BLOOD

BY
DR WAHID SAKA
 BLOOD
• It is a fluid connective tissue which
circulates in vascular channels to all tissues
of the body.
• It is composed of the cellular elements
which are wbc, rbc & platelets all
suspended in the fluid portion called the
plasma.
• Total volume of circulating blood in a man is
about 5.6litters in male and 4.6-6 Litters in
female.
• About 7-8% by weight in a 70kg man.
• Plasma volume is about 55% accounting for
3L.
• The formed element accounts for between
43-45% of the total blood volume.
 CHARACTERISTICS OF BLOOD

1. Bright red (oxygenated).

2. Dark red/purplish (deoxygenated).

3. Much more dense than pure water.

4. pH range from 7.35 to 7.45 (slightly alkaline).

5. Slightly warmer than body temperature 100.4 o

F.

6. Typical volume in adult male 5-6 L.

7. Typical volume in adult female 4-5L.

8. About 8% of body weight.

 PRODUCTION OF BLOOD CELLS
• In fetus: Blood cells are formed in yolk sac
and later in the liver and spleen.

• In infants: Blood cells are produced in bone

marrow of all bones.

• Adults: Blood cells are formed in bone

marrow of the long bones i.e. upper
humerus and femur.

• The active marrow responsible for blood

cells production is known as red marrow
while the inactive one is called yellow
marrow.
 FUNCTIONS OF BLOOD

TRANSPORT FUNCTION

Transport of various substance suspended in the blood such as

1. Amino acids
2. Lipids
3. Carbohydrate (glucose)
4. Minerals
5. Vitamins
6. Hormones
7. Oxygen
8. CO2
9. Heat-maintenance of body temperature by distributing heat
10. Excess body water
11. Immunoglobulin
12. Blood clotting factors and Platelets
13. Waste product of excretory organs
 HOMEOSTATIC FUNCTIONS

 Blood is involved in regulation of the

following;

• Interstitial fluid compartment

• Body pH- maintenance of acid-base

balance with the help of buffers

• Body temperature

• Protection against infection

• Blood clotting
 PROTECTION.
Blood can clot (become gel-like), which
protects
against its excessive loss from the
cardiovascular
system after an injury.

White blood cells protect against disease by

carrying
on phagocytosis.

Several types of blood proteins, including

antibodies,
interferons, and complement help protect
against
disease in a variety of ways.
 CELLULAR COMPONENTS OF THE BLOOD
• All cellular components of the blood stem
from same multipotent uncommitted stem cell.

• The population of these committed stem cells

in the marrow showed that 75% are white
blood cells and 25% are red blood cells.
 HAEMOPOIESIS
 In order to form blood cells, pluripotent stem cells in red
bone
marrow produce two further types of stem cells, which have
the
capacity to develop into several types of cells.

 These stem cells are called myeloid stem cells and

lymphoid stem cells.
 Myeloid stem cells begin their development in red
bone marrow and give rise to red blood cells,
platelets, monocytes, neutrophils, eosinophils,
basophils, and mast cells.

 Lymphoid stem cells, which give rise to

lymphocytes, begin their development in red bone
marrow but complete it in lymphatic tissues
Lymphoid stem cells also give rise to natural killer
(NK) cells.

 Although the various stem cells have distinctive

cell identity markers in their plasma membranes,
they cannot be distinguished histologically and
resemble lymphocytes.
 COMPONENTS OF BLOOD
 Whole blood has two components:
 blood plasma, a watery liquid extracellular matrix that
contains dissolved substances, and

 formed elements, which are cells and cell fragments.

 Blood is about 45% formed elements and 55% blood

plasma.

 Normally, more than 99% of the formed elements are

cells named
for their red color—red blood cells (RBCs).

 Pale, colorless white blood cells (WBCs) and platelets

occupy less than 1% of the formed elements. Because
they are less dense than red blood cells but more dense
than blood plasma, they form a very thin buffy coat layer
between the packed RBCs and plasma in centrifuged
blood.
 ERYTHROCYTE
• Erythrocytes are also known as red blood cells.

• Mature red blood cell is non nucleated & has a

biconcave shape.

• It has a diameter of 8.5micrometer, edge thickness of

2.5 & center thickness of 1.5 micrometer.

• There are about 5 million/mm3of blood with variation

between the two sexes.

• Male 4.5-6 & female 4.3-4.5 million cells/mm3of blood.

 The variation is due to the following;

1. Gonadal hormone testosterone in male which is a red
blood cell differentiation inducer.
2. Greater mass musculature in male requires more oxygen
supply.

• The shape of the red blood cell provides maximum surface

area for the small volume of the cell and large diffusion
surface for passage of gases.

• It also allows for squeezing of red blood cell when passing

through narrowed vessels without damage to the integrity of
the cell.

