Fluid loss from the peritoneal cavity to surrounding tissue varies directly with intraperitoneal hydrostatic pressure (P_ip). According to Darcy's law [Q = KA(dP_if/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 (dP_if/dx, where x is distance). Previously, we demonstrated that in the anterior abdominal muscle (AAM) of rats, dP_if/dx increases by only 40%, whereas K rises fivefold between P_ip of 1.5 and 8 mmHg. Because K is a function of interstitial volume (_if), we hypothesized that perturbations of P_ip would change P_if and expand the interstitium, increasing _if. To test this hypothesis, we used dual-label quantitative autoradiography (QAR) to measure extracellular fluid volume (_ec) and intravascular volume (_iv) in the AAM of rats within the P_ip range from 2.8 to +8 mmHg. _if was obtained by subtraction (_ec  iv). dP_if/dx was measured with a micropipette and a servo-null system. Local _iv did not vary with P_ip and averaged 0.010 ± 0.002 ml/g, and _if averaged 0.19 ± 0.01 ml/g at P_if 1.2 mmHg. However, _if doubled between P_if of 1.2 and 4.2 mmHg (from 0.20 ± 0.00 to 0.39 ± 0.01 ml/g, respectively) but did not increase with further increases in P_if. This nonlinear pressure-volume relationship does not explain the fivefold increase in K with P_ip. Because the interstitial matrix contributes to the interstitial resistance to fluid flow, and because hyaluronan (HA) is the only component of the matrix that is not anchored to the tissue, we hypothesized that the loss of interstitial HA was responsible for the continued decrease in interstitial resistance to fluid flow. We determined HA concentration in the rat AAM and adjacent subcutaneous tissue (SC) at P_ip = 0 mmHg and after 2 h of dialysis at constant P_ip = 6 mmHg. The HA content (normalized to dry weight) in the AAM was reduced from 487 ± 16 to 360 ± 27 µg/g dry tissue (n = 4, P < 0.05) and increased from 528 ± 72 to 1,050 ± 136 mg/g dry tissue (n = 4, P > 0.001) in the SC. We conclude that the mechanisms responsible for the increase in K with P_ip 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.

convection; hydraulic conductivity; compliance; peritoneal dialysis

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