Jaundice

Definition

Jaundice refers to the yellowish discoloration of the skin, sclerae, and mucous membranes caused by elevated levels of bilirubin in the blood (hyperbilirubinemia). The yellow color becomes clinically visible when serum bilirubin levels exceed approximately 2–3 mg/dL (34–51 µmol/L).

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Pathophysiology

Bilirubin is produced from the breakdown of heme, primarily from senescent red blood cells. It exists in two main forms:

• Unconjugated (indirect) bilirubin: Lipid-soluble, transported in plasma bound to albumin, processed in the liver.

• Conjugated (direct) bilirubin: Water-soluble, formed in the liver by conjugation with glucuronic acid, excreted in bile into the intestines.

Jaundice occurs when there is:

1. Overproduction of bilirubin (pre-hepatic).

2. Impaired conjugation by the liver (hepatic).

3. Obstruction of bile flow (post-hepatic).

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Classification

1. Pre-Hepatic (Hemolytic) Jaundice

• Cause: Excess breakdown of red blood cells.

• Bilirubin type: Unconjugated.

• Common causes:

  • Hemolytic anemia (autoimmune, hereditary spherocytosis, G6PD deficiency).

  • Sickle cell disease.

  • Transfusion reactions.

2. Hepatic (Hepatocellular) Jaundice

• Cause: Impaired bilirubin conjugation and excretion by damaged hepatocytes.

• Bilirubin type: Both unconjugated and conjugated.

• Common causes:

  • Hepatitis (viral, alcoholic, drug-induced).

  • Cirrhosis.

  • Gilbert’s syndrome.

  • Crigler–Najjar syndrome.

3. Post-Hepatic (Obstructive/Cholestatic) Jaundice

• Cause: Obstruction to bile flow.

• Bilirubin type: Conjugated.

• Common causes:

  • Gallstones.

  • Pancreatic cancer.

  • Cholangiocarcinoma.

  • Primary sclerosing cholangitis.

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Clinical Features

Symptoms

• Yellowing of skin and eyes.

• Dark urine (conjugated bilirubin excreted in urine).

• Pale stools (lack of stercobilin).

• Pruritus (in cholestatic jaundice).

• Fatigue, malaise.

• Abdominal pain (in obstructive causes).

Signs

• Hepatomegaly, splenomegaly.

• Signs of chronic liver disease (spider naevi, ascites).

• Fever (in infective causes like cholangitis).

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Diagnosis

History and Examination

• Onset and duration.

• Associated symptoms (fever, abdominal pain, weight loss).

• Past liver disease or gallbladder disease.

• Alcohol, drug, and transfusion history.

Laboratory Tests

• Serum bilirubin (total and direct).

• Liver function tests (AST, ALT, ALP, GGT).

• Complete blood count.

• Coagulation profile (PT/INR).

• Viral hepatitis panel.

• Hemolysis work-up (reticulocyte count, LDH, haptoglobin, peripheral smear).

Imaging

• Ultrasound (first-line for suspected obstruction).

• CT scan or MRI (for masses, stones).

• MRCP or ERCP (for biliary tree assessment).

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Treatment

Management depends on the cause.

1. Pre-Hepatic Jaundice

• Treat hemolysis:

  • Autoimmune hemolytic anemia: Prednisolone (1–2 mg/kg/day orally) or other immunosuppressants.

  • G6PD deficiency: Avoid oxidant drugs and treat infections promptly.

  • Sickle cell crisis: Hydration, oxygen, analgesia, transfusion if needed.

2. Hepatic Jaundice

• Viral hepatitis: Supportive care, antiviral therapy for hepatitis B and C (e.g., tenofovir disoproxil fumarate 300 mg once daily for HBV; sofosbuvir 400 mg + velpatasvir 100 mg once daily for HCV).

• Alcoholic hepatitis: Abstinence, nutritional support, corticosteroids in severe cases (prednisolone 40 mg daily for 28 days).

• Drug-induced liver injury: Stop offending drug, consider N-acetylcysteine in paracetamol toxicity (loading dose 150 mg/kg IV over 1 hr, then 50 mg/kg over 4 hrs, then 100 mg/kg over 16 hrs).

3. Post-Hepatic Jaundice

• Gallstones: Endoscopic removal via ERCP.

• Malignant obstruction: Surgery, stenting, or palliative care.

• Cholangitis: Urgent antibiotics (e.g., ceftriaxone 2 g IV once daily + metronidazole 500 mg IV every 8 hrs) and biliary drainage.

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Supportive Management

• Adequate hydration.

• Nutritional support.

• Pruritus relief: Cholestyramine (4 g orally once or twice daily).

• Vitamin K supplementation for coagulopathy (e.g., phytomenadione 10 mg IV/IM).

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Complications

• Chronic liver disease and cirrhosis.

• Hepatic encephalopathy.

• Biliary sepsis.

• Renal impairment (hepatorenal syndrome).

• In neonates, risk of kernicterus if unconjugated bilirubin is high.

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Prevention

• Safe food and water to prevent viral hepatitis.

• Vaccination against hepatitis A and B.

• Alcohol moderation.

• Early treatment of gallbladder disease.