Erythropoiesis: How EPO, Iron, B12, and Folate Drive Red Blood Cell Production

Central Regulator: Erythropoietin (EPO)

Produced by peritubular fibroblasts in the kidney (90%) and hepatocytes (10%) in response to tissue hypoxia (low O₂ delivery). EPO binds receptors on erythroid progenitors in bone marrow → promotes survival, proliferation, differentiation.

Essential Nutrients

Other Factors Affecting Erythropoiesis

• Chronic inflammation: Hepcidin ↑ → iron sequestration (anemia of chronic disease).
• Kidney disease: ↓ EPO production.
• Bone marrow failure: Aplastic anemia, infiltration (leukemia, metastasis), radiation/chemo.
• Hemolysis: Compensatory erythropoiesis (reticulocytosis).
• Endocrine: Thyroid hormone, androgens, growth hormone stimulate erythropoiesis.

Anemia Workup

CBC with indices (MCV, RDW), reticulocyte count, iron studies (ferritin, TSAT), B12/folate, peripheral smear, renal function, inflammatory markers.

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Nutrient	Role	Deficiency → Anemia Type
Iron	Heme synthesis (Fe2+ in protoporphyrin)	Microcytic, hypochromic
Vitamin B12 (cobalamin)	DNA synthesis (methylmalonyl-CoA mutase, methionine synthase)	Macrocytic, megaloblastic
Folate (B9)	DNA synthesis (thymidylate synthase)	Macrocytic, megaloblastic