The Blood 2022

Blood :
is a specialized type of connective tissue, red in color, syrupy
fluid which has specific gravity 1.055 and the viscosity 2.5 times
that of water. Blood is alkaline (PH=7.4) and appear scarlet red
when taken from arteries and purplish from veins. The difference
in color is due to its content .
In adult blood volume is 5 – 6 L whereas in a new born baby it is
300 ml. In the adult blood constitute 8 % ( or ) of body weight
Blood plays a role in maintaining the cellular environment by
serving as a transport medium of the body. The various functions
of blood result from specialization withen the cellular elements
or the plasma or the interaction between the two .
Composition
1- Blood cells (formed elements) : W.B.C , R . B.C & platelets
suspended in the plasma .
The plasma is a straw coloured liquid , its normal volume is about
5 % of body weight or 3.5 L in a 70 kg man, 92 % of plasma is
water and 8 % is solid of which 7% is plasma protein (The
remaining are inorganic salts, pigments, enzymes , non-
nitrogenous substances as glucose, fat etc , and non-protein
nitrogenous sulostances as urea, uric acid , creative etc. ) .
The plasma remain fluid only if anti-coagulant is added to the
whole blood ; but if the blood is allowed to clot and the clot is
removed , the remaining fluid is called Serum.
The serum has the same composition as plasma except that its
clotting factors; fibrinogen (Factor I) Prothrombin ( factor II ) ,
factor v and factor vlll have been removed . and it has a higher
Serotonin content due to the breakdown of platelets during
clotting .
Serum = plasma - fibrin
A high hematocrit reading indicates an increase in the No. of
circulating cells or a reduction in plasma (e.g P.C.V of 65% or
more seen in cases of cholera due to large loss of water ) . A low

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The Blood 2022

hematocrit indicates a reduction in the No. of the R.B.C or

increase in plasma volume .
Blood
volume 5 - 6 L (8 % of body weight)
PH =7.4

plasma : 55 % of blood 45 % of blood

vol. 3 - 3.5 L (5% of body weight.) Blood cells
(formed elements)

White blood cells Red blood cells Platelets

(Leukocytes) (Erythrocytes) (Thrombocyte)

Hematopoiesis : (cell production)

Before birth cell production occurs in the liver, in mid fetal life
the spleen and lymph nodes play a minor role in cell production .
After birth, the bone marrow becomes the only site of erythrocyte
, thrombocyte , granulocyte formation (polymorph nuclear) and
also the agranular monocytes, whereas lymphocyte production
may also takes place in lymphoid tissues , spleen , tonsils and
other lymph nodes. The bone marrow contain multipotent ,
pluripotential cells that differentia into progenitor cells, these
inturn differential into the various types of blood cells .
Normally. 75 % of bone marrow activity is in the formation of
W.B.C. and only 25 % of its activity involves R.B.C formation
; it appears that the life span of W.B.C. is shorter (few hours to
weeks ) as compared to life span of R.B.C (120 days) and the
No. of R.B.C is about 500 times more than that of W.B.C. in
circulation .

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The Blood 2022

Erythropoiesis (R.B.C formation)

is stimulated during anemia , hemorrhage and in the presence of
low content in the blood . In such cases, the renal arteries will
be constricted this will stimulate renal tissue to release
Erythropoietin hormone which circulate in blood for 2 days and
during this period it stimulates hemocytoblast cells in the bone
marrow to divide and produce R.B.C. In the presence of renal
disease, the process of erythropoiesis will decrease.
Leukopoiesis : (W.B.C formation )
is stimulated during infection by the effect of a globular protein
called Leukocytosis promoting factor released from infected
tissue . The white blood cells : (Leukocytes) W. B.C. count
4000-11000 W. B.C / m . The W. B.C serve as one of the
major means of defensive against infections by microorganisms .
Two different ways are involved :
1- Phagocytosis .
2- Immune system . (Formation of antibodies against the
invading agent ; antigen )
* The W. B.C in the circulation can be grouped into Two major
groups based on appearance of their cytoplasm and nuclei
Granulocytes (polymorphnuclear) 65% of total count
Neutrophils :50 – 70 % , Eosinophil's :1 - 4 % , Basophils : 0.4%
Characterized by granular cytoplasm and many lobed nucleus,
their defensive. mechanism by phagocytosis.
Agranuloytes : 30 % of total count .
Monocytes : 2 – 8 % (phagocytic)
Lymphocytes 20 – 40 % (Immune system) Characterized by their
single nucleus and no cytoplasmic granules .

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The Blood 2022

Granulocytes
Neutrophils are the most numerous of the W. B.C types (62 %
of total W. B.C count ; 4300 / cmm of blood ). It is 10-12 u in
diameter , The nuclus compound of 1 – 5 lobes according to the
age of the cell . It granules stain pale violet. Neutrophils function
primarily. as phagocytes. They ingest by phagocytosis foreign
particles or injured cell debris. During an Infection the No. can
increase up to 20,000 / c.mm of to hole blood . By means of
amoeboid movement they can pass through the pores of
capillaries (by process of diapedesis) & can move through
intercellular spaces to locate the contaminants. Then life span is
2 - 4 days ( average half life in the circulation is about 6 hour's ) .

Eosinophil : Represent 1- 4 % of total W. B.C characterize by 2

lobed nucleus & the cytoplasm contain, coarse granules. It
phagocytose antigen antibody complex flts level in the
circmtation increased in presence of foreign protein, allergy and
parasitic infractions Life span 10 -12 days .

