Pathophysiology of iron toxicity.
Pathophysiology of iron toxicity.
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DOI：
10.1007/978-1-4615-2554-7_26
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发表时间：
1994
影响因子：
--
通讯作者：
R. Britton;G. Ramm;J. Olynyk;R. Singh;R. O'Neill;B. Bacon
中科院分区：
文献类型：
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作者：
R. Britton;G. Ramm;J. Olynyk;R. Singh;R. O'Neill;B. Bacon
研究表明，在250-300个欧洲血统的个体中，约有1个是血色病基因纯合型，1因此，遗传性血色病被确定为最常见的遗传性疾病之一。在遗传性血色素沉着症和各种形式的继发性铁过载中，主要由于饮食铁吸收的增加，存在身体铁储存的病理性扩张。2，3循环过量铁的细胞摄取导致铁蛋白和含铁血黄素的形成增加，在几个器官的实质组织中发现最高浓度（例如，肝脏、心脏、胰腺）。在高组织铁水平下，这些器官中发生纤维化，并伴有功能性损害。2 - 6虽然在肝脏中进行了最好的研究，但病理学研究也支持铁过载影响的其他器官中的这种关联。因此，对遗传性血色病患者的研究提供了肝铁过载毒性和纤维化的临床证据，4，5非洲铁过载，7和二次铁过载，地中海贫血8，其中肝铁浓度与肝损伤的发生之间的相关性已被证实，或其中通过静脉切开术或螯合疗法治疗性降低肝铁已导致临床改进.尽管临床证据表明过量铁的细胞和组织毒性，但慢性铁超负荷中组织损伤和纤维化的具体病理生理机制仍知之甚少。
It has been shown that approximately 1 in 250–300 individuals of European descent are homozygous for the hemochromatosis gene,1thus identifying hereditary hemochromatosis as one of the most common inherited disorders. In both hereditary hemochromatosis and in the various forms of secondary iron overload, there is a pathologic expansion of body iron stores, due mainly to an increase in absorption of dietary iron.2,3Cellular uptake of circulating excess iron results in increased formation of ferritin and hemosiderin found in highest concentration in the parenchymal tissues of several organs (e.g., liver, heart, pancreas). At high tissue iron levels, fibrogenesis occurs in these organs accompanied by functional insufficiency.2-6Although best studied in the liver, pathological studies support this association in other organs affected in iron overload as well. Thus, clinical evidence for toxicity and fibrosis in hepatic iron overload has been provided by studies of patients with hereditary hemochromatosis,4,5African iron overload,7and secondary iron overload due to ß-thalassemia8in which a correlation between hepatic iron concentration and the occurrence of liver damage has been demonstrated or in which therapeutic reduction of hepatic iron by either phlebotomy or chelation therapy has resulted in clinical improvement. Despite clinical evidence for the cellular and tissue toxicity of excess iron, the specific pathophysiologic mechanisms of tissue injury and fibrogenesis in chronic iron overload are still poorly understood.