Development and maturation of erythrocytes require variety of factors, which are classified into three categories:

1. General factors

2. Maturation factors

3. Factors necessary for hemoglobin formation.


General factors necessary for erythropoiesis are:

i. Erythropoietin

ii. Thyroxine

iii. Hemopoietic growth factors

iv. Vitamins.

i. Erythropoietin

Most important general factor for erythropoiesis is the hormone called erythropoietin. It is also called

hemopoietin or erythrocyte stimulating factor.


Erythropoietin is a glycoprotein with 165 amino acids.

Source of secretion

Major quantity of erythropoietin is secreted by peritubular capillaries of kidney. A small quantity is also secreted from liver and brain.

Stimulant for secretion

Hypoxia is the stimulant for the secretion of erythropoietin.

Actions of erythropoietin

Erythropoietin causes formation and release of new RBCs into circulation. After secretion, it takes 4 to 5 days to show the action.

Erythropoietin promotes the following processes:

a. Production of proerythroblasts from CFU-E of the bone marrow

b. Development of proerythroblasts into matured

RBCs through the several stages – early normoblast, intermediate normoblast, late normoblast

and reticulocyte

c. Release of matured erythrocytes into blood. Even some reticulocytes (immature erythrocytes) are

released along with matured RBCs. Blood level of erythropoietin increases in anemia.

ii. Thyroxine

Being a general metabolic hormone, thyroxine accelerates the process of erythropoiesis at many levels.

So, hyperthyroidism and polycythemia are common.

iii. Hemopoietic Growth Factors

Hemopoietic growth factors or growth inducers are the interleukins and stem cell factor (steel factor). Generally these factors induce the proliferation of PHSCs. Interleukins (IL) are glycoproteins, which belong to the cytokines family.

Interleukins involved in erythropoiesis:

a. Interleukin-3 (IL-3) secreted by T-cells

b. Interleukin-6 (IL-6) secreted by T-cells, endothelial cells and macrophages

c. Interleukin-11 (IL-11) secreted by osteoblast.

iv. Vitamins

Some vitamins are also necessary for the process of erythropoiesis. Deficiency of these vitamins cause

anemia associated with other disorders. Vitamins necessary for erythropoiesis:

a. Vitamin B: Its deficiency causes anemia and pellagra (disease characterized by skin lesions,

diarrhea, weakness, nervousness and dementia).

b. Vitamin C: Its deficiency causes anemia and scurvy (ancient disease characterized by impaired collagen synthesis resulting in rough skin, bleeding gum, loosening of teeth, poor wound healing, bone pain, lethargy and emotional changes).

c. Vitamin D: Its deficiency causes anemia and rickets

d. Vitamin E: Its deficiency leads to anemia and malnutrition.


Vitamin B12, intrinsic factor and folic acid are necessary for the maturation of RBCs.

1. Vitamin B12 (Cyanocobalamin)

Vitamin B12 is the maturation factor necessary for erythropoiesis.


Vitamin B12 is called extrinsic factor since it is obtained mostly from diet. Its absorption from intestine requires the presence of intrinsic factor of Castle. Vitamin B12 is stored mostly in liver and in small quantity in muscle. When necessary, it is transported to the bone marrow to promote maturation of RBCs. It is also produced in the large intestine by the intestinal flora.


Vitamin B12 is essential for synthesis of DNA in RBCs. Its deficiency leads to failure in maturation of the cell and reduction in the cell division. Also, the cells are larger with fragile and weak cell membrane resulting in macrocytic anemia.

Deficiency of vitamin B12 causes pernicious anemia. So, vitamin B12 is called antipernicious factor.

2. Intrinsic Factor of Castle

Intrinsic factor of castle is produced in gastric mucosa by the parietal cells of the gastric glands. It is essential for the absorption of vitamin B12 from intestine. In the absence of intrinsic factor, vitamin B12 is not absorbed from intestine. This leads to pernicious anemia.

Deficiency of intrinsic factor occurs in:

i. Severe gastritis

ii. Ulcer

iii. Gastrectomy.

Hematinic principle

Hematinic principle is the principle thought to be produced by the action of intrinsic factor on extrinsic

factor. It is also called or antianemia principle. It is a maturation factor.

3. Folic Acid

Folic acid is also essential for maturation. It is required for the synthesis of DNA. In the absence of folic acid, the synthesis of DNA decreases causing failure of maturation. This leads to anemia in which the cells are larger and appear in megaloblastic (proerythroblastic) stage. And, anemia due to folic acid deficiency is called megaloblastic anemia.


Various materials are essential for the formation of hemoglobin in the RBCs. Deficiency of these substances decreases the production of hemoglobin leading to anemia.

Such factors are:

1. First class proteins and amino acids: Proteins of high biological value are essential for the formation

of hemoglobin. Amino acids derived from these proteins are required for the synthesis of protein

part of hemoglobin, i.e. the globin.

2. Iron: Necessary for the formation of heme part of the hemoglobin.

3. Copper: Necessary for the absorption of iron from the gastrointestinal tract.

4. Cobalt and nickel: These metals are essential for the utilization of iron during hemoglobin formation.

5. Vitamins: Vitamin C, riboflavin, nicotinic acid and pyridoxine are also essential for the formation of


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