Physiology of red cell production


  • They develop at various sites during embryonic periods.
  • Initially yolk sac produces them, then later placenta.
  • During second and third trimester the site shifts to bone marrow and spleen.
  • Yolk sac- produces embryonic hemoglobin and tissue resident macrophages.
  • intraembryonic sites- RBC, platelets, cells of adaptive immunity.


  • differentiation of multipotent stem cells -> primitive erythroid precursors.
  • IL-3, GM-CSF, SCF (stem cell factor/ kit ligand or steel factor) are important for amplification of progenitor cells.
  • EPO (erythropoietin) is a growth factor essential for amplification and terminal differentiation of erythroid progenitors and precursors.
  • BFU-E and CFU-E are two erythroid progenitors.
  • EPO is produced in the kidney (inner cortex and outer medulla) and fetal liver in response to hypoxia/ anemia.

BFU-E: burst forming unit (seen in in vitro cultures)

  • EPO + SCF/IL-3/ GM-CSF = BFU-E  CFU-E.
  • This process takes approximately 2 weeks in vitro.

             CFU-E: colony forming unit.

  • Under the influence of EPO  small colonies of erythroblasts in 7 days’ time.


  • Proerythroblasts -> basophilic normoblast -> polychromatic normoblast -> orthochromatic normoblast -> reticulocyte -> mature erythrocyte.
  • This process involves reduction of cell size, nuclear condensation and extrusion and hemoglobin accumulation.
  • Each proerythroblast  8 reticulocytes (5 days’ time)
  • Erythrocyte  mature RBC (1 day time in circulation)
  • Life span of circulating mature RBC is 4 months (120 days)

In acute anemia- 

  • The length of this transit time may decrease to as little as one or two days because of skipped divisions.
  • The red cells are macrocytic; they may also bear surface i antigen and other fetal characteristics, such as increased (HbF).
  • As a result, stress erythropoiesis is associated with circulating-
    1. Pappenheimer bodies (iron granules), 
    2. basophilic stippling (ribosomes), 
    3. Heinz bodies (haemoglobin inclusions), and 
    4. Howell-Jolly bodies (nuclear remnants) 



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