Haemopoiesis:

Dr. Anu Elizabeth Joy

Asst. Professor
Department of Physiology
School of Medicine
Dire Dawa University.
 Erythropoiesis.

Leucopoiesis.

Megakaryocytopoiesis.
 Types of bone marrow
Red Bone marrow.

Yellow bone marrow.

ERYTHROPOIESIS:-
ERYTHROPOIESIS
 Process of formation and
Process of formation and maturation of
maturation of RBC .
RBC
Site of formation:
 During intra uterine life: 3 stages

Mesoblastic stage : Up to 3 months

Mesoderm of yolk sac.

Hepatic stage : After 3 months 5 months.

Liver and Spleen.

Myeloid stage : From the 6th month .

Mainly bone marrows.
 In children:

All bones with red marrow.

Liver .

Spleen.
 In adults :
After 18-20 yrs.

Red bone marrow of

Ends of long bone.
Skull.
Ribs .
Vertebrae.
Sternum.
Pelvis .
 Changes during Erythropoiesis:

Cell Size reduces

Cytoplasm increases .

Cytoplasm : Basophilic Polychromatophilic Eosinophilic

Decrease in the size of nucleus and later disappearance of

nucleus

Takes about 7-10 days for the formation of matured RBC

 Stages:
Stem Cell (Haemocytoblast).

Proerythroblast.

Basophil erythroblast / Early Normoblast .

Polychromatophil erythroblast / Intermediate Normoblast.

Orthochromic erythroblast / Late Normoblast.

Reticulocyte.

Mature RBC.
 Stage 1: Stem Cell (Haemocytoblast):

Cell size: 19-23 m in diameter

Very big nucleus open chromatin

4-6 nucleoli

Deep basophilic cytoplasm

Hb absent

Mitosis present.
 STAGE 2: PRONORMOBLAST ( PRO ERYTHROBLAST):

Cell size: 15-20m in diameter

Cytoplasm deep basophilic, Hb absent

Nucleus large (3/4), Open chromatin.

2-3 distinct nucleoli.

Mitosis present

Vit B12 and Folic acid necessary for the next stage.
 Stage 3: Basophil erythroblast / Early Normoblast .

Cell size: 14-16m in diameter.

Nucleus size decreases.

Nucleoli disappeared.

Chromatin network is fine and shows few nodes of condensation.

Active mitosis.

Less basophilic cytoplasm.

 Stage 4 : Polychromatophil erythroblast / Intermediate
Normoblast.

Cell size: 10-14m in diameter.

Further condensation of chromatin.

Nucleus size further decreases.

Hb starts appearing.

Cytoplasm Polychromatophilic .

Mitosis present
 Stage 5: Orthochromic erythroblast / Late Normoblast.

Maturation of the previous stage.

Cell size: 7-10m in diameter

Nucleus small, condensed chromatin having a cart wheel shape.

Hb increases.

Acidophilic cytoplasm.

Mitosis has now ceased.

PYKNOSIS occurs
 Stage 6: Reticulocyte:

Cell size: 7-8 m in diameter.

No nucleus

Network of reticulum in the cytoplasm (remnants of RNA).

Acidophilic cytoplasm.

Reticulocyte present in
Peripheral blood: 1 to 2%
New born: 2-6%
Haemolysis: 25-30%
 Stage 7: Matured RBC.

Cell size: 7.2-7.4m in diameter.

Biconcave disc shape.

Non nucleate.

Cytoplasm acidophilic.

Increase in Hb.
 Regulation of Erythropoiesis:

General factors. Special maturation factors.

Hypoxia.
Dietary factors.
Proteins, Iron ,ca2+ , Vit B12,
Folic acid, Vit C.

Castles intrinsic factor.

Absorption of Vit B12.
 liver
HYPOXIA

Renal Erythropoietic factor

Erythropoietinogen

Erythropoietin
Variation in RBC Count:
 Physiological increase:

High altitude.
New born and Infants.
Muscular exercise.
Males.

Physiological decrease:

Children
Pregnancy
Old age.
 Pathological increase:

Polycythaemia
Polycythaemia Vera.
Congenital heart disease.
Chronic lung disease.
Hyperthyroidism.

