SN3 SHORT NOTE 5M ★ High-yield

Define jaundice. Classify it and describe how the types are distinguished.

Pathology · 2nd Professional — Para-Clinical

Definition

Jaundice (icterus) is yellow discolouration of the skin, sclerae and mucous membranes caused by an excess of bilirubin in the blood.

Normal serum bilirubin is 0.3–1.2 mg/dL; jaundice becomes clinically detectable above about 2–2.5 mg/dL, first in the sclerae because of their high elastin content
Bilirubin comes chiefly from senescent red cells broken down by macrophages; unconjugated bilirubin is water-INsoluble and travels bound to albumin, is conjugated with glucuronic acid in hepatocytes by UDP-glucuronyl transferase, and is then water-soluble and excreted in bile

Classification

Type	Bilirubin raised	Mechanism	Causes
Pre-hepatic (haemolytic)	Unconjugated	Excessive production overwhelms conjugation	Haemolytic anaemias, malaria, ineffective erythropoiesis, large haematomas, mismatched transfusion
Hepatic (hepatocellular)	Both, usually conjugated predominant	Impaired uptake, conjugation or excretion; cell injury	Viral hepatitis, alcoholic liver disease, cirrhosis, drugs, leptospirosis
Post-hepatic (obstructive, cholestatic)	Conjugated	Obstruction to bile flow	Gallstones in the common bile duct, carcinoma of the head OF pancreas, cholangiocarcinoma, strictures, biliary atresia, worms (ascaris)

Distinguishing the Three Types

Feature	Pre-hepatic	Hepatic	Post-hepatic
Serum bilirubin	Unconjugated	Mixed	Conjugated
Urine bilirubin	Absent — "acholuric jaundice"; unconjugated bilirubin is bound to albumin and cannot be filtered	Present	Present — dark urine
Urine urobilinogen	Increased	Variable	Absent — no bile reaches the gut
Stool	Dark	Normal or pale	Pale, clay-coloured; may be bulky and offensive (steatorrhoea)
Alkaline phosphatase	Normal	Mildly raised	Markedly raised
ALT and ast	Normal	Markedly raised	Mildly raised
Pruritus	Absent	Variable	Prominent — from retained bile salts
Prothrombin time	Normal	Prolonged, not corrected by vitamin K	Prolonged, corrected by vitamin K

CLINICAL PEARL

The prothrombin time separates hepatic from obstructive jaundice, and vitamin K is the test. In obstruction, bile salts do not reach the gut so fat-soluble vitamin K is not absorbed — giving it parenterally corrects the clotting. In hepatocellular disease the liver cannot synthesise the factors whatever vitamin K is available, so it does not correct. A simple bedside experiment with real diagnostic value.

Congenital Hyperbilirubinaemias

Disorder	Defect	Bilirubin	Course
Gilbert syndrome	Mildly reduced UDP-glucuronyl transferase	Unconjugated	Common (up to 7%), benign; mild jaundice on fasting, stress or infection; needs no treatment
Crigler–NAJJAR type I	Complete absence of the enzyme	Unconjugated, very high	Fatal in infancy from kernicterus without transplantation
Crigler–Najjar type II	Partial deficiency	Unconjugated	Responds to phenobarbitone (enzyme induction)
DUBIN–johnson syndrome	Defective canalicular excretion (MRP2)	Conjugated	Benign; the liver is black from a pigment resembling melanin
Rotor syndrome	Defective storage and excretion	Conjugated	Benign; liver not pigmented

Applied Aspects

Neonatal jaundice — physiological jaundice appears after 24 hours from immature conjugation; jaundice within the first 24 hours is always pathological and suggests haemolysis
Kernicterus — unconjugated bilirubin crosses the immature blood–brain barrier and stains the basal ganglia, causing permanent neurological damage; prevented by phototherapy and exchange transfusion
Courvoisier law — in a jaundiced patient, a palpable, non-tender gallbladder is unlikely to be due to stones, because chronic stone disease makes the gallbladder fibrotic and unable to distend; it suggests carcinoma of the head of the pancreas
Ultrasound is the first investigation — it answers the crucial question of whether the bile ducts are dilated, and so whether the jaundice is obstructive
Falciparum malaria and leptospirosis are important causes in India, and both may present with jaundice and fever
Never assume jaundice with fever is hepatitis — ascending cholangitis (charcot triad of fever with rigors, jaundice and right upper quadrant pain) is a surgical emergency needing urgent biliary drainage

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