BY

IDIONGO O. UMOH
 Overview
 Composition and functions
 Red blood cells:
 Characteristics & functions, formation and
destruction
 White blood cells:
 Characteristics, functions, formation
 Platelets :
 Haemostasis, fibrinolysis
 Blood groups and transfusion problems

20-Feb-18 Blood 2
Blood Composition
 Is an opaque, red liquid
 Consisting of several types of cells
 Suspended in a complex, amber fluid
 plasma

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Blood Composition
 Composed of
 Cells
 Plasma, liquid in which the cells are suspended
 The cells (formed elements) include
 Erythrocytes (RBCs)
 Leukocytes (WBCs)
 Platelets (cell fragments)

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Blood Composition
 99% of the cells are RBC
 Which are the O2 carrying cells of blood
 WBC protect against infections
 Platelets function in blood clotting

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Blood Volume
 Average blood volume = 8% of body wt
 = 5.6 (70*0.08)
 On the average
 60% of blood vol = plasma ( 3 liters)
 40% of blood vol = RBC (2 liters)
 Values vary considerably in different people depending
on
 Sex and other factors

20-Feb-18 Blood 7
The haematocrit
 Defined as the % of total
blood that is erythocytes
 It is determined by
Plasma = 55% centrifuging a sample of
blood in a haematocrit
Leukocytes and
tube
platelets  Erythrocytes are forced to the
bottom
 Plasma remains at the top
RBC = 45%  Leucocyte and platelets form
(Hct = 45%) a thin layer in between

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Plasma
 Non cellular part of blood
 Contain large amount of organic and inorganic
substances dissolved in water
 Contains water, proteins, gases and other
constituents

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 Plasma Constituents

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 Serum
 Serum is the clear straw-colored fluid that oozes from
blood clot.
 When the blood is shed or collected in a container, it
clots. In this process, the fibrinogen is converted into
fibrin and the blood cells are trapped in this fibrin
forming the blood clot. After about 45 minutes, serum
oozes out of the blood clot.
 Volume of the serum is almost the same as that of
plasma (55%). It is different from plasma only by the
absence of fibrinogen. Fibrinogen is absent in serum
because it is converted into fibrin during blood
clotting.
 Thus, Serum = Plasma – Fibrinogen

20-Feb-18 Blood 11
 FUNCTIONS OF BLOOD
 NUTRITIVE FUNCTION
Nutritive substances like glucose, amino acids, lipids and
vitamins derived from digested food are absorbed from
gastrointestinal tract and carried by blood to different
parts of the body for growth and production of energy.
 RESPIRATORY FUNCTION
Transport of respiratory gases is done by the blood. It
carries oxygen from alveoli of lungs to different tissues and
carbon dioxide from tissues to alveoli.
 EXCRETORY FUNCTION
Waste products formed in the tissues during various
metabolic activities are removed by blood and carried to
the excretory organs like kidney, skin, liver, etc. for
excretion.

20-Feb-18 Blood 12
 FUNCTIONS OF BLOOD
 TRANSPORT OF HORMONES AND ENZYMES
 REGULATION OF WATER BALANCE
Water content of the blood is freely interchangeable
with interstitial fluid. This helps in the regulation of
water content of the body.
 REGULATION OF ACID-BASE BALANCE
Plasma proteins and hemoglobin act as buffers and
help in the regulation of acid-base balance
 REGULATION OF BODY TEMPERATURE
 DEFENSIVE FUNCTION

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Formed Elements of Blood
 Formed elements of blood include
 Erythrocytes
 Leukocytes
 Platelets

20-Feb-18 Blood 14
 Introduction
 Red blood cells (RBCs) are the non-nucleated
formed elements in the blood. Red blood cells are also
known as erythrocytes (erythros = red).

 Red color of the red blood cell is due to the presence of

the coloring pigment called hemoglobin.

 RBCs play a vital role in transport of respiratory gases.

RBCs are larger in number compared to the other two
blood cells, namely white blood cells and platelets.

