Rise In Serum Bilirubin Research Articles

Season of Birth and Early Neonatal Events. The Rise of Serum Bilirubin

A prospective study on the rise of serum bilirubin during the first 24 hours of life has been carried out in a sample of 343 newborns from the population of Rome. The rise of serum bilirubin level during the first 24 hours of life depends on season of birth showing a minimum in the Autumn. The phenomenon is much more marked in female than in male newborn infants. Recent studies suggest a beneficial action of bilirubin due to its protective effect from secondary oxidants. Since the newborn infant is very sensible to oxidative damage, it is possible that seasonal variation of bilirubin level during the first few days of life may influence further development and susceptibility to pathological manifestations.

Biochemical indicators of occupational health hazards in Nkalagu cement industry workers, Nigeria

Routine diagnostic tests for some organ-system functions were adopted as biochemical probes in health screening of cement milling workers. Thirty-five volunteers from the Nkalagu cement industry, Nigeria were screened. Out of 14 biochemical parameters studied, raised levels of serum bicarbonates (HCO −), aspartic transaminase (AST) and alanine transaminase (ALT) were observed among cement milling workers compared with a control population. Elevated bicarbonate values were found to differ statistically ( P<0.05) between the quarry workers and the rest of the volunteer work population. In a similar manner, elevated ALT values differ statistically ( P<0.05) between the kilning workers and the rest of the study population. Elevated bicarbonate values are associated with chronic bronchitis, while elevated values of AST and ALT suggest susceptibility to hepatitis, particularly anicteric hepatitis as the elevated values of the transaminase were not matched by a corresponding rise in serum bilirubin. The implications of this study to occupational health screening cannot be overemphasized.

Impact of Venous Catheters on Packed Red Blood Cells

This study was designed to test the hypothesis that there would be increased hemolysis, as indicated by an increase in plasma free hemoglobin and potassium, when packed cells were infused through small gauge percutaneous catheters (24 and 28 g, PC) compared with short catheters (24 g; SC). We were unable to study the 28 g PC because after 1 hour, at a flow rate of 10 ml/hr, only 2.4 ml packed cells were infused. There was a significant increase in plasma free hemoglobin when pre- and postinfusion values were compared (SC, p = 0.005; PC, p = 0.009), but a statistically significant increase in potassium only for the SC (p = 0.008). There were no significant differences between the catheters for either potassium or free hemoglobin. For either catheter the quantity of free hemoglobin transfused could potentially cause a significant rise in serum bilirubin and hemoglobinuria.

Variation of initial serum bilirubin rise in newborn infants with type of illness

Hyperbilirubinaemia in newborn infants is generally regarded as a problem, and bilirubin itself as toxic metabolic waste, but the high frequency in newborn infants suggests that the excess of neonatal bilirubin may have a positive function. To investigate the hypothesis that bilirubin has a role as a free-radical scavenger, the rate of rise in serum bilirubin in the first few days of life was measured in 44 infants with five illnesses thought to enhance free-radical production and in 58 control infants. The infants were selected from 2700 consecutive births by exclusion of those with factors known to affect bilirubin metabolism, including enteral feeding. The control infants were those who seemed to be ill and received treatment, including restriction of enteral feeds, but in whom no illness, or disorders not related to free-radical production, were found. The mean serum bilirubin rise was significantly lower in the combined illness group than in the control group (36·1 [95% Cl 26·9-45·3] vs 66·7 [55·9-77·5] μmol.l -1.day -1; p<0·0001). In subgroup analyses the mean rises in infants with circulatory failure, neonatal depression/ asphyxia, aspiration syndromes, and proven sepsis were significantly lower than in controls matched for gestational age and birthweight, but rises in infants with respiratory distress and their matched controls did not differ. These findings are consistent with the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such consumption may operate in vivo in addition to the standard pathways for bilirubin metabolism (production, isomerisation, and excretion).

