Cardio vascular physiology

BY TEFERA D.(MSC IN MEDICAL PHYSIOLOGY)

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 Components of cardiovascular physiology:

Blood

Heart

Blood vessels

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 Blood
 Blood is a connective tissue composed of a liquid extracellular
matrix called blood plasma that dissolves and suspends various cells
and cell fragments.

 Is a transport liquid pumped by the heart to all parts of the body,

after which it is returned to the heart to repeat the process.

 The branch of science concerned with the study of blood, blood-

forming tissues, and the disorders associated with them is
hematology
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 Characteristics

A. Color: bright red (Hgb – arterial blood, oxygenated blood)

dark red (venous blood, deoxygenated)

B. Viscosity: Refers to internal resistance of a liquid to flow.

Blood is 3X thicker and denser than pure water.

C. pH range: from 7.35 to 7.45 (blood is slightly alkaline)

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D. Volume of blood : Typical volume in
- adult male: 5-6 liters
- adult female: 4-5 liters
E. Density (Specific gravity):
a. Refers to the weight of blood compared to that of water
b. Specific gravity of H2O is taken as 1 (i.e., 1 ml of H2O
weighing 1 gm at 40C)
Male: 1.052- 1.063
Female: 1.050 – 1.058
(i.e., 1 ml of whole blood weighing 1.060 gm)

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.

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.

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Major Functions of the blood
1. Transport
a. Gases (O2 and CO2 )
b. Nutrients (organic and inorganic like electrolytes )
c. Hormones
d. Waste products
2. Defense: against infections by means of
a. WBC (phagocytosis, antibody formation)
b. Platelets (prevention from bleeding)
3. Regulation
a. Temperature regulation
b. Acid-base balance- Hb-acting as a buffer.
c. Blood volume regulation etc.
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Major Components of blood

1. Formed elements (45%) - the actual cellular components of

blood
a. Erythrocytes (Red blood cells)
b. Leukocytes (White blood cells)
c. Thrombocytes (Platelets)

2. Plasma(55%) - is the fluid portion of the blood

• Blood represents about 8% of total body weight (about 5 L).

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Hematocrit (Ht) = packed cell volume (PCV)

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Hematocrit (Ht) = packed cell volume (PCV)

3-layers after centrifugation

1. Upper suspension: is the blood plasma

that accounts to 55% of the blood
volume.

2. Buffy coat: thin, cream-colored layer.

Accounts to < 1% of the volume. It
consists of WBC & platelets

3. Lower portion : is a reddish mass of RBC

that settles at the bottom of the test tube.
Accounts to 45% of the whole blood.

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 The cells that settle down to the bottom (mainly RBCs) form the
hematocrit or packed cell volume (PCV).

 Def: The Hematocrit (Ht) is the percentage of erythrocytes

in the total blood volume (normal = 45%).

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.

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 Plasma
 Plasma is the liquid portion of the blood and accounts to about 55% of the total blood
volume. It is cloudy, pale, or grayish-yellow liquid

 Plasma is composed of (plasma vs serum):

 Water (>93 %)

 Electrolytes (Na+ and Cl- and HCO3-, K+, Ca2+ in small

amount)

 Proteins (~ 7 %)

 Nutrients (glucose, amino acids, lipids, and vitamins)

 Waste products (Creatinine, bilirubin, and nitrogenous

substances such as urea)

 Dissolved gases (O2, CO2)

 Hormones
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 Serum vs. plasma

 Serum is a clear, watery fluid after blood is left to clot.

 Serum has more or less similar composition to plasma except

that its fibrinogen and clotting factors (II. VI, VII) have been

removed

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 Parts of plasma proteins

 Plasma proteins : 3 groups

A. Albumin (~ 60% or 4.5 gm/dl)

B. Globulins ( ~ 40% or 2.5 gm/dl)

C. Fibrinogen (0.3 gm/dl)

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 Characteristics of plasma proteins
1. Albumin:
 Is formed in the liver
 Helps to maintain blood volume, b/s it can not easily pass through the
capillary membrane and thus, exerts the so called plasma colloid osmotic
pressure (oncotic pressure)
 During malnourished conditions (deficiency of protein intake), blood
volume decreases due to decreased albumin and this effect results in
edema
 Albumin also serves in transporting nutrients (FFA, hormones, bilirubin,
penicillin etc.)

