title: The origins and kinetics of bilirubin in healthy dogs, in comparison with man.
abstract: The origins and the kinetics of unconjugated bilirubin were assessed in 25 healthy dogs. Bilirubin kinetics were measured by the analysis of the plasma disappearance of [3H]bilirubin in a two-compartment model. The relative bilirubin productions from erythrocyte haem degradation and early labeled bilirubin were determined by measuring the incorporation of [14C]glycine in erythrocyte haem and in fecal stercobilin. The incorporation of this relation into the model permitted the quantitation of the bilirubin production from erythrocyte destruction, ineffective erythropoiesis and the catabolism of hepatic haemoproteins. The contribution of the three bilirubin sources to the plasma concentration was derived from the calculated fraction reflux into the plasma of bilirubin produced in the liver from hepatic haemoproteins. Other calculated model-dependent and -independent parameters were plasma bilirubin clearance, hepatic bilirubin extraction efficiency, pool sizes, and the fractional transfer rates which reflect the hepatic uptake process, reflux from liver to the plasma, and the conjugating enzyme activity. In plasma of healthy dogs only unconjugated bilirubin was detected. It averaged 0.68 mumol/l, which is far below levels in man. This is probably due to the 20-fold higher hepatic clearance rate in dogs (median 32.2; range 21.6-43.9 ml/kg per min). In addition, fasting hyperbilirubinaemia could not be documented in the dog. The total bilirubin turnover was 14.9 (12.6-17.1) mumol/kg (median and 95% range), with 67 (60-70)% derived from erythrocyte degradation, 5.3 (4.7-5.5)% from ineffective erythropoiesis and 27.7 (24.5-35.3)% from hepatic haemoproteins. The figures for the plasma bilirubin turnover were 12.3 (10.3-14.2) mumol/kg per day, 79 (75-84)%, 6.3 (6.0-6.6)% and 14.8 (9.2-18.9)%, respectively. The presented model permits the simultaneous quantitation of both the origins and the kinetics of bilirubin. The application of this approach in pathological conditions is expected to provide better insight in the pathophysiology of acquired hyperbilirubinaemia.
authors.affiliation: Department of Clinical Sciences of Companion Animals, University of Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
authors.forename: W E
authors.initials: WE
authors.lastname: van den Brom
authors.forename: J
authors.initials: J
authors.lastname: Fevery
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D014316:Tritium; D001663:Bilirubin; D005998:Glycine