Jaundice Approach and Liver Function Patterns
On this page
Direct answer
Jaundice is yellow discolouration from raised bilirubin, and its approach begins by splitting bilirubin into unconjugated and conjugated fractions before reading the liver enzyme pattern. Raised unconjugated bilirubin points to haemolysis or impaired conjugation, while conjugated bilirubin with dark urine points to hepatocellular or obstructive disease. The enzyme pattern then separates hepatocellular injury from cholestasis.
What you must remember
- Clinical threshold: the sclera turns yellow once bilirubin exceeds about 2.5 to 3 mg/dL, so mild jaundice can be missed on the skin.
- Unconjugated: haemolysis, Gilbert syndrome or Crigler-Najjar syndrome; no bilirubin in urine.
- Conjugated: dark urine, pale stools and pruritus in cholestasis; bilirubin is present in urine.
- Hepatocellular pattern: ALT and AST rise markedly, as in viral or toxic hepatitis, with a relatively modest ALP rise.
- Cholestatic pattern: ALP and GGT rise out of proportion to transaminases, and GGT confirms a liver rather than bone source of ALP.
- R ratio: ALT divided by ALP, each expressed as a multiple of its upper limit of normal; above 5 suggests hepatocellular injury, 2 to 5 mixed, and 2 or less cholestatic.
A stepwise pathway for painless jaundice
Consider a 60-year-old woman with three weeks of painless jaundice, pruritus, pale stools and a palpable, non-tender gallbladder. Her bilirubin is 12 mg/dL and mostly conjugated, with raised ALP and GGT and moderately raised ALT.
- Confirm conjugated jaundice. Fractionating bilirubin and checking urine for bilirubin confirm that the jaundice is conjugated rather than haemolytic.
- Establish the enzyme pattern. Raised ALP and GGT, with ALT only moderately raised, make this a cholestatic picture.
- Image the ducts. Ultrasonography shows dilated intrahepatic and extrahepatic ducts, which establishes obstruction.
- Define the level. Cross-sectional imaging such as MRCP defines the level of obstruction and the likely cause.
- Weigh the clues. The painless presentation and palpable gallbladder push the differential towards malignant obstruction of the distal duct, such as carcinoma of the pancreatic head or ampulla, a pattern described in Courvoisier's law. Gallstone obstruction usually causes pain, so its absence is informative.
- Obtain tissue. Endoscopic ultrasound or ERCP, with biopsy or stenting, follows once the level is known, and tumour markers are supportive only and never replace tissue diagnosis.
Where the exam tries to catch you
Four look-alike situations catch candidates out in jaundice questions.
- Trap: assuming raised bilirubin means hepatic disease. Correct: unconjugated hyperbilirubinaemia with normal enzymes points to haemolysis or Gilbert syndrome, so the next step is a reticulocyte count, smear and LDH rather than a hepatitis work-up.
- Trap: treating an isolated raised ALP as liver disease. Correct: bone disease, pregnancy and growth in children all raise ALP, so GGT is measured to confirm a hepatobiliary source.
- Trap: labelling Dubin-Johnson syndrome as obstruction. Correct: it is a benign conjugated hyperbilirubinaemia with normal enzymes and a dark liver on histology.
- Trap: missing that pale stools with dark urine are a cholestatic clue. Correct: the combination signals conjugated bilirubin failing to reach the gut.
Frequently asked questions
Which bilirubin fraction is raised in haemolytic jaundice?
Unconjugated, or indirect, bilirubin is raised in haemolytic jaundice, with normal or only mildly altered liver enzymes. Bilirubin is absent from urine in this setting, while urinary urobilinogen is usually increased.
What does an R ratio above 5 indicate in liver injury?
An R ratio above 5 indicates a hepatocellular pattern of liver injury, while a value of 2 or less indicates cholestasis. Values between 2 and 5 suggest a mixed pattern.
Which sign suggests malignant obstruction in painless jaundice?
A palpable, non-tender gallbladder in painless jaundice suggests malignant obstruction of the distal bile duct, such as pancreatic head or ampullary carcinoma. This is described in Courvoisier's law, and gallstone obstruction usually causes pain.
Why is GGT measured when ALP is raised?
GGT is measured with a raised ALP to confirm a hepatobiliary source, because GGT is high in liver and biliary disease but normal in bone disease. This distinguishes cholestasis from bone-origin ALP elevation.