What causes jaundice?

Causes of Yellow Eyes (Jaundice)

Jaundice is primarily caused by hepatitis/sepsis, alcoholic liver disease, blockage of the common bile duct by stones or tumors, and toxic reactions to drugs or herbal supplements. 1

Classification of Jaundice

Jaundice can be categorized into three main types based on the underlying pathophysiology:

1. Prehepatic (Unconjugated/Nonobstructive)

   • Hemolysis (2.5% of cases) 2, 1
   • Hematoma resorption 3
   • Gilbert syndrome (5.6% of cases) 1

2. Intrahepatic (Can be Unconjugated or Conjugated)

   • Hepatitis/sepsis (22% of cases) 2, 1
   • Alcoholic liver disease (16% of cases) 2, 1
   • Drug-induced liver injury 2, 1
   • Decompensation of pre-existing liver disease (20.5% of cases) 1

3. Posthepatic (Conjugated/Obstructive)

   • Common bile duct obstruction by stones (14% of cases) 2, 1
   • Malignancy (6.2% of cases) 2, 1
   • Biliary strictures 4
   • Pancreatic disorders (pancreatitis, pseudocysts) 5

Pathophysiology

Jaundice becomes clinically apparent when serum bilirubin levels exceed 2.5-3 mg/dL, resulting in yellowing of the skin and eyes 6, 4. The underlying mechanisms include:

• Bilirubin overproduction: Excessive breakdown of red blood cells leads to increased unconjugated bilirubin
• Impaired bilirubin conjugation: Genetic disorders or liver dysfunction prevent proper processing of bilirubin
• Hepatocellular dysfunction: Liver cells cannot properly process bilirubin
• Biliary obstruction: Blockage prevents conjugated bilirubin from being excreted into the intestines

Diagnostic Approach

Laboratory evaluation should include:

• Fractionated bilirubin (conjugated vs. unconjugated) 4
• Liver function tests (ALT, AST, alkaline phosphatase, GGT) 1, 6
• Complete blood count 4
• Prothrombin time and INR (to assess liver synthetic function) 6, 4

Imaging studies:

• Abdominal ultrasound: First-line imaging modality with sensitivity of 65-95% for cirrhosis and 32-100% for biliary obstruction 2, 1
• CT or MRI: Second-line options when ultrasound is inconclusive 1
• MRCP: Particularly useful for evaluating biliary and pancreatic ductal systems 2

Clinical Pearls and Pitfalls

• Important distinction: Unconjugated hyperbilirubinemia suggests prehepatic or hepatocellular causes, while conjugated hyperbilirubinemia points toward obstructive or severe hepatocellular causes 2, 6

• AST/ALT ratio: A ratio >2 suggests alcoholic liver disease, whereas a ratio <1 is more typical of non-alcoholic fatty liver disease 1

• Regional variations: The prevalence of different causes varies significantly based on geographical location, healthcare setting (tertiary vs. community), and patient demographics 2

• Pitfall to avoid: Don't assume gallstones are the cause without proper workup, as malignancy accounts for 6.2% of jaundice cases 2, 1

• Common misconception: Not all biliary obstructions are easily detected on ultrasound—CBD stones have a detection sensitivity of only 22.5-75% on ultrasound 2

By systematically evaluating patients with jaundice using this approach, clinicians can efficiently identify the underlying cause and initiate appropriate treatment to improve outcomes.