Characterization of mechanisms causing hypoalbuminemia in rats with long-term bile duct ligation.
Albumin kinetics and albumin synthesis were studied in rats with chronic bile duct ligation and compared with pair-fed control rats. The plasma albumin concentration was significantly reduced in bile duct ligated rats as compared to control rats, averaging 35 +/- 1 vs 40 +/- 2 g/l after 2 weeks and 28 +/- 3 vs 38 +/- 5 g/l after 4 weeks of bile duct ligation. Two weeks after bile duct ligation, the transcapillary escape rate of albumin was increased by 60% in bile duct ligated rats, whereas the plasma volume was unchanged. Albumin synthesis expressed as a fraction of total liver protein synthesis, as assessed by the 'flooding' dose method using [3H]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 longer different, whereas the plasma volume was increased by 38% in bile duct ligated rats. At this time point, albumin synthesis as a fraction of total liver protein synthesis was decreased by 60% in bile duct ligated rats, and absolute albumin synthesis expressed per 100 g body weight averaged 80 +/- 8 vs 53 +/- 12 mg/(day x 100 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 ligated rats at both 2 and 4 weeks after surgery. The studies suggest that reduced plasma albumin concentrations in bile duct ligated rats are caused by increased capillary permeability and lack of compensatory increase in albumin synthesis 2 weeks, and by increased plasma volume and decreased albumin synthesis 4 weeks after surgery.
Division of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland.
S
S
Krähenbühl
U
U
Marti
I
I
Grant
P J
PJ
Garlick
P E
PE
Ballmer
D000818:Animals; D001652:Bile Ducts / Q000503:physiopathology*; D015152:Blotting, Northern; D001835:Body Weight / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002779:Cholestasis / Q000097:blood / Q000503:physiopathology; D005355:Fibrosis / Q000473:pathology; D008026:Ligation; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010649:Phenylalanine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D012709:Serum Albumin; D010649:Phenylalanine