Jaundice

Basics

Description

  • Yellow staining of tissues and body fluids due to hyperbilirubinemia, usually present at levels of >2–2.5 mg/dL
  • Hyperbilirubinemia is classified as unconjugated (indirect) or conjugated (direct), based on the predominant fraction of bilirubin in plasma
  • Unconjugated (indirect) hyperbilirubinemia:
    • Direct breakdown product of hemoglobin
    • Water insoluble, circulates bound to albumin
  • Conjugated (direct) hyperbilirubinemia:
    • Water-soluble bilirubin conjugated with glucuronic acid in hepatocytes
    • Measured as direct bilirubin
    • Conjugated bilirubin is returned to the bloodstream after conjugation in the liver instead of draining into the bile ducts
    • Pseudojaundice (sclerae anicteric)
  • Jaundice results from 3 primary mechanisms:
    • Prehepatic (hemolytic): Excess RBC breakdown → ↑ unconjugated bilirubin, liver overwhelmed but functional
    • Hepatic (liver disease): Impaired uptake, conjugation, or excretion → mixed (unconjugated/conjugated) bilirubin accumulation:
      • Defective uptake (eg, drugs, Crigler–Najjar syndrome)
      • Defective conjugation (eg, Gilbert syndrome, drugs)
      • Defective excretion of bilirubin by the liver cell (eg, drugs, Dubin–Johnson syndrome)
    • Posthepatic (obstructive): Blocked bile flow → conjugated bilirubin buildup, impaired excretion into intestines.
  • Jaundice accounts for approximately 52,000 emergency department visits annually in the US
  • In neonates, jaundice occurs in 60% of term and 80% of preterm infants, often due to physiologic processes
  • Elderly patients presenting with jaundice are more likely to have malignancies or obstructive pathology

Etiology

  • Prehepatic (Unconjugated Hyperbilirubinemia):
    • Hemolysis (autoimmune, hereditary spherocytosis, G6PD deficiency, sickle cell disease, microangiopathic hemolytic anemia)
    • Ineffective erythropoiesis (megaloblastic anemia, lead poisoning)
    • Decreased hepatic uptake (drug-induced, sepsis, heart failure)
    • Impaired conjugation (Gilbert syndrome, Crigler–Najjar syndrome, neonatal jaundice, hypothyroidism)
    • Prolonged fasting
    • Cardiopulmonary bypass (ECMO)
    • Hematoma reabsorption
  • Hepatocellular (mixed hyperbilirubinemia):
    • Hepatitis (infectious, alcoholic, autoimmune, toxin, drug induced)
    • Cirrhosis
    • Postischemic
    • Hemochromatosis
  • Intrahepatic cholestasis (Conjugated hyperbilirubinemia):
    • Idiopathic cholestasis of pregnancy
    • Drugs (TPN, statins, etc.)
    • Dubin–Johnson syndrome
    • Rotor syndrome
    • Benign recurrent cholestasis
    • Familial syndromes
    • Sepsis
    • Postoperative jaundice
    • Lymphoma
  • Extrahepatic obstruction (conjugated hyperbilirubinemia):
    • Common duct stone
    • Biliary stricture
    • Bacterial cholangitis
    • Sclerosing cholangitis
    • Carcinoma (ampulla, gallbladder, pancreas), cholangiocarcinoma
    • Pancreatitis, pancreatic pseudocyst
    • Hemobilia
    • Duodenal diverticula
    • Parasites
    • Postlaparoscopic cholecystectomy complications
    • Congenital biliary atresia
    • Congenital choledochal cyst

Pregnancy Considerations

  • Hyperemesis gravidarum
  • Fatty liver of pregnancy
  • HELLP (hemolysis and elevated liver enzymes)
  • Intrahepatic cholestasis of pregnancy

Pediatric Considerations

  • Noncholestatic jaundice:
    • Breastmilk jaundice
    • Breastfeeding jaundice
    • Physiologic jaundice
  • Intrahepatic cholestasis:
    • Cardiovascular (congenital heart disease, congestive heart failure, shock, asphyxia)
    • Metabolic or genetic (α1-antitrypsin deficiency, trisomy 18 and 21, cystic fibrosis, Gaucher disease, Niemann–Pick disease, glycogen storage disease type IV)
    • Infectious (bacterial sepsis, cytomegalovirus, enterovirus, herpes simplex virus, rubella, syphilis, TB, varicella, viral hepatitis)
    • Hematologic (severe isoimmune hemolytic disease)

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