Synopsis
Classify jaundice by the site of bilirubin disturbance, connect fractionated bilirubin and enzyme patterns to physiology, and identify obstruction, haemolysis or liver failure that requires urgent action.
- Pre-hepatic jaundice usually increases unconjugated bilirubin because bilirubin production exceeds hepatic uptake and conjugation, most often through haemolysis or ineffective erythropoiesis.
- Hepatic jaundice may disturb uptake, conjugation, hepatocyte integrity or canalicular export, so bilirubin fractions and enzyme patterns can be mixed rather than neatly categorical.
- Post-hepatic jaundice causes conjugated bilirubin to reflux into blood; dark urine, pale stool, pruritus and a cholestatic ALP/GGT pattern support impaired bile flow.
Key red flags
Fever, right-upper-quadrant pain, hypotension or altered mental state with jaundice suggests infected biliary obstruction and demands urgent source-control assessment.
Encephalopathy or a rising INR in a person without established cirrhosis raises acute liver failure and requires immediate specialist discussion.
Painless progressive jaundice, pale stools, dark urine or weight loss can indicate malignant obstruction. Adults aged 40 or over with jaundice meet the suspected pancreatic-cancer referral criterion; acute illness may additionally require same-day hospital assessment.
Hypotension, fever, confusion, bleeding or hypoglycaemia matters more urgently than the bilirubin category because it may reveal sepsis or failing hepatic synthesis.
Reasoning priorities
Separate predominantly conjugated from unconjugated accumulation and determine whether bilirubin is entering urine.
Urinary bilirubin supports a conjugated component; an isolated indirect rise directs attention to haemolysis and conjugation disorders, but laboratory fractions are not perfectly disease-specific.
Worked reasoning
A 36-year-old develops scleral icterus after a viral illness: bilirubin is 82 micromol/L, conjugated bilirubin 9 micromol/L, ALT 27 U/L, ALP 91 U/L, haemoglobin 86 g/L, reticulocytes 9%, LDH raised and haptoglobin undetectable.
- Calculate that the bilirubin is predominantly unconjugated and note that ALT and ALP do not show hepatocellular or cholestatic injury.
- Integrate anaemia, reticulocytosis, raised LDH and low haptoglobin: increased red-cell destruction is the actual demonstrated mechanism, so classify this as pre-hepatic jaundice.
- Review the blood film, direct antiglobulin test, medicines, transfusion history and infection context; the direct antiglobulin test is positive and haematology confirms warm autoimmune haemolysis.
- After treatment directed by haematology, haemoglobin rises and bilirubin falls with the haemolysis markers; this biochemical response verifies the mechanism rather than an assumed diagnosis of Gilbert syndrome.