Transport of Water Soluble Solutes Between the Peritoneal Cavity and the Plasma in the Rat.

Abstract

Using the Sprague-Dawley female rat, a systems-level research proram was carried out to investigate and quantify the mechanisms involved in the transport of water soluble solutes between the peritoneal cavity and plasma. A two-compartment lumped-parameter approach to peritoneal modelling was applied to experiments which focused on the effects of dialysis fluids with different osmotic pressures on the resulting fluid shifts and the transport of several solutes. Moderate fluid shifts did not significantly affect the transport of substances greater than the size of inulin, but were significant for urea and sucrose. Permeability-area product values were computed and correlated with solute molecular weight. A new conceptual model and its corresponding mathematical formulation were developed which incorporated two major hypotheses: (1) that the blood capillary system is distributed in tissue and therefore interstitial diffusion and convection are important mechanisms in the transport process, and (2) that the lymphatic transport mechanism is significant with regard to fluid transport and transport of large solutes. Concentration gradients in peritoneal tissue were examined by freezing and sectioning. The results showed that the concentration gradients are significant for the first 400-600 microns from the peritoneal surface and extend to 1500 microns. Lymphatic uptake experiments using the protein tracer I-125 fibrinogen and Cr-51 red blood cells indicated that the calculated lymph flow from the cavity (4.30 (+OR-) 1.74 and 2.65 (+OR-) 1.35 microliters/min, respectively) was an order of magnitude less than the observed fluid loss. Most of the protein tracer loss from the cavity was due to local tissue uptake of the substance. The model was evaluated for transport in both directions in experiments with labelled substances whose molecular weight ranged from 180 to 160,000. These were injected dissolved in dialysis fluid into the cavity or in an i.v. bolus and the time course of concentration in the plasma and the peritoneal fluid was followed for three to four hours. Effective tissue diffusivities corresponded to those given in the literature. Membrane transport parameters for small solutes (MW: 180-5,500) corresponded closely to those derived from Pore Theory with a single-sized pore radius of 40 angstroms and a pore density of 600/sq. cm. In the case of macromolecules, peritoneal to plasma transport occurs via lymphatic uptake, while plasma to peritoneal transport is due to filtration through large pores or unidirectional pinocytosis.