A 43-year-old previously healthy man is hospitalized after sustaining a head injury in a motor vehicle collision. Several days later, the patient develops worsening serum electrolyte disturbances. Further evaluation reveals the cause is inappropriate antidiuretic hormone secretion. Treatment with a vasopressin V2 receptor antagonist is initiated. Which of the following changes are most likely to occur as a direct result of the administered medication?
Show Explanatory Sources
This patient developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH) following a head injury. Antidiuretic hormone (ie, vasopressin) is normally secreted in response to elevated plasma osmolality (eg, dehydration) or decreased arterial blood volume. It stimulates the renal collecting ducts to reabsorb water back into the systemic circulation, which then lowers the serum osmolality and suppresses further ADH secretion. In SIADH, uncontrolled ADH secretion leads to excessive water reabsorption, which results in the following:
Vaptans (eg, tolvaptan) are vasopressin V2 receptor antagonists (ie, aquaretics) used to treat hyponatremia. They increase free water excretion by blocking the antidiuretic action of ADH in the kidney and have no direct effect on sodium or potassium excretion. As such, vaptans produce the following alterations that help correct SIADH:
(Choice A) Central diabetes insipidus is characterized by decreased ADH release, which causes increased plasma osmolality (ie, hypernatremia) and production of dilute urine; treatment with desmopressin, a vasopressin receptor-2 agonist, results in decreased plasma osmolality and urine output without directly affecting sodium excretion.
(Choice B) Thiazide diuretics inhibit the sodium-chloride cotransporter in the distal convoluted tubule, increasing renal excretion of sodium and water (associated with an increase in urine volume). Thiazides also increase water reabsorption in the inner medullary collecting duct, which can contribute to decreased plasma osmolality (ie, hyponatremia).
(Choice C) Volume contraction (eg, dehydration) results in increased plasma osmolality. The resulting activation of the renin-angiotensin-aldosterone system along with increased ADH secretion reduces urine output (due to ADH) and sodium excretion (due to aldosterone).
(Choice D) Mannitol is an osmotic diuretic that is used to treat acutely elevated intracerebral pressure (eg, intracranial hematoma). It raises plasma osmolality and inhibits water reabsorption in the renal tubules. Sodium excretion is variably increased due to solvent drag (high flow of water carries sodium through the tubules into urine).
Educational objective:
Vaptans (eg, tolvaptan) are vasopressin V2 receptor antagonists (ie, aquaretics) used to treat hyponatremia. Vaptans block the effects of antidiuretic hormone (vasopressin), increasing renal free water excretion without directly affecting excretion of sodium or potassium. Diuresis of free water with vaptans results in increased plasma osmolality, increased serum sodium, increased urine output, and lowered urine osmolality.