Edema, oncotic pressure, and free entropy: Novel considerations for the treatment of edema through attention to thermodynamics

Over 170 years after Richard Bright and a century after Ernest H. Starling, the development, location, and severity of edema in patients with renal impairment continue to baffle the predictions of most nephrologists. While much of the phenomenon can be explained by levels of serum proteins, or hydrostatic pressures, there are stunning exceptions well known to any practicing nephrologist. Some of the derangement. is undoubtedly due to unmeasured but well-known variables, such as membrane permeability; however, other factors such as free entropy of plasma are also clearly involved. The study of other polyelectrolyte colloids, similar to plasma proteins, for industrial purposes has led to the identification of various phenomena such as counterion condensation that can result in loss of entropy and consequently osmotic pressure. Variables known to result in a loss of free entropy, such as pH, oxidation products and ligand binding, are discussed. Older equations developed by van't Hoff and Donnan might require replacement by newer mathematical models such as the nonlinear Poisson-Boltzmann equation or the Monte Carlo simulator. Attempts to restore free entropy to plasma would be a more physiological treatment of edema than diuretic use. Implications are noted for future drug development to treat edema.