Erythropoiesis

Erythropoiesis is the process by which red blood cells (erythrocytes) are produced. In human adults, this usually occurs within the bone marrow; in humans with certain diseases, in fetuses and in some animals, erythropoeiesis also occurs outside the bone marrow, within the spleen, liver, or yolk sac. This is termed extramedullary erythropoiesis.

The tibia and femur cease to be important sites of hematopoeisis by about age 25; the vertebrae, sternum, and ribs continue to produce red blood cells throughout life.

In the process of red blood cell maturation, a cell undergoes a series of differentiations. A pluripotent stem cell becomes a multipotent stem cell, in turn becoming a unipotential stem cell, a pronormoblast, a basophilic normoblast, a polychromatophilic normoblast, and orthochromatic normoblast, a reticulocyte, at which point the cell is released from the bone marrow, and ultimately becomes an erythrocyte or mature red blood cell circulating in the peripheral blood. These stages correspond to specific appearances of the cell when stained with Wright's stain and examined by light microscopy, but correspond to other biochemical changes.

In the process of maturation a basophilic pronormoblast is converted from a cell with a large nucleus and a volume of 900µm3 to an enucleated disc with a volume of 90µm3.

A feedback loop involving erythropoietin helps regulate the process of erythropoiesis, so that, in non-disease states, the production of red blood cells is equal to the destruction of red blood cells and the red blood cell number is sufficient to sustain adequate tissue oxygen levels but not so high as to cause sludging, thrombosis, or stroke. Erythopoeitin is produced in the kidney in response to low oxygen levels. In addition, erythropoeitin is bound by circulating red blood cells; low circulating numbers lead to a relatively high level of unbound erythropoeitin, which stimulates production in the bone marrow.

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