Fig. 2.  Regulation of iron metabolism in the anemia of a critically ill patient. Two opposite stimuli regulate hepcidin, the master regulator of iron metabolism. Inflammation induces hepcidin synthesis, whereas iron deficiency, blood loss, and erythropoiesis stimulation (modulated by erythropoietin synthesis) repress it. A low hepcidin concentration is required to allow iron export and its utilization for erythropoiesis. Apo-Tf = apo-transferrin (i.e. , transferrin free of iron); EPO = erythropoietin; Fe-Tf = transferrin binding iron; Hepc = hepcidin; RBC = erythrocytes.