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Haematology: Presented By: Prof - Mirza Anwar Baig
Haematology: Presented By: Prof - Mirza Anwar Baig
Haematology: Presented By: Prof - Mirza Anwar Baig
Haematology
1. Composition of blood
2. Functions of blood elements
3. Erythropoiesis and life cycle of RBC.
4. Synthesis of Haemoglobin
5. Leucopoiesis
6. Immunity: Basics and Types
7. Coagulation of blood
8. Blood groups
Learning outcomes
1.Describe the chemical composition of plasma
3
What is Blood ?
•Blood is a connective tissue. It provides one of the
means of communication between the cells of different
parts of the body and the external environment.
4
COMPOSITION OF BLOOD
6
Composition of Whole Blood
7 Figure 19.1b
Composition of Whole Blood
8 Figure 19.1c
9 Table 17.1
Erythrocytes – Red Blood Cells (RBCs)
• Oxygen-transporting cells
– 7.5 µm in diameter (diameter of capillary 8 –
10µm)
10
RBC Structure And Function
• Have no organelles or nuclei
• Can neither reproduce nor carry extensive metabolic activities.
• Hemoglobin in cytoplasm – oxygen carrying protein
– Each RBC has about 280 million hemoglobin molecules
• Biconcave shape – 30% more surface area
11
Routine assessments in clinical practice
• Erythrocyte count.
This is the number of erythrocytes per litre or per cubic millimetre
(mm3) of blood.
• Packed cell volume or haematocrit.
This is the volume of red cells in 1 litre or 1 mm3 of whole blood.
• Mean cell volume.
This is the average volume of cells, measured in femtolitres
(fl = 10-15 litre).
• Haemoglobin.
This is the weight of haemoglobin in whole blood, measured in
grams per 100 ml.
• Mean cell haemoglobin.
This is the average amount of haemoglobin in each cell, measured
in picograms (pg = 10-12 gram).
• Mean cell haemoglobin concentration.
This is the amount of haemoglobin in 100 ml of red cells.
12
RBC Life Cycle
1. Red blood cells live only about 120 days because of the
wear and tear their plasma membranes undergo as they
squeeze through blood capillaries.
15
Erythropoiesis
18
19
Destruction of erythrocytes
Ø The life span of erythrocytes is about 120 days and their
breakdown, or haemolysis, is carried out by phagocytic
reticuloendothelial cells.
Ø These cells are found in many tissues but the main sites of
haemolysis are the spleen, bone marrow and liver.
Ø As erythrocytes age, changes in their cell membranes make
them more susceptible to haemolysis.
Ø Iron released by haemolysis is retained in the body and reused
in the bone marrow to form haemoglobin. Biliverdin is formed
from the protein part of the erythrocytes.
Ø It is almost completely reduced to the yellow pigment bilirubin,
before it is bound to plasma globulin and transported to the liver.
Ø In the liver it is changed from a fat-soluble to a water-soluble
form before it is excreted as a constituent of bile.
20
Hemostasis
1. Vasoconstriction.
i. When platelets come in contact with a damaged blood vessel,
their surface becomes sticky and they adhere to the damaged wall.
21
3. Coagulation (blood clotting).
Blood coagulation refers to the process of forming a clot
to stop bleeding.
Ø This is a complex process that also involves a positive
feedback system.
Ø Their numbers represent the order in which they were
discovered and not the order of participation in the
clotting process.
Ø These factors activate each other and known as the
clotting cascade.
Ø Blood clotting results in formation of an insoluble
thread-like mesh of fibrin which traps blood cells and is
much stronger than the rapidly formed platelet plug.
Ø In the final stages of this process prothrombin activator
acts on the plasma protein prothrombin converting it to
thrombin.
22
Hemostasis:
•The clotting cascade occurs through two separate
pathways that interact, the intrinsic and the extrinsic
pathway.
1. Extrinsic Pathway:
The extrinsic pathway is activated by external trauma
that causes blood to escape from the vascular system.
This pathway is quicker than the intrinsic pathway. It
involves factor VII.
2. Intrinsic Pathway:
The intrinsic pathway is activated by trauma inside the
vascular system, and is activated by platelets, exposed
endothelium, chemicals, or collagen. This pathway is
slower than the extrinsic pathway, but more important.
It involves factors XII, XI, IX, VIII.
3. Common Pathway:
Both pathways meet and finish the pathway of clot
production in common pathway. The common pathway
involves factors I, II, V, and X.
