Liver Flashcards
Cats with primary copper associated hepatopathy are usually what age?
young, median 2 years
1) A side effect of treatment with penacillamine in cats with primary copper-associated hepatopathy
hemolytic anemia
How do you determine qualitative hepatic copper concentrations
rhodanine staining
quantitative is done by atomic absorption spectroscopy
How does accumulation of copper in the hepatocytes cause cellular toxicity?
Accumulated hepatic copper, especially Copper 2+ is a poten cellular toxin that increases oxidant stress in hepatocytes. the oxidative impact of excessive intracellular copper compromises availability of glutathione and damages nucleic acids, proteins and lipids. these effects interrupt the function of metabolic pathways, generation of energy and structural components of cells.
In treating copper hepatopathy, why should zinc not be used with chelators?
Mostly used for maintenance after chelation. Zinc decreases intestinal copper absorption by inducing synthesis of enterocyte metallothionein. Copper binds more avidly than zinc, causing increased fecal loss with normal enterocyte exfoliation. To prevent toxicity, plasma zinc levels should be measured every 2 to 3 months and maintained at 200 to 500 µg/dL.
What is considered normal hepatic copper levels in the dog? In dogs with primary disease vs secondary?
Normal is <400 ppm
Generally, copper levels above 2,000 ppm are consistent with primary disease, and levels below 1,000 ppm indicate secondary disease.
Describe where copper accumulates in primary copper excretion defect vs accumulation secondary to chronic hepatitis.
Copper-containing lysosomes can typically be detected when values exceed 400 ppm. In animals with a primary copper excretion defect, these lysosomes tend to accumulate in a centrilobular pattern. In contrast, copper accumulation secondary to chronic hepatitis tends to have a periportal distribution consistent with cholestasis.
Breeds frequently seen with chronic copper hepatopathy?
Bedlington terriers, West Highland white terriers, Doberman pinschers, cocker spaniels, Labrador retrievers, Dalmatians, Skye terriers.
Bedlingtons and cockers usually present at earlier age <2years
Two forms of chronic copper toxicity?
1) Copper excretion pathway defect
2) Secondary to chronic hepatitis (due to cholestasis)
Mechanism of accumulation of copper secondary to hepatitis.
as the copper levels increase, the binding capacity of metallothionein becomes exceeded, allowing for release of free copper into the hepatic cytosol. It is suspected that the free copper then damages the mitochondria, initiating reactive oxygen species formation and lipid peroxidation and leading to hepatocyte death.
