Abnormalities of cell volume regulation and their functional consequences.

Disturbances of body fluid osmolality are common as clinical entities. The primary clinical manifestations of both hyper- and hyposmolal states are central nervous system dysfunction. With hyperosmolal perturbations in plasma osmolality, the brain, like other tissues, initially acts as a "perfect osmometer," passively shrinking as a result of secondary substantial cellular water loss. In hours to days, depending on the extracellular solute, restoration of brain volume may be achieved if the solute is endogenous (Na+, urea, glucose). This occurs largely by the generation of new, nonelectrolyte intracellular solute in brain. This de novo solute appears only when hyperosmolality is caused by endogenous substances and not with mannitol, glycerol, or radiographic contrast media. Under the latter circumstances, the brain remains dehydrated and idiogenic osmoles are not observed. In hyposmolal states, the brain initially acts as an "imperfect osmometer," expanding its volume less than expected on the basis of passive water movement. Other tissues (red cell, muscle, and liver) behave more as perfect osmometers. In time, restoration of cell volume is achieved largely through loss of intracellular electrolytes (Na+ and K+) and other solutes such as amino acids. Teleologically, these mechanisms appear to protect brain volume at the expense of the intracellular milieu. The resultant alteration of intracellular composition may be largely responsible for the diffuse alterations in brain function observable in patients and experimental animals with such afflictions.