Normal Hematopoiesis and Erythrocyte Physiology
Hematopoietic hierarchy and erythrocyte physiology
Hematopoiesis begins with self-renewing hematopoietic stem cells in marrow niches, progressing through multipotent and lineage-committed progenitors. Erythroid commitment runs from the common myeloid progenitor to the megakaryocyte-erythroid progenitor, then BFU-E, CFU-E, proerythroblast, and the normoblast series (basophilic, polychromatophilic, orthochromic) before enucleation yields the reticulocyte. Erythropoietin, made by renal peritubular interstitial cells in response to hypoxia via HIF, is the principal survival and proliferation signal; iron, vitamin B12, and folate supply heme and DNA synthesis. The mature red cell lacks a nucleus and mitochondria, depends on glycolysis and the hexose monophosphate shunt, and survives about 120 days before splenic clearance. Its membrane skeleton-spectrin, ankyrin, band 3, protein 4.1-maintains deformability and surface area. Hemoglobin A (α2β2) binds oxygen cooperatively; 2,3-BPG, pH, and temperature shift the dissociation curve. Laboratory assessment includes MCV, MCH, MCHC, RDW, reticulocyte count, and peripheral smear.
Traps: MCHC above about 360 g/L suggests spherocytes or a preanalytical artifact such as lipemia or cold agglutinin, not true hyperchromia. A normal RDW favors thalassemia trait over iron deficiency. Correct the reticulocyte percentage for anemia; a high raw percentage may still represent an inadequate marrow response. Fetal erythropoietin comes from the liver, but adult production is renal.
Worked example: a reticulocyte count of 10% with hematocrit 22.5% gives a corrected count of 10 × (22.5/45) = 5%, indicating a poor response for that degree of anemia.