Total serum bile acids and the bile acid profile as tests of liver function

Total serum bile acid assay for the evaluation of liver function has been available for many years but its application has been limited primarily by factors such as methodology, equipment and cost. New and improved methods for bile acid assay such as the radioimmunoassay or the hydroxysteroid dehydrogenase techniques have brought the assay for bile acids into the realm of the clinical laboratory. The efficacy of bile acids for clinical diagnostic use in the evaluation of liver function has not been firmly established. Newer methods using high pressure liquid chromatography to develop a profile of the different bile acids may clarify its usefulness and define its role among the many available tests of liver function in animals.     

Total serum bile acids and the bile acid profile as tests of liver function

Total serum bile acid assay for the evaluation of liver function has been available for many years but its application has been limited primarily by factors such as methodology, equipment and cost. New and improved methods for bile acid assay such as the radioimmunoassay or the hydroxysteroid dehydrogenase techniques have brought the assay for bile acids into the realm of the clinical laboratory. The efficacy of bile acids for clinical diagnostic use in the evaluation of liver function has not been firmly established. Newer methods using high pressure liquid chromatography to develop a profile of the different bile acids may clarify its usefulness and define its role among the many available tests of liver function in animals.     

Serum bile acids in captive bustards

Blood samples were collected from clinically normal male and female houbara (Chlamydotis undulata macqueenii), kori (Ardeotis kori), buff-crested (Eupodotis ruficrista gindiana) and white-bellied bustards (E. senegalensis) to determine serum bile acid concentrations. Bile acid concentrations were determined by analysis with an Ultrospec 3000 ultraviolet/visible spectrophotometer, using an enzymatic bile acid test. The results provided values of serum bile acid concentrations for the four species, with means +/- standard errors of 35.8 +/- 2.8 mumol; 51.1 +/- 5.0 mumol; 18.4 +/- 2.1 mumol and 20.8 +/- 5.4 mumol for the houbara, kori, buff-crested and white-bellied bustard, respectively. Although no gender or age differences were detected within species, the results demonstrated significant differences in concentrations in clinically normal individuals between the different species.     

Blood serum level of primary bile acids in cattle, horses, swine and dogs

The levels of the two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were determined by radioimmunoassay in cattle, horse, pig and dog serum. The mean serum cholic acid (SCA) and deoxycholic acid (SCDCA) levels of cows varied with their reproductive status, being 7.8 (+/- 3.3) and 1.5 (+/- 1.0) mumol/l in dry cows, 17.8 (+/- 6.9) and 2.3 (+/- 1.0) mumol/l in freshly calved dams, and 15.8 (+/- 5.7) and 2.3 (+/- 0.8) mumol/l, respectively, in lactating cows. The SCA level found in the immediate prepartal period and also on the day of calving corresponded to those found during the dry period, then, they tended to rise 2 days after calving and attained the peak characteristic for freshly calved dams on day 3 or 4 post partum. Feed consumption had no influence on the serum levels of primary bile acids, and circadian variations of SCA and SCDCA were also negligible. Suckling calves had much lower SCA levels (2.3 (+/- 1.0) mumol/l before feeding than cows. This initial concentration rose to 10.3 (+/- 2.9) mumol/l 1 h after feeding and returned to 5.0 (+/- 2.1) mumol/l 3 h later. Like cows, horses showed no appreciate difference between pre- and post-feeding levels of SCA (2.2 (+/- 1.2) mumol/l) and SCDCA (1.1 (+/- 0.3) mumol/l). Unlike bovines, pigs and dogs showed a considerable increase in the serum levels of the primary bile acids after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma bile acids,plasma amino acids,and hepatic enzyme pools as indices of functional impairment in liver-damaged sheep

Plasma bile acids, plasma amino acids, and the total hepatic pools of aspartate aminotransferase, gamma glutamyltransferase, glutamate dehydrogenase, and sorbitol dehydrogenase were compared in control sheep (Group 1), sheep with subclinical pyrrolizidine alkaloid toxicosis (Group 2), and in sheep with acute hepatocellular necrosis associated with the hemolytic phase of chronic copper poisoning (Group 3). Subclinical pyrrolizidine alkaloid toxicosis was not associated with any changes in bile acid or amino acid status but was associated with a significant decline in the hepatic pools of sorbitol dehydrogenase and aspartate aminotransferase. This observation could not be explained in terms of enzyme leakage from damaged hepatocytes and suggested that pyrrolizidine alkaloids might specifically inhibit hepatocellular enzyme synthesis. Group 3 sheep also had reduced hepatic enzyme pools which were at least partly referable to enzyme leakage from damaged hepatocytes. In these sheep, increases in plasma bile acids were a more sensitive index of hepatic function than were either increased aromatic amino acid concentration or the ratio between branched chain and aromatic amino acids.     