20-Feb-18 Blood 16
 Erythrocytes (RBC)
 Functions of RBC
 To transport O2 from lungs to tissue: Hemoglobin in
RBC combines with oxygen to form oxyhemoglobin.
About 97% of oxygen is transported in blood in the
form of oxyhemoglobin.

 Transport of CO2 from the Tissues to the Lungs

 Hemoglobin combines with carbon dioxide and
form carbhemoglobin. About 30% of carbon
dioxide is transported in this form.RBCs
Contain carbonic Anhydrase which catalyze
 H2o + Co2 H2co3 Hco3- + H+
 Thus transport CO2 from tissues to lungs in the form of
HCO3-

20-Feb-18 Blood 17
 Erythrocytes
 Other functions of RBC include
 Buffer function
 Hemoglobin functions as a good buffer. By this action, it
regulates the hydrogen ion concentration and
thereby plays a role in the maintenance of acidbase
balance
 In Blood Group Determination
RBCs carry the blood group antigens like A antigen,
B antigen and Rh factor. This helps in determination
of blood group and enables to prevent reactions due to
incompatible blood transfusion.

20-Feb-18 Blood 18
Erythrocytes

 Shape and size of RBC

 Biconcave discs
 Diameter = 7.8 µm
 Thickness at the periphery = 2.5 µm
 and at the center it is thinner with 1 μ
 This difference in thickness is because of the biconcave
shape.

20-Feb-18 Blood 19
 Erythrocytes
 The shape of the RBC can change remarkably
 It is a bag which can be deformed
 To any shape; This allows it to
 Pass through capillaries without problem

 Normal RBC
 Red blood cells are non nucleated. Only mammal, which has
nucleated RBC is camel.

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 Shape Of The Erythrocytes

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Concentration of RBC in Blood
 In normal men avge number of RBC
 Is 5,200,000 (+/- 300,000) per cubic ml
 In women avge number of RBC
 Is 4,700,000 (+/- 300,000)
 Quantity of Hb in RBC
 RBC have the ability to conc HB up to 34 g/dl
 When Hb formation is deficient in bone marrow
 % Of Hb in RBC may fall
 vol of RBC may decrease

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Concentration of RBC in Blood
 When Hct = 40 - 45%
 Quantity of Hb in each cell is normal
 Whole blood of men contain 16 gm Hb/dl
 Whole blood of women contain 14 gm Hb/dl

 Each gram of pure Hb

 Combine with 1.39 ml of O2
 Hence in normal man total amount carried
 Is = 1.39 * 16 = 22 ml of O2 per dl of blood

 In normal woman
 Is = 1.39 * 14 = 19 ml of O2 per dl of blood

20-Feb-18 Blood 23
 Properties Of Red Blood Cell
 ROULEAUX FORMATION
When blood is taken out of the blood vessel, the RBCs pile up
one above another like the pile of coins. This property of the
RBCs is called rouleaux (pleural = rouleau) formation. It is
accelerated by plasma proteins globulin and fibrinogen.
 „SPECIFIC GRAVITY
Specific gravity of RBC is 1.092 to 1.101.
 „PACKED CELL VOLUME
Packed cell volume (PCV) is the proportion of blood occupied by
RBCs expressed in percentage. It is also called hematocrit value.
It is 45% of the blood and the plasma volume is 55%.
 „SUSPENSION STABILITY
During circulation, the RBCs remain suspended uniformly in the
blood. This property of the RBCs is called the suspension
stability.

