Physiology of red cell production

Development-

• 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.

Erythropoiesis-

• 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.

Precursors-

• 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- 

• 

  basophilic stippling

• 

  heinz bodies

• 

  Howell- jolly bodies

• 

  Pappenheimer bodies

• 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)