BLOOD AND BLOOD

FORMING ORGANS

Presented
by:
Dr.Esther
priyadarshini

CONTENTS
INTRODUCTION
PROPERTIES OF BLOOD
COMPOSITION OF BLOOD
PLASMA
BLOOD CELLS
FORMATION OF BLOOD CELLS
RED BLOOD CELLS
WHITE BLOOD CELLS
PLATELETS
BLOOD COAGULATION
BLOOD GROUPS

INTRODUCTION

Blood is a fluid connective tissue

It is considered as fluid of life because it carries oxygen

from lungs to all parts of the body and cabondioxide
from all parts of the body to lungs

Fluid of growth - it carries nutritive substances from

digestive system & hormones from endocrine glands to
all the tissues

Fluid of health- protects the body against the diseases

PROPERTIES OF BLOOD
COLOUR - Blood is RED in
colour
VOLUME - Average volume
of blood in a normal
individual is 5L
New borns 450ml
Females it is slightly less
4.5L
It is 8% of the body weight
in a normal individual
weighing about 70 kg

Blood is slightly alkaline with pH 7.4

Specific gravity of blood is 1.052-1.061

VISCOSITY - 5 times more viscous than water, mainly

due to RBCs & plasma proteins

FORMATION OF BLOOD CELLS

HEMOPOIESIS is the process by which the mature

blood cells develop from the precursor cells

It includes erythropoiesis , leukopoiesis and

thrombopoiesis

HEMOPOIESIS is initiated in the early embryonic

development

During fetal life , both erythrocytes and leukocytes are

formed in several organs before the differentiation of
bone marrow

1) First or yolk sac phase of hemopoiesis: Begins in the 3rd

week of gestation

Characterized by the formation of blood islands in the wall

of yolk sac of embryo

2) Second or hepatic phase: in the 3rd month of IU life

Hemopoietic centres appear in the liver & spleen

Liver is the major blood forming organ in the second

trimester

3)Third or Bone marrow phase: as the bones develop

during 5th month of IU life hemopoiesis begins in the
bone marrow

By birth hemopoiesis is almost exclusive to the bone

marrow although liver and spleen may resume the
activity in times of need

In adults hemopoiesis takes place in the bone marrow

mainly of skull, ribs, sternum, vertebral column, pelvis
and proximal ends of long bones

BONE MARROW

Highly vascular tissue

found in medullary
cavities of long bones &
trabecular spaces of
spongy bone

It consists of meshwork
of vascular sinuses and
fibroblasts with the
interstices packed with
hemopoietic cells

10

Red bone marrow- active

bone marrow

Consists of dividing stem

cells & the precursors of
maturing blood cells

Predominance of maturing
erythrocytes conferring a deep
red color hence the name
RED BONE MARROW
11

Yellow bone marrow : With increasing age , marrow of

long bones become less active and is progressively
dominated by fat cells

Yellow in color hence called yellow bone marrow

Reactivated when need arises for increased hemopoiesis

12

COMPOSITION OF BLOOD

Blood is composed of
LIQUID PLASMA and
FORMED ELEMENTS

Formed elements include

RED BLOOD CELLS OR
ERYTHROCYTES
WHITE BLOOD CELLS
OR LEUCOCYTES
PLATELETS OR
THROMBOCYTES
13

HEMATOCRIT VALUE

If the blood is collected in a hematocrit tube along with a

suitable anticoagulant and centrifuged for 30min at the
speed of 3000rpm, the red blood cells settle down at the
bottom having a clear plasma at the top

Plasma
(55% of whole blood
Buffy coat:
leukocyctes and platelets
(<1% of whole blood)

Withdraw
blood and
place in tube

Centrifuge

Erythrocytes
(45% of whole
blood)

14

Plasma forms 55% and the red

blood cells form 45% of total
blood

The volume of red blood cells

expressed in percentage is called
the HEMATOCRIT VALUE or
PACKED CELL VOLUME

In between the plasma and the red

blood cells there is a thin layer of
white buffy coat,formed by the
aggregation of WBCs and
platelets

15

PLASMA

Intercellular substance of blood is liquid called plasma in

which blood cells are suspended

Plasma is a straw coloured clear liquid

It contains 91-92% of water and 8-9% of solids

The solids are the organic and the inorganic substances

16

Organic substances include- Plasma proteins

carbohydrates
amino acids
fats
enzymes

Inorganic substances include electrolytes like sodium,

potassium,calcium,magnesium,bicarbonate,chloride,
phosphate

Gases like Oxygen,carbondioxide,nitrogen

17

PLASMA PROTEINS

Plasma proteins are - ALBUMIN

GLOBULIN
FIBRINOGEN

The normal values of plasma proteins are

Total proteins-7.3 g/dl
Albumin
- 4.7g/dl
Globulin
- 2.3g/dl
Fibrinogen
- 0.3g/dl

18

ALBUMIN /GLOBULIN RATIO

The ratio between plasma level of albumin and globulin

is called albumin/globulin ratio

It is an important indicator of some diseases involving

liver and kidney

Normal A/G ratio is 2:1

19

ALBUMIN

Main protein constituent of plasma

Smallest plasma protein 70 kilodaltons

Produced in the liver

It is responsible for exerting the concentration gradient

between blood and extracellular tissue fluid , this is called
the COLLOID OSMOTIC PRESSURE

