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Hematology

Lecturer:Dr Mohamed Daud

MBBS : Mogadishu University

General Director :BDH


Function of blood
Blood is a fluid tissue, a suspension solution of blood Cells
in plasma that is circulating through the cardiovascular,
which performs a number of functions dealing with:

● Substance distribution
- Oxygen from the lungs and nutrients from the digestive tract

- Hormones from endocrine glands to target organs

- Metabolic wastes from cells to the lungs and kidneys for

elimination
● Regulation

- Appropriate body temperature by absorbing and distributing heat

- Normal pH in body tissues using buffer Systems

● Protection

- Initiating clot formation when a vessel is broken(hemostasis)

- Activating WBCs to defend the body against foreign invaders


Composition and Characteristics of Blood
Plasma

Straw-colored liquid consisting of water and dissolved solutes


Plasma Proteins – constitute 7-9%
of the plasma

 1.Albumins (60% - 80%)

 2.Globulins, divided into


three types:
Alpha and beta globulin
transporters

Gamma globulins anti


bodies

3. Fibrinogen, it
functions in blood clotting
Formed Elements(cells)

■ Erythrocytes(RBCs), leukocytes(WBCs), and


platelets make up the formed elements

■ Most blood cells do not divide but are renewed


by cells in bone marrow
Red blood
cells
HAEMATOCRIT
It is defined as the percentage of blood volume that is occupied by
erythrocytes
After centrifugation the heavier
red cells settle to the bottom of
1.0 the tube. The straw-coloured
plasma remains at the top.
plasma The two layers are separated by
centri- a ‘buffy coat’ of white cells and
platelets.
fuge
0.5
buffy coat So the packed red blood cell
volume sit in the bottom of tube
red cells after centrifuging is termed
hematocrit value or hematocrit
0 (Ht)
Normal range in male is
blood approximately 45% and in
sample female is 42%
□ Blood volume
males : 5–6 L
females: 4–5 L

Blood loss
<10% nothing
10 ~30 % clinic symptom
>30% danger
Calculating haematocrit Important

Erythrocyte Volume = 0.45 ×5.5L= 2.5L

Plasma Volume = 5.5 L─2.5 L = 3.0 L


Physical and chemical characteristics of blood
Effects of Osmosis
 H20 moves by osmosis into the lower concentration

area until equilibrium is reached

Higher Lower
concentration concentration

Semi-permeable
Membrane
高 低
Hypertonic solution Isotonic solutiion Hypotonic solution

Animal
cell

shriveled normal lysed


Hemopoiesis
Hemopoiesis is the process only by which the origin,
development & maturation for all blood cell. In adults, it
occurs only in bone marrow

vertebrae Vertebrae
ilium
sternum
Life Span Erythrocytes (RBCs)
 Erythrocytes lack a nucleus and mitochondria
 Because of these deficiencies, erythrocytes have a circulating life span
of only about 120 days before they are destroyed in the liver, spleen
and bone marrow.
 Reticulocytes. Immature young RBCs appear (reticular) when stained.
They contain a few ribosomes & can be seen in bone marrow.

EM of normal red blood cells


● Suspension stability

When the blood is anticoagulated and added in a narrow tube,


rouleaux of the red cells are formed and then its sedimentation
The length of sedimentation of the red cells within one hour is termed
erythrocyte sedimentation rate (ESR).

? mm
Normal range

Male : 3--7 mm
Female: 5 – 10 mm
● Rouleaux formation
- more erythrocytes adhibit with concavity one another
□ cause ( RBC ? plasma ?)

RBC from patient with high ESR RBC from the health

plasma from the health plasma patient with high ESR

RBC
Rouleaux

 the tuberculosis and rheumatism are accompanied by a rise of


globulin which can accelerate ESR.
albimin globulin 、 Fibrinogen

inhibit promote

Rouleaux formation

down up

ESR

Factors Suspension stability : change of blasma component


● Osmotic fragility
□ Changes (swell and burst) in RBC put into lower osmotic salty solution.
□ Osmotic fragility of aged RBC is large and easily results in rupture

Hypotonic solution Hypotonic solution


Isotonic solutiion
Hypertonic solution

Effect of Different Crystal osmotic pressure on RBCs shape


Functions of RBCs
1.To transport oxygen from the lungs to the tissue (function of hemoglobin)
& transport of carbon dioxide from the tissues back to blood & then lungs.

