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Red Blood Cell Production

By Evan M. Braunstein, MD, PhD, Assistant Professor of Medicine, Division of Hematology, Department of Medicine, Johns Hopkins School of Medicine

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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 oxygen delivery (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 Iron and discussed in Iron Deficiency Anemia. For heme synthesis, see Overview of Porphyrias.

RBCs survive 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. Hemoglobin (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.

With aging, Hb and hematocrit (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.