A three-year evaluation of metabolic changes in Singaporean Norplant-2 rod acceptors

In this longitudinal study involving 100 Singaporean women, the effects of Norplant-2 rods on metabolic function were evaluated. With respect to liver function, the results indicate possible hepatocellular dysfunction as evidenced by a significant rise in serum bilirubin and a significant fall in total proteins and globulin during the three years of use. As regards lipid metabolism total triglycerides, cholesterol and LDL cholesterol were significantly decreased as compared to their preinsertion values at the end of three years. The HDL-cholesterol was also significantly decreased during the second and third year of use. Despite this, the HDL-cholesterol/total-cholesterol-HDL-cholesterol remained above 0.200. Thus, though speculative, it still appears to indicate that use of Norplant-2 rods is not directly contributory to cardiovascular risk. The use of Norplant-2 was not associated with any significant effect on carbohydrate metabolism after three years of use.

A three-year evaluation of metabolic changes in Singaporean Norplant acceptors

In a longitudinal study involving 100 Singaporean women, the effect of NorplantR on metabolic function was evaluated. With respect to liver function, the results indicate possible hepatocellular dysfunction as evidenced by a significant rise in serum bilirubin and a significant fall in total proteins and globulin during the period under review. As regards lipid metabolism, total triglycerides and total cholesterol still remained significantly decreased at the end of the three years. The LDL, which was significantly decreased in the first year, increased during the subsequent two years to its preinsertion value at the end of three years. The HDL-cholesterol levels continued to decrease in the second and third year after a significant increase in the first year. Despite this, the HDL cholesterol/total cholesterol-HDL cholesterol remained above 0.200. As we have not incorporated a simultaneous non-pill treated control group, the observed changes in lipoprotein lipids could be attributed to extraneous factors such as diet, exercise, or other environmental changes. Nevertheless, the findings at the end of three years, though speculative, still appear to indicate Norplant use to be not directly contributory to cardiovascular risk. The use of Norplant was not associated with any significant effects on carbohydrate metabolism after three years of use.

Benign recurrent intrahepatic cholestasis in a Chinese girl

A 15 year old Chinese girl presented with features of benign recurrent intrahepatic cholestasis, confirmed by liver biopsies performed during attack and remission. Her only younger brother also has features of this syndrome. Serial biochemistry monitoring during a recent attack demonstrated that a rise in the serum bile acids preceded the clinical onset of symptoms and the rise in serum bilirubin and ductal enzymes by 8 weeks. Whether this earlier rise in serum bile acids is related to the pathogenetic mechanism of this syndrome remains to be elucidated.

Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity. II. Biochemical and morphological characterization of the injury and its prevention by phenobarbital.

The present study characterizes the biochemical, morphological, and histological sites of CCNU-induced hepatotoxicity and investigates the effect of modifiers of drug metabolism on this toxicity. A single oral dose (100 mg/kg) of CCNU caused four- and ninefold increases in serum GOT and GPT respectively 48 h after administration in rats. A 25-fold rise in serum bilirubin, a total loss of bile flow, and a decrease in BSP clearance were also observed. Cytochrome P-450 content and EM-N-demethylase activity were significantly decreased to 88% and 66% of control values respectively. A histopathological time course study of CCNU-induced injury showed a progression of acute inflammation, edema, and fibrin deposition in portal areas over 24 h with necrosis and sloughing of bile duct epithelium at 24 and 36 h. Treatment of rats with PB (40 mg/kg/day for 4 days, i.p.) 24 h prior to CCNU administration protected against CCNU-induced hepatotoxicity. Thus, the levels of serum GOT, GPT, and bilirubin were only 2.5 and 4 times higher than in untreated or PB-treated controls. Histopathological examination also showed reduced severity of bile duct lesions in PB-pretreated animals. In rats receiving both PB and CCNU, bile flow was restored and BSP clearance was increased compared to the CCNU-treated rats. The mixed-function oxidase activity in PB + CCNU-treated rats was not significantly different from that in PB-treated controls. It is concluded that pretreatment of rats with PB can markedly suppress the hepatotoxic manifestations, including histopathological changes, the rise in serum bilirubin, and the cholestasis observed in CCNU-treated rats.

