Blood

Physiology
Overview
By the end of the lecture you should be able to
understand:
Composition and functions of blood
Red blood cells:

Characteristics & functions, formation and

destruction

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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
In CVS
 Motion of blood keeps the cells well
dispersed through out plasma

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Blood Volume
Avg blood volume = 7% of body wt
◦ = 4.9(70*0.07)
◦ 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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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
 0ver 90% water
 7% plasma proteins
 created in liver
 confined to bloodstream
◦ albumin
 maintain blood osmotic pressure
◦ globulins (immunoglobulins)
 antibodies bind to foreign
substances called antigens
 form antigen-antibody complexes
◦ fibrinogen
 for clotting
 2% other substances
◦ electrolytes, nutrients, hormones, gases, waste
products

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Blood Cells
Formed elements of blood include
◦ Erythrocytes
◦ Leukocytes
◦ Platelets

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Erythrocytes
Erythrocytes (RBC)
Functions of RBC
◦ To transport Hb
 Hb carries O2
 Hb carries O2 form 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
 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

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Erythrocytes
Shape and size of RBC
7.8
◦ Biconcave discs micromet
◦ Diameter = 7.8 µm 2.5 micrometers ers
◦ avge vol = 90 - 95 µ3

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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

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Erythropoeisis
 Sites of RBC production include
 Yolk sac
◦ 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
Pluripotent Haematopoietic stem cell
(PHSC)
◦ 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
 Erythropoietin 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 &
Basophil erythroblast differentiation
Basophil erythroblast inducers
 The
committed stem cell
Polychromatophil
erythroblast CFU -E
reticulocytes
◦ Undergoes series of
division
Mature erythrocyte

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Stages of RBC Differentiation
PHSC
 The
committed stem cell
CFU-B CFU-E CFU -E
Proerythroblast ◦ Undergoes series of
division to form
Basophil erythroblast mature erythrocyte
Basophil erythroblast Throughout the
Polychromatophil division
erythroblast ◦ Cell becomes filled
reticulocytes with Hb to conc =
Mature erythrocyte 34gm/dl

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 Stages of RBC Differentiation
PHSC
 The nucleus condenses
CFU-B CFU-E to small mass and is
finally extruded
Proerythroblast
◦ This is stage of
Basophil erythroblast reticulocyte
 reticulocyte pass from
Basophil erythroblast
bone marrow to
Polychromatophil capillaries
erythroblast ◦ By
reticulocytes
diapedesis( squeezin
g through capillary
Mature erythrocyte pores)
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Regulation of RBC Production
 Regulated within narrow limits:
1. adequate number is always available to provide
sufficient transport of O2
2. cells do not become so numerous that they impede
blood flow
 Tissue oxygenation is the most essential regulator of
RBC
 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 erythropoietin
Erythropoietin is a glycoprotein MW
34,000
During hypoxia
◦ Rate of production of erythropoietin
increases
 Erythropoietin is produced mainly by the
kidneys (90%)
 The remaining amount is produced in some
other tissue (liver)

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Role of erythropoietin
Erythropoietin 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 Proerythroblast
A P
stage
C C ◦ Continue up to reticulocyte stage
 Stages of Hb synthesis
HC CH
◦ 2 succinyl CoA combine with 2
N
glycine molecule to form a
H
pyrole molecule
Pyrole molecule

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Formation of haemoglobin
CH
2
= 4 pyrole molecules
CH CH
3

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
=  Protoporphyrin combine
CH CH
3

CH
3

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

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

Haeme

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Formation of haemoglobin

= CH
2
 Eachhaeme molecule
CH CH
3

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

(CH2 ) - COO-
 There are different types
- COO- - (CH2 )
of chains formed
Poypeptide chain depending on amino acid
(Globin) composition of the
polypeptide chain
Haemoglobin chain
( or )

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Formation of haemoglobin
= CH
2
 The different types of
CH CH
3

CH
3 haemoglobin chains
CH=CH2 include
N N ◦  Chain contain 141 AA
Fe++ O2
N residues
N CH
3

◦  Chain contain 146 AA

3
CH

(CH2 ) - COO-
residues
- COO- - (CH2 )
◦  Chain contain 146 AA
Poypeptide chain residues
(globin)  10 individual residues 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

chain form Haemoglobin
chain
molecule (Hb-A)
 
chain ◦ Each chain has MW
chain
=16,000
 Total MW of Hb
 = 64,000
Haemoglobin Molecule
(Hb-A)

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Haemoglobin
The most common type of haemoglobin
◦ 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)
O binds loosely with iron (Fe++)
2
◦ 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

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Haemoglobin
Hb can combine also with carbon
monoxide
◦ To form carbon monoxyhaemoglobin
(carboxyhaemoglobin)
 The affinity of Hb for O2 is lower than that
for CO
 CO displaces O2 from Hb
 This lowers O2 carrying capacity of Hb

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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

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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

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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

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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
 Porphyrin portion

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Destruction of RBC
Pophyrin 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

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THANK YOU

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