Differential diagnosis of jaundice

Normal bilirubin values ​​are 2.0-17.0 µmol/l. If serum bilirubin rises above about 20 μmol/l, we speak of hyperbilirubinemia. At higher levels, it begins to build up in the tissues, developing a subicterus (yellowing of the sclera-covered parts of the eyelids, soft palate; serum bilirubin around 30-80 μmol/l), and then jaundice. Pathologies of low bilirubin are not physiologically described, total bilirubin in the blood is mainly represented by unconjugated bilirubin. The terms "direct" and "indirect" bilirubin come from Van den Bergh, according to the method of determination. Roughly direct = conjugated, indirect = unconjugated. In the urine the bilirubin is always conjugated. In the CNS (in newborns kernikterus) tissue with immature or damaged blood-brain barrier is always unconjugated bilirubin. According to the etiology, we distinguish hyperbilirubinemia and jaundice:


 * unconjugated - larger supply of bilirubin, the liver does not have time to conjugate it,
 * conjugated - binding bile secretion
 * mixed.



Hyperbilirubinaemia with increased bilirubin production

 * Most often hemolysis, less often rhabdomyolysis, crush-syndrome, etc.;
 * the capacity of the liver is large, hemolytic jaundice occurs only during massive and/or prolonged hemolysis;
 * in autoimmune hemolysis, in sickle cell disease anemia, hereditary spherocytosis, toxic or allergic reaction, in disorders of erythropoiesis (thalassemia…), hypersplenism.

Icterus neonatorum



 * In addition to hemolysis, the immaturity of conjugation enzymes in the liver also plays a role;
 * occurs in almost half of newborns (70-80 μmol/l) in the first five days;
 * breastfed infants have higher values ​​(UGTA1 enzyme inhibitor in milk) - this is not usually associated with neurological damage;
 * other problems are e.g. fetal erythroblastosis, ABO incompatibility…;
 * pathological jaundice - within 24 hours after delivery, over 220 μmol/l;
 * phototherapy - decomposition of bilirubin in the skin by light 425–475 nm - photoisomer s are polar (they are no longer dangerous for the CNS).

Gilbert's syndrome

 * Chronic, small increase in bilirubin, usually no more than 50–70 μmol/l, subicterus only, decreased hepatic activity UGTA1 ([TATA box] disorder], decreased expression, AD, 10–12% of population);
 * is often diagnosed randomly;
 * bilirubin acts as free radical scavenger, hyperbilirubinemia protects against oxidative stress.

Crigler-Najjar's syndrome

 * AR, complete (type I) or partial (type II) UGTA defect;
 * type I completely lacks conjugated bilirubin, unconjugated levels are around 300–800 μmol/l;
 * jaundice occurs shortly after birth, without phototherapy, individuals soon die of CNS involvement;
 * for type II - concentration approx. 350 μmol/l.

Hyperbilirubinaemia with predominantly conjugated bilirubin

Dubin-Johnson syndrome

 * Benign, AR, symptoms: jaundice only;
 * coproporphyrin I is elevated in the urine for unknown reasons;
 * a defect in the canalicular system by which bilirubin is secreted from hepatocytes.

Rotor syndrom

 * Also rare, similar to the previous one.

Hyperbilirubinemia in biliary outflow disorders

 * Obstruction or inflammation, obstructive jaundice - cholecystitis, cholangioitis, cholelithiasis, primary biliary cirrhosis, tumors of the head of the pancreas or bile ducts.

Intrahepatic cholestasis

 * A number of drugs - estrogen s, steroids, some ATB…;
 * also increasing levels of bile acids and liver enzymes in the blood.

Related articles

 * Icterus • Hyperbilirubinemia in newborns and infants • Juvenile hyperbilirubinemia
 * Biliary obstruction parameters

Literature