Serum free fatty acids and bilirubin concentration during fasting in patients with Gilbert's syndrome and normal controls.

The increments in serum concentrations of unconjugated bilirubin and free fatty acids (FFA) were measured 24 and 48 h after reduction of the caloric intake (400 cal/day) in 17 patients with Gilbert's syndrome (GS) and in 12 healthy control subjects. In males, both normal and with GS, the rise in serum bilirubin was statistically higher (p less than 0.01) as compared to females. On the contrary, no sex difference was found in FFA concentrations. A linear correlation (p less than 0.01) between bilirubin and FFA serum levels was present in normal males and in patients with Gilbert's syndrome of both sexes. Because bilirubin and FFA partly share a common, bilitranslocase-mediated, hepatic uptake mechanism, data reported support the hypothesis that a bilitranslocase function may be one of the metabolic defects in Gilbert's syndrome.

Shock liver.

The clinical syndrome of "shock liver," also known as ischemic hepatitis, is characterized by sudden elevation (to more than 20 times the upper limit of normal) of SGOT and SGPT in response to cellular anoxia, followed by resolution to near normal levels within seven to ten days. In our experience with ten cases, systemic hypotension was documented in only four, but processes characterized by decreased cellular perfusion were identified in all and included cardiac failure or arrhythmia, sepsis, cerebrovascular accidents, renal failure, and chronic obstructive pulmonary disease. We were also able to document the transient rise in serum bilirubin and alkaline phosphatase levels and prolonged prothrombin time that followed the transaminase elevations by 24 to 48 hours in most cases, followed by rapid resolution. In neither of the two cases in which tissue was available by biopsy after resolution of the biochemical abnormalities did we find the classic histologic picture of necrosis in zone 3 ("centrilobular necrosis"). The clinical picture of shock liver is so characteristic and resolves so rapidly that there should be no confusion with other causes of marked elevations of transaminase levels.

Use of Liver Function Tests as Predictors of Rifampicin Metabolism in Cirrhosis

Normal subjects taking rifampicin regularly, show a fall in serum and urinary drug concentrations from enzyme induction and increased biliary excretion. In cirrhosis, hepatocellular dysfunction and impaired biliary excretion may prevent these changes, but there is little information on how the drug should be prescribed in such patients. Serum and urinary rifampicin concentrations were therefore measured in thirteen patients and five controls during a seven-day course (600 mg/day). In controls, peak serum concentrations on Day 7 were lower than on Day 1 (7.0 +/- 3.0 and 8.0 +/- 1.0 microgram/ml respectively) and this was also the case for nine cirrhotic patients with mild impairment of liver function (6.0 +/- 1.0 and 11.0 +/- 2.0 microgram/ml (p less than 0.02). In both groups there was an accompanying fall in urinary rifampicin excretion due to a decrease in desacetylrifampicin excretion. In the remaining four cirrhotic patients, peak serum rifampicin levels rose from 11.0 +/- 5.0 to 17.0 +/- 6.0 microgram/ml and urinary excretion of desacetylrifampicin did not fall. Although values for serum albumin and prothrombin time were of limited value in predicting drug accumulation, pretreatment levels of bilirubin exceeding 50 mumol/l were present in all four patients showing an increase in serum rifampicin concentration. Furthermore, only in this group was there a rise in serum bilirubin during treatment, almost certainly the result of competition between rifampicin and bilirubin for hepatic uptake and excretion. In all patients with cirrhosis, bilirubin concentrations exceeding 50 mumol/l should be an indication for reduction of rifampicin dosage.

Serum bilirubin: a prognostic factor in primary biliary cirrhosis.

