Toxic Hepatopathy

Introduction: Hepatic injury caused by exposure to environmental toxins or by specific therapeutic agents is the definition of hepatic toxicity. There are a multitude of agents reported or suspected to be hepatotoxic in companion animals. Cats appear to be far less commonly affected than dogs, most likely due to discriminatory eating habits. However, cats are particularly sensitive to phenolic toxicity due to the limited ability of their liver to excrete waste via glucuronide transferase activity.

The degree and severity of hepatic injury attributed by toxins depends upon substance, dose, and duration of exposure. Most toxic reactions seen in cats are acute in nature. Chronic toxicity is seldom seen. Drugs which cats are particularly sensitive to are acetaminophen, griseofulvin, megesterol acetate, ketoconazole, tetracycline, and diazepam. Environmental toxins are pine oil, inorganic arsenicals (lead, sodium arsenate, and sodium arsenite), thallium, zinc phosphate, white phosphorus, aflatoxin, toluene and phenols.

Acetaminophen toxicity in a cat. A swollen face is common in this type of poisoning.

Pathogenesis: The pathogenesis depends upon the toxin and how it is metabolized. Many toxins have a classic distribution of lesions. The common lesion seen with hepatotoxins is centrilobular hepatic necrosis. Several factors contribute to this particular lesion. First, centrilobular hepatocytes hold most of the enzymes for metabolism of drugs and other compounds. If the agent was not toxic at first, it may be broken down to a toxic metabolite. Second, the centrilobular region is the area of least oxygen tension, thus most susceptible to injury. Necrosis can be seen in the periportal or midzonal regions, but is a great deal less common.

Gross Pathology: Possible findings are a swollen liver, accentuation of lobular pattern, and white areas of necrosis or red hemorrhagic lesions.

Click on the image for a larger view and more information.

Histopathology: There is no true pathognomonic lesion. However, necrosis with minimal inflammation and lipid accumulation are commonly seen with acute hepatotoxicity.

Other changes that may be seen are mild cholangiohepatitis, suppurative cholangitis, and mild lipid accumulation. Still, the classic lesion tends to be centrilobular necrosis.

Clinical Pathology: This depends upon the contributing agent. Laboratory findings tend to be compatible with acute hepatic injury. Abnormalities seen with acute injury are: