Approach Hyperbilirubinemia
Bilirubin Metabolism
- General information
• Bilirubin is a pigment formed from the breakdown of hemoglobin and other HEM proteins and must be eliminated from the body.
- Indirect (unconjugated) bilirubin: It is insoluble in water and cannot be excreted in the urine. It is transported to the liver by binding to albumin. The serum normal level is between 0.3-0.7 mg/dl.
• Indirect bilirubin that comes to the liver with albumin is converted to direct bilirubin in the liver.
• UDP-glucuronyl transferase enzyme makes this conjugation.
- Direct (conjugated) bilirubin: It dissolves in water. The serum level is 0.1-0.3 mg/dl.
• Conjugated bilirubin formed in the liver is excreted in the bile ducts and comes to the intestines.
• Direct bilirubin is first converted to urobilinogen and then to stercobilinogen in the intestines. Stecobilinogen is excreted in the stool and gives the stool its color.
• Some of the urobilinogen enters the liver with the enterohepatic circulation and is excreted in the urine by joining the systemic circulation. A small amount of direct bilirubin also returns to the liver and passes into the serum.
• In obstructive jaundice, because bilirubin cannot pass into the intestines, urobilinogen and stercobilinogen cannot be formed, stool color becomes lighter and urobilinogen is lost in the urine.
• If the bilirubin level is above 2.5 mg/dl, jaundice is seen in the sclera and skin.
• Serum bilirubin level is related to the degree of liver damage and prognosis.
Differential diagnosis of hyperbilirubinemia
The rising bilirubin fraction is very valuable in the management of hyperbilirubinemias and is used in the differential diagnosis.
Indirect or unconjugated bilirubin dominance: in prehepatic events
rises.
Excessive bilirubin formation: Hemolytic anemias (reticulocytosis)
• Decreased indirect bilirubin uptake and/or conjugation to the liver: Gilbert and Crigler-Najjar syndromes
Height of both direct and indirect bilirubin: In hepatic events
rises.
Hepatic damage (all hepatitis)
direct or conjugated bilirubin dominance: in posthepatic events
rises (cholestasis).
Decreased flow in intra or extra hepatic bile ducts (stone, tumor, pressure, etc.)
• Impaired excretion of conjugated bilirubin in the liver: Dubin-Johnson and Rotor syndromes
Complete blood count and reticulocyte level should be checked first in indirect bilirubin dominance.
• Cholestasis enzymes should be checked first in direct bilirubin dominance.
• Upper abdominal ultrasonography is the first preferred radiological examination in direct bilirubin dominance.
Bilirubin in the urine:
• Direct bilirubin passes into the urine and shows the increase in direct bilirubin in the serum.
• Indirect bilirubin cannot pass into the urine.
Urobilinogen in urine: Urobilinogen is excreted in the urine and is normally found in the urine.
If the patient has high direct bilirubin but no urobilinogen in the urine, biliary tract obstruction is considered.
• Due to excessive bilirubin production in hemolytic anemia, bilirubin turnover increases and urobilinogen may increase in the urine.
Herditary Hyperbilirubinemias
• Liver function tests and ultrasonography of the liver are normal in all of these diseases. The only affected is bilirubin metabolism.
In Gilbert and Crigler-Najjar 1-2 syndromes, only an increase in indirect bilirubin is seen.
Only direct bilirubin increase is seen in Dubin Johnson and Rotor syndromes.
