Blood

Overview

 Composition and functions

1.Red blood cells:
– Characteristics & functions,
formation destruction and
anaemias

Oct 9, 2020 Blood 2

 Overview

2.White blood cells:

– Characteristics, functions,
formation
3.Platelets :
– Haemostasis, fibrinolysis
– bleeding tendencies
4.Blood groups and transfusion
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problems
(I)Composition of
Blood
 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
 In CVS
– Motion of blood keeps the cells well
dispersed through out plasma

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 Blood Volume
 Avg 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, wt, and other factors

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 The haematocrit
 Defined as the % of
total blood that is
erythocytes
Plasma = 55%  It is determined by
centrifuging a
Leukocytes and sample of blood in a
platelets haematocrit tube
– Erythrocytes are forced
RBC = 45% to the bottom
(Hct = 45%) – Plasma remains at the
top
– Leucocyte and platelets
form 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 (next slides)

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 Plasma Constituents
Constituent Functions
1 Water =93% of Medium for carrying all other constituents
plasma wt
2 Electrolytes Keep water in ECF, act as buffers, for blood
(inorganic) clotting, for excitability of cells
Total < 1%
plasma wt
3 Proteins 7% of Provide non penetrating solute of plasma,
plasma wt.= Act as buffers, transport protein,clotting
7.3 g/100 ml factors, enzymes, antibodies
Albumin,
globulin,
fibrinogen

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 Plasma Constituents
Constituent Functions
4 Gases CO2 is waste product, O2, for oxidative
CO2, O2, N2 metabolism, N2 inert
5 Nutrients Nutrition
Glucose,
amino acids,
lipids and
cholesterol,
vitamins, trace
elements

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 Plasma Constituents
Constituent Functions
6 Waste
products:
urea,
creatinine,
uric acid,
bilirubin
7 Individual Metabolic, Control system
hormnes

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 Formed Elements of
Blood
 Formed elements of blood
include
– Erythrocytes
– Leukocytes
– Platelets

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(II) Erythrocytes
 Erythrocytes (RBC)
 Functions of RBC
– To transport Hb
 Hb carries O2 from lungs to tissue
 In lower animals Hb circulates as free
protein in plasma
 In human being when it is free
– 3% leaks from capillaries
 Into tissue spaces; glomerular filtrate

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 Erythrocytes
 Hence for Hb to remain in blood
stream
– It must exist inside the RBC
 OTHER functions of RBC include
– Buffer function
 Contain carbonic Anhydrase which catalyze
 H2o + Co2 H2co3 Hco3- + H+
– Thus transport CO2 from tissues to lungs
in the form of HCO3-

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 Erythrocytes
 Hb is an excellent acid/base buffer
 Thus RBC are responsible for most
buffering capacity of the blood
 Shape and size of RBC
– Biconcave discs
– Diameter = 7.8 µm
– Thickness at the thickest point = 2.5 µm
– avge vol = 90 - 95 µl3

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 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
– Has great excess cell membrane for
quantity inside
– Hence deformation does not stretch the
membrane to cause it to rapture

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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 = 21 ml of O2 per dl of blood
– In normal woman
 Is = 1.39 * 14 = 19 ml of O2 per dl of blood

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 Erythropoeisis
 Sites of RBC production include
 York sack
– During early weeks of embryonic life
 Liver, spleen, lymph nodes
– Middle trimester
 Bone marrow
– Last trimester, after birth
 Bone marrow of all bones
– Up to 5 yrs
 Bone marrow of membranous bones
– > 20yrs

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 Substances Required for
Synthesis of RBC
 The production of RBC requires
the usual things for normal
production of any cell
– Amino acids, lipids, carbohydrates
– Iron,
– Vit. B12, folic acid

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 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)

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 Genesis of RBC
– Colony forming unit - megakaryocytes
(CFU-M)
– Lymphoid stem cell (LSC)
 Also PHSC differentiates into other
PHSC
– Maintain line of stem cell

