Blood Physi-

ology
Arba Minch University
College of Medicine and Health Sciences
School of Medicine
Department of Biomedical Sciences
Physiology Unit
By:
Tariku A. (Msc in Medical Physiology)

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 Objectives
 At the end of this lesson, the student are expected
to:
1. List functions of blood.
2. Explain the components of blood.
3. Discuss about blood types.
4. Enumerate the functions of the immune system.
5. List the blood abnormalities.

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 Outlines
• Introduction
• Blood composition & circulation
• Functions of blood
• Blood plasma
• Formed elements (cells) in blood
• Human blood types (group)
• Immunity
• Clinical correlates of blood

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 Introduction
• Blood, vital fluid found in humans & other animals
that provides important nourishment to all body
organs & tissues & carries away waste materi-
als.
• Sometimes referred to as “the river of life,” blood is
pumped from the heart through a network of blood
vessels collectively known as the circulatory system.
• An adult human has about 5 - 6 liters of blood,
which is roughly 7- 8% of total body weight.

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 Introduction…
• Infants & children have comparably lower volumes
of blood, roughly proportionate to their smaller
size.
• The volume of blood in an individual fluctuates.
– During dehydration, for example while running a
marathon, blood volume decreases.
– Blood volume increases in circumstances such as
pregnancy, when the mother’s blood needs to carry ex-
tra oxygen and nutrients to the baby.

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 Overview of Blood Circulation
• Blood leaves the heart via arteries that branch re-
peatedly until they become capillaries.
– O2 & nutrients diffuse across capillary walls & enter tissues
– CO2 & wastes move from tissues into the blood

• Oxygen deficient blood leaves the capillaries and

flows in veins to the heart.
• This blood flows to the lungs where it releases CO2
& picks up O2
• The oxygen rich blood returns to the heart.
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 Composition of Blood
• Blood is the body’s only fluid tissue composed of:
– liquid plasma (55%) and
– formed elements (45%)

• Formed elements include:

1. Erythrocytes = Red blood cells (RBCs)
2. Leukocytes = White blood cells (WBCs)
3. Thrombocytes = Platelets

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 Composition of Blood…

Plasma
(55% of whole blood)

Buffy coat:
leukocyctes and
platelets
1 Withdraw blood 2 Centrifuge (<1% of whole Formed
and place in tube blood) ele-
Erythrocytes ments
( 45% of whole blood)

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 Composition of Blood…

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 Composition of Blood…

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Physical Characteristics & Volume
• Blood is a sticky, opaque fluid with a metallic
taste.
• Color varies from scarlet (oxygen-rich) to dark red
(oxygen-poor).
• The pH of blood is 7.35 – 7.45.
• Temperature is 38C, slightly higher than “normal”
body temperature.
• Average volume of blood is 5–6 L for males, and
4–5 L for females.

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 Functions of Blood
1. Substance distribution.
2. Regulation of blood levels of particular substances.
3. Protection.

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 Distribution
Blood transports:
1. Oxygen from the lungs
and nutrients from the
digestive tract.
2. Metabolic wastes from
cells to the lungs and to
kidneys for elimination.
3. Hormones from en-
docrine glands to target
organs.

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 Regulation Protection
Blood maintains: Blood prevents blood loss
by:
1. Appropriate body
temperature by ab- 1. Activating plasma proteins
sorbing & distributing & platelets.
heat. 2. Initiating clot formation
2. Normal pH in body when a vessel is broken.
tissues using buffer Blood prevents infection by:
systems.
3. Synthesizing & utilizing an-
3. Adequate fluid vol- tibodies.
ume in the circulatory
system. 4. Activating WBCs to defend
the body against foreign
invaders.
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 Blood Plasma (liquid portion of blood)
Blood plasma contains over 100 solutes, including:
 Proteins
- albumin, globulins, clotting proteins, …
 Non-protein nitrogenous substances
- lactic acid, urea, creatinine
 Organic nutrients
- glucose, carbohydrates, amino acids, fats
 Electrolytes
- sodium, potassium, calcium, chloride, bicarbonate
 Respiratory gases
- oxygen and carbon dioxide

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 Formed Elements (cells in blood)
• Erythrocytes, leukocytes, & thrombocyte make up
the formed elements
– Only WBCs are complete cells
– RBCs have no nuclei or organelles, and platelets
are just cell fragments

• Most formed elements survive in the bloodstream

for only a few days
• Most blood cells do not divide but are renewed by
cells in bone marrow.

