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 erythropoietin in response to decreased oxygen delivery (as in anemia and hypoxia) or increased levels of androgens. In addition to erythropoietin, red blood cell production requires adequate supplies of substrates, mainly iron, vitamin B12, folate, and heme.
RBCs survive about 120 days. They then lose their cell membranes and are then largely cleared from the circulation by the phagocytic cells of the spleen and liver. Hemoglobin is broken down 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 amino acids. 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.
With aging, hemoglobin and hematocrit (Hct) decrease slightly, but not below normal values. In menstruating women, the most common cause of lower RBC levels is iron deficiency due to chronic blood loss resulting from menstruation.