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 Genesis of Blood Cells
Erythrocytes

CFU -E Granulocytes
CFU-B
Monocytes
PHSC CFU -Spl

CFU-GM Macrophages
Megakaryocytes

Platelets
CFU-M
PHSC T - Lymphocytes

B - Lymphocytes
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 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
CFU-B CFU-E into committed
stem cells under the
Proerythroblast
influence of
– Growth inducers
& differentiation
Basophil erythroblast
inducers
Polychromatophil  The committed
erythroblast stem cell CFU -E
reticulocytes – Undergoes series
Mature erythrocyte
of division

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 Stages of RBC
Differentiation
PHSC
 The committed
CFU-B CFU-E stem cell CFU -E
Proerythroblast – Undergoes series
of division to
form mature
erythrocyte
Basophil erythroblast
 Throughout the
Polychromatophil
erythroblast
division
– Cell becomes
reticulocytes filled with Hb to
Mature erythrocyte conc = 34gm/dl
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 Stages of RBC
Differentiation
PHSC
 The nucleus
CFU-B CFU-E condenses to small
mass and is finally
Proerythroblast extruded
– This is stage of
Basophil erythroblast reticulocyte
Basophil erythroblast  reticulocyte pass
from bone marrow
Polychromatophil to capillaries
erythroblast
– By
reticulocytes diapedesis( squeezing
through capillary
Mature erythrocyte pores)

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 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

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 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)

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 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

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 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

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 Formation of
Haemoglobin
 The synthesis of HB
– Begins at the
A P
Proerythroblast stage
C C – Continue up to
reticulocyte stage
HC CH  Stages of Hb synthesis
N – 2 succinyl CoA combine
H
with 2 glycine molecule
to form a pyrole
Pyrole molecule
molecule

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 Formation of haemoglobin
CH
2

CH
=
CH
3  4 pyrole molecules
CH
3

CH=CH2
combine to form
N N protoporphyrin IX
N
N CH
3
3
CH

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

Protoporphyrin IX

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 Formation of haemoglobin
CH
2

CH
=
CH
3  Protoporphyrin
CH
3

CH=CH2
combine with Fe++
N N to form Haeme
Fe++
N
N CH
3
3
CH

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

Haeme

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 Formation of haemoglobin
CH Each haeme molecule
2
= 
CH CH
3

CH
3 combine with a long
CH=CH2 polypeptide chain
N N
Fe++ O2 (Globin)
N – To form haemoglobin
N CH
3
3
CH

chain
- COO- - (CH2 )
(CH2 ) - COO-  There are different
types of chains
Poypeptide chain formed depending on
(Globin) amino acid
composition of the
polypeptide chain
Haemoglobin chain
( or )
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 Formation of haemoglobin
CH The different types of
2
= 
CH CH
3
haemoglobin chains
CH
3

CH=CH2 include
N N   Chain contain 141 AA
Fe++ O2 residues
N
N CH
3
  Chain contain 146 AA
3
CH

residues
(CH2 ) - COO-
- COO- - (CH2 )   Chain contain 146 AA
residues
Poypeptide chain  10 individual residues
(globin) differ from the 
Chain
  Chain contain 146 AA
Haemoglobin Chain residues
 37 individual residues
differ from  Chain
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 Formation of haemoglobin
 2 alpha chains combine
 with 2 beta chains to
 form Haemoglobin
chain
chain molecule (Hb-A)
– Each chain has MW
  =16,000
chain chain  Total MW of Hb

 = 64,000

Haemoglobin Molecule
(Hb-A)
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 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

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 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

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 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

Oct 9, 2020 Blood 44

 Haemoglobin
 Hb can combine also with carbon
monoxide
– To form carbon
monoxyhaemoglobin
(carboxyheamoglobin)
 Theaffinity of Hb for O2 is lower than
that for CO
– CO displaces O2 from Hb
• This lowers O2 carrying capacity of Hb

Oct 9, 2020 Blood 45