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Formation of Blood Cells (Hematopoiesis)
 Occurs in the red bone marrow.

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 Erythrocytes (RBCs)
• Biconcave discs, anucle-
ate, essentially no or-
ganelles.
• Filled with hemoglobin
(Hb), a protein that func-
tions in gas transport.
• Plasma membrane of RBCs
is comprised of flexible pro-
teins
– allow them to change
shape as necessary.
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 Erythrocytes (RBCs)…
• Are an example of how structure drives function.
Structural characteristics contribute to its gas trans-
port function
Biconcave shape that has a huge surface area
relative to volume.

Discounting water content, erythrocytes are more

than 97% hemoglobin.

ATP is generated anaerobically, so the erythro-

cytes do not consume the oxygen they transport.

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 Erythrocyte Function
Erythrocytes are dedicated to respiratory gas transport
 Hemoglobin
• Reversibly binds with O2 & most O2 in the blood is
bound to hemoglobin.
• Is composed of the protein globin, made up of 2α
& 2β chains, each bound to a heme group
Each heme group bears an atom of iron, which
can bind to one O2 molecule
• Each hemoglobin molecule can transport 4 mole-
cules of O2.

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 Structure of Hemoglobin

The body stores iron in :

 Hemoglobin (65%), liver, spleen & bone marrow.
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 Production of Erythrocytes
(Erythropoiesis)

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Regulation & Requirements for Erythropoiesis

• Circulating erythrocytes - the number remains con-

stant & reflects a balance between RBC production
& destruction.
– Too few RBCs leads to tissue hypoxia
– Too many RBCs causes blood viscosity
• Erythropoiesis is
1. Hormonally controlled and
2. Depends on adequate supplies of:
• Iron, proteins, lipids, carbohydrates, vitamin B12, and
folic acid

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 Hormonal Control of Erythropoiesis
• Erythropoietin (EPO) release by the kidneys is
triggered by hypoxia due to:
1. Decreased RBCs count.
2. Decreased oxygen availability.
3. Increased tissue demand for oxygen.

• Enhanced erythropoiesis increases the:

– RBC count in circulating blood and
– Oxygen carrying ability of the blood.

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 Erythropoietin Mechanism
I mb
ala
nce Start

Normal blood oxygen levels

Stimulus: Hypoxia due to de-
creased RBC count, decreased
I mb
al a availability of O2 to blood, or in-
nce
creased tissue demands for O2
Increases
O2-carrying
ability of blood
Reduces O2 lev-
els in blood

Erythropoietin
Kidney (and liver to a
Enhanced ery- stimulates red
smaller extent) releases
thropoiesis in- bone marrow
erythropoietin
creases RBC
count

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 Fate & Destruction of Erythrocytes
• The life span of an erythrocyte is 100–120 days.
• Old erythrocytes become rigid and fragile, and their
hemoglobin begins to degenerate.
• Dying erythrocytes are engulfed by macrophages.
• Heme & globin are separated & the iron is salvaged
for reuse:
* Heme: broken down into iron and bilirubin
* Globin: a reusable protein

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 Human Blood Groups
• Grouping depends on the presence of antigens or
agglutinogens on the surface of RBCs.
• RBCs contain protein (glycoproteins /lipoproteins) on
their surface with antigenic effect. These antigens
are:
– Unique to the individual
– Recognized as foreign if transfused into another individual
who does not have those same antigens on RBC membrane

• Presence or absence of these antigens is used to

classify blood groups.
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 Major blood groups
• Over 14 blood groups and over 100 antigens are
identified from erythrocytes.
• Major blood groups are
1. ABO blood group
2. Rh system
3. Other blood groups (medically less important)
 MNS system
 P, Kell, Kide, Duffy system
 Diego, Lutheran system

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 Importance of Knowing Blood groups:
1.Very essential medically, socially & Judicially.
• Socially, one should know his or her own blood group &
become a member of the blood donor's club so that he
or she can be approached during emergency conditions.
• Judicially it is helpful in medicolegal cases to sort out
parental disputes.
2.Among the couple helps to prevent the complica-
tions due to Rh incompatibility & save the child from
hemolysis.