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 2. Globulin:
 Types : alpha, beta, gamma
 alpha and beta globulins are involved with several activities:
• transport substances: hormones, cholesterol, iron

• function as clotting factors

• serve as precursor molecules - angiotensinogen
 The majority of the immunoglobulin (antibodies) are part of
gamma globulins

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 Alpha and beta globulins are synthesized in the liver; the gamma

globulins are made by the lymphocytes (a type of white blood

cell).

C. Fibrinogen:

- Fibrinogen is synthesized in the liver

- It is mainly involved in blood clotting

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Red Blood Cells (RBC’s)
(Erythrocytes)

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 Red Blood cells (RBC)

 Shape:
• RBC is a flexible biconcave cell
that is thinner at the center and
thicker at the edges
 Diameter: ~ 7.5 um
• Matured RBC does not have
nucleus & lack most organelles
• Therefore, can bend and twist to
pass through the narrow
capillaries very easily

 Life span-120days

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 Hb structure and function

 Hemoglobin – is large molecule inside RBC. It has:

a. Globin part: protein with 4-polypeptides (2
alpha & 2 beta polypeptides)

b. Heme group: Fe 2+ containing central part to

which oxygen binds.

 Each polypeptide has one heme group, each heme with Fe2+
carries one O2 molecule, total = 4-O2 molecules are carried
within Hb molecule
1g Hb binds with 1.34 ml O2
 15g Hb/dl x 1.34 ml O2 = 20.1 ml O2/100 ml blood

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 Types of Globin Chains

• The polypeptide chain (the globin unit) determines the physical

characteristics of the Hb-molecule and its binding affinity for
O2.
• Thus, they exists:
a. Adult Hb (Hb A): 2 alpha + 2 beta
b. Fetal Hb (Hb F): 2 alpha + 2 gamma (it has higher
O2 affinity)
c. Sickle cell Hb(Hb-S): valine is replaced by
glutamic acid at beta- chain so on.
d. Also there HBA2 and HBC.????

Function of Hb: Carries O2 and CO2 gases

It is a buffer to maintains acid-base balances

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 Function of RBCs

1. Carries hemoglobin that in turn transports respiratory gases

(O2 and CO2)
2. Hb also helps as a buffer (pH balance)
3. Carbonic anhydrase (CA):
 an enzyme located in RBC membrane
 is critical in CO2 transport

CO2 + H2O CA
H2CO3 = HCO-3 + H+

• HCO-3 is the primary form in which CO2 is transported in the

blood
- CA increases the rate of this reaction 5000 fold.

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 RBC number

Average RBC number

o 5.5 million/ mm3 blood in male

o 4.7million/mm3 in female

o Average: Hb(hemoglobin): 15 g/dl

o Average Hct (hematocrit): 45%

 Why male has more RBC than females???

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• The pluripotential hematopoietic stem cells, will divide and

differentiate into myeloid stem cell and lymphoid stem cells

• The myeloid stem cells will divide and differentiate in to

o RBCs

o Granulocyte WBCs

o Platelets and

o Monocytes

• Lymphoid stem cells will differentiate to lymphocytes

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 Haematopoiesis (Hemopoiesis)

• Is production (genesis) of all blood cells

• In the early weeks of embryonic life, primitive nucleated red

blood cells are produced in the yolk sac.

• During the middle trimester of gestation, the liver is the main

organ for production of red blood cells, but reasonable numbers

are also produced in the spleen and lymph nodes.

• Then, during the last month and after birth, red blood cells are
produced exclusively in the bone marrow.

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• After 20 years most blood cells continue to be produced in the

marrow of the membranous bones, such as the vertebrae,

sternum, ribs, and ilia

• The blood cells begin their lives in the bone marrow from a single

type of cell called the pluripotential hematopoietic stem cell, from

which all the cells of the circulating blood are eventually derived

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 Cont..

