Concomitant bidirectional transport during peritoneal dialysis can be explained by a structured interstitium

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.

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Distributed model of peritoneal fluid absorption

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01320.2005 ◽

2006 ◽

Vol 291 (4) ◽

pp. H1862-H1874 ◽

Cited By ~ 32

Author(s):

J. Stachowska-Pietka ◽

J. Waniewski ◽

M. F. Flessner ◽

B. Lindholm

Keyword(s):

Peritoneal Dialysis ◽

Peritoneal Cavity ◽

Strong Dependence ◽

Surrounding Tissue ◽

Distributed Model ◽

Blood Capillary ◽

Fluid Absorption ◽

Blood Capillaries ◽

Intraperitoneal Pressure ◽

Tissue Hydration

The process of water reabsorption from the peritoneal cavity into the surrounding tissue substantially decreases the net ultrafiltration in patients on peritoneal dialysis. The goal of this study was to propose a mathematical model based on data from clinical studies and animal experiments to describe the changes in absorption rate, interstitial hydrostatic pressure, and tissue hydration caused by increased intraperitoneal pressure after the initiation of peritoneal dialysis. The model describes water transport through a deformable, porous tissue after infusion of isotonic solution into the peritoneal cavity. Blood capillary and lymphatic vessels are assumed to be uniformly distributed within the tissue. Starling's law is applied for a description of fluid transport through the capillary wall, and the transport within the interstitium is modeled by Darcy's law. Transport parameters such as interstitial fluid volume ratio, tissue hydraulic conductance, and lymphatic absorption in the tissue are dependent on local interstitial pressure. Numerical simulations show the strong dependence of fluid absorption and tissue hydration on the values of intraperitoneal pressure. Our results predict that in the steady state only ∼20–40% of the fluid that flows into the tissue from the peritoneal cavity is absorbed by the lymphatics situated in the tissue, whereas the larger (60–80%) part of the fluid is absorbed by the blood capillaries.

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Computer simulations of osmotic ultrafiltration and small-solute transport in peritoneal dialysis: a spatially distributed approach

AJP Renal Physiology ◽

10.1152/ajprenal.00301.2011 ◽

2012 ◽

Vol 302 (10) ◽

pp. F1331-F1341 ◽

Cited By ~ 23

Author(s):

Joanna Stachowska-Pietka ◽

Jacek Waniewski ◽

Michael F. Flessner ◽

Bengt Lindholm

Keyword(s):

Peritoneal Dialysis ◽

Computer Simulations ◽

Peritoneal Cavity ◽

Sodium Concentration ◽

Solute Concentration ◽

Distributed Model ◽

Peritoneal Surface ◽

Distributed Approach ◽

Peritoneal Tissue ◽

Spatially Distributed

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.

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Clearance of Tracer Albumin from Peritoneal Cavity to Plasma at Low Intraperitoneal Volumes and Hydrostatic Pressures

Peritoneal Dialysis International ◽

10.1177/089686089801800507 ◽

1998 ◽

Vol 18 (5) ◽

pp. 497-504 ◽

Cited By ~ 11

Author(s):

Qing Zhu ◽

Ola Carlsson ◽

Bengt Rippe

Keyword(s):

Peritoneal Dialysis ◽

Peritoneal Cavity ◽

Fluid Volume ◽

Free Fluid ◽

Annual Conference ◽

Lymphatic Absorption ◽

Tissue Samples ◽

Essentially Normal ◽

Peritoneal Tissue ◽

Tracer Distribution

Objective To assess the clearance of radiolabeled tracer albumin (RISA) from peritoneal cavity to plasma (CI → P) in rats under essentially “normal” conditions, that is, when intraperitoneal hydrostatic pressure (IPP) is subatmospheric and the intraperitoneal (IP) “free” fluid volume (IPV) is low. Methods A volume of 0.3 mL of RISA was injected IP into anesthetized Wistar rats (wt = 300 g) when the IPV was approximately 2 mL (normal) or the IPV was approximately 10 mL, and IPP was either -1.8 mmHg (normal) or +1.5 mmHg (produced by an external cuff). Plasma samples (25 μL) were obtained repeatedly during the dwell, which lasted 30 300 min, after which the peritoneal cavity was opened to recover the IPV and residuallP RISA activity. The CI → P was assessed as the mass transfer of RISA into plasma, occurring per unit time,-divided by the calculated mean IP RISA concentration (CD). The interstitial RISA space was measured as the mass of RISA accumulated, per unit tissue weight, in peritoneal tissue samples divided by the CD. Results A markedly lower CI → P (2.47 ± 0.67 μL/min), as well as total RISA clearance out of the peritoneal cavity (CI), was found under “normal” conditions (an IPV of approximately 2 mL and an IPP of approximately -1.8 mmHg) compared to the situation during peritoneal dialysis (an IPV of approximately 20 mL and an IPP of +1 mmHg). Furthermore, the interstitial RISA space increased linearly over time even at negative IPPs and at an unchanging peritoneal interstitial fluid volume. At a low (normal) IPV the CI → P did not increase significantly with elevating IPP, and increased only marginally when tracer distribution was improved by artificial vibration of the rats. However the CI → P increased when larger volumes were infused to increase the totallPV. Conclusions It is concluded that the CI → P and CI at low IPPs and IPVs are not as high as during peritoneal dialysis. Increases in CI → P were, however, coupled to increases in IPV. This highlights the importance of the IPV per se and of a sufficient IP tracer distribution for direct lymphatic absorption to be efficient. This study was presented in part at the XVIth Annual Conference on Peritoneal Dialysis, Denver, Colorado, U.S.A., 1997 (33).

