Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia

Abstract

Hyponatremia is the most common electrolyte abnormality in hospitalized patients. When symptomatic (hyponatremic encephalopathy), the overall morbidity is 34%. Individuals most susceptible to death or permanent brain damage are prepubescent children and menstruant women. Failure of the brain to adapt to the hyponatremia leads to brain damage. Major factors that can impair brain adaptation include hypoxia and peptide hormones. In children, physical factors--discrepancy between skull size and brain size--are important in the genesis of brain damage. In adults, certain hormones--estrogen and vasopressin (usually elevated in cases of hyponatremia)--have been shown to impair brain adaptation, decreasing both cerebral blood flow and oxygen utilization. Initially, hyponatremia leads to an influx of water into the brain, primarily through glial cells and largely via the water channel aquaporin (AQP)4. Water is thus shunted into astrocytes, which swell, largely preserving neuronal cell volume. The initial brain response to swelling is adaptation, utilizing the Na(+)-K(+)-ATPase system to extrude cellular Na(+). In menstruant women, estrogen + vasopressin inhibits the Na(+)-K(+)-ATPase system and decreases cerebral oxygen utilization, impairing brain adaptation. Cerebral edema compresses the respiratory centers and also forces blood out of the brain, both lowering arterial Po(2) and decreasing oxygen utilization. The hypoxemia further impairs brain adaptation. Hyponatremic encephalopathy leads to brain damage when brain adaptation is impaired and is a consequence of both cerebral hypoxia and peptide hormones.

The Agony of Ecstasy

“…It is interesting that this gender difference has been seen in other causes of hyponatremia such as that occurring postoperatively (85,86). The gender susceptibility to the effects of hyponatremia may be secondary to the effects of estrogen to inhibit cerebral membrane Na-K-ATPase activity (87). Normally, Na-K-ATPase is the primary defense against the osmotic shifts caused by severe hyponatremia, and inhibition by estrogen makes the development of cerebral edema more likely.…”

“…Normally, Na-K-ATPase is the primary defense against the osmotic shifts caused by severe hyponatremia, and inhibition by estrogen makes the development of cerebral edema more likely. Estrogen may also lead to increased cerebral vasoconstriction in response to AVP leading to relative cerebral ischemia (87). Other factors that may increase the risk for fatal cerebral edema by impairing brain adaptation to cell volume changes include hypoxia and high vasopressin levels (86).…”

On water, salt and more …

“…In vielen Fallberichten wurden schwere Komplikationen und deletäre Verläu-fe (hyponatriämische Enzephalopathie mit Hirnödem und respiratorischer Insuffizienz) berichtet, die im Zusammenhang mit hypotonen glucosehaltigen Infusionslösungen aufgetreten waren [7]. Kinder sind perioperativ besonders gefährdet, da sie geringere intrakranielle Raumreserven haben und durch stressbedingte Ausschüttung des antidiuretischen Hormons (ADH) die Wasserausscheidung gehemmt wird [2].…”

Bone Disease as a New Complication of Hyponatremia

“…rain injury is the main result of acute symptomatic hyponatremia, and it is associated with significant morbidity and mortality (1,2). The symptoms of hyponatremic encephalopathy primarily result from cerebral edema, which is caused by an influx of water into the brain down a concentration gradient (2).…”

“…The symptoms of hyponatremic encephalopathy primarily result from cerebral edema, which is caused by an influx of water into the brain down a concentration gradient (2). Patients at high risk for this complication include postoperative patients, young female individuals, children, and patients with hypoxia or central nervous system disease (1-3); however, although the brain seems to be the main target for hyponatremia, it can no longer be considered the only organ affected by this condition.…”