Haemopoetic system

Seema Mehdi
JSSCPM

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What is Blood?
• Blood is a connective tissue
• Its volume is 5-6 L in males and 4-5 L in females
• It is slightly alkaline, with a pH of ~ 7.4
• Its color varies from bright to dark red
• It has a salty metallic taste
Function
3 major functions
• Transportation
• Regulation
• Protection
Transportation
• Respiratory
Red blood cells or erythrocytes transport Oxygen from lungs to cells
and Carbon dioxide from cells to lungs
• Nutritive
Blood absorb nutrients from digested foods in gastrointestinal tract and
transport to all the cells in body
• Excretory
Metabolic wastes, excess water and ions , and other molecules not
needed by the body are carried by the blood to the kidneys and
excreted in the urine
Regulation

• Hormonal
Blood carries hormones from their site of origin to distant target tissues
, where they perform the regulatory functions
• Temperature
Blood is responsible to carry body heat to the surface in high
temperature environment as well as to keep body heat in within low
temperature environment
Protection

• Clotting
The clotting mechanism protects against blood loss when vessels are
damaged
• Immune
The immune function of blood is performed by the leukocytes that
protects against many disease causing agents
Composition of the Blood
• Blood consists of formed elements that are suspended and carried in
a fluid called plasma
• The formed elements
- Erythrocytes Oxygen transport
- Leukocytes Immune defence
- Platelets Blood clotting
Plasma
• Straw colored fluid made of water (~90%), other
contents include:
• Proteins make the bulk of the solutes:
Albumins (60%), manufactured in the liver are the
most abundant
Globulins (36%) are immune bodies
Fibrinogen (4%) for blood clotting
• Nutrients: glucose, amino acids, lipids, cholesterol
• Electrolytes: Na+, K+, Ca++, Mg++, H+, Cl-, HCO3-, PO4--,
SO4--
• Waste: urea, creatinine, uric acid, bilirubin
• Gases: O2 , CO2 , N2
• Protein bound hormones
• Plasma without clotting factors is called “serum”
 Formed Elements
I. Red blood cells
II. White blood cells
A. Granular leukocytes (contain conspicuous granules that are visible under a light
microscope after staining)
1. Neutrophils
2. Eosinophils
3. Basophils
B. Agranular leukocytes (no granules are visible under a light microscope after
staining)
1. T and B lymphocytes and natural killer (NK) cells
2. Monocytes
III. Platelets

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RBC/ Erythrocytes
• RBC is a 7.5 micron disc shaped body with a central depression
• The cell is without a nucleus or mitochondria
• RBC contains hemoglobin and filamentous proteins attached to the
cell wall to impart flexibility on it
• Life span 120 days
• Erythrocytes are produced in bone marrow
• Older erythrocytes are removed from the circulation
by phagocytic cells in the liver, spleen and bone
marrow.
• Antigens are embedded in the cell membrane, they
decide the blood group
• The RBC cytoplasm provides energy to maintain
intracellular homeostasis
• This energy is generated mostly through anaerobic
glycolysis
• RBCs function is gas exchange: O2 to the tissues and
CO2 to the lungs
White Blood Cells/Leukocytes
• Leukocytes contain nuclei and mitochondria and can move in an
amoeboid fashion
• Because of their amoeboid ability, leukocytes can squeeze through
pores in capillary walls and move to a site of infection.
• Produced in bone marrow and destructed in spleen
Types
• The total number of WBCs is 4000 to 11,000/mm3
• There two main types of WBCs: granulucytes and agranulocytes
• Granulocytes, are of three types:
Neutrophils (polymorphs) 50-70%, destroy
bacteria
Eosinophils, 2-4% bilobed nuclei, attack parasites
Basophils, 1% in peripheral blood, reside in the
tissues, contain histamine, involved in
hypersensitivity reaction
• Agranulocytes are of two types
Lymphocytes, the smallest and second most
abundant
T cells (80%) mediate cellular immunity
B cells mediate humoral immunity

Monocytes, the largest, migrate to the tissues and

become macrophages involved in cellular immunity
Neutrophils
 Monocytes

Eosinophils
 Lymphocytes
Basophils
Platelets
• Platelets are only about 20% of the diameter of red
blood cells, the most numerous cell of the blood.
• The normal platelet count is 150,000-350,000 per
microliter of blood
• Platelets are produced in bone marrow and destroyed
in the spleen and liver
• Life span 5 to 9 days
• They are fragments of cells called megakaryocytes,
they have no nuclei but like leukocytes are capable of
amoeboid movements
• Platelets play an important role in blood clotting
• They constitute most of the mass of the clot, and
phospholipids in their cell membranes activate the
clotting factors in plasma that result in threads of
fibrin, which reinforce the platelet plug.
• Platelets that attach together in a blood clot release
serotonin , a chemical that stimulates constriction of
blood vessel.

