Home « Causes « Iron Metabolism

Iron Metabolism and Normal Iron Homeostasis

Under normal conditions, most iron in the body is tightly bound either to functional molecules such as hemoglobin, to transport proteins such as transferrin, or to intracellular storage proteins such as ferritin. In this tightly bound state, iron cannot cause cellular damage because it cannot participate in oxidative reactions (1).

Maintaining iron balance

Iron homeostasis is maintained by regulating both the absorption of iron from the diet, and its distribution within the body (2). Iron stores are normally at roughly steady state because dietary iron intake is generally balanced by normal, gradual iron loss (about 1 mg/day in men and 1.5 mg/day in menstruating women).

Maintaining iron balance

Iron is absorbed in the duodenum by enterocytes and transferred to the plasma. There it is bound by transferrin, and becomes available for uptake throughout the body by any tissue with transferrin receptors. Liver parenchymal tissue is especially rich in transferrin receptors, and stores large quantities of iron. In muscle tissue, iron is used to make myoglobin, and in bone marrow erythrocytes use it to make hemoglobin. Circulating red blood cells normally comprise the largest iron pool. When they become senescent, red blood cells are engulfed by reticuloendothelial macrophages, which make their iron available for redistribution to other tissues via transferrin.
Adapted with permission from Andrews, et al (3).

Top

Iron distribution in primary iron overload

In hereditary hemochromatosis, increased iron absorption results in a gradual accumulation of storage iron in hepatocytes and other parenchymal cells, but only modest increases in reticuloendothelial macrophages. By reducing the red blood cell iron pool through regular phlebotomies, excess storage iron in vital organs is redistributed to erythrocytes and from there back into the red blood cells, thereby providing effective management in patients whose ability to make new red blood cells is unimpaired. In this respect, excess iron absorption is similar to acute or chronic iron poisoning, for which phlebotomy can be an effective management option.

Top

Iron distribution in transfusional iron overload

In transfusional iron overload, the sudden large increase in the red blood cell iron pool following each transfusion result, after red blood cell degradation, in a gradual redistribution of this iron to reticuloendothelial macrophages. From these cells, iron is later shuttled to hepatocytes and other parenchymal cells (4). After multiple transfusions, excess iron storage in reticuloendothelial, parenchymal, and hepatic cells rapidly reaches and exceeds the levels that can be controlled by normal iron homeostatic mechanisms — and cellular damage results. The level of excess storage iron is dependent on the number of transfusions, but in general is greater than in patients with hereditary iron overload.

Top