• Glucose-6-phosphate dehydrogenase is present on the

membrane helping to utilize glucoce, O2and ATP.

• Life span is 120 days.

• The count is higher in new born (6mmillion/mm3

) than in an
adult.

• Its production is stimulated by hypoxia with the release of

erythropoietin (EPO) 85% from kidney % 15% from liver.
 ERYTHROPOIETIN (EPO)
• A glycoprotein
• Contains 165 amino acid residues & 4
oligosaccharide chains.
• It is a differentiation inducer
• Half life is about 5 hours.
• Production stimulated by hypoxia, but can also
be stimulated by cobalt salt and androgens.
• 85% from kidney, 15% from liver
• Principal site of inactivation is liver.
• Chonic renal disease will adversely affect its
production.
• The gene is cloned and recombinant EPO is
available for clinical use.
 PACKED CELL VOLUME (PCV)
• If one takes a sample of blood, treats is with
an agent to prevent clotting [anticoagulant],
and spins it in a centrifuge, the red cells
settle to the bottom the white cells settle on
top of them forming the “Buffy coat”.

• The fraction occupied by the red cells is

called the haematocrit. Normally it is
approximately 45%. (47% in male, 42% in
female). Values much lower than this are
sign of anemia.
 ERYTHROCYTE SEDIMENTATION RATE (ESR)
• This is the rate of settlement of red blood cell
without being centrifuged. It depends on
• Shape of the cells
• Concentration of plasma proteins
• Infection
• The stacking of red blood cell on one another is
termed Rouleux formation.

 USES
• Monitoring recovery from diseases or efficiency
of treatment.
• Varies with ages and sex.
• Normal values are
• New born = 2mm/hr
• Adult male = 3-7mm/hr (5.7)
• Adult female = 3-15mm/hr (9.5)
REQUIREMENTS FOR RBC PRODUCTION
A. Erythropoietin:-
• A glycoprotein
• Molecular weight of 35kdalton
• 165 amino acid residue & 4
oligosaccharide chain
• Produced primarily from kidney (85%) &
liver (15%) & other areas such as
astrocytes in brain
• Produced in response to hypoxia as a
result of production of REE (renal
erythropoietic factor) by the kidney
• Erythropoietin stimulates red blood cell
production from bone within 2 days.
B. Iron
• Absorb from first part of the small intestine by
active transport 3× rapidly if in ferrous state
(Fe2+), than in the ferric state (Fe3+)
• Form the core element of heme porphyrin
structure.
• It is able to combine reversibly with oxygen.
• The amount needed daily = 0.5mg in male and
2mg in menstruating female.
• Iron is released when red blood cell are broken
down, transported by transferrin (β-globulin) to
the liver.
• The liver stores about 60% of the body iron as
ferritin.
• Iron is distributed in the body as follows;
Hemoglobin (65%), Myoglobin (4%), Ferritin (15
-30%), Trasferrin (0.1%)
C. Vitamin B12

• Important for all cell functions and tissue growth and also for
conversion of ribose nucleotide to deoxyribonucleotide which is an
important component of DNA.

• Absorption occur at the terminal ileum and this is enhanced by

intrinsic factor from parietal cell.

• Amount needed to maintain normal red blood cell production is about

1ng.

• Deficiency leads to pernicious anaemia (failure of nuclear maturation

and division).

• Other materials needed

•
• 1. Folic acid
• 2. Lipids
• 3. Protein
• 4. Amino acid
 HEMOGLOBIN
• Is the red oxygen carrying pigment in the red blood
cell in vertebrates
• It’s a globular molecule.
• A protein with molecular weight of 64,450.
• Has 2 parts, heme portion and globin part
• Heme part is attached to 4 polypeptide chain which
constitute the globin portion of the hemoglobin.
• The heme has an iron central dormain.
• A fully saturated hemoglobin can carry 4 molecules
of Oxygen.
• Hemoglobin concentration is about 14g/dl in female
and 16g/dl in male
 JAUNDICE
• A clinical condition seen in patients with
yellowish discoloration of the sclera of the
eyes and other soft tissues of the body
• It usually occurs when more than 300 - 500
mls of blood is hemolysed [destroyed] in
less than a day

• CAUSES OF JAUNDICE
• Hemolysis.
• Infection or toxic effect on liver cells.
• Obstruction of the bile duct.
 WHITE BLOOD CELLS
• The white blood cells are also known as
leucocytes.

• There are about 4-11 thousand white blood

cells/mm of blood.
3

• The amount varies with the health state of the

subject with increased concentration during
infection.