It also acts as a carrier protein, it binds harmones, bilirubin,

drugs

20

GLOBULIN

Globulins include -

Immunoglobulins (- globulins)

Immunoglobulins are antibodies secreted by plasma cells

Non immune globulins( & globulins)

Non immune globulins are secreted by liver
They maintain the osmotic pressure within the vascluar
system
They serve as carrier proteins for substances such as
copper (by ceruloplasmin), iron (by transferrin), and
hemoglobin (by haptoglobin)

21

FIBRINOGEN

Is the largest plasma protein (340 kilodaltons)

It is produced in the liver

In a series of cascade reactions with other coagulation

factors ,soluble fibrinogen is transformed into fibirn (323
kilodaltons)

22

SERUM

It is a clear straw colored fluid that is left after the blood

has clotted

Fibrinogen is converted into fibrin

After about 45min, straw colored serum oozes out of the

blood clot

It is different from plasma only by the absence of

FIBRINOGEN

Serum = plasma - fibrinogen

23

RED BLOOD CELLS

RBCs are the non

nucleated formed elements
in the blood

Also known as Erythrocytes

( erythros = red)

Red color - pigment

hemoglobin

Vital role in the transport of

respiratory gases

24

ERYTHROPOIESIS

Erythropoiesis is the process of the origin, development

and maturation of ERYTHROCYTES

Bone marrow is the site for production of all blood cells

comparitively 75% of bone marrow is involved in the
production of leucocytes & 25% is involved in the
production of erythrocytes

But still leucocytes are less in number than erythrocytes

Mainly because of life span of these cells

25

STEM CELLS

Stem cells are the primary cells capable of self renewal and
differentiating into specialized cells

Hemopoietic stem cells are primitive cells in the bone marrow which
give rise to blood cells

Hemopoietic stem cells in the bone marrrow are called

uncommitted pluripotent hemopoietic stem cell (PHSC)

PHSC is defined as a cell which can give rise to all types of blood
cells

In early stages PHSC are not designed to form a particular type of

cell hence the name UNCOMMITTED PHSC

26

When the cells are designed to form a particular cell type

they are called COMMITTED PHSC

Restricted to give rise to one group of blood cells

Committed PHCS are of two types:

1)LYMPHOID STEM CELLS which give rise to
lymphocytes and natural killer (NK) cells
2)COLONOY FORMING BLASTOCYTES- which give
rise to myeloid cells

Myeloid cells are the blood cells other than lymphocytes

27

When grown in culture these cells form colonies hence the

name COLONY FORMING BLASTOCYTES

Different units of colony forming cells are:

i) Colony Forming Unit- Erythrocytes (CFU-E)--- cells of

this unit develop into erythrocytes

ii)Colony Forming Unit Granulocytes/Monocytes (CFUGM )----cells of this unit develop into granulocytes and
monocytes

iii) Colony Forming Unit-Megakaryocytes (CFU-M)---platelets are developed from these cells

28

CHANGES DURING ERYTHROPOIESIS

The cells of CFU-E pass through different stages and

finally become the matured RBCs .

During these stages four important changes are noticed:

1)Reduction in the size of the cell
2)Disappearance of nucleoli and nucleus
3)Appearance of hemoglobin
4)Change in the staining properties of the cytoplasm

29

STAGES OF ERYTHROPOIESIS

The various stages

between CFU-E cells
and matured RBC
are
1)Proerythroblast
2)Early normoblast
3)Intermediate
normoblast
4)Late normoblast
5)Reticulocyte
6)Matured
erythrocyte

30

PROERYTHROBLAST(MEGALOBLAST)
Is the first cell derived from CFU-E
Large in size with diameter of 20
Nucleus is large ,occupies the cell almost completely
Nucleus has two or more nucleoli
Does not contain hemoglobin
Cytoplasm is basophilic

31

EARLY NORMOBLAST / ERYTHROBLAST

It is smaller than proerythroblast with diameter of about
15
Condensation of chromatin network occurs
Cytoplasm is basophilic in nature because of large
number of ribosomes
This cell is also called basophilic erythroblast

32

INTERMEDIATE NORMOBLAST
Smaller than the early normoblastwith diameter 10-12
Nucleus is still present
Chromatin network shows further condensation
Hemoglobin starts appearing
Cytoplasm is already basophilic, because of the presence
of hemoglobin, it stains with both acidic as well as basic
stains
This cell is called polychromatophilic erythroblast

33

LATE NORMOBLAST
The diameter of the cell decreases further to about 8-10

Nucleus becomes very small , very much condensed

chromatin network

Quantity of hemoglobin increases

Cytoplasm becomes acidophilic, cell is now called

orthochromic erytroblast

34

In the final stage of late normoblast just before it passes

to the next stage , the nucleus disintegrates and
disappears
The final remnant is extruded from the cell
Late normoblast develops into next stage called
RETICULOCYTE