• The bone marrow of essentially all bones produces red

blood cells until a person is 5 years old.

• The marrow of the long bones, except for the proximal

portions of the humeri and tibiae, becomes quite fatty and

produces no more red blood cells after about age 20 years

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 RBC-production

• Erythropoiesis: Production of RBC in the body occurs by the process of erythropoiesis

by negative feed back mechanism.

Physiological Mechanism

• The stimulus for erythropoiesis is hypoxia (low O2) that occurs in the kidney cells 

Kidney then releases a hormone called erythropoietin  Erythropoietin is transported by

the blood to bone marrow  Bone marrow produces and releases an increased RBC

that in turn supply O2 to hypoxic tissues. Increased or adequate O2 then blocks the

formation of more RBC.

• Erythropoietin is produced by the kidneys (90%) and liver (10%)

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 Mechanism of erythropoiesis
4. Additional circulating
1.Kidneys detect reduced O2-carrying
erythrocytes increase O2-
capacity of blood carrying capacity of
blood.
2.When less O2 is delivered to the kidneys,
5. Increased O2 carrying
they secrete erythropoietin into blood.
capacity

3. Erythropoietin stimulates erythropoiesis relieves initial stimulus

that triggered
by bone marrow.
erythropoietin secretion.

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Mechanism of erythropoiesis

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 RBC- Stages of development or Genesis

 Stem cells differentiate to produce committed stem cells called

hematocytoblasts.

1. Hematocytoblasts (proerythroblast): where Hb synthesis begins, big

nucleus

2. Basophil erythroblast : little Hb

3. Polychromatophil erythroblast (Hb synthesis increases and fills the

cytoplasm, nucleus size decreases)

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4. Orthochromatic normocyte: Nucleus size further decreases

5. Reticulocytes: contains Hb, no nucleus and the cell is expelled

from the bone to circulation

6. Erythrocytes: mature form of RBC without nucleus, filled

with Hb

* Stress, hemorrhage, hypoxia are factors that increases the No

of reticulocytes above normal (> 1%)

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 Substances necessary for RBC maturation

a. Vitamin B12 (Cyanocobalamin)

• Important for DNA synthesis and thus for cell

division.

• Deficiency of Vit. B12 causes macrocytic cells

• Because of their big size, the cells rupture when

passing through the capillary wall (so, cause

megaloblastic anemia) 37
 Substances necessary for RBC maturation

• Deficiency caused by poor absorption of vit. B12 from the

gastrointestinal tract due to a deficiency of intrinsic factor.

• Vit. B12 requires intrinsic factor (glycoprotein secreted by

parietal cells of the gastric glands) for absorption

b. Folic acid: Obtained from green vegetables, fruits, liver, meat.

Also important in DNA synthesis.

c. Iron: Necessary for RBC formation (Co, Vit. Copper etc)

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 Blood groups

• In humans, there are two known blood groups that are clinically important:

a. ABO-blood groups,

b. Rh- blood group system

• In the ABO system, blood is classified primarily on the basis of the A

and B antigens present on the surface of red blood cell membranes
(erythrocytes).

• Antigen (agglutinogen) is a large, complex molecule that triggers a

specific immune response against itself when it gains entry to the body
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 Cont.…

• Secondly, blood is classified on the basis of the naturally

occurring antibodies (agglutinins) in the plasma

• Antibodies are specialized molecules produced by the immune

system to attack foreign antigens

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 ABO-blood groups

• A person whose red cells possess the A -antigen has anti-B

antibody in his serum and is classified as blood group A.
• If B antigen is present in the red cell membranes, Anti-A antibody is
present in his serum and the person is designated as blood group B.

• If both A & B antigens are present on red cells, then he has no

antibody, so is AB blood group.

• If No antigens are present on red cells, he is O Type and has both

anti A and B antibody in his serum.
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.

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 Universal donor

• Blood group “O” is called universal donor, because people with

this blood types have no antigens on their cell-membrane surfaces

and therefore can not agglutinate if transfused to any blood types.

