Bilirubin is the a breakdown product of hemoglobin (blood pigment). Bilirubin is formed by hemolysis (breakdown of red blood cells) through several intermediate steps in the reticuloendothelial system indirect (unconjugated) bilirubin. It is then further broken down in the liver to direct (conjugated) bilirubin and passed with the bile to the intestine. There it is further broken down to urobilinogen and stercobilin. Some is reabsorbed, the other is excreted through the intestine and kidney. Direct bilirubin, together with γ-GT (gamma(γ)-glutamyl transferase), is one of the cholestasis-indicating enzymes (cholestase enzymes).
The procedure
Material needed
- Blood serum Note: To avoid hemolysis, serum should be centrifuged if sample transport is prolonged.
Preparation of the patient
- Not necessary
Disruptive factors
- Exposure to light → store in the dark
- Hemolysis of whole blood leads to elevated indirect bilirubin
- Medication (eltrombopag → false-low/normal bilirubin levels).
Normal values – total bilirubin
| Age | Normal values in mg/dl |
| 1st day of life (LT) | < 4,0 |
| 2. LT | < 9,0 |
| 3RD-5TH LT | < 13,5 |
| Adults | < 1,1 |
Normal values – direct (= conjugated) and indirect (= unconjugated) bilirubin
| Normal values in mg/dl | |
| Direct bilirubin | < 0,25 |
| Indirect bilirubin | 0,2-0,8 |
Indications
- Determination of direct bilirubin for diagnosis, differential diagnosis, and progression of jaundice (for values of total bilirubin > 1.1 mg/dl)
- Suspicion of liver disease
- Suspicion of hemolysis – destruction of red blood cells.
- Suspicion of cholangitis
- Suspicion of cholestasis
- Suspicion of cholelithiasis (gallstones)
- Suspicion of tumor disease in the area of the bile ducts / pancreas (pancreas).
Interpretation
Interpretation of increased values
- Bilirubin metabolism disorder
- Alcohol intoxication (alcohol poisoning)
- Cholangitis (bile duct inflammation)
- Cholestasis (bile stasis)
- Criggler-Najjar syndrome – genetic disorder leading to deposition of bilirubin in the brain.
- Drug intoxication
- Hepatitis (inflammation of the liver)
- Hepatocellular carcinoma (liver cancer)
- Infection with leptospires (bacteria).
- Intoxications by fungi
- Cirrhosis of the liver – connective tissue remodeling of the liver associated with functional impairment.
- Meulengracht’s disease – genetic disease associated with intermittent icterus (jaundice).
- Rotor syndrome – genetic disease that leads to chronic jaundice (icterus).
- Salmonella infection
- Sepsis (blood poisoning)
- Steatosis hepatis (fatty liver)
- Medications:
- Lapatinib (EGFR tyrosine kinase inhibitor).
- Nintedanib (tyrosine kinase inhibitor (TKI))
- Probenecid (uricosuric agent)
- Rifampicin (antibiotic)
Interpretation of decreased values
- Not relevant to the disease
Further notes
- To determine liver function, aspartate aminotransferase (AST=GOT), alanine aminotransferase (ALT=GPT), glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (AP) should also always be measured.
- Direct bilirubin is equivalent to conjugated bilirubin (intra- and posthepatic jaundice) and is elevated in: Alcoholic hepatitis, hepatitis (acute, chronic, autoimmune), extrahepatic cholestasis, hepatotoxic hepatocellular damage, hepatocellular carcinoma, posthepatic cirrhosis, primary biliary cholangitis/biliary duct inflammation (PBC, synonyms: nonpurulent destructive cholangitis; formerly primary biliary cirrhosis).
- The laboratory parameter bilirubin is more sensitive than transaminases in the presence of drug-toxic liver damage.
A distinction is made between the following causes of jaundice:
- Prehepatic jaundice – ineffective hematopoiesis (blood formation) → increased Hb (hemoglobin) degradation → increase in bilirubin (especially indirect bilirubin; proportion of indirect bilirubin > 80% of total bilirubin ) – e.g. due to hemolytic anemia, large hematomas (bruises), rhabdomyolysis (muscle dissolution), burns, etc.
- Intrahepatic jaundice – intrahepatic cholestasis (bile stasis in the liver) or disturbed bilirubin metabolism → disturbance of uptake or conjugation, secretion → increase in bilirubin (especially indirect bilirubin).
- Physiological: neonatal icterus (Icterus neonatorum) due tolow activity of glucuronyltransferase in the first days of life.
- Primary disorders of bilirubin metabolism (e.g., Meulengracht disease; Crigler-Najjar syndrome; Dubin-Johnson syndrome; Rotor syndrome).
- Secondary disorders of bilirubin metabolism (liver parenchymal damage, e.g., due to intrahepatic cholestasis/cholangitis; viral hepatitis; fatty liver; liver cirrhosis; hepatocellular carcinoma; intoxications (see below); leptospirosis, salmonella).
- Posthepatic icterus – extrahepatic cholestasis (bile stasis outside the liver) → increase in direct bilirubin (e.g., due to choledocholithiasis; cholangiocellular carcinoma (CCC, cholangiocarcinoma, bile duct carcinoma, bile duct cancer); pancreatic carcinoma; biliary atresia; Ascaris infection).