35

RETICULOCYTE
Othewise known as immature RBC

Slightly larger then the mature RBC

Cytoplasm contains reticular network which is formed by

remnants of disintgrated organelles, hence the name
reticulocyte

In new borns the reticulocyte count is 2-6% of RBCs

Reticulocyte count decreases during the first week after birth

36

Reticulocytes still retain residual nuclear material

They also contain mitochondria , ribososmes and golgi

elements to complete the cytoskeleton and hemoglobin
synthesis

37

Reticulocytes cannot normally be seen in routinely

stained blood smears
A special procedure is performed in which fresh blood
sample is incubated with the basic dye, brilliant cresyl
blue
A blue stained reticular precipitate is formed in the
reticulocyte due to the interaction of the dye with RNA
remnants
This technique is called supravital staining

38

MATURED ERYTHROCYTES
The reticular network disappears and the cell becomes
matured RBC and attains BICONCAVE SHAPE

The cell decreases in size to 7.2 diameter

The matured RBC is with HEMOGLOBIN and without

nucleus

39

It requires seven days for the development and

maturation of RBC from PROERYTHROBLAST

It requires 5 days upto the stage of reticulocyte

Reticulocytes take 2 or more days to become mature

RBC

40

FACTORS NECESSARY FOR ERYTHROPOIESIS

ERYTHROPOEITIN

HEMOPOEITIC GROWTH FACTORS

THYROXINE

VITAMINS

41

ERYTHROPOIETIN

Also called hemopoietin or erythrocyte stimulating

factor

Its is a glycoprotein with 165 amino acids

Source of secretion: secreted by the peritubular

capillaries of kidney

Also secreted in liver and brain

42

ERYTHROPOIETIN MECHANISM
Imbalance

Normal blood oxygen levels

Imbalance

Increases
O2-carrying
ability of blood

Enhanced
erythropoiesis
increases RBC count

Stimulus: Hypoxia due to

decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2

Reduces O2
levels in blood

Erythropoietin
stimulates red
bone marrow

Kidney (and liver to

a smaller extent)
releases
erythropoietin

43

HEMOPOIETIC GROWTH FACTORS

Are the interleukins and stem cell factors

Induces the proliferation of PHSCs

Interleukins involved in erythropoiesis are:

1)Interleukin-3 secreted by T-cells
2)Interleukin-6 secreted by T-cells ,endothelial cells &
macrophages
3) Interleukin -11 secreted by osteoblasts

44

THYROXINE
Thyroxine accelerates the process of erythropoiesis
Polycythemia is common in hyperthyroidism

VITAMINS
Vitamin B12 , Intrinsic factor and Folic acid are
necessary for the maturation of RBCs

45

Normal value

RBC count ranges between 4 and 5.5 millions per cubic

mm of blood

Adult males - 5 millions / cu mm

Adult females 4.5 millions/cu mm

46

MORPHOLOGY OF RED BLOOD CELLS

Normal shape

RBCs are disc like and

biconcave in shape

The central portion is thinner

and the periphery is thicker

Biconcave shape-RBCs
squeeze through the
capillaries easily without
getting damaged

47

Normal size

Diameter 7.5

Thickness periphery 2
centre - 1

Difference in the thickness is

because of biconcave shape

48

RBC has a special type of

cytoskeleton which is made
up of actin and spectrin

Both the proteins are

anchored to transmembrane
proteins by means of
another protein called
ankyrin

49

ROULEAUX FORMATION

When blood is taken out of

the blood vessel, the RBC,s
pile up one above the other
like pile of coins

This property of the RBCs is

called ROULEAUX
formation

It is accelerated by plasma
proteins globulin and
fibrinogen

50

HEMOGLOBIN
Hemoglobin is the iron containing coloring pigment of
RBCs
Carries respiratory gases
Molecular weight of hemoglobin is 68,000

51

STRUCTURE OF HEMOGLOBIN

Hemoglobin is a conjugated protein

It consists of protein with an iron containing pigment

Protein- globin

Iron containing pigment - heme

52

Complex quaternary
structure

Globin is a protein
composed of 4 parallel
layers of closely packed
polypeptide chains
2 alpha (141 Aa)
2 beta (146Aa)

53

Pigment part of heme is

Porphyrin

Heme is a tetrapyrrole
structure with 1 Fe
attached to 4 nitrogen
atoms from 4 pyrrole rings

1 heme &1 globin 1unit

4 units form 1 Hb molecule

54

TYPES OF NORMAL HEMOGLOBIN

Hemoglobin is of two types

1) Adult hemoglobin - HbA

2) Fetal hemoglobin- HbF

Replacement of fetal hemoglobin by adult hemoglobin

starts immediately after birth .