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 ABO Blood Group
- Based on the + of 2 agglutinogen
Blood Antigen
(A and B), the ABO blood group can type present
be classified into 4 types of blood.
1. When agglutinogen A is present on A A
RBCs, the blood is type-A
2. When agglutinogen B is present on B B
RBCs, the blood is type-B
3. When both agglutinogen A & B exist AB A&B
together, type-AB
4. When neither agglutinogen A nor B neither A
O
nor B
are present, type-O
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 Agglutinins (antibodies)
• In the ABO blood grouping, plasma contains 2
genetically determined agglutinins (antibodies):
 Anti-A antibodies (agglutinin-α)
 Anti-B antibodies (agglutinin-β)

• Existence of agglutinogen and agglutinins

1. When agglutinogen A is present on RBCs, anti-B antibody
2. When agglutinogen B is present on RBCs, anti-A antibody
3. When agglutinogen A & B exist together, neither anti-A
nor anti-B antibody present in the serum
4. When no agglutinogen on RBCs both anti-A and anti-B an-
tibodies are present in the serum
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Ag-Ab coexistence in the ABO Blood groups

Blood type Antigen Antibody

A A anti-B

B B anti-A

AB A&B Neither

O Neither both anti-A & anti-B

AB = universal receiver O = universal donor

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 Ag-Ab coexistence …

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 Ag-Ab coexistence …

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 Rh Factor
 It was first worked out on Rhesus monkey to the
name Rh-system.
 Grouped as Rh+ and Rh- based on the + of agglu-
tinogen D on the surface of RBCs:
 Presence of agglutinogen D on RBCs = Rh+
 Missing agglutinogen D on RBCs = Rh-
 Agglutinin (anti-D antibodies) are not normally
present in the serum, produced secondary to expo-
sure of an Rh- blood to Rh+ blood (antigen-D).

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 Erythroblastosis Fetalis
• Disease that destroys red blood cells.
• A serious blood disease of fetuses & newborn babies,
in which the antibodies produced by Rh- mother
destroy the RBCs of Rh+ fetus.
• Occurs when Rh- mother marries Rh+ father &
conceives Rh+ fetus.
• During delivery, there could be a leakage of Rh+
blood from the fetus to the circulation of the mother.

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 Erythroblastosis Fetalis...
 Rh+ blood induces production of anti-D antibodies in
the circulation of the mother.
 During 2nd conception of Rh+ fetus, anti-D antibodies
cross the placenta and attack RBCs of the fetus.
Treatment
Rho Gam injection after 1st birth which blocks
mother from forming anti-Rh antibody
 Limits risk for subsequent births

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Prevalence of ABO &
Rh blood groups among
different ethnic groups

Frequency of blood groups (%)

Races
O A B AB Rh+
Whites 45 41 10 4 85
Blacks 48 27 21 4 88
Chinese 36 28 23 13 100
Ethiopians 47 28 20 5 97
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 Compatibility between the Donor's Cells
& Recipient’s Serum
Recipients Serum
Donor's Cells
A B AB O

A  Х  Х
B Х   Х
AB Х Х  Х
O    

 No Agglutination Х Agglutination
Agglutination = clumping of red blood cells in the presence of an antibody
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 Blood Transfusions
• Blood transfusion is giving of blood of one person
to another when there is a need. It can be:
1. Whole blood transfusion
– When blood loss is substantial.
– In treating thrombocytopenia.
• the state of having fewer than the normal
number of blood platelets per unit volume of
blood, often associated with hemorrhaging.
2. Packed red cells transfusion
- cells with plasma removed
- are used to treat anemia.
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 Transfusion Reactions
• Transfusion reactions occur when mismatched
blood is infused.
• Donor blood cells are attacked by the recipient’s
plasma:
– Diminished oxygen-carrying capacity.
– Clumped cells that impede blood flow.
– Ruptured RBCs that release free hemoglobin
into the bloodstream
• Circulating hemoglobin precipitates in the kid-
neys and causes renal failure
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 Diagnostic Blood Tests
 Laboratory examination of blood can assess an indi-
vidual’s state of health
 Microscopic examination:
 Variations in size & shape of RBCs
- predictions of anemias
 Type and number of WBCs
- diagnostic of various diseases
 Chemical analysis can provide a comprehensive pic-
ture of one’s general health status in relation to
normal values.

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 Leukocytes (White Blood Cells)

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 Leukocytes (WBCs)…
• WBCs only make up about 1% of blood, but their
small number belies their immense importance.
• Play a vital role in the body’s immune system.
– the primary defense mechanism against invading bacte-
ria, viruses, fungi, and parasites.
• Often accomplish this goal through direct attack,
– which usually involves identifying the invading organism
as foreign, attaching to it, and then destroying it.
This process is referred to as phagocytosis.