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Water Removal Cycle-By-Cycle During Automated Peritoneal Dialysis: Assessment by Remote Patient Monitoring and Modelling of Peritoneal Tissue Hydration

10.21203/rs.3.rs-429738/v1 ◽

2021 ◽

Author(s):

Joanna Stachowska-Pietka ◽

Beata Naumnik ◽

Ewa Suchowierska ◽

Rafael Gomez ◽

Jacek Waniewski ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Patient Monitoring ◽

Water Removal ◽

Remote Patient Monitoring ◽

Automated Peritoneal Dialysis ◽

Fluid Exchange ◽

Tissue Hydration ◽

Peritoneal Tissue ◽

Remote Patient ◽

The Impact

Abstract Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile-third quartile]) during first and second vs. consecutive exchanges in APDDD (-61 [-148—27], 170 [78—228] vs. 213 [126—275] mL; p<0.001), but not in APDWD (81 [-8—176], 81 [-4—192] and 115 [4—219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.

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Water removal during automated peritoneal dialysis assessed by remote patient monitoring and modelling of peritoneal tissue hydration

Scientific Reports ◽

10.1038/s41598-021-95001-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joanna Stachowska-Pietka ◽

Beata Naumnik ◽

Ewa Suchowierska ◽

Rafael Gomez ◽

Jacek Waniewski ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Patient Monitoring ◽

Water Removal ◽

Remote Patient Monitoring ◽

Automated Peritoneal Dialysis ◽

Fluid Exchange ◽

Tissue Hydration ◽

Peritoneal Tissue ◽

Remote Patient ◽

The Impact

AbstractWater removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APDDD (−61 [−148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p < 0.001), but not in APDWD (81 [−8, 176], 81 [−4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.

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Intraperitoneal Hyaluronan Administration in Conscious Rats: Absorption, Metabolism, and Effects on Peritoneal Fluid Dynamics

Peritoneal Dialysis International ◽

10.1177/089686080102100204 ◽

2001 ◽

Vol 21 (2) ◽

pp. 130-137 ◽

Cited By ~ 4

Author(s):

Andrzej Breborowicz ◽

Alicja Polubinska ◽

Krzysztof Pawlaczyk ◽

Malgorzata Kuzlan–Pawlaczyk ◽

James Moberly ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Peritoneal Cavity ◽

Total Protein ◽

Peritoneal Fluid ◽

Intraperitoneal Administration ◽

Blood Levels ◽

Interstitial Tissue ◽

Conscious Rats ◽

Peritoneal Tissue ◽

Peritoneal Permeability

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.

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A distributed model of fluid and mass transfer in peritoneal dialysis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.4.r958 ◽

1990 ◽

Vol 258 (4) ◽

pp. R958-R972 ◽

Cited By ~ 5

Author(s):

E. L. Seames ◽

J. W. Moncrief ◽

R. P. Popovich

Keyword(s):

Peritoneal Cavity ◽

Mesothelial Cell ◽

Distributed Model ◽

Model Parameters ◽

Interstitial Tissue ◽

Peritoneal Tissue ◽

Capillary Membrane ◽

Dual Pathway ◽

Tissue Space ◽

Fluid Transfer

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.

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Role of the liver in small-solute transport during peritoneal dialysis.

Journal of the American Society of Nephrology ◽

10.1681/asn.v51116 ◽

1994 ◽

Vol 5 (1) ◽

pp. 116-120

Author(s):

M F Flessner ◽

R L Dedrick

Keyword(s):

Mass Transfer ◽

Peritoneal Dialysis ◽

Surface Area ◽

Peritoneal Cavity ◽

Distributed Model ◽

Blood Capillaries ◽

Peritoneal Surface ◽

Small Solute ◽

Good Agreement

Peritoneal dialysis (PD) is dependent on the transport of water and solutes from the blood capillaries within the tissues that surround the peritoneal cavity. Because of their large blood supply and surface area, the viscera have been considered the most important tissues for PD transport. In animals, however, removal of the gastrointestinal tract decreases PD small-solute mass transfer by only 10 to 27%. To investigate the theoretical basis for these observations, a distributed model of peritoneal transport was extended to take into account the transport characteristics of four tissue groups that surround the cavity: the liver, the hollow viscera, the abdominal wall, and the diaphragm. The mass transfer-area coefficient (MTAC) of sucrose for each tissue was calculated from the following: MTAC = ([D(pa)]0.5)A, where D is the effective solute interstitial diffusivity, pa is the solute transcapillary permeability-area per unit tissue volume, and A is the apparent peritoneal surface area of the tissue. Our results for the adult human predict that the MTAC for the liver is comparable to that of all of the other viscera and makes up 43% of the total MTAC for the peritoneal cavity. The predicted MTAC is 4 cm3/min (plasma) or 6 cm3/min (blood), in good agreement with published values. It is concluded that the liver is responsible for a major portion of the small-solute MTAC. This also explains the earlier observations in eviscerated animals whose PD transport was likely preserved by intact livers.

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