Completed at about 10th to 12th week after birth

55

Adult hemoglobin - 2 alpha & 2 beta chains

Fetal hemoglobin- 2 alpha & 2 gamma chains

Fetal hemoglobin has more affinity for oxygen than adult

hemoglobin

56

NORMAL HEMOGLOBIN CONTENT

Average Hb content is 14 -16 g/dl

Age
At birth : 25g/dl
After 3rd month: 20g/dl
After 1 yr: 17g/dl
From puberty: 14-16g/dl

Sex
In adult male : 14-17g/dl
In adult femle : 12-16 g/dl

57

Life span of RBCs

Average lifespan of RBC is about 120 days

After the lifetime the senile RBCs are destroyed in

reticuloendothelial system

58

FATE OF RED BLOOD CELLS

When the cells become older the cell becomes more

fragile

Older cells are destroyed while trying to squeeze through

capillaries

Occurs mainly in the capillaries of red pulp of spleen

SPLEEN is called GRAVE YARD of RBCs

59

Destroyed RBCs are fragmented & hemoglobin is

released

Hemoglobin is immediately phagocytized by

macrophages , particularly present in liver ( kuffer
cells),spleen and bone marrow

60

Hb is degraded into
iron, globin ,
porphyrin (heme)

Iron combines with

protein called apoferritin
to form ferritin, which is
stored in the body and
reused later

Globin- Globin is
metabolized into amino
acids and is released
into the circulation

61

Heme is degraded to a
yellow pigment called
bilirubin

The liver secretes bilirubin

into the intestines as bile

The intestines metabolize it

into urobilinogen

This degraded pigment

leaves the body in feces, in
a pigment called stercobilin

62

VARIATIONS IN NUMBER OF RBCS

Physiological variations
Increase in RBC count
Age
Sex
High altitude
Muscular exercise
Emotional conditions

Decrease In RBC count

High barometric pressure
During sleep

pregnancy

63

Pathological variations

Increase in RBC count

Primary polycythemia

Decrease in RBC count

Secondary polycythemia

Anemia

64

ERYTHROCYTE SEDIMENTATION RATE

ESR is the rate at which the erythrocytes settle down

If blood is mixed with an anticoagulant and allowed to

stand on a vertical tube,red blood cells settle down due
to gravity with a supernatant layer of clear plasma

Two methods are used to determine ESR

1)Westergrens method
2)Wintrobes method
65

NORMAL VALUES OF ESR

Two methods:
1) Westergren method: commonly used
Normal values: Male: 3 - 5mm/hr
7 - 15mm/2hrs
Female: 4 - 8mm/hr
12 - 17mm/2hrs
2) Wintrobes method:
Male: 0-9mm/hr
Female: 0-20mm/hr
66

ESR - Increase:

physiological conditions: Pregnancy

Menstruation
Old age
After a meal

Pathological conditions: Infections like TB

Rheumatoid arthritis
Malignancy
albumin conc

67

SIGNIFICANCE OF ESR

It is an easy, inexpensive & non specific test which helps

in diagnosis &prognosis of a disease

It is non specific because it cannot indicate the exact

location or cause of the disease

It is helpful in assessing the progress of patients treated

for certain chronic inflammatory disorders such as
1)Pulmonary tuberculosis
2)Rheumatoid arthritis
68

WHITE BLOOD CELLS

WHITE BLOOD CELLS or LEUCOCYTES are the

colorless and nucleated formed elements of blood

Leukos= white or colorless

Leucocytes play very important role in the defence

mechanism of body and protect the body from invading
organisms

69

WBCs differ from RBCs in many aspects

Larger in size
Irregular in shape
Nucleated
Many types
Granules are present in some types of WBCs
Life span is shorter
They do not contain hemoglobin

70

CLASSIFICATION

Some of the WBCs have granules in the cytoplasm

Based on the presence or absence of granules in the

cytoplasm leucocytes are classified as

GRANULOCYTES
1)Neutrophils
2)Eosinophils
3)Basophils
AGRANULOCYTES
1)monocytes
2)lymphocytes

71

LEUCOPOIESIS

Leucopoiesis is the
development and
maturation of leucocytes

Colony Forming Unit

CFU-GM gives rise to
myeloid stem cell

Myeloid stem cells gives

rise to myeloblast
72

Myeloblast gives rise to

promyelocyte

The next stage in

differentiation is
myelocyte, marked by the
development of specific
granules

The process continues

through 3 cell divisions
73

From myelocyte to
metamyelocyte to mature
granulocyte nucleus
becomes segmented

The immediate precursors

of mature granulocytes tend
to have an irregular horse
shoe or ring shaped
nucleus called band forms
74

MORHOLOGY OF WHITE BLOOD CELLS

NEUTROPHILS

Neutrophils constitute 40-75%

of circulating leucocytes

Are also known as

POLYMORPHS

Most prominent feature is

highly lobulated nucleus

Lobes are connected by fine

strands of nuclear material

75

Number of lobes in the nucleus depends upon the age of

the cell

In younger cells nucleus is not lobulated

In older neutrophils nucleus has 2-5 lobes

76

Neutrophils contain three types of granules in their

cytoplasm
1)Primary granules
2)Secondary granules
3)Tertiary granules

77

Primary granules:

These are the first granules to appear during neutrophil

differentiation

They are not simply modified lysosomes ,these granules

contain a number of microbial agents including
myeloperoxidase and neutrophil defensins

Mainly contribute to the killing & degradation of

engulfed micro organisms rather than secreting contents

78

Secondary granules:

