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Water is the largest constituent of the human body. It accounts for 50% to 60% of body weight in adult females and males1 and from 60% to 70% in newborns and infants up to 2 months of age.2 Normally, about two-thirds of body water is intracellular and the rest is distributed between the smaller intravascular (plasma) and larger extravascular (interstitial) compartments. The solutes in extracellular and intracellular water differ because cell membranes possess an array of transport systems that take up or exclude specific minerals or organic compounds (Chapter 43). Sodium and its anions, which are largely excluded from cells, make up approximately 95% of extracellular solute. The others are mostly urea and glucose which normally enter cells readily by passive diffusion or active transport. The principal intracellular solutes are potassium, magnesium, and various organic compounds or phosphates. Despite these differences, the total molar concentration of solute in the two compartments is the same because cell membranes also contain channels that permit water to flow freely into or out of the cell to equalize osmotic pressure.3,4,5 The total molar concentration of the solutes that are osmotically active—that is, those that are excluded or retained by cells—is referred to as the tonicity of the fluid. It cannot be measured directly but is approximated closely by the plasma concentration of sodium and its anions. Normally, the tonicity is also similar to the osmolality or osmolarity of the fluid, which is determined by the molar concentration of all solutes and can be measured by vapor pressure or freezing point depression. The values are reported as mOsm per kilogram of water (osmolality) or mOsm per liter of water (osmolarity). Numerically, there is very little difference between them and the choice of terminology is largely a matter of personal preference. In this chapter, the term osmolarity is used to avoid confusion with references to body weight.

In healthy humans, plasma osmolarity and its principal determinants, plasma sodium and its anions, are normally maintained within a relatively narrow range. This constancy is important for the regulation of cell volume since the extracellular concentration of sodium and other solutes that are excluded from cells determines the distribution of water between the intracellular and extracellular compartments. An increase in extracellular tonicity rapidly reduces cell volume by inducing an outward flow of water. A decrease has the opposite effect. The effects on cell volume may be counteracted to some extent by changes in the intracellular concentration of certain other solutes, principally potassium and certain amino acids or other organic compounds that are actively retained or produced by the cells.6 However, the primary regulator of cell volume is the tonicity of extracellular fluid. This property in turn is controlled by an elegant osmoregulatory system that raises or lowers total body water by modifying the intake and/or urinary excretion of water via changes in thirst and release of the antidiuretic ...

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