Unconjugated Hyperbilirubinemias

Depending on the type of bilirubin present in plasma—ie, unconjugated or conjugated—hyperbihru-binemia may be classified as retention hyperbilirubinemia, due to overproduction, or regurgitation hyperbilirubinemia, due to reflux into the bloodstream because of bihary obstmction. 

Unconjugated hyperbilirubinemia can result from toxin-induced liver dysfunction such as that caused by chloroform, arsphenamines, carbon tetrachloride, acetaminophen, hepatitis virus, cirrhosis, and Amanita... 

Drug interaction with proton pump inhibitors, unconjugated hyperbilirubinemia Twice daily dosing lipids Twice-daily dosing lipids... 

Answer C. Only option C is characteristic of hemolytic jaundice indirect hyperbilirubinemia with no spillover of the water-insoluble unconjugated form into the urine. 

Partial or total deficiency, or inhibition of bilirubin UDP-glucuronyltransferase may cause unconjugated hyperbilirubinemia. Increased production (hemolysis, ineffective erythropoiesis) should be excluded by investigating hematologic parameters. Determination in vitro of bilirubin UDP-glycosyltransferase activities can contribute to a differential diagnosis. To minimize the effect of cytoplasmic carrier proteins, in in vitro... 

AlO. Arias, I. M., Gartner, L. M., Seifter, S., and Furman, M., Prolonged neonatal unconjugated hyperbilirubinemia associated with breast feeding and a steroid, pregnane-3a,20/3-diol, in maternal milk that inhibits glucuronide formation in vitro. J. Clin. Invest. 43, 2037-2047 (1964). 

P6. Powell, L. W., Clinical aspects of unconjugated hyperbilirubinemia. Semin. Hematol. 9, 91-105 (1972). 

Hyperbilirubinemia Most patients taking atazanavir experience asymptomatic elevations in indirect (unconjugated) bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). This hyperbilirubinemia is reversible upon discontinuation of atazanavir. 

Miyaoka T, Yasukawa R, Mizuno S, Sukegawa T, Inagaki T, et al. 2005. Proton magnetic resonance spectroscopy (lh-mrs) of hippocampus, basal ganglia, and vermis of cerebellum in schizophrenia associated with idiopathic unconjugated hyperbilirubinemia (gilbert s syndrome). J Psychiatr Res 39 29-34. 

Figure 13.3. Allelic polymorphisms of the human UGT1A1 gene and association with unconjugated hyperbilirubinemia. (Adapted from Annu. Rev. Pharmacol. Toxicol. 40, 581-616,...

Since mutism with olanzapine has been reported in cases of overdose, and detoxification of bilirubin by conjugation with glucuronic acid, the pathway olanzapine uses, is altered in Gilbert s syndrome, which affects 10% of the population, the authors claimed that we should keep in mind idiopathic unconjugated hyperbilirubinemia when prescribing olanzapine. 

Arias, M. Chronic unconjugated hyperbilirubinemia without overt signs of hemolysis in adolescents and adults. J. Clin. Invest. 1962 41 2233-2245... 

E222 Ou, C.-N., Buffone, G.J., Herr-Calomeni, P.J., Finegold, M.J. and Shirey, T.L. (1985). Unconjugated hyperbilirubinemia is overestimated in neonates with cholestasis. A more reliable method is proposed. Am. J. Clin. Pathol. 84, 752-756. 

Gilbert syndrome is a benign condition manifested by mild unconjugated hyperbilirubinemia. This abnormality, affecting 3% to 5% of the population, is clinically important, because it is often misdiagnosed as chronic hepatitis. The serum concentration of bihrubin fluctuates between 1.5 and 3mg/dL (26 and 51 Limol/L) and tends to increase with... 

Lucey-Driscoll syndrome is a familial form of unconjugated hyperbilirubmemia caused by a circulating inhibitor of bilirubin conjugation. The hyperbilirubinemia is mild and lasts for the first 2 to 3 weeks of life. 

Disorders that cause jaundice in the neonate are classified as either unconjugated or conjugated hyperbilirubinemia (see Box31-l). " ... 

Unconjugated hyperbilirubinemia poses a risk for development of kernicterus (acute bilirubin encephalopathy), espe-... 

Causes of unconjugated hyperbilirubinemia in the neonate are physiological jaundice of the newborn, hemolytic disease, and breast milk hyperbilirubinemia. 

Breast Milk Hyperbilirubinemia. This type of hyperbilirubinemia affects about 30% of breast-fed newborns. It is due to a-glucuronidase in breast milk, which hydrolyzes conjugated bilirubin in the intestine. The unconjugated bilirubin, being more lipophilic, is passively absorbed. The condition lasts for a few weeks and is treated by discontinuing breast feeding. 

Jaundice occurs when plasma becomes supersaturated with bilirubin (>2-2.5 mg/dL) and the excess diffuses into the skin, sclera, and other tissues. The sclera is particularly affected because it is rich in elastin, which has a high affinity for bilirubin. Reddish yellow pigments, particularly carotene and lycopene, may give a yellowish tinge to the skin but they do not usually produce scleral coloration. Hyperbilirubinemia may result from elevation of unconjugated or conjugated bilirubin levels. 

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