Serum bile acids and the assessment of hepatic function in dogs and cats

Current literature in veterinary internal medicine regarding the clinical use of the serum bile acids test to assess hepatobiliary function in dogs and cats is reviewed. The test is best used in cases where clinical signs and routine laboratory tests are suggestive of liver disease. It is a highly sensitive and specific test of hepatic function, and is the best method of assessing liver function available to the private practitioner. Abnormal results do not determine etiology, severity, or prognosis of the disorder. They merely indicate the need for hepatic biopsy. The serum bile acids concentration should always be measured in both a fasting and a two-hour postprandial sample.     

Plasma bile acids, lactate dehydrogenase and sulphobromophthalein retention test in canine carbon tetrachloride intoxication

This paper studies the progression of various hepatic function tests (fasting and post prandial plasma bile acids, lactate dehydrogenase [LDH], hydroxybutyrate dehydrogenase [HBDH], LDH isoenzymogram, and 45 minutes sulphobromophthalein retention) in a classic model of canine hepatic injury. Sulphobromphthalein and plasma bile acid determination are excellent indicators of hepatic damage. Post prandial bile acid quantification does not improve the diagnostic capacity of this test. LDH alters only in the first 48 hours after poisoning and the study of the HBDH/LDH ratio makes it possible to differentiate the origin of plasma LDH. LDH isoenzymogram is not a practical test for routine clinical diagnosis.     

Diurnal and individual variations in bile acids in the plasma of normal dairy cows

Blood samples were collected every 2 h during a 24 h period from 6 cows of one herd and 10 cows of another herd. In a third herd 9 cows were sampled every 2 h from 6 a.m. to 8 p.m. Concentrations of total bile acids, acetoacetate, glucose and free fatty acids were determined in blood plasma. A marked difference in individual bile acid concentrations and patterns of diurnal variation was found. For most cows the highest bile acid values were observed between 2 and 6 a.m. (overall mean (+/- SD) at 6 a.m.: 104 +/- 84 mumol/l, range: 20-307 mumol/l). Fourteen cows with a bile acid value greater than 90 mumol/l at 6 a.m. ("high BA") were characterized as a group by showing a pronounced decrease in the mean bile acid concentration after morning feeding. In the group of 11 cows with a 6 a.m. bile acid value less than 90 mumol/l ("low BA") the time of day did not contribute significantly to the bile acid variation. For the "high BA" group a nearly synchronous variation between the mean values of the 3 feeding dependent parameters (acetoacetate, glucose and free fatty acids) and the mean values of bile acids was found. The within animal coefficients of correlation between bile acids and the feeding dependent parameters were significantly higher in the "high BA" group than in the "low BA" group. No direct connection was found between bile acid levels and the quantity of concentrates fed or the individual milk yield.     

Changes in the serum levels of primary bile acids in dairy cows

Serum cholic acid (SCA) and serum chenodeoxycholic acid (SCDCA) concentrations were determined in healthy dairy cows by radioimmunoassay (RIA). The levels of these two primary bile acids were correlated with the cows' reproductive status. The lowest concentrations were measured in dry cows (SCA: 7.8 +/- 3.3 mumol/l, SCDCA.: 1.5 +/- 1.0 mumol/l). In freshly calved cows SCA and SCDCA was 17.8 +/- 6.9 mumol/l and 2.3 +/- 1.0 mumol/l, respectively, while in milking cows SCA and SCDCA was 15.8 +/- 5.7 and 2.3 +/- 0.8 mumol/l, respectively. SCA concentration showed a characteristic change on the days immediately after calving: on calving day it was close to the mean SCA concentration found for dry cows, then it underwent a striking abrupt rise and reached the value typical of post-parturient cows by post-partum (PP) day 4-5. Cholic acid was found to be the major primary bile acid in the blood of dairy cows. In dry cows the SCA:SCDCA ratio is 5:1. If the serum bile acid concentration rises, the SCA:SCDCA ratio will increase further.     

Elevated bile acids in the plasma of laying hens fed rapeseed meal

A simple procedure was developed for the estimation of bile acid taurine conjugates in fowl plasma. Laying hens fed a diet containing rapeseed meal (RSM) (400 g kg-1) for 12 weeks had higher bile acid levels (154 mumol litre-1) than hens fed a control soyabean diet (116 mumol litre-1) (P less than 0.01). The incidence of liver haemorrhages was higher (34.8 per cent) in RSM-fed hens than in controls (21 per cent), but the severity of the lesions did not correlate with the bile acid concentration in affected birds. Histological examination of sections from livers of RSM-fed birds did not reveal significant hepatocyte degeneration outside the immediate vicinity of the haemorrhage. Canalicular bile plugs were never seen. The incidence of liver haemorrhages (13 per cent) and plasma bile acids (85 mumol litre-1) were lower in hens fed a diet containing beta-aminopropionitrile (0.5 g kg-1), a known lathyrogen. Acute treatment of hens with the hepatotoxin alpha-naphthyl isothiocyanate over four days induced necrosis of hepatocytes and resulted in elevated bile acid concentrations (262 mumol litre-1) compared with controls (73 mumol litre-1) given arachis oil. It was concluded that laying hens fed high levels of RSM develop cholestasis but the toxic principle is not known.     

