Clinical biochemistry

Reference range

S_ALT males: < 1 µkat/L; females: < 0.7 µkat/L

S_AST  males: < 0.8 µkat/L; females: < 0.6 µkat/L

S_ALP > 2,2 µkat/L

S_GGT males: < 1.9 µkat/L; females: < 1.3 µkat/L

S_bilirubin (total) < 25 µkat/L

S_albumin 35 - 50 g/L

Laboratory examination can help in detecting hepatocyte damage, the presence of cholestasis and in testing liver function and its ev. failure. A sovereign test for detecting hepatocyte damage alanine aminotransferase (ALT). It is a cytoplasmic enzyme that is released even with mild damage to the hepatocyte. It is relatively specific for liver tissue. In special cases, the activity of aspartate aminotransferase (AST) can also help us a mitochondrial enzyme that is released only in more severe damage to the hepatocyte, in its necrosis. The disadvantage is considerable tissue nonspecificity - it is also found in high concentrations in skeletal muscle and myocardium. The AST/ALT ratio is sometimes used - high is found in necrosis of the hepatocyte and in alcoholic liver disease. Alcohol along with non-alcoholic fatty liver disease (NAFLD) and viral hepatitis are among the most common liver diseases.

For the detection of cholestasis alkaline phosphatase (ALP) - an enzyme abundantly found in the cytoplasmic membrane of the biliary lining, but also in the bones, placenta and intestine. The enzyme gammaglutamyltransferase (GGT) helps in distinguishing whether an increase in ALP is of hepatic origin - if both are elevated, ALP is probably of hepatic origin. GGT measurement alone is of little clinical significance; it rises both in cholestasis and with excessive ethanol consumption, as well as induction by many drugs. ALP activity does not distinguish whether the obstruction is intra or extrahepatic, for this requires imaging (usually ultrasound). The most common cause of extrahepatic cholestasis is cholelithiasis or tumour (e.g. pancreatic). Intrahepatic cholestasis is often related to e.g. drug administration, and occurs in autoimmune diseases.

Hyperbilirubinemias occur when there is an imbalance between bilirubin production and its breakdown. Bilirubin is produced in the reticuloendothelial system by the breakdown of heme from erythrocytes, myoglobin and other hemoproteins. Subsequently, this lipophilic unconjugated bilirubin is transported bound to albumin to the liver. Here it is taken up and conjugated by the enzyme UDP-glucuronyltransferase and then excreted by active transport into the bile. Increased hydrophilic conjugated bilirubin freely passes into the urine, in contrast to unconjugated - bound to albumin.Increased production of bilirubin is found in intravascular hemolysis (e.g. neonatal icterus, hemolytic anemia, malaria) or in rhabdomyolysis. Here, unconjugated bilirubin predominates and we do not find evidence of hepatocyte damage or cholestasis. Disordered uptake, conjugation and excretion is caused by damage to the hepatocyte (see below) - both bilirubin are then elevated. There are isolated congenital defects in the transporters or enzymes that process bilirubin. Probably the most common is reduced UDP-glucuronyltransferase activity - Gilbert's syndrome, where we find mild unconjugated hyperbilirubinemia. When bile outflow is impeded or prevented, e.g. by a gallstone, mainly conjugated bilirubin rises, later also unconjugated bilirubin. Signs of cholestasis are also typically found.

Of the many liver functions we are trying to capture in the laboratory the failure of the following: bilirubin metabolism (impaired uptake, conjugation and excretion), proteosynthesis and possibly also urea synthesis + ammonia degradation. Acute changes in proteosynthesis can be detected by measuring a simple coagulation test: prothrombin time (PT) - reflects the synthesis of coagulation factors = proteins often with short half-life (several hours). Measurement of the concentration of albumin in serum is of rather prognostic importance due to its long half-life (about 20 hours) and considerable reserves.Hyperbilirubinemia as a marker of hepatic failure occurs as a consequence of hepatocellular injury, therefore in these cases it is always found together with elevated ALT, and possibly ALP and other enzymes. The cause of hyperbilirubinemia here is failure first of excretion of conjugated bilirubin into bile (the most demanding, ATP-dependent step of bilirubin metabolism), and later of the ability of the hepatocyte to uptake and conjugate bilirubin.Elevated ammonia levels in the blood may result from increased ammonia production (e.g., in the intestine during GIT bleeding) or from impaired incorporation of ammonia into urea (one of the liver's functions). Hyperammonaemia can also be considered a sign of liver failure, but e.g. it does not correlate well with the degree of hepatic encephalopathy and is rather of prognostic significance.