A distributed model of fluid and mass transfer in peritoneal dialysis

1990 ◽  
Vol 258 (4) ◽  
pp. R958-R972 ◽  
Author(s):  
E. L. Seames ◽  
J. W. Moncrief ◽  
R. P. Popovich

A mathematical model has been developed to study peritoneal fluid and solute transfer. The model uses the concept of a distributed capillary system within the peritoneal tissue. The model accounts explicitly for transport across the capillary membrane, through interstitial tissue, and across the mesothelium. The capillary and mesothelial membranes are modeled using pore theory and a dual pathway (through pores and across cells) for fluid transfer. The nonperitoneal tissues are modeled as a single body pool. Lymphatic uptake from the peritoneal cavity is included. Model parameters were found from the literature and by simultaneously fitting experimental data for dialysate volume and dialysate concentrations of blood urea nitrogen, glucose, creatinine, and inulin. The model was also shown to predict concentration gradients within several tissues surrounding the peritoneal cavity. Variation of the model parameters revealed the importance of the mesothelial cell layer in peritoneal ultrafiltration. The results of model simulations indicate an initial transfer of fluid from the tissue space to the peritoneal cavity followed by transcapillary fluid transfer.

2016 ◽  
Vol 310 (11) ◽  
pp. H1501-H1511 ◽  
Author(s):  
Joanna Stachowska-Pietka ◽  
Jacek Waniewski ◽  
Michael F. Flessner ◽  
Bengt Lindholm

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data.


2001 ◽  
Vol 21 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Alicja Polubinska ◽  
Krzysztof Pawlaczyk ◽  
Malgorzata Kuzlan–Pawlaczyk ◽  
James Moberly ◽  
...  

Background Hyaluronan (HA) is a major component of interstitial tissue that participates in fluid homeostasis, response to inflammation, and wound healing. Previous studies have shown that intraperitoneal administration of HA can affect peritoneal fluid transport during short peritoneal dialysis exchanges in anesthetized rats. We sought to investigate the effect of high molecular weight HA on peritoneal permeability in conscious rats during dialysis exchanges up to 8 hours in duration. In addition, we sought to investigate the absorption of HA from the peritoneal cavity, its accumulation in peritoneal tissues, and its metabolism in normal and uremic rats. Methods Experiments were performed on male Wistar rats infused with 30 mL peritoneal dialysis solution (Dianeal, Baxter Healthcare; Castelbar, Ireland) containing 10 mg/dL HA or with Dianeal alone (control). Peritoneal fluid removal (net ultrafiltration), permeability to glucose, creatinine, and total proteins, and tissue and blood levels of HA were determined in separate groups of rats at 1, 2, 4, 6, and 8 hours after intraperitoneal infusion. Hyaluronan appearance and disappearance from plasma were also studied for 24 hours in separate groups of normal and uremic rats. Results Net ultrafiltration was significantly greater (27%) in rats infused with HA at 4, 6, and 8 hours ( p < 0.01) compared to controls. Transperitoneal equilibration of protein was reduced by 27% ( p < 0.001) at 4 hours and by 30% ( p < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clearance of creatinine increased by 27% ( p < 0.01), whereas the clearance of total protein decreased by 27% ( p < 0.005). After 8 hours, 25.7% ± 3.1% of the administered HA was absorbed from the peritoneal cavity, peritoneal tissue HA concentration was increased by 117% ( p < 0.001), and plasma HA levels increased by 435% ( p < 0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal administration in both healthy and uremic rats. Conclusions Hyaluronan added to dialysis fluid is absorbed from the peritoneal cavity and accumulates in peritoneal tissues. Hyaluronan supplementation produces changes in peritoneal permeability, leading to higher net ultrafiltration and peritoneal creatinine clearance, whereas total protein clearance decreases. The HA that is absorbed from the peritoneal cavity appears to be rapidly metabolized in both healthy and uremic rats.


2012 ◽  
Vol 302 (10) ◽  
pp. F1331-F1341 ◽  
Author(s):  
Joanna Stachowska-Pietka ◽  
Jacek Waniewski ◽  
Michael F. Flessner ◽  
Bengt Lindholm

The aim of this study was to simulate clinically observed intraperitoneal kinetics of dialysis fluid volume and solute concentrations during peritoneal dialysis. We were also interested in analyzing relationships between processes in the peritoneal cavity and processes occurring in the peritoneal tissue and microcirculation. A spatially distributed model was formulated for the combined description of volume and solute mass balances in the peritoneal cavity and flows across the interstitium and the capillary wall. Tissue local parameters were assumed dependent on the interstitial hydration and vasodilatation induced by glucose. The model was fitted to the average volume and solute concentration profiles from dwell studies in 40 clinically stable patients on chronic ambulatory peritoneal dialysis using a 3.86% glucose dialysis solution. The model was able to describe the clinical data with high accuracy. An increase in the local interstitial pressure and tissue hydration within the distance of 2.5 mm from the peritoneal surface of the tissue was observed. The penetration of glucose into the tissue and removal of urea, creatinine, and sodium from the tissue were restricted to a layer located within 2 mm from the peritoneal surface. The initial decline of sodium concentration (sodium dip) was observed not only in intraperitoneal fluid but also in the tissue. The distributed model can provide a precise description of the relationship between changes in the peritoneal tissue and intraperitoneal dialysate volume and solute concentration kinetics. Computer simulations suggest that only a thin layer of the tissue within 2–3 mm from the peritoneal surface participates in the exchange of fluid and small solutes between the intraperitoneal dialysate and blood.


