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.