Effect on the Brain 

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The most significant clinical adverse effects
associated with hyponatremia are the result of its
impact on the brain1

Cerebral Edema in Acute Severe Hyponatremia
    • Patients exhibiting symptoms of hyponatremia usually have brain edema.3
    • If the brain has not adapted sufficiently to the swelling, the resulting pressure on the skull can cause a decrease in cerebral blood flow and pressure necrosis.3

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Adaptive responses by the brain to edema4

Effect of Hyponatremia on the Brain

Effect of Hyponatremia on the Brain

Adapted with permission from Adrogué HJ, et al. N Engl J Med. 2000;342(21):1581-1589.

Hyponatremic encephalopathy often precedes brain damage5

  • A leading factor causing an adverse outcome in patients with hyponatremic encephalopathy is the inability of the brain to regulate its volume. Uncontrolled brain swelling often leads to brain damage or death.5
  • The outcome for patients with hyponatremic encephalopathy depends on the ability of the brain to regulate its volume to prevent swelling and therefore adapt to the hyponatremia.5

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The majority of morbidity associated with uncorrected symptomatic hyponatremia is due to brain damage3

  • Important risk factors for hyponatremic brain damage have been defined as5:
    • Gender (women of childbearing age)
    • Age (prepubescent children)
    • Physical factors including discrepancy between skull size and brain size
    • Actions of multiple hormones (particularly vasopressin and estrogen)
    • Presence of hypoxia (low oxygen)

Acute versus chronic hyponatremia

Mortality Rates with Acute and Chronic Hyponatremia
Brain Volume Regulation Accounts for the
Differences in Mortality Rates Between
Acute and Chronic Hyponatremia6
  • In chronic hyponatremia, the brain can compensate for falling sodium levels by the cellular exit of solutes that promote water loss and lessen brain swelling.4
  • This process of chronic adaptation by the brain can account for the potentially asymptomatic state of some patients with moderate to severe hyponatremia.7

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Complications of severe and rapidly evolving hyponatremia include seizures, coma, permanent brain damage, respiratory arrest, brain-stem herniation, and death—thus, constant monitoring is warranted4,7


  1. Sterns RH, Silver SM. Brain volume regulation in response to hypo-osmolality and its correction. Am J Med. 2006;119(7A)(suppl 1):S12-S16.
  2. Gross P. Treatment of severe hyponatremia. Kidney Int. 2001;60(6):2417-2427.
  3. Arieff AI. Management of hyponatraemia. BMJ. 1993;307(6899):305-308.
  4. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581-1589.
  5. Ayus JC, Achinger SG, Arieff A. Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am J Physiol Renal Physiol. 2008;295(3):F619-F624.
  6. 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.
  7. Adrogué HJ. Consequences of inadequate management of hyponatremia. Am J Nephrol. 2005;25(3):240-249.

Recent Studies in Hyponatremia

Recent Studies in Hyponatremia

Listen to Dr. Tomas Berl,
the internationally renowned nephrologist, present his review of recent hyponatremia studies. This clinical slide video discusses key papers in epidemiology and bone disease.

Watch Now

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