Bilirubin serum concentration

UGT activity is modulated by various hormones. Excess thyroid hormone and ethinyl oestradiol (but not other oral contraceptives) inhibit bilirubin glucuronidation. In contrast, the combination of progestational and oestrogenic steroids results in increased enzyme activity. Bihrubin glucuronidation can also be inhibited by certain antibiotics (e.g. novobiocin or gentamicin, at serum concentrations exceeding therapeutic levels) and by chronic hepatitis, advanced cirrhosis and Wilson s disease. 

In a double-blind, randomized, placebo controlled trial of praziquantel in 42 patients with clonorchiasis and an open study in 32 patients, the adverse effects of praziquantel were transient and included nausea and vomiting (15%), vertigo (12%), hepatomegaly (4.5%), headache (1.5%), rash (1.5%), and hypotension (1.5%) (9). Of 20 patients who received placebo, one developed a transient skin rash, fever, and chills. There were minor and transient, albeit statistically significant, changes in hemoglobin and serum concentrations of total protein, uric acid, cholesterol, and bilirubin. 

There is better agreement between the serum concentrations or activities of several constituents in monozygotic twins than in dizygotic twins.This evidence indicates the importance of genetic constitution in determining the concentration of blood constituents. An influence of heredity has been substantiated on the plasma concentrations of cholesterol, glucose, urea nitrogen, urate, and bilirubin. 

Exposure to sunshine for a weekend during summer may cause enough photodegradation of bilirubin to reduce the serum concentration by 20%. Protracted exposure to sun during the summer leads to a consistently lower bdirubin concentration than during winter. Some seasonal effects on the composition of body fluids are listed in Table 17-11. 

Serum y-glutamyl transpeptidase (GGT) and cholesterol (Section 3.2.2.6.2.2), but not serum ALT or bilirubin, were positively correlated with serum PCB levels in 458 residents of Triana, Alabama (Kreiss et al. 1981). These associations were independent of factors such as age and alcohol and fish consumption, although the natural partitioning of PCBs into serum lipids could contribute to the correlation. Consumption of contaminated fish was the only known source of PCB exposure. The mean serum concentration of PCBs (analyzed as Aroclor 1260) was 17.2 ppb. Levels of DDT were also increased in residents and fish, and there was a strong positive correlation between serum concentrations of DDT and PCB. Serum DDT levels did contribute to the variance in serum GGT and other effects, but this does not preclude the possibility of an interaction between PCB and DDT. 

When the biliary tract becomes blocked, bilirubin is not excreted and serum concentrations rise. The patient becomes jaundiced. The jaundiced patient is de.scribed further on pages 52-5.T. 

Systemic ribavirin causes dose-related anemia due to extravascular hemolysis and dose-related suppression of bone marrow. Reversible increases of serum bilirubin, serum iron, and uric acid concentrations occur during shortterm oral administration. Bolus intravenous infusion may cause rigors. In HIV-infected patients, chronic oral therapy is also associated with dose-related lymphopenia and gastrointestinal and CNS complaints, including headache, lethargy, insomnia, and mood alteration. 

TABLE V. Comparison of Average Serum Concentrations of Bile Salts, Bilirubin, and Alkaline Phosphatase for Groups of Patients with Various Hepatobiliary Disorders... 

Serum lithocholate concentrations can be lowered with either neomycin or cholestyramine, as can the serum concentrations of the other bile salts if they are elevated. This is often associated with a similar decline in serum bilirubin concentrations, alkaline phosphatase activity, and BSP retention (7,95,105,106). This response has been interpreted as at least one piece of evidence that high serum bile salt concentrations, especially of lithocholate, may be injurious to the liver. In three jaundiced children with a paucity of intrahepatic bile ducts and pruritus, lowering of the serum bile salt concentrations to normal values with cholestyramine was accompanied by a return to normal of all previously abnormal liver chemistries except alkaline phosphatase, and the patients growth curves returned to normal (95). 

This rare inherited disorder also results from mutations in the gene encoding bilirubin-UGT, but some activity of the enzyme is retained and the condition has a more benign course than type I. Serum bilirubin concentrations usually do not exceed 20 mg/dL. Patients with this condition can respond to treatment with large doses of phenobarbital. 

The Group II (biliary tract) enzymes are abnormal usually when the serum bilirubin concentration is also abnormal. Most commonly used is alkaline phosphatase which is a highly sensitive indicator of biliary tract obstruction, perhaps because the enzyme is synthesized as an induced response to obstruction of even small bile ducts. Most techniques used to identify the origin of an elevated serum alkaline phosphatase are not very useful from a clinical viewpoint (23). The simultaneous measurement of GMT activity has been found to be useful in differentiating between the hepatic and bony origin of alkaline phosphatase. An increased GMT activity in a patient with an increased ALP activity is a good indication that there is biliary biliary tract disease (62,63). 

Hyperbilirubinemia Abnormally high concentrations of the bile pigment bilirubin in the bloodstream. Hyperbilirubinemia is defined as a total serum bilirubin level greater than 5 mg/dL. 