Pathological decrease:

Anaemia
 Haemoglobin

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 The haemoglobin is a red globular conjugate
protein, comprise almost one third of the weight of
a red cell.

Composed of Haem and Globin.

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 Globin is made from two similar proteins that "stick
together".

One of the component proteins is called Alpha, the

other is Beta. (2 chains each)(141,146 amino acids)

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 Iron and Hemoglobin

The mineral iron plays an important role in the

bodys delivery and use of oxygen.

It binds oxygen to hemoglobin, which then travels

in the bloodstream to locations throughout the
body.

The iron is in the ferrous form (fe2+)

Combine loosely and Reversible

10 November 2017 Oxygenation
 Oxygen binding at the four haem sites in
hemoglobin does not happen simultaneously.

Once the first haem binds oxygen, it introduces

small changes in the structure of the corresponding
protein chain.
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Oxygenation of 1st haem molecule increases the
affinity of 2nd haem for oxygen

Oxygenation of 2nd haem molecule increases the

affinity of 3rd haem for oxygen

Oxygenation of 3rd haem molecule increases the

affinity of 4th haem for oxygen

Affinity of 4th haem to oxygen is many times that of 1st

haem

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 Oxygen-haemoglobin dissociation curve
Sigmoid shape

P 50 (partial pressure
of O2 at which Hb is
half saturated with O2)
26.6mmHg

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Oxy-Haemoglobin
Hb+o2=HBO2

Carbamino -Haemoglobin
CO2+HbNH2=Hb NH COOH

Reduced /Deoxygenated Haemoglobin

Hb

Carboxy/Carbon -Monoxy Haemoglobin

CO +Hb (affinity is 200 times that of o2 )

Methaemoglobin
Various drugs/ oxidizing agents : fe2+ fe3+
HbOH
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 Normal value:
At birth: 23gm%

Adult:
Males: 14-18gm%
Females : 12-16gm%

Clinically 14.8 gm % of Hb is regarded as 100% Hb

1 gm% Hb when fully saturated combines with 1.34ml of oxygen.

Oxygen carrying capacity of blood in

Males:21ml% Females :18ml%

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 Functions of Hb

Transport of oxygen

Transport of carbon-di-oxide

Act as an excellent acid base buffer(70% buffering power of

whole blood)

Vasodilation .(Nitric oxide binding site in chain)

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 Haemoglobin Reused for synthesis

Globin Haem

Enter amino acid pool

Remaining part Iron

Bilirubin Ferritin
(stored in liver)
Excreted in bile.

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 Types of Hb

Foetal Hb(Hb F):

Structure same as adult Hb except that chain is replaced by

chain

Has greater affinity to oxygen

Life span is less ( about 80 days)

At birth Hb F predominates it gradually disappears 2-3 months

after birth.

If it10persist after 4-6 months after birth=> Thalassaemia(/)

November 2017
 Adult Hb:

Hb A ( 2 , 2)
Predominately seen

Hb A2 (2, 2)
2.5%of total Hb
Produces no abnormalities
Regarded as normal Hb.

Hb appears in foetus after 5 months of intra uterine life

At birth : 20%

More than 1 year: >99%

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 Haemoglobin S (Hb S)
In chain of Hb A at 6th position one Glutamic acid is replaced by
Valine.

When reduced less soluble Hb precipitates in to

crystals within the RBC

Damages the cell membrane.

Crystals elongate and RBC becomes Sickle Shape.

Cells more fragile

Sickle Cell Anaemia

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 Jaundice

Yellowish discoloration of the skin, conjunctiva and other tissues caused

by the presence of excess amount of Bilirubin in the plasma and
tissue fluids.

Normal serum level : 0.2-0.8 mg % (Avg: 0.5 mg %)

Clinically jaundice occurs when serum bilirubin level exceeds 2mg%.

 Physiological jaundice/jaundice of new born :

In the newborn the plasma bilirubin level will be more than I

mg/100ml. It continues to rise during the first week and
then declines .if the level exceeds 12 mg % = physiological
jaundice

Causes :
Excessive haemolysis.
May be due to immaturity of the hepatic conjugating enzyme
system.
November 10, 2017 Dept of Physiology 48