Difference between revisions of "Category:Liver - Toxic Pathology"

As well as playing a central role in detoxification in the body, the liver itself is very susceptible to intoxication. A vast number of hepatoxic agents are known, and it is impossible to describe and list all of them. Drugs, plant and fungal products, metals and other chemicals are all absorbed from the gut and passed to the liver for detoxification. In the course of this process, new products may be formed, and it can be these metabolites rather than the original compound which is hepatotoxic.

Hepatoxicity, Acute

Hepatoxicity, Chronic

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Hepatic toxicity due to drugs

Primidone

• an anticonvulsant will cause periacinar necrosis in dogs
• prolonged thereapy will result in a small cirrhotic liver

Sulphonamides

• some of these casue hepatic necrosis in susceptible animals
• has been associated with a reduced capability of detoxifying the metabolites
• Doberman Pincher breed appear to be susceptible

Paracetamol

• cats are very susceptible to this drug
• causes periacinar necrosis

Copper and liver disease

• Copper – cofactor for enzymes (lysyl oxidase), electron transport proteins (cytochrome c oxidase) and antioxidant molecules (superoxide dismutase).
• Primarily absorbed through the small intestine and stomach (upper small intestine in the dog).
• Enterocyte regulation of absorption – metallothionein and a copper transport protein – ATPase7A.
• Metallothionein is a low molecular wt cytoplasmic protein, in all tissues; expression in response to heavy metals, various hormones and stress. metallothionein in cytoplasm of enterocytes leads to absorption of copper.
• ATPase7A – transmembrane copper transporter in a number of cell types.
• Defective in people with Menke’s disease – the animal model is the mottled mouse – results in faulty transport of copper out of the cell –leads to copper accumulation in enterocytes. Liver and brain that have little of the transporter experience copper deficiency.
• Chronic diet XS of copper leads to accumulation in the liver .
• Serum copper – in 2 pools
  • Exchangeable pool – loosely bound to carrier molecules; 80% of it bound to transcuperin, the rest bound to albumin.
  • Other pool – tightly bound to carrier molecules.