HAEMOPOEISIS

DEF: formation of blood cells from stem cells

Theories of hemopoeisis:
i) Monophyletic theory- each cell line has a
separate precursor stem cell
ii) Polyphyletic theory- all cell lines are derived from
a single cell line
evidence- bone marrow of rat is destroyed using
radiation & pluripotent stem cell is injected→
colonies of all cell lines formed in spleen
Totipotent stem cells- blastocysts of embryo

Pluripotent (uncommitted) stem cell- can give

rise to any type of blood cell.
Best source- umbilical cord blood

Committed (progenitor) stem cell- can give rise

to a particular cell line
 Pluripoient stem cell
IL-1,IL-6,IL-3 GM-CSF,G-CSF, SCF

Committed pluripotent stem cell

Colony forming blastocyte Lymphoid stem cell

EP

GM-CSF,IL-3,4,5

CFU--E CFU-GM CFU-M

granulocyte megakaryocyte

RBC N B E M P L
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 Pluripotent stem cell

Committed stem cell Committed stem cells of

of myeloid series lymphoid series

progenitors BFU-E

CFU-E CFU-GM CFU-mega CFU- Eo CFU-B

megakaryo myelob myelob

Blast cells normoblast myeloblast
monoblast blast last last

lymphocyte
Matured neutrophil monocyte platelet eosinophil basophil
cells RBC

T B
erythropoisis
 ERYTHROPOIESIS
❖DEFINITION
❖SITE OF ERYTHROPOIESIS
❖STAGES OF ERYTHROPOIESIS
❖CHANGES DURING ERYTHROPOIESIS
❖FACTORS REGULATING ERYTHROPOIESIS

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 Erythropoiesis
Def:
PROCESS WHICH INVOLVES ORIGIN,
DEVELOPMENT & MATURATION OF
ERYTHROCYTES.
 Sites of Erythropoiesis
fetus 0-2 months (Yolk Sac)
2-7 months ( liver, Spleen)
7-9 months (bone marrow)
infants Bone marrow (practically all bones)

Adults Vertebrae, ribs, sternum, skull, sacrum

and pelvis, proximal ends of femur
Site of erythropoiesis:
In fetal life:-
1.Mesoblastic stage:-
Up to 3 months of fetal life, RBCs are formed from mesoderm of
yolk sac. In this stage erythropoiesis occurs in the blood vessels, so
its also called intravascular erythropoiesis
2. Hepatic stage:
Liver is the main organ. Spleen and lymphoid organs also produce
some RBCs
3. Myeloid stage:
The e bone marrow start producing non –nucleated RBCs
In post l life and adults :
Upto 6years: red bone marrow
6-20 years: long bones & membranous bones
After 20 yrs: all membranous bones
• Cranial
• Ribs
• Sternum
• Vertebrae
• Pelvic bone
• Ends of long bone
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Graph indicating the age and distribution of red bone marrow
 STAGES OF
ERYTHROPOEISIS
Stages of erythropoiesis:
1. Proerythroblast
2. Early normoblast
3. Intermediate normoblast
4. Late normoblast
5. Reticulocyte
6. Mature RBC
Proerythroblast (megaloblast) :
diameter 15-20µ
-cytoplasm basophilic
-nucleus large and occupies most of the cell, distinct nucleoli
-Hb absent
-active mitoses only during stress
-vit B12 & folic acid required for conversion to next stage
Early Normoblast (basophilic erythroblast) :
-diameter 11µ -17µ
-nucleoli absent or rudimentary
-dense nucleus & chromatin
-cytoplasm basophilic
-active mitoses
-no Hb
Intermediate normoblast(polychroamatophil erythroblast)
• Diameter 10-14µ
• Nucleus often eccentric
• No nucleolus
• Hb appears at this stage
• Cytoplasm-polychromatic (eosinophil staining)
• Active mitoses

Late normoblast (orthochromatic erythroblast):

Diameter 7-10µ
No Mitosis
Nucleus assume cartwheel appearance,dense & pyknotic
Nucleus gets extruded or disintegrated
Staining- eosinophil
• Reticulocyte
• Is also known as immature RBC (8-9µ)
• On vital staining, Remnant of RNA appear as reticulum in the
cytoplasm.
• NO nucleus & No cell division
• Hemoglobin content increases
• Cytoplasm is eosinophilic.
• The cells are present both in bone marrow & peripheral blood.

• Normal count is about 1% of total RBCs

• In New born-2-6%
• Haemolysis- 25-30%

Mature RBC
Diameter-7.2µ
Circular & non-nucleated,biconcave disc
 RBC (Erythrocyte)

Normal count -Men- 4.5 – 5.5 millon/mm3

-Women- 4 – 5 millon/mm3

Life span: about 120 days

Site of destruction- RES (predominantly in spleen)

Duration: About 7 days PROERYTHOBLAST

5 DAYS
RETICULOCYTE

2 DAYS
RED BLOOD CELLS
Mature RBC
 Common features during erythropoiesis
1. Gradual decrease in cell size.

2. Gradual disappearance of nucleoli and nucleus.

3. Arrest of mitotic division after loss of nucleus.

4. Gradual increase in hemoglobin concentration.

5. Change in the staining property of cytoplasm.

FACTORS REGULATING
ERYTHROPOIESIS
 Internal External

hormonal Others Maturation factor Hb

•Interleukins
•CSFs
•Erythropoietin •Iron
Intrinsic factor •VitB12 •Copper
•Androgen
•Oestrogen •Cobalt
•Folic acid •Proteins
•Thyroxine
•Growth hormone
•Cortisol
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 ERYTHROPOIETIN
• Erythropoietin is a glycoprotein,

• Most potent stimulus for

erythropoiesis hypoxia.