The arterial and venous red cell

2. RBCs also function as a good buffer. By this action, hydrogen ion


concentration is regulated & acid-base balance is maintained ( carbonic anhydrase)
3. RBCs carry blood group antigens like A, B. Helpful for blood grouping &
transfusion.
● Maturation of RBCs
– Requirment for Vitamin B12 and folic acid

Both folic acid & vitamin B12 are necessary co-factors for DNA
synthesis, which is essential for maturation of the red cells.

folic acid
Absorption of Vit.B12 requires
vitamin B12
a protein called intrinsic
tetrahydrofolic acid factor secreted by stomach
(THFA)

pernicious anemia is due to Vit.B12


folic acid or intrinsic factor deficiency
DNA synthesis

erythroblast
Leukocytes ( white blood cells )
Our bodies have special system to defend against infecant agents,
including leukocytes and tissue cells from leukocytes

 Destroying viruses, bacteria by phagocytosis

 Inactivating the invader by antibodies or sensitized lymphocytes


General characteristics of Leukocyte

Granulocyte and monocyte


protect body against invading
organism by ingesting them
(phagocytosis)

granulocyte
Lymphocytes function in
connection with the immune
system
Granular Leukocytes
Neutrophils. 60 % - 70%.
Function: Cellular immunity by phagocytosis.
Eosinophils. 2-4%.
Function: Limit the action of
basophils in the rapid allergic
reactions, participate in the
immune response to parasites

Basophils, less than 1%,


Function: release heparin and
histamine that are responsible
for the allergic reaction.

urticaria asthma
Agranular Leukocytes
Monocytes. 3% - 8%.
Function: fixed tissue macrophages.

Lymphocytes. 20% - 40%


Function:
T (thymus dependent) lymphocytes,
responsible for the cellular immunity
or cell-mediated immunity
B lymphocytes, responsible for the
humoral immunity
■ Increase of WBC
● physiological

- Newborn Number is higher, 15×109/L, after birth 3 or 4 days to


3
months, mainly, neutrophil, 70%; secondarily, lymphocyte.
- Circadian changes Number of WBC is more in the afternoon
than in the morning.
- Food taking, ache and mood excitation: Number of WBC is
remarkably higher.
- Terminal pregnancy of female: during parturition, 34×109/L,
and after parturition 2~5 days, number return to original level.
- Heavy exercise and laboring
● pathological :

- Acute suppurative inflammation ;


- Chronic inflammation ;
- Parasitic disease 、 anaphylaxis 。
● Leukocyte Disorders
* Leukopenia lower than normal numbers of WBC`s

* Leukocytosis - often associated with infection


* Leukemias - more immature WBCs in blood
Platelets (thrombocytes)
(100-300)×109 / L
Structure: Colorless, non-nucleated, irregularly shaped,
minute cells, 1-4 µm in diameter.
Composition:
1. Glycoproteins cause adherence to collagen &
damaged endothelium in ruptured blood vessels.
2. Phospholipids accelerate the clotting reaction & are
precursors of thromboxane A2
3. Proteins. The major proteins of platelets are actin
& myosin, responsible for contraction of platelets. A
contractile protein called thrombosthenin is
responsible for clot retraction also. Other proteins
are;
i. von Willbrand factor—responsible for adherence of
platelets
ii. Fibrin stabilizing factor—a clotting factor
iii. growth factors such as PDGF—involved in repair of
damaged blood vessels.
4. Hormonal substances present in platelets are
adrenaline, 5HT(5-hydroxytryptamine also called
serotonin ) & histamine.
Function
Normally platelets are inactive & execute their
action only when activated.
1. Blood clotting. They produce intrinsic
prothrombin activator, a substance
responsible for onset of clotting.
2. Clot retraction. The fibrin clot is retracted
by contractile proteins present in platelets
cytoplasm.
3. Prevention of blood loss (hemostasis). By
three ways; i. 5HT cause the constriction of
blood vessels. ii. Their adhesive property
seal the damage in blood vessels. iii.
Platelet plug formation.
4. Repair of ruptured blood vessel. PDGF is
useful for the repair of endothelium
Hemostasis and blood coagulation
The Hemostasis means prevention of blood when a vessel
is ruptured, Hemostasis is achieved by several mechanisms

