STEPTRACKERGASTROINTESTINAL | PATHOLOGY + BIOCHEMISTRY | HIGH-YIELD REVIEW

Jaundice & Hyperbilirubinemias

Follow bilirubin from red cell to stool — every jaundice is a jam somewhere along that path.

FOCUS ON
Unconjugated (indirect): too much made (hemolysis) or too little conjugated (Gilbert, Crigler-Najjar, neonatal) — no bilirubin in urine. Conjugated (direct): hepatocyte excretion defect (Dubin-Johnson, Rotor) or obstruction — dark urine, pale stool, pruritus. Crigler-Najjar II responds to phenobarbital; type I doesn't.
DISORDER
MECHANISM
FEATURES
CLUE
Hemolysis (prehepatic)
↑ heme breakdown overwhelms conjugation
Unconjugated ↑; ↑ urine urobilinogen; no bilirubinuria
Anemia, ↑ LDH, ↓ haptoglobin, pigment stones
Physiologic neonatal jaundice
Immature UGT1A1 + high RBC turnover + sterile gut (↑ enterohepatic recirculation)
Unconjugated, appears after 24 h, resolves in 1–2 weeks
Jaundice in the first 24 h is pathologic (hemolysis)
Breastfeeding vs breast milk jaundice
Breastfeeding: poor intake → ↑ enterohepatic circulation · breast milk: β-glucuronidase in milk
Breastfeeding: first week · breast milk: after the first week, lasts weeks
Continue feeding; phototherapy if high
Kernicterus
Unconjugated bilirubin (lipid-soluble, unbound) crosses the BBB
Deposits in basal ganglia → lethargy, hypotonia, seizures, deafness, choreoathetosis
Phototherapy makes water-soluble isomers; exchange transfusion
Gilbert syndrome
Mildly ↓ UGT1A1 activity (promoter variant), ↓ uptake; AR
Mild unconjugated ↑ with fasting, stress, illness, exercise; otherwise normal
Benign · most common inherited hyperbilirubinemia
Crigler-Najjar type I
Absent UGT1A1; AR
Severe unconjugated ↑ in neonates → kernicterus
Phototherapy, plasmapheresis, liver transplant
Crigler-Najjar type II
Severely ↓ (not absent) UGT1A1
Milder; rarely kernicterus
Phenobarbital induces UGT and lowers bilirubin
Dubin-Johnson syndrome
Defective MRP2 canalicular excretion of conjugated bilirubin; AR
Conjugated ↑; black liver (epinephrine metabolite pigment)
Benign
Rotor syndrome
Defective hepatic uptake and storage (OATP1B1/1B3); AR
Conjugated ↑; normal-colored liver
Milder than Dubin-Johnson, benign
Biliary obstruction (posthepatic)
Stones, pancreatic head cancer, cholangiocarcinoma, strictures, biliary atresia
Conjugated ↑; dark urine, pale stool, pruritus (bile salts), ↑ ALP
↓ urine urobilinogen; fat-soluble vitamin loss

Mechanism — the bilirubin pathway

HemeMacrophages
→
BiliverdinHeme oxygenase
→
Unconjugated bilirubinBound to albumin
→
Liver: UGT1A1Conjugation
→
Bile (MRP2)
→
Gut bacteriaUrobilinogen → stercobilin (brown stool)

About 10% of urobilinogen is reabsorbed and excreted as urobilin in urine (yellow color).

Lab pattern by type

TYPE
BILIRUBIN
URINE
STOOL
Hemolytic
Unconjugated
↑ urobilinogen, no bilirubin
Normal / dark
Hepatocellular
Mixed
Bilirubin ⁺, urobilinogen normal/↑
Normal / pale
Obstructive
Conjugated
Bilirubin ⁺ (dark), ↓ urobilinogen
Pale (acholic)
Gilbert / CN
Unconjugated
No bilirubin
Normal

How it's tested

COMMON CONFUSIONOnly conjugated bilirubin is water-soluble and appears in urine. Unconjugated jaundice has no bilirubinuria, however high it gets.
THE TRAPDubin-Johnson and Rotor both give conjugated hyperbilirubinemia with normal enzymes. Dubin-Johnson has the black liver; Rotor does not.
YOUR APPROACHConjugated or unconjugated? Then: hemolysis labs, timing (newborn, fasting), urine and stool color, ALP and imaging for obstruction.

If you see… think…

Mild jaundice after fasting or a cold, normal tests otherwise → Gilbert syndrome
Neonate with severe unconjugated jaundice, no response to phenobarbital → Crigler-Najjar I
Bilirubin falls with phenobarbital → Crigler-Najjar II
Conjugated hyperbilirubinemia + black liver on biopsy → Dubin-Johnson
Conjugated hyperbilirubinemia + normal liver color → Rotor syndrome
Jaundice in a newborn within 24 hours → hemolysis (e.g., Rh/ABO)
Lethargic jaundiced neonate with abnormal movements → kernicterus
Dark urine, pale stool, itching → obstructive (posthepatic) jaundice
Anemia + unconjugated bilirubin + ↑ LDH → hemolytic jaundice
Enzyme that conjugates bilirubin → UGT1A1