Jaundice¶
Chapter 52 | Part 2: Cardinal Manifestations and Presentation of Diseases
KEY CLINICAL POINTS¶
- Jaundice is a yellow discoloration of body tissues due to bilirubin deposition, indicating liver dysfunction, hemolysis, or biliary obstruction.
- Bilirubin metabolism involves hepatic uptake, conjugation, and excretion; abnormalities in any step lead to hyperbilirubinemia.
- Diagnostic evaluation includes serum bilirubin fractionation, liver function tests, imaging (ultrasound, MRCP), and specific tests for hemolysis or biliary disease.
1. DEFINITION & OVERVIEW¶
Jaundice is a yellowish discoloration of body tissues resulting from the deposition of bilirubin. It is a sign of either liver disease, hemolytic disorders, or disorders of bilirubin metabolism. The degree of serum bilirubin elevation can be estimated by physical examination, with scleral icterus indicating serum bilirubin ≥ 51 µ mol/L (3 mg/dL).
Table 52-1: Causes of Isolated Hyperbilirubinemia¶
| Category | Causes |
|---|---|
| Indirect Hyperbilirubinemia | Hemolytic disorders, Ineffective erythropoiesis, Drugs (Rifampin, Probenecid), Inherited conditions (Crigler-Najjar, Gilbert’s syndrome) |
| Direct Hyperbilirubinemia | Dubin-Johnson syndrome, Rotor syndrome |
1.1 Bilirubin Metabolism¶
Bilirubin is a breakdown product of heme. Unconjugated bilirubin is insoluble and bound to albumin, transported to the liver for conjugation with glucuronic acid. Conjugated bilirubin is excreted into bile and reabsorbed in the intestine, with enterohepatic cycling contributing to bilirubin levels.
1.2 Clinical Presentation¶
Clinical features include scleral icterus, skin yellowing, and dark urine. Differential diagnosis includes carotenoderma, drug-induced jaundice, and hemolytic disorders. The distribution of yellowing (uniform vs. localized) helps distinguish jaundice from carotenoderma.
2. ETIOLOGY & PATHOPHYSIOLOGY¶
Jaundice arises from overproduction, impaired uptake, conjugation, or excretion of bilirubin. Hemolytic disorders (e.g., sickle cell anemia) increase bilirubin production, while liver disease (e.g., cirrhosis) impairs conjugation. Biliary obstruction (e.g., cholangiocarcinoma) prevents excretion. Drug-induced cholestasis (e.g., chlorpromazine) disrupts bile flow.
Table 52-2: Hepatocellular Conditions That May Produce Jaundice¶
| Category | Conditions |
|---|---|
| Viral Hepatitis | Hepatitis A, B, C, D, E, Epstein-Barr, Cytomegalovirus |
| Alcoholic Hepatitis | Alcoholic liver disease |
| Drug Toxicity | Acetaminophen, Isoniazid, Vinyl Chloride |
| Chronic Liver Disease | Cirrhosis, Wilson’s Disease, Autoimmune Hepatitis |
2.1 Bilirubin Production and Transport¶
Bilirubin is produced from heme breakdown in senescent red blood cells. Unconjugated bilirubin is transported to the liver via albumin binding. Conjugation with glucuronic acid by UDPGT enables excretion into bile.
2.2 Genetic Disorders¶
Inherited conditions like Dubin-Johnson syndrome (MRP2 defect) and Rotor syndrome (OATP1B1/1B3 deficiency) cause conjugated hyperbilirubinemia. Gilbert’s syndrome (reduced UDPGT activity) leads to mild unconjugated hyperbilirubinemia.
3. CLINICAL FEATURES¶
Clinical features vary by etiology. Scleral icterus and skin yellowing are hallmark signs. Dark urine (bilirubinuria) indicates conjugated hyperbilirubinemia. Pruritus, abdominal pain, and fatigue are common. In hemolytic disorders, spherocytes or reticulocytosis may be present.
Table 52-3: Cholestatic Conditions That May Produce Jaundice¶
| Category | Conditions |
|---|---|
| Intrahepatic | Primary biliary cholangitis, Sclerosing cholangitis, Vanishing bile duct syndrome |
| Extrahepatic | Cholangiocarcinoma, Choledocholithiasis, Mirizzi’s syndrome |
| Other | Drug-induced cholestasis, Pregnancy cholestasis, TPN-related cholestasis |
3.1 Signs and Symptoms¶
Scleral icterus, skin yellowing, dark urine, pruritus, and fatigue. In severe cases, kernicterus (neurological complications) may occur in neonates or untreated Crigler-Najjar syndrome.
3.2 Differential Diagnosis¶
Carotenoderma (yellow skin without scleral involvement), drug-induced jaundice (e.g., rifampin), hemolytic anemia, and hemochromatosis. Bilirubinuria confirms conjugated hyperbilirubinemia.
4. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic workup includes serum bilirubin fractionation (direct/indirect), liver enzymes (ALT, AST, ALP), prothrombin time, and imaging. Ultrasound, MRCP, and ERCP help identify biliary obstruction. Liver biopsy may be required for autoimmune or infiltrative diseases.
4.1 Laboratory Tests¶
Total and direct bilirubin, ALT, AST, ALP, prothrombin time, albumin, and liver function tests. Direct bilirubin >15% indicates conjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia may suggest hemolysis or genetic disorders.
4.2 Imaging¶
Ultrasound (first-line for biliary dilation), MRCP (non-invasive cholangiography), ERCP (diagnostic and therapeutic), and CT for assessing liver parenchyma and metastases.
5. MANAGEMENT & TREATMENT¶
Management depends on the underlying cause. Hemolytic disorders require transfusion and addressing the trigger. Biliary obstruction may require ERCP or surgery. Drug-induced cholestasis necessitates discontinuation of the offending agent. Liver disease may require antiviral therapy, corticosteroids, or liver transplantation.
5.1 Hemolytic Disorders¶
Treat underlying cause (e.g., malaria, sickle cell crisis). Blood transfusions for severe anemia. Monitor for gallstone formation in chronic hemolysis.
5.2 Biliary Obstruction¶
ERCP for stone removal, stent placement, or surgery for tumors. Antibiotics for cholangitis. Percutaneous transhepatic cholangiography (PTC) for complex cases.
5.3 Drug-Induced Cholestasis¶
Discontinue offending drugs. Supportive care with ursodeoxycholic acid. Monitor for liver function recovery.
6. PROGNOSIS & COMPLICATIONS¶
Prognosis varies by etiology. Acute viral hepatitis has a good prognosis, while cirrhosis or cholangiocarcinoma may be fatal. Complications include kernicterus, cholangitis, and hepatic encephalopathy. Early diagnosis and treatment improve outcomes.
6.1 Complications¶
Kernicterus (Crigler-Najjar syndrome), cholangitis, hepatic encephalopathy, and portal hypertension. Chronic cholestasis may lead to fat-soluble vitamin deficiencies.
6.2 Special Populations¶
Pregnancy cholestasis resolves postpartum. Alcoholic hepatitis requires abstinence and nutritional support. Drug-induced cholestasis may resolve with discontinuation.
7. KEY POINTS & CLINICAL PEARLS¶
- Bilirubin fractionation (direct/indirect) guides etiology. 2. Scleral icterus indicates serum bilirubin ≥ 51 µ mol/L. 3. Ultrasound is first-line for biliary obstruction. 4. Drug-induced cholestasis requires discontinuation of the offending agent. 5. Liver biopsy is essential for autoimmune or infiltrative diseases.