● Vascular constriction
● Formation of a platelet plug
● Formation of a blood clot as a result of blood coagulation
● Growth of fibrous tissue into the blood clot to close the
hole
in vessel permanently

1 2 3
Vasoconstriction

Tissue Factor
2. Formation of the Platelet Plug
 Platelets Adhere to the damaged vascular wall, such as
the collagen fibers and damaged endothelium.
3. Blood Coagulation
 The third stage for hemostasis is formation of the blood clot, which
is the production of a web of fibrin proteins that penetrates and
surrounds the platelet. Blood clots therefore contain platelets and
fibrin, trapped red blood cells. Finally, contraction of the
platelet mass in the process of clot retraction forms a more
compact and effective plug. Fluid squeezed from the clot as it
retracts is called serum, which is plasma without fibrinogen, the
soluble precursor of fibrin.
Vessel injured

collagen in
subendothe-
lium exposed to blood

5-HT platelet activated Coagulation


Vessel
(adhesion, Aggregation,
Temporary releasing)
platelet Plug activated
contraction TXA2

fibrin
Temporary platelet Plug platelet plug formation
formation

Tight platelet blood clot formation

Hemostasis progress
● General Mechanism of blood coagulation
i. In response to rupture of the vessel , a complex cascade of
chemical reactions is initiated. The net result is formation of a
complex of activated substance collectively called prothrombin
activator
ii. The prothrombin activator catalyzes the conversion of
prothrombin into thrombin
iii. The thrombin acts as an enzyme to convert fibrinogen into
fibrin fibers that enmesh platelets, blood cells, and plasma to
form the clot
 iv. The conversion of fibrinogen into fibrin may occur via
either of two pathways. (1) intrinsic pathway that begin
in the blood itself and (2) extrinsic pathway that begins
with trauma of the vascular wall and surrounding tissues
Coagulation cascade
Intrinsic system (surface contact) Extrinsic system (tissue damage)

XII XIIa Tissue factor

XI XIa

IX IXa VIIa VII

VIII VIIIa

X Xa
V Va

II IIa (Thrombin)
Fibrinogen Fibrin

Vitamin K dependant factors


Prevention of blood clotting in the normal vascular system
---intravascular anticoagulants
Limiting the clot formation & dissolving it after it is formed.
So defects in any of these natural anticoagulants & mechanisms can
cause hypercoagulability
●Endothelial Surface Factors.
Important factors for preventing the clotting in the normal
vascular systems
(1) the smoothness of the endothelial cell surface, which prevents
activation of the intrinsic clotting system;
(2) a layer of glycocalyx on the endothelium, which repels clotting
factors & platelets;
(3) a protein bound with the endothelial membrane named,
thrombomodulin binds with thrombin & remove it.
Thrombomodulin-thrombin complex also activates a
plasma protein called protein C
● Protein C
1. it acts as an anticoagulant by inactivating the factors
Va & VIIIa
2. blocking the combination of the factor Xa with
platelet
3. increasing the process of fibrinolysis due to
stimulating the release of plasminogen activators
Plasmin. A proteolytic
enzyme That is formed
from plasminogen in
blood plasma and
dissolves the fibrin in
blood clots. Also called
fibrinolysin.
Fibrinolysis
The fibrin formed within blood vessels is gradually dissolved to restore
the fluidity of the blood. The process of liquefaction or lysis of the fibrin
is called fibrinolysis.

Plasminogen Activator

Plasminogen Plasmin
Inhibitor

Fibrin and Fibrinogen Fibrin Degradation


Products (FDP)
Plasminogen
t-PA
PG

Plasmin
t-PA
FDPs
PG PL

Fibrin

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