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 Leukocytes (WBCs)…
• WBCs also produce antibodies, which are released
into the circulating blood to target and attach to
foreign organisms.
– after attachment, the antibody may neutralize the or-
ganism, or it may elicit help from other immune system
cells to destroy the foreign substance.
• There are several varieties of WBCs, including neu-
trophils, monocytes & lymphocytes,
– all of which interact with one another & with plasma pro-
teins & other cell types to form the complex & highly ef-
fective immune system.

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 Leukocytes (WBCs)…
• The only blood components that are complete cells.
– contain nucleus, and other organelles
• Less numerous than RBCs and platelets.
• WBC count :
– Normal (4,000-11,000/mm3)
• Average (7,000/mm3)
– Decrease in WBC count = Leukopenia

– Increase in WBC count = Leukemia

* normal response to bacterial or viral invasion

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Function = defense/protection Tare-Blood
against disease. 46
 Types of WBCs
Granular leukocytes Agranular leukocytes
PMN-cells: Neutrophils Monocytes
Eosinophils Lymphocytes
Basophils
WBC differential count
 Neutrophils: 50-60% (60%), 3000-7000/mm3
 Eosinophils: 1-4% (2.4%), 100-440/mm3
 Basophils: 0.3-0.5% (0.4%), 20-50/mm3
 Monocytes: 2-8% (5.3%), 100-700/mm3
 Lymphocytes: 20-40% (30%), 1500-3500/mm3

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 Primary Functions of WBCs
1. Neutrophils
• The most abundant WBC & the first line of defense.
• Phagocytic cells (ingest bacteria)

2. Monocytes
• The largest WBCs & highly phagocytic cells.
• Leave the circulation, enter tissue & differentiate
into macrophages:

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 The tissue macrophage system
(reticuloendothelial 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 Lymph nodes
Osteoclastes
macrophage cells cells cells reticular cells
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 Primary Functions of WBCs...
3. Basophils
• Liberate heparin, histamine & serotonin in al-
lergic reactions that intensify the overall in-
flammatory response.
4. Eosinophils
• Absorb histamine during allergic conditions so that
lessen the severity of allergies
• Produce hydrolytic enzymes to kill big parasites.
Increase in number during parasitic infection
– Eosinophilia

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 Primary Functions of WBCs...
5. Lymphocytes
• Are responsible for acquired immunity.
• Of 2 types; B and T lymphocytes.
• An important cell class in the immune system that
produces antibodies:
– to attack infected & cancerous cells, and
– to reject foreign tissue.

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 The Immune System
• A complex system that is responsible for protecting
us against infections & foreign substances.
• There are three lines of defense:
1. Keep invaders out (skin, mucus membranes).
2. Non-specific ways to defend against pathogens that
have broken through the first line of defense (inflamma-
tory response & fever).
3. Mounted against specific pathogens that are causing
disease.
• B cells produce antibodies against bacteria or viruses
in the ECF,
• T cells kill cells that have become infected.

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 The Immune System …
• The immune system is closely tied to the lym-
phatic system, with B & T lymphocytes being
found primarily within lymph nodes.
– Tonsils & thymus gland are also considered
lymph organs & are involved in immunity.
• We often don't realize how effective the immune
system is until it fails or malfunctions, such as when
the lymphocytes are attacked by HIV in an AIDS pa-
tient.

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 The Immune System …
• Body's ability to resist or eliminate potentially
harmful foreign materials or abnormal cells consists
of the following activities:
1. Defence against invading pathogens (viruses & bacteria).
2. Removal of 'worn-out' cells (old RBCs) & tissue
debris (from injury or disease).
3. Identification & destruction of abnormal or mutant cells -
primary defence against cancer.
4. Rejection of 'foreign' cells (organ transplant ).

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 Types of Immunity
A. Innate / Natural / Non-specific immunity
Examples:
 Phagocytosis
 HCl in the stomach
 Skin barrier
 Lysozymes in saliva

B. Acquired/ Adaptive / Specific immunity

Features:
 Specific
 Memory
 Recognition of self and non-self
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 Innate Immunity
• It is also known as Natural / Non specific immunity.
• It is present since from the birth & it is the inborn
capability of the body to resist the entry of
microorganisms into the body.
• This type of immunity represents the first line of
defense against any pathogens.
• Therefore it is called Non Specific Immunity.

