Dynamics of albumin in plasma and ascitic ¯uid in patients with cirrhosis Jens H. Henriksen 1 , Ole Siemssen 2 , Jens Jacob Krintel 2 , Axel Malchow-Mùller 2 , Flemming Bendtsen 2 , Helmer Ring-Larsen 3 1 Department of Clinical Physiology & Nuclear Medicine, 239 Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark 2 Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark 3 Department of Hepatology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark Background/Aims: To determine dynamics of albumin in plasma and ascitic ¯uid of patients with cirrhosis. Methods: Forty-seven patients were classi®ed in four groups: I ± patients without ¯uid retention; II± patients with ascites not resistant to subsequent diuretic treatment; III ± recompensated patients during diuretic treatment; and IV ± patients with diuretic-resistant ascites. Transvascular and transperitoneal albumin transports were quanti®ed by 131 I-/ 125 I-labelled human albumin. Results: TER p (i.e. the fraction of intravascular albumin (IVM) passing from plasma into the interstitial space per hour) was increased in all groups. In group IV patients the transport rate of albumin from plasma into the ascitic ¯uid (TER PA ) was signi®cantly higher than the transport rate from the ascitic ¯uid back into the plasma: TER AP (0.45 vs. 0.26% IVM/h, P , 0.002). In group II patients TER PA was similar to TER AP (0.27 vs. 0.25% IVM/h, ns). A direct correlation was found between TER PA and TER AP in both groups of patients (r  0.78, P , 0.001). Conclusion: In non-resistant ascites, there is a steady state between the transport of albumin into the peritoneal cavity and back into the plasma, but in resistant ascites the former transport is elevated. Thus, local factors may be important to treatment of ascites. q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. Keywords: Albumin; Ascites; Cirrhosis; Diuretic-resistant ascites; Transperitoneal albumin kinetics; Transvascular albumin transport 1. Introduction Since Starling reported the fundamental principles of transcapillary ¯uid dynamics [1], regulation of the transvas- cular transport has attracted considerable interest [2]. Thus, the balance between plasma and interstitial volume is main- tained by re®ned mechanisms that include haemodynamic and oncotic forces, and lymph drainage [2,3]. Advanced liver disease is often associated with profound abnormalities in ¯uid homeostasis, including avid sodium±water retention and abnormal distribution of body ¯uids [4]. In addition, transvascular and in particular the transperitoneal dynamics of proteins may be abnormal [5±8]. The presence of oncotic material, i.e. albumin, in the peritoneal space is a prerequi- site for ¯uid accumulation here and hence for the genesis and perpetuation of ascites [3,5±10]. The transvascular and transperitoneal passage of albumin into the interstitial and intraperitoneal spaces, respectively, may be accelerated by increased transvascular ®ltration or changed microvascular permeability [3,5,11]. However, the back transport of onco- tic material into the bloodstream is equally important to the dynamic balance between intra- and extravascular albumin [3,5,12,13], but hitherto no report has dealt with the simul- taneous determination of these transport rates in patients with cirrhosis. The present study was undertaken to determine blood to interstitial space, blood to peritoneal space, and peritoneal to blood transport rates of albumin in different categories of patients with cirrhosis and ¯uid retention in order to eluci- date abnormalities in ¯ux and drainage in the hepatic ascites syndrome, especially in relation to response of therapy. Journal of Hepatology 34 (2001) 53±60 0168-8278/01/$20.00 q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S0168-8278(00)00009-X www.elsevier.com/locate/jhep Received 27 December 1999; received in revised form 3 May 2000; accepted 20 July 2000