Reticuloendothelial iron metabolism and recycling. Reticuloendothelial cells (macrophages in the bone marrow and spleen, Kupffer cells in the liver) receive their iron from the phagocytosis of nonviable or senescent red blood cells. Heme is catabolized by heme oxygenase 1, and the processed iron is either rapidly recycled to the plasma through the iron exporter ferroportin, or is stored in cytoplasmic ferritin or hemosiderin. This latter is an aggregated and partially denatured form of cytoplasmic ferritin enclosed in membrane-encapsulated lysosomes (siderosomes). Plasma ferritin is a small fraction of cytoplasmic ferritin, glycosylated and secreted through the Golgi apparatus: its concentration reflects the amount of ferritin (and iron) in the macrophage. Ferroportin is the iron exporter from the cell to plasma transferrin: hepcidin, a small peptide produced in the liver, regulates cellular iron efflux by binding to and inducing the degradation via internalization of ferroportin.

In anemic patients receiving regular blood transfusions, iron is primarily taken up by the reticuloendothelial cells and then exported by ferroportin to plasma transferrin, and thereby redistributed to parenchymal cells. This redistribution is modulated by several factors, including the degree of ineffective erythropoiesis through its suppressive effect on hepcidin production.