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Jaundice (Hyperbilirubinemia)   

A. Predominantly Direct Bilirubin (Conjugated bilirubin)
1. Impaired hepatic excretion (intrahepatic defects)
a. Acquired disorders
  • Biliary obstruction: Gall-bladder or biliary tract stone (choledocholithiasis), pancreatic tumor, biliary stricture, primary sclerosing cholangitis, biliary duct carcinoma.
  • Hepatocellular disease (viral , drug or toxin, or alcohol induced hepatitis or cirrhosis, liver abscess or tumor); viral, infiltrative liver disease (as TB, sarcoidosis, lymphoma, metastatic liver cancer), or primary liver cancer.
  • Drug induced cholestasis
  • Sepsis

b. Familial or hereditary disorders

  • Dubin Johnson syndrome; Rotor syndrome
  • Recurrent (benign) intrahepatic cholestasis
  • Cholestatic jaundice of pregnancy

2. Extrahepatic biliary obstruction stone, stricture, tumor of bile duct

* Other causes of yellow skin (normal bilirubin):

  • Carotenemia  (excessive carrot intake)


B. Predominantly Indirect Bilirubin (Unconjugated bilirubin)
1. Overproduction
  • Hemolysis intravascular or extravascular
  • Hematoma
  • Ineffective erythropoiesis

2. Decreased hepatic uptake

  • Drugs (e.g. flavaspidic acid)
  • Prolonged fasting (<300 cal/day) c. Sepsis

3. Decreased bilirubin conjugation

  • Gilbert's syndrome (mild decrease in glucuronyl transferase)
  • Crigler Najjar syndrome (marked decreased or absent transferase)
  • Neonatal jaundice
  • Sepsis
  • Acquired transferase deficiency:
    Drug inhibition (e.g. chlorampphenicol, pregnanediol)
    Hepatocellular disease (hepatitis, cirrhosis)                                                                                         


3 serious causes of life-threatening jaundice:
  1. Fulminating hepatic failure
    - Hepatitis A, B, C, D, or E; Alcohol hepatitis; Acetaminophen overdose; Autoimmune hepatitis; Wilson's disease, Budd-Chiari causes; Fatty infiltration of liver (acute fatty liver of pregnancy); Drug hepatotoxicity; herpes simplex virus.
  2. Massive hemolysis
    - as malaria hemolysis
  3. Acute cholangitis
    - jaundice, fever, RUQ abd tenderness, obstructing stone in the common bile duct, "pus under pressure" - need antibiotics & decompression urgently.

    REF: Dr. Sanjiv Chopra's Primed lecture 2006

Jaundice secondary to Hepatocellular Disorders:
  • Viral hepatitis A-E (specific viral serologies)
  • Medications: acetaminophen, INH, etc.
  • Toxins: alcohol, mushrooms
  • Ischemia
  • Thrombosis:  Budd-Chiari syndrome (hepatic vein obstruction by blood clot or tumor), veno-occlusive disease
  • Autoimmune hepatitis (ANA, smooth muscle Ab; IgG)
  • Genetic:  Hemochromatosis (ferritin, iron study), Wilson's disease (Ceruloplasmin level), Alpha-1-antitripsin deficiency


Jaundice secondary to Cholestasis:

Intrahepatic cholestasis

  • Medications: dilantin, chlorpromazine, phenothiazines, bactrim, etc
  • Primary Biliary Cirrhosis: anti-mitochondrial Ab, serum IgM
  • Granulomatous disease:  sarcoidosis, TB
  • Lymphoma, esp. Hodgkin's disease
  • Parasitic diseases
  • Fungal diseases

Extrahepatic cholestasis

  • Stones
  • Strictures: Primary sclerosing cholangitis: AIDS cholangiopathy
  • "Silent" malignancy: CBC obstruction by otherwise asymptomatic malignancy