Most numerous granules in the cytoplasm

Also termed as specific granules

Smaller than primary granules

Rich in antimicrobial substances and contain lysozyme,

gelatinase,collagenase

79

Tertiary granules:
Also termed as gelatinase granules

Mainly secrete enzymes to degrade the tissues

Contain gelatinase which break down the extracellular

matrix
Neutrophils also contain secretory granules which act
as reservoir of memebrane associated receptors needed
for neutrophil function in acute inflammation

80

Granules of neutrophils take both acidic and basic stains

When stained with Leishmans stain the granules appear

violet in color

Neutrophils are motile cells moving in a crawling

fashion with undulating psuedopodium

Help in phagocytosis
81

PATHOLOGOICAL VARIATIONS

NEUTROPHILIA

Increase in neutrophil count

1)Acute infections

NEUTROPENIA

Decrease in neutrophil count

1)Bone marrow disorders

2)Metabolic disorders
3)Poisoning by chemicals and
drugs like lead, mercury
&benzene derivatives
4)Acute hemorrhage

2)Tuberculosis
3)Typhoid
4)Autoimmune disesases

82

EOISNOPHILS

Eosinophils account for 2-6% of

leucocytes in circulating blood

Eosinophil(12-17) in diameter
and is larger than neutrophil

It is easily recognised by its large

specific granules in the cytoplasm,
which are coarse and stain red
with eosin

Nucleus is typically bilobed and

spectacle shaped

83

The specific granules of eosinophils contain a crystalloid

body that is readily seen with TEM surrounded by a less
electron dense matrix

They contain four major proteins

i) An arginine rich protein called major basic protein

(MBP) which accounts for the intense acidophilia of the
granule
ii) Eosinophil cation protein
iii)Eosinophil peroxidase
iv)Eosinophil derived neurotoxin

84

Specific granules also

contain histaminase

Smaller granules in the

mature eosinophils contain
aryl sulphatase and acid
phosphatase

Eosinophils are associated

with allergic reactions,
parasitic infections
85

PATHOLOGICAL VARIATIONS

Eosinophilia

Asthma & other allergic

conditions
Malaria ,filariasis
Scarlet fever

Eosinopenia

Cushings syndrome
Bacterial infections

Stress

Prolonged administration of steroids

86

BASOPHILS

Are the least common leucocyte and

constitute less than 1% of leucocytes in
circulating blood

They are characterised by large intense

basophilic cytoplasmic granules and
share many structural and functional
similarities with mast cells

It is 14-16m in diameter, intermediate in

size between neutrophil and eosinophil

Nucleus is bilobed usually obscured by

large densely basophilic specific granules

87

Specific granules contain heparin, histamin ,heparan

sulphate

Intense basophilia of these granules correlates with the

high concentration of sulfates in heparin and heparan
sulfate

88

PATHOLOGICAL VARIATIONS
Basophilia
Chicken pox
Small pox
Polycythemia vera

Basopenia

Urticaria

Stress

Prolonged exposure to chemotherapy or radiation

therapy

89

MONOCYTES

Largest of the white blood cells

measures upto 20 in diameter

Constitute 2-10% of leucocytes

in peripheral blood

Characterised by large
eccentrically placed nucleus,
with indentation adjacent to
the centre of the cell

Gives a horse shoe shaped

appearance

90

The extensive cytoplasm stains pale greyish blue and

contains numerous lysosomal granules and cytoplasmic
granules which gives frosted glass appearance

They are motile phagocytic cells and precursors of

macrophages

91

PATHOLOGICAL VARIATIONS
Monocytosis
Tuberculosis
Syphilis
Kala azar
Glandular fever

Monocytopenia

Prolonged use of prednisone

AIDS

Chronic lymphoid leukemia

92

LYMPHOCYTES

Lymphocytes approximates the size

of the erythrocyte

Most common agranulocytes

account for 30% of total blood
leucocytes

Nucleus is round and densely

stained and relatively small amount
of pale basohilic non granular
cytoplasm

93

Depending upon the size, lymphocytes are divided into

two groups

Large lymphocytes: younger cells with a diameter of 1012

Small lymphocytes: older cells with a diameter of 7-10

94

Depending upon the function lymphocytes are divided

into two types:

T-lymphocytes: concerned with cellular immunity

B-lymphocytes: concerned with humoral immunity

95

PATHOLOGICAL VARIATIONS

Lymphocytosis
Measles

Mumps
Whooping cough

Other Infections - Hepatitis

Infectious mononucleosis
Influenza
TB

Drug reactions - certain

anticonvulsants

Leukemias ALL, CLL.