Hepatic Effects. An increase in serum iron, which may reflect an adverse liver effect, was observed in workers exposed for 6 months to phenol in a wood treatment liquid (Baj et al. 1994). Elevated concentrations of hepatic enzymes in serum, and an enlarged and tender liver suggestive of liver injury, were reported in an individual who had been exposed repeatedly to phenol vapor for 13.5 years (Merliss 1972). Since phenol was also spilled on his clothes resulting in skin irritation, dermal and inhalation exposures were involved. A 2-fold increase in serum bilirubin was observed in a man who was accidentally splashed with a phenol solution over his face, chest wall, hand, and both arms (Horch et al. 1994). Changes in liver enzymes were not observed in persons exposed to phenol in drinking water for several weeks after an accidental spill (Baker et al. 1978). This study is not conclusive because the measurements were completed 7 months after the exposure. 

Lampe, J.W., Bigler, J., Horner, N.K., et al. (1999) UDP-glucuronosyltransferase (UGTIAI 28 and UGT1A6 2) polymorphisms in Caucasians and Asians relationships to serum bilirubin concentrations. Pharmacogenetics. 9, 341-349. 

The most frequent protein in the plasma, at around 45 g is albumin. Due to its high concentration, it plays a crucial role in maintaining the blood s colloid osmotic pressure and represents an important amino acid reserve for the body. Albumin has binding sites for apolar substances and therefore functions as a transport protein for long-chain fatty acids, bilirubin, drugs, and some steroid hormones and vitamins. In addition, serum albumin binds Ca "" and Mg "" ions. It is the only important plasma protein that is not glycosylated. 

Bilirubin effects depend on the method used for analysis. Interferences in direct serum protein methods are observed at bilirubin levels greater than 5 mg/100 ml (K7). A sample containing 20 mg of bilirubin per 100 ml increased the apparent total protein by 0.2 g/100 ml. Concentrations of bilirubin as high as 20 mg/ml do not effect albumin assays using bromocresol green binding (D12), but have a marked effect on these assays when [2-(p-hydroxyphenylazo)-benzoic acid] (HABA) dye is used (A7b). 

Premenopausal use There is no indication for premenopausal use of raloxifene. Hepatic function impairment Raloxifene was studied, as a single dose, in Child-Pugh class A patients with cirrhosis and serum total bilirubin ranging from 0.6 to 2 mg/dL. Plasma raloxifene concentrations were approximately 2.5 times higher than in controls and correlated with total bilirubin concentrations. Safety and efficacy have not been evaluated further in patients with severe hepatic insufficiency. Carcinogenesis In long term carcinogenicity studies in animals there was an increased incidence of ovarian tumors, testicular interstitial cell tumors, and prostatic adenocarcinomas. 

Transient abnormalities in liver function tests (eg, elevation in serum bilirubin, alkaline phosphatase, serum transaminases), and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed. Drug/Food interactions Food interferes with the absorption of rifampin, possibly resulting in decreased peak plasma concentrations. Take on an empty stomach with a full glass of water. 

Exposure of male Fischer 344 rats to ptzra-xylene (0-1600 ppm [0-6940 mg/m- ], 6 h per day for one or three days) had negligible effect on hepatic morphology and serum activities of alanine or aspartate aminotransferases, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase or serum bilirubin concentration (Simmons et al., 1991). Liver size was increased and its cytochrome P450 content was elevated. 

Treatment of male Charles-Foster rats with sublethal doses of xylene (0.2 mL of 5 mmol/L extra-pure xylene solution on alternate days for 30 days isomeric composition not indicated) resulted in slight increases of serum aspartate and alanine aminotransferase and alkaline phosphatase activities and bilirubin concentration (Rana Kumar, 1993). A slight increase in alanine aminotransferase activity was also observed after a 3.5-week treatment of male Wistar rats with zneto-xylene (800 mg/kg bw per day on five days per week, by gavage) (Elovaara et al., 1989). Inhalation exposure of C3H/HeJ mice to /jora-xylenc (1200 ppm [5200 mg/m ], 6 h per day for four days) did not affect the serum alanine or aspartate aminotransferase or lactate dehydrogenase activities, or bilirubin level (Selgrade et al., 1993). 

In a retrospective review of 497 patients taking propylthiouracil for hyperthyroidism, clinically overt hepatitis developed in six patients at 12-49 days after starting the drug (50). Jaundice and itching were present in five, fever in two, rash in two, and arthralgia in one. Serum bilirubin, alanine transaminase, and alkaline phosphatase were increased in five, four, and six patients respectively. The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two. There were no differences in age, sex, drug dose, or serum thyroid hormone concentrations at time of diagnosis in those with hepatic injury compared with those without. Liver function normalized in all patients at 16-145 days after withdrawal of propylthiouracil. In addition to these cases of overt liver injury, 14% of the cohort had mild asymptomatic liver enzyme rises at a mean of 75 days after the start of treatment. 

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