Regulation of Interstitial Fluid Volume and Pressure*

Summary Three recent discoveries in the field of interstitial fluid dynamics make it pos‐ sible to construct a relatively complete analysis of the regulation of interstitial fluid volume and interstitial pressure. These three discoveries are the following: First, the normal interstitial fluid pressure is about ‐7 mm Hg in contrast to the previously believed values of + 1 to +8 mm Hg. Second, the volume‐pressure curve of the interstitial spaces is very nonlinear: a very slight increase in interstitial fluid volume above normal will increase the interstitial fluid pressure from ‐7 mm Hg up to equal atmospheric pressure (0 mm Hg), but, once the interstitial fluid pressure has risen above this level, the tissue spaces balloon outward rapidly, in such a way that tremendous volumes of fluid can then be accommodated in the tissue spaces with almost no further rise in interstitial fluid pressure. Indeed, at positive pressures of +2 to +5 mm Hg, 4+ edema occurs in the S.C. tissues of the body. Third, the fluids normally present in the interstitial spaces appear not to be motile but instead bound and held firmly in place. This fluid can diffuse back and forth between the circulation and interstitial spaces because of the tremendous pressures (up to one million mm Hg) that exist for causing the process of diffusion to occur. On the other hand, this fluid cannot be removed from the tissue spaces by the usual, comparatively weak hydrostatic forces that develop in the lymphatic system or that develop as a result of osmosis at the capillary membrane. When edema occurs, essentially all the extra fluid that appears in the tissues is in the motile state and can be moved easily from one part of the tissue to another with only 0 to 5 mm Hg pressure gradient. Under normal conditions, two different factors, (a) lymphatic flow caused by arterial pulsation and other types of motion in the tissues, and (b) osmosis of fluid from the tissue spaces through the capillary membrane, keep the tissues “dry” of motile fluid and thereby maintain a negative interstitial fluid pressure of about ‐7 mm Hg. Therefore, the normal interstitial fluid volume is regulated to essentially zero motile fluid in the interstitid spaces, and the fluid that is present in the interstitial spaces appears to be only that amount entrapped by the gel in the ground substance of the tissue spaces or held by capillarity in very minute tissue spaces.