We followed up 55 patients with proven primary biliary cirrhosis for several years or until death. A graph of the level of serum bilirubin versus time that was constructed for each patient shows an initial period of variable length in which the serum bilirubin level remained constant. This was followed by a period of rapid rise in serum bilirubin which culminated in the patient's death. Whenever two successive serum bilirubin values taken six months apart exceeded 34 mumol/l (2.0 mg/dl) the patient had entered a late phase of disease and lived an average of 49 months. Ninety-five per cent confidence limits on survival time were 32-74 months. If two successive six month bilirubin values exceeded 102 mumol/l (6.0 mg/dl), calculated survival time was 25 months, and if two successive six month bilirubin values exceeded 170 mumol/l (10.0 mg/dl), survival time was 17 months. Fifteen of the 41 living patients had two consecutive serum bilirubin levels greater than 34 mumol/l (2.0 mg/dl). However, the slope of the rising bilirubin in the living patients is only 35 mumol/l/yr (1.5 mg/dl/yr) compared with 42 mumol/l/yr (2.5 mg/dl/yr) in the dead patients. This means that patients with this disease not may be living considerably longer.

Bilirubin Secretion and Conjugation in the Crigler-Najjar Syndrome Type II

Features characteristic of the Crigler-Najjar syndrome (type II) are described in an adolescent boy with severe congenital unconjugated hyperbilirubinemia. Bilirubin encephalopathy developed only in early puberty after surgery and fasting, coincident with a dramatic rise in serum bilirubin, which responded to intensive therapy. Fasting was later shown to increase markedly the serum bilirubin levels and probably was a major factor in precipitating the initial acute event. One year later, while the patient was in a metabolic steady state, the secretion rate of bilirubin was measured by aduodenal marker-perfusion technique, and the nature of the secreted bilirubin conjugates was characterized. Total bilirubin secretion rates were low, 4.39 mg per hr and 4.44 mg per hr on two separate studies. The major pigment detected in bile was bilirubin monoglucuronide. Bilirubin diglucuronide comprised only a minor fraction of the pigments, and other conjugates were not detected. The present study documents a reduced biliary bilirubin secretion and suggests that the addition of the second glucuronic acid moiety to the bilirubin molecule may be defective in Crigler-Najjar syndrome (type II).

Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy.

Plasma half-lives of amobarbital were determined in newborn children of 10 mothers who had been treated with barbiturates for hypertension in pregnancy for 6 to 42 days prior to delivery. Five mothers had received amobarbital, 200 mg daily, and 5, phenobarbital, 60 to 180 mg daily. Half-lives in 7 of the babies ranged from 16.6 to 49.4 hr, comparable to those previously reported in babies of mothers who had received only a single dose of amobarbital. Thus there was no evidence of induction of amobarbital hydroxylation in these children. Two babies who had a greater than normal rise in serum bilirubin had longer half-lives (86.1 and 117.7 hr). In 1 baby whose mother had membranous glomerulonephritis, plasma amobarbital concentration did not significantly change over the period of the study.

Variations in total serum bilirubin and alkaline phosphatase in the normal postoperative cholecystectomy course

Total serum bilirubin and serum alkaline phosphatase were studied in eighty-seven patients who underwent simple cholecystectomy and radiomanometry without complications. It was found that in most patients a rise in serum bilirubin occurred early in the postoperative course with return to normal preoperative values in approximately two days. A similar rise in alkaline phosphatase was noted later, reaching its peak by the fifth or sixth postoperative day and returning to normal shortly thereafter. These variations all occurred within the limits of normal. Similar variations, but beyond upper normal limits, are found in bile peritonitis. It is unlikely that peritoneal absorption of bilirubin and alkaline phosphatase is responsible for all these changes.Elevation of total serum bilirubin and alkaline phosphatase to normal limits can be expected in the postoperative course of patients undergoing uncomplicated cholecystectomy. Any rise beyond this point should alert the surgeon to the possibility of a complication due to bile leakage into the peritoneal cavity.

Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants.