• They are broadly divide into;

1.GRANULOCYTE :- contains cytoplasmic

granules that pick up stains. It includes;
 Eosinophils
• Staining colour-Bright red
• No of lobes of nucleus. 1-2
• Concentration- 150-300 cells/mm blood
3

• % of wbc- 1- 4%
• Half life-12-20 hours

 Basophil
• Staining colour – Blue
• No of lobes of nucleus – No definite lobe
• Concentration – 0-100 cell/mm of blood
3

• % white blood cell- 1-4%

• Half life – 12-20 hour
 Neutrophil
• Staining – Neutral
• No of lobes- 3-5
• Concentration - 3000 -6000 cells/mm of
3

blood.
• Half life – 6 hours.

2. AGRANULOCYTES
 Monocytes
• Has horse shoe shaped nucleus occupying
2/3 of the cytoplasm
• Concentration is 300-600 cells/mm of
3

blood
• % white blood cell – 2-8%
• Half life – 72 hours to months
• When these cells are released into the blood
from bone marrow, they are still very
immature cells.

• They migrate into the tissues, enlarge up to

five times and develop numerous
cytoplasmic granules (lysosomes).

• These cells are called macrophages and

they are much more powerful phagocytes
than neutrophils.

• Macrophages have a powerful lysosomal

lipase which breaks down the lipid-rich cell
memebranes of many bacteria.
 Usually, monocytes circulates for about 72 hours in
the blood after which they enter the tissue and are
transformed into tissue macrophages where they
can survive for months.

• Example of tissue macrophages;

• 1. Kupffer cell of the liver
• 2. Pulmonary alveolar macrophages
• 3. Osteoclast in bones
• 4. Microglia cells in the brain and nervous system
• 5. Microphages of the lymph nodes
• 6. Macrophages of the spleen

• They are activated by lymphokines from T-

lymphocytes and are called histocytes or wandering
cells.
 LYMPHOCYTES
• Lymphocytes are produced from lymph nodes,
thymus and spleen. The precursors, all came from
the bone marrow.

• Approximately one-fourth of the blood’s circulating

leucocytes are lymphocytes. They are actively motile
cells second only to the neutrophils in this respect.
They are also capable of phagocytosis, but rarely
display it.

• They are of two main types:

• B- lymphocytes, which are responsible for humoral
immunity i.e. they synthesize circulating antibodies.
• T-lymphocytes, which are processed by or in some
way dependent on the thymus gland. They are
responsible for cell- mediated immunity i.e. the
production of lymphocytes which are sensitized
against specific antigens.
• They have single large nucleus occupying almost the
whole cytoplasm concentration.

• Concentration- 1500- 4000 cells/mm3of blood.

Concentration decreased by glucocorticoids from zonal
fasculata of adrenal cortex.

• % white blood cells: 20-40%

• Half life – 200 days.

• Lymphocytes are important component of body immune

system

• Reticulum cell in lymph node can change to lymphoblast

which form lymphocyte, plasma blast which form plasma
cell (immunoglobulins)
• Examples of lymph nodes are:
i. Cervical duct lymph node
ii. thoracic duct lymph node
iii.The axillary duct lymph node (armpit)
iv.The inguinal duct lymph node (thigh)

• White blood cells and all other nucleated

cells in the body have proteins, called major
histocompatibility (MHC) antigens,
protruding from their plasma membrane
into the extracellular fluid.
• These “cell identity markers” are unique
for each person (except identical twins).
Although RBCs possess blood group
antigens, they lack the MHC antigen.
 Functions of White Blood Cells
• In a healthy body, some WBCs, especially lymphocytes,
can live for several months or years, but most live only
a few days. During a period of infection, phagocytic
WBCs may live only a few hours.

• WBCs are far less numerous than red blood cells; at

about 4000–11,000 cells per microliter of blood, they
are outnumbered by RBCs by about 700:1.

• Leukocytosis, an increase in the number of WBCs

above 11,000/L, is a normal, protective response to
stresses such as invading microbes, strenuous exercise,
anesthesia, and surgery.

• An abnormally low level of white blood cells (below

4000/L) is termed leukopenia. It is never beneficial and
may be caused by radiation, shock, and certain
chemotherapeutic agents.
• RBCs are contained within the bloodstream, but WBCs
leave the bloodstream by a process termed emigration,
also called diapedesis, in which they roll along the
endothelium, stick to it, and then squeeze between
endothelial cells.

• The precise signals that stimulate emigration through a

particular blood vessel vary for the different types of
WBCs.

• Molecules known as adhesion molecules help WBCs stick

to the endothelium. For example, endothelial cells display
adhesion molecules called selectins in response to nearby
injury and inflammation.

• Selectins stick to carbohydrates on the surface of

neutrophils, causing them to slow down and roll along the
endothelial surface.
• On the neutrophil surface are other adhesion
molecules called integrins, which tether
neutrophils to the endothelium and assist their
movement through the blood vessel wall and into
the interstitial fluid of the injured tissue.