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 Innate Immunity…
The mechanisms involved in Innate Immunity are:
1. Destruction of bacteria by gastric HCl.
2. Protective function of ciliated epithelium in the respiratory
tract.
3. Reflex mechanisms like sneezing, coughing, & vomiting.
4. Protective function of keratinised stratum corneum of
skin, a physical barrier against entry of microorganisms.
5. Presence of proteolytic enzymes & lysosomes in secretions
like sweat, saliva, sebum etc. destroys or inactivate the
bacteria.

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 Acquired Immunity
•It is the resistance developed in the body against
any specific foreign body like bacteria, viruses, toxins.
• It is the most powerful immune mechanism that
protects the body from the invading organisms or
toxic substances.
• Of 2 types:
1. Passive Immunity
2. Active Immunity
 Active immunity is the function of Lymphocytes.

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 Acquired Immunity…
1. Passive Immunity:
- Immunity developed in a non immune individual by
transfer of blood, serum, lymphocytes/antibodies
from an immune individual.
2. Active Immunity:
• Immunity developed by the production of anti-
bodies in response to the specific foreign antigen
or
• Immunity developed by the production of antibod-
ies by injecting antigen into the body through
vaccination.
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 Active Immunity
 Active Immunity is of 2 types:
1. Cell Mediated Immunity (Cellular Immunity)
2. Antibody Mediated Immunity (Humoral Immunity)
1. Cell Mediated Immunity:
• It is provided by the activation of T lymphocytes.
• It is particularly effective against intracellular
pathogens that reside within host cells primarily
fungi, parasites, & viruses.

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 Active Immunity …
2. Antibody Mediated Immunity
• It is provided by the activation of B lymphocytes.
• B lymphocytes fight against the invading organisms
by secreting antibodies into the blood & lymph.
(Humors).
• It is particularly effective against extracellular
pathogens that multiply in body fluids, mostly the
bacteria.

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 Development & Processing of Lymphocytes:
Lymphoid stem cell
Lymphocyte
From bone marrow
Thymus processing [Maturation]
Thymopoietin
Mature T lymphocyte Mature B lymphocyte
Antigen
Sensitised T cell Sensitised B cell
Memory cells
Helper Memory Suppressor Cytotoxic Plasma cells
T cells cells T cells T cells Antibodies
Cell mediated immunity
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Development of Cell Mediated Immunity:
• For the development of cell mediated immunity,
T cells must be activated by exposure to an antigen
• Antigenic materials are released from invading
organisms & presented particularly to helper T- cells
 It is done by a special type of cells called
Antigen Presenting Cells (APC).
• Role of Antigen Presenting Cells, Helper T Cells,
Cytotoxic T Cells, Suppressor T Cells & Memory T
Cells will be discussed later.

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 1. Role of Antigen Presenting cells:
• Only Macrophages & B lymphocytes function as
APCs & synthesize class II MHC proteins.
• Helper T cells require class II MHC proteins to func-
tion.
• When foreign organisms invade the body the APCs
engulf them by phagocytosis.
• Later the antigen from the engulfed organism is
partially digested into smaller peptide fragments by
the proteolytic enzymes of macrophage.

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 The resulting
digested frag-
mented then
bind to class II
MHC proteins
IL 1 & TNF of
macrophage.

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 2. Role of helper T cells:
• The binding between helper T cell receptor & antigen
bound
to class II MHC is an essential event for the activation of
helper T cells.
• Finally the antigenic binding of the APC to the helper T cell
causes the APC to secrete interleukin – 1 (IL-1) & tissue
necrosis factor (TNF),which facilitates the activation of
helper T cells.
• Activated helper T cell now secretes various cytokines like
• IL2 which inturn activates the same helper T cell &
as well as the nearby cytotoxic T cells.
• IL4 & IL5 which activates the B lymphocytes & caus-
ing the production of antibodies.
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 3. Role of Cytotoxic Cells:
• The activated cytotoxic T cells circulate through blood &
lymph & destroy the invading organisms by attacking them
directly in the following way:-
1. The binding between cytotoxic T cell receptor & antigen
causes the release of cytotoxic substances like lysosomal en-
zymes which destroys large number of microorganisms.
2. Cytotoxic T cells destroy even body’s own tissues which
are affected by the foreign bodies particularly the viruses.
Many viruses are entrapped in the membrane of affected
cells.
• The antigen of the viruses attracts the T cell, the cyto-
toxic cells kill the affected cells also along with viruses b/
se of this cytotoxic T cell is called Killer cell.
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 4. Role of Suppressor T Cells:
• The suppressor T cells are also called as regulatory
T cells.
• These T cells suppress the activities of cytotoxic T
cells & plays an important role in preventing the
cytotoxic T cells from destroying the body’s own
tissues along with invaded organisms.
• The suppressor T cells also suppress the activities
of helper T cells.

