ErythropoiesisDef. 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.
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
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.
1 – Oxygen supply to the tissues and role of
erythropoietinConditions that decrease O2 supply to the tissues increases the rate of production of erythrocytes as occurs in:
• High altitude
• Increase demands for O2 in atheletes
• Chronic respiratory disease e.g. COPD.
• Anemia
• Prolonged heart failure.
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).
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
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.
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:
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.
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
4- Hormones.
Erythropoietin hormone
Androgens stimulate erythropoietin secretion
Thyroid hormone stimulates general metabolism
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. B12.
3 -Vitamins:
Vitamin C. Vitamin B12. Folic acid.
Iron metabolism Iron is a component of:
- HB
- Myoglobin
- Several enzymes as
• cytochrome oxidase,
• peroxidase
• catalase.
• 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.
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 .
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
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. B12 and folic acidFailure of
DNA synthesis
Storage
daily requirement of vitamin
B12 is 1 – 3 µg
daily requirement of vitamin
B12 is 1 – 3 µg
Vit. B12 present in most foods of
animal origin
Vit. B12 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
Absorption of vitamin B12
Terminal ileum
Intrinsic factor
7mg
Intrinsic factor is a glycoprotein of M.W. 4500.
Vit. B12 combine with intrinsic factor forming a complex that resist digestion by GIT enzymes.
This complex is absorbed at terminal ileum by pinocytosis.
Vit. B12 is transported to the liver where it is stored.
Terminal ileum
Intrinsic factor
B12 deficiency infood (<3µg/d)
Gastrectomy, atrophicgastritis, etc.
Gut resection,Ileitis, Malabsorbtion
Causes of vit.B12
deficiency
Macrocytic anemia due to failure of maturation of RBC’sNeurological manifestations because the vitamin is needed for myelination of nerves.
Deficiency of vitamin B12 causes:
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.