20-Feb-18 Blood 24
Erythropoeisis
 Sites of RBC production include
 Yolk sack
 During early weeks of embryonic life (Mesoblastic stage)
 Liver, spleen, lymph nodes
 Middle trimester (Hepatic stage)
 Bone marrow
 Last trimester, after birth (Myeloid stage)
 Bone marrow of all bones
 Up to 5 yrs
 Bone marrow of membranous bones
 > 20yrs

20-Feb-18 Blood 25
 Factors Necessary for erythropoiesis
 Development and maturation of erythrocytes require
variety of factors, which are classified into three
categories:
1. General factors
2. Maturation factors
3. Factors necessary for hemoglobin formation

20-Feb-18 Blood 26
 Factors Necessary for erythropoiesis
 General factors necessary for erythropoiesis are:
Erythropoietin, Thyroxine, Hemopoietic growth
factors, Vitamins (Vit B, C, D, E).
 Maturation factors necessary for erythropoiesis are:
Vitamin B12, intrinsic factor and folic acid are
necessary for the maturation of RBCs.
 Factors Necessary For Hemoglobin Formation
Deficiency of these substances decreases the
production of hemoglobin leading to anemia. Such
factors are: First class proteins and amino acids, Iron,
Copper, Cobalt and nickel

20-Feb-18 Blood 27
Genesis of RBC
 Pluripotential Haemopoetic stem cell (PHSC)
 Derived from blood islands in the embryonic yolk sac
whose cells colonize liver, spleen & marrow
 All cells in circulating blood are derived from these stem
cells

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 Genesis of RBC
 PHSC
 Produce committed stem cells which produce colonies
of specific types of blood cells
 Colony forming unit - erythrocytes (CFU -E)
 Colony forming unit - granulocytes & Monocytes (CFU-
GM) – These cells give rise to granulocytes (neutrophils,
basophils and eosinophils) and monocytes.
 Colony forming unit-megakaryocytes (CFU-M)– Platelets
are developed from these cells
 Lymphoid stem cell (LSC)
 Also PHSC differentiates into other PHSC
 Maintain line of stem cell

20-Feb-18 Blood 29
Genesis of Blood Cells
Erythrocytes

CFU -E Granulocytes

CFU-B Monocytes
PHSC

CFU-GM Macrophages
Megakaryocytes

Platelets
CFU-M
PHSC T - Lymphocytes

CFU -LSC B - Lymphocytes

20-Feb-18 Blood 30
Genesis of RBC
 Growth and reproduction of different stem
cells
 Controlled by multiple protein (growth inducers)
 interleukin 3

 Promote growth and reproduction of all different stem

cells
 Differentiation inducers
 Cause one stem cell to differentiate into one or two
stages towards adult form

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Genesis of RBC
 The formation of growth inducers &
differentiation inducers
 Controlled by other factors
 erythropoeitin in case of RBC

 In case of some WBC

 Infectious diseases cause growth, differentiation and

formation of specific types of WBC

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Stages of RBC Differentiation
PHSC
 PHSC differentiates into
CFU-B CFU-E committed stem cells
under the influence of
Proerythroblast
 Growth inducers &
differentiation
inducers
Basophil erythroblast
 The committed stem cell
Polychromatophil CFU -E
erythroblast  Undergoes series of
reticulocytes division
Mature erythrocyte

20-Feb-18 Blood 33
Stages of RBC Differentiation
PHSC
 The committed stem cell
CFU-B CFU-E CFU -E
Proerythroblast  Undergoes series of
division to form
mature erythrocyte
Basophil erythroblast  Throughout the
division
Polychromatophil
erythroblast  Cell becomes filled
with Hb
reticulocytes
Mature erythrocyte

20-Feb-18 Blood 34
Stages of RBC Differentiation
PHSC
 The nucleus condenses
CFU-B CFU-E to small mass and is
finally extruded
Proerythroblast
 This is stage of
reticulocyte
 reticulocyte pass from
Basophil erythroblast bone marrow to
Polychromatophil capillaries
erythroblast  By diapedesis(
squeezing through
reticulocytes capillary pores)
Mature erythrocyte

20-Feb-18 Blood 35
Regulation of RBC Production
 Total mass of RBC in circulation
 Regulated within narrow limits
 Tissue oxygenation provides the basic regulation
of RBC production
 Conditions that decrease oxygen transport to tissue
 Anaemia, high altitude, low blood volume, poor blood flow, lung
diseases
 Increase rate of RBC production

