Blood is composed of plasma (55%) and cells (45%). Cells include leukocytes, RBCs, and platelets. RBCs comprise one-half the total number of cells. RBCs are made in the bone marrow in response to a low oxygen level in arterial blood, which triggers the kidneys to produce the hormone erythropoietin. Erythropoietin stimulates the development of RBCs, which must pass through several stages before they enter the bloodstream. Initially, a large poorly differentiated cell called a proerythrocyte develops. The proerythrocyte contains no hemoglobin but is programmed, under the influence of the erythropoietin, to pass on the capacity to produce it. When proerythrocytes divide, they produce cells much smaller than themselves called erythroblasts. An erythroblast contains a nucleus that shrinks as the cell’s cytoplasm fills with hemoglobin synthesized from the endoplasmic reticulum. When the cell is about 80% filled with hemoglobin, its nucleus is expelled and the cell is sent into the general circulation to complete its development. The newly developed, immature RBC is called a reticulocyte. Mature RBCs live about 120 days but cannot reproduce because they have no nucleus. When they wear out, they are sent to the spleen to be reduced to their component parts for recycling. For the process to occur as described there must be a normal stem cell pool in the bone marrow, sufficient caloric intake, and adequate supplies of erythropoietin, iron, folate, and vitamin B₁₂.