Basophil : 0 – 1 % : ( 0 . 4 % ) of total W. B.C The granules

contain histamine and heparin so it may help in preventing
spontaneous clots during normal blood circulation . It's life span
is about 15. Days .
Granulocytes : The defensive action :-
The average half-life of neutrophil in circulation is 6 hours . To
maintain normal circulatory level daily production is 100 billion
neutrophils / day . Invasion of body by bacteria stimulate the
inflammatory response Many of neutrophils enter tissue . They
are attracted to endothelial surface by selectin then they bind to
integrin which attach them to the vessel wall & enter the tissue
through endothelial cells by process & diapedesis . Many of
those that leave circulation enter GIT and lost from body .
Bone marrow is stimulated to produce large No of neutrophils.
The neutrophils are attracted to in fected area by bacterial
products that interact with plasma factors (chemotactic agent) the

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The Blood 2022

process known as chemo taxis . The chemotactic agents are part

of chemokine's family, include a component of complement
system ( , Leukotriene's and polypeptide from Lymphocytes,
mast cells & basophils .
other plasma factors act on bacteria to make them testy to
Phagocytes by process of opsonizastion .
The principal opsonins that coat bacteria are IgG & complement
protein . The coated bacteria then bind to receptors on neutrophil
cell membrane this will motor activity of cell ; exocytosis &
respiratory burst the incased motor activity lead to ingestion of
bacteria by phagocytosis (endocytosis).
By exocytosis , neutrophil granules discharge their content into
phagocytic vacuoles contain bacteria . The granules contain
various proteases plus antimicrobial proteins called defensins.
Two types of defensins α and β are found in mammals .
In addition the cell membrane bound enzyme NADPH oxidase is
activated .
Activation of NADPH oxidase is associated with a sharp in
uptake and metabolism in neutrophil (the respiratory burst) &
generation of super oxide anion by the following reaction
NADPH + +2 NADP + 2 is free
radical formed by addition of one electron to ).
Two react spontaneously with 2 to form O2
a reaction Catalyzed by cytoplasmic form of superoxide
dismutase (SOD). SOD

are oxidants that are effective bactericidal agents but is

converted to & by enzyme catalyze .
Neutrophils also discharge enzyme myeloperoxidase which
catalyzes conversion of B & SC to corresponding
acids Hocl , HOBr etc the principal product is HOCl (bec. C is
abundant in body) . The acids are also oxidant . In addition

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The Blood 2022

granules contain elastase & variety of proteases that destroy

invading organism .

These enzymes (myeloperoxidase , defensin elastase & other) act

with to produce a killing zone around the
activated neutrophil to kill invading organism .
The movements of cell in phagocytosis as well as migration to a
site of infection function of microfilament i.c interaction of actin
& myosin on cell membrane .
Neutrophil also release thromboxane's that are vasoconstrictors
& platelet aggregating agents , Leukotriene's that vascular
permeability & attract other neutrophil to site & other
prostaglandins that exert a moderate anti-inflammatory effect .

Monocytes : represent 5 % total W.B.C. originates in the

B.M , have a kidney shape nucleus without granules in the
cytoplasm. It is similar to neutrophil in this ameboid movements
contains lysosomal and peroxidase enzymes and phagocytic
actively . it remains in the circulation for 72 hours then enters the
tissue to become Tissue Macrophages- , Kupffer cells of the liver,
pulmonary alveolar macrophage, microglia in the brain,
histocytic in the skin and reticulum cell in spleen lymph nodes
and bone marrow .
The macrophages become activated by Lymphokines from T-
lymphocytes, they grow very large and have phagocytic activity
They play a role in immunity and secrete about 100 substances
that affect lymphocytes and other cells.
Activation of the Macrophage System.
The lymphokines affect the macrophages.by First, they slow or
stop the migration of the macrophages after they have been
chemotactically attracted into the inflamed tissue area, thus
causing much accumulation of macrophages. Second, they
activate the macrophages to cause more efficient phagocytosis,
allowing them to attack and destroy increasing numbers of
invading bacteria or other tissue-destroying agents.

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The Blood 2022

Mast cells
are heavily granulated cells that are found in areas rich in
connective tissue & are abundant beneath epithelial surfaces .
Their granules contain histamine, heparin & many proteases .
They have IgE receptors on their cell membrane & like basophils
they degranulate when IgE-Coated antigens bind to their surface
in addition to produce allergic responses they may play a role in
defense against parasitic infection .
Lymphocytes :
are small mononuclear leukocytes with Large nucleus and
reduced amounts of cytoplasm. Small lymphocytes has a
diameter of 8 u whereas large lymphocytes diameter is between
15 – 20 u. Lymphocytes constitutes about 25 % of total W.B.C
count.
After birth some lymphocytes that originate from the bone
marrow invade Lymphoid tissues (lymph nodes, Spleen, thymus
gland etc) where they establish lymphocyte colonies to produce
additional lymphocytes without involving the bone marrow .
Two types of lymphocytes can be recognized : B cells and T
cells
The B cell lymphocytes ( Bursal lymphocytes) colonize in
lymphoid tissue and carry there functions without involving the
thymus gland. It occurs in bursal equivalent i.e Fetal liver and
after birth in the bone marrow, their life span few hours .
The Thymus glands : is a large gland above the heart in the
space between the lungs. Although the thymus atrophies or
disappear with the onset of puberty , it is involved and play a
major role in cellular immunity before it lost .
The T cell lymphocytes :Around the time of birth the stem cells
(precursors of lymphocytes) are released from the bone marrow
and infiltrate the thymus gland. After exposure to the thymus they
undergo modification to produce T-cell lymphocytes . From the
thymus gland the T-cell invade and establish colonies with in the
lymph nodes and other lymphoid tissues.

