Pathology Associates Of Lexington, P.A.

Bilirubin Test, Blood

Bilirubin, serum

Bilirubin is a breakdown product from the physiological degradation of old red blood cells in the cells of the RES and from additional red cell destruction from blood in tissues or diseases accelerating red cell destruction. Bilirubin is initially unconjugated (lipophilic); and it is able to move properly when bound to watery serum albumin. It reaches liver cells which conjugate it so that it becomes water soluble, itself; and, it is thereafter able to spill over into urine if levels are high enough to exceed the renal threshold. Unconjugated, lipophylic bilirubin, which is either in excess of albumin carrying capacity or becomes abnormally dissociated from the albumin, can cross the blood-brain barrier and be drawn especially into cerebral basal ganglia. The mere presence in brain location is not automatically neurotoxic. So, with some atypical situations, there can be toxic injury at hyperbilrubinemia levels lower than usual. And autopsy of infants jaundiced infants who died of other reasons and were negative for clinical stigmata of kernicterus may still show discolored basal ganglia.

**Increased:**
conjugated hyperbilirubinemia (total bilirubin > 3 & more than 30% of total bilirubin is direct reacting/conjugated): pure obstructive: extrahepatic (surgical) cholestasis (dilated bile ducts usually [91% of cases]): post surgical causes...surgery on or near biliary tract obstructing lesions of or near biliary system intrahepatic cholestasis: intrahepatic segmental or smaller benign or malignant focal lesions (sclerosing cholangitis), primary biliary cirrhosis, biliary inflammation resulting in ductopenic bile hypoelimination, excretory deficiencies of cannalicular obstruction or stasis due to either compressive hepatocellular cannalicular obstruction (intracellular edema) or bile stoicochemical changes retarding flow. pure nonobstructive (duct imaging normal): infants manifest all causes of jaundice as conjugated³. luetic & bacterial galactosemia tyrosinosis Dubin-Johnson syndrome, Rotor's syndrome sepsis Metabolic disorder- alpha1-antitrypsin deficiency, cystic fibrosis, galactosemia, glycogen storage disease, hypothyroidism Chromosomal abnormality- Turner's syndrome, trisomy 18/21 Drugs- aspirin, acetaminophen, rifampin, alcohol, corticosteroids (acetaminophen increased anion gap, increased SGPT, evidence renal injury)
Unconjugated hyperbilirubinemia (less than 15% of total bilirubin is direct reacting/conjugated...due to the overproduction of bilirubin, impaired bilirubin uptake by the liver, or abnormalities of bilirubin conjugation): adult fasting²: some normals Gilbert's constitutional hyperbilirubinemia some with hepatocellular disease occasionally those with hemolysis Gilbert's constitutional hyperbilirubinemia premenstrual cyclic constitutional hyperbilirubinemia increased red cell destruction: within bone marrow: intramedullary hemolysis, ineffective erythropoiesis vitamin B12 or folate deficiency Myelodysplastic syndrome (MDS) outside of bone marrow: Coombs positive Coombs negative intravascular hemolysis: DIC, mechanical, RBC membrane defects (spherocytosis, elliptocytosis), RBC enzyme defects (G6PD, pyruvate kinase deficiency), drugs (streptomycin, vitamin K), hemoglobinopathies, sepsis extravascular hemolysis newborn physiologic: peaks 3rd to 5th day, declining thereafter. newborn exaggerated enterohepatic circulation: cystic fibrosis, ileal atresia, pyloric stenosis, Hirschsprung's disease newborn & breast feeding: quit breast milk a few days & jaundice disappears & does not return when resume breast feeding. neonatal hemolysis or resorption of enclosed hemorrhage newborn or adult hypothyroidism Crigler-Najjar syndrome Lucey-Driscoll (newborn) syndrome: persists after 1st week of life & gradually disappears adult hepatocyte injury giving deficiency of conjugation functions
mixed:

**Decreased:**
conjugated:
unconjugated:

References:

Fischer MG, et. al., Cholestatic Jaundice in Adults..., JAMA, 245(19):1945-48. 15 May 1981.
Baldassare V, et. al., Specific Pattern..., Ital. J. Gastroent. 25:375-379, 1993.
Thaler MM, Jaundice in the Newborn, JAMA, 237(1):58-62, 3 Jan. 1977.

(5 November 2004)