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