Hyponatremia: mechanisms and newer treatments

To review the neural and renal mechanisms of osmotic homeostasis, provide a rationale for the sensitivity of the central nervous system to hyponatremia, and outline modern approaches to therapy of acute and chronic hyponatremia.

Review of relevant literature with focus on physiologic mechanisms.

With careful monitoring, acute hyponatremia can be managed, while minimizing risks both of continued hyponatremia and the osmotic demyelination that can occur with overly rapid correction of severe hyponatremia. Chronic hyponatremia due to disorders of volume regulation (congestive heart failure or cirrhosis) or to syndrome of inappropriate antidiuretic hormone release can be managed effectively with vasopressin V2 receptor antagonists, but there is no evidence that controlling the hyponatremia enhances survival associated with the underlying diseases.

Therapy in the acute setting balances the risk of the osmotic disturbance with the risk of overly rapid correction. The V2 receptor antagonist tolvaptan has enhanced our ability to improve chronic hyponatremia in conditions such as congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone hypersecretion.