• Neutrophils and macrophages are active in

phagocytosis; they can ingest bacteria and
dispose of dead matter.

• Several different chemicals released by microbes

and inflamed tissues attract phagocytes, a
phenomenon called chemotaxis.

• The substances that provide stimuli for

chemotaxis include toxins produced by microbes;
kinins, which are specialized products of
damaged tissues; and some of the colony-
stimulating factors (CSFs).
• The CSFs also enhance the phagocytic activity of
neutrophils and macrophages.

• Among WBCs, neutrophils respond most quickly to

tissue destruction by bacteria.

• After engulfing a pathogen during phagocytosis, a

neutrophil unleashes several chemicals to destroy the
pathogen.

• These chemicals include the enzyme lysozyme which

destroys certain bacteria, and strong oxidants, such as
the superoxide anion (O2), hydrogen peroxide (H2
- O2
), and
the hypochlorite anion (OCl ), which is similar to
-

household bleach.

• Neutrophils also contain defensins, proteins that exhibit

a broad range of antibiotic activity against bacteria and
fungi.
• Defensins form peptide “spears” that
poke holes in microbe membranes; the
resulting loss of cellular contents kills the
invader.

• Eosinophils leave the capillaries and enter

tissue fluid. They are believed to release
enzymes, such as histaminase, that combat
the effects of histamine and other
substances involved in inflammation during
allergic reactions.

• Eosinophils also phagocytize antigen–

antibody complexes and are effective
against certain parasitic worms.
• A high eosinophil count often indicates an
allergic condition or a parasitic infection.
• At sites of inflammation, basophils leave capillaries,
enter tissues and release granules that contain heparin,
histamine, and serotonin.

• These substances intensify the inflammatory reaction

and are involved in hypersensitivity (allergic) reactions.

• Basophils are similar in function to mast cells,

connective tissue cells that originate from pluripotent
stem cells in red bone marrow.

• Like basophils, mast cells release substances involved

in inflammation, including heparin, histamine, and
proteases.

• Mast cells are widely dispersed in the body, particularly

in connective tissues of the skin and mucous
membranes of the respiratory and gastrointestinal
tracts.
• Lymphocytes are the major soldiers in lymphatic
system battles. Most lymphocytes continually move
among lymphoid tissues, lymph, and 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,

and natural killer (NK) cells.

• B cells are particularly effective in destroying

bacteria and inactivating their toxins.

• T cells attack viruses, fungi, transplanted cells,

cancer cells, and some bacteria, and are responsible
for transfusion reactions, allergies, and the rejection
of transplanted organs.
• Immune responses carried out by both B
cells and T cells help combat infection and
provide protection against some diseases.

• Natural killer cells attack a wide variety of

infectious microbes and certain
spontaneously arising tumor cells.

• Monocytes take longer to reach a site of

infection than neutrophils, but they arrive in
larger numbers and destroy more microbes.

• On their arrival, monocytes enlarge and

differentiate into wandering macrophages,
which clean up cellular debris and microbes
by phagocytosis after an infection.
• In conclusion, an increase in the number of
circulating WBCs usually indicates
inflammation or infection.

• A physician may order a differential white blood

cell count or a count of each of the five types of
white blood cells, to detect infection or
inflammation, determine the effects of possible
poisoning by chemicals or drugs, monitor blood
disorders (for example, leukemia) and the
effects of chemotherapy, or detect allergic
reactions and parasitic infections.

• Because each type of white blood cell plays a

different role, determining the percentage of
each type in the blood assists in diagnosing the
condition.
 PLATELETS
• Besides the immature cell types that
develop into erythrocytes and leukocytes,
hemopoietic stem cells also differentiate
into cells that produce platelets.

• Under the influence of the hormone

thrombopoietin, myeloid stem cells develop
into megakaryocyte colony-forming cells
that in turn develop into precursor cells
called megakaryoblasts.

• Megakaryoblasts transform into

megakaryocytes, huge cells that splinter
into 2000 to 3000 fragments
• Each fragment, enclosed by a piece of the
plasma membrane, is a platelet. Platelets break
off from the megakaryocytes in red bone
marrow and then enter the blood circulation.
• Between 150,000 and 400,000 platelets are
present in each microliter of blood.
• Each is irregularly disc-shaped, 2–4 m in
diameter, and has many vesicles but no
nucleus.
• Their granules contain chemicals that, once
released, promote blood clotting. Platelets help
stop blood loss from damaged blood vessels by
forming a platelet plug.
• Platelets have a short life span, normally just 5
to 9 days. Aged and dead platelets are
removed by fixed macrophages in the spleen
and liver.
 BLOOD GROUPS
• Blood groups existence is based on the two
types of agglutinogens (antigens) on the
surface of red blood cells.