• Even though they lack antigens, they have anti- A & anti-B

antibodies in the plasma. So, they can receive blood from persons

with blood group “O” only.

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 Universal recipient

• People with this blood group can take (be transfused) blood

from any blood types, because they have no antibodies in their

blood to cause agglutination reactions.

• AB can donate blood only to a person with blood AB, not to

other.

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 Donators and Recipients
Donators
1. O can donate blood to group A, B, AB, and O
2. A “ A & AB only
3. B “ B & AB only
4. AB “ AB only
Recipients
1. O can receive blood from group O only
2. A “ A & O only
3. B “ B & O only
4. AB “ A, B, O, & AB

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 Rh-factor

• How is it first identified: Blood of Rhesus monkey (antigen) is

transfused to Guinea Pigs or Rabbits (1940)

• The serum of Rabbits or Guinea Pigs agglutinated the

monkey’s RBC.

• These anti-Rhesus antibody was also found to a agglutinate the

majority (85%) of red cells of humans.

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 Cont.…

• There are many kinds of Rh-antigens (e.g., C, D, E, c,

d, e), the most potent one is antigen D.

• Thus, people are classifies as Rh+, if their red cells

possess the Rh-antigen (called D antigen) or Rh- , if

they do not posses the D- antigen on their Red cells.

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• Rh- subjects can however produce antibodies against that

antigen only when they are exposed to Rh+ blood.

• Rh-negative people should be given only Rh-negative blood,

whereas Rh-positive people can safely receive either Rh-

negative or Rh-positive blood.

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 Rh Incompatibility

• Compatibility is determined by mixing the red blood cells

from the potential donor with plasma from the recipient.

• If no clumping occurs, the blood is considered an adequate

match for transfusion.

• Father Rh+ = Rh+ means he has D-antigen on his RBC

membrane

• Mother Rh- = No Rh factor, so it is depicted as Rh-

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 Cont.…

Marriage:

1. Rh+ father X Rh- mother = Rh + fetus

2. During birth through placenta , Rh+ blood (antigens) of

the fetus leak (enter) to mothers blood and sensitizes her.

3. Mother ‘s blood produces anti-Rh antibodies (anti-D

antibodies ) against the Rh+ blood.

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• During the 2nd pregnancy and there after, the Anti-Rh+ antibodies
(agglutinins) enter into the fetus and agglutinate or hemolyze the
RBC’s the fetus.
• This type of hemolytic disease is called Erythroblastosis fetalis.

• If the baby is born alive from the incidence, then there is a higher risk
of being anemic and jaundiced (yellow coloration on his skin, eyes,
finger nails due to excess circulation of bilirubin.)

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.

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 Clinical correlates

1. Jaundice

• The older red cells are phagotizised by macrophage cells of the

reticuloendothelial system that are located in the liver, spleen,
and bone marrow cells.
• The macrophages release the Hb-molecule that is broken down
into:
a. its protein part (Globin) and,
b. Heme part

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 Steps in the destruction of RBC

1. RBC has Globin + Heme

2. Globin will be broken to amino acids which are used for

protein synthesis
3. Heme has Fe2+ + porphyrin rings
4. Fe 2+ will be stored in the liver and used for new Hb synthesis
5. Porphyrin rings will oxidize to green pigment called
biliverdin and later reduced to bilirubin

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• Bilirubin is excreted through feces in the form of stercobilin

and through urine in the form of urobilin

• Excess bilirubin in the blood causes yellowish discoloration

of the skin and the sclera. This yellowish discoloration is

called jaundice.

