Specific Considerations with Liver Disease - Hepatic Function
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Synthesis and Storage
Synthesis and Storage
- Proteins. The normal adult liver produces 12 to 15 g of protein per day including the following:
- Albumin is manufactured exclusively in the liver and has a half-life of approximately 20 days. It comprises 50% of all circulating plasma proteins and is the most important drug-binding protein, especially for organic acids such as penicillins and barbiturates. Albumin contributes to oncotic pressure and also serves as a carrier protein for bilirubin and hormones.
- α1-Acid glycoprotein is an “acute phase reactant” and is responsible for binding basic drugs such as amide local anesthetics, propranolol, and opioids.
- Pseudocholinesterase is responsible for the degradation of succinylcholine, mivacurium, and ester-type local anesthetics. In the presence of severely depressed hepatocellular function or a genetically mediated enzyme deficiency, decreased plasma levels may cause profound clinical effects.
- All proteinaceous clotting factors are produced in the liver with the exception of factor VIII, which is produced in the vascular endothelium. Synthesis of factors II (prothrombin), VII, IX, and X as well as proteins C, S, and Z are vitamin K dependent; deficiency of vitamin K or disturbances of liver function may lead to deficiencies of clotting factors and excess bleeding. Factor VII has the shortest half-life (4 to 6 hours) and therefore declines at nearly the same rate as protein C (9 hours). Because factor VII is located in the extrinsic pathway, which is assessed by the prothrombin time (PT), this early decline in the factor VII activity prolongs the PT even though other pathways have not yet been affected. Factors II, IX, and X have half-lives of approximately 60, 24, and 36 hours, respectively. Consequently, it takes 4 to 6 days before their activities are at a minimum level, and an antithrombotic effect is achieved that correlates with the INR.
- Carbohydrates. The liver is actively involved in the homeostatic regulation of plasma glucose levels (glycogen synthesis and gluconeogenesis). The normal liver can store enough glycogen to provide glucose during a fast of 12 to 24 hours. After that time, glucose is derived by gluconeogenesis from amino acids, glycerol, and lactate.
- Lipids. Most of the body's lipoproteins, as well as cholesterol and phospholipids, are formed in the liver.
- Heme and bile.
- The liver is the primary erythropoietic organ of the fetus and continues to be a major site of hematopoiesis until approximately 2 months of age. In healthy adults, the liver is responsible for 20% of heme production. Abnormalities in heme synthesis can result in porphyria.
- The liver forms approximately 800 mL of bile per day. Bile salts are detergents that aid in absorbing, transporting, and excreting lipids. Bile also carries metabolic waste products and drug metabolites to the intestine from the liver. As an emulsifier, bile facilitates fat absorption by the small intestine. Failure to produce or release bile causes jaundice and an inability to absorb fat and fat-soluble vitamins (A, D, E, and K) and can result in steatorrhea, vitamin deficiencies, and coagulopathy.