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The Blood 2022

The Functions of lymphocytes

Involve the body immune mechanism when the body is exposed
to foreign materials (antigen) they produce antibody Proteins .
The antibodies are proteins that are specifically structured to react
with specific antigenic material. The reaction makes the antigen
harmless. Thus the body can be Protected from the foreign
materials or invading microorganism .
Resistance of the Body to Infection-immunity
The human body has the ability to resist almost all types of
organisms or toxins that tend to damage the tissues and organs.
This capability is called immunity. Much of the immunity is
acquired immunity that does not develop until after the body is
first attacked by a bacterium, virus, or toxin; often, weeks or
months are required for the immunity to develop. An additional
element of immunity that results from general processes, rather
than from processes directed at specific disease organisms, is
called innate immunity, which includes the following aspects:
1. Phagocytosis of bacteria and other invaders by white blood
cells and cells of the tissue macrophage system,
2. Destruction of swallowed organisms by the acid secretions of
the stomach and the digestive enzymes
3. Resistance of the skin to invasion by organisms
4. Presence in the blood of certain chemicals and cells that attach
to foreign organisms or toxins and destroy them. Some of these
are:
(1) lysozyme, a mucolytic polysaccharide that attacks bacteria
and causes them to dissolute;
(2) basic polypeptides, which react with and inactivate certain
types of gram-positive bacteria
(3) the complement complex, described later, a system of about
20 proteins that can be activated in various ways to destroy
bacteria;

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The Blood 2022

(4) natural killer lymphocytes that can recognize and destroy

foreign cells, tumor cells, and even some infected cells.
Immune mechanism : Basic types of acquired immunity ,
humoral and cell-mediated are initiated by antigens
The immune system has ability to produce antibodies against
many millions of different foreign agents that may invade the
body . The antibodies kill the invaders in variety of ways .
There are 2 types of immune defense systems Humoral &
cellular , both act to antigen . The most potent antigen are
complex proteins & polypeptide but antibodies can be formed
against carbohydrates, nucleoproteins & lipoproteins .
Humoral immunity is mediated by B lymphocytes . These cells
produce circulating antibodies in the λ-globulin fraction of
plasma protein . The antibody activate the complement systems
& attack & neutralize antigens . Humoral immunity is a major
defense against bacterial infections .
Cellular immunity is mediated by T Lymphocytes. It is
responsible for delayed allergic reactions & rejection of
transplant of foreign tissue. The cytotoxic T cells attack &
destroy the cells that have antigen , activated them one
mechanism by which they kill by insertion of a pore forming
molecules (Perforins) in the membrane of their target calls which
leads to destruction of the cells by osmotic lysis .
Cellular immunity constitutes a major defense against infections
due to viruses, persist for longer time (10-20 years) than humoral
immunity fungi & few bacteria such as tubercle bacillus. It also
helps defend against tumors .
Development of the immune system:
B – lymphocytes differentiate into plasma cells & memory B cell
B cells can bind antigens directly but they must contact helper
cells to produce full activation & antibody formation. The
activated B cell proliferate & transform into memory B cells and
plasma cells .

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The Blood 2022

The plasma cell secrete large quantities of antibodies into the

general circulation. The antibodies circulate in globulin fraction
of plasma ; called immunoglobulin's (IgG , IgA , IgM , IgD ,
IgE). The immunoglobulin's are actually the secreted form of
antigen binding receptors on the B cell membrane .
The circulating immunoglobulin's protect their host by :
1- binding to & neutralizing some protein toxins.
2- blocking the attachment of some viruses to sells.
3- Opsonizing bacteria .
4- activating complement
5- activating NK cells.

five general types of immunoglobulin antibodies are produced by

the lymphocyte - plasma cell system :
IgG , IgA , IgM , IgD , & IgE

T – cells differentiate to 4 varieties of cell :

1. Helper T cell : Helper T cell I ( ) – in relation to
cellular immunity secrete IL 4 and IL5
2. Helper T cell 2 ( ) – with B cell in relation to humeral
immunity secrete IL 2 and y interferon
3. suppressor T cell : involved in regulation of cellular &
humeral immunity .
4. Cytotoxic T cell : (which are also known as cell , effector
T' cells or killer cells) . It destroys transplanted & other
foreign cells
5. Memory. T cells

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The Blood 2022

CD 8 : glycoprotein present on surface of cytotoxic &

suppressor T- cells. can detected by monoclonal antibodies
CD 4 : glycoprotein on helper T cells .
Memory B & T cells are cells that have been exposed to an
antigen and are readily converted to affecter cells by a later
encounter with same antigen, unlike other lymphocyte they
persist in body for months or even years .
The no. of different antigens recognized by lymphocytes in body
is very large , so stem cells differentiate into many millions
different T & B lymphocytes each has ability to respond to a
particular antigen. When antigen first enters the body, it can bind
directly to appropriate receptors on B cells . However a full
antibody response requires that B cells contact helper cells .
In the case of T cells the antigen is taken up by an antigen
presenting cell & partially digested & a peptide fragment of it is
presented to the appropriate receptors on T cells.

In either case the cells are stimulated to divide forming clones of

cells that respond to this antigen ( clonal selection) .

