Holliday M A, Kalayci M N, Harrah J
J Clin Invest. 1968 Aug;47(8):1916-28. doi: 10.1172/JCI105882.
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.
分别通过输注高渗盐水或水使大鼠急性高钠血症或低钠血症。其他大鼠维持在这些状态1至7天以观察时间的影响。将脑组织中的水、钠、氯和钾与血清钠和氯浓度（Na(E)和Cl(E)）进行比较。观察到以下情况：脑氯含量与Cl(E)直接相关，脑氯空间（Na(e)）中的脑钠含量与Na(E)直接相关，这表明钠或氯从脑氯空间的向内或向外移动几乎没有或没有受到限制。作为总水量与氯空间之差得出的脑细胞内液体积（V(i)），在高钠血症时减少，在低钠血症时增加。急性研究中V(i)的变化并未伴随着脑钾含量或计算得出的细胞内钠含量的任何变化，并且大约是根据细胞渗透行为预测变化的0.6倍，细胞渗透行为基于四个假设：(a) Na(E)与渗透压成正比；(b) 脑渗透压保持等于血浆渗透压；(c) V(i)具有渗透活性；(d) V(i)中溶质没有净增加或减少。考虑了这些假设的有效性。当渗透压变化持续时，V(i)比急性期更接近对照值。高钠血症时钾含量增加，低钠血症时钾含量减少。钾含量的变化可以解释在高钠血症或低钠血症延长期间观察到的V(i)的一些调整。(Na + K)/v对Na(E)的回归描述了一个小于1.0的斜率和一个等于对照(Na + K)/v 40%的(Na + K)/v截距。这些特征被解释为意味着脑中大量的钠和钾是渗透惰性的。大脑通过钠和氯从氯空间自由移动、V(i)不会像一般细胞渗透特性预测的那样急剧变化以及V(i)中大量的Na + K是渗透惰性的，来保护自身免受因Na(E)变化而引起的急性体积变化。随着渗透压的持续变化，V(i)接近正常值，脑钾发生变化以解释部分后期调整。
