What causes hyponatremia with concentrated (less than maximally dilute) urine?
Electrolyte-free water reabsorption. Water reabsorption is mediated by binding of vasopressin, or antidiuretic hormone (ADH—same stuff, 2 names), to vasopressin 2 (V2) receptors on the basolateral membranes of principal cells in the collecting ducts of nephrons. Vasopressin binding in turn stimulates insertion of aquaporin water channels into the luminal membrane. Water then flows through these aquaporin channels into cells and onward to the hypertonic medullary interstitium via constitutively active basolateral aquaporin channels. ADH release is regulated by osmoreceptors in the hypothalamus. Normally, vasopressin release is inhibited when the serum sodium concentration falls below 135 mEq/L. However, poor effective circulating volume—as sensed by carotid baroreceptors as a decrease in arterial pressure—serves as a potent stimulus for ADH secretion despite osmoregulatory inhibition. Hyponatremia in the setting of hypovolemia arises from hemodynamically driven ADH release and should improve with volume repletion. ADH secretion in the setting of arterial underfilling, due either to a low output state in the case of heart failure or to splanchnic vasodilation in cirrhosis, occurs by the same hemodynamic mechanism. These patients, conversely, will appear hypervolemic on exam. They are hyponatremic and hypotonic despite a clear excess in total body sodium content.