Hepatic copper toxicosis.
Hepatic copper toxicosis.
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肝铜中毒。
DOI：
10.1111/j.1440-1746.1989.tb00823.x
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发表时间：
1989
影响因子：
4.1
通讯作者：
Sternlieb,I
中科院分区：
文献类型：
--
作者：
Sternlieb,I
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Copper homeostasis is maintained through a finely tuned interplay of genetically determined functions which affect intestinal absorption, tissue distribution and biliary excretion of the metal. Absorption and distribution are controlled by an X-linked gene which is defective in patients with Menkes’ syndrome and in mottled and brindled mice, resulting in deficiency and maldistribution of copper.’Copper excretion from the hepatocyte also appears to be controlled genetically through the regulation of biliary copper flow. 2 When the biliary excretion is reduced, as it is in patients with Wilson’s disease and in Bedlington terriers with an inherited form of hepatic copper toxic~ sis,~’~ excessive amounts of copper are retained by the liver. A murine mutation displayed by ‘toxic milk ‘mice also results in the selective accumulation of enormous concentrations of hepatic copper as a prelude to progressive and ultimately fatal injury to hepatocytes.’The nature of the defects in the genetic control mechanisms expressed in the three disorders is still unknown because species-specific diversity of organelle pathology, changes related to the subject’s age and the stage of the disease and the intervention of adaptive phenomena contribute confounding variables. Under certain physiologic and pathologic conditions, mammals accumulate variable amounts of copper in the liver. For example, under physiologic conditions, the hepatic copper concentration in newborns and in the normal dog are 10 times higher than those of human adults without any pathologic consequences. However, sheep grazing on pastures rich in copper are subject to sudden hepatic necrosis, haemolysis and renal insufficiency, a fatal syndrome similar to that seen in patients with fulminant Wilson’s disease and in certain Bedlington terriers. In contrast, the rat liver seems to adapt to increased copper loads, apparently by increasing its excretory capacity!