20-Feb-18 Blood 36
Role of erythropoeitin
 Erythropoetin is a glycoprotein MW 34,000
 During hypoxia
 Rate of production of erythropoeitin increases
 Erythropoeitin is produced mainly by the kidneys (90%)
 The remaining amount is produced in some other tissue
(liver)

20-Feb-18 Blood 37
Role of erythropoeitin
 Erythropoeitin stimulates
 Production of proerythroblasts from PHSC
 Rapid differentiation of erythroblastic stages to form
mature erythroblast
 Hence there is rapid production of RBC

20-Feb-18 Blood 38
Regulation of Erythropoiesis
O2 delivery to
Kidney
Erythopoietin prod
by Kidney

Plasma Erythopoietin

Production of RBC by
Bone marrow

Blood Haemoglobin
conc

Blood O2 carrying restoration of O2

capacity delivery to tissues

20-Feb-18 Blood 39
Formation of Haemoglobin
 The synthesis of HB
 Begins at the Proerythroblast
A P
stage
C C  Continue up to reticulocyte
stage
HC CH  Stages of Hb synthesis
N  2 succinyl CoA combine with
H
2 glycine molecule to form a
pyrole molecule
Pyrole molecule
(aminolevulinic acid)

20-Feb-18 Blood 40
Formation of haemoglobin
 4 pyrole molecules
CH=CH2
combine to form
N N protoporphyrin IX
N N

(CH2 ) - COO-
- COO- - (CH2 )

Protoporphyrin IX

20-Feb-18 Blood 41
Formation of haemoglobin
 Protoporphyrin
CH=CH2
combine with Fe++ to
N N form Haeme
Fe++
N N

(CH2 ) - COO-
- COO- - (CH2 )

Haeme

20-Feb-18 Blood 42
Formation of haemoglobin
 Each haeme molecule
combine with a long
CH=CH2 polypeptide chain (Globin)
N N  To form haemoglobin chain
Fe++ O2
N  There are different types of
N chains formed depending
on amino acid composition
- COO- - (CH2 ) (CH2 ) - COO- of the polypeptide chain
 Each globin molecule is
Poypeptide chain
(Globin)
formed by the
combination of 2 pairs of
chains and each chain is
Haemoglobin chain made of 141 to 146 amino
( or ) acids

20-Feb-18 Blood 43
Formation of haemoglobin
 The different types of
haemoglobin chains include
CH=CH2   Chain contain 141 AA
N N residues
Fe++ O2
N   Chain contain 146 AA
N residues
  Chain contain 146 AA
(CH2 ) - COO-
- COO- - (CH2 ) residues
 10 individual residues differ
Poypeptide chain from the  Chain
(globin)
  Chain contain 146 AA
residues
 37 individual residues differ
Haemoglobin Chain from  Chain

20-Feb-18 Blood 44
Formation of haemoglobin
 2 alpha chains combine with
 2 beta chains to form
 Haemoglobin molecule (Hb-
chain
chain A)
 Each chain has MW
  =16,000
chain chain  Total MW of Hb

 = 64,000

Haemoglobin Molecule
(Hb-A)

20-Feb-18 Blood 45
 Haemoglobin

 The most common type of heamoglobin

 Haemoglobin A (Hb A)

 Formed by a combination of 2 chains and 2  chains

 Others
 Haemoglobin A2 (Hb A2)

 Formed by a combination of 2 chains and 2  chains

 Fetal haemoglobin (Hb F)
 Formed by combination of 2 chains and 2  chains

20-Feb-18 Blood 46
Haemoglobin
 Each chain has a haeme prosthetic group
 Hence there are 4 iron atoms in each Hb molecule
 Each iron atom can combine with 1 molecule of oxygen: total of 4
oxygen molecules (8 oxygen atoms)
 O2 binds loosely with iron (Fe++)
 To form oxyhaemoglobin
 A reversible reaction
 At the lungs Hb binds with O2