The endogenous production of carbon monoxide ( V(CO)) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean V(CO) in nine full-term infants was 13.7 +/-3.6 mul CO/kg per hr (SD), and in four erythroblastotic infants V(CO) ranged from 37 to 154 mul CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from V(CO). MLS in normal newborns was 88 +/-15 days (SD), and bilirubin production was 8.5 +/-2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 +/-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.The measurement of V(CO) should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.

Early versus late feeding of low birth weight neonates--a controlled study.

The effect on body weight, blood glucose, serum bilirubin and certain clinical parameters like regurgitation, difficulty with the first feed, morbidity, etc. was studied in 32 low birth weight babies randomly allotted to 4 different feeding schedules. The babies fed with milk or 5% glucose within the first 24 hours, had significantly higher blood glucose values at 48 hours when compared with the group who had been starved till that time. There was no significant difference regarding weight loss and rise in serum bilirubin between early and late fed babies. The morbidity was similar in the four groups and there was no mortality. In conclusion, there is no distinct advantage of forcing early feeding in low birth weight babies and no serious harm is likely to occur if feeds are delayed till 48 hours. The decision to start feeding in low birth weight babies should be individualised depending upon the vigour, colour, and respiratory rate of the infant.

Bile peritonitis: Diagnosis and course

Eight patients with bile peritonitis are reported upon. Two of these patients died. All patients displayed a rise in serum bilirubin and a lag in rise of serum alkaline phosphatase. Data from rats confirm that the bilirubin levels are conjugated. Data from dogs displayed the lag phase of rise of serum alkaline phosphatase. Bacterial contamination of bile peritonitis probably makes the disease worse.

A comparison of the toxicity of prothionamide and ethionamide: A report from the research committee of the british tuberculosis association

The present study was planned to assess the tolerance of patients for and liver toxicity of 0·75 g. prothionamide daily compared with 0·75 g. ethionamide in the treatment of pulmonary tuberculosis. The patients were also treated with 300 mg. isoniazid and 0·75 g. or 1 g. streptomycin daily. The trial was of ‘double blind’ design. The drug regimen was allocated to each patient at random. The duration of treatment was 10 weeks. Tolerance was assessed by weekly recordings of relevant symptoms and signs and liver toxicity by fortnightly estimations of serum bilirubin and transaminase. Fifty-three patients received prothionamide and 48 ethionamide. Anorexia, nausea or vomiting were reported in 17 (32%) patients treated with prothionamide and in 24 (50%) patients treated with ethionamide. This difference is not significant (P > 0·10). In 14 (26%) patients in the prothionamide group and in 15 (31%) patients in the ethionamide group these symptoms were graded as slight, and in 3 (6%) patients treated with prothionamide and in 9 (19%) patients treated with ethionamide they were classified as severe. These differences are not significant (0·10 > P > 0 ·05). Two (4%) patients in the prothionamide group were withdrawn from treatment because of severe gastro-intestinal intolerance. Elevation of serum transaminase was more commonly detected than a rise in serum bilirubin. Five (9%) patients in the prothionamide group and 5 (10%) patients in the ethionamide group had elevated transaminase or serum bilirubin levels in two consecutive estimations. Abnormal liver function tests in two consecutive estimations occurred more often in patients with a pre-treatment weight of less than 64 kg. (140 lbs.). The average weight gain in patients treated with prothionamide was significantly greater than in patients treated with ethionamide. The results suggest that prothionamide may be better tolerated than ethionamide, though the difference, if it exists, is not great. It is equally liable to cause disturbance of liver function. Regular liver function tests are advised for all patients treated with these drugs.

Jaundice following cardiopulmonary bypass.

Serial liver function tests were performed in 29 adult patients following cardiopulmonary bypass for various open-heart procedures. In 22 patients there was a rise in serum bilirubin above 1·5 mg./100 ml., with clinical jaundice in 19 and bilirubinuria in 15 patients. The incidence of jaundice was related to age, the severity of pre-operative cardiac failure, and the duration of perfusion. Possible mechanisms for jaundice are discussed, and evidence is presented that liver damage may follow extracorporeal circulation.