The antigen - presenting cells (APC s ) include specialized cells

called dendritic cells in lymph nodes & spleen & Langerhans

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The Blood 2022

dendritic cells in the skin. Macrophages & B cells themselves can

also function as antigen presenting cells. In the ApCs ,
polypeptide products of antigen digestion are coupled to protein
products of major histo compatibility complexe (MHC) genes
& presented on surface of cell. The products of the MHC genes
are called human leukocyte antigens (HL . A) The MHC
complexes on surface of APCs bind to appropriate T cells.
Therefore receptors on T cells must recognize a wide variety of
complexes. C the glycoprotein on the surface of Suppressor
& cytotoxic T cells and the C on helper T cell facilitate the
binding of MHC protein's to the T cell receptors . (C cluster of
C differentiation )

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The Blood 2022

Innate Immunity :
Mediated neutrophil macrophages and natural killer (NK) cells A
third type of lymphocyte found in body is the natural killer cell
(NK cell) which is sometimes called the non-T , non-β but are
cytotoxic . The natural killer cells are large lymphocytes that
make up 10 – 15 % of circulating mononuclear cell . They
destroy cells that have undergone malignant transformation & so
help prevent the establishment of cancerous tumors . In addition
they attack viruses & have receptors that permit them to kill
antibody coated viruses. The activated cell produced their effects
through the release of cytokines as well as in some cases
complement and other systems .
Their activity is increased by interleukin 2 (IL - 2) , they
represent an important first line defense against viral infections ,
combating spread of disease while more specific T & B cells
are activated Thus there are 3 types of cytotoxic T cell : α β T ,
γδT & NK . cells .
Cytokines the lymphocytes secrete a variety of hormone
like chemical messengers that affect the immune response these
have been called the lymphokines . However since they are
produced by other cells as well they are now called cytokines .
When the a.a sequence of a factor in humans is known its name is
changed to interleukin .
The complement system :
The effects of circulating antibodies & cellular immunity are
mediated in part by plasma enzymes called complement system.
The enzymes are identified by the No.
The classic pathway for activation occur when binds to
immunoglobulin's that have bound antigen , & this stimulate a
sequent of events that activate .

The alternative or properdin pathway occur when a circulating

protein Factor I recognize repetitive sugar structures. Such as
polyglucose or polyfructose in cell membranes . These sequences
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The Blood 2022

are found in bacteria & viruses but not in mammalian cells.

Interaction of factor I with the surface of invading cells triggers
reactions that activate Propendin is another circulating
protein that stabilizes the activating enzyme complex

The classic & alternative pathways both produce convertase

which cleaves C3 into C3a and b, a remain in fluid
(anaphylotoxin) whereas b promotes opsonization of bacteria
promoting phagocytosis . It also initiate reactions that activate
rest of the complement system . Activation of produce
chemotactic substances , they also cause lysis of bacteria , (like
cytotoxic T cell ) , some viruses & foreign cells by inserting pore
forming perforins in their membrane .
Tissue Transplantation
The T lymphocyte system is responsible for the rejection of
transplanted tissue. When tissues such as skin & kidneys are
transplanted from a donor to a recipient of same species, the
transplants take & function for a while but then become necrotic
& are rejected because recipient develops an immune response to
transplanted tissue. The only transplants that are never rejected
are those from an identical twin .
A No. of treatments have been developed to overcome rejection
of transplanted in humans:
1- Kill T lymphocytes by killing rapidly dividing cells with
drugs such as azathioprine but this makes patient susceptible to
infection and cancer .
2- Administer glucocorticoids which inhibit cytotoxic T cell but
these cause osteoporosis mental changes & other changes .
3-A third treatment with cyclosporine drug inhibit all T cell
mediated immune responses and may causes kidney damage &
cancer .
Clinical Correlates :
Over 50 immunodeficiency syndromes due to abnormalities in
function of immune cells have been described. ranging from

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The Blood 2022

moderate in incidence of infection to severe and fetal conditions

.Acquired immune deficiency syndrome (AIDS)
is due to HIV (human immunodeficiency virus) , binds to C
(glycoprotein to helper T cell ) & No. of helper T which cell .
The loss of helper T cells lead to a failure & proliferation to C
& B cells with a loss & immune function & death from
infections due to normally nonpathogenic bacteria or cancer .
Passive Immunity
Thus far, all the acquired immunity we have discussed has been
active immunity—that is, the person’s own body develops
antibodies or activated T cells in response to invasion of the body
by a foreign antigen. However, temporary immunity can be
achieved in a person without injecting any antigen. This
temporary immunity is achieved by infusing antibodies, activated
T cells, or both obtained from the blood of someone else or from
some other animal that has been actively immunized against the
antigen. Antibodies last in the body of the recipient for 2 to 3
weeks and, during that time, the person is protected against the
invading disease. Activated T cells last for a few weeks if
transfused from another person but only for a few hours to a few
days if transfused from an animal. Such transfusion of antibodies
or T lymphocytes to confer immunity is called passive immunity.
Allergy and sensitivity undesirable side effects of immunity
1-Allergy caused by activated T cells not by antibodies (Delayed
reaction allergy)
On repeated exposure the activated T Cell diffuse from blood to
the tissue in large no. release toxin and with invasion of
macrophage causing tissue damage.
2- Allergy Associated with excess IgE antibodies called reagins,
when an allergin (antigen) enters the body an allergin reagin
reaction takes place and allergic reaction takes place. This type
occur in some people who has allergic tendency it is called (
atopic allergies) it may pass from parent to child.

