II. 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. Most Urobilinogen excreted in stool
    3. Small levels Urobilinogen reabsorbed and excreted in urine

III. Lab: Normal

  1. Total Bilirubin <1.0 mg/dl

IV. 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

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Ontology: Bilirubin (C0005437)

Definition (NCI) A dark orange, yellow pigment that is the product of the breakdown of iron in the blood; it is conjugated in the liver and excreted in the bile.
Definition (NCI_NCI-GLOSS) Substance formed when red blood cells are broken down. Bilirubin is part of the bile, which is made in the liver and is stored in the gallbladder. The abnormal buildup of bilirubin causes jaundice.
Definition (MSH) A bile pigment that is a degradation product of HEME.
Definition (CSP) bile pigment that is a degradation product of heme.
Concepts Organic Chemical (T109) , Biologically Active Substance (T123)
MSH D001663
SnomedCT 79706000
LNC LP15448-1, MTHU002437
English Bilirubin, total, Bilirubin, Bilirubin IX alpha, 21H-Biline-8,12-dipropanoic acid, 2,17-diethenyl-1,10,19,22,23,24-hexahydro-3,7,13,18-tetramethyl-1,19-dioxo-, Conjugated & unconjugated bili, Bilirubin [Chemical/Ingredient], total bilirubin, bilirubin, BILIRUBIN, Conjugated and unconjugated bilirubin, Bilirubin (substance), Bilirubin, NOS, Total bilirubin
Swedish Bilirubin
Czech bilirubin
Finnish Bilirubiini
French Bilirubine IX alpha, Bilirubine
Italian Bilirubina IX alfa, Bilirubina
Russian BILIRUBIN, БИЛИРУБИН
Croatian BILIRUBIN
Polish Bilirubina
Japanese ビリルビン, 胆赤素
Spanish bilirrubina (sustancia), bilirrubina, Bilirrubina
German Bilirubin
Portuguese Bilirrubina

Ontology: Hyperbilirubinemia (C0020433)

Definition (CSP) pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice.
Definition (MSH) A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME, is normally excreted in the BILE or further catabolized before excretion in the urine.
Concepts Disease or Syndrome (T047)
MSH D006932
SnomedCT 143932000, 235904007, 154770008, 267509000, 166612004, 14783006, 20505009
English Bilirubinemia, Bilirubinemias, Hyperbilirubinemias, BILIRUBINAEMIA, HYPERBILIRUBINAEMIA, HYPERBILIRUBINEMIA, Hyper bilirubinemia, hyperbilirubinemia (diagnosis), hyperbilirubinemia, Hyper bilirubinaemia, Hyperbilirubinemia [Disease/Finding], bilirubinaemia, bilirubinemia, hyperbilirubinaemia, hyperbilirubinemias, Serum bilirubin raised (situation), Serum bilirubin concentration increased above normal, Disorder characterized by elevated serum bilirubin, Hyperbilirubinaemia, Serum bilirubin raised, Bilirubinaemia, Hyperbilirubinemia (disorder), Serum bilirubin raised (finding), Bilirubinemia, NOS, Hyperbilirubinemia, NOS, Hyperbilirubinemia [dup] (disorder), Hyperbilirubinemia
French HYPERBILIRUBINEMIE, BILIRUBINEMIE, Hyperbilirubinémie, Bilirubinémie
Portuguese HIPERBILIRRUBINEMIA, BILIRRUBINEMIA, Bilirrubinemia, Hiperbilirrubinemia
Spanish HIPERBILIRRUBINEMIA, BILIRRUBINEMIA AUMENTADA, bilirrubinemia, hiperbilirrubinemia [dup] (trastorno), bilirrubina sérica elevada (hallazgo), bilirrubina sérica elevada, hiperbilirrubinemia (trastorno), hiperbilirrubinemia, Hiperbilirrubinemia, Bilirrubinemia
German HYPERBILIRUBINAEMIE, Bilirubinaemie, BILIRUBINAEMIE, Hyperbilirubinaemie, Bilirubinämie, Hyperbilirubinämie
Dutch bilirubinemie, hyperbilirubinemie, Bilirubinemie, Bilirubinemie, hyper-, Hyperbilirubinemie
Italian Presenza di bilirubina nel sangue, Bilirubinemia, Iperbilirubinemia
Swedish Hyperbilirubinemi
Japanese ビリルビンケッショウ, コウビリルビンケツショウ, コウビリルビンケッショウ, 高ビリルビン血症, 高Bilirubin血症, ビリルビン血症, ビリルビン過剰血, ビリルビン過剰血症, 高ビリルビン血, ビリルビン血
Czech hyperbilirubinémie, Bilirubinemie, Hyperbilirubinemie, hyperbilirubinemie, bilirubinemie
Finnish Hyperbilirubinemia
Russian GIPERBILIRUBINEMIIA, BILIRUBINEMIIA, БИЛИРУБИНЕМИЯ, ГИПЕРБИЛИРУБИНЕМИЯ
Croatian HIPERBILIRUBINEMIJA
Polish Hiperbilirubinemia
Hungarian Hyper bilirubinaemia, Hyperbilirubinaemia, Bilirubinémia, Bilirubinaemia
Norwegian Hyperbilirubinemi

Ontology: Bilirubin, total measurement (C0201913)

Definition (NCI) Bilirubin is a breakdown product of hemoglobin. Total and direct bilirubin are usually measured to screen for or to monitor liver or gall bladder dysfunction. (from MedlinePlus Medical Encyclopedia)
Definition (NCI_CDISC) A measurement of the total bilirubin in a biological specimen.
Concepts Laboratory Procedure (T059)
SnomedCT 166613009, 143933005, 26966005, 359986008
CPT 82247, 80076, 1011294
Dutch bilirubine totaal
French Bilirubine totale
German Bilirubin insgesamt
Italian Bilirubina totale
Portuguese Bilirrubina total
Spanish Bilirrubina total, medición total de bilirrubina, medición total de bilirrubina (procedimiento), bilirrubina total, bilirrubina, dosaje total (procedimiento), bilirrubina, dosaje total, medición total de bilirrubina (concepto no activo)
Japanese 総ビリルビン, ソウビリルビン
English Bilirubin total, Bilirubin; total, Total Bilirubin Measurement, bilirubin level test, BILIRUBIN TOTAL, Measurement of total bilirubin, Total bilirubin (& level) (procedure), Total bilirubin (& level), BILI, Bilirubin, Total Bilirubin, Total bilirubin, Total bilirubin level, Bilirubin, total measurement (procedure), Bilirubin, total measurement, Bilirubin, total measurement (procedure) [Ambiguous]
Czech Celkový bilirubin
Hungarian Teljes bilirubin