Hyponatremia Revisited: Translating Physiology to Practice

Abstract

The complexity of hyponatremia as a clinical problem is likely caused by the opposite scenarios that accompany this electrolyte disorder regarding pathophysiology (depletional versus dilutional hyponatremia, high versus low vasopressin levels) and therapy (rapid correction to treat cerebral edema versus slow correction to prevent osmotic demyelination, fluid restriction versus fluid resuscitation). For a balanced differentiation between these opposites, an understanding of the pathophysiology of hyponatremia is required. Therefore, in this review an attempt is made to translate the physiology of water balance regulation to strategies that improve the clinical management of hyponatremia. A physiology-based approach to the patient with hyponatremia is presented, first addressing the possibility of acute hyponatremia, and then asking if and if so why vasopressin is secreted non-osmotically. Additional diagnostic recommendations are not to rely too heavily of the assessment of the extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis as a diagnosis of exclusion, and to rationally investigate the pathophysiology of hyponatremia rather than to rely on isolated laboratory values with arbitrary cutoff values. The features of the major hyponatremic disorders are discussed, including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise-associated hyponatremia. The treatment of hyponatremia is reviewed from simple saline solutions to the recently introduced vasopressin receptor antagonists, including their promises and limitations. Given the persistently high rates of hospital-acquired hyponatremia, the importance of improving the management of hyponatremia seems both necessary and achievable.

The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation

“…The side-effect profile of thiazide diuretics resembles Gitelman syndrome with the exception of hyponatremia, which is only seen with thiazides [22,24,48]. …”

The Effect of Serum Sodium on Survival in Patients Treated by Peritoneal Dialysis in the United Kingdom

“…in patients with chronic liver disease and cardiac failure), or a failure to adequately excrete water as in cases of inappropriate vasopressin secretion, which may be drug induced, or alternatively due to polydipsia and reduced dietary sodium intake excessive water or beer ingestion, and also due to increased sodium losses associated with hypovolaemia from diuretics and purgatives [2]. Inflammatory states with increased secretion of IL-6 and C reactive protein (CRP) have also been documented to be associated with hyponatraemia due to vasopressin release [3].…”

Hyponatremia and Cerebral Edema Associated with Radioiodine Therapy for Papillary Thyroid Carcinoma

“…16 There is also a decrease in renal blood flow and glomerular filtration and this can directly diminish free water excretion by diminishing water delivery to the diluting segments. 17,18 These however do not lead to significant hyponatremia unless there are other contributory factors such as diuretic use, excessive extra-renal losses as in diarrhea and vomiting or large volumes of fluid intake, 18 as in our case. Reduced cardiac output in hypothyroidism may also play a role, stimulating volume-mediated ADH release via the carotid sinus baroreceptors.…”