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The Blood 2022

The IgE antibody attach to mast cells and basophil then binding
of allergin to reagin change the membrane of mast cells and
basophil resulting in rupture of the membrane with release of
different special agents that cause the allergy (histamine,
Protease,eosinophil chemotactic agent and others.

The Red blood cells

The R.B.C carry the Hb in the circulation , they are biconcave
disc that has a flexible membrane which allow the cells to change
shape without breaking as they pass through small diameter blood
vessel R.B.C NO. : 4.8 - 5.4 million /m .
life span = 120 days (I % of the R.B.C. are replaced each day .
Each R.B.C contain 29p.g Hb (P.g = g) .
Hemoglobin :is the carrying pigment in the R.B.C . It is a
protein the content in blood :
14 g /d L blood in women .
16 g /d L blood in men .
Chemical steps in Hb formation :
I- succinyl CO A + glycine pyrrole
II- 4 pyrrole protoporphyrin lx
III- Protoporphyrin lx + Fe Heme
IV- 4 Heme + globin Hemoglobin .
Therefore the Hb molecule is made up of 4 components (Heme),
each of which is bounded to a polypeptide chain. In adult Hb -A
has 2 α chains and 2 β chains . Each heme group contain an
(F ) that gives the Hb its red color, The heme group carry
loosely so it can pick up when the is abundent & loose it
when concn. is low .

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The Blood 2022

Diagrammatic representation of a molecule of hemoglobin A, showing the four

subunits. There are two and two polypeptide chains, each containing a heme moiety.
These moieties are represented by the disks.
The polypeptides form the globin portion of the Hb molecule. In
normal adult humn Hb (Hb-A) has 2 α chains (each α chain
contain 141 a.a residue ) and 2 β chains, ( each β chain contains
146 and residue ), Hb - A form about 97.5 % of the Hb. The
remaining 2.5 % is Hb in which the β chains are replaced by
delta ) chains ( ) the delta chain ( δ ) also contain 146 a.a
residue but 10 individual residues differ from those in β chain .

In Hb-A , there are small derivatives of Нb – А :

НЬ —
НЬ — glycosylated Hb
НЬ —
Hb has glucose attached to the terminal amino acid valine in
each β - chain. It is of special interest because the quantity of HB
increased in uncontrolled D.M and reduced after 6 weeks of
good. diabetes control .
Hb – F : (Hb in the fetus)
contain 2α chains and two gamma chains ( ‫ ) גּ‬. The y chain
also contain 146 a.a residue but 37 a.a residue differ from those
in the β – chain .
In Hb – f , the content (at a given P is greater than that of
Hb –A because it (Hb – f ) bind 2,3 BpG (2,3 Biphospho
glycerate that cause release of from Hb to the tissue). with
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The Blood 2022

less affinity. This facilitate movement of from meternal to the

fetus circulation

Red cell formation and destruction :

In normal adult (70 kg man) there is about 3x10 13 R.B.C
containing 900g of Hb, about 0.3g Hb is synthesized every hour
& 0.3g Hb / hour is destroyed .

Red cell formation and destruction. RBC, red blood cells.

Physiological Function of Hb :
1- Transport of :
Each gm of Hb carry 1.34 ml thus 15 (average 15 g / dL
blood) x 1.34 = 20 ml / dL of blood (when Hb is 100 %
saturated with ) . The real value is 19.8 ml / dL blood
(97.5 % Saturation) in arterial blood . In venous blood 15 ml
/ dL blood (75 % saturation ) . Therefore the released
to the tissue is about 4.8 md / dL blood.
2- Transport of C :
In R.B.C : 93 %
1- 70 % as bicarbonate :
Carbonic anhydrase
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The Blood 2022

C + O +
2- 23 % as carbamino Compound (react with protein of Hb).
C + Hb Hb C
In plasma : 7 %
1- dissolved
2- Carbamino compounds with plasma Protein
N
C + R R.C
COOH
3- Hydration : ( no carbonic anhydrase)
Slow reaction
C +
3- Regulation of blood PH :
Hb – oxy Hb buffer system
when the blood passes through active tissue (systemic
circulation) it picks up C that increase its acidity
by the formation of (from ) but as the
R . B . C release to the tissue it becomes less acidic which
allow the Hb to pick-up from the plasma to prevent the PH
becoming too acidic.
In lung capillaries , level are high, Hb loads & loses
. If the remain the lung capillaries become acidic therefore
the combined with HC to form. C + O. The lose
by expiration. Therefore removing extra help to keep blood
PH stable .
Reactions of Hb
1- Hb bind with to form oxy – Hb in which the is
attached to of the heme. The affinity of Hb for is
affected by:
1- PH 2- Temp. 3- concn. of 2,3 BpG

