Electrolyte concentration values in interstitial fluid samples that have been reported by a number of authors were markedly different from those of a hypothetical ultrafiltrate of plasma. Because no adequate explanation has been provided for the discrepancy, we attempted to study the question 1) by measuring ion and protein concentration in the plasma and in the interstitial fluid samples, and 2) by constructing a theoretical model for ion distribution. Subcutaneous interstitial fluid samples were collected in rats by the implanted capsule and by the liquid paraffin cavity techniques. The samples were analyzed for sodium, potassium, calcium, chloride, total protein, and protein fractions. The ion distribution between vascular and interstitial compartments was found to correspond to the Donnan equilibrium. On theoretical ground it was concluded: the Donnan distribution is valid, if the size of "free-fluid spaces" is relatively large (r greater than 0.03 micron) compared with the rather short range of electrostatic interactions (approximately 0.8 nm). Due to the relatively small difference in protein concentrations between blood plasma and interstitial fluid and to the short range of electrostatic interactions, the influence of proteins on the distribution of small ions is negligible.

It has been suggested that electrostatic interactions between the electric charges on the interstitial gel matrix play a significant role in determining tissue elasticity and interstitial fluid pressure (IFP). The relationship between the net charge and IFP, however, has not been adequately established. Our purpose was to explore the net electric charge-IFP relationship, and in vivo experiments were performed to test its validity. IFP was measured in the subcutaneous tissue of anesthetized rats with the chronically implanted capsule method, and the acid-base status in blood and interstitial fluid was monitored. The net charge, which can be varied by pH, was altered by electrolysis procedure. H+ and OH- generated inside the capsule caused transient and dose-dependent IFP responses. The curve, describing the relationship between capsular pressure changes and amount of generated H+ and OH-, has a maximum at zero net charge, and the excess electric charge, either positive or negative, results in a significant decrease in capsular pressure in accordance with the hypothesis. The time course, as well as the dose dependency, of IFP suggests that the subcutaneous tissue gel in control condition has slightly positive net charge.

Inherent problems concerning the interstitial fluid pressure (IFP) are reinvestigated on theoretical grounds. Analyzing the thermodynamic and mechanical equilibria in the interstitium, it is concluded that IFP includes a pressure term originating from the elastic forces and an osmotic pressure term. A quantitative relationship is established between the IFP and all of the parameters responsible for the changes in the recorded pressure. The theoretical results suggest that, under control conditions, 1) there are no permanently existing free fluid spaces, 2) the gel pressure is atmospheric, and 3) the fluid equilibration techniques measure an osmotic pressure difference between the gel phase and the fluid phase created artificially by any of the pressure measuring devices. The pressure response during acute volume changes is attributed to the changes in the osmotic pressure term, gel volume, and elasticity. Volume and elasticity changes are reflected in the recorded IFP as promptly developing and permanent effects; on the other hand, osmotic processes result in slowly developing and transient effects. The volume-pressure relationship is also analyzed.