Platelets
Blood component (summing-up)

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 FORMATION OF BLOOD CELLS
• The process by which the formed elements of blood develop is called
hemopoiesis or hematopoiesis
• Before birth, hemopoiesis first occurs in the yolk sac of an embryo
• Later in the liver, spleen, thymus, and lymph nodes of a foetus.
• Red bone marrow becomes the primary site of hemopoiesis in the last three
months before birth, and continues as the source of blood cells after birth and
throughout life.

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• Several hormones called hemopoietic growth factors regulate the differentiation
and proliferation of particular progenitor cells.
• Erythropoietin or EPO increases the number of red blood cell precursors. EPO is
produced primarily by cells in the kidneys that lie between the kidney tubules
(peritubular interstitial cells). With renal failure, EPO release slows and RBC
production is inadequate.
• Thrombopoietin or TPO is a hormone produced by the liver that stimulates the
formation of platelets (thrombocytes) from megakaryocytes.
• Cytokines are small glycoproteins that are typically produced by cells such as red
bone marrow cells, leukocytes, macrophages, fibroblasts, and endothelial cells.

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 RED BLOOD CELLS
➢Red blood cells (RBCs) or erythrocytes contain the oxygen-carrying
protein hemoglobin, which is a pigment that gives whole blood its red
color
➢A healthy adult male has about 5.4 million red blood cells per
microliter of blood
➢A healthy adult female has about 4.8 million.
➢RBCs are biconcave discs with a diameter of 7–8 µm

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➢Their plasma membrane is both strong and flexible, which allows them to deform
without rupturing as they squeeze through narrow capillaries.

➢RBCs lack a nucleus and other organelles and can neither reproduce nor carry on
extensive metabolic activities

➢The cytosol of RBCs contains hemoglobin molecules; these important molecules

are synthesized before loss of the nucleus during RBC production and constitute
about 33% of the cell’s weight

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A hemoglobin molecule consists of a protein called globin, composed of four
polypeptide chains (two alpha and two beta chains)

 A ring like non protein pigment called a heme is bound to each of the four
chains.

 At the center of each heme ring is an iron ion (Fe2 ) that can combine reversibly
with one oxygen molecule allowing each haemoglobin molecule to bind four
oxygen molecules.

Hemoglobin also transports about 23% of the total carbon dioxide, a waste
product of metabolism

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The iron portion of a heme group binds oxygen
for transport by hemoglobin

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 RBC Life Cycle
• Red blood cells live only about 120 days because of the wear and tear their
plasma membranes undergo as they squeeze through blood capillaries.
• Ruptured red blood cells are removed from circulation and destroyed by fixed
phagocytic macrophages in the spleen and liver, and the breakdown products are
recycled,

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1 Macrophages in the spleen, liver, or red bone marrow phagocytize ruptured and
worn-out red blood cells.

2 The globin and heme portions of hemoglobin are split apart.

3 Globin is broken down into amino acids, which can be reused to synthesize other
proteins.

4 Iron is removed from the heme portion in the form of Fe3 , which associates
with the plasma protein transferrin, a transporter for Fe3 in the bloodstream.

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5 In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe3
detaches from transferrin and attaches to an iron-storage protein called ferritin.

6 Upon release from a storage site or absorption from the gastrointestinal tract,
Fe3 reattaches to transferrin.

7 The Fe3 –transferrin complex is then carried to red bone marrow, where RBC
precursor cells take it up through receptor-mediated endocytosis for use in
hemoglobin synthesis.
Iron is needed for the heme portion of the hemoglobin molecule, and amino acids
are needed for the globin portion. Vitamin B12 is also needed for the synthesis of
hemoglobin

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8 Erythropoiesis in red bone marrow results in the production of red blood cells,
which enter the circulation.

9 When iron is removed from heme, the non-iron portion of heme is converted to
biliverdin a green pigment, and then into bilirubin, a yellow orange pigment.

10 Bilirubin enters the blood and is transported to the liver.

11Within the liver, bilirubin is released by liver cells into bile, which passes into the
small intestine and then into the large intestine.

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12 In the large intestine, bacteria convert bilirubin into urobilinogen .

13 Some urobilinogen is absorbed back into the blood, converted to a yellow

pigment called urobilin and excreted in urine.

14 Most urobilinogen is eliminated in feces in the form of a brown pigment called

stercobilin which gives feces its characteristic color.

