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Four potential iron overload causes
INTRODUCTION TO IRON OVERLOAD CAUSES
Iron overload can result from either primary or secondary causes:
Iron distribution in normal iron homeostasis
In normal iron homeostasis, iron storage in reticuloendothelial macrophages and hepatocytes maintains a reserve that can be mobilized to provide functional iron to red blood cells, erythrocytes, and parenchymal cells. The balance between iron intake and iron loss is maintained, and there is little accumulation of storage iron in hepatocytes, and virtually none in other parenchymal cells.
Iron distribution in hereditary hemochromatosis
The increased iron absorption observed in hereditary hemochromatosis leads to the gradual accumulation of storage iron in hepatocytes and other parenchymal cells. Iron accumulation in reticuloendothelial macrophages is, initially at least, modest.
For patients with hereditary hemochromatosis the excess iron absorption can be counterbalanced with regular phlebotomy, which reduces the red blood cell iron pool. Excess storage iron in vital organs is redistributed to erythrocytes and then back into the red blood cells, thereby providing effective treatment in patients whose ability to make new red blood cells is unimpaired.
Iron distribution in transfusional iron overload
In transfusional iron overload, phlebotomy is not a viable option. The anemia that originally led to the need for transfusions will have already reduced the red blood cell iron pool. The sudden large increase in the red blood cell iron pool following each transfusion results, after red blood cell degradation, in a gradual redistribution of this iron to reticuloendothelial macrophages. From these cells, it is later shuttled to hepatocytes and other parenchymal cells by transferrin [1]. After repeated 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, leading to the formation of non transferrin bound iron and subsequent cellular damage [2].
Imbalance of iron distribution and turnover during transfusion therapy
Hershko et al [2]. © 1998 Blackwell Publishing, reprinted with permission.
In transfusional iron overload, the levels of excess storage iron and the speed of iron loading are dependent on the number of transfusions received by a patient. However, iron levels are generally greater and the associated morbidities more common than in patients with primary iron overload.
Effective iron chelation therapy is required to reduce body iron levels in regularly transfused patients. The effect of chelation therapy is two-fold: (i) To chelate the 'free' or labile plasma iron (LPI) in the blood in order to help prevent iron loading of organs; and (ii) to remove excess iron from within hepatic, myocardial, and endocrine cells. The chelation of labile iron is extremely important since LPI is highly toxic and, if iron overload is sufficiently high, is produced 24 hours a day. However, the effective control of LPI can be achieved by constant presence of an iron chelator in the plasma.
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