B38. Differential diagnosis of jaundice.

Jaundice or icterus refers to the yellowish discoloration of the skin, sclerae, and mucous membranes due to deposition of bilirubin. Jaundice is the clinical manifestation of increased concentration of bilirubin in the blood, called hyperbilirubinaemia. Discoloration of the sclerae occurs at lower concentrations of bilirubin than the skin.

The reference range of total bilirubin is 5 – 20 µmol/L. Scleral icterus (sometimes called subicterus, but different definitions for subicterus exists) occurs when the bilirubin level reaches approx 40 µmol/L, while icterus occurs at approx 70 µmol/L.

We distinguish two types of hyperbilirubinaemia: unconjugated hyperbilirubinaemia, where the elevation in bilirubin is predominantly due to elevation in unconjugated bilirubin, and conjugated hyperbilirubinaemia.

The most common cause of jaundice is obstruction of the bile ducts, causing conjugated hyperbilirubinaemia. This is called cholestasis.

Etiology

There are many possible causes of hyperbilirubinaemia and jaundice, each of which can be classified according to the type and pathomechanism.

Clinical features

Subicterus is usually the first sign of jaundice. If due to cholestasis, symptoms like pruritus, and fat malabsorption may occur. Other symptoms and findings of cholestasis depends on the type and etiology:

Type Color of stool Indirect bilirubin Direct bilirubin Bilirubin in urine Urinary urobilinogen Common cause
Prehepatic jaundice Dark Increased Normal Normal Increased Haemolytic conditions
Intrahepatic jaundice Pale, acholic Increased Increased Increased (dark urine) Normal or increased Cirrhosis
Posthepatic jaundice Pale, acholic Normal Increased Increased (dark urine) Absent Biliary obstruction

Evaluation

Further evaluation depends on the clinical and laboratory findings. AST and ALT are useful markers of liver injury, while ALP and GGT are markers of cholestasis.

If prehepatic jaundice is supected, the patient should be evaluated for haemolysis (LDH, haptoglobin, blood smear).

If intrahepatic jaundice is suspected, the patient should be evaluated for hepatitis, cirrhosis, and possible causes of them.

If posthepatic jaundice is suspected, the patient should be examined with ultrasound or CT. If this shows signs of biliary obstruction by stone, an ERCP should be performed, which may remove the stone. If imaging shows signs of malignancy, surgery may be indicated.