Скачать или смотреть Wilson's Disease // Pathophysiology and Diagnosis

Wilson's disease is a rare inherited disorder that causes copper to accumulate in your liver, brain and other vital organs.
Normally, ingested copper is absorbed in the duodenum and is transported to the portal circulation. Then copper is taken up by hepatocytes in the liver. In the hepatocytes ATP7B protein binds copper to apoceruloplasmin to form ceruloplasmin, which is secreted into the blood. And excess copper is transported into the bile by ATP7B protein.
But in Wilson disease there is a mutations in the ATP7B gene. ATP7B gene, encodes ATP7B protein. Thus in Wilsons disease there is a deficiency in the ATP7B protein.Deficiency in the ATP7B protein causes a decrease in copper transport into bile, impairs its incorporation into ceruloplasmin, and inhibits ceruloplasmin secretion into the blood. These changes cause copper accumulation in the liver and a decrease in circulating ceruloplasmin.
The copper builds up inside the hepatocyte and starts to produce free radicals.Eventually, all this built up copper and free radical damage injures or destroys the hepatocyte. This damage eventually leads to chronic active hepatitis, fibrosis and cirrhosis. And also causes free copper to spill out into the interstitial space and from there into the blood supply, where it’s circulated to and deposited in other tissues, where it also causes free radical damage over time. One organ in particular is the brain, and for this reason Wilson
disease can have serious neurological symptoms and complications. Neurologic involvement presents as movement disorders like tremor, poor coordination, chorea or rigid dystonia like spastic dystonia, mask like facies, rigidity and gait disturbances.
One place that it can deposit that can be helpful for
diagnosis, is in Descemet’s membrane of the cornea, which is
this membrane between the stroma and the endothelial layer of
the cornea, So you’ll look for something called Kayser- Fleischer rings, which are visible copper deposits in the cornea.
The biochemical diagnosis of Wilson disease is based on a decrease in serum ceruloplasmin, an increase in hepatic copper content (the most sensitive and accurate test), and increased urinary excretion of copper. Demonstration of Kayser-Fleischer rings further favors the diagnosis.
Testing for mutations in ATP7B can be done and is recommended for a definitive diagnosis.
Treatment for Wilson disease involves an initial acute decoppering therapy followed by maintenance therapy to keep copper levels within the normal range.
Treatment options include copper chelators including trientine, penicillamine, an alpha amino acid metabolite
of penicillin without antibiotic properties; and tetrathiomolybdate; and zinc salts. Copper chelating agents, bind free copper in the blood and tissues to facilitate excretion.
Also though, patients can be given zinc salts, which increases the production of metallothionein proteins in intestinal cells. This protein binds to copper and traps it in the cell which are shed and excreted in the feces.




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