2009 ◽  
Vol 13 (6) ◽  
pp. 893-904 ◽  
Author(s):  
N. Bulygina ◽  
N. McIntyre ◽  
H. Wheater

Abstract. Data scarcity and model over-parameterisation, leading to model equifinality and large prediction uncertainty, are common barriers to effective hydrological modelling. The problem can be alleviated by constraining the prior parameter space using parameter regionalisation. A common basis for regionalisation in the UK is the HOST database which provides estimates of hydrological indices for different soil classifications. In our study, Base Flow Index is estimated from the HOST database and the power of this index for constraining the parameter space is explored. The method is applied to a highly discretised distributed model of a 12.5 km2 upland catchment in Wales. To assess probabilistic predictions against flow observations, a probabilistic version of the Nash-Sutcliffe efficiency is derived. For six flow gauges with reliable data, this efficiency ranged between 0.70 and 0.81, and inspection of the results shows that the model explains the data well. Knowledge of how Base Flow Index and interception losses may change under future land use management interventions was then used to further condition the model. Two interventions are considered: afforestation of grazed areas, and soil degradation associated with increased grazing intensity. Afforestation leads to median reduction in modelled runoff volume of 24% over the simulated 3 month period; and a median peak flow reduction ranging from 12 to 15% over the six gauges for the largest simulated event. Uncertainty in all results is low compared to prior uncertainty and it is concluded that using Base Flow Index estimated from HOST is a simple and potentially powerful method of conditioning the parameter space under current and future land management.


1994 ◽  
Vol 14 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Ger C.M. Koomen ◽  
Michiel G.H. Betjes ◽  
Oésirée Zemel ◽  
Raymond T. Krediet ◽  
Frans J. Hoek

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10 23), dialysate CA 125 18 U/mL (range 5.2 76), dialysate/plasma ratio 1. 9 (range 0.61 -5.4), and number of mesothelial cells 400/mL (range 10 5000). Peritoneal concentrations of mesothelial cellsand CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/1 06 cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.


2014 ◽  
Vol 307 (7) ◽  
pp. F777-F782 ◽  
Author(s):  
Kunal Chaudhary ◽  
Harold Moore ◽  
Ashish Tandon ◽  
Suneel Gupta ◽  
Ramesh Khanna ◽  
...  

Peritoneal dialysis (PD) is a life-sustaining therapy for end-stage renal disease (ESRD), used by 10–15% of the dialysis population worldwide. Peritoneal fibrosis (PF) is a known complication of long-term PD and frequently follows episodes of peritonitis, rendering the peritoneal membrane inadequate for dialysis. Transforming growth factor (TGF)-β is an inducer of fibrosis in several tissues and organs, and its overexpression has been correlated with PF. Animal models of peritonitis have shown an increase in expression of TGF-β in the peritoneal tissue. Decorin, a proteoglycan and component of the extracellular matrix, inactivates TGF-β, consequently reducing fibrosis in many tissues. Recently, gold nanoparticles (GNP) have been used for drug delivery in a variety of settings. In the present study, we tested the possibility that GNP-delivered decorin gene therapy ameliorates zymosan-mediated PF. We created a PF model using zymosan-induced peritonitis. Rats were treated with no decorin, GNP-decorin, or adeno-associated virus-decorin (AAV-decorin) and compared with controls. Tissue samples were then stained for Masson's trichrome, enface silver, and hematoxylin and eosin, and immunohistochemistry was carried out with antibodies to TGF-β1, α-smooth muscle actin (α-SMA), and VEGF. Animals which were treated with GNP-decorin and AAV-decorin gene therapy had significant reductions in PF compared with untreated animals. Compared with untreated animals, the treated animals had better preserved peritoneal mesothelial cell size, a significant decrease in peritoneal thickness, and decreased α-SMA. Quantitative PCR measurements showed a significant decrease in the peritoneal tissue levels of α-SMA, TGF-β, and VEGF in treated vs. untreated animals. This study shows that both GNP-delivered and AAV-mediated decorin gene therapies significantly decrease PF in vivo in a rodent model. This approach has important clinical translational potential in providing a therapeutic strategy to prevent PF in PD patients.


