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 oF.

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
 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
 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
 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/mm 3 of blood with variation between the

two sexes.

• Male 4.5-6 & female 4.3-4.5 million cells/mm 3 of 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, O2 and ATP.

• Life span is 120 days.

• The count is higher in new born (6mmillion/mm 3) 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 aa 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, 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

hematocrit. 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)
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 adult and 2mg in
menstruating female.
• Iron is released when red blood cell are broken down,
transported by transferring (β-globulin) to the liver.
• The liver stores about 60% of the body iron as Apoferritin.
• Iron is distributed in the body as follows; Hemoglobin
(65%), Myoglobin (4%), Ferritin (15-30%), Trasferin
(0.1%)
C. Vitamin B12

• Important for all cell functions and tissue growth and also for conversion of ribose nucleotide to
deoxyribonucleotide 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 mw 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 O2
• 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 300-500mls of
blood is hemolysed 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/mm3 of

blood.

• 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/mm3 blood
• % 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/mm3 of blood
• % white blood cell- 1-4%
 Neutrophil
• Staining – Neutral
• No of lobes- 3-5
• Concentration - 3000 -6000 cells/mm 3 of 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 3 of blood
• % white blood cell – 2-8%
• 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
• They have single large nucleus occupying almost the whole
cytoplasm concentration.

• Concentration- 1500- 4000 cells/mm 3 of 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
• 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-
• 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 (H2O2), and the hypochlorite
anion (OCl-), which is similar to household bleach.

• Neutrophils also contain defensins, proteins that exhibit a broad

• 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,
• 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.
Blood group Agglutinogen Agglutinin
(red cell) (plasma)
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
 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
• 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
 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
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, Ca2+, and serotonin.

• Also present are enzymes that produce thromboxane A2, a

prostaglandin; fibrin-stabilizing 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 A2 play 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
• 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
• 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 Ca2+, TF begins
a sequence of reactions that ultimately activates clotting factor X.

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

of Ca2+ to form the active enzyme 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
• 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 Ca2+ catalyze the conversion of prothrombin
to thrombin.

• In the third stage, thrombin, in the presence of Ca2+, 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
• 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 (Ca2+). 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 CO2 in blood

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

 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

 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.
• 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