• In hypoxia - oxygen supply to

tissues is decreased.

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 INCREASE EP PRODUCTION

•Hypoxia
•Low blood volume
•Anemia
•Lung disease
•Hormones like Epi, androgen ,thyroxine
DECREASE Ep PRODUCTION

• Oestrogen

• Chronic renal disease

• Cirrhosis of liver
 FORMATION & RELEASE OF
ERYTHROPOIETIN
Liver Kidney
Hypoxia

Renal erythropoietic factor

Erythropoietinogen Erythropoietin
(  globulin)

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ANDROGEN: Stimulates erythropoiesis
i.e. stimulates Ep production & directly
stimulates erythropoiesis.

OESTROGEN: inhibits erythropoiesis→

inhibiting Ep production & decrease
response of stem cell to Ep

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OTHER FACTOR

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 Intrinsic factor
• Glycoprotien
• Secreted from oxyntic cells of stomach
• Helps in absorptn of vit-B12 from ileum
• One molecule of I.F binds one molecule
vitB12 form i.f-B12 complex
• I.F-B12 complex is resistant to
proteolytic enzyme

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• This complex binds to specific receptor
on surf of mucosal cells of the ileum
• IF is split off from the complex
• Vitamin B12 is released into the portal blood
• Transported in circulation in bound to globulin-
transcobalamin

• Absence of I.F →pernicious anemia

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EXTERNAL / DIETARY
FACTORS

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 MATURATION FACTORS
• VIT-B12

• FOLIC ACID

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 VITAMIN B12

• DIETARY SOURCE: Absent in plants,

present in all animal tissues
• DAILY REQUIREMENT: 2µgm

• Deficiency→ Megaloblastic anemia

i.e. failure in maturation & reduction in
cell division

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 VITAMIN B12
ACTION
• Both vitamin B12 and folic acid are necessary for the
synthesis thymine which is found in DNA but not in
RNA

• Maturation of red cell precursors abnormal due

to abnormal DNA synthesis
• Leads formation of megaloblast in the marrow
• Macrocyte in the circulation

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 FOLIC ACID
• DAILY REQUIRMENT: 100—200µgm
• DIETARY SOURCE: Green leafy vegetable
• Absorbed from intestine-Jejunum
• Deficiency: Synthesis of DNA decreases -
failure maturation→megalobastic anemia

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• Anisocytosis – different sized RBC eg, macrocytic anaemia

• Poikilocytosis – different shaped RBC eg, Sickle cell anaemia

• Erythrocytosis or polycythemia : RBC count above 6.5 million/cmm

• Sperocytosis – shape of RBC is sperical

• Elliptocytosis – elliptical shaped RBC

• Siderocytosis – RBC containing non heaem iron granules

 Regulation of Erythropoiesis

General factors Special maturation factors

1. dietary Maturation factors

Hypoxia 2. Castle’s intrinsic factors (IF)
3. Extrinsic factors
 Factors necessary for erythropoiesis:
1. General factors—
➢ Erythropoietin
➢ Hormones-testosterone, thyroxin, growth hormone and estrogen
➢ Hemopoietic growth factor
➢ Colony stimulating factor
➢ Vitamins

2. Maturation factors—
Vitamin B12 , intrinsic factor and folic acid

3. Factors for Hb synthesis—

Proteins and amino acids, iron, copper,
cobalt and nickel ,vitamins.
MCQs
1. The progression of erythropoiesis from prenatal life to
adulthood is
A.yolk sac—red bone marrow—liver and spleen
B. yolk sac—liver and spleen—red bone marrow
C. red bone marrow—liver and spleen—yolk sac
D. liver and spleen—yolk sac—red bone marrow

2. Percentage of formed elements in the blood is

a) 45%
b) 50%
c) 55%
d) 60%
3. The life span of RBC is
a)100 days
b)110 days
c)120days
d)130days

4. Erythropoietin is formed in the

a)Kidney
b)Spleen
c)Red bone marrow
d)Liver
5. The formation of erythrocytes in foetus takes
place in
a) Liver and spleen
b) Red bone marrow
c) Blood plasma
d) All of these
6.Which of the following statements about
erythrocyte is correct?
a) They fight infection
b) They clot blood
c) They lack nucleus
d) They are produced in the spleen
7. Hemoglobin appears at the stage of:
a)Early normoblast
b)Late normoblast
c)Reticulocyte
d)None
• ANS:
• 1.B
• 2.A
• 3.C
• 4.A
• 5.A
• 6.C
• 7.