 Exercise: exercise can increase COP up to 700% in trained athletes
 Pregnancy: due to increase uterine blood flow and placental
arterio-venous shunt
[C] Cardiac output is decreased in:
 Sitting or standing from lying down decrease COP by 20 -30%.
 Marked arrhythmia (tachycardia or bradycardia).
 In all conditions which destroy the cardiac muscle fibers.

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:
 Pressure provided that flow is constant
 Length of blood vessel
  Viscosity of blood , which is affected by no of blood cells and
diameter of arterioles
and inversely proportional with:
 Fourth power of radius of blood vessel
 Flow provided that pressure is constant
Arterioles
Functions of arterioles:
 Determination of the peripheral resistance : They are called the
resistance vessels.
 They control the blood flow to the tissues : by changing their
diameter through producing V.D. or V.C.
 They are responsible for regulation of body temperature
Factors regulate arteriolar diameter:
[1] Factors causing vasodilatation of arterioles and thus decreasing
blood pressure :
 Hypoxia , except in pulmonary blood vessels
 Other metabolites as K lactic acid and pyruvic acids , and
hyperthermia
 Prostacycline ,
 Endothline Drived Relaxing Factor ( EDRF =NO=VIAGRA )
 Histamine , released from mast cell
 Bradykinin released in inflammation
 ANP ( atrial natriuretic peptide )
[2] Factors causing vasoconstriction of arterioles and thus causing
increase in blood pressure :

 O2 except in pulmonary blood vessels

 ThroboxaneA2
 Endothelines: intake of low dose of aspirin will increase
prostacycline and decrease throboxane A2 , this protects adults
from hypertension and thrombus formation
 Serotonin ( 5HT ) released from platelets
 ADH (= antidiuretic hormone )
 Angiotensin II
 Arterial Blood Pressure
Definitions:
Arterial blood pressure (ABP): 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: 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: 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:
 Direct Method:-By cardiac catheter cannulated through a large
artery under local anesthesia. It transmits the blood pressure to
manometer.
 Indirect Method:- using sphygmomanometer and stethoscope.
Physiological variations of ABP :
 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.
 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.
 Body built:
-The blood pressure usually higher in obese persons.
 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.
 Sleep:
-During quiet sleep the ABP is decreased due to parasympathetic
activity. But it is increased in REM sleep
 Emotions:
-In different emotional state (e.g. anger) the ABP is elevated due
to sympathetic over activity.
 Meals:
-After meals the ABP increases
 Gravity:
-During standing, the blood pressure increases in all vessels below
the heart and decreases in vessels above the heart level.
-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.
 Exercise:
-The systolic blood pressure increases sharply, while the diastolic
blood pressure remains constant or even decreases.
 Respiration:
-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 part of expiration, while it falls during the remainder of the
respiratory cycle".
 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 HR but in REM sleep HR increases
Shock
Definition: Circulatory shock means inadequate tissue perfusion with
blood due to decreased CO & ABP.
Types and causes of shock:
(I)Low-resistance shock: (= primary shock)(=Normovolumic shock): -It is
caused by acute severe VD ( but bl. volume is normal) as in:
 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.
 Psychogenic shock: due to severe psychic trauma. This sometimes
leads to severe hypotension.
 Anaphylactic shock: due to exaggerated antigen-antibody
reaction with release of histamine or kinin causing severe
vasodilation with drop in blood pressure.
 Septic shock: severe infection will release bacterial endotoxin and
depress the vasomotor center of medulla oblongata. This will with
result in 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:
 Post hemorrhagic shock with failure of compensatory
mechanisms.
 Burn shock: loss of plasma & VD.
  Traumatic shock: Hemorrhage, pain, loss of plasma to tissue &
toxic substance.
 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 :
 There is increase in HR, some hormones as ADH , renin,
catecholamines, ACTH , cortisol and T3 & T4 ., sweating, irritability
and thirst
 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:

 Reversible (compensated) shock:

-The compensatory mechanisms (immediate and delayed) tries
gradually to restore the ABP up to normal level in negative
feedback manner.
 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 feedback manner.
Edema
Definition: the presence of excess fluid in the body tissues spaces.
Types :
 Extra or intra cellular: It may be extracellular (most common) or
intracellular (less common).
 Localized or generalized: It may be localized (in one fingers as in
inflammation) or generalized (all over the body).
 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:
Causes & types:
[1] Increased capillary and venous pressures as in:
 Hypertension
 High venous pressure as in:
- Heart failure generalized edema, called cardiac edema
- Venous obstruction (thrombotic edema), as in deep venous
Thrombosis (=DVT )
- Pregnancy (lower limb edema), called pregnancy edema
- Failure of muscular pump to venous return as in muscle
paralysis.
[2] Decreased plasma proteins: 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:
 Nutritional edema: as in lactating infants without protein diet
support. Due to lack of intake of protein as in kowashirkor
 Hepatic edema: protein synthesis as in liver diseases.
 Renal edema: albumin loss in urine as in nephrotic disease.
 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:

 Immune reaction by released histamine.

 Toxins, bacterial infection.
 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.