Lymphocytopenia

After burns and trauma

SLE

Acute appendicitis

AIDS

Following radiation and

cytotoxic drugs

96

Differential count (DC): No of individual types out of 100

leucocytes
Normal values: N - 60-70%
E - 1-4%
B - 0-1%
L - 25-30%
M - 5-10%
Total count (TC): Total no of WBC present per unit volume of
whole blood
Normal: 4000 - 11000/cmm

97

BLOOD PLATELETS

Platelets or thrombocytes are small ,colorless ,non

nucleated formed elements of blood

Considered to be the fragments of cytoplasm of cells

called megakaryocytes

98

Megakaryoblast is a large cell about 30m in diameter,

with non lobed nucleus
Successive endomitoses occur in megakaryoblast
The cell then becomes promegakaryocyte,which develops
into platelet producing megakaryocyte
It has complex multilobed nucleus and scattered
azurophilic granules

99

Peripheral cytoplasm of the megakaryocytes divided into

small compartments by invagination of the plasma
membrane

100

Platelets are of several shapes spherical or rod shaped

Oval or disc shaped when inactivated

Platelets in normal
state

The activated platelets

101

Structurally platelets are divide into 4 zones

Peripheral zone

Structural zone

Organelle zone

Membrane zone
102

Platelets have 3 types of granules dispersed in the

cytoplasm

Most numerous granules are granules which contain

fibrinogen ,coagulation factors, plasminogen, platelet
derived growth factor

Contents of these granules play an important role in the

initial phase of vessel repair, blood coagulation, and
platelet aggregation
103

Smaller ,denser granules granules contain serotonin,

histamin, which facilitates platelet adhesion and
vasoconstriction

The granules are similar to lysosomes found in other

cells and contain hydrolytic enzymes

104

PATHOLOGICAL VARIATIONS
Thrombocytosis
1)Following trauma
2)Acute blood loss
3)Chronic myeloid leukemia
4)Polycythemia vera
5)Splenectomy
6)Hodgkin's disease

Thrombocytopenia

1)ITP
2)Splenomegaly
3)Acute infections
4)Acute leukemia
5)Aplastic anemia
6)X-ray irradiation

105

HEMOSTASIS

Hemostasis is defined as arrest or stoppage of bleeding

STAGES OF HEMOSTASIS
1)Vascular phase(vasocontriction)
2)Platelet phase( platelet plug formation)
3)Coagulation phase(coagulation of blood)
106

VASCULAR PHASE:
Immediately after injury, the
blood vessel constricts and
decreases the loss of blood

When the blood vessels are cut,

endothelium is damaged,
collagen is exposed

Platelets get adhered, and secrete

serotonin and other
vasoconstrictor substances which
cause constriction of blood
vessels

107

PLATELET PHASE/ PLATELET

PLUG FORMATION:

Adherence of platelets to the

collagen is accelerated by von
willebrand factor

Platelets get adhered to the

collagen of ruptured blod
vessel and secrete ADP &
thromboxane A2

These attract more platelets

and activate them

108

Platelets aggregate together

and form a loose
temporary platelet plug or
temporary hemostatic plug

Platelet aggregation is
accelerated by platelet
activating factor(PAF)

109

COAGULATION OF
BLOOD

During this process, the

fibrinogen is converted into
fibrin

Fibrin threads get attatched

to the loose platelet
plug,prevents the loss of
blood completely
110

COAGULATION OF BLOOD

Coagulation or clotting is
defined as the process in which
blood looses its fluidity and
becomes a jelly like mass few
minutes after it is shed out or
collected in a container

The clot is a mesh of thin

fibrils entangling the blood
cells

These fibrils consists of fibrin

threads

111

FACTORS INVOLVED IN BLOOD CLOTTING

Coagulation of blood occurs through a serious of

reactions due to activation of a group of substances

The substances necessary for clotting are called

CLOTTING FACTORS

Thirteen clotting factors are identified

112

FIBRINOGEN

IX CHRISTMAS FACTOR

II

PROTHROMBIN

III

THROMBOPLASTIN

XI

IV

CALCIUM

XII

LABILE FACTOR

XIII FIBRIN STABILIZING

(PROACCELERIN)

STUART-PROWER
FACTOR

PLASMA THROMBOPLASTIN
ANTECEDENT

HAGEMAN FACTOR

FACTOR

VI PRESCENCE HAS NOT

BEEN PROVED

VII STABLE FACTOR

VIII ANTIHEMOPHILIC
FACTOR

113

SEQUENCE OF CLOTTING MECHANISM

ENZYME CASCADE THEORY:

Clotting factors are proteins in the form of enzymes

All the factors are present in the form of inactive

proenzyme

These proenzymes must be activated into enzymes to

enforce clot formation

It is carried out by series of proenzyme-enzyme conversion

114

Enzyme cascade theory explains the conversion of

proenzymes to active enzymes take place in the form of
cascade

CASCADE refers to a process that occurs through a

series of steps, each step initiating the next,until the final
step is reached

115

STAGES OF BLOOD CLOTTING

Blood clotting occurs in three stages:

STAGE I: Formation of prothrombin activator

STAGE II:Conversion of prothrombin to thrombin
STAGE III:Conversion of fibrinogen to fibrin

116

STAGE 1- FORMATION OF PROTHROMBIN ACTIVATOR

Blood clotting commences with the formation of a

substance called prothrombin activator

It converts prothrombin to thrombin

It is formed either within the blood itself or outside the

blood

Thus it occurs through two pathways:

i)Extrinsic pathway
ii)Intrinsic pathway

117

EXTRINSIC PATHWAY:
Initiated by tissue thromboplastin which is formed in the
injured tissues

