Blood #3, Erythropoiesis - Physiology

1. Erythropoiesis
Def. It is the manufacture of RBC’s
Sites of Erythropoiesis:
•In the fetus, erythrocytes are formed in
the liver and spleen.
·After birth, erythropoiesis is
restricted to the red bone marrow.

2. ·As the person grows older, the
contribution from red marrow of
long bones decreases as it
becomes inactive due to infiltration
with fat.
·After the age of 20 years, the
membranes bones only such as
skull, ribs, vertebrae and pelvis are
the sites of erythropoiesis

3. Factors affecting erythropoiesis
1- Oxygen supply to the tissues and role of
erythropoietin.
2- Healthy bone marrow.
3- Healthy liver.
4- Hormones.
5- Diet.
The number of erythrocytes is regulated so that
they can provide sufficient tissue oxygenation.

4. 1 – Oxygen supply to the tissues
and role of erythropoietin
Conditions that decrease O2 supply to the tissues
increases the rate of production of erythrocytes as
occurs in:
• High altitude
• Increase demands for O
2
in atheletes
• Chronic respiratory disease e.g. COPD.
• Anemia
• Prolonged heart failure.

5. Erythropoietin
hormone
Nature : Glycolipid.
M.W. : 35000
Concentration : Low
Half life : 5 hours
Source :
1- during fetal life : Liver
2- Adult
• 85 % by endothelial cells of peritubular
capillaries in the kidney.
• 15% by tissue macrophages of the liver
(Kupffer cells).

6. Mechanism of action:
Stem cell
Erythropoietin acts on specific receptors on stem cells
mitosis
Erythroblast
Mature erythrocyte
Erythropoietin causing speeding up of all the stages of
development of proerythroblasts into mature erythrocytes

7. N.B.:
Patient with renal failure develop
severe anemia due to inability of
the kidneys to produce the
hormone and the liver can not
compensate this.
Treatment:
Erythropoietin injection.
Blood transfusion.

8. 1- Hypoxia: There is
evidence that oxygen
tension in the kidney is
the major factor regulating
erythropoiesis.
2- Alkalosis: That develops
during acclimatization to
high altitude.
3- Cobalt salts and androgens.
4- β-adrenergic stimulants and adenosine facilitate
erythropoietin secretion.
Stimulation of secretion:

9. 2- Healthy bone marrow.
•A healthy bone marrow is essential
for the production of erythrocytes.
•The bone marrow is destroyed by x
ray, atomic radiation, and drugs as
chloramphenicol and by malignant
tumors leading to aplastic anemia.

10. 3- Healthy
liver.
The liver is essential for erythrpoiesis
because it is the site of :
• Formation of the globin portion of hemoglobin.
• Formation of 15 % of erythropoietin hormone.
• Storage of iron and vitamin B12

11. 4- Hormones.
Erythropoietin
hormone
Androgens stimulate erythropoietin
secretion
Thyroid hormone stimulates general
metabolism

12. 5- Diet.
The following are essential for adequate erythropoiesis
1- Proteins of high biological value .
2- Minerals:
• Iron
• Copper and cobalt as Co-factors for formation of Hb.
• Cobalt as a part of vit. B
12.
3- Vitamins:
Vitamin C. Vitamin B
12. Folic acid.

13. Iron metabolism
Iron is a component of:
- HB
- Myoglobin
- Several enzymes as
• cytochrome oxidase,
• peroxidase
• catalase.

14. • Daily iron intake about 20 mg
• Average daily iron loss is about 0.6
mg/day in and 1.2 mg/day in
• Total body iron is 4 gm distributed as
follows:
70% in Hb
3% in myoglobin.
27% as iron store in liver, spleen
and B.M. as ferritin.

15. Normal plasma iron level is 130 ug/dl
in and 110 ug/dl in .
Iron is transported in plasma bound to
transferring protein, which is normally
35% saturated with iron.
The total body stores of iron are regulated
by changes in the rate of iron absorption.

16. Iron absorption
•Most of the dietary iron is in the
ferric form; however iron is readily
absorbed in the ferrous state.
•Hcl secreted by the stomach
together with ascorbic acid dissolve
the dietary iron into soluble ferrous
complexes which can be absorbed.
•Most of the iron absorbed in the
upper part of the small intestine

17. Vitamin B12
Extrinsic factor
Maturation factor
Cobalt containing vitamin
Erythroblast Erythrocyte
Megaloblast ( Lose their nuclei )
Vit B12 + Folic acid
Megalocyte ( Large irregular RBC’s that can easily destroyed (
Lack of vit. B
12
and folic acid
Failure of
DNA synthesis

18. StorageasnucDimronimRmBID
tCD’nIsRnBD
SEyDnpDED:D,DdhD
daily requirement
of vitamin
B12 is 1 – 3 µg lnI.DS
Ey
DvimpmBID
nBDRtpIDCttapDtCD
sBnRsuDtinhnBD
Vit. B
12
present
in most foods of
animal origin
Lack of vitamin B12 in diet is very rare, since it is
present in most foods of animal origin and its
daily requirement is very little
7mg

19. Absorption of vitamin B
12
Terminal ileum
Intrinsic
factor
7mg
Intrinsic factor is a
glycoprotein of M.W. 4500.
Vit. B
12
combine with
intrinsic factor forming a
complex that resist
digestion by GIT enzymes.
This complex is absorbed
at terminal ileum by
pinocytosis.
Vit. B
12
is transported to
the liver where it is stored.

20. Terminal ileum
Intrinsic factor
B12 deficiency in
food (<3µg/d(
Gastrectomy, atrophic
gastritis, etc.
Gut resection,
Ileitis, Malabsorbtion
Causes of
vit.B
12
deficiency
Macrocytic anemia due to failure of maturation of
RBC’s
Neurological manifestations because the vitamin is
needed for myelination of nerves.
Deficiency of
vitamin B12 causes:

21. Folic acid:
** It is present in green vegetables,
some fruits,
liver and meat.
** It is easily destroyed by cooking.
Deficiency of folic acid could be due to:
deficiency in the diet or
the presence of GIT disease interfering
with its absorption,
** it results in macrocytic anemia.