![]() ![]() Below, we briefly discuss iron overload in HH, thalassemia, SCD, and chronic hepatopathy. After saturation, the iron accumulates in hepatocytes and in parenchymal cells of the pancreas, myocardium, and endocrine glands 7.Ĭonditions associated with hepatic iron overload include hereditary hemochromastosis (HH), thalassemia, sickle cell cell disease (SCD), sideroblastic anemia, chronic hemolytic anemias, transfusional and parenteral iron overload, dietary iron overload, myelodysplasia, and chronic hepatopathies 14. Red blood cell transfusions provide 200 to 250 mg iron per unit, and the iron contained in the transfused red blood cells accumulates in the reticuloendothelial cells of liver, spleen, bone marrow, and lymph nodes, where it is safely sequestered as ferritin until the storage capacity of the retioculoendothelial system (10 gm of iron, or the amount of iron delivered by 40 to 50 transfusions) is saturated 7. Intravenous blood transfusions lead to preferential involvement of the reticuloendothelial system. Extra-hepatic reticuloendothelial organs (spleen, marrow, and lymph nodes) are relatively spared. The transferrin delivers the excess iron to organs with high transferrin-receptor density (pancreas, myocardium, thyroids, gonads, hypophysis, skin), leading to iron overload at these sites. Eventually, there is spillage of iron into the circulation, where it binds to transferrin 7. ![]() With further progression, iron accumulates in Kupffer cells and biliary epithelium. ![]() Iron overload may result from excess intestinal absorption, repeated intravenous blood transfusions, or a combination of the two:Įxcess intestinal absorption leads initially to accumulation of iron in periportal hepatocytes and later to hepatocytes throughout the liver lobule. Clinical manifestations depend on the pattern and severity of organ involvement, which in turn depend on the route and cause of the iron overload. The damage, if sustained, leads to progressive fibrosis and organ dysfunction. The free intracellular iron reacts with hydrogen and lipid peroxides and generates toxic hydroxyl and lipid radicals that attack cell membranes, cellular proteins and nucleic acids 11, 12. Thus, in normal conditions, iron is stored mainly as ferritin molecules in the cytoplasm, but in iron overload states, iron is stored not only as cytoplasmic ferritin molecules but also as cytoplasmic ferritin clusters, lysosomal ferritin clusters, and insoluble hemosiderin aggregates. Some of the ferritin denatures to form insoluble aggregates of hemosiderin 8, 10, nanoscale particles with a relatively broad range of size and shape 10. Additionally, ferritin molecules cluster in the cystoplasm and inside lysosomes of affected cells. When ferritin storage capacity is exceeded, free iron accumulates in the cells of the affected organ or organs. If sustained, the overload eventually overwhelms the capacity of ferritin to sequester the excess iron. Thus, increased supply of iron leads to systemic iron overload. While the body is capable of regulating intestinal absorption of iron, the body has no mechanism for regulating iron elimination. In normal mammalian liver tissues, ferritin is found mainly in the cytoplasm of hepatic Kupffer cells as well as spleen and in bone marrow macrophages. About 20% of body iron is in storage form and contained within the storage protein, ferritin, a hollow apoprotein shell with a central cavity, (7–8 nm in diameter, filled with iron oxyhydroxide nanocrystals) 8, 10. A small fraction of iron is bound to transferrin, an intravascular transport protein that delivers iron to the liver, bone marrow, and other tissues 7, 9. About 80% of body iron is functional, located in hemoglobin in red blood cells, myoglobin in muscle, and in iron-containing enzymes 7, 8. As a result, iron concentration is normally maintained in a narrow homeostatic range, about 40 mg Fe/kg body weight in women and 50 mg Fe/kg in men 1, 3. The intestinal absorption of iron adjusts to physiological needs and is carefully regulated to balance losses 3. ![]() An additional 2 mg/day is lost in premenopausal women due to menstruation 4. Under physiologic conditions, about 10% of dietary iron (1 to 2 mg/day) is absorbed daily, while a similar amount of iron is lost via sloughing of cells from the skin and mucosal surfaces 4- 6. An essential nutrient, iron is required by every human cell 1, 3. ![]()
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