INTRINSIC PATHWAY:
Initiated by platelets which are within the blood itself

118

SEQUENCE OF EVENTS IN INTRINSIC AND

EXTRINSIC PATHWAYS

119

STAGE -2 CONVERSION OF PROTHROMBIN TO

THROMBIN

Blood clotting is all about

thrombin formation

Once thrombin is formed,it

definitely leads to clot formation

Prothrombin activator converts

prothrombin to thrombin in the
presence of calcium

Once formed thrombin initiates

the formation of more thrombin
molecules

120

Initially formed thrombin

activates factor V

Factor V in turn accelerates

formation of both intrinsic
& extrinsic prothrombin
activator

This effect of thrombin is

called POSITIVE
FEEDBACK EFFECT

121

STAGE3-CONVERSION OF FIBRINOGEN INTO FIBRIN

Thrombin converts fibrinogen into activated fibrinogen due to

loss of 2 pairs of polypeptides from each fibrinogen molecule

The activated fibrinogen is called fibrin monomer

Fibrin monomer molecules polymerises to form loosely

arranged strands of fibrin

Later these loose strands are modified into dense fibrin strands
by fibrin stabilizing factor in the presence of calcium ions

All the fibrin threads are aggregated to form a meshwork

122

BLOOD CLOT

Blood clot is defined as the

mass of coagulated blood
which contains RBCs, WBCs
and platelets entrapped in
fibrin meshwork

RBCs and WBCs are not

necessary for clotting process.

The trapped RBCs are

responsible for the red color of
the clot

123

BLEEDING TIME:
Time interval from oozing of blood after a cut or injury
till arrest of bleeding
It is determined by DUKES method using blotting paper
Normal duration- 1 -5 min

CLOTTING TIME:
Time interval from oozing of blood after a cut till the
formation of clot
Determined by capillary tube method
Normal duration- 3-8 min

124

BLOOD GROUPS

Blood groups are determined by the presence of antigen

in RBC membrane

When blood from two individuals is mixed sometimes

clumping (agglutination) occurs

This clumping is because of immunological reactions

But ,why clumping occurs in some cases ,and not in

other cases remained mystery until the discovery of
blood groups

125

1901 - Karl Landsteiner

discovered the first known
blood group system (ABO)

He was honoured with

NOBLE PRIZE in 1930 for
this discovery

126

ABO BLOOD GROUPS

Determination of ABO blood groups depends upon the

immunological reaction between antigen &antibody

LANDSTEINER found two antigens on the surface of

RBCs and named them as A antigen & B antigen

These antigens are also called agglutinogens because of

their capacity to cause agglutination of RBCs

127

He also noticed the corresponding antibodies or

agglutinins in the plasma

Named them anti A or antibody and anti B or

antibody

However particular agglutinogen and the corresponding

agglutinin cannot be present together

If present it causes clumping of the blood

128

LANDSTEINERS LAW :

If a particular antigen (agglutinogen) is present in the

RBCs ,corresponding antibody(agglutinin) must be
absent in the plasma

If a particular antigen is absent in the RBCs, the

corresponding antibody must be present in the plasma

129

BLOOD GROUP SYSTEMS

More than 20 genetically determined blood group

systems are known today

But, Landsteiner discovered two blood group systems

called ABO system and Rh system

These are important to be determined before blood

transfusion

130

ABO SYSTEM

Based on the presence or absence of antigen A and

antigen B, blood is divided into 4 groups
1) A group
2)B group
3)AB group
4)O group

131

A group
The blood having antigen A
is called A group
This group has anti B
antibody in the plasma

B group
The blood with antigen B is
called B group
This group has anti A
antibody

132

AB group
If both the antigens are
present, the blood group is
called AB group
Plasma does not contain
any antibody

O group
If both the antigens are
absent
Plasma contains both anti B
and anti A antibodies

133

DETERMINATION OF ABO GROUP

Blood grouping, blood matching or blood typing

Principle of blood typing agglutination

Agglutination means collection of separate particles like
RBCs into clumps or masses
Agglutination occurs if an antigen is mixed with the
corresponding antibody which is called isoagglutination
Agglutination occurs when A antigen is mixed with anti
A or when B antigen is mixed with anti B

134

REQUISITIES FOR BLOOD TYPING

To determine the blood group of a person ,a suspension

of his RBC and testing antisera are required

Suspension of RBC is prepared by mixing blood drops

with isotonic saline (0.9%)

The test sera are:

1)Antiserum A, containing anti A
2)Antiserum B, containing anti B

135

PROCEDURE:

1) One drop of antiserum A is

placed on one end of a glass
slide and one drop of
antiserum B on the other end

One drop of RBC suspension

is mixed with each antiserum .
The slide is slightly rocked for
2min

The presence or absence of

agglutination is observed by
naked eyes

136

Results:

If agglutination occurs with

antiserum A:

The antiserum A contains anti

A antibody.
Agglutination occurs if the
RBC contains A antigen
So the blood group is A

137

If agglutination occurs
with antiserum B :

Antiserum B contains
Anti B antibody,
agglutination occurs if the
RBC contains B antigen
So the blood group is B