Serum bile acids concentrations in healthy and clinically ill neonatal foals

BACKGROUND: Reference ranges for serum bile acids (SBA) concentration are well established in healthy adult horses. Increased values are indicative of hepatic disease. HYPOTHESES: SBA concentrations are significantly greater in the neonatal period compared with mature horses, and illness in the neonatal period will further increase SBA. ANIMALS: Ten healthy mature horses, 12 healthy foals, and 31 clinically ill foals. METHODS: Prospective cross-sectional study. Blood samples were obtained once from the mature horses, from healthy foals immediately after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of age; and from ill foals less than 1 month of age at the time of admission to the Veterinary Teaching Hospital. SBA concentrations were determined enzymatically and by radioimmunoassay. Total and direct bilirubin and triglyceride concentrations were measured, as well as sorbitol dehydrogenase (SDH) and gamma-glutamyltransferase (GGT) activities. RESULTS: There was a significant negative correlation between age and SBA concentration. Compared with mature horses, SBA concentrations were significantly greater in healthy foals at each collection time over the first 6 weeks of life. Radioimmunoassay values were lower than enzymatic SBA values, with increasing bias as the mean difference between values increased. When comparing age-matched values between healthy and ill foals, there were no significant differences in SBA. None of the ill foals had a primary diagnosis of hepatic disease. There was no significant correlation between the SBA concentration and the bilirubin or triglyceride concentrations or the GGT activity. There was a significant direct correlation between increased SBA and serum SDH activity in healthy foals only. CONCLUSION AND CLINICAL IMPORTANCE: SBA concentrations in foals are significantly higher in the early neonatal period, underscoring the importance of using age-matched references when evaluating clinical pathology values during the neonatal period.     

Quantification of plasma bile acids in the dog with a direct spectrophotometric method

Plasma bile acid estimation has recently been shown to be an excellent indicator of hepatic function in the dog. At the moment the only reported quantification method useful for routine clinical purposes in dogs is a direct spectrophotometric enzymatic technique. This article describes a modification of this method which improves its sensitivity. The problem of processing samples with high levels of lactate dehydrogenase (and more specifically of LDH5), and its clinical significance is also discussed.     

Changes in the concentration and composition of biliary and serum bile acids in the young domestic fowl

1. Concentrations of biliary and serum bile acids, their molecular compositions and serum cholesterol concentrations were determined in chicks at 2, 3, 4 and 6 weeks of age. 2. The concentration of biliary bile acid was maximal at 3 to 4 weeks, decreasing by 6 weeks of age. 3. The serum concentration of bile acid was maximal at three weeks of age. 4. Serum total cholesterol increased from two weeks and was maximal at 6 weeks of age. 5. Chenodeoxycholic acid was the predominant biliary unconjugated bile acid. 6. Tauro-chenodeoxycholic acid and tauro-cholic acid were the dominant molecular species of biliary and serum conjugated bile acid.     

Determination of serum bile acids in fasting dogs with hepatobiliary disease

The diagnostic value of determining total conjugated serum bile acid (SBA) concentrations was evaluated in fasting dogs with spontaneous liver disease. Conjugated primary SBA values were determined by radioimmunoassay in 12 healthy dogs, 64 dogs with hepatobiliary disease, and 9 dogs with intestinal disorders unassociated with clinical or biochemical evidence of liver disease. Reference values for SBA concentrations ranged from 0 to 5 mumol/L and were not significantly different from those determined in dogs with intestinal disease (P less than 0.05). Mean SBA concentrations determined in dogs with portosystemic shunts, glucocorticoid-induced hepatopathy, hepatic neoplasia, hepatitis, cholestasis, and cirrhosis were significantly greater than reference values (P less than 0.05). The mean SBA concentration in dogs with glucocorticoid-induced hepatopathy was significantly (P less than 0.05) lower than that in all other clinical groups of dogs with liver disease, except in dogs with cholestasis. Although these 2 groups were statistically indistinguishable, dogs with glucocorticoid-induced hepatopathy generally had lower SBA values (2 to 37 mumol/L) than did the group with cholestasis (2 to 562 mumol/L). The SBA concentrations in fasting dogs were weakly correlated with histologic evidence of hepatic damage, as determined by a total biopsy score (r = 0.28, P less than 0.02). Because total SBA concentrations were increased in 89% of all dogs with hepatobiliary disease, the determination of SBA appears to be a sensitive test of hepatic dysfunction.