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 2. Anemia
• Anemia is a decrease in number of circulating RBCs in the blood
(low Hb concentration)
• Anemia may be caused by reduced production of RBcs OR blood
loss
3. Polycythemia
• Polycythemia means high number of RBC
2 types
1. Primary polycythemia
 RBC count may reach (8-9 million/mm 3)
 Tumerous or cancerous production which causes highly
engorged blood
 Increases blood’s viscosity up to five to seven times normal
2. Secondary Polycythemia:
 Is mostly physiologic, hypoxic tissues (low O2) 6-8 million/mm3
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White blood cells(WBCs)
( Leukocytes)

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• Nucleus: Have nucleus all the time, but lack Hb
• Normal number: 4000-10,000 / mm3 of blood
• Defense: WBC’s fight infection by:
o direct destruction (e.g., Phagocytosis)
o producing : i. antibodies &
ii. sensitized lymphocytes
• Mobility: Are highly mobile and reach tissue fluids
• When infection occurs, WBC increase in number
e.g., Neutrophils
• Life span: Many (not all) live only a few days, may be b/c of
their engagement with pathogens

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 Types of WBCs
1. Granulocytes
a. Neutrophils (~ 62%), life span 4-5 days
b. Eosinophils (~ 2-3%) “
c. Basophils (~ 0.1-0.4%) “
• They are also called polymorphonuclear WBc’s (i.e. their nuclei
have 3-5 lobes)
• Contains an abundance of membrane-enclosed granules in their
cytoplasm
2. Agranulocytes
 Lymphocytes (~ 30%), weeks or months
 Monocytes (~ 5 %), 20 hrs

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Normal blood cellular elements

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 - circulate in blood and change into macrophages
that attach to tissues. e.g. alveolar macrophages
in the lung, kupffer cells in the liver etc.
• Both have a single, large, nonsegmented nucleus and few
granules
• Macrophages live longer times (months- years).

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 Functions of WBCs

• Granulocytes (Neutrophils, Eosinophils, basophils) and

monocytes destroy invading organisms by phagocytosis.
• The granulocytes and monocytes are formed only in the bone
marrow
• Lymphocytes , to the contrary, attack infections through the
immune system by producing sensitized lymphocytic cells and
plasma cells that produce antibodies.
• Lymphocytes and plasma cells produced in lymphogenous
(spleen, thymus, tonsils etc) organs
 Neutrophils
• Attack and destroy invading bacteria by phagocytosis.
• They can engulf 3-20 bacteria's at once.

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• They are also involved in removal of tissue debris and
therefore play a role in the healing process.
• Macrophages: They can phagocytize >100 bacteria at once
and even engulf bigger ones like RBC’s, malaria parasites
etc.
 Eosinophils
• are bi-lobed and weak phagocytes .
• Have granules in the cytoplasm that have enzymes
• Their number increases during asthma, parasitic infections
(for example, worms) and other allergic attacks
• They cannot engulf a much larger parasitic worm, but they do
attach to the worm and secrete substances that kill it.

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 Basophils
• Constitute < 1%
• Have granules
• Granules contain heparin and histamine, which have
anticoagulant and vasodilating properties, respectively
increases regional blood flow and attracts other leukocytes,
including eosinophils, to areas of infection
 Monocytes
• Have no granules and the nucleus is not lobed
• When attach to tissues they become macrophages
• Macrophages are highly phagocytic cells that can ingest many
bacteria's, parasites and debris etc.

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 Lymphocytes
• Have no granules and the nucleus is not lobed
Types:
• B-lymphocytes:
 produce antibodies, which circulate in the blood, that find

and mark pathogens for destruction

= antibody-mediated, or humoral , immunity
• T-lymphocytes:
 they directly destroy their specific target cells by
releasing chemicals that punch holes in the victim cells
= cell-mediated immunity
Target cells = body cells invaded by viruses and cancer
cells.

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.

