Erythropoiesis

Erythropoiesis is the process by which red blood cells develop from hematopoietic stem cells into mature erythrocytes. In adults, this process occurs predominantly in the red bone marrow, with the spleen and liver serving as sites of extramedullary hematopoiesis only under stress. During fetal life, primitive erythropoiesis begins in the yolk sac and later shifts to the fetal liver.

The erythroid lineage progresses through a series of developmental stages: rubriblast (pronormoblast), prorubricyte, rubricyte, and metarubryte (orthochromatic erythroblast). These nucleated precursors synthesize hemoglobin; enucleation occurs late in the orthochromatic stage, and reticulocytes are released into the bloodstream, where they mature into erythrocytes within a day or two. Erythrocytes circulate for about 120 days in humans and are then cleared primarily by macrophages in the spleen and liver, with iron recycled for reuse in hematopoiesis.

Regulation of erythropoiesis is tightly linked to oxygen availability. Erythropoietin (EPO), mainly produced by the kidneys in response to hypoxia, stimulates erythroid progenitors and enhances maturation. Hypoxia-inducible factors (HIF) mediate this response. Adequate iron, vitamin B12, and folate are essential for heme synthesis and DNA replication in erythroid precursors; deficiencies can impair erythropoiesis and cause anemia.

Clinically, reticulocyte counts reflect marrow activity in response to erythropoietic stress. Disorders of erythropoiesis include anemias due to iron deficiency, chronic disease, marrow failure, or dysregulated EPO signaling.