Iron is essential to life because it is the central oxygen ligand in the heme proteins hemoglobin and myoglobin. Accordingly, there are many interactions between iron homeostasis and oxygen regulation and delivery. Iron is also required for cytochrome P-450 enzyme oxidative metabolism and DNA synthesis. In health, body iron content is controlled by absorption that responds to iron losses and the rate of erythropoiesis. Multiple mechanisms provide functional feedback control of iron homeostasis, tissue oxygen sensing and delivery, and the tempo of red blood cell production. The physiologic capacity to excrete iron is very limited. Thus, body iron content is regulated almost entirely by controlled absorption. This chapter reviews the basic physiologic and molecular characteristics of iron metabolism and homeostasis, and their pertinence to iron overload disorders.

Iron physiology

Normal iron homeostasis is maintained by absorption of iron from the diet that precisely balances iron loss, and by controlled iron distribution in the body. Normal healthy adults have 4000–5000 mg of iron (Table 2.1). Daily iron loss occurs due to perspiration, desquamation from skin, and minor injuries, and from the gastrointestinal tract. The rate of this unavoidable iron loss is proportional to body iron stores. Women lose additional iron due to menstruation, pregnancy and childbirth, and lactation. Overall, daily iron losses in adult men and post-menopausal women are approximately 1.0 mg and in menstruating women approximately 1.5 mg. The median iron loss ascribable to pregnancy is 500 mg.