Body iron metabolism and pathophysiology of iron overload

Abstract

Iron is an essential metal for the body, while excess iron accumulation causes organ dysfunction through the production of reactive oxygen species. There is a sophisticated balance of body iron metabolism of storage and transport, which is regulated by several factors including the newly identified peptide hepcidin. As there is no passive excretory mechanism of iron, iron is easily accumulated when exogenous iron is loaded by hereditary factors, repeated transfusions, and other diseased conditions. The free irons, non-transferrin-bound iron, and labile plasma iron in the circulation, and the labile iron pool within the cells, are responsible for iron toxicity. The characteristic features of advanced iron overload are failure of vital organs such as liver and heart in addition to endocrine dysfunctions. For the estimation of body iron, there are direct and indirect methods available. Serum ferritin is the most convenient and widely available modality, even though its specificity is sometimes problematic. Recently, new physical detection methods using magnetic resonance imaging and superconducting quantum interference devices have become available to estimate iron concentration in liver and myocardium. The widely used application of iron chelators with high compliance will resolve the problems of organ dysfunction by excess iron and improve patient outcomes.

Sobrecarga de ferro transfusional em portadores de anemia falciforme: comparação entre ressonância magnética e ferritina sérica

“…By comparing the iron-overload intensity between the patient groups submitted to two different transfusion regimens, it is possible to conclude that the group undergoing regular transfusions is more subject to the overload complications as, on average, such group presents three times the EHIC as compared with the group undergoing sporadic transfusions. Such result is in agreement with data in the literature, as the number of transfusions is already a well established predictive factor for iron overload (3,12) . The other variables that are predictive of overload (signal intensity and serum ferritin levels) were also altered in that group.…”

“…There are direct and indirect methods to estimate body iron levels (3) . Serum ferritin test is the most available method and is easily reproducible, in spite of not providing a good specificity (3) .…”

“…Serum ferritin test is the most available method and is easily reproducible, in spite of not providing a good specificity (3) . Hepatic biopsy, in spite of being validated as a reference standard, is an invasive method and, therefore, involves risks inherent to the procedure (4) .…”

Iron, Oxidative Stress and Health

“…Within macrophages, heme derived from phagocytized RBCs is catalyzed by hemeoxygenase (HO). The liberated iron is released via FPN1, donated to Tf and reutilized (Kohgo et al, 2008;Tanna and Miller, 2010). The iron that is not used for metabolic purposes is stored in ferritin.…”

“…NTB1 is taken up by liver and has been shown to contribute to iron loading and hemochromatosis (Mackenzie et al, 2008). Unlike Tf-bound iron, cellular uptake of NTBI is not dependent on TfR and therefore the resulting iron is diffusely distributed throughout the organ (Kohgo et al, 2008). Whether long-term iron supplementation will have adverse effects in humans is also determined by one's antioxidant status.…”