Elevated Bilirubin in Urine or Plasma

CLINICAL DIAGNOSTIC MANUAL

Bilirubin is a yellow pigment produced by the breakdown of red blood cells in the liver. Normally, bilirubin is processed by the liver and excreted in bile.

When there is an increase in bilirubin levels in the urine or plasma, it may indicate an issue with bilirubin metabolism, either at the hepatic level, in the bile ducts, or due to increased hemolysis.

This increase can manifest clinically through various symptoms and signs, with jaundice (yellowing of the skin and mucous membranes) being one of the most noticeable.

Pathology	Clinical Symptoms and Signs	Suspected Diagnosis	Confirmatory Diagnosis
Hepatocellular jaundice	Jaundice, dark urine, pale stools, pruritus, fatigue, general malaise	Blood tests (elevated transaminases), history of liver diseases	Liver biopsy, CT/MRI imaging, hepatitis serologies, liver biopsy
Obstructive jaundice	Jaundice, dark urine, pale stools, pruritus, right upper quadrant pain, weight loss	Blood tests (elevated alkaline phosphatase and GGT), abdominal ultrasound	Endoscopic retrograde cholangiopancreatography (ERCP), CT/MRI imaging, biopsy if neoplasia is suspected
Hemolytic anemia	Jaundice, fatigue, weakness, pallor, splenomegaly, dark urine	Blood tests (elevated indirect bilirubin, high LDH, low haptoglobin)	Coombs test, peripheral blood smear, genetic testing if a hereditary disorder is suspected
Gilbert’s syndrome	Mild intermittent jaundice, generally asymptomatic	Blood tests (elevated indirect bilirubin), family history	Genetic testing, exclusion of other causes of hyperbilirubinemia
Crigler-Najjar syndrome	Persistent neonatal jaundice, very high levels of unconjugated bilirubin	Blood tests (elevated indirect bilirubin)	Genetic testing, family history
Dubin-Johnson syndrome	Jaundice, generally asymptomatic	Blood tests (elevated conjugated bilirubin), family history	Genetic testing, liver function tests
Rotor syndrome	Mild jaundice, generally asymptomatic	Blood tests (elevated conjugated bilirubin), family history	Genetic testing, liver function tests
Liver tumours	Jaundice, weight loss, abdominal pain, hepatomegaly, fatigue	Blood tests (elevated tumour markers, abnormal liver function)	Liver biopsy, CT/MRI imaging
Acute liver failure	Jaundice, hepatic encephalopathy, ascites, bleeding, fatigue, nausea, vomiting	Blood tests (elevated transaminases, bilirubin, prolonged coagulation times)	Detailed medical history, viral serologies, liver function tests, CT/MRI imaging