hematology and oncology
Iron Deficiency Anemia
Pathophysiology of Iron Deficiency Anemia
Iron is distributed in active metabolic and storage pools. Total body iron is about 3.5 g in healthy men and 2.5 g in women; the difference relates to women's smaller body size and dearth of stored iron because of iron loss due to menses. The distribution of body iron is Hemoglobin: 2 g (men), 1.5 g (women) Ferritin: 1 g (men), 0.6 g (women) Hemosiderin: 300 mg Myoglobin: 200 mg Tissue enzymes (heme and nonheme): 150 mg Transport-iron compartment: 3 mg Iron is absorbed in the duodenum and upper jejunum. Iron absorption is determined by its source and by what other substances are ingested with it. Iron absorption is best when food contains heme iron (meat). Dietary nonheme iron is usually in the ferric state (+3) and must be reduced to the ferrous state (+2) and released from food binders by gastric secretions. Nonheme iron absorption is reduced by other food items (eg, milk products, vegetable fiber phytates and polyphenols; tea tannates, including phosphoproteins; bran) and certain antibiotics (eg,tetracycline).Ascorbic acidis the only common food element known to increase nonheme iron absorption. 6 mg/day unless supplemental iron is added ( Pathophysiology reference ). Children have a greater need for iron and appear to absorb more to meet this need. Iron from intestinal mucosal cells is transferred to transferrin, an iron-transport protein synthesized in the liver; transferrin can transport iron from cells (intestinal, macrophages) to specific receptors on erythroblasts, placental cells, and liver cells. For heme synthesis, transferrin transports iron to the erythroblast mitochondria, which insert the iron into protoporphyrin IX for it to become heme. Transferrin (plasma half-life, 8 days) is extruded for reutilization. Synthesis of transferrin increases with iron deficiency but decreases with any type of chronic disease. Iron not used for erythropoiesis is transferred by transferrin to the storage pool; iron is stored in 2 forms: Ferritin Hemosiderin The most important storage form is ferritin (a heterogeneous group of proteins surrounding an iron core), which is a soluble and active storage fraction located in the liver (in hepatocytes), bone marrow, and spleen (in macrophages); in red blood cells (RBCs); and in serum. Iron stored in ferritin is readily available for any body requirement. Circulating (serum) ferritin level parallels the size of the body stores (1 ng/mL=8 mg of iron in the storage pool). The second storage pool of iron is in hemosiderin, which is relatively insoluble and is stored primarily in the liver (in Kupffer cells) and in the bone marrow (in macrophages). Because iron absorption is so limited, the body recycles and conserves iron. Transferrin binds and recycles available iron from aging RBCs undergoing phagocytosis by mononuclear phagocytes. This mechanism provides approximately 90 to 95% of the daily iron needed . Iron Deficiency develops in stages. In the first stage, iron requirement exceeds intake, causing progressive depletion of bone marrow iron stores. As stores decrease, absorption of dietary iron increases in compensation. During later stages, deficiency impairs RBC synthesis, ultimately causing anemia. Severe and prolonged iron deficiency also may cause dysfunction of iron-containing cellular enzymes. 1.Nemeth E, Tuttle MS, Powelson J, et al:Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.Science306(5704):2090–2093, 2004. 