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
- 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
- Small levels of Urobilinogen are reabsorbed and excreted in urine
- Most Urobilinogen is excreted in stool
- Although Urobilinogen and its metabolite stercobilinogen are colorless, it's second generation metabolite stercobilin is brown
- Stercobilin gives stool its brown coloration
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