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 The tissue macrophage system (reticulo-endothelial system)
Monocytes are formed in the bone marrow

Enter the circulation

Leave the circulation & enter the tissue,

↑size, ↑lysosomal activities

Become tissue macrophages

Lungs Skin Liver Brain Bone Spleen,

Alveolar Histocytic Kupffer Microglial Osteoclasts lymph nodes
Macrophages cells cells cells Reticular cells

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 Leukocytes Disorders: Leukemia
• Leukemia refers to cancerous conditions involving white blood
cells (causing proliferation of immature WBCs)
• Leukemias are named according to the abnormal white blood cells
involved
– Myelocytic leukemia: – involves myeloblasts
– Lymphocytic leukemia: – involves lymphocytes
• Acute leukemia
– Rapid onset (children and adults)
• Chronic leukemia
– Symptoms develop slowly
(mostly in adults)

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 Leukemia…cont’d
Immature white blood cells are found in the bloodstream in
all leukemia in large number.
Bone marrow becomes totally occupied with cancerous
white blood cells
The WBCs produced in numerous, but are not functional
Death is caused due to internal hemorrhage and massive
infections

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 Symptoms of Leukemia
• Night sweats and fever
• Infections
• Weakness/chronic fatigue
• Headaches
• Bleeding/bruising
• Joint/bone pain
• Abdominal swelling from
enlarged spleen
• Lymph node swelling
• Weight loss
Treatments: include
irradiation, anti-leukemic
drugs, and bone marrow
transplants
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 Immunity
• Immunity is body's ability to resist or eliminate potentially
harmful foreign materials or abnormal cells
• Consists of the following activities:
– Defence against invading pathogens (viruses & bacteria)
– Removal of 'worn-out' cells (e.g., old RBCs) & tissue debris
(e.g., from injury or disease)
– Identification & destruction of abnormal or mutant cells
(primary defence against cancer)
– Rejection of 'foreign' cells (e.g., organ transplant)

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 Types of Immunity
Two types:
A. Non-specific immunity or Natural/innate immunity
Examples:
 Phagocytosis
 HCl in the stomach
 Skin barrier
 Lysozymes in saliva
 Interferons:
 proteins made and released by host cells in
response to the presence of pathogens such as
viruses, bacteria, parasites or tumor cells.

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 Types of Immunity...cont’d
B. Specific immunity or acquired/adaptive immunity
Features:
 Specific
 Memory:
 The ability to remember and respond more
robustly against a second encounter with the same
pathogen
 Recognition of self and non-self:
 The ability to distinguish between the body’s own
cells, recognized as “self,” and foreign cells, or
“non-self
 Involves lymphocytes (a type of WBC) called T
lymphocytes (T cells) & B lymphocytes (B cells).
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 Types of acquired immunity

1. Humoral immunity/Antibody mediated immunity

– B-Lymphocytes are specialized for this type of immunity
2. Cellular immunity/Cell mediated immunity
– T-Lymphocytes are specialized for this type

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 Lymphocytes
• They are the major soldiers in immune system battles.
• Most lymphocytes continually move among lymphoid tissues,
lymph, & blood, spending only a few hours at a time in blood.
 Thus, only a small proportion of the total lymphocytes are
present in the blood at any given time.
• Three main types of lymphocytes are B cells, T cells, &
natural killer (NK) cells.
• B cells are particularly effective in destroying bacteria &
inactivating their toxins.

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 Lymphocytes …cont’d

• T cells attack viruses, fungi, transplanted cells, cancer cells, &

some bacteria, and are responsible for transfusion reactions,
allergies, & the rejection of transplanted organs.
 Immune responses carried out by both B cells & T cells
help combat infection & provide protection against some
diseases.
• Natural killer cells attack a wide variety of infectious microbes
& certain spontaneously arising tumor cells.

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 Lymphocytes and their origin
Bone Marrow (IUL)
Lymphoblasts (lymphocyte stem cells)

Lymphocytes

Thymus gland Bursa Fabricus in Birds

Bone marrow in man

T-Lymphocytes B-Lymphocytes

Enter the circulation

Filtered in to lymphoid tissues
(Lymph node, Spleen),

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 Activation of B-Lymphocytes for humoral immunity

+ B-Lymphocytes
in lymphoid tissues

Antigens Activated B- cells

Macrophages
(Antigen presenting cells) Actively divided

Intermediate
Cells: clones

Memory B-cells Plasma B-cells

Dormant in the 1o-exposure Produce antibodies
Vigorous during 2nd-exposure γ-Immunoglobulins 80
 Activation of B-cells to make antibodies
• The B cell uses its receptor to bind
a matching antigen, which it
proceeds to engulf and process.
• Then it combines a fragment of
antigen with its special marker, the
class II protein.
• This combination of antigen and
marker is recognized and bound by
a T helper cell carrying a matching
receptor.
MHC=Major histocompatibility complex 81
 Activation of B-cells to ...cont’d
• The binding activates the T cell,
which then releases interleukins
– That transform the B cell into
an antibody- secreting plasma
cell.

