Erythropoiesis

Erythropoiesis, the formation of red cells (erythrocytes), occurs in the red bone marrow of adults and the liver and spleen of the fetus. It can also occur in the liver and spleen of adults following bone marrow damage. Erythropoiesis is primarily controlled by erythropoietin, a glycoprotein hormone secreted primarily by the kidneys in response to hypoxia; about 10–15% is produced by the liver, the major source for the fetus. Other factors such as corticosteroids and growth hormones can also stimulate erythropoiesis.

Erythropoiesis begins when uncommitted stem cells commit to the erythrocyte lineage and under the influence of erythropoietin transform into rapidly growing precursor cells (colony forming unit erythroid cells, CFU-E) and then proerythroblasts (Figure 6). These large cells are packed with ribosomes, and it is here that haemoglobin synthesis begins. Development and maturation proceeds through early (basophilic), intermediate (polychromatic) and finally late (orthochromatic) erythroblasts (or normoblasts) of decreasing size. As cell division ceases, ribosomal content decreases and haemoglobin increases. The late erythroblast finally loses its nucleus to become a reticulocyte, a young erythrocyte still retaining the vestiges of a ribosomal reticulum. Reticulocytes enter the blood and, as they age, the reticulum disappears and the characteristic biconcave shape develops. About 2 × 10¹¹ erythrocytes are produced from the marrow each day, and normally 1–2% of circulating red cells are reticulocytes. This increases when erythropoiesis is enhanced, for example by increased erythropoietin due to hypoxia associated with respiratory disease or altitude. This can greatly increase erythrocyte numbers (polycythaemia) and haematocrit. Conversely, erythropoietin levels may fall in kidney disease, chronic inflammation and liver cirrhosis, resulting in anaemia.

Erythrocytes are destroyed by macrophages in the liver and spleen after ∼120 days. The spleen also sequesters and eradicates defective erythrocytes. The haem group is split from haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled via transferrin, an iron transport protein, or stored in ferritin. Bilirubin is a brown–yellow compound that is excreted in the bile. An increased rate of haemoglobin breakdown results in excess bilirubin, which stains the tissues (jaundice).

Haemoglobin

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