2016 ◽  
Vol 48 (4) ◽  
pp. 1118-1130 ◽  
Author(s):  
I. G. Pechlivanidis ◽  
N. McIntyre ◽  
H. S. Wheater

The significance of spatial variability of rainfall on runoff is explored as a function of catchment scale and type, and antecedent conditions via the continuous time, semi-distributed probability distributed model (PDM) hydrological model applied to the Upper Lee catchment, UK. The impact of catchment scale and type is assessed using 11 nested catchments, and further assessed by artificially changing the catchment characteristics and translating these to model parameters (MPs) with uncertainty using model regionalisation. Dry and wet antecedent conditions are represented by ‘warming up’ the model under different rainfall time series. Synthetic rainfall events are introduced to directly relate the change in simulated runoff to the spatial variability of rainfall. Results show that runoff volume and peak are more sensitive to the spatial rainfall for more impermeable catchments; however, this sensitivity is significantly undermined under wet antecedent conditions. Although there is indication that the impact of spatial rainfall on runoff varies as a function of catchment scale, the variability of antecedent conditions between the synthetic catchments seems to mask this significance. Parameter uncertainty analysis highlights the importance of accurately representing the spatial variability of the catchment properties and their translation to MPs when investigating the effects of spatial properties of rainfall on runoff.


2013 ◽  
Vol 16 (4) ◽  
pp. 758-771 ◽  
Author(s):  
Alireza Safari ◽  
F. De Smedt

In the second phase of the Distributed Model Intercomparison Project (DMIP2), the WetSpa model is applied to simulate flows at basin and subbasin scales. Parent basins and their nested subbasins are modeled as gaged and ungaged basins, respectively. Available observations in the subbasins were only used to validate the model predictions. Gaged basins simulation results show that the predictions and observations are in good agreement. However, major peaks are underestimated, as is often the case in runoff modeling. Underestimation of high flows and in particular peak flows indicates that the prediction of actual runoff coefficients in the current WetSpa model needs to be improved. Also, sensitivity analysis of the model parameters reveals that the baseflow recession coefficient is the most sensitive parameter and care should be taken when modeling ungaged basins. Hence, by estimating this parameter for each subbasin separately, the model performance for the subbasins can be improved. To do this, a Boussinesq groundwater flow equation is used to improve the prediction of baseflow recession coefficients in the subbasins. Comparison between the original and the modified WetSpa models shows that the modified model yields relatively higher performances for the subbasins, creating a more accurate model for predicting ungaged subbasins.


2009 ◽  
Vol 6 (2) ◽  
pp. 1907-1938 ◽  
Author(s):  
N. Bulygina ◽  
N. McIntyre ◽  
H. Wheater

Abstract. Data scarcity and model over-parameterisation, leading to model equifinality and large prediction uncertainty, are common barriers to effective hydrological modelling. The problem can be alleviated by constraining the prior parameter space using parameter regionalization. A common basis for regionalization in the UK is the HOST database which provides estimates of hydrological indices for different soil classifications. In our study, Base Flow Index is estimated from the HOST database and the power of this index for constraining the parameter space is explored. The method is applied to a highly discretized distributed model of a 12.5 km2 upland catchment in Wales. To assess probabilistic predictions against flow observations, a probabilistic version of the Nash-Sutcliffe efficiency is derived. For six flow gauges with reliable data, this efficiency ranged between 0.70 and 0.81, and inspection of the results shows that the model explains the data well. Knowledge of how Base Flow Index and interception losses may change under future land use management interventions was then used to further condition the model. Two interventions are considered: afforestation of grazed areas, and soil degradation associated with increased grazing intensity. Afforestation leads to median reduction in modelled runoff volume of 24% over the simulated 3 month period; and a median peak flow reduction ranging from 12–15% over the six gauges for the largest simulated event. Uncertainty in all results is suprisingly low and it is concluded that using Base Flow Index estimated from HOST is a simple and potentially powerful method of conditioning the parameter space under current and future land management.


1994 ◽  
Vol 14 (2_suppl) ◽  
pp. 33-38 ◽  
Author(s):  
Carola W.H. De Fijter ◽  
P. Liem Oe ◽  
Ab J.M. Donker ◽  
Jan Verhoef ◽  
Henri A. Verbrugh

The success of continuous ambulatory peritoneal dialysis (CAPD) lies in preserving the peritoneum as a dialyzing membrane. Repeated infusions of nonphysiological fluids are potentially detrimental to the peritoneal membrane and its host defense. The disadvantages of the currently used peritoneal dialysis fluids (PDPs) containing glucose as an osmotic agent (short ultrafiltration profile, systemic carbohydrate load, nonphysiological composition) have stimulated the search for alternative, less toxic osmotic agents devoid of metabolic side effects and capable of sustaining ultrafiltration. PDFs containing glycerol, amino acids, or glucose polymers have had clinical usage in CAPD patients and were reviewed with regard to their compatibility with cells present in the peritoneal cavity. Overall, glycerol appears to have no advantage over glucose-based PDFs, although it is less inhibitory for mesothelial cell proliferationin vitro. The optimum formulation of amino acid-based PDFs has not yet been established; its lactate and specific amino acid content may limit their biocompatibility. The virtually iso-osmolar glucose polymer (icodextrin)-containing PDFs were associated with improved biocompatibility compared to glucose monomer-based solutions. Modifications of PDFs towards a more balanced salt solution with a neutral pH may further increase their compatibility with peritoneal host defense as well as with the integrity of the mesothelial membrane. Such improvement in PDF biocompatibility may result in clinical benefit, that is, enhanced resistance to infection and preservation of peritoneal ultrafiltration capacity.


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