Disturbances of metabolic homeostasis is liver disease.

Abstract

The liver occupies a major role in metabolic homeostasis with important functions in carbohydrate, fat and protein metabolism. Abnormalities in glucose homeostasis are common in all forms of liver disease although fasting hypoglycaemia is surprisingly rare. Blood concentrations of the gluconeogenic precursors, lactate and pyruvate, are raised in liver disease, particularly hepatic cirrhosis, although glucogenic amino acid levels tend not to be raised except in hepatic coma. The lipid fuels, non-esterified fatty acids and glycerol, are present in elevated concentration in plasma although ketone body levels tend not to be raised. Plasma triglycerides show variable changes. The metabolic hormones, insulin, glucagon, cortisol and growth hormone both act on and are degraded by, the liver, while catecholamines and thyroid hormones also have major effects on normal hepatic metabolism. In liver disease, particularly cirrhosis, insulin degradation is impaired, with consequent hyperinsulinaemia. There is also insulin resistance due presumably to impaired action of insulin on the liver. Growth hormone levels tend to show paradoxical elevation, while cortisol half-life is prolonged although levels are only variably raised. Plasma glucagon levels are raised only in association with severe liver damage although glucagon action on liver is more often impaired. The changes in metabolic functions of the liver in liver disease may be explained by the combination of parenchymal damage and disordered hormonal action, although changes are less than expected owing to the large reserve capacity of the liver.