• These agglutinogens are A and B and they

are responsible for the four types of blood
groups i.e., A, B, AB and O.

• Blood plasma usually contains antibodies

called agglutinins that react with the A or B
antigens if the two are mixed.

• These are the anti-A antibody, which reacts

with antigen A, and the anti-B antibody,
which reacts with antigen B.
 (red cell)
Blood group
(plasma) Agglutinogen
Agglutinin
A A
β
B B
α
AB AB
Nil
O Nil
α and β
• You do not have antibodies that react with
the antigens of your own RBCs, but you do
have antibodies for any antigens that your
RBCs lack.

• For example, if your blood type is B, you

have B antigens on your red blood cells, and
you have anti-A antibodies in your blood
plasma.

• The agglutinogens are mucopolysaccarides,

which are not only present on the red blood
cells, but also, in body secretions, such as,
saliva, gastric juice and in tissues of liver,
kidney and lungs.
• There are at least 24 blood groups and
more than 100 antigens that can be
detected on the surface of red blood cells
but they do not induce any transfusion
reactions.

• Other blood groups include the Lewis, Kell,

Kidd, and Duffy systems.

• For the purpose of blood transfusion, A, B,

O and AB groups cross matching is done
with donor’s red cell and recipient’s
plasma.

• The red cell surface in 85% of the individuals,

show another type of the agglutinogen
called Rh agglutinogen.
• This is present in addition to the A ,B
agglutinogens and such individuals are called Rh .+

• The blood group will be called Rh , if the Rh

-

agglutinogen is absent on the red cell membrane.

• Normally, blood plasma does not contain anti-Rh

antibodies.

• If an Rh person receives an Rh blood transfusion,

- +

however, the immune system starts to make anti-

Rh antibodies that will remain in the blood.

• If a second transfusion of Rh blood is given later,

+

the previously formed anti-Rh antibodies will

cause agglutination and hemolysis of the RBCs in
the donated blood, and a severe reaction may
occur.
 Transfusions
• A transfusion is the transfer of whole blood or blood
components (red blood cells only or blood plasma
only) into the bloodstream or directly into the red
bone marrow.

• A transfusion is most often given to alleviate anemia,

to increase blood volume (for example, after a
severe hemorrhage), or to improve immunity.

• In an incompatible blood transfusion, antibodies in

the recipient’s plasma bind to the antigens on the
donated RBCs, which causes agglutination or
clumping, of the RBCs.

• Agglutination is an antigen–antibody response in

which RBCs become cross-linked to one another.
(Note that agglutination is not the same as blood
clotting.)
• When these antigen–antibody complexes
form, they activate plasma proteins of the
complement family.

• In essence, complement molecules make

the plasma membrane of the donated RBCs
leaky, causing haemolysis or rupture of the
RBCs and the release of hemoglobin into
the blood plasma.

• The liberated hemoglobin may cause kidney

damage by clogging the filtration
membranes.
•. Consider what happens if a person with
type A blood receives a transfusion of type B
blood.
• People with type AB blood do not have anti-A or
anti-B antibodies in their blood plasma are called
universal recipients because theoretically they can
receive blood from donors of all four blood types.
They have no antibodies to attack antigens on
donated RBCs.

• People with type O blood have neither A nor B

antigens on their RBCs and are sometimes called
universal donors because theoretically they can
donate blood to all four ABO blood types. Type O
persons requiring blood may receive only type O
blood.

• In practice, use of the terms universal recipient

and universal donor is misleading and dangerous.
Blood contains antigens and antibodies other than
those associated with the ABO system that can
cause transfusion problems.
 HEMOLYTIC DISEASE OF THE NEWBORN (HDN)
• The most common problem with Rh
incompatibility, hemolytic disease of the newborn
(HDN), may arise during pregnancy.

• Normally, no direct contact occurs between

maternal and fetal blood while a woman is
pregnant.

• However, if a small amount of Rh blood leaks

from the fetus through the placenta into the
bloodstream of an Rh mother, the mother will
start to make anti-Rh antibodies.

• Because the greatest possibility of fetal blood

leakage into the maternal circulation occurs at
delivery, the firstborn baby usually is not affected.
• If the mother becomes pregnant again, however, her
anti-Rh antibodies can cross the placenta and enter the
bloodstream of the fetus.

• If the fetus is Rh , there is no problem, because Rh

- -

blood does not have the Rh antigen. If the fetus is Rh ,+

however, agglutination and hemolysis brought on by

fetal–maternal incompatibility may occur in the fetal
blood.

