CHARACTERIZATION OF MECHANISMS CAUSING HYPOALBUMINEMIA IN RATS WITH LONG-TERM BILE-DUCT LIGATION

Albumin kinetics and albumin synthesis were studied in rats with chron ic bile duct ligation and compared with pair-fed control rats. The pla sma albumin concentration was significantly reduced in bile duct ligat ed rats as compared to control rats, averaging 35+/-1 vs 40+/-2 g/l af ter 2 weeks and 28+/-3 vs 38+/-5 g/l after 4 weeks of bile duct ligati on. Two weeks after bile duct ligation, the tr anscapillary escape rat e of albumin was increased by 60% in bile duct ligated rats, whereas t he plasma volume was unchanged, Albumin synthesis expressed as a fract ion of total liver protein synthesis, as assessed by the 'flooding' do se method using [H-3]phenylalanine, was decreased by 46% in bile duct ligated rats. However, absolute albumin synthesis expressed per 100 g body weight was not different from control rats. Four weeks after bile duct ligation, the transcapillary escape rate of albumin was no longe r different, whereas the plasma volume was increased by 38% in bile du ct ligated rats. At this time point, albumin synthesis as a fraction o f total liver protein synthesis was decreased by 60% in bile duct liga ted rats, and absolute albumin synthesis expressed per 100 g body weig ht averaged 80+/-8 vs 53+/-12 mg/(dayx100 g) in control and bile duct ligated rats (p<0.05). The hepatic steady-state levels of albumin mRNA determined by Northern blot analysis were decreased in bile duct liga ted rats at both 2 and 4 weeks after surgery. The studies suggest that reduced plasma albumin concentrations in bile duct ligated rats are c aused by increased capillary permeability and lack of compensatory inc rease in albumin synthesis 2 weeks, and by increased plasma volume and decreased albumin synthesis 4 weeks after surgery. (C) Journal of Hep atology.