Jaundice

JAUNDICE 

1️⃣ WHAT IS JAUNDICE?

Jaundice (icterus) is the yellow discoloration of skin, sclera, and mucous membranes due to elevated serum bilirubin (>2–3 mg/dL).

• Scleral icterus appears first (high elastin affinity for bilirubin)
• Visible when bilirubin >2 mg/dL

Not all yellow skin is jaundice!

2️⃣ BILIRUBIN METABOLISM – CORE PHYSIOLOGY

Step 1: Production

• 80–85% from breakdown of hemoglobin (senescent RBCs)
• Rest from myoglobin, cytochromes
• Heme → biliverdin → unconjugated bilirubin (indirect)

Characteristics:

• Lipid soluble
• Albumin-bound
• Not excreted in urine

Step 2: Hepatic Uptake

• Taken up by hepatocytes via OATP transporters

Step 3: Conjugation

• Enzyme: UDP-glucuronyl transferase
• Converts to conjugated (direct) bilirubin
• Water soluble

Step 4: Excretion

• Secreted into bile canaliculi via MRP2 transporter
• Goes to intestine → urobilinogen
• From urobilinogen  Some reabsorbed (enterohepatic circulation)
• And some Converted to stercobilin → brown stool

3️⃣ CLASSIFICATION OF JAUNDICE

I. Pre-hepatic (Hemolytic)

Problem: Excess bilirubin production
Type: Unconjugated hyperbilirubinemia

Causes:

• Hemolytic anemia
• Malaria
• Thalassemia
• G6PD deficiency
• Massive transfusion
• Resorption of large hematoma

Lab Pattern:

• ↑ indirect bilirubin
• Normal LFTs
• ↑ LDH
• ↓ haptoglobin(Haptoglobin is a liver-produced plasma protein that binds free hemoglobin released from destroyed RBCs.)
• Reticulocytosis
• No bilirubin in urine(indirect bilirubin is Lipid soluble)
• ↑ urine urobilinogen but why

More unconjugated bilirubin produced—>Liver conjugates more bilirubin—>More bilirubin reaches intestine—>More urobilinogen formed—>More reabsorbed into blood—>More excreted in urine

II. Hepatocellular (Intrahepatic)

Problem: Hepatocyte dysfunction
Type: Mixed (conjugated + unconjugated)

Causes:

• Viral hepatitis (A, B, C, E)
• Alcoholic hepatitis
• Drug-induced liver injury
• Autoimmune hepatitis
• Sepsis
• Ischemic hepatitis

Lab Pattern:

• ↑ AST/ALT (often > ALP)
• Mixed bilirubin elevation
• Variable INR elevation
• Urine bilirubin present

III. Cholestatic / Obstructive (Post-hepatic)

Problem: Impaired bile flow
Type: Predominantly conjugated hyperbilirubinemia

Causes:

• Choledocholithiasis
• Pancreatic cancer
• Cholangiocarcinoma
• Biliary strictures
• PSC
• PBC

Lab Pattern:

• ↑ ALP (marked) ALP >3× ULN
• ↑ GGT
• ↑ Direct bilirubin
• Dark urine
• Pale stool(Bile cannot reach intestine)
• Pruritus(bile salts skin deposition)

4️⃣  WHY DARK URINE?

Conjugated bilirubin is water-soluble.

When bile duct is blocked:

• Conjugated bilirubin cannot enter intestine
• It regurgitates back into bloodstream
• Kidney filters it
• Appears in urine

➡ Urine becomes tea-colored / cola-colored

5️⃣ IMPORTANT HEREDITARY HYPERBILIRUBINEMIA

1️⃣ Gilbert syndrome

• Mild unconjugated bilirubin (<3 mg/dL)
• Triggered by stress, fasting
• No treatment needed

2️⃣ Crigler-Najjar syndrome

• Severe unconjugated hyperbilirubinemia
• Type I → fatal without transplant
• Type II → responds to phenobarbital

3️⃣ Dubin-Johnson syndrome

• Defect in MRP2 transporter
• Conjugated hyperbilirubinemia
• Black liver

4️⃣ Rotor syndrome

• Similar to Dubin-Johnson
• No liver pigmentation

6️⃣ CLINICAL APPROACH TO JAUNDICE 

Step 1: History

• Duration
• Fever → think infection
• Pain → obstruction
• Alcohol intake
• Drug history
• Blood transfusion
• Travel history
• Weight loss → malignancy

Step 2: Examination

Look for:

Step 3: Initial Lab Panel

• Total & direct bilirubin
• AST, ALT
• ALP
• GGT
• INR
• CBC
• LDH
• Haptoglobin

7️⃣ PATTERN RECOGNITION TABLE 

8️⃣ IMAGING APPROACH

First-line: Ultrasound abdomen

• Dilated bile ducts? → obstruction
• Mass?
• Gallstones?

If obstruction suspected:

• MRCP
• ERCP
• CT abdomen

9️⃣ JAUNDICE IN ICU (Critical Care Perspective)

Common causes in ICU:

• Sepsis-associated cholestasis
• Drug-induced liver injury
• Ischemic hepatitis (shock liver)
• Massive transfusion
• TPN-related cholestasis

Key ICU concept:

Bilirubin elevation is a SOFA score component

1️⃣2️⃣ MANAGEMENT PRINCIPLES

Hemolytic

• Treat cause
• Transfusion if severe

Hepatocellular

• Antivirals if indicated
• Stop hepatotoxic drugs
• Steroids in autoimmune hepatitis
• NAC in acute liver failure

Obstructive

• ERCP stone removal
• Stenting
• Surgery for malignancy