24
Coagulation Pathway:
4 Positive
chemotaxi
Inflammator s
y chemicals
diffusing
from the
inflamed
site act as
1 Neutrophils chemotactic
enter blood agents
from bone 3 Diapedesis
marrow 2 Marginatio
n
Endothelium
Capillary wall
Basal lamina
Figure
44
21.3
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Flowchart of Events in Inflammation
Figure
45
21.2
4. Antimicrobial Proteins
Figure
55
21.6
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Cells of the Adaptive Immune System
• Secreted antibodies:
– Bind to free antigens
– Mark the antigens for destruction by
specific or nonspecific mechanisms
• Clones that do not become plasma
cells become memory cells that can
mount an immediate response to
subsequent exposures of the same
antigen
Figure
76
21.11
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Antibodies
Figure 21.12a,
80
b
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Antibody Structure
Figure
92
21.14
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Importance of Humoral Response
• Soluble antibodies
– The simplest ammunition of the immune
response
– Interact in extracellular environments such
as body secretions, tissue fluid, blood, and
lymph
Figure9821.15a
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Class II MHC Proteins
Figure
107
21.16
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
T Cell Activation: Step Two – Co-stimulation
• Examples include:
– Perforin and lymphotoxin – cell toxins
– Gamma interferon – enhances the killing
power of macrophages
– Inflammatory factors
Figure 21.17a
116
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Helper T Cell
Figure 21.17b
118
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Cytotoxic T Cell (Tc)
Figure
124
21.19
COMPILED BY: PROF.ANWAR BAIG
(AIKTC,SOP)
Blood group
125
Anaemias
In anaemia there is not enough haemoglobin available to
carry sufficient oxygen from the lungs to supply the needs
of the tissues. It occurs when the rate of production of
mature cells entering the blood from the red bone marrow
does not keep pace with the rate of haemolysis.
126
Signs and symptoms of anaemia:
Tachycardia
Palpitations (an awareness of the heartbeat)
Angina pectoris
Breathlessness on exertion
127
1. Iron deficiency anaemia
This is the most common.
The normal daily requirement of iron intake in men is
about 1 to 2 mg derived from meat and highly coloured
vegetables. The normal daily requirement in women is 3 mg.
The increase is necessary to compensate for loss of blood
during menstruation and to meet the needs of the growing
fetus during pregnancy.
Children, during their period of rapid growth, require more
than adults.
The anaemia is regarded as severe when the haemoglobin
level is below 9 g/dl blood.
It is caused by deficiency of iron in the bone marrow and
may be due to dietary deficiency,excessively high requirement
or malabsorption.
128
2. Megaloblastic anaemias
1.Maturation of erythrocytes is impaired when deficiency of vitamin B12
and/or folic acid occurs and abnormally large erythrocytes
(megaloblasts) are found in the blood.
3.When deficiency of vitamin B12 and/or folic acid occurs, the rate of
DNA and RNA synthesis is reduced, delaying cell division.
4.The cells can therefore grow larger than normal between divisions.
Circulating cells are immature, larger than normal and some are
nucleated (MCV >94 fl).
ii. Since the bone marrow produces leukocytes and platelets as well
as erythrocytes, leukopenia (low white cell count) and
thrombocytopenia (low platelet count) are likely to accompany
diminished red cell numbers.
iii. When all three cell types are low, the condition is called
pancytopenia, and is accompanied by anaemia, diminished
immunity and a tendency to bleed.
130
Known causes include:
131
4. Vitamin B12 deficiency anaemia
a. Pernicious anaemia
This is the most common form of vitamin B12 deficiency
anaemia.
It occurs more often in females than males, usually between 45
and 65 years of age.
It is an autoimmune disease in which auto-antibodies destroy
intrinsic factor (IF) and parietal cells in the stomach.
132
Other causes of vitamin B12 deficiency
i. Gastrectomy — this leaves fewer cells available to produce IF
after partial resection of the stomach.
iii. Blind loop syndrome — this occurs when the contents of the
small intestine are slow moving or static, allowing microbes to
colonise the small intestine and use or destroy the intrinsic
factor-vitamin B12 (IF-B12) complex before it reaches the
terminal ileum where it is absorbed.
133
Complications of vitamin B12 deficiency
anaemia
These may appear before the signs of anaemia. They
include:
134
Haemolytic anaemias
These occur when red cells are destroyed while in circulation or are removed
prematurely from the circulation because the cells are abnormal or the spleen is
overactive.
