Exposure of a cell to nonisotonic extracellular fluid (ECF) can lead to changes in cell volume, either swelling or shrinking. To counteract these changes, cells have mechanisms that activate volume-regulatory responses within seconds to minutes. In the case of cell swelling, a regulatory volume decrease response occurs, which transports osmotically active particles (osmolytes) out of the cell, reducing the intracellular osmotic pressure and restoring cell volume to normal. Conversely, when a cell shrinks, a regulatory volume increase response takes place, transporting osmolytes into the cell and raising the intracellular osmotic pressure to restore cell volume to normal. These osmolytes include ions and organic molecules such as polyols (sorbitol and myo-inositol), methylamines (glycerophosphorylcholine and betaine), and some amino acids (taurine, glutamate, and β-alanine). If the cell is exposed to nonisotonic ECF for an extended period, it will adjust the intracellular levels of organic osmolytes through metabolic processes.

In the presence of a semipermeable membrane, the Gibbs-Donnan effect occurs. This effect is demonstrated when two solutions with different concentrations of Na+, Cl-, and H2O are separated by the membrane, which is permeable to these substances but not to proteins (P-). As Cl- diffuses from one compartment to another down its concentration gradient, the compartment with higher Cl- concentration becomes electrically negative compared to the other compartment. This difference in membrane voltage drives the diffusion of Na+ from the compartment with lower Na+ concentration to the compartment with higher Na+ concentration. The accumulation of additional Na+ and Cl- in the latter compartment increases its osmolality and causes water to flow from the former compartment to the latter (note: this results in a lower volume in the former compartment). If the container containing the two solutions is sealed at the top, preventing water movement between compartments, the pressure in the latter compartment will increase as the number of osmotically active particles increases.

Most cells in the body are surrounded by isotonic ECF, which is tightly regulated. However, certain regions of the body, such as the medulla of the kidney, may not have isotonic ECF. In cases of water balance disorders, the ECF can become either hypotonic or hypertonic, leading to cell swelling or shrinkage. These changes in cell volume can cause damage or death, particularly in neurons within the confined space of the skull.

Neurons and glial cells respond to a decrease in ECF osmolality by swelling as water enters the cell. To minimize this swelling, neurons and glial cells reduce the levels of intracellular osmolytes. If the ECF osmolality is corrected too quickly by increasing it, neurons and glial cells may shrink due to the reduced number of intracellular osmolytes. Rapid correction of ECF osmolality can result in cell damage. Damage to the glial cells responsible for synthesizing myelin in the brain can lead to demyelination, known as osmotic demyelinization syndrome. This syndrome can affect any white matter of the brain but is especially prevalent in regions of the pons. These effects are often irreversible. Therefore, correcting water balance disorders is usually done slowly to avoid this serious neurological complication.
B the intracellular osmotic pressure and thereby restoring cell volume to normal. Conversely with cell shrinking a regulatory volume increase response transports osmolytes into the cell, raising the intracellular osmotic pressure and thereby restoring cell volume to normal. These osmolytes include ions and organic molecules such as polyols (sorbitol and myo-inositol), methylamines (glycerophosphorylcholine and betaine), and some amino acids (taurine, glutamate, and β-alanine). If the cell is exposed to the nonisotonic ECF for an extended period of time, the cell alters the intracellular levels of the organic osmolytes through metabolic processes.
•Fig. 2.6 The Gibbs-Donnan Effect. Top, TwosolutionsareseparatedbyamembranethatispermeablebyNa+ ,Cl− ,andH2Obutnotpermeablebyprotein(P−).TheosmolalityofsolutionAisidenticaltothatofsolutionB.Bottom, Cl− diffusesfromcompartmentBtocompartmentAdownitsconcentrationgradient.ThiscausescompartmentAtobecomeelectricallynegativewithregardtocompartmentB.ThemembranevoltagethendrivesthediffusionofNa+ fromcompartmentBtocompartmentA.TheaccumulationofadditionalNa+ andCl− incompartmentAincreasesitsosmolalityandcauseswatertoflowfromcompartmentBtocompartmentA(Note:theincreasevolumeofcompartmentAresultsinalower[P−]).IfthecontainercontainingthetwosolutionsweresealedatthetopsothatwatercouldnotmovefromcompartmentBtocompartmentA,thepressureincompartmentAwouldincreaseasthenumberofosmoticallyactiveparticlesincreasesinthatcompartment.
reduced from what would be caused by the Gibbs-Donnan effect, and cell volume is maintained in isotonic solutions.
Most cells throughout the body are bathed with isotonic ECF, the composition of which is tightly regulated (see ). However, certain regions within the body are not isotonic (e.g., the medulla of the kidney), and with disorders of water balance, the ECF can become either hypotonic or hypertonic. When this occurs, cells either swell or shrink. Cell swelling or shrinkage can result in cell damage or death, but many cells have mechanisms that limit the degree to which the cell volume changes. These mechanisms are particularly important for neurons, in which swelling within the confined space of the skull can lead to serious neurological damage.
In general, when a cell is exposed to nonisotonic ECF, volume-regulatory responses are activated within seconds to minutes to restore cell volume (
Fig. 2.7 ). With cell swelling, a regulatory volume decrease response transports osmotically active particles (osmolytes) out of the cell, reducing
TheECFofindividualswithdisordersinwaterbalancemaybeeitherhypotonic(positivewaterbalance)orhypertonic(negativewaterbalance).WithadecreaseinECFosmolality,neuronsandglialcellsswellaswaterentersthecell.Tominimizethisswelling,theneuronsandglialcellsreduceintracellularosmolytes.IftheECFosmolalityiscorrected(i.e.,increased)tooquickly,theneuronsandglialcellsthenshrinkbecauseofthereducednumberofintracellularosmolytes.ThisresponsetoarapidcorrectionofECFosmolalitycanleadtocelldamage.Damagetotheglialcellsthatsynthesizemyelinwithinthebraincanresultindemyelinization.Thisdemyelinizationresponse,termedosmotic demyelinization syndrome, canaffectanyofthewhitematterofthebrain,butespeciallyregionsofthepons.Theseeffectsareoftenirreversible.Therefore,correctionofdisordersofwaterbalanceisusuallyaccomplishedslowlytoavoidthisseriousneurologicalcomplication.