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 Immunoglobulins
• B-cells that bind with an antigen will
subsequently differentiate into Plasma
cells & Memory cells
 Plasma cells - begin to produce
antibodies (up to 2,000 per second)
 Memory cells - remain dormant until
a person is again exposed to the same
antigen
• There are 5-classes of antibodies (γ-
Immunoglobulins, Ig)
 IgA, IgE, IgD, IgG and IgM
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 Five classes of Immunoglobulin
• IgM - B cell surface receptor for antigen
attachment, usually combines in star-shaped
clusters.
 secreted early in an immune response, it
tends to remain in the blood stream,
where it is very effective in killing
bacteria.
• IgG - most abundant antibody; produced in
large numbers
• IgE - mediator for common allergic
responses (hay fever (allergic rhinitis),
asthma, & hives)

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 Five classes of Immunoglobulin…cont’d

• IgA - found in secretions of digestive,

respiratory, urinary, & reproductive systems,
as well as in breast milk and in tears
• IgD - found on the surface of many B cells;
function is unknown

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 Active immunity Vs. Passive immunity

• Active ('natural') = production of antibodies as a result of

exposure to an antigen (vaccine)
• Passive = direct transfer of antibodies formed by another
person (or animal), e.g., transfer of IgG antibodies from
mother to fetus across placenta or in colostrum ('first milk')
OR treatment for rabies or poisonous snake venom

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 Mechanism of action of antibodies
• Antibodies act mainly in two ways to protect the body against
invading agents:
1. By direct attack of invaders
− Agglutination of microbial agents
− Precipitation of antigens
− Neutralization of toxic antigens
− Lyses or killing of infectious agents
2. By activation of the complement system

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 Complement System 
• The complement system consists of a series of proteins that
work to "complement" the work of antibodies in destroying
bacteria. 
• Complement proteins circulate in the blood in an inactive form.
• The so-called "complement cascade" is set off when the first
complement molecule, C1, encounters antibody bound to
antigen in an antigen-antibody complex.
• Each of the complement proteins performs its specialized job in
turn, acting on the molecule next in line.
• The end product is a cylinder that punctures the cell membrane
and, by allowing fluids molecules to flow in and out, dooms the
target cell.

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…cont’d

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 Activation of T-Lymphocytes for cellular immunity

+ T-Lymphocytes
in lymphoid tissues

Activated T- cells
Antigens Actively divided and
Macrophages
differentiated
(Antigen presenting
cells)
Intermediate
Cells: clones

Memory T-cells
Helper T-cells Suppressor
Killer (Cytotoxic) T-cells • Stimulate B-cells Dormant in the
• Produce cytotoxic 10-exposure T-cells
• Stimulate killer cells
Chemicals to kill Ag • Stimulate Vigorous during
• Stimulate macrophages macrophages 2nd-exposure 90
Platelets (Thrombocytes)

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 General Characteristics
1. The smallest cells of the blood (cell fragments)
2. 2-4 micrometers in diameter
3. Range: 250,000 – 500,000 mm3
4. Life Span 4-12 days
5. Mostly have no nucleus
6. Their function is related to hemostasis, the prevention and
control of bleeding
7. Release ADP, serotonin, thromboxane (cause vasoconstriction)
8. Formed in the bone marrow by segmentation of the cytoplasm
of cells known as megakaryocyte (the largest cells of the
marrow)

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 Hemostasis
• Hemostasis is the arrest of bleeding from a broken blood vessel-
that is, the stopping of hemorrhage.
• Three inherent mechanisms contribute to hemostasis:
• Vascular constriction
• Formation of platelet plug
• Blood coagulation