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 The Blood 2022

2,3 BpG and compete with for binding this

decreasing the affinity of Hb to . the released to the
tissue.
2- When blood is exposed to any oxidizing agent that convert
F to F
Met hemoglobin formed, it has a dark color and if present in large
quantity in the circulation it causes discoloration of the skin.
Normally some oxidation of Hb to Met – Hb occurs in the body
but the presence of the enzyme NADH Met – Hb reductase
convert Met- Hb back to Hb .
3- Carbon monoxide (C ) react with Hb to form carboxy
hemoglobin (Carbon monoxy – Hb ) . The affinity of Hb for
is less than the affinity for CO which displaces on Hb
reducing the carrying capacity of blood.
General characteristics of human R.B.C
Normal count : 4.8 - 5.4 m/m life span : 120 days (1 % of
R.B.C. care replaced each day.
Mean R . B . C diameter = 7.5 um .
Hematocrit (Hct) : 47 % in male
42 % in Female
Hemoglobin : 14 – 16 g / dL (900 g of Hb in the circulating blood
of an adult man) .
Each gm of Hb carry 1.34 ml .
1.34 15 (average) = 20 ml / dL blood is carried when the
Hb is fully saturated withe . As the real saturation is 97.5 %
thus 19.8 ml dL arterial blood and the saturation in venous
blood is 75 % ; 15 ml / dL venous blood .
Theis the released to the tissue =
19.8 - 15.0 = 4.8 ml / dL blood .
Hemoglobin lndecis :
Mean corpuscular volume , (MCV) . (volume of single R.B.C)

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The Blood 2022

MCV = = 87 FL

MCV > 95 macrocytic

Femtoliter (FL) =
MCV < 80 microcytic

Mean corpuscular Hb ( MCH )

( amount of Hb in R.B.C )

MCH = = 29 p.g

p.g =

MCH < 25 are hypochromic .

Mean corpuscular Hb concn. (MCHC) :

MCHC = = 34 g / dL blood .

Anemia :is a clinical condition caused by reduction in ; No. of

R.B.C and low concn. of Hb in circulating blood.
Cause
1- Impaired R.B.C production ; due to various factors involved
in process of erythropoiesis e.g Fe , vitalnines ( , , vit.
C and folic acid ) and proteins .
2- Excessive loss of blood.
(acute or chronic).
3- Bone marrow destruction :
Drug poisoning or irradiation ,
4- Hemolysis (destruction) of R.P.C due to Hereditary disease or
poisoning or Erythroblastosis fetalis .
5- Infection
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The Blood 2022

Types of anemia
1- Iron deficiency anemia (micro cytic).
2- Pernicious anemia (macrocytic).
3- Hemolytic anemia .
4- Aplastic anemia .

1- Iron deficiency anemia :

Fe has important role in formation of Heme. fraction of Hb
. Deficiency of Fe may be due to low dietary or reduced
absorption of Fe in the GIT .

The R.B.C become smaller (microcytic ) and contain

smaller quantity of Hb (hypochromic). The result is a lower
supplied to the tissue .
Iron deficiency anemia may occur in :
a- infants & young children .
b- women during the reproductive life .
c- blood loss .
d- presence of infection . ( especially in infants ) .
Treatments :
The normal intake of Fe is about 15 – 20 mg / day. In Fe
deficiency anemia more Fe is needed 25 – 50 mg / day that
cannot be supplied by diet therefore Fe therapy is needed.
The utilization of Fe depend on the % of Fe administered which
is converted to Hb . Each gm of Hb contain 3.3 mg Fe so about
25 mg Fe are required to increase the Hb conc. by 1% .
2- Pernicious anemia : (Macrocytic anemia)
due to lack of vit ( maturation factor) required for
conversion of RNA to DNA essential for all division &
reproduction of stem cell of bone marrow to produce mature
R.B.C.

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The Blood 2022

ViT. from diet protected from being destroyed by G. I

enzymes by intrinsic factor secreted by the cell of the stomach
Absorption of vit occur in the ileum , stored in the liver and
slowly released as needed .
In absence of Vit the R . B . C are large (Macrocytic) ,
abnormally shaped , few in NO . (1 million / m ) , the
average diameter of the cell is about 11 u (normal 8 u ) , the
volume of the Cell 95 – 160 FL (normal 87 FL) and the mean
Hb in the cell is 50 p.g ( normal 30 p.g ) .
The granulocyte and platelet are reduced in No. partly because of
the increase bone marrow activity to form this abnormal R.B.C.
In addition lack affect degeneration of sensory & motor n.f
in spinal cord that may lead to loss of sensation .
3- Hemolytic anemia
Due to excessive and rapid R.B.C destruction . It is inheried
disorder may be A – due to abnormalities of Hb
production : -
1- sickle cell anemia : ( Intra corpuscular defects )
The defect in the β – chain of the Hb ( the amino acid valine
replaces the amino acid glutamic acid on each of the β – chain ) .
The Hb form crystal inside the R . R . C ; ( Hb – s ) The cell
assume a sickle shape , easily ruptured and the Hb – s loss its
ability to carry .

he rigid shape of the sickle cell inhibit their movement through

the capillaries so they stick forming a pile behind the stuck cells
that inhibit supply to the tissue . The severe lack some
times cause death .
2- Thala cemia
The chain Hb chains are normal but they are produced in small
amount :
α-Thalassemia : absence or decrease in α - chain
β - thalassemia : absence or decrease in β - chain .

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The Blood 2022

The R .B.C have very short life and readily hemolysis .

B- Extra corpuscular defects may affect the cells: various
infections physical agents (heat , burns) chemical agents (drugs &
poisons) .
4- Aplastic anemia :
Failure of the bone marrow function due to various factors as
irradiation and toxic effects of certain drugs.
There is anemia , Leucopenia (decrease in W . B . C ) and
thrombocytopenia (decrease in platelet ).

Polycythemia
Higher R . B . C count
1- Physiologic polycythemia : (secondary polycythemia occur
when level in the atmosphere is decreased (high altitude )
that stimulate production , the RBC count rise to about 6-8
m/m .
2- Polycythemia vera (primary polycythemia ) . It may be due to
tumorous conditions that increase R.B.C production up to 8 –
9 m/m and the hematocrit is about 70 – 80 %. The W . B .
C and platelet counts also increases. The viscosity of blood
(50% of viscously is related to the R.B.C) increases from the
normal which is 3 times that of water to about 15 times so
many of the capillaries become plugged by the viscous blood
as a result the total blood volume may be increases to twice
normal .

