title: Brain volume regulation in response to hypo-osmolality and its correction.
abstract: Hyponatremia exerts most of its clinical effects on the brain. An acute onset (usually in <24 hours) of hyponatremia causes severe, and sometimes fatal, cerebral edema. Given time, the brain adapts to hyponatremia, permitting survival despite extraordinarily low serum sodium concentrations. Adaptation to severe hyponatremia is critically dependent on the loss of organic osmolytes from brain cells. These intracellular, osmotically active solutes contribute substantially to the osmolality of cell water and do not adversely affect cell functions when their concentration changes. The adaptation that permits survival in patients with severe, chronic (>48 hours' duration) hyponatremia also makes the brain vulnerable to injury (osmotic demyelination) if the electrolyte disturbance is corrected too rapidly. The reuptake of organic osmolytes after correction of hyponatremia is slower than the loss of organic osmolytes during the adaptation to hyponatremia. Areas of the brain that remain most depleted of organic osmolytes are the most severely injured by rapid correction. The brain's reuptake of myoinositol, one of the most abundant osmolytes, occurs much more rapidly in a uremic environment, and patients with uremia are less susceptible to osmotic demyelination. In an experimental model of chronic hyponatremia, exogenous administration of myoinositol speeds the brain's reuptake of the osmolyte and reduces osmotic demyelination and mortality caused by rapid correction.
authors.affiliation: Department of Medicine, Rochester General Hospital, University of Rochester School of Medicine and Dentistry, Rochester, New York 14621, USA. richard.sterns@viahealth.org
authors.forename: Richard H
authors.initials: RH
authors.lastname: Sterns
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Silver
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007010:Hyponatremia / Q000150:complications* / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D017410:Practice Guidelines as Topic; D012965:Sodium Chloride / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D014508:Urea / Q000378:metabolism
chemical_list: D012965:Sodium Chloride; D007294:Inositol; D014508:Urea