Encephalopathies bilirubin encephalopathy

Bilirubin oxidase [80619-01 -8], derived from Mjrothecium verrucaria, was modified with polyethyleneglycol when this conjugate was injected intravenously to jaundiced rats, the plasma bilirubin dropped to normal levels. This approach might have potential in the treatment of hyperbilimbinemia, fulminant hepatitis, and neonatal bilirubin encephalopathy (177). 

B16. Bowen, W. R., and Waters, W. J., Bilirubin encephalopathy Studies related to the site of inhibitory action of bilirubin on brain metabolism. A.M.A. J. Diseases Children 93, 21 (1956). 

W2. Waters, W. J., and Briton, H. A., Bilirubin encephalopathy Preliminary studies related to production. Pediatrics 15, 45-48 (1955). 

Prevention alone is often not enough. Children still become jaundiced even after careful assessment. When this occurs.it is important to assess the risk of developing significant hyperbilirubinemia. The main concern is that the child will develop acute bilirubin encephalopathy, which is caused by the toxicity of bilirubin on the basal ganglia and other brain stem nuclei. There are early, middle, and late stages of acute bilirubin encephalopathy (Table 22-3). The term kernicterus is applied to chronic... 

Table 22-4. Description of Chronic Bilirubin Encephalopathy (Kernicterus)...

Amit, Y., Poznansky, M.J., Schiff, D. Neonatal jaundice and bilirubin encephalopathy a clinical and experimental reappraisal. Isr. X Med. Sci. 

Labrune, P.H., Myara, A., Francoual, J., Trivin, F., Odievre, M. Cerebellar symproms as the presenting manifestations of bilirubin encephalopathy in children with Crigler-Najjar type I disease. Pediatrics 1992 89 768-770... 

Sulfonamides should not be given to pregnant women in the third trimester of pregnancy. They can displace bilirubin from plasma albumin and cause kernicterus (bilirubin encephalopathy) (205-208). For the same reason, the administration of sulfonamides to lactating women or premature infants should be avoided. Successful treatment of neonatal hyperbilirubinemia with higher bilirubin concentrations has been established using exchange transfusion and phototherapy. 

Diamond I, Schmid R. Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system. J Clin Invest 1966 45(5) 678-89. 

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

The neonate is at risk for kemicterus if the serum unconjugated bilirubin level is higher than 17 mg/dL. Kemicterus is characterized by yellow staining of clusters of neuronal cell bodies in the basal ganglia, cerebellum, and brain stem, leading to motor and cognitive deficits or death. Immaturity and f)erhaps hypoxia make the blood-brain barrier permeable to bilirubin and contribute to the likelihood of kemictems. The biochemical basis of bilirubin encephalopathy is due to many causes inhibition of RNA and protein synthesis, carbohydrate metabolism (both cAMP-mediated and Ca " -activated), phospholipid-dependent protein kinases, enzymes involved in the electron transport system, and impaired nerve conduction. 

An infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency developed severe hyperbilirubinemia and transient bilirubin encephalopathy that the reporting authors indicated as being likely related to consumption of Chinese herbs, including coptis. The peak serum bilirubin was 562 pmol/1 (Yeo and Tan 1996). A review of G6PD deficiency indicated that this condition is a potential source of severe neonatal hyperbilirubinemia and kernicterus (Kaplan and Hammerman 2002). 

This chapter examines various aspects of bilirubin encephalopathy including bilirubin metabolism, bilirubin toxicity, in-vivo studies and studies in Gunn rats, human studies, and treatment modalities. 

The underlying cause of human bilirubin encephalopathy is almost always erythroblastosis foetalis or a deficiency of the fiver bilirubin conjugating enzyme... 

Fig. 16.1 Effect of severe bilirubin encephalopathy on cerebellar ATP in newborn Gunn rats. The mean SEM is expressed as nmoles mg" dry weight. = p<0.05...

Schutta, H.S. and Johnson, L. (1971). Fine structure observations on acute bilirubin encephalopathy in Gunn rats induced by sulfadimethoxine. Lab. Invest. 24 82-96 Siegfied, E.C., Stone, M.S., Madison, K.C. (1992). Ultraviolet light burn a cutaneous complication of visible light phototherapy of neonatal jaundice. Pediatr. Dermatol. 9 (3) 278-282 Tenhunen, R., Marver, H.S., and Schmid, R. (1968). The enzymatic conversion of heme to bilimbin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. USA. 61 748-755... 

Liver Fever, lethargy, change in color or quantity of bile in patients w/ biliary T-tube, graft tenderness and swelling, back pain, anorexia, ileus, tachycardia, jaundice, ascites, encephalopathy Abnormal LFTs, increased bilirubin, alkaline phosphatase, transaminases, biopsy positive for mononuclear cell infiltrate with evidence of tissue damage... 

Population PK screening in Phase II and Phase III is useful in assessing the impact of altered hepatic function (as a covariate) in PKs, if those patients are not excluded from Phase II and III trials, and if there is sufficient PK information collected about the patients to characterize them reasonably well. If a population PK approach is used, patients in Phase II and III studies are assessed for encephalopathy, ascites, serum bilirubin, serum albumin, and prothrombin time (which are components of the Child-Pugh score) or a similar group of measures of hepatic function. The population PK study, then, would include the following features ... 

Jaundice is notitseifa disease but is an important diagnostic indicator of many underiying conditions, in newborns, jaundice can iead to toxic encephalopathy due to deposition of bilirubin within the lipid regions of membranes of the brain (kernicterus). 

Sulfonamides compete for sites on plasma proteins that are responsible for the binding of bilirubin. As a result, less bilirubin is bound, and in the newborn, the unbound bilirubin can be deposited in the basal ganglia and subthalamic nuclei, causing kernicterus, a toxic encephalopathy. For this reason, sulfonamides should not be administered to newborns or to women during the last 2 months of pregnancy. 

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