In general as the color of the skin is dependent on the quantity of

blood , cyanosis (blue color of the skin ) may be seen in
secondary polycythemia due to hypoxia , whereas in
polycythemia Vera cyanosis may be at times seen due to the slow
movement of blood in the skin capillary of venous blood masks
the color of oxygenated blood .

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The Blood 2022

Platelets : ( Thrombocytes )
are active unrucleated cells formed by fragmentation of
megakaryocytes of the bone marrow .
Bone marrow committed stem cell ( Progenitor cell that form all
cellular elements )

Megakaryoblast

Megakaryocytes

platelets Fragmentation of the extensions of the cytoplasm

The platelets are oral bodies appear as biconvex discs 2-4u in

diameter . Normal count 250,000 - 400,000 / m .
A physiological rise occur in response to bleeding ; low count
appear after large doses of x – rays that may produce injury in
the B.M or in severe infection that may damage the B.M . on the
other hand the count increased up to 1 m / m in myloid
leukemia .The life span is about 4 days. The platelets are
destroyed in the spleen Thus often spleenoctomy then NO .
increases temporarily while in splenic over activity they
disappear from the circulation .
structure of platelets : They have an outer coat celled the
glycocalyx which play a role in the interaction of platelet with
other cells .

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The Blood 2022

Beneath the coat is the plasma membrane that contain actin and
myosin in its protein portion, and glycoprotein on the outer
surface

Two types of granules are present in the cytoplasm

1- Dense granules :contain non protein substance secreted in
response to activation. including :Serotonin, ADP and C
2- alpha granules
proteins including clotting factors (fibrinogen, factors Vl and
VIII) and platelet derived growth factor ( PDGF ) that stimulate
wound healing .

Blood vessel wall and platelets contain von wille brand factor
which is a large molecule secreted by endothelial cells activate
the platelet to release the content of their granules. The released
ADP act on ADP receptor on platelet membrane to produce more
accumulation of platelet (platelet aggregation) .
Platelet aggregation occur when blood vessel wall is injured .
Aggregation is also increased by platelet activating factor (PAF)
secreted by platelet , neutrophils and monocycles. It has
inflammatory activity. It increase the production of arachidonic
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The Blood 2022

acid derivatives from membrane phospholipid ; arachidonic acid

is converted into thromboxane (vasoconstrictor) which
facilitate further C influx and increase platelet aggregation .
Aspirin causes a moderate inhibition of thromboxane formation
and there is evidence that when aspirin is taken in low doses it is
of value in preventing myocardial infarction (M.I), unstable
angina and ischemic attacks.

Therefore when blood vessel wall is injured the process of

aggregation is initiated by adherence of the platelet to the
exposed collagen through integrin that bind to collagen and
laminin . This will activate the platelet in presence of ADP and
thrombin . The activated platelet alter its shape ; Put out pseudo
podia, discharge their granules and stick to other platelets
Regulation of platelet productions :
platelet production is regulated by factors that regulate the
production of megakaryocytes plus thrombopoietin which is a
circulating protein produced by the liver and kidney.
Thrombopoietin facilitate megakaryocyte maturation .
There are thrombopoietin receptors on platelet , when the No. of
platelets is low , less is bound and more is available to stimulate
production of platelets conversely when the No . of platelets is
high more is bound and less is available producing a form of
feedback control of platelet production .

When the platelet count is low , clot retraction is deficient and

there is a poor constriction of ruptured vessels. The resulting
Thrombocytopenic purpura is a clinical syndrome characterized
by multiple subcutaneous hemorrhages Thrombocytopenic
purpura is an autoimmune disease and can also be produced by
toxins or drugs.
Thrombasthenic purpura : 0.5 – 1 cm in diameter
The purpura occur when the platelet count is normal but the
circulating platelets are abnormal .

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The Blood 2022

Blood groups
Blood groups is based on the presence of blood group antigens
(agglutinogen on the surface of the R . B . C which are inherited.

The Important blood groups are : - ABO , Mn , Rh , P & Lewis

etc
Blood group ABO

The membranes of human red cell contain a variety of antigens

called agglutinogens . The most impotent & best known of these
are the A&B agglutinogens & the individual are divided into 4
major Blood types A , B , AB & O on the base of the
agglutinogens preset in them cell . There are A & B antgens
in many tissues other than blood. They have been found in
salivary glands , Saliva pancreas , Kidney , liver , lung testes ,
semen & amiotic fluid .
Antibodies against agglutinogens called agglutinin they any occur
(inherited ) or they may be produced by exposure to red cell of
another individual .
Agglutinins – α and B
( anti A ) ( anti B )
The agglutinogens are dominant & agglutinins are recessive in
character Thus blood groups are classified according to presence
or absence of agglutingen on cells :
Cell
ABO gmp Plasma Agglmtinin
agglutinogen
A A β ( anti B ) 42 %
B B α ( anti A ) 10 %
AB A.B ______ 40 %
α β
O _______ 44 %
( anti A – anti B )

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The Blood 2022

Agglutinogen start developing the 6th week of foetal life .