• An injection of anti-Rh antibodies called anti-Rh

gamma globulin (RhoGAM®) can be given to prevent
HDN. Rh women should receive RhoGAM® before
delivery, and soon after every delivery, miscarriage, or
abortion.

• These antibodies bind to and inactivate the fetal Rh

antigens before the mother’s immune system can
respond to the foreign antigens by producing her own
anti-Rh antibodies.
 Haemostasis
 Haemostasis , not to be confused with the very similar term
homeostasis, is a sequence of responses that stops bleeding.

• When blood vessels are damaged or ruptured, the

haemostatic
response must be quick, localized to the region of damage,
and carefully controlled in order to be effective.

 Three mechanisms reduce blood loss:

(1) vascular spasm,

(2) platelet plug formation, and
(3) blood clotting (coagulation).

• When successful, hemostasis prevents hemorrhage, the loss

of a large amount of blood from the vessels. Hemostatic
mechanisms can prevent hemorrhage from smaller blood
vessels, but extensive hemorrhage from larger vessels
usually requires medical intervention.
 Vascular Spasm
• When arteries or arterioles are damaged,
the circularly arranged smooth muscle in
their walls contracts immediately, a reaction
called vascular spasm.

• This reduces blood loss for several minutes

to several hours, during which time the
other haemostatic mechanisms go into
operation.

• The spasm is probably caused by damage

to the smooth muscle, by substances
released from activated platelets, and by
reflexes initiated by pain receptors.
 Platelet Plug Formation
• Considering their small size, platelets store an
impressive array of chemicals. Within many
vesicles are clotting factors, ADP, ATP, Ca , and
2+

serotonin.

• Also present are enzymes that produce

thromboxane A , a prostaglandin; fibrin-stabilizing
2

factor, which helps to strengthen a blood clot;

lysosomes; some mitochondria; membrane
systems that take up and store calcium and
provide channels for release of the contents of
granules; and glycogen.

• Also within platelets is platelet-derived growth

factor (PDGF), a hormone that can cause
proliferation of vascular endothelial cells, vascular
smooth muscle fibers, and fibroblasts to help
repair damaged blood vessel walls.
 Platelet plug formation occurs as follows:
1. Initially, platelets contact and stick to parts of a
damaged blood vessel, such as collagen fibers of the
connective tissue underlying the damaged endothelial
cells. This process is called platelet adhesion.

2. Due to adhesion, the platelets become activated, and

their characteristics change dramatically. They extend
many projections that enable them to contact and
interact with one another, and they begin to liberate the
contents of their vesicles.

• This phase is called the platelet release reaction.

Liberated ADP and thromboxane A2play a major role by
activating nearby platelets. Serotonin and thromboxane
A2
function as vasoconstrictors, causing and sustaining
contraction of vascular smooth muscle, which
decreases blood flow through the injured vessel.
• A platelet plug is very effective in preventing
blood loss in a small vessel. Although initially
the platelet plug is loose, it becomes quite tight
when reinforced by fibrin threads formed
during clotting.

• A platelet plug can stop blood loss completely

if the hole in a blood vessel is not too large.

 Blood Clotting
• Normally, blood remains in its liquid form as
long as it stays within its vessels. If it is drawn
from the body, however, it thickens and forms a
gel.

• Eventually, the gel separates from the liquid.

The straw-colored liquid, called serum, is
simply blood plasma minus the clotting proteins.
• The gel is called a blood clot. It consists of a
network of insoluble protein fibers called
fibrin in which the formed elements of blood
are trapped.

• The process of gel formation, called clotting

or coagulation, is a series of chemical
reactions that culminate in formation of
fibrin threads.

• If blood clots too easily, the result can be

thrombosis, a condition of clotting in an
undamaged blood vessel.
• If the blood takes too long to clot,
hemorrhage can occur.
• Clotting is a complex cascade of enzymatic reactions in which
each clotting factor activates many molecules of the next one in a
fixed sequence. Finally, a large quantity of product (the insoluble
protein fibrin) is formed. Clotting can be divided into three stages

1. Two pathways, called the extrinsic pathway and the intrinsic

pathway which will be described shortly, lead to the formation of
prothrombinase. Once prothrombinase is formed, the steps
involved in the next two stages of clotting are the same for both
the extrinsic and intrinsic pathways, and together these two stages
are referred to as the common pathway.

2. Prothrombinase converts prothrombin (a plasma protein

formed by the liver) into the enzyme thrombin.

3. Thrombin converts soluble fibrinogen (another plasma protein

formed by the liver) into insoluble fibrin. Fibrin forms
the threads of the clot.
 The Extrinsic Pathway
• The extrinsic pathway of blood clotting has fewer steps
than the intrinsic pathway and occurs rapidly—within a
matter of seconds if trauma is severe.