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 5. Role of Memory T Cells:
• Some of the T cells activated by an antigen do not enter the
circulation but remain in lymphoid tissue. These T cells are
called memory T cells.
• In later periods, the memory cells migrate to various
lymphoid tissues throughout the body.
• When the body is exposed to the same antigen for the 2nd
time, the memory cells identify the organism & immediately
activates the other T cells. So, the invading organism is
destroyed very quickly.
• The response of the T cells is also more powerful at
this time.

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 Development of
Antibody Mediated Immunity
• The Antibody Mediated Immunity is developed by
the antibodies, which are circulating in the blood.
• The antibodies are produced by the B lymphocytes.
– These antibodies fight against the invading organisms.
• The Antibody Mediated Immunity is the major de-
fensive mechanism against the bacterial infec-
tion.
• As in the case of Cell Mediated Immunity, the
macrophages & other APC play an important role in
the development of Antibody Mediated Immunity.

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 1. Role of Antigen Presenting cells.
• Antigen Presenting Cells (Macrophages) present the
antigen bound to class II MHC to B cells in addition
to presenting to T cells.
• The B cell receptor recognizes the antigen bound to
MHC which is displayed on the surface of the APC.
• The antigenic products activate B cells. Macrophages
also secrete a cytokine called IL-1. This causes the
activation & proliferation of lymphocytes.
• The B cells proliferated & transformed into 2 types of cells.
1. Plasma Cells
2. Memory Cells
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 2. Role of Plasma Cells:
• Produce antibodies which are globulin in nature. The
antibodies are called Immunoglobulin's.
• The rate of antibody production is very high & are released
into lymph & then transported into the circulation.

3. Role of Memory B cells:

• Occupy the lymphoid tissues throughout the body.
• Are in inactive condition until the body is exposed to the
same antigen for the second time.
• The antibodies produced during the 2nd exposure to the
foreign antigen are also more potent than those produced
during 1st exposure.
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 4. Role of helper T cells:

 The activated helper T cells in response to antigen

secrete two substances called :
 IL-2 &
 B cell growth factor which promote;
• Activation of more number of B lymphocytes.
• Proliferation of lymphocytes.
• Production of Antibodies.

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 Antibodies (Immunoglobulin's)
• Are produced by plasma cells in response to antigen.
• The antibodies produced by B lymphocytes are found in
almost all the tissues of the body.
• Among these antibodies,
Ig G forms 75% of the
antibodies in
the body.
Types:
1. Ig G
2. Ig A
3. Ig M
4. Ig E
5. Ig D
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 Mechanism of Action of Antibodies

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 Platelets
• The smallest cells in the
blood which are designed
for coagulation/ forming
a clot, whenever a blood
Inactive platelets
vessel is broken.
• As soon as an artery or
vein is injured, the
platelets in the area of
the injury begin to
clump together & stick
to the edges of the cut.
Active platelets
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 Platelets and clotting
• Platelets also release messengers into the blood
that perform a variety of functions:
1. Constricting the blood vessels to reduce
bleeding.
2. Attracting more platelets to the area to enlarge
the platelet plug.
3. Initiating the work of plasma-based clotting
factors, such as fibrinogen.
•

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 Platelets and clotting…
• Through a complex mechanism involving many
steps and many clotting factors,
– the plasma protein fibrinogen is transformed
into long, sticky threads of fibrin.
•

• Together, the platelets and the fibrin create an

intertwined meshwork that forms a stable clot.
• This self-sealing aspect of the blood is crucial to
survival.

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 Genesis of Platelets
• The stem cell for platelets is the hemocytoblast

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 Hemostasis
o A series of reactions designed for stoppage of
bleeding.
o During hemostasis, 3 phases occur in rapid se-
quence:
1. Vascular spasm
- immediate vasoconstriction in response to injury

2. Platelet plug formation

3. Coagulation (blood clotting)

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 Hemostasis…
1. Vascular spasm
• Local vasoconstriction that is caused by:
 Reflex sympathetic discharge and
 Local myogenic contraction of the vascular wall

• In effect both reaction minimize rate of bleeding

by narrowing the diameter of the hole (rupture)
on the wall of the blood vessels.