1.Congenital haemolytic anaemias:
Sickle cell anaemia
Thalassaemia
Haemolytic disease of the newborn
2. Acquired haemolytic anaemia
Chemical agents
Autoimmunity
Blood transfusion reactions
Other causes of haemolytic anaemia
eg: Parasitic diseases, e.g. malaria
Ionising radiation, e.g. X-rays, radioactive isotopes
Destruction of blood trapped in tissues in, e.g., severe
burns, crushing injuries
Physical damage to cells by, e.g., artificial heart valves, kidney
dialysis machines.
135
Normocytic normochromic anaemia
1.In this type the cells are normal but the numbers are
reduced.
2.The proportion of reticulocytes in the blood may be
increased as the body tries to restore erythrocyte numbers
to normal.
3.This occurs:
• In many chronic disease conditions, e.g. in chronic
inflammation following severe haemorrhage in
haemolytic disease.
136
Congenital haemolytic anaemias
In these diseases genetic abnormality leads to the synthesis of abnormal
haemoglobin and increased red cell membrane friability, reducing cell
oxygen-carrying capacity and life span.
The most common forms are sickle cell anaemia and thalassaemia.
a. Sickle cell anaemia:
1.The abnormal haemoglobin molecules become misshapen.
2.When deoxygenated, making the erythrocytes sickle shaped.
3.A high proportion of abnormal molecules makes the sickling permanent.
4.The life span of cells is reduced by early haemolysis.
5.Sickle cells do not move smoothly through the small blood vessels.
6.This tends to increase the viscosity of the blood, reducing the rate of
blood flow and leading to intravascular clotting,ischaemia and infarction.
7.The anaemia is due to early haemolysis of irreversibly sickled cells.
8.Blacks are more affected than other races.
9.Some affected individuals have a degree of immunity
to malaria because the life span of the sickled cells is
less than the time needed for the malaria parasite to
mature inside the cells.
137
b. 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. This
condition is most common in Mediterranean countries.
138
139
Polycythaemia
There are an abnormally large number of erythrocytes in
the blood.
This increases blood viscosity, slows the rate of flow and
increases the risk of intravascular clotting, ischaemia and
infarction.
140
Ø This occurs in people living at high altitudes where
the oxygen tension in the air is low and the partial
pressure of oxygen in the alveoli of the lungs is
correspondingly low.
Ø Each cell carries less oxygen so more cells are needed
to meet the body's oxygen needs
a. Polycythaemia Pathological.
141
b. Polycythaemia rubra vera
In this primary condition of unknown cause there is
abnormal excessive production of the erythrocyte
precursors, i.e.myeloproliferation.
142
LEUKOCYTE DISORDERS
• Leukopenia --Granulocytopenia (neutropenia)
• Leukocytosis
• Leukaemia
143
1.Leukopenia
This is the name of the condition in which the total blood
leukocyte count is less than 4000/mm3.
a. Granulocytopenia (neutropenia)
i. This is a general term used to indicate an abnormal
reduction in the numbers of circulating granulocytes
(polymorphonuclear leukocytes), commonly called
neutropenia because 40 to 75% of granulocytes are
neutrophils.
ii. A reduction in the number of circulating granulocytes
occurs when production does not keep pace with the
normal removal of cells or when the life span of the cells
is reduced.
iii. Extreme shortage or the absence of granulocytes is
called agranulocytosis. A temporary reduction occurs in
response to inflammation but the numbers are usually
quickly restored.
144
Inadequate granulopoiesis may be caused by:
1. Drugs, e.g. cytotoxic drugs, phenylbutazone, phenothiazines,
some sulphonamides and antibiotics
2. Irradiation damage to granulocyte precursors in the bone marrow
by, e.g., X-rays, radioactive isotopes
3. Diseases of red bone marrow, e.g. leukaemias, some anaemias
4. Severe microbial infections.
5. In conditions where the spleen is enlarged, excessive numbers of
granulocytes are trapped, reducing the number in circulation.
145
Leukocytosis
i. An increase in the number of circulating leukocytes
occurs as a normal protective reaction in a variety of
pathological conditions, especially in response to
infections.
ii. When the infection subsides the leukocyte count returns
to normal.
iii.Pathological leukocytosis exists when a blood leukocyte
count of more than 11000/mm3 is sustained and is not
consistent with the normal protective function.
146
Leukaemia
•Leukaemia is a malignant proliferation of white blood
cell precursors by the bone marrow.
•A malignant progressive disease in which the bone
marrow and other blood-forming organs produce increased
numbers of immature or abnormal leucocytes. These
suppress the production of normal blood cells, leading to
anaemia and other symptoms.