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 Vascular constriction
• The first mechanism to occur is vascular constriction.
• Vascular smooth muscle automatically constricts
decrease BF through the vessel limit blood loss.
• The vasoconstriction is caused by several factors:
– Sympathetic nerve reflexes in response to pain
– Local myogenic vasospasm in response to injury
– Locally produced vasoconstrictors released from damaged
tissue and from platelets

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Formation of a platelet plug
• Physically blocks small holes in blood vessels
• Normally, platelets are unable to adhere to the endothelial lining
of the blood vessels (coat of glycoproteins that repels the normal
endothelium).
• These same glycoproteins enable the platelets to adhere to
damaged vessels.
• Platelets become activated when come into contact with a
damaged vascular surface, in particular collagen fibers in the
vessel wall or damaged endothelial cells. These platelets become
“sticky” and adhere to the damaged tissue
• They also release ADP and thromboxane, a prostaglandin
metabolite, which enhance the stickiness of other platelets, more
and more platelets adhere to the damaged vessel, ultimately
forming a plug
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 Blood coagulation
• The third major step in hemostasis is coagulation, or the
formation of a blood clot.
• A complex process involves a series of reactions that result in
formation of a protein fiber meshwork that stabilizes the
platelet plug.
• Three essential steps lead to clotting.
– Activation of factor X
– Conversion of prothrombin into thrombin
– Conversion of fibrinogen into fibrin
• Altogether, 12 plasma clotting factors participate in essential
steps that lead to the final conversion of fibrinogen into a
stabilized fibrin mesh

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 • They are proteins synthesized in the liver
• Found circulating in plasma in their inactive forms
• Activation of one of these factors leads to activation of another
factor, and so on cascade of rxns.

Clotting Factors in Blood and Their Synonyms

1. Fibrinogen - Factor I
2. Prothrombin- Factor II
3. Factor III- tissue thromboplastin
4. Calcium - Factor IV
5. Factor V - labile factor
6. Factor VII - stable factor
7. Factor VIII- Antihemophilic factor (AHF)

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8. Factor IX - Christmas factor
9. Factor X -Stuart factor
10. Factor XI- Plasma thromboplastin antecedent
11. Factor XII- Hageman factor
12. Factor XIII- Fibrin-stabilizing factor

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Extrinsic pathway Intrinsic pathway Inhibitors

Tissue factor pathway

Tissue Factor
inhibitor
XII XI IX
Collagen
VII VIIa XIIa XIa IXa +

VIIIa
Protein C +
Protein S
X Xa

Va V Positive Feedback

Prothrombin Thrombin Antithrombin III

Fibrinogen Fibrin

XIII
Fibrinolytic
Cross-linked fibrin
2nd Year Pathology 2010 cascade
• The clotting cascade may be elicited by means of two
mechanisms
 Extrinsic mechanism
 Intrinsic mechanism
Extrinsic mechanism:
• Begins when a blood vessel is ruptured and the surrounding
tissues are damaged & coagulates the blood that has escaped
into the tissue.
• The traumatized tissue releases a complex of substances referred
to as tissue thromboplastin.
Intrinsic mechanism:
• causes the blood to clot within the vessel.
• It is activated when blood comes into contact with the exposed
collagen of a damaged vessel wall.
• This contact activates factor XII(Hageman factor) in the blood.
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• Thrombin promotes clot formation at several points in the
coagulation cascade through positive feed-back.
Acts on prothrombin to make more thrombin, thus
facilitating its own formation
 Accelerates the actions of several blood clotting factors
(VIII, IX, X, XI, and XII)
 Enhances platelet adhesion and activation
 Activates factor XIII, which strengthens and stabilizes
the fibrin meshwork of the clot

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 Clot dissolution

• Clots must be removed in order to prevent permanent

obstruction

• Plasmin is a proteolytic enzyme that digests fibrin.

• It is synthesized from its precursor, plasminogen.

• The conversion of plasminogen into plasmin involves several

substances, including factor XII (Hageman factor)

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