Viral Hepatitis and Liver Disease Website Course

Evaluating Liver Test Abnormalities

Understanding the Pathophysiology of Liver Disease

for Health Care Providers

Normal Liver Function

The liver is essential in maintaining metabolic homeostasis. The function of the liver can be categorized as follows:

  1. Processing of nutrients. These processes include glycogenesis, gluconeogenesis, lipogenesis, lipolysis, vitamin storage and amino acid metabolism. The liver also produces bile acids, essential mediators of fat absorption.
  2. Synthesis of plasma proteins. Examples of these proteins include albumin, prothrombin, fibrinogen and various clotting factors.
  3. Detoxification and metabolism of endogenous and exogenous substances. Lipid soluble drugs cannot be excreted by the body and the liver is responsible for converting them to water soluble formulations so they can be excreted. The Cytochrome P450 system (CYP 450) is comprised of more than 50 human P450 enzymes. Liver dysfunction can lead to increased or decreased drug metabolism by the CYP450 system. The resulting higher or lower drug concentrations can further lead to loss of effectiveness as well as toxicity. Note: 1. Most drugs are metabolized by more than one enzyme. 2. Genetic polymorphisms exist among different individuals which can lead to variable drug response. 3. There are other non-cytochrome P450 enzymes in the liver which are also involved in the metabolism of endogenous and exogenous compounds.
  4. Immunologic function. As a gateway between the splanchnic and systemic circulation, the liver can also remove microbes from the gastrointestinal tract before they reach the systemic circulation.