New borne have 1 / 4 of adult level .
Agglutinin develop during first year of life .
When group A red cells come in contact with plasma that contain
Anti- A they become sticky & clump together. This is termed
agglutination .
Agglutinogen A + Agglutinin anti A agglutination
(α)
Agglutnigen B + Agglutinin anti B agglutination
(β)
To safeguard against agglutination it is desirable in a transfusion
to give patient blood of the same group as his own . If this is not
possible then blood may be used that will not head to an
agglutination reaction between the donor cell & the recipient
plasma .
Recipient

____ ++++ ____ ++++

++++ ____ ____ ++++

++++ ++++ ____ ++++

____ ____ ____ ____

Universal O AB universal
Donar B Recipient

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The Blood 2022

Rhesus Factor (Rh- factor)

In additional to aglutinogens A & B further agglutniogens as C

, D , E , D is the chief & when present the cells are said to
be R

85 % of population R
15 % of population R
Unlike the ABO system no performed Rh agglutinin (Anti D)
is found. However R person can make Anti – D Following
sensitization with R blood .
The R individual cannot form Anti – D & for them it is
immaterial . whether the receive R or R

R
R
R

when red blood cells containing Rh factor are injected into an Rh

negative person anti - agglutinin ( Anti - D) develope slowly
Maximum concn. occur 2 - 4 months later .
On multiple exposure to ( ) blood the (R ) person become
strongly sensitized to the (R ) factor & if transfused with
additional ( ) blood a serious transfusion reaction
takesplaces .
In case of man for future transfusion these serious affects can.
be prevented by giving the correct group & the correct Rh factor
The position in regard to (R ) women is very different & care
must be taken to prevent sensitization & the formation of
anti D in her plasma because Anti - D during pregnancy can
cross the placental barrier to the fetus and cause destruction the
fetus or babies blood . A condition known as Erythroblastosis
fetalies .
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The Blood 2022

Erythroblastosis fetalsis :(Hemolytic disease of the newborn )

This disuse occurs in babies when the mother is (R ) & the

father is ( ) . the mother is likely to become immunized
against the baby's ( ) cell :

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The Blood 2022

Later the baby develop its own R cell & by that time all the
anti-D will have disappeared from the circulation
Since sensitization of (R ) mother by carry first child is
usually normal . However hemolytic fetuses born to (R )
mothers who have previously been pregnant one or more times
with R fetus Fortunately it is possible to prevent sensitization
from occurring the first time by giving a single does of anti – Rh
antibodies in the form of Rh immune globulin (Rho GAM)
during the postpartum period (72 hours after delivery ) . Such
passive immunization does not harm the mother & has been
demonstrated to prevent retinue antibody formation by the
mothers .
In obstetric clinics , such treatment is a routine to unsensitiznel (
R woman who have delivered an (R baby. this
treatment reduce the incidence of hemolytic disease by more
than 90 % . treatment with a small dose during pregnancy will
also prevent sensitization due to fetal – meternal hemorrhage
before delivery . If the baby is (R ) the R.B.C are not
affected by the anti – D in the mother .
If the father is (R ) , then all the babies are negative .

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The Blood 2022

Blood transfusion
The Principle is to ensure the cell of the donor should not be
agglutinated by the plasma of the recipient . For this purpose the
Blood groups & the Rh factor of both the donor & recipient
should have the same blood group & Rh factor .
Furthermore a cross matched test is carried between the cells of
donor and the serum of recipient and visa versa to detect any
evidence of agglutination .
Effects of Incompatible blood Transfusion :
1- agglutination of R.B.C & hemolysis .
2- Hemolytic jaundice by R.B.C break down .
3- Renal Failure due to precipitation of Hb .
4- Death in severe cases .
Hemostasis
process of stopping the loss of blood from injured blood vessel
it involves :
1- Local constriction of blood vessel (vascular spasm) . The
irregularities in injured blood vessel wall cause the platelet
to rupture & release serotonin which is a vasoconstrictor , it
cause the muscle in blood vessel to contract this will narrow
the diameter of the vessel around the site of injury.
2- The temporary Hemostatic plug . In injured blood vessel ,
the underlying layer of collagen is exposed attracting
platelet that adhere together and liberate serotonin , ADP &
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The Blood 2022

it will stick to the injured vessel wall forming a white

hemostatic plug to reduce the loss of blood
3- Clot formation :
conversion of soluble plasma protein fibrinogen into
insoluble fibrin

thrombin
Fibrinogen Fibrin monomer Fibrin (loose)

factor Xlll
Fibrin ( tight )

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 The Blood 2022

Haemostasis ( Blood clot mechanism )

Intrinsic System

activation occur when blood is exposed to the collagen

fibers underlying the endothelium in the blood vessel . The
activation is catalyzed by high mol. wt kininogen &
kallikrein .
inactive Xll Xll a cactive

XI XIa Extrinsic System

‫هءش‬
Tissue
IX IXa Thromboplastic
‫هءش‬
platelet
(TPL)
phospholipid Vlla
( PL)
VIII 𝐶𝑎 platelet
𝐶𝑎
phospholipid
( PL) ( TPL)
Villa
Thromboplastic

X Xa
PL (phospholipid )
V 𝐶𝑎
Va
Prothrombin liver Thrombin active

Fibrinogen Fibrin monomer

XIIIa ( stabilization )
Fibrin ( Tight ) Fibrin ( loose )
𝐶𝑎
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The Blood 2022

Thrombin is the active form of prothronbin which is plasma

protein formed by the liver and activated by the action of
activated factor Xa . Factor X can be activated by reactions in
either of two systems , Intrinsic & Extrinsic sys

36