Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia.

Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (Na(E) and Cl(E)). The following observations are noted: Brain Cl content varies directly with Cl(E) and brain Na content in the Cl space (Na(e)) varies directly with Na(E), indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (V(i)) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in V(i) in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) Na(E) is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) V(i) is osmotically active; and (d) there is no net gain or loss of solute from V(i). The validity of these assumptions is considered. When changes in osmolality are sustained, V(i) is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in V(i) observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon Na(E) describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in Na(E) by the freedom for Na and Cl to move from the Cl space, by V(i) not changing acutely to the degree predicted from osmotic properties of cells in general, and by significant quantities of Na + K in V(i) being osmotically inactive. With sustained changes in osmolality, V(i) approaches normal values and brain K changes to account for part of this later adjustment.