Q1 LONG ANSWER 10M ★ High-yield

Define erythropoiesis. Describe its sites, stages, and the factors regulating it. Add a note on the fate of red blood cells.

Physiology · 1st Professional — Pre-Clinical

Definition

Erythropoiesis = the process of formation, development and maturation of red blood cells from a pluripotent haemopoietic stem cell.

Sites

Period	Site
0–3 months (fetal)	Yolk sac (mesoblastic)
3–6 months	Liver and spleen (hepatic)
6 months onward	Bone marrow (myeloid)
Birth – 5 years	Marrow of all bones
After 20 years	Membranous bones only — vertebrae, sternum, ribs, pelvis, skull, proximal ends of humerus and femur

Stages of Development

Pluripotent stem cell → CFU-E → Proerythroblast → Early (basophilic) normoblast → Intermediate (polychromatophilic) normoblast → Late (orthochromatic) normoblast → Reticulocyte → Mature RBC

Changes during maturation

Feature	Change
Cell size	Decreases (20 µm → 7.2 µm)
Nucleus	Shrinks, then extruded at the late normoblast stage
Haemoglobin	Appears at the intermediate normoblast stage and increases
Cytoplasm	Basophilic → polychromatic → acidophilic
Mitochondria, ribosomes	Lost

Total time about 7 days
Reticulocyte spends 1–2 days in marrow, 1 day in blood
Normal reticulocyte count 0.5–1.5%

Factors Necessary for Erythropoiesis

A. Growth factor

Erythropoietin — a glycoprotein hormone

– 90% from the kidney — peritubular interstitial cells

– 10% from the liver

– Stimulus: tissue hypoxia

– Acts on CFU-E → ↑ proliferation and differentiation

B. Maturation factors

Factor	Role	Deficiency
Vitamin B12	DNA synthesis; needs intrinsic factor for absorption in terminal ileum	Megaloblastic (pernicious) anaemia
Folic acid	DNA synthesis	Megaloblastic anaemia
Iron	Haem synthesis	Microcytic hypochromic anaemia
Proteins	Globin synthesis	Anaemia of malnutrition
Vitamin C	Converts Fe3+ → Fe2+; folate metabolism	Anaemia in scurvy
Vitamin B6	Haem synthesis (ala synthase cofactor)	Sideroblastic anaemia
Thyroxine, androgens, GH	General stimulation	Anaemia of hypothyroidism

Regulation

↓ Tissue O2 (anaemia, hypoxia, haemorrhage, altitude) → Renal peritubular cells sense hypoxia → ↑ Erythropoietin → ↑ Erythropoiesis in marrow → ↑ RBC count → ↑ O2 delivery → Negative feedback switches EPO off

Fate of RBC

Lifespan 120 days
Destroyed in the reticuloendothelial system — spleen (the "graveyard of RBC"), liver, bone marrow
Iron is recycled; globin returns to the amino acid pool; haem → bilirubin

Normal Values Related to RBC

Parameter	Male	Female
RBC count	5.0–6.0 million/µL	4.5–5.5 million/µL
Haemoglobin	14–18 g/dL	12–16 g/dL
PCV (haematocrit)	45%	40%
Diameter / thickness	7.2 µm / 2.2 µm	Same
Surface area	120 µm2	Same

Biconcave shape → ↑ surface area for gas exchange, and flexibility to pass through 3 µm capillaries
No nucleus and no mitochondria → energy from anaerobic glycolysis only

Applied Aspects

Chronic renal failure → ↓ erythropoietin → normocytic normochromic anaemia; treated with recombinant EPO
Pernicious anaemia — autoimmune loss of intrinsic factor; needs parenteral B12, oral is useless
Polycythaemia — primary (vera, a myeloproliferative disorder, EPO low) vs secondary (altitude, cyanotic heart disease, EPO high)
EPO abuse in endurance athletes → ↑ haematocrit → thrombosis
Reticulocyte count is the best index of marrow response to therapy

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