138

If agglutination occurs
with both antisera A and
B:

RBC contains both A and

B antigens to cause
agglutination
The blood group is AB

139

If agglutination does not occur either with antiserum

A or antiserum B:

The agglutination does not occur if the RBC does not

contain any antigen
The blood group is O

140

IMPORTANCE OF ABO BLOOD GROUPS IN BLOOD

TRANSFUSION

During blood transfusion ,only compatible blood must be

used

Person who gives the blood is called DONAR

Person who receives the blood is called RECIPIENT

While transfusing the blood , antigen of the donar and

the antibody of the recipient are considered
141

RBC of O group has no antigen, so agglutination does

not occur with any other group of blood

So people of this group blood are UNIVERSAL

DONARS

Plasma of AB group has no antibody,this does not cause

agglutination of RBC from any other blood group

So people with this group blood are called UNIVERSAL

RECIPIENTS

142

OTHER BLOOD GROUPS

Lewis blood group
MNS blood group
Bombay bloodgroup
Lutheran group
P group
Kell group

143

RH FACTOR

Rh factor is the antigen present in RBC

This antigen was discovered by Landsteiner and Wiener

It was first discovered in RHESUS monkey and hence

the name Rh factor

There are many Rh antigens but only D is more antigenic

144

Persons having D antigen are called Rh positive

Those without D antigen are called Rh negative

Rh group system is different from ABO group system

because ,the antigen D does not have corresponding
natural antibody

145

RH INCOMPATIBILITY

146

BLOOD TRANSFUSION

Blood transfusion is the process of transferring blood or

blood components from one person to another person

Blood transfusion is essential in the following

conditions:
1)anemia
2)hemorrhage
3)trauma
4)burns
5)surgery

147

1)WHOLE BLOOD TRANSFUSION

Is carried out when the patient has lost the whole

blood due to.

Accidental injuries
During and after major surgery

2) PACKED CELL TRANSFUSION :

Is given to patients with severe anaemia in whom the

Hb conc is less than 4 gms%. This causes dramatic
improvement in the condition of the patient

148

PLATELET TRANSFUSION :

Is carried out in patients who is suffering from

bleeding disorders due to Thrombocytopenia

149

TRANSFUSION REACTIONS

Mild fever and chills

Severe acute kidney failure

shock
death

150

Best way to honour Karl Landsteiner is to donate

blood to save a life

151

CONCLUSION

Blood is the fluid of life ,and is a diagnostic tool which

provides information of almost all the systems of the
body

Understanding the physiology of blood is important in

the diagnosis & treatment of the patient and prolong the
life of the patient
152

REFERENCES:
Essentials of medical physiology-k.Sembulingam Prema
sembulingam-5th edition
Wheaters functional histology-5th edition
Histology A text and atlas-Michael H.Ross-5th edition
Text book of human histology Inderbir singh
Text book of medical physiology- Guyton Hall

153

Thank you
154

Question and
answers
155

Depending upon the deficiency of the granules condition

associated with neutrophils?
Specific granule deficiency-it represents a failure to pack
whole group of protiens into granules
Deficiency of these components results in diminished
ability to respond to chemotaxis and poor phagocytosis

156

Difference between thrombus & clot?

Thrombosis is the process of formation of solid mass in
circulation from the constiuents of flowing blood, the
mass itself is called a THROMBUS
A BLOOD CLOT is the mass of coagulated blood
formed invitro eg: in a test tube

157

Rouleaux formation is pathological or physiological?

Erythrocyte aggregation is a physiological phenomenon that
takes places in normal blood under low-flow conditions or
at stasis.
The presence or increased concentrations of proteins,
particularly fibrinogen, results in enhanced erythrocyte
aggregation
Surface properties of erythrocytes, such as surface
charge density strongly influence the extent and
time course of aggregation.
The flat surface of the discoid RBCs give them a large
surface area to make contact and stick to each other; thus,
forming a rouleaux

158

Significance of Prothrombin Time

Measure the extrinsic pathway of coagulation.
Sensitive to deficiency of factors I,V,VII,X
To determine the clotting tendency of blood, in the
measure of warfarin dosage, liver damage, and vitamin
K status

159

Sickle cell anaemia

It results from the single glutamic acid to valine
substitution at position 6 in the beta globin polypeptide
chain
When hemoglobin S is deoxygenated, the molecules of
hemoglobin polymerize to form pseudocrystalline
structures known as TACTOIDS
These distort the red cell membrane and produce the
characteristic sickle shaped cell

160

Why there is hepatospleenomegaly in anemias?

There is hepatospleenomeagaly in anemias due to
extramedullary hemopoiesis ,where liver and spleen
can resume their fetal hemopoietic role and thus increase
in size

161

BLEEDING TIME is prolonged in

thrombocytopenic purpura & von willebrands
disease
CLOTTING TIME is prolonged in hemophilias

162

Life span of RBCs

Due to decrease oxygen carrying capacity of RBCS
,macrophages engulf the degenerating RBC

163

Percentage of hemopoietic stem cells and other stem

cells in bone marrow?

164