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HEMOSTASIS

Is a sequence of responses that stops bleeding.

Three mechanisms reduce blood loss:
(1) vascular spasm,
(2) platelet plug formation
(3) blood clotting (coagulation)

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 Hemostasis is process of*
forming clots in walls of
damaged blood vessels and
preventing blood loss, while
maintaining
blood in a fluid state within
vascular
system
Haima + Stasis

Prevent blood
loss
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 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 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 culminates in formation of fibrin threads.

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• If blood clots too easily, the result can be thrombosis—clotting in an undamaged blood
vessel. If the blood takes too long to clot, hemorrhage can occur.

• Clotting involves several substances known as clotting (coagulation) factors.

• These factors include calcium ions (Ca2 ), several inactive enzymes that are synthesized
by hepatocytes (liver cells) and released into the bloodstream, and various molecules
associated with platelets or released by damaged tissues.

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• 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

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

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T he blood-clotting cascade.

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• 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
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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.

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 Injury in blood vessels Platelets
Platelets clump at the wound

Release of thrombokinase
Vitamin
K
Thrombokinase
Prothrombin Thrombin
Calcium
ions

Fibrinogen

Clot forms to stop further blood loss

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Red Blood Cell Antigens and
Blood Typing
The surfaces of erythrocytes contain a genetically determined assortment of
antigens composed of glycoproteins and glycolipids called as agglutinogens.
Based on the presence or absence of various antigens, blood is categorized into
different blood groups.
 There are at least 24 blood groups and more than 100 antigens that can be
detected on the surface of red blood cells.
Here we discuss two major blood groups— ABO and Rh.
Other blood groups include the Lewis, Kell, Kidd, and Duffy systems.

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ABO System
• There are several groups of red blood cell antigens, but the major
group is known as ABO system
• In terms of the antigens present on the red blood cell surface , a
person may be :
Type A – with only A antigens
Type B – with only B antigens
Type AB – with both A and B antigens
Type O – with neither A nor B antigens
Plasma Antibodies
Type A – with only B antibodies
Type B – with only A antibodies
Type AB – with neither A nor B antibodies
Type O – with both A and B antibodies
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.
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.

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 Rh Blood Group
The Rh blood group is so named because the antigen was discovered in
the blood of the Rhesus monkey.

People whose RBCs have Rh antigens are designated Rh positive those

who lack Rh antigens are designated Rh negative.

Normally, blood plasma does not contain anti-Rh antibodies. If an Rh

negative person receives an Rh positive blood transfusion, however, the
immune system starts to make anti-Rh antibodies that will remain in the
blood.

If a second transfusion of Rh positive 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.
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 Transfusions
• Despite the differences in RBC antigens reflected in the blood group systems,
blood is the most easily shared of human tissues, saving many thousands of lives
every year through 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

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The normal components of one person’s RBC plasma membrane can trigger
damaging antigen–antibody responses in a transfusion recipient.
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
crosslinked to one another. (Note that agglutination is not the same as blood
clotting.)


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• When these antigen–antibody complexes form, they activate plasma proteins of
the complement family

• Complement molecules make the plasma membrane of the donated RBCs leaky,
causing hemolysis (rupture) of the RBCs and the release of haemoglobin into the
blood plasma.

• The liberated hemoglobin may cause kidney damage by clogging the filtration
membranes.

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 Development of hemolytic disease of the
newborn (HDN).
(a) At birth, a small quantity of fetal blood usually leaks across the placenta into the
maternal bloodstream. A problem can arise when the mother is Rh negative
and the baby is Rh positive, having inherited an allele for one of the Rh antigens
from the father.
(b) Upon exposure to Rh antigen, the mother’s immune system responds by
making anti-Rh antibodies.
(c) During a subsequent pregnancy, the maternal antibodies cross the placenta into
the fetal blood. If the second fetus is Rh negative, the ensuing antigen–antibody
reaction causes agglutination and hemolysis of fetal RBCs. The result is HDN

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 Disorders of blood components

1. Anemia
Anemia is a condition in which the oxygen-carrying capacity of blood is reduced. All of the
many types of anemia are characterized by reduced numbers of RBCs or a decreased
amount of hemoglobin in the blood.
The person feels fatigued and is intolerant of cold, both of
which are related to lack of oxygen needed for ATP and heat production. Also, the skin
appears pale, due to the low content of redcolored hemoglobin circulating in skin blood
vessels.

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2. Thalassaemia
There is reduced globin synthesis with resultant reduced haemoglobin production and increased
friability of the cell membrane, leading to early haemolysis. Severe cases may cause death in
infants or young children.

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