Hepatocellular Leakage Enzymes The hepatocellular leakage enzymes are useful in detecting injury to liver parenchymal cells. Generally, increased serum activity represents enzyme leakage from cells through damaged cell membranes. AST: Used in small and large animals. Present liver as well as skeletal muscle and erythrocytes. ALT: Used in small animals only. Largely liver-specific, but can also increase in severe myopathies (release of muscle enzyme) and hemolysis. SDH: Liver specific in nearly all species. Used in large animals in place of ALT. Disease effects Serum activity of the leakage enzymes increases when a sufficient number of hepatocytes experience increased membrane permeability. Serum levels depend on both the number of cells affected and the severity of injury to individual cells. Serum levels do not correlate with reversibility. Diffuse hypoxia (reversible injury) may result in greater serum activity than end-stage cirrhosis (irreversible injury). Increases are not specific with regard to the nature of the injury. "Primary" hepatic disorders inflammation: Viral, bacterial, fungal, immune-mediated, idiopathic. Inflammation can be suppurative or non-suppurative. Note that primary bile duct obstruction may result in secondary hepatocellular injury as accumulated bile acids are toxic to cells. Leakage enzyme levels in end-stage liver disease or portosystemic shunts may be normal or only mildly increased due to reduced number of cells and minimal active injury. intoxications: Drugs, chemicals, plants. These can cause very high enzyme activity if associated with diffuse necrosis. neoplasms: Hepatocellular and bile duct carcinomas, metastatic neoplasia. Variable increases are possible depending on the extent of active hepatocellular injury. Disorders with secondary hepatic effects circulatory: Heart failure, shock, severe anemia, portosystemic shunts, septicemia. metabolic: Endocrine disease (producing fatty liver, e.g. diabetes mellitus, Cushing's disease, and idiopathic lipidosis), hyperthyroidism (? toxic effect of thyroid hormone on liver cells), acute pancreatitis.