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 Hemostasis…
2. Platelet Plug Formation
• Normally, platelets do not stick to each other or to the en-
dothelial lining of blood vessels. Upon damage to blood vessel
endothelium (which exposes collagen) platelets:
– Adhere & stick to exposed
collagen fibers and form a
platelet plug
– Release serotonin and ADP,
which attract additional
platelets
• The platelet plug is limited to
the immediate area of injury.

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 Hemostasis…
3. Coagulation
• A set of reactions in which blood is transformed from a
liquid to a gel (clot).
• It is slow but has long lasting effect to stop bleeding.
• Follows intrinsic & extrinsic pathways, undergoes three
steps of reactions:
1. Formation of prothrombin activators through the in-
trinsic & extrinsic pathways
2. Convertion of prothrombin into thrombin by the action
of prothrombin activators (prothrombinase)
3. Conversion of fibrinogen into fibrin thread by the ac-
tion of thrombin

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Tare-Blood 86
07/05/2022 Tare-Blood 87
 Injury to the Blood vessel

Damage to the endothelium &

Local smooth
Exposure of Collagen fibrinogen
muscle
contraction
Adherence of Platelets
or
Release of Activation of Platelets Fibrin thread
Vasoconstrictor
Serotonin by Secretion of ADP, & Thromboxane A2
the platelets
Aggregation of more & more Platelets Blood clo
Formation of loose Platelet plug ting
Vasoconstriction
Formation of tight
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Hemostatic plug
Tare-Blood 88
 Hemostasis…
• Coagulation is formed
primarily of fibrin threads
(or polymers),
– but also including blood
cells and platelets.
•

• Blood clots:
– in the right places
prevent the loss of blood
from ruptured vessels,
– but in the wrong place
can cause problems such
as a stroke .

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 Clot Retraction & Repair

 Clot retraction
– stabilization of the clot by
squeezing serum from the
fibrin strands

 Repair
– Platelet-derived growth factor
(PDGF) stimulates rebuilding of
blood vessel wall
– Fibroblasts form a tissue patch
– Stimulated by vascular endothelial growth factor (VEGF),
endothelial cells multiply & restore the endothelial lining

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 Prevention of unwanted intravas-
cular clotting
1. Smoothness of the endothelium
- prevents platelet adhesion
2. The presence of intravascular anticoagulants
produced by endothelial cells, platelets and WBCs.
 Heparin
 Anti-thrombin-III
 Protein-C
 Prostaglandin-I2
 Oral anticoagulant drugs

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 Prevention of Undesirable Clots…
• Substances used to prevent undesirable clots include:
 Aspirin
– inhibits initiation of clotting mechanism so platelets are
less likely to stick together
 Heparin
– anticoagulant used clinically for pre- and postoperative
cardiac care
 Warfarin
– used for those prone to atrial fibrillation

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 Abnormal intravascular clotting
Thrombo-embolism
• Blockage of a blood vessel by a blood clot thrombus
Causes
1. Damage to the endothelium.
e.g. Atherosclerosis
2. Sluggishness of blood flow.

3. Increase in viscosity of blood due to high platelet or

high RBC count.

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 Abnormal intravascular clotting…
Thrombus – a clot that develops & persists in blood vessel
• Thrombi can block circulation, resulting in tissue death and
organ failure
• Coronary thrombosis – thrombus in blood vessel of the heart
e.g. Myocardial infarction (heart attack)

Embolus - a thrombus (blood clot) freely floating in the blood

• Pulmonary emboli can impair the ability of the body to obtain
oxygen (600,000 per yr in US causing 60,000 deaths)
• Cerebral emboli can cause strokes

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 CLINICAL
COORELATES
OF BLOOD

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 Erythrocyte Disorders
I. Anemia
• Insufficient Erythrocytes
• Decreased Hemoglobin Content
– blood has abnormally low oxygen-carrying capacity
• Blood O2 levels can not support normal metabolism
• The symptoms are :
– fatigue, paleness, shortness of breath, and chills
• Of 5 types

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 Erythrocyte Disorders…
1. Hemorrhagic anemia
- result of acute or chronic loss of blood
2. Hemolytic anemia
- prematurely ruptured erythrocytes
3. Aplastic anemia
- destruction or inhibition of red bone marrow
4. Iron-deficiency anemia
- results from inadequate intake of iron-
containing foods & impaired iron absorption