 At the tissue level HB release the O2

20-Feb-18 Blood 47
Haemoglobin
 If the Fe++ is oxidized to Fe+++
 Then methaemoglobin is formed
 It is dark coloured and causes cyanosis if it is in large amount

 Oxidation of Hb to methaemoglobin
 Does occur to some extent in circulation but
 NADH – methaemoglobin reductase enzyme system in RBC
 Converts methaemoglobin back to Hb

 Absence of this enzyme system

 Causes methaemoglobinaemia

20-Feb-18 Blood 48
Haemoglobin
 Hb can combine also with carbon monoxide
 To form carbon monoxyhaemoglobin
(carboxyheamoglobin)
 The affinity of Hb for O2 is lower than that for CO
 CO displaces O2 from Hb

 This lowers O2 carrying capacity of Hb

20-Feb-18 Blood 49
Iron Metabolism
 Iron is important for the formation of
 Haemoglobin, myoglobin, cytochromes, cytochrome
oxidase, peroxidases, catalasese
 Total quantity of iron in the body
 4 to 5 grams

20-Feb-18 Blood 50
Iron Metabolism
 Different forms into which body iron exist include
 Haemoglobin 65%
 Myoglobin 4%
 Various forms of Haeme compounds 1%
 Combined with Transferrin 0.1%
 Stored in RES, liver (in form of ferritin) 15 – 30%

20-Feb-18 Blood 51
Transport of Iron
 After absorption in GIT
 Iron is combined with  - globulin (apotransferrin)
 To form Transferrin

 This is transported in plasma

 Iron is loosely combined to the globulin

 Easily released to tissue cells

 Excess iron in blood

 Deposited in cells of the body
 Liver, RES, bone marrow

20-Feb-18 Blood 52
Transport of Iron
 In the cell’s cytoplasm
 Iron combine with apoferritin to form ferritin
 Ferritin is a storage form of iron
 Small quantity of iron is stored as
 Haemosiderrin

20-Feb-18 Blood 53
Transport of Iron
 When the quantity of iron in plasma falls
 Iron is easily removed from Ferritin
 It is transported in plasma as Transferrin
 In bone marrow
 Transferrin mol binds strongly to receptors of cell membrane
of erythroblasts
 Iron is transported directly to mitochondria for haeme
synthesis

20-Feb-18 Blood 54
Transport of Iron
 When RBC are destroyed
 Hb released from RBC is ingested by macrophages
 Free iron is released and it is either
 Stored as ferritin or

 Re-used again in the formation of new Hb

20-Feb-18 Blood 55
Daily Loss of Iron
 Man excretes about 1 mg of iron per day
 Mainly through faeces
 During haemorrhages
 For women menstrual blood loss
 Brings the total iron loss to about 2 mg per day

20-Feb-18 Blood 56
Destruction of RBC
 RBC normally circulate for an average of 120 days
before destruction
 Mature RBC
 Do not have nucleus,mitochondria or endoplasmic
reticulum
 Have some cytoplasmic enzymes
 Capable of metabolizing glucose to form
 ATP
 NADPH

20-Feb-18 Blood 57
Destruction of RBC
 NADPH serves the RBC
 Maintaining the pliability of the cell membrane
 Maintaining membrane transport of ions
 Keeping the iron in Hb in Fe++ rather than Fe+++ state

20-Feb-18 Blood 58
Destruction of RBC
 As the cells become old
 Metabolic processes become progressively less active
 Membrane become fragile
 Ruptures easily especially
 During RBC passage through spleen

20-Feb-18 Blood 59
Destruction of RBC
 When RBC membrane rapture
 Released Hb is phagocytosed by macrophages RES
 Hb is split into
 Globin and haeme

 Haeme ring is opened to give

 Free iron

 Transported in blood by Transferrin

 Phorphyrin portion

20-Feb-18 Blood 60
Destruction of RBC
 Phophyrin portion of the haeme
 Converted into biliverdin
 Biliverdin is further converted into bilirubin
 Bilirubin is gradually released from the macrophages into
plasma
 Free bilirubin is bound to plasma proteins

