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SPECULATIONS ON PHYSICOCHEMICAL FLUID PROPERTIES IN PHYSIOLOGICAL REGULATION J. C. DeHAVEN and N. Z. SHAPIRO* I. Preface The speculations in this paper arose while we were constructing mathematical models of the chemistry of some physiological subsystems. We wondered why modern solution theory was not used more widely to assist in explaining certain chemical phenomena occurring in and between body fluids. It is known, for example, that various classes of chemical substances have different steady-state concentration gradients between various intracellular and extracellular media. When relatively large amounts of some of these substances are added to the system, the concentration gradients of other substances may be altered in one way or another, or not at all. Fluxes of such substances into or out of cells, sometimes to regions of higher concentration, are similarly affected. Substances of greatest interest include metabolic fuels, intermediates, and products— various carbohydrates, amines, amides, and amino acids. The mutual antagonistic or augmentative influences of such substances are noted in many parts ofthe body: for example, between plasma and gastrointestinal fluid, cerebrospinal fluid, urine, saliva, sweat, bile, and aqueous humor. The most widely accepted explanation for these phenomena is based entirely on the characteristics ofthe membranes separating the compartments . Such an explanation postulates, for example, membrane carriers that supposedly combine differentially, or not at all, with the large number of substances involved. As many as fifty separate carriers need to be postulated for some systems. Inasmuch as few, if any, carriers have yet * RAND Corporation, 1700 Main Street, Santa Monica, California 90406. We acknowledge the expert computational assistance of M. L. Shapley and useful suggestions by N. S. Assali and T. H. Kirschbaum. Research is supported by the U.S. Air Force under Project RAND. 31 been identified, and hundreds or thousands of kinetic and diffusion constants (few now known and varying from system to system) must somehow be estimated in order to construct models incorporating the membrane -carrier hypothesis, this hypothesis entails grave difficulties for the model builder. Whatever the present deficiencies of chemical solution theory for application to complex body fluids, physicochemical experience with somewhat similar types of non-biological solutions enables one to state with a great deal of certainty that the properties of the fluids will affect fluxes and concentration gradients. The only question is whether their influence will be ofa significant degree. Of all chemicals that influence body composition, the hormones are among the most potent. Although they exist in tiny amounts in the body, changes in their levels—as brought about by various psychological or pharmaceutical stresses or disease—can exert major acute and chronic chemical changes in the body. Hormones react both antagonistically and augmentatively with each other. There is no generalized theory of hormonal action; the science is still largely at the level of qualitative classification ofhormonal effects. Any quantitative model ofhormonal action must of necessity, then, be limited in nature, empirical, and inflexible. If, however, an important mode of hormonal action can be shown to occur through its effects on body fluids rather than solely on membranes, one might hope to call on solution theory to help provide the basis for a more generalized predictive model. We make no attempt in this paper to derive de novo expressions for the activity coefficients of neutral substances and water in electrolytic solutions . To do so would be both unnecessary and beyond the scope ofthis paper. Rather, we have drawn on the derivations of others (especially of Edsall and Wyman [i]) and modified their results where necessary to suit our special purposes. The basic derivations involve considerations of the electrical effects imposed on the solvent water by dissolved and ionized strong electrolytes and the resulting influences on the properties of other dissolved substances ofdiffering electrical characteristics. We first examine the implications of this relatively simple electrostatic solution theory in terms of "salting-in" and "salting-out" of substances between phases as determined by the electrostatic properties of the adjacent solutions and ofthe substances. A measure ofthe electrostatic properties ofsubstances, 32 f. C. DeHaven and N. Z. Shapiro · Physicochemical Fluid Properties Perspectives in Biology and Medicine · Autumn 1968 the dielectric increment, is subsequently correlated with gradients of chemicals reported to exist between compartments...


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