Chemistry: Liver function & bilirubin – page 3

Conjugated bilirubin backs up into blood and is water soluble, so it appears in urine. Little bilirubin reaches the gut, so urobilinogen falls and stools become pale.

Gut bacteria deconjugate and reduce bilirubin to urobilinogen; part is reabsorbed and a small amount appears in urine. Broad-spectrum antibiotics can reduce its formation.

Caffeine–benzoate acts as an accelerator, freeing unconjugated bilirubin so both fractions react with diazotized sulfanilic acid. Alkaline tartrate, not caffeine, shifts azobilirubin to the blue form.

Water-soluble conjugated bilirubin and albumin-bound delta bilirubin react directly with diazo reagent. Unconjugated bilirubin needs an accelerator and forms the 'indirect' fraction.

Crigler–Najjar type I has no UGT1A1 activity, so unconjugated bilirubin rises very high with kernicterus risk; phenobarbital does not help. Type II responds partly to phenobarbital, and Gilbert is mild.

Dubin–Johnson syndrome is a defect of the canalicular transporter MRP2, causing conjugated hyperbilirubinemia and a dark liver pigment. Rotor syndrome looks similar but without pigment.

Physiological jaundice appears after 24 hours; jaundice in the first day suggests hemolysis (for example HDFN) and needs prompt bilirubin measurement. Unconjugated bilirubin is the usual cause at this age.

Blue-green light converts bilirubin in the skin into photoisomers, including lumirubin, which can be excreted in bile and urine without conjugation.

Conjugated bilirubin above 1.0 mg/dL (17 µmol/L) in an infant indicates cholestasis; biliary atresia must be excluded quickly because early surgery improves outcome. Breast milk and physiological jaundice are unconjugated.

Hepatocellular injury impairs uptake, conjugation and excretion, so both bilirubin fractions rise; conjugated bilirubin enters urine, and ALT rises strongly. Isolated unconjugated rise suggests hemolysis or Gilbert syndrome.

Ammonia rises in vitro from red cell metabolism and deamination of amino acids, so the sample should be put on ice and separated and tested quickly. Hemolysis and patient smoking also raise ammonia.

GLDH combines ammonia with 2-oxoglutarate to form glutamate while oxidizing NADPH; the fall in absorbance at 340 nm is proportional to ammonia. The indophenol (Berthelot) reaction is a different method.

Reye syndrome causes acute encephalopathy and fatty liver after aspirin use in viral illness, with high ammonia and aminotransferases but little or no jaundice. Hepatitis A usually causes clear jaundice.

Several clotting factors have half-lives of hours, so the PT/INR rises quickly when synthesis fails. Albumin has a half-life of about 3 weeks, so it falls slowly.

5′-nucleotidase rises in hepatobiliary disease but not in bone disease or pregnancy, so it helps confirm a liver source of ALP, similar to GGT.

Antimitochondrial antibody with a cholestatic pattern in a middle-aged woman is typical of primary biliary cholangitis. Primary sclerosing cholangitis is linked with inflammatory bowel disease and often p-ANCA.

Without bile, fat-soluble vitamin K is poorly absorbed, but the liver can still make factors once vitamin K is given by injection. In cirrhosis the PT does not correct because synthesis is impaired.

Evelyn–Malloy uses 50% methanol to release unconjugated bilirubin from albumin. Jendrassik–Grof uses caffeine–sodium benzoate instead and is less affected by protein precipitation.

Hemoglobin reacts with the diazonium salt and interferes with azobilirubin formation, giving negative bias in diazo methods. Hemolyzed samples should be recollected.

Type II (Arias syndrome) has some UGT1A1 activity that phenobarbital can induce, lowering bilirubin. Type I has no activity and does not respond. Dubin–Johnson and Rotor cause conjugated hyperbilirubinemia.