Albertine Donker

General Introduction 15 1 liver disease with impaired synthesis function of the liver and (supplementation of) the sex hormones testosterone and estrogen cause a decrease of hepcidin production. 22,23 Also genetic factors play an important role. Thalassemia syndromes characterized by ineffective erythropoiesis and pathologic variants of the hemochromatosis genes cause inappropriately suppressed serum hepcidin levels. 22,24,25 Figure 1. Systemic iron homeostasis: key role of hepcidin 20 25 mg/day Bone marrow ~ 300mg Erythrocytes ~ 2500mg Macrophages ~ 600 mg Fe-Tf ~ 3mg Iron loss 1-2 mg/day Increased erythroid demand Hypoxia Fe Inflammation + Hepcidin + Iron uptake 1-2 mg/day The majority of body iron in the circulation is derived from the recycling of senescent erythrocytes by macrophages and its subsequent incorporation in new erythroid precursors in the bone marrow. Only ±1-2 mg of iron is absorbed from the diet and lost from the body every day. Hepcidin regulates the systemic iron concentration by inhibiting iron export from duodenal enterocytes and reticulo-endothelial macrophages. It is predominantly produced by hepatocytes. The synthesis of hepcidin is controlled by certain physiologic and pathologic triggers that reflect circulating and stored iron levels, erythropoietic activity, hypoxia and inflammatory signals. Quantities represent the situation in a male adult with a replete iron status. Abbreviations: Fe denotes iron; Fe-Tf, transferrin-bound iron. Figure adapted from Swinkels et al, 2006. 19