Brain volume regulation in response to changes in osmolality.
ABSTRACT Hypoosmolality and hyperosmolality are relatively common clinical problems. Many different factors contribute to the substantial morbidity and mortality known to occur during states of altered osmotic homeostasis. The brain is particularly vulnerable to disturbances of body fluid osmolality. The most serious complications are associated with pathological changes in brain volume: brain edema during hypoosmolar states and brain dehydration during hyperosmolar states. Studies in animals have elucidated many of the mechanisms involved with brain adaptation to osmotic stresses, and indicate that it is a complex process involving transient changes in water content and sustained changes in electrolyte and organic osmolyte contents. Appreciation of the nature of the adaptation process, and conversely the deadaptation processes that occur after recovery from hypoosmolality and hyperosmolality, enables a better understanding of the marked variations in neurological sequelae that characterize hyperosmolar and hypoosmolar states, and provides a basis for more rational therapies.
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ABSTRACT: 1. An attempt was made to evaluate the pathophysiology of symptoms of hyponatremia as related to changes in brain water and electrolytes. Studies were carried out in 66 hyponatremic patients and 5 groups of experimental animals. 2. In hyponatremic patients, symptoms (depression of sensorium, seizures) correlated well with plasma Na+ (r = 0.64, p less than .001), but there was substantial overlap. In patients with acute hyponatremia, all were symptomatic and 50% died. Among patients with hyponatremia of at least 3 days duration, sympatomatic patients had plasma Na+ (115 +/- 1 mEq/L) which was significantly less (p less than .001) than that of asymptomatic patients (plasma Na+ = 122 +/- 1 mEq/L). Among symptomatic patients, mortality was 12% and 8% had seizures, while none of the asymptomatic patients died or had seizures. 3. Among 14 patients with acute (less than 12 hrs) hyponatremia, the mean plasma Na+ was 112 +/- 2 mEq/L. All such patients had some depression of sensorium and four had grand male seizures. Seven of these patients were treated with hypertonic (862 mM) NaCl, while four were treated only with fluid restriction. Of the seven patients treated with hypertonic NaCl, five survived, while three of four patients treated with fluid restriction died. There was no evidence of circulatory congestion or cerebral damage in the patients treated with hypertonic NaCl. 4. Among rabbits with acute (2-3 hours) hyponatremia (plasma Na+ = 119 +/- 1 mEq/L), all had grand mal seizures and 86% died. All such animals had cerebral edema (brain H2O content 17% above control value) but brain content of Na+, K+ and Cl- was normal. 5. Rabbits with 3 1/2 days of hyponatremia (plasma Na+ = 122 +/- 2 mEq/L) appeared to be asymptomatic, even though brain water content was 7% above normal (p less than .01). 6. Rabbits with 16 days of more severe hyponatremia (plasma Na+ = 99 +/- 3 mEq/L) were weak, anorexic, lethargic and unable to walk. Brain water content was 7% above normal, although brain osmolality (218 +/- 12 mOsm/kg H2O) was similar to plasma (215 +/- 8 mOsm/kg). Brain content of Na+, K+, Cl- and osmoles was 17 to 37% less than normal values, so that the brain established osmotic equilibrium with plasma primarily by means of a loss of electrolytes. 7. These studies suggest that in patients with hyponatremia, symptoms and morbidity are only grossly correlated with either magnitude or duration of hyponatremia. Symptoms appear to correlate best with the interplay between a net increase in brain water versus a loss oof brain electrolytes. However, even asymptomatic animals have subclinical brain edema when plasma Na+ is below 125 mEq/L, and such edema may cause permanent brain damage. Thus, many patients with similar levels of plasma Na+, particularly when they are symptomatic, should probably be treated with hypertonic NaCl infusions.Medicine 04/1976; 55(2):121-9. · 4.23 Impact Factor
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ABSTRACT: Previous studies from this laboratory showed that both acute and chronic hyponatremia impaired active brain buffering. These studies were performed to determine whether correcting the plasma sodium restored normal buffering in hyponatremic rats. Acute (1- and 2-day) and chronic (7- and 14-day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration combined with a liquid diet. Plasma sodium was corrected by stopping desmopressin for 6 h, substituting solid chow, and allowing free access to water. Studies were performed 24 h later. Uncorrected hyponatremic rats who continued to receive desmopressin and liquid diet served as controls. Brain pH was determined by [31P]NMR in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was determined by the response to CO2 loading. Resting brain pH was the same in corrected and uncorrected rats, but the two groups responded differently to CO2 loading. Thus, 55 min after ventilation with 20% CO2, corrected rat brain pH was 0.13 pH units higher than in uncorrected rats despite statistically similar changes in CO2 tension and arterial pH in both groups. Moreover, 15 min into recovery from CO2 exposure, brain pH in corrected rats overshot resting pH by 0.07, whereas no overshoot occurred in uncorrected rats. Buffering in corrected rats was identical to that shown previously in normonatremic rats. The complete restoration of late-phase buffering achieved by normalizing the plasma sodium of hyponatremic rats indicates that at least some portion of active hydrogen ion transport is sodium dependent in the brain.Journal of the American Society of Nephrology 08/1994; 5(1):85-92. · 8.99 Impact Factor
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ABSTRACT: 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.Journal of Clinical Investigation 09/1968; 47(8):1916-28. · 12.81 Impact Factor