SN1 SHORT NOTE 5M

Write a short note on the approach to jaundice and interpretation of liver function tests.

General Medicine · Final Professional

Definition

Jaundice is yellow discoloration of the skin, sclerae and mucous membranes due to raised serum bilirubin. It becomes clinically detectable at a bilirubin of about 2.5–3 mg/dL, and is best appreciated in the sclerae in natural daylight. Scleral icterus is the earliest sign because of the high elastin content of the sclera, which binds bilirubin.

BILIRUBIN METABOLISM — the basis of classification

1. Production: breakdown of haem from senescent red cells → unconjugated (indirect) bilirubin, which is water-insoluble and albumin-bound, and therefore does NOT appear in urine.

2. Hepatic uptake and conjugation by UDP-glucuronyl transferase → conjugated (direct) bilirubin, which is water-soluble.

3. Excretion into bile → intestine → converted by bacteria to urobilinogen and stercobilinogen (the latter colouring the stool).

Classification

Type	Mechanism	Bilirubin	Urine	Stool	Examples
Pre-hepatic (haemolytic)	Excess production	Unconjugated	Normal colour; urobilinogen ↑; NO bilirubin	Normal or dark	Haemolysis, ineffective erythropoiesis, large haematoma
Hepatic (hepatocellular)	Impaired uptake, conjugation or excretion	Mixed	Dark; bilirubin present	Normal or pale	Viral hepatitis, alcohol, drugs, cirrhosis, Wilson's, autoimmune hepatitis; Gilbert's (unconjugated)
Post-hepatic (obstructive/cholestatic)	Obstruction to bile flow	Conjugated	DARK (bilirubin present)	PALE, clay-coloured	Gallstones, carcinoma head of pancreas, cholangiocarcinoma, stricture, PBC, drugs

Congenital hyperbilirubinaemias: Gilbert's syndrome (common and benign — mild unconjugated hyperbilirubinaemia, worse with fasting, stress and intercurrent illness, with otherwise normal liver tests; requires reassurance only), Crigler–Najjar (severe unconjugated), and Dubin–Johnson and Rotor syndromes (conjugated).

Liver Function Tests — What Each Actually Measures

Test	Reflects	Comment
ALT and AST	Hepatocellular injury	ALT is more liver-specific; AST is also in muscle, heart and red cells. AST:ALT > 2 suggests ALCOHOLIC liver disease; ALT > AST suggests viral or NAFLD
Alkaline phosphatase (ALP)	Cholestasis / biliary obstruction	Also from bone, placenta and intestine — confirm hepatic origin with GGT
GGT	Biliary epithelium; enzyme induction	Raised with ALP confirms a hepatic source; isolated rise suggests alcohol or enzyme-inducing drugs
Bilirubin (total and direct)	Excretory function	Fractionation classifies the jaundice
ALBUMIN	SYNTHETIC function — long half-life (~20 days)	Reflects chronic liver disease; also low in sepsis, malnutrition and nephrotic syndrome
PROTHROMBIN TIME / INR	SYNTHETIC function — SHORT half-life	The best marker of ACUTE hepatic synthetic failure and the most important prognostic test. Correct with vitamin K to distinguish cholestasis (corrects) from hepatocellular failure (does not)

Note the misnomer: transaminases and ALP measure damage, not function. Albumin, INR and bilirubin are the true tests of function.

Pattern Recognition

Pattern	ALT/AST	ALP	Suggests
Hepatocellular	Markedly raised (often > 10× normal)	Mildly raised	Viral hepatitis, drug injury, ischaemic hepatitis, autoimmune hepatitis
Cholestatic	Mildly raised	Markedly raised	Biliary obstruction, PBC, drug cholestasis, infiltration
Mixed	Both raised	Both raised	Drugs, sepsis, alcohol
Isolated hyperbilirubinaemia	Normal	Normal	Gilbert's syndrome, haemolysis

Very high transaminases (> 1000 IU/L) narrow the differential sharply to: acute viral hepatitis, drug or toxin injury (paracetamol), ischaemic hepatitis ("shock liver"), and autoimmune hepatitis.

Clinical Approach

History:

onset and duration
pruritus, pale stools and dark urine (cholestasis)
fever with rigors and right upper quadrant pain (cholangitis)
painless progressive jaundice with weight loss (malignancy — carcinoma head of pancreas)
alcohol intake
drugs, including herbal, ayurvedic and over-the-counter preparations
risk factors for viral hepatitis (transfusion, injections, tattoos, sexual history, travel)
family history (Wilson's, Gilbert's, haemolysis)
previous biliary surgery.

Examination:

depth and type of jaundice
stigmata of chronic liver disease
hepatomegaly and its character
palpable gall bladder (Courvoisier's law — a palpable, non-tender gall bladder with jaundice suggests malignant obstruction rather than stones)
splenomegaly
ascites
lymph nodes (Virchow's)
scratch marks
xanthelasma
Kayser–Fleischer rings in any young patient.

Investigations

Liver function tests with fractionated bilirubin, INR and albumin; CBC with reticulocyte count and peripheral smear if haemolysis is suspected; direct Coombs test, LDH and haptoglobin.
Urinalysis — bilirubin and urobilinogen.
Viral serology — hepatitis A, B, C and E.
Ultrasound abdomen — the first imaging test, distinguishing dilated ducts (obstructive) from non-dilated (hepatocellular) and identifying stones, masses and liver texture.
MRCP for biliary anatomy; endoscopic ultrasound for distal lesions; ERCP when intervention is anticipated; CECT for masses and staging.
Autoantibodies (ANA, ASMA, AMA), immunoglobulins, caeruloplasmin, ferritin, alpha-1 antitrypsin for chronic disease.
Liver biopsy where the diagnosis remains uncertain after non-invasive assessment.

CLINICAL PEARL

The single most useful early discriminator is the ultrasound answer to one question — are the bile ducts dilated? Dilated ducts mean obstruction, and the patient needs biliary imaging and intervention. Non-dilated ducts mean hepatocellular or intrahepatic cholestatic disease, and the patient needs serology and a hepatological workup. This one question restructures the entire investigation pathway, and it is available cheaply at the bedside.

All questions in Hepatology / GIT

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