The liver performs numerous functions including lipid, carbohydrate, and protein metabolism; storage, metabolism, and activation of vitamins; storage of minerals, glycogen, and triglycerides; extramedullary hematopoiesis; and synthesis of coagulant and anticoagulant proteins. It also influences immunologic responses, contributes to digestion through synthesis of bile acids and their enterohepatic circulation, and detoxifies many endogenous and exogenous compounds. Because the liver has a large functional reserve and the ability to regenerate, hepatic injury must be considerable or chronic and recurrent to cause overt hepatic dysfunction or failure.

Injury is usually accompanied by increased liver enzyme activity, with cytosolic transaminases (ALT, AST) acutely reflecting altered membrane permeability or viability and membrane-affiliated enzymes (alkaline phosphatase [AP], γ-glutamyl transferase [GGT]) reflecting cholestasis and enzyme induction. The liver is predisposed to secondary injury owing to its sentinel position between the systemic circulation and GI tract and because it contains the largest population of fixed macrophages (Kupffer cells) in the body. Macrophage phagocytosis can initiate a cascade of inflammatory cytokine/interleukin release leading to focal hepatic damage and local recruitment of inflammatory cells. The considerable metabolic activity of the liver exaggerates its exposure to noxious products, particularly in the centrilobular region, where high cytochrome p450 activity produces noxious products and where hepatocytes are more easily injured by hypoxia. The ability of the liver to store copper and iron can initiate and augment injury through oxidative mechanisms.

Clinical signs of liver injury vary depending on the type, mechanism, and chronicity of injury. Common clinical features may include anorexia, vomiting, diarrhea, weight loss, fever, jaundice, polyuria (PU) and polydipsia (PD), coagulation abnormalities, ascites, and change in fecal color (acholic feces with complete occlusion of bile ducts; green feces with increased enteric bilirubin elimination). Ascites indicates portal hypertension and development of acquired portosystemic shunts and (APSS) usually develops in association with concurrent hypoalbuminemia. Hepatic encephalopathy (HE) develops in acquired liver disease only when diffuse fibrosis and acquired shunts have developed, in acute fulminant liver failure, or secondary to congenital portosystemic shunts. Hepatomegaly is found with diffuse infiltrative or storage disorders, acute extrahepatic bile duct obstruction (EHBDO), or with congenital biliary cystic malformations, whereas microhepatica usually reflects portal venous hypoperfusion and diversion of enteric hepatotrophic factors, or the presence of chronic hepatic fibrosis in dogs.

Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM