Effect of intraperitoneal pressures on tissue water of the abdominal muscle.

A major factor that affects solute and water transport through tissue is the state of tissue hydration. The amount of interstitial water directly affects the transport coefficients for both diffusion and convection. To investigate the effect of simultaneous exposure of tissue to hydrostatic and osmotic pressures on the state of tissue hydration and the pattern of distribution of tissue water, we dialyzed rats with isotonic (290 mosmol/kg) or hypertonic (510 mosmol/kg) solution at intraperitoneal pressures (P(ip)) between 0 and 6 mmHg, and we infused isotopic markers intravenously and determined their equilibrium distribution volumes (V(D)) in the anterior abdominal muscle (AAM) by quantitative autoradiography. Total tissue water volume (theta(TW)) was determined from dry-to-wet weight ratios. theta(urea), the V(D) of [(14)C]urea, equals the sum of the extracellular water volume (theta(EC), V(D) of [(14)C]mannitol) and intracellular water volume (theta(IC) = theta(urea) - theta(EC)). If theta(if) = interstitial water volume and theta(IV) = vascular water volume (V(D) of (131)I-labeled IgG), then theta(EC) = theta(if) + theta(IV). AAM hydrostatic pressure profiles were measured by a micropipette/servo-null system and demonstrated that elevation of P(ip) above 3 mmHg significantly (P < 0.05) increases mean tissue pressure (P(T)) to the same level regardless of intraperitoneal osmolality. The increase in P(T) resulted in a nonlinear tissue expansion primarily in the interstitium regardless of osmolality. From 0 to 6 mmHg, theta(if) (in ml/g dry tissue) increased from 0.59 +/- 0.02 to 1.7 +/- 0.05 and to 1.5 +/- 0.05 after isotonic and hypertonic dialysis, respectively, whereas theta(IC) increased from 2.8 +/- 0.08 to 3.0 +/- 0.1 after isotonic dialysis and decreased to 2.6 +/- 0.1 after hypertonic dialysis. After dialysis at 6 mmHg with isotonic or hypertonic solutions, theta(IV) increased from 0.034 +/- 0.001 to 0. 049 +/- 0.001 and 0.042 +/- 0.002, respectively. theta(urea) during hypertonic dialysis at P(ip) between 0 and 6 mmHg increased in a nonlinear fashion (F = 26.3, P < 0.001), whereas theta(IC) invariably decreased (F = 11.1, P < 0.001) and theta(if) doubled from its control value at low P(ip). In conclusion, elevation of intraperitoneal hydrostatic pressure causes tissue expansion, primarily in interstitium, irrespective of osmolality of the bathing solution. Tissue hydrostatic pressure is therefore the primary determinant of tissue properties with respect to hydration, which in turn affects diffusive and convective transport.

Hydrostatic and osmotic pressures modulate partitioning of tissue water in abdominal muscle during dialysis.

OBJECTIVES: To investigate the effect of simultaneous exposure of anterior abdominal muscle (AAM) to changes in intraperitoneal hydrostatic pressure (Pip) and to osmolality of peritoneal fluid on total tissue water (TTW) and on the pattern of distribution of TTW in the AAM. DESIGN: A pilot study of single 60-min dwells in anesthetized Sprague-Dawley (SD) rats, dialyzed with either isotonic (290 mOsm/kg) or hypertonic (510 mOsm/kg) dialysis solutions at nominal Pip of 0 mmHg or 6 mmHg. MEASUREMENTS: TTW (from dry-weight-to-wet-weight ratios) can be divided into the extracellular volume [theta(ec), from quantitative autoradiography (QAR) with 14C-mannitol] and intracellular volume (theta(ic) = TTW - theta(ec)). Theta(ec) = theta(if) + theta(iv), where theta(if) = interstitial volume and theta(iv) = vascular volume [from QAR with 131I-immunoglobulin G (IgG)]. All measured parameters are standardized to tissue dry weight and expressed as mean +/- standard error. RESULTS: Regardless of the osmolality of the dialysis solution, elevation of Pip to 6 mmHg results in tissue expansion, primarily in theta(if), which is doubled to 1.71+/-0.11 mL/g dry weight and 1.60+/-0.17 mL/g dry weight with isotonic and hypertonic dialysis, respectively, as compared to controls (0.64+/-0.04 mL/g dry weight). The local theta(iv) was not affected by Pip or osmolality of the bathing solution. The overall theta(iv) is 0.046+/-0.006 mL/g dry weight. A two-way analysis of variance (ANOVA) to access the effect of osmolality and Pip on theta(ic) demonstrated no significant change in theta(ic) (F = 1.2, p > 0.1) as calculated for controls (3.13+/-0.19 mL/g dry weight), after isotonic dialysis (3.13+/-0.20 mL/g dry weight), or after hypertonic dialysis (2.77+/-0.30 mL/g dry weight). CONCLUSION: Elevation of Pip to 6 mmHg significantly increased TTW and expanded the tissue. Tissue expansion is primarily in interstitium (theta(if)), which is doubled from control value regardless of dialysis fluid osmolality.

In vivo effects of hydrostatic pressure on interstitium of abdominal wall muscle.

Fluid loss from the peritoneal cavity to surrounding tissue varies directly with intraperitoneal hydrostatic pressure (Pip). According to Darcy's law [Q = -KA(dPif/dx)], fluid flux (Q) across a cross-sectional area (A) of tissue will increase with an increase in either hydraulic conductivity (K) or the interstitial fluid hydrostatic pressure gradient (dPif/dx, where x is distance). Previously, we demonstrated that in the anterior abdominal muscle (AAM) of rats, dPif/dx increases by only 40%, whereas K rises fivefold between Pip of 1.5 and 8 mmHg. Because K is a function of interstitial volume (thetaif), we hypothesized that perturbations of Pip would change Pif and expand the interstitium, increasing thetaif. To test this hypothesis, we used dual-label quantitative autoradiography (QAR) to measure extracellular fluid volume (thetaec) and intravascular volume (thetaiv) in the AAM of rats within the Pip range from -2.8 to +8 mmHg. thetaif was obtained by subtraction (thetaec - thetaiv). dPif/dx was measured with a micropipette and a servo-null system. Local thetaiv did not vary with Pip and averaged 0.010 +/- 0.002 ml/g, and thetaif averaged 0. 19 +/- 0.01 ml/g at Pif 0.001) in the SC. We conclude that the mechanisms responsible for the increase in K with Pip include expansion of the interstitium, dilution of interstitial macromolecules, and washout from the AAM to SC of interstitial macromolecules responsible for resistance to fluid flow.

Liver is not essential for solute transport during peritoneal dialysis.

Based on theoretical calculations on solute exchange capacities of various peritoneal tissues, the liver has been predicted to account for up to 43% of the permeability-surface area product (PS) of the entire peritoneal "membrane" for a small solute (sucrose) during peritoneal dialysis (PD). In these calculations, the abdominal wall and the diaphragm were found to contribute only approximately 10 to 15% of the total PS. However, evisceration has in previous studies been shown to affect the PS characteristics during PD only marginally (10 to 30%). In such evisceration experiments the liver was usually not removed, and therefore it has been suggested that an intact liver might have significantly contributed to the solute exchange under these premises. We assessed the peritoneal PS of 51Cr-EDTA (constantly infused intravenously) and the plasma-to-peritoneal clearance (ClB-->P) of 125I-human serum albumin (RISA) (given as an i.v. bolus) in Wistar rats during acute PD. In one group of rats the liver surface was sealed off using Histoacrylate glue (N = 6) and in another group a 90% hepatectomy was performed, the remaining portion of the liver, usually the right lower lobe, being sealed off by glue (N = 6). A third group was sham operated to serve as control (N = 12). The PS for 51Cr-EDTA was 0.32 +/- 0.03(+/- SE) ml. min-1 (N = 12) during control, 0.32 +/- 0.04 ml.min-1 after "sealing" of the liver surface (N = 6, P > 0.1) and 0.40 +/- 0.03 after hepatectomy (N = 6, P > 0.1), that is, remained unchanged after experimental intervention. The CIB-->P of RISA during control was 5.88 +/- 1.0 microliter.min-1 (N = 10), and was not altered after hepatectomy, 6.17 +/- 0.48 microliters.min-1 (N = 5, P > 0.1), but slightly increased after liver surface sealing (9.69 +/- 1.09 microliters.min-1, N = 5, P < 0.05). In conclusion, the present experiments indicate that the liver does not play an essential role in the overall solute exchange between the plasma and the peritoneal cavity (PC) during PD.

Transport of tracer albumin from peritoneum to plasma: role of diaphragmatic, visceral, and parietal lymphatics.

Using a technique to acutely seal off various parts of the peritoneal membrane surface, with or without evisceration, we investigated the role of diaphragmatic, visceral, and parietal peritoneal lymphatic pathways in the drainage of 125I-labeled albumin (RISA) from the peritoneal cavity to the plasma during acute peritoneal dialysis in artificially ventilated rats. The total RISA clearance out of the peritoneal cavity (Cl) as well as the portion of this Cl reaching the plasma per unit time (Cl--> P) were assessed. Under non-steady-state conditions, the Cl was fivefold higher than the Cl--> P. Evisceration caused a 25-30% reduction in both Cl--> P and Cl. Sealing of the diaphragm, however, reduced the Cl--> P by 55% without affecting the Cl. A further reduction in the Cl--> P was obtained by combining sealing of the diaphragm with evisceration, which again markedly reduced the Cl. However, the greatest reduction in the Cl was obtained when the peritoneal surfaces of the anterior abdominal wall were sealed off in eviscerated rats. The discrepancy between the Cl and the Cl--> P can be explained by the local entrance of fluid and macromolecules into periabdominal tissues, where fluid is rapidly absorbed through the capillary walls via the Starling forces, while macromolecules are accumulating due to their very slow uptake by tissue lymphatics under non-steady-state conditions. Of the portion of the total Cl that rapidly entered the plasma, conceivably by lymphatic absorption, 55% could be ascribed to diaphragmatic lymphatics 30% to visceral lymphatics, and only some 10-15% to parietal lymphatics.

Intraperitoneal fluid volume changes during peritoneal dialysis in the rat: indicator dilution vs. volumetric measurements.

In order to validate the single injection RISA (125I human serum albumin) indicator diluation technique for assessing the alterations in intraperitoneal (i.p.) dialysate volume (IPV) which occur vs. time [V(t)] during peritoneal dialysis (PD), the RISA dilution technique was compared to V(t) determinations using a direct volume recovery method in Wistar rats. Sixteen milliliters of either 1.36 or 3.86% Dianeal or 0.9% NaCl were used as dialysis fluids in exchanges lasting between 1 and 360 min. Approximately 4% (4.41 +/- 0.59 (SE; n = 8) for 1.36% Dianeal and 4.07 +/- 0.72 (n = 4) for 3.86% Dianeal) of the RISA dose given intraperitoneally was lost from the dialysate during the first 1(-1.5) min after instillation, conceivably due to rapid tracer adsorption to peritoneal surfaces. Following the initial instant tracer loss and RISA dilution due to a residual volume (3.07 +/- 0.18 ml; n = 12), RISA disappeared at a fractional rate (FDR) of 2.10 +/- 0.14 x 10(-3) min-1 and 1.67 +/- 0.09 x 10(-3) min-1, during the first 30 min for 1.36 and 3.86% Dianeal, respectively. The overall FDR was 1.33 +/- 0.10 x 10(-3) and 0.707 +/- 0.082 x 10(-3) min-1 for 1.36% Dianeal (0-150 min) and 3.86% Dianeal (0-360 min), respectively, while the overall (0-150 min) FDR for the NaCl exchanges was 1.40 +/- 0.21 x 10(-3) min-1. These values correspond to RISA clearances out of the peritoneal cavity (KE) of 29.2 +/- 1.8, 22.1 +/- 1.6, and 25.7 +/- 2.4 microliter x min-1 for 1.36 and 3.86% Dianeal and 0.9% NaCl, respectively. The KE value for 3.86% Dianeal was significantly (p < 0.05) lower than for the two dialysates with lower osmolality. The slightly enhanced FDR of RISA during the first 30 min was partly due to the presence of nonprotein-bound free iodine in the RISA preparation used, and also to an enhanced disappearance of albumin during the first portion of the dwell. V(t) data from individual experiments using the RISA dilution technique (RISA curves) were analyzed by computer-aided nonlinear least-squares regression analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Peritoneal fluid and tracer albumin kinetics in the rat. Effects of increases in intraperitoneal hydrostatic pressure.

OBJECTIVES: To study the peritoneal fluid loss rate, the clearance (CI) of radioactive tracer albumin (RISA) eliminated from the peritoneal cavity (PC), as well as the peritoneal-to-plasma RISA clearance (CI-->P) during acute peritoneal dialysis (PD) at large elevations in intraperitoneal hydrostatic pressure (IPP). DESIGN: Experimental study in anesthetized Wistar rats. METHODS: The intraperitoneal volume (IPV) was assessed using RISA dilution, correcting for the RISA CI from the PC. Volume recovery at termination of the dwells was obtained using graduated cylinders and preweighed gauze tissues. Measurements of CI and CI-->P were obtained by repeated micro-sampling of dialysate and plasma, respectively. The IPP was continuously measured, and could be varied by external concentric abdominal compression using an inflatable cuff. On termination of the experiments, samples from tissues lining the PC were analyzed with respect to their content of RISA and edema, the latter being assessed from wet/dry weight ratios. RESULTS: At 2 mm Hg of IPP (control) the RISA CI was 27.1 +/- 2.0 (+/- SE) microL.min-1, whereas CI-->P was only 8.07 +/- 0.67 microL.min-1, at a total fluid loss rate of 10.1 +/- 5.4 microL.min-1 for 1.36% Dianeal. At an IPP of 14 mm Hg, the CI increased to 55.3 +/- 4.1 microL.min-1 and the peritoneal fluid absorption rate was 34.4 +/- 5.6 microL.min-1, whereas CI-->P was just moderately increased as compared to control (11.2 +/- 1.4 microL.min-1). Furthermore, a pleural effusion of 1.16 +/- 0.08 mL was detectable at elevated IPPs. The degree of edema formation in the anterior abdominal muscles (AAM) and the diaphragm (DIA) was largely insignificant during 150 min at 2 mm Hg of IPP, but increased markedly at 14 mm Hg, as did the RISA uptake to the AAM and DIA. The discrepancy between CI and CI-->P was largely accounted for by tracer entrance into tissues lining the peritoneal cavity, mainly the AAM. CONCLUSIONS: At a nearly unchanging capillary Starling equilibrium, the losses of fluid and of RISA from the PC were markedly elevated at increased IPPs. However, the RISA clearance to the plasma appeared to be only moderately altered at elevated IPP and represented only a minor fraction of the RISA clearance out of the PC. Tissues lining the PC apparently act as a variable 'sink' for intraperitoneal proteins and fluid during peritoneal dialysis (PD).

Osmotic barrier properties of the rat peritoneal membrane.

In this study the osmotic barrier characteristics of the rat peritoneal membrane were investigated. Fluid movements between the peritoneal cavity and the blood were measured following instillation of isotonic saline (control) and hypertonic solutions of NaCl, glucose, sucrose, raffinose and myoglobin (test solutions). Moreover, 5 and 8% albumin in NaCl were investigated. Osmotic transients were assessed using a simple volume recovery technique. Peritoneal osmotic conductances (i.e. products of peritoneal hydraulic conductances [LpS] and solute reflection coefficients [sigma]) were calculated from the differences in the rates of peritoneal fluid loss and in osmotic pressures between test solutions and the isotonic saline control solution. The osmotic conductance to glucose was estimated to be 1.63 microliters min-1 mmHg-1 m-2 and that for albumin to be 59.6 microliters min-1 mmHg-1 m-2. Assuming an albumin sigma of 0.9, the sigma of glucose was estimated to be 0.025, in accordance with previous measurements for the cat peritoneal membrane. The osmotic conductances assessed here were compatible with an 'overall' peritoneal equivalent small pore radius of 47-48 A, but could also be fitted to a three-pore model of peritoneal permselectivity, including a transcellular (ultra-small pore) pathway and a large pore pathway. The great discrepancy between peritoneal sigma for small solutes and that for albumin obtained in this study indicates that small solute reflection coefficients are close to zero while that for albumin is not far from unity. Furthermore, the peritoneal hydraulic conductance (ultrafiltration coefficient) is large enough to allow for a substantial absorption of fluid directly into the plasma when the crystalloid osmotic pressures in blood and peritoneal dialysate are in equilibrium.

Lymphatic versus nonlymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties.

In this article we discuss the role of capillary fluid absorption via Starling mechanisms (the transcapillary hydrostatic pressure gradient opposed by the colloid osmotic pressure gradient as multiplied by the capillary UF coefficient) vs. lymphatic fluid absorption as determinants of the total fluid loss from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). We also mention that, under nonsteady state conditions, there is in addition some net absorption of fluid into the interstitium of tissues surrounding the peritoneal cavity. Support for the contention that nonlymphatic fluid absorption directly into the capillaries is the major mode of fluid transport from the peritoneal cavity to the blood is given by measurements of the peritoneal-to-blood clearance of tracer albumin (or other proteins). Such measurements yield clearance values of the order of 0.2-0.3 ml/min in CAPD. This represents only about 20% of the total peritoneal fluid loss rate (1.2-1.3 ml/min) in ordinary CAPD dwells. Indirect support for a relatively low lymph flow is also derived from capillary physiology. Like continuous capillary walls, the peritoneal membrane shows a bimodal selectivity towards molecules of graded molecular size. Thus, small solute transport can be described as occurring by diffusion through numerous 'small' (approximately 50 A radius) pores, whereas large solute transport is consistent with blood-peritoneal convection through smaller numbers of 'large' (radius approximately 250 A) pores. Furthermore, peritoneal sieving data are compatible with the notion that large crystalloid osmotic pressure gradients cause fluid flow through a water-exclusive ('ultra-small' pore) pathway. A three-pore model of peritoneal selectivity can explain why small solute sieving coefficients are only 0.5-0.6, even though small solute reflection coefficients are close to zero. Another important implication of the three-pore concept is that the peritoneal UF-coefficient is much higher than previously thought, emphasizing the role of capillary absorption in the fluid loss from the peritoneal cavity in CAPD. It is concluded that fluid loss from the peritoneal cavity is dominated by capillary fluid absorption. Hence, lymphatic absorption accounts for just a small fraction of the peritoneal-to-blood absorption of fluid in peritoneal dialysis.