Bilirubin, Total Bilirubin, Serum Bilirubin, Hyperbilirubinemia

  • Physiology
  1. Heme product degradation yields Hemoglobin
    1. Red Blood Cells (responsible for 80% of heme product)
    2. Myoglobin
    3. Maturing Red Blood Cells
  2. Hemoglobin transported to reticuloendothelial system
    1. Hemoglobin bound to Haptoglobin in plasma
    2. Hemoglobin metabolized in reticuloendothelial system
      1. Heme is oxidized to bilverdin
      2. Iron
      3. Globin
  3. Bilverdin converted to Unconjugated Bilirubin
    1. Normal production of Bilirubin: 4 mg/kg/day (250 mg/day in an average adult)
  4. Unconjugated Bilirubin circulates
    1. Tightly bound to albumin and fat soluble
      1. Causes of displaced (or free) Unconjugated Bilirubin
        1. Albumin saturated with Bilirubin or
        2. Medications (e.g. Sulfisoxazole, Streptomycin, Vitamin K)
      2. Free Unconjugated Bilirubin is typically absorbed by hepatocytes which conjugate Bilirubin (see below)
      3. Displaced or free Unconjugated Bilirubin crosses blood-brain barrier and placenta
        1. Results in toxicity (e.g. Hepatic Encephalopathy, Kernicterus)
    2. Unconjugated Bilirubin is insoluble in water
      1. Not found in tears or Saliva
      2. Unconjugated Bilirubin can not be excreted
    3. Concentrates in high albumin containing tissues
      1. Skin (especially face and trunk): Jaundice
      2. Sclera: Scleral Icterus
  5. Unconjugated Bilirubin converted to Conjugated Bilirubin by hepatocytes
    1. Bilirubin conjugated with glucuronic acid in liver
      1. Conjugated by glucuronosyltransferase enzyme
    2. Conjugated Bilirubin is water soluble
    3. Only Conjugated Bilirubin can be excreted
  6. Conjugated Bilirubin excreted into biliary tract
    1. Stored in gallbladder
    2. Ultimately excreted into duodenum
  7. Conjugated Bilirubin passes into feces
    1. Converted by Bacterial enzymes to Urobilinogen
    2. Small levels of Urobilinogen are reabsorbed and excreted in urine
    3. Most Urobilinogen is excreted in stool
    4. Although Urobilinogen and its metabolite stercobilinogen are colorless, it's second generation metabolite stercobilin is brown
      1. Stercobilin gives stool its brown coloration
  • Lab
  • Normal
  1. Total Bilirubin <1.0 mg/dl
  • Causes
  • Increased Total Bilirubin
  1. Diagnosis depends on whether Bilirubin is conjugated
    1. See Unconjugated Bilirubin (Hemolytic Jaundice)
    2. See Conjugated Bilirubin (Obstructive Jaundice)
  2. General Hyperbilirubinemia Causes
    1. See Medication Causes of Jaundice
    2. Hemolysis (indirect Hyperbilirubinemia)
      1. Hemolytic Anemia
      2. Septic Shock
      3. Disseminated Intravascular Congestion
      4. Rhabdomyolysis
      5. Tick Borne Illness (e.g. Tick-Borne Relapsing Fever, Ehrlichiosis)
    3. Liver disease
      1. Hepatitis
      2. Cirrhosis
      3. Liver tumor
      4. Cholangitis
      5. Biliary Tract Obstruction
      6. Epstein Barr Virus (EBV)
      7. Cytomegalovirus (CMV)
      8. Hereditary (indirect Hyperbilirubinemia)
        1. Gilbert's disease
        2. Crigler Najjar Syndrome
        3. Dubin-Johnson syndrome
      9. Hepatic congestion (e.g. CHF)
    4. Pulmonary Causes
      1. Pulmonary Infarction
      2. Pulmonary Embolus