Loop diuretics (eg, furosemide) are sometimes abused by patients with eating disorders (eg, anorexia nervosa, bulimia nervosa) in an effort to lose weight.  These drugs inhibit the Na⁺-K⁺-2Cl⁻ transporter in the loop of Henle, resulting in increased urinary excretion of Na⁺, Cl⁻, K⁺, and water.  These changes in electrolyte handling also increase renal H⁺ excretion, leading to metabolic alkalosis (elevated serum HCO₃⁻).  Overuse of loop diuretics leads to massive electrolyte and fluid losses with intravascular volume depletion and activation of the renin-angiotensin-aldosterone system.  This secondary hyperaldosteronism stimulates increased Na⁺ reabsorption in the renal tubular collecting duct, as well as a lesser degree of passive Cl⁻ reabsorption.  The relatively high loss of Cl⁻ that occurs is responsible for a characteristic hypochloremia.

Secondary hyperaldosteronism also stimulates increased K⁺ and H⁺ excretion in the collecting duct, exacerbating the hypokalemia and metabolic alkalosis.  The alkalosis is further compounded by an angiotensin II-mediated increase in proximal tubule sodium bicarbonate reabsorption.  Chloride depletion then perpetuates the alkalosis because low Cl⁻ levels in the tubular lumen impair HCO₃⁻ excretion via the pendrin Cl⁻/HCO₃⁻ exchanger on beta intercalated cells in the collecting duct.

The urine electrolyte findings in loop diuretic abuse depend on how recently the medication was last ingested.  Within several hours after ingestion (as in this patient with positive urine screening), increased urine Na⁺, Cl⁻, and K⁺ is expected.  Once the medication effect wears off, urine Na⁺ and urine Cl^- are low as the kidneys attempt to increase blood volume.  Urine K⁺ is likely to remain increased due to ongoing aldosterone-mediated losses (Choice C).

(Choices B, D, and E)  Because Cl⁻ and HCO₃⁻ are the most abundant anions in the body, they are the primary determinants of total body electronegativity.  Therefore, when one of these anions is depleted the kidneys and intestines retain the other to maintain electronegative balance.  This results in a typical inverse relationship between serum Cl⁻ and serum HCO₃⁻ levels (when one is low the other tends to be elevated).  The presence of additional anions in the body (eg, anion gap metabolic acidosis) may disrupt this relationship.

Educational objective:
Overuse or abuse of loop diuretics (eg, furosemide) characteristically causes hypokalemic, hypochloremic metabolic alkalosis.  Urine electrolyte findings depend on how recently the diuretic was last ingested; increased urine Na⁺, Cl⁻, and K⁺ are expected with recent ingestion.