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Erythropoiesis

Definition

Erythropoiesis is the process of the origin, development and maturation of erythrocytes

Hemopoiesis or Hematopoiesis

It is the process of origin, development and maturation of all the blood cells

Sites of Erythropoiesis

Fetal stage: yolk sack, liver, spleen, lymphoid tissue

Newborns & Children: long and flat bones

Adults: Membranous bones like vertebra, sternum, skull

Process of Erythropoiesis

From Hemopoietic stem cells: also called uncommitted pluripotent hemopoietic stem cells (PHSC): primitive cells in the bone marrow which gives rise to all types of blood cells

When the cells are designed to form a particular type of blood cell, the uncommitted PHSCs are called committed PHSCs, which is restricted to give rise to one group of blood cells

Committed PHSCs are of 2 types:

  1. Lymphoid stem cells: gives rise to lymphocytes & natural killer (NK) cells
  2. Colony forming cells: which gives rise to myeloid cells

Colony forming myeloid cells are of 3 types:

  • Colony forming unit-erythrocytes (CFU-E) – develops  into erythrocytes
  • Colony forming unit-granulocytes/monocytes (CFU-  GM) – develops into granulocytes and monocytes
  • Colony forming unit-megakaryocytes (CFU-M) –  develops into platelets

Changes during Erythropoiesis

Colony forming unit-erythrocytes (CFU-E) pass through  different stages and finally become the matured RBCs

During these stages 4 important changes occur

  • Reduction in size of the cell (from 25 to 7.2 µ)
  • Disappearance of nucleoli and nucleus
  • Appearance of hemoglobin
  • Change in the staining properties of the cytoplasm

Stages of Erythropoiesis

  • Proerythroblast
  • Early normoblast
  • Intermediate normoblast
  • Late normoblast
  • Reticulocyte
  • Matured erythrocyte

Duration of Erythropoiesis:

  • Proerythrblast to Reticulocyte: 5 days
  • Reticulocyte to Matured RBC: 2 days
  • Total: 7 days

Proerythroblast (Megaloblast)

  • First cell derived from CFU-E
  • Size: Large with a diameter of 20µ
  • Nucleus: Large, occupying the cell completely
  • Haemoglobin: Not present
  • Cytoplasm: Basophilic in nature

Early normoblast

  • Cell derived from multiplication of proeythroblast
  • Size: Little smaller with a diameter of 15µ
  • Nucleus: Condensation of chromatin
  • Haemoglobin: Starts synthesis
  • Cytoplasm: Basophilic in nature

Intermediate normoblast

  • Cell derived from early normoblast
  • Size: Smaller with a diameter of 10-12µ
  • Nucleus: Further condensation of chromatin
  • Haemoglobin: Starts appearing
  • Cytoplasm: Both Acidophilic & Basophilic in nature

Late normoblast

  • Cell derived from intermediate normoblast
  • Size: Much smaller with a diameter of 8-10µ
  • Nucleus: More condensation of chromatin, small in size
  • Haemoglobin: Present
  • Cytoplasm: Acidophilic in nature

Reticulocyte

  • Cell derived from late normoblast
  • Size: Slightly larger than mature RBCs
  • Nucleus: Disappears, only network of reticulum
  • Haemoglobin: Present
  • Cytoplasm: Basophilic in nature

Matured Erythrocyte

  • Cell derived from Reticulocyte
  • Size: 7.2µ
  • Nucleus: Not present
  • Haemoglobin: Present
  • Cytoplasm: Contains Hb
  • Shape: Biconcave

Factors necessary for Erythropoiesis

  1. General factors
  2. Maturation factors
  3. Factors necessary for hemoglobin formation

General Factors

  • Erythropoietin
  • Thyroxine
  • Hemopoietic growth factors
  • Vitamins

Erythropoietin

Secreted by peritubular capillaries of kidney, little  quantities by liver and brain

Hypoxia is the stimulant for the secretion of Erythropoietin

Actions of erythropoietin

  • Promotes production of proerythroblasts from CFU-E
  • Development of proerythroblasts into matured RBCs
  • Release of matured erythrocytes into blood

Thyroxine

Secreted by thyroid gland

Thyroxine accelerates the process of erythropoiesis

Hyperthyroidism secretes excess of Thyroxine leading to Polycythemia

Hemopoietic growth factor

They are interleukins which induce the proliferation of  PHSCs

Interleukins involved are

  • Interleukin-3 (IL-3) & secreted by T-cells
  • Interleukin-6 (IL-6) secreted by T-cells, endothelial cells and  macrophages
  • Interleukin-11 (IL-11) secreted by osteoblast

Vitamins

  • Deficiency of these vitamins cause anaemia  associated with other disorders
  • Vitamin B deficiency causes anaemia and pellagra
  • Vitamin C causes anaemia and scurvy
  • Vitamin D deficiency causes anaemia and rickets
  • Vitamin E deficiency leads to anaemia and  malnutrition

Maturation Factors

  • Vitamin B12 (Cyanocobalamin)
  • Intrinsic Factor of Castle
  • Folic Acid

Vitamin B12 (Cyanocobalamin)

  • It is called extrinsic factor since it is obtained from diet
  • Its absorption from intestine requires the presence of  intrinsic factor of Castle
  • It is stored mostly in liver and in small quantity in  muscle
  • It is essential for synthesis of DNA in RBCs
  • Its deficiency leads to failure in maturation of the cell and reduction in the cell division
  • Deficiency of vitamin B12 causes Pernicious Anaemia

Intrinsic factor of Castle

  • It is produced in gastric mucosa by parietal cells of  gastric glands
  • It is essential for the absorption of vitamin B12 from
  • intestine, failure of which leads to Pernicious Anaemia
  • Deficiency of intrinsic factor occurs in Severe gastritis
  • Ulcer
  • Gastrectomy

Folic Acid

  • It is required for the synthesis of DNA
  • In its absence the synthesis of DNA decreases causing failure of maturation of cells
  • This leads to anaemia in which the cells are cause Magaloblastic Anaemia

Factors necessary for Hemoglobin formation

They are essential for the formation of hemoglobin  in the RBCs, deficiency of which leads to anaemia

The factors are

  • First class proteins and amino acids: Globin
  • Iron: For Heme part of Hb
  • Copper: For absorption of iron from intestine
  • Cobalt and nickel: For utilization of iron during Hb
  • formation
  • Vitamins: Vitamin C, riboflavin, nicotinic acid and  pyridoxine are necessary for formation of Hb

Summary

Erythropoiesis is the process of the origin, development  and maturation of erythrocytes

Uncommitted PHSCs → committed PHSCs

Committed PHSCs → CFU-E (Colony Forming Unit Erythrocyte)

CFU-E → Proerythroblast → Early normoblast →  Intermediate normoblast → Late normoblast →  Reticulocyte → Matured RBC

Duration 7 days

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