Jaundice and Cholestasis

Jaundice and Cholestasis - Yellow Peril Primer

• Jaundice (Icterus): Yellowing of skin/sclera; serum bilirubin > 2-3 mg/dL.
• Cholestasis: Impaired bile formation/flow; leads to pruritus, dark urine (bilirubinuria), pale stools, malabsorption.

Bilirubin Metabolism Overview:

Types & Key Features:

• Pre-hepatic (e.g., Hemolysis): ↑UCB; acholuric jaundice (UCB not in urine).
• Hepatic (e.g., Hepatitis, Gilbert's): ↑UCB and/or ↑CB; liver enzyme (AST, ALT) elevation.
• Post-hepatic (Obstructive, e.g., Stones): ↑CB; pruritus, dark urine, pale stools; cholestatic enzyme (ALP, GGT) elevation.

Diagnostic Pointers:

• UCB (Indirect): Insoluble, albumin-bound; not in urine.
• CB (Direct): Water-soluble; appears in urine (bilirubinuria → dark urine) if elevated.

⭐ Dubin-Johnson Syndrome: AR defect in MRP2 (canalicular CB export). Results in conjugated hyperbilirubinemia & a black liver. Good prognosis.

📌 Mnemonic (Inherited Conjugated Hyperbilirubinemias): Dubin-Johnson (Dark liver, Defective excretion of CB) & Rotor (Regular liver, Reduced uptake/storage of CB).

Jaundice and Cholestasis - Hue Clues

• Jaundice: Yellow sclera/skin (serum bilirubin > 2-3 mg/dL).
• Cholestasis: Impaired bile flow; leads to accumulation of bile (bilirubin, bile acids, cholesterol).

• Key Types & Findings:
  • Pre-hepatic (e.g., Hemolysis): ↑ Unconjugated Bilirubin (UCB). Normal AST/ALT, ALP. Urine: no bilirubin, ↑ urobilinogen. Stool: dark.
  • Hepatic (e.g., Hepatitis, Gilbert's): ↑ UCB and/or Conjugated Bilirubin (CB). ↑↑ AST/ALT (hepatocellular pattern) or isolated bilirubin rise (Gilbert's). Urine: bilirubin present if CB ↑.
  • Post-hepatic (Obstructive; e.g., Stones, Pancreatic Ca): ↑ CB. ↑↑ ALP, GGT (cholestatic pattern). Urine: bilirubin present (dark). Stool: pale (acholic). Pruritus common.

⭐ Courvoisier's Law: In jaundice, a palpable, non-tender gallbladder suggests malignancy (e.g., pancreatic head), not stones.

📌 Mnemonic "COLD" for Obstructive Jaundice Features:

• Cholestasis (pruritus)
• Obstruction signs (pale stool, dark urine)
• LFTs (↑ALP, ↑GGT, ↑CB)
• Dilated ducts (on imaging)

Jaundice and Cholestasis - Bile Duct Blues

• Cholestasis: ↓ bile flow, accumulation of bilirubin, bile acids, cholesterol.
  • Lab: ↑ ALP, ↑ GGT, ↑ conjugated bilirubin, ↑ bile acids.
• Types & Causes:
  • Intrahepatic Cholestasis: Defect in hepatocyte bile secretion.
    • Hepatocellular disease: Viral hepatitis, alcoholic liver disease, drugs (e.g., OCPs, anabolic steroids, chlorpromazine), TPN, sepsis.
    • Ductular: Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) (small ducts), infiltrative diseases (sarcoidosis, lymphoma).
    • Genetic: Dubin-Johnson, Rotor (conjugated hyperbilirubinemia); Crigler-Najjar, Gilbert (unconjugated hyperbilirubinemia).
  • Extrahepatic Cholestasis: Mechanical obstruction of large bile ducts.
    • Choledocholithiasis (most common).
    • Biliary strictures (post-surgical, PSC).
    • Malignancy (pancreatic head, cholangiocarcinoma, ampullary).
    • Biliary atresia (neonates).
• Clinical Features: Jaundice, pruritus (due to bile acids), dark urine, pale stools, fatigue, malabsorption (steatorrhea, vitamin A, D, E, K deficiency), xanthomas.

⭐ In cholestasis, serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) are typically elevated disproportionately to aminotransferases (AST/ALT).

High‑Yield Points - ⚡ Biggest Takeaways

• Jaundice: Yellow discoloration from ↑ bilirubin (>2.5-3 mg/dL).
• Cholestasis: Impaired bile flow; bile pigment accumulates in liver.
• Unconjugated hyperbilirubinemia: Gilbert syndrome (mild, ↓ UGT), Crigler-Najjar syndrome (absent/severe ↓ UGT).
• Conjugated hyperbilirubinemia: Dubin-Johnson syndrome (black liver, MRP2 defect), Rotor syndrome (coproporphyrinuria).
• Neonatal jaundice: Physiologic (resolves 1-2 wks); Pathologic (e.g., biliary atresia, hemolysis).
• Obstructive jaundice: ↑ conjugated bilirubin, ↑ ALP, ↑ GGT; pale stools, dark urine.
• Intrahepatic cholestasis: Causes include drugs, viral hepatitis, PBC, PSC.