•It results in the uncontrolled reduction of leukocytes
and/or their precursors.
•As the tumour cells enter the blood the total leukocyte
count is usually raised but in some cases it may be normal
or even low.
•The proliferation of immature leukaemic blast cells crowds
out other blood cells formed in bone marrow, causing
anaemia,thrombocytopenia and leukopenia (pancytopenia).
147
Causes of leukaemia
Ionising radiation.
Radiation such as that produced by X-rays and radioactive
isotopes causes malignant changes in the precursors of white
blood cells. The DNA of the cells may be damaged and some
cells die while others reproduce at an abnormally rapid rate.
Leukaemia may develop at any time after irradiation, even
20 or more years later.
Chemicals.
Some chemicals encountered in the general or work
environment alter the DNA of the white cell precursors in
the bone marrow. These include benzene and its derivatives,
asbestos, cytotoxic drugs, chloramphenicol.
Viral infections.
Genetic factors. Identical twins of leukaemia sufferers have a
much higher risk than normal of developing the disease,
suggesting involvement of genetic factors.
148
149
Types of leukaemias
Acute leukaemias
Ø These types usually have a sudden onset and affect
the poorly differentiated and immature 'blast' cells .
Ø They are aggressive tumours that reach a climax
within a few weeks or months. The rapid progress of
bone marrow invasion impairs its function and
culminates in anaemia, haemorrhage and susceptibility
to infection.
Ø The mucous membranes of the mouth and upper
gastrointestinal tract are most commonly affected.
Acute myeloblastic leukaemia. This occurs at any
age, but most commonly between 25 and 60 years.
Acute lymphoblastic leukaemia. This disease is most
common in children under 10 years, although a number
of cases may occur up to about 40 years of age.
150
Chronic leukaemias
These conditions are less aggressive than the acute forms and the
leukocytes are more differentiated, i.e. at the 'cyte' stage.
Chronic granulocytic leukaemia. There is a gradual increase in
the number of immature granulocytes in the blood. In the later stages,
anaemia, secondary haemorrhages, infections and fever become
increasingly severe.
It is slightly more common in men than women and usually occurs
between the ages of 20 and 40 years. Although treatment may
appear to be successful, death usually occurs within about 5 years.
Chronic lymphocytic leukaemia.
There is enlargement of the lymph nodes and hyperplasia of
lymphoid tissue throughout the body. The lymphocyte count is
considerably higher than normal. Lymphocytes accumulate in the
bone marrow and there is progressive anaemia and
thrombocytopenia.
It is three times more common in males than females and it occurs
mainly between the ages of 50 and 70 years. Death is usually due to
repeated infections of increasing severity, with great variations in
survival times.
151
Thrombocytopenia
This is defined as a blood platelet count below (150 000/mm3) but
spontaneous capillary bleeding does not usually occur unless the
count falls below (30 000/mm3).
It may be due to a reduced rate of platelet production or increased
rate of destruction.
Reduced platelet production
This is usually due to bone marrow deficiencies, and therefore
production of erythrocytes and leukocytes is also reduced, giving rise
to pancytopenia. It is often due to:
Ø Platelets being crowded out of the bone marrow in bone marrow
diseases, e.g. leukaemias, pernicious anaemia, malignant tumours
Ø Ionising radiation, e.g. X-rays or radioactive isotopes,that damage
the rapidly dividing precursor cells in the bone marrow
Ø Drugs, e.g. cytotoxic drugs, chloramphenicol,chlorpromazine,
phenylbutazone, sulphonamides.
Increased platelet destruction A reduced platelet count occurs
when production of new cells does not keep pace with destruction of
damaged and worn out cells.
152
Autoimmune thrombocytopenic purpura.
• This condition, which usually affects children and young
adults,
• may be triggered by a viral infection such as measles.
• Antiplatelet antibodies are formed that coat platelets,
• leading to platelet destruction and their removal from
• the circulation.
• A significant feature of this disease is the presence of
purpura, which are haemorrhages into the skin ranging in
size from pinpoints to large blotches.
• The severity of the disease varies from mild bleeding into
• the skin to severe haemorrhage. When the platelet count
• is very low there may be severe bruising, haematuria,
• gastrointestinal or cranial haemorrhages.
153
Secondary thrombocytopenic purpura.
This may occur in association with red bone marrow
diseases,
excessive irradiation and some drugs, e.g. digoxin,
chlorthiazides, quinine, sulphonamides.
154