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 Erythrocyte Disorders…
Sickle blood cells
5. Sickle-cell anemia
- Results from a defective gene,
single aa substitution in the
β-chain.
- This defect causes RBCs to
become sickle-shaped after
O2 is released to tissue Normal RBCs
- RBC becomes rigid & can get
stuck in blood vessels
* tissue hypoxia (severe
pain & organ damage)

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 Erythrocyte Disorders…
II. Polycythemia
– excess RBCs that increase blood viscosity of 3 types:
1. Primary polycythemia (polycythemia Vera)
- occurs when excess RBCs are produced as a result of an
abnormality of the bone marrow
2. Secondary polycythemia
- caused by either natural or artificial increases in the
production of erythropoietin
3. Blood doping
- the practice of boosting the number of RBCs in the
bloodstream in order to enhance athletic performance.

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 Leukocytes Disorders
I. Leukemia
• An abnormal increase of white blood cells
• Cancerous conditions causing proliferation of immature WBCs
• Symptoms
 night sweats and fever, infections, weakness/chronic fa-
tigue, headaches, bleeding/bruising, Joint/bone pain, ab-
dominal swelling from enlarged spleen, lymph node
swelling, weight loss
• Of 2 types :
1.Acute leukemia - rapid onset (children and adults)
2.Chronic leukemia - symptoms develop slowly
(mostly adults)

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 Leukocytes Disorders…
• Immature WBC are found in the bloodstream in all leukemia
in large number.
• Bone marrow becomes totally occupied with cancerous WBC.
• The WBC produced, though numerous, but are not functional
• Death is caused due to internal hemorrhage and massive
infections
• Treatments include :
– irradiation, antileukemic drugs, & bone marrow transplants

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 Leukocytes Disorders…
II. Leukopenia (leukocytopenia)
• A decrease in the number of WBCs (leukocytes) found in
the blood, w/c places individuals at increased risk of infection.
Causes
• May be due to a recent infection such as a cold/flu.
• It can also be associated with chemotherapy, radiation ther-
apy, and aplastic anemia.
• HIV AIDS, influenza, a deficiency in certain minerals such
as copper and zinc.

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 Leukocytes Disorders…
Symptoms of Leukopenia
• Fatigue, headache and fever are frequent symptoms. One
also experiences hot flashes and irritability.
• The person becomes susceptible to various infections and
oral ulcers.
Treatment for Leukopenia
• Steroids & vitamins are prescribed by doctors to activate the
bone marrow in order to produce more white blood cells.
• Some therapies like cytokine therapy and chemotherapy are
used.

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 Bleeding disorders
• Inability to synthesize procoagulants (factors regulating
clotting mechanism) by the liver results in severe
bleeding disorders.
• Causes can range from vitamin K deficiency to hep-
atitis and cirrhosis
• Inability to absorb fat can lead to vitamin K deficiencies
as it is a fat-soluble substance and is absorbed along
with fat
• Liver disease can also prevent the liver from producing
bile, which is required for fat & vitamin K absorption.

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 Bleeding disorders…

Haemophilia
• Hereditary sex-linked recessive bleeding disorder
in males
XXh x XY = XX, XY, hXX, hXY
• It is a genetic disorder characterized by prolonged
bleeding, occurs due to deficiency of factor VIII.
Treatment:
 regular infusions of the deficient clotting factor,
replacement therapy

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 Bleeding disorders…

Mother Father
Carrier
X X X Y

XX XY XX XY
Normal Normal Carrier Defective
healthy healthy healthy haemophilic
daughter son daughter son
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 Bleeding disorders…
Purpura:
• A disorder with prolonged
bleeding time.
• Characterized by spontaneous
hemorrhage in the skin.
• Whenever damage to the
small blood vessels occurs
platelets plays a role in
arresting the bleeding.

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 Bleeding disorders…
• But deficiency of platelets causes small tiny hemor-
rhagic spots in many areas of the body.
• These spots under the skin are called purpuric spots
(purpuric patch like appearance) that is why the
disease is called purpua.
• Caused by
– suppression/destruction of bone marrow
e.g. malignancy, radiation
• Treated with whole blood transfusions

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 Bleeding disorders…
3 Types of purpura
1. Thrombocytopenic purpura
- due to decreased platelet count in bone
marrow disease.
2. Thromboesthenic purpura
- due to formation of abnormal platelets
3. Idiopathic thrombocytopenic purpura
- exact cause not known

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