Bilirubin plasma

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

Higher plasma bilirubin values were observed in groups exposed to 891 ppm, and decreased urinary pH values occurred in... 

B14. Billing, B. H., Williams, R., and Richards, T. G., Defects in hepatic transport of bilirubin in congenital hyperbilirubinaemia an analysis of plasma bilirubin disappearance curves. Clin. Sci. 27, 245-257 (1964). 

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). 

Bilirubin, but not the conjugated pigments, has an affinity for brain tissue (B5, C2, W3), and in newborn infants, with high plasma bilirubin levels due to erythroblastosis or prematurity, staining of the brain nuclei may occur. This causes brain damage and subsequent neurological difficulties, a detailed account of which is given in a review by Claireaux et al. (C3). 

So-called physiological jaundice in infants is attributable to a rise in plasma bilirubin, the conjugated bile pigments being absent. Billing et al. (Bll) found that the maximum increase in bilirubin concentration... 

Levy G, Khanna NN, Soda DM, Tsuzuki O, Stern L (1975) Pharmacokinetics of acetaminophen in the human neonate Formation of acetaminophen glucuronide and sulphate in relation to plasma bilirubin concentration and d-glucaric acid excretion. Pediatrics, 55 818-825. 

Tenoxicam protein binding has been shown in single-dose studies to be unrelated to the plasma concentration of albumin however, patients with cirrhosis and very high plasma bilirubin levels (100-200 pmol/L) have demonstrated a significant increase in the unbound concentration of tenoxicam [42]. 

Less extensive binding of drugs to plasma proteins is generally without clinical importance but there is a significant risk of elevation of plasma bilirubin (in the neonate) following its displacement from protein binding sites by vitamin K, x-ray contrast media or indomethacin. 

The INR (prothrombin time) is preferred to plasma bilirubin and hepatic enzymes as a monitor of liver damage, and renal impairment is better assessed by plasma creatinine than urea (which is metabolised by the liver). The clinical signs (jaundice, abdominal pain, hepatic tenderness) do not become apparent for 24-48 h and liver failure, when it occurs, does so between 2 and 7 days after the overdose. It is vital... 

Synthetic tin protoporphyrin is a specific inhibitor of heme oxygenase and reduces plasma bilirubin concentrations in both adults and neonates, thereby preventing jaundice (1-3). A variety of heme analogues, such as tin, zinc, chromium, and manganese metalloporphyrins, act by competitive inhibition of cleavage of heme to biliver-din and carbon monoxide. Stannic porphyrins seem to be the most effective. The adverse effects are few, with only occasional erythema attributable to the phototoxicity of the metalloporphyrins. 

Reduced BSP removal in neonates is probably due to an insufficient rate of excretion into the bile because hepatic uptake and conjugation are adequate (V7, V8). However, changes in BSP handling with age in neonates has been attributed to circulatory changes (01). No correlation has been found between plasma bilirubin and BSP retention in the neonatal period (M28, Yl). 

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