• It is so named because a tissue protein called tissue

factor (TF), also known as thromboplastin, leaks into
the blood from cells outside (extrinsic to) blood vessels
and initiates the formation of prothrombinase.

• TF is a complex mixture of lipoproteins and

phospholipids released from the surfaces of damaged
cells. In the presence of Ca , TF begins a sequence of
2 +

reactions that ultimately activates clotting factor X.

• Once factor X is activated, it combines with factor V in

the presence of Ca to form the active enzyme
2 +

prothrombinase, completing the extrinsic pathway.

 The Intrinsic Pathway
• The intrinsic pathway of blood clotting is more
complex than the extrinsic pathway, and it occurs
more slowly, usually requiring several minutes.

• The intrinsic pathway is so named because its

activators are either in direct contact with blood
or contained within (intrinsic to) the blood;
outside tissue damage is not needed.

• If endothelial cells become roughened or

damaged, blood can come in contact with
collagen fibers in the connective tissue around the
endothelium of the blood vessel.

• In addition, trauma to endothelial cells causes

damage to platelets, resulting in the release of
phospholipids by the platelets.
• Contact with collagen fibers (or with the glass
sides of a blood collection tube) activates
clotting factor XII, which begins a sequence
of reactions that eventually activates clotting
factor X.

• Platelet phospholipids and Ca2+ can also

participate in the activation of factor X.

• Once factor X is activated, it combines with

factor V to form the active enzyme
prothrombinase (just as occurs in the extrinsic
pathway), completing the intrinsic pathway.
 The Common Pathway
• The formation of prothrombinase marks the
beginning of the common pathway. In the second
stage of blood clotting prothrombinase and Ca 2+

catalyze the conversion of prothrombin to thrombin.

• In the third stage, thrombin, in the presence of Ca , 2+

converts fibrinogen, which is soluble, to loose fibrin

threads, which are insoluble. Thrombin also activates
factor XIII (fibrin stabilizing factor), which strengthens
and stabilizes the fibrin threads into a sturdy clot.
Plasma contains some factor XIII, which is also
released by platelets trapped in the clot.

• Thrombin has two positive feedback effects. In the

first positive feedback loop, which involves factor V,
it accelerates the formation of prothrombinase.
Prothrombinase in turn accelerates the production of
more thrombin, and so on.
• In the second positive feedback loop,
thrombin activates platelets, which
reinforces their aggregation and the release
of platelet phospholipids.

 Clot Retraction
• Once a clot is formed, it plugs the ruptured
area of the blood vessel and thus stops
blood loss. Clot retraction is the
consolidation or tightening of the fibrin clot.

• The fibrin threads attached to the damaged

surfaces of the blood vessel gradually
contract as platelets pull on them. As the
clot retracts, it pulls the edges of the
damaged vessel closer together,
decreasing the risk of further damage.
• During retraction, some serum can escape
between the fibrin threads, but the formed
elements in blood cannot.

• Normal retraction depends on an adequate

number of platelets in the clot, which
release factor XIII and other factors, thereby
strengthening and stabilizing the clot.

• Permanent repair of the blood vessel can

then take place. In time, fibroblasts form
connective tissue in the ruptured area, and
new endothelial cells repair the vessel lining.
 Coagulation
Blood coagulation pathways in vivo showing the central role played by thrombin
Clotting (Coagulation) Factors
No NAME(S) SOURCE ACTIVATION
I Fibrinogen. Liver.
Common.
II Prothrombin. Liver.
Common.
III Tissue factor (thromboplastin). Damaged tissues and activated
platelets.
IV Calcium ions (Ca 2+ ). Diet, bones, and platelets. All.
V Proaccelerin, labile factor, Liver and platelets.
or accelerator globulin (AcG).
VII Serum prothrombin conversion Liver. Extrinsic.
accelerator (SPCA), stable factor,
or proconvertin.
VIII Antihemophilic factor (AHF), or Liver. Intrinsic.
antihemophilic globulin (AHG).
IX Christmas factor, plasma thromboplastin Liver.
Intrinsic.
component (PTC), or antihemophilic factor B.
X Stuart factor, Prower factor, Liver.
Extrinsic and intrinsic.
or thrombokinase.
XI Plasma thromboplastin antecedent Liver.
Intrinsic.
(PTA) or antihemophilic factor C.
XII Hageman factor, glass factor, Liver.
Intrinsic.
contact factor, or antihemophilic factor D.
XIII Fibrin-stabilizing factor (FSF). Liver and platelets. Common.
*There is no factor VI. Prothrombinase (prothrombin activator) is a combination of
activated factors V and X.
 Role of Vitamin K in Clotting
• Normal clotting depends on adequate levels
of vitamin K in the body.

• Although vitamin K is not involved in actual

clot formation, it is required for the
synthesis of four clotting factors.

