Adverse effects of hyponatremia on the brain
Neurologic complications in hyponatremia are often due to brain edema that is caused by hyponatremia.1-3 Brain edema in hyponatremia is the result of the low extracellular sodium concentration causing water to move from outside the cells to inside the cells to keep the extracellular and intracellular osmolalities equal.3
Complications resulting from brain edema include1-3:
- Brain-stem herniation
- Permanent brain damage
- Respiratory arrest
High mortality rates that are associated with hyponatremia are often due to osmotically induced brain edema.3,4
Cases when neurologic complications typically occur
Neurologic complications typically only occur in cases of hyponatremia that are severe and rapidly evolving1-3 and in cases of hyponatremia in which the brain is unable to regulate its volume.5
An adaptation process occurs in the brain to ameliorate the cell swelling that takes place in the presence of hyponatremia. The entire adaptation process, which is described below, takes time, and in acute hyponatremia or hyponatremia that is severe and rapidly evolving, the complications from edema occur more quickly than the adaptation process.1-3
In other cases in which complications occur, there are factors present that impair the brain’s ability to adapt to the edema. Factors that impair adaptation include5:
- Sex (premenopausal females)
- Due to estrogen-inhibiting Na+-K+-ATPase
- Age (prepubescent children)
- Due to a discrepancy between skull size and brain size
- Increased vasopressin
Effects of hypotonic hyponatremia on the brain
The onset of hypotonic hyponatremia immediately causes cells in the brain to swell.1,3
Adaptation of the brain to hypotonic hyponatremia
Within a few hours, the swollen cells in the brain adapt to the swelling by extruding electrolytes from their cytoplasm. Because intracellular and extracellular osmolalities must be equal, the extrusion of electrolytes results in water leaving the cell, causing a decrease in the cell swelling, thereby partially restoring brain volume.1-3
Brain volume is fully restored after several days following a loss of organic osmolytes from the cells that results in a further extrusion of water.1,3
Mortality in acute versus chronic hyponatremia
In chronic hyponatremia, the brain has time to adapt to the cell swelling that occurs, so neurologic complications are not often seen because these complications are related to brain edema. In acute hyponatremia, complications arise before the brain has time to adapt.1-3 Because of this, mortality rates are higher in acute hyponatremia.2,3,6
Brain volume regulation accounts for the differences in mortality rates between acute and chronic hyponatremia6
- Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;343(21):1581-1589.
- Arieff AI, Guisado R. Effects on the central nervous system of hypernatremia and hyponatremic states. Kidney Int. 1976;10(1):104-116.
- Sterns, RH, Silver SM. Brain volume regulation in response to hypo-osmolality and its correction. AM J Med. 2006;119(7 Suppl 1): S12-16.
- Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-S42. doi:10.1016/j.amjmed.2013.07.006.
- Ayus JC, Achinger SG, Arieff A. Brain cell volume regulation in hyponatremia: role of sex, age, vasdopressin, and hypoxia. AM J Renal Physiol. 2008;295:F619-F624. doi: 10.1152/ajprenal.00502.2007.
- Kleeman CR. The kidney in health and disease: X. CNS manifestations of disordered salt and water balance. Hosp Pract. 1979;14(5):59-68,73.