Hypovolemia from both renal and extrarenal causes is associated with hyponatremia. Renal causes of hypovolemia include primary adrenal insufficiency and hypoaldosteronism, salt-losing nephropathies (e.g., reflux nephropathy, nonoliguric acute tubular necrosis), diuretics, and osmotic diuresis. Random “spot” urine Na⁺ is typically >20 meq/L in these cases but may be <20 meq/L in diuretic-associated hyponatremia if tested long after administration of the drug. Nonrenal causes of hypovolemic hyponatremia include GI loss (e.g., vomiting, diarrhea, tube drainage) and integumentary loss (sweating, burns); urine Na⁺ is typically <20 meq/L in these cases.

Hypovolemia causes profound neurohumoral activation, inducing systems that preserve arterial circulatory integrity, such as the renin-angiotensin-aldosterone (RAA) axis, the sympathetic nervous system, and AVP (Table 1-1). The increase in circulating AVP serves to increase the retention of ingested free H₂O, leading to hyponatremia. The optimal treatment of hypovolemic hyponatremia is volume administration, generally as isotonic crystalloid, i.e., 0.9% NaCl (“normal saline”). If the history suggests that hyponatremia has been “chronic,” i.e., present for 48 h, care should be taken to avoid overcorrection (see below), which can easily occur as AVP levels plummet in response to volume-resuscitation; if necessary, the administration of desmopressin (DDAVP) and free water can reinduce or arrest the correction of hyponatremia (see below).