Erythropoiesis

Mechanism of RBC Production

1. By: SATHISH RAJAMANI ERYTHROPOIESIS

2. DEFINITION Erythropoiesis is the process of the orogin , development and maturation of erythrocytes Hemopoiesis or Hematopoiesis is the process of origin, development and maturation of all the blood cells.

3. SITE OF ERYTHROPOIESIS IN FETAL LIFE Erythropoiesis occurs in three stages. Mesoblastic Stage – during the first 2 months of intrauterine life, the RBCs are produced from mesenchyme of yolk sac. Hepatic Stage – from third month of intra-uterine life, liver is the main organ that produces RBCs. Spleen and Lymphoid organs are also involved in erythropoiesis.

4. SITE OF ERYTHROPOIESIS ( Cont ) Myeloid Stage – during the last three months of intrauterine life, the RBCs are produced from the red bone marrow and liver. IN NEW BORN BABIES, CHILDREN AND ADULTS Up to the Age of 20 Years: RBCs are produced from the red bone marrow of all the bones (long bones and flat bones). After the Age of 20 Years: RBCs are produced from membranous bones like vertebrae, sternum, ribs, scapula, iliac bones and skull bones and from the end of long bones.

5. Though bone marrow is the site of production of all blood cells, comparatively 75 % of the bone marrow is involved in the production of leukocytes and only 25 % is involved in the production of erythrocytes.

6. PROCESS OF ERYTHROPOIESIS STEM CELLS Stem cells are the primary cells capable of self-renewal and differentiating into specialized cells. Hemopoietic stem cells are the primitive cells in the bone marrow, which give rise to the blood cells. Hemopoietic stem cells in the bone marrow are called uncommitted pluripotent hemopoietic stem cells (PHSC). PHSC is defined as a cell that can give rise to all types of blood cells.

7. PROCESS OF ERYTHROPOIESIS ( Cont ) Committed PHSC – these cells are restricted to give rise to one group of blood cells.\Committed PHSC are of two types: Lymphoid Stem Cells (LSC) & Colony forming Blastocytes . Lymphoid Stem Cells – It gives rise to lymphocytes and natural killer cells. Colony forming blastocytes gives rise to myeloid cells. Myeloid cells are the blood cells other than lymphocytes. Myeloid cells when grown in cultures, these cells form colonies hence the name new colony forming blastocytes .

8. Different units of colony forming cells are CFU – E Means Colony Forming Unit – Erythrocytes. Cells of this unit develop into erythrocytes. Colony Forming Unit Granulocytes / Monocytes (CFU – GM): These cells gives rise to granulocytes (Granulocytes, basophills , and eosinophills ) and Monocytes. Colony Forming Unit – Megakaryocytes (CFU – M) – Platelets are developed from these cells.

9. CHANGES DURING ERYTHROPOIESIS Cells of CFU – E pass through different stages and finally become the matured RBCs, during these stages four important changes are noticed. 1. Reduction in size of the cell (from the diameter of 25 to 7.2 microns). Disappearance of nucleoli and nucleus. Appearance of hemoglobin. Change in the starting properties of the cytoplasm.

10. STAGES OF ERYTHROPOIESIS Various stages between CFU – E Cells and matured RBCs are Pro-erythroblast Early Erythroblast Intermediate Normoblast Late Normoblast Reticulocyte Matured Erythrocyte

11. Pro-Erythroblast ( Megaloblast ) It is the first cells derived from CFU – E. It is very large in size with a diameter of about 20 microns. Its nucleus is large and occupies the cell almost completely. The nucleus has two or more nucleoli and a reticular network. Pro-erythroblast does not contains hemoglobin. The cytoplasm is basophilic in nature. Pro- Erythoblast multiplies several times and finally forms the cell of next stage.

12. EARLY NORMOBLAST This cell is smaller than pro-erythroblast with a diameter of about 15 microns. In the nucleus, the nucleoli disappear. Condensation of chromatin network occurs. The condensed network becomes dense. The cytoplasm is basophillic in nature. Hence this cell is also called as Basophillic erythroblast. The cells develops into next stage called intermediate normoblast .

13. INTERMEDIATE NORMOBLAST Cell is smaller than the early normoblast with a diameter of 10 to 12 microns. The nucleus is still present, but the chromatin network shows further condensation. The hemoglobin starts appearing. Cytoplasm is already basophilic. The cell develops into next stage called late normoblast .

14. Late Normoblast Diameter of the cell decrease further to about 8 to 19 microns. Nucleus becomes very small with very much condensed chromatin network and it is known as ink – spot nucleus. Quantity of hemoglobin increases. Cytoplasm becomes almost acidophilic, so the cell is called as orthochromic erythroblast. In the final stage of late normoblast just before it passes to next next stages. The nucleus disintegrates and disappears. The process by which nucleus disappears is called Pyknosis .

15. RETICULOCYTE It is otherwisw known as immature RBC. It is slightly larger than matured RBC. The cytoplasm contains the reticular network. Due to the presence of reticular network it is called as reticulocyte.

16. MATURED Erythrocyte Reticular network disappears and the cell becomes the matured RBC and attains the bioconcave shape. The cell decreases in size to 7.2 microns in diameter. The matured RBC is with hemoglobin but without nucleus. It requires 7 days for the development and maturation of RBC from pro-erythroblast. It requires 5 days up to the stage of reticulocyte. Reticulocute takes 2 more days to become the matured RBC.