Red blood cell (RBC) production (erythropoiesis) takes place in the bone marrow under the control of the hormone erythropoietin (EPO). Juxtaglomerular cells in the kidney produce EPO in response to decreased O₂delivery (as in anemia and hypoxia) and increased levels of androgens. In addition to EPO, RBC production requires adequate supplies of substrates, mainly iron, vitamin B₁₂, and folate. Vitamin B₁₂ and folate are discussed in Vitamin Deficiency, Dependency, and Toxicity; iron is discussed in Mineral Deficiency and Toxicity: Iron Deficiency and Toxicity and discussed in Anemias Caused by Deficient Erythropoiesis: Iron Deficiency Anemia.

RBCs become senescent after about 120 days. They then lose their cell membranes and are largely cleared from the circulation by the phagocytic cells of the spleen, liver, and bone marrow. Hb is broken down in these cells and in hepatocytes primarily by the heme oxygenase system with conservation (and subsequent reutilization) of iron, degradation of heme to bilirubin through a series of enzymatic steps, and reutilization of protein. Maintenance of a steady number of RBCs requires daily renewal of 1/120 of the cells; immature RBCs (reticulocytes) are continually released and constitute 0.5 to 1.5% of the peripheral RBC population.

Low levels of androgens leading to decreased EPO levels in women and girls and in elderly patients can predispose to anemia, as does the decline in the capacity of bone marrow to produce RBCs. With aging, Hb and Hct decrease slightly, but not below normal values. In women, other factors that frequently contribute to lower levels of RBCs include cumulative menstrual blood loss and increased demand for iron due to multiple pregnancies.

Last full review/revision June 2008 by Alan E. Lichtin, MD

Content last modified February 2012