Section 2: Scientific Principles
Part D: Physiology and Anesthesia
Chapter 17: Hepatic Physiology



The liver is the major site of amino acid metabolism, encompassing both the breakdown of amino acids to form substrates for the carbohydrate and fat metabolic pathways and the synthesis of a large number of biologically essential proteins.

Albumin, the major protein in human serum, accounts for 15 percent of the total hepatic protein synthesis. Albumin synthesis ranges from 120 to 300 mg/kg/dL. The higher figure is noted in the neonatal liver, and there is a progressive decline in synthesis rate with age. 36  Factors that regulate albumin synthesis include dietary availability of amino acids, 37  hormonal balance, and plasma oncotic pressure. 38  Intravascular albumin accounts for about 40 percent of the exchangeable albumin pool, and in this location it exerts its principal function, maintenance of normal oncotic pressure. Various substances bind to albumin in the serum, a feature that makes albumin an important transport vehicle for drugs, hormones, metals, and metabolites. The half-life of albumin is approximately 20 days, so that a decrease in serum albumin is unlikely to occur within a short time of acute liver injury. In patients with ascites and chronic liver disease, the total exchangeable pool of albumin may be normal, but the serum level is often low. 39 

The vitamin K–dependent coagulation factors II, VII, IX, and X are synthesized in the liver, together with factors V, XI, XII, and XIII and fibrinogen, which are not dependent on vitamin K for synthesis. If the fat-soluble vitamin K is deficient, as in obstructive jaundice, or if it is antagonized by one of the coumarin anticoagulants, the coagulation factors are synthesized at the normal rate, but they lack the g-carboxylglutamic acid residues, which are attached in a post-translational event under the influence of vitamin K. The half-lives of the coagulation factors are relatively short; thus, abnormalities in coagulation quickly become apparent in acute liver damage. The actual level of clotting factors in the plasma represents a balance between synthesis and catabolism, and because the liver also synthesizes inhibitors of both coagulation and fibrinolysis, a combination of decreased synthesis and increased removal may arise in acute liver disease. Thus, prolongation of prothrombin time resulting from a deficiency of factors II, V, VII, and X is observed in parenchymal liver disease. When used as a liver function test, the prothrombin time has proved of some value in predicting the outcome of patients suffering from acute liver cell failure after hepatotoxin ingestion, 40  as well as that of patients with liver disease who are undergoing surgery. 41 

Ceruloplasmin, the copper-containing a-globulin, is synthesized in the liver. The plasma level is increased in biliary cirrhosis, Hodgkin‘s disease, pregnancy, and myocardial infarction, and as such it is considered an acute-phase reactant protein. 42 

Breakdown of amino acids by transamination and oxidative deamination leads to the formation of keto acids, ammonia, and glutamine within the liver. The Krebs-Henseleit urea cycle converts the ammonia and most of the other nitrogenous excretory products into urea. Both severe acute and chronic liver disease are characterized by a failure to synthesize urea, as a result of which its blood concentration is significantly reduced. There is also an excessive accumulation of ammonia, which in some way contributes to the encephalopathy often noted in hepatic failure. 43 

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