20-Feb-18 Blood 61
Anaemia
 Anaemia means reduction of RBCs/ PCV/ Hb
concentration below normal accepted ranges for age/
sex of an individual which can be due to;
 Too rapid loss of RBCs
 Slow production of RBCs
 Simply: reduction in oxygen carrying capacity of blood
 Types
 Blood loss anaemia
 Aplastic anaemia
 Magaloblastic anaemia
 Haemolytic anaemia

20-Feb-18 Blood 62
Blood Loss Anaemia
 After haemorrhage
 Body replaces plasma within 1 to 3 days
 This leaves low conc of RBC in plasma
 RBC can return to normal within 3 to 6 weeks
 In chronic blood loss
 An individual cannot absorb iron rapidly enough to cope with
HB synthesis
 RBC are formed with little Hb

 They are pale (Hypochromia)

 They are small in size (Microcytosis)

 Microcytic hypochromic anaemia

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Aplastic anaemia
 Due to lack of function of bone marrow
 Exposure to gamma radiation, certain industrial
chemicals, excessive X-rays, certain drugs

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Megaloblastic anaemia
 Due to lack or deficiency of vitamin B12, folic acid
 Required for DNA synthesis
 Deficiency of these leads to
 Slow reproduction of erythroblasts in bone marrow
 They become large with odd shapes
 Megaloblasts (have fragile membrane) easily rapture

 Development of anaemia

 Megaloblastic anaemia

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Haemolytic anaemia
 In this condition normal number of RBC is being
formed but
 They have abnormalities which make their membrane
fragile
 They rapture easily as they go through the capillaries
 Hence life span greatly reduced
 Anaemia develops

20-Feb-18 Blood 66
Haemolytic anaemia
 Examples
 Hereditary spherocytosis
 RBC are small and have spherical shape
 They are easily ruptured as they pass through the spleen pulp

 Haemolysis

20-Feb-18 Blood 67
Haemolytic anaemia
 Sickle cell anaemia
 RBC contain abnormal type of HB known as Hb-s
  Chain of Hb are abnormal
 Valine is substituted for glutamic acid at one point

 When it is exposed to low O2

 It precipitates into long crystal inside the RBC

 Which elongate the cell into a sickle shape

 Fragile membrane

 Breakdown of RBC –(Haemolysis)

20-Feb-18 Blood 68
Erythroblastosis foetalis
 Affect a child of
 Rh negative mother married to Rh positive man
 Rh positive RBC in foetus
 Attacked by antibodies from Rh negative mother
 Antibodies make the cell fragile

 Rapture
 Haemolysis
 Anaemia

20-Feb-18 Blood 69
Pathological Polycythemia
 Pathological polycythemia is the abnormal increase in
the RBC count. Red cell count increases above 7
million/cu mm of the blood.
 Polycythemia is of two types, the primary
polycythemia and secondary polycythemia.

20-Feb-18 Blood 70
Primary Polycythemia
 Primary polycythemia is otherwise known as
polycythemia vera. It is a disease characterized by
persistent increase in RBC count above 14 million/cu
mm of blood. This is always associated with increased
white blood cell count above 24,000/cu mm of blood.
 Polycythemia vera occurs in myeloproliferative
disorders like malignancy of red bone marrow.

20-Feb-18 Blood 71
Secondary Polycythemia
 This is secondary to some of the pathological
conditions (diseases) such as:
1. Respiratory disorders like emphysema.
2. Congenital heart disease.
3. Ayerza’s disease (condition associated with
hypertrophy of right ventricle and obstruction of
blood flow to lungs).
4. Chronic carbon monoxide poisoning.
5. Poisoning by chemicals like phosphorus and arsenic.
6. Repeated mild hemorrhages.
All these conditions lead to hypoxia which stimulates
the release of erythropoietin. Erythropoietin
stimulates the bone marrow resulting in increased
RBC count. 72