• Normally produced by bacteria that inhabit

the large intestine, vitamin K is a fat soluble
vitamin that can be absorbed through the
lining of the intestine and into the blood if
absorption of lipids is normal.
• People suffering from disorders that slow
absorption of lipids (for example,
inadequate release of bile into the small
intestine) often experience uncontrolled
bleeding as a consequence of vitamin K
deficiency.
PLASMA
Plasma is the fluid portion of the blood. It contains
the following;
.

COMPONENT PERCENTAGE (%)

Water 92
Proteins 6-8

Salts 0.8
Lipids 0.6
Glucose (blood glucose) 0.1

Plasma protein concentration varies with health status of

individuals with a decrease during starvation, liver damage
and renal damage
 FUNCTIONS OF PLASMA PROTEIN
1. Contribute to the viscocity of the plasma

2. Responsible for osmotic return of filtered

fluid from interstitial fluid compartment.

3. Create suspension stability in blood aiding

maintenance of dispersion of materials.

4. Reserve of amino acid for the body.

5. transport CO in blood
2

6. Transport of Hormones, urea, lipids, and

glucose.
 EXAMPLE OF PLASMA PROTEINS
 ALBUMIN
• Most abundant (55-64%)
• 4-5g/100mls of blood (3.5-5g/dl)
• The smallest size with molecular weight of
69000-70,000
• Total exchangeable albumin is 4-5g/kg body
weight
• 38.45% intravascular
• 10% of exchangeable pool degraded daily
• Replacement comes from hepatic cells
producing 200 to 400mg/kg/day
• Synthesis decreases in fasting and increasse in
nephrosis because of loss in urine
 GLOBULIN
• Form about 20% of total plasma protein
• Amount in circulating blood is about 2
-3g/100ml of blood
• Occurs in various form
- α- globulin (150,000-160,000).Transport
retinol and Thyroxine
-Y-globulin (150,000 – 900,000). E.g. iron
transporting protein called trasferrin.
-β- globulin (90,000) e.g. antibodies
• Albumin-globulin ratio = 2:1
 FIBRINOGEN
• Only soluble plasma protein

• Molecular weight = 350,000

• Amount in circulation = 0.15 – 0.3g/100ml

• Converted to fibrin as blood coagulates

 IMMUNITY
• Immunity is the abilityof the body to resist
invasion by foreign organism or toxins that tend
to damage the tissue and organs of the body.

 There are 2 types of immunity.

A. Innate immunity: Non specific nor directed

at a specific disease causing organism
includes;

a. Phagocytic action of white blood cells

b. Action of digestive enzymes in the GIT

c. Destruction of swallowed organisms by the

acid secretions of the stomach
 d. Resistance pose by the skin secretions like tear, mucosa
lining the airway etc. These act as barrier by trapping bacteria,
which may try to enter the body.

e. Presence in the blood of certain chemical compounds that

attach to foreign organism or toxins and destroy them.

 Some of these compounds are:

 Lysozyme, a mucolytic polysaccharide that attacks bacteria

and causes them to dissolute.

 The compliment complex, a system of 20 proteins that can be

activated in various way to destroy bacteria.

 Natural killer cell that can recognize and destroy foreign cells,
tumour cells and even some infected cells.

 Basic polypeptides which react with and inactivate certain

types of gram-positive bacteria
 B. Acquired immunity: This is developed against a
specific invading organism or toxins after first experience

 Involves production of specific antibodies

 There are two forms of acquired immunity

 Humoral immunity:

• This is immunity produced by circulating antibodies (γ-

globulin)

 Cellular immunity:

• This is achieved via production of large number of

activated lymphocytes designed to destroy the foreign
agent.

• It is responsible for delayed allergic reaction and rejection

of foreign tissue transplant.
 Humoral Immunity
 B-cell lymphocytes are involved in recognising the
antigen and release specific antibodies against it.

 This is only possible if the helper T- cell activates B-cell.

 There are 2 ways of activating the helper T- cell which in

turn stimulate B-cell proliferation:

1, Macrophages, after taken the antigen, combine with the

classII major histocompatibility complex (MHC).

• This combination is then presented to the helper T-cells.

• Helper T-cells release cytokines (interleukins) which

activate B- cells to proliferate and transform into plasma
cells.

• The plasma cells elaborate immunoglobulins

• In the second mechanism, the antigen can bind
directly to the B-cell surface receptors which
also have class II protein (MHC).

• This combination on the surface of the B-cell

results in the activation of helper T-cells. This
inturn leads to B-cells transforming in to plasma
cells and liberate immunoglobulins.

• The activated B-cells also form memory B-cells.

• These cells are specialized to liberate specific

antibodies against the specific antigens, when
there is subsequent entry of the antigen into the
body.