What is the mechanism of action of loop diuretics?

Loop diuretics function primarily by inhibiting the Na+/K+/2Cl− cotransporter located in the thick ascending limb of the loop of Henle. This action prevents sodium, potassium, and chloride reabsorption from the renal tubule back into the bloodstream, leading to an increase in the osmotic concentration of tubular fluid. As a result, more water remains in the renal tubule, ultimately promoting diuresis (increased urine production).

This mechanism is particularly effective because the loop of Henle is a critical site for electrolyte reabsorption, and blocking this transporter disrupts the countercurrent multiplier system in the kidney, affecting the kidney's ability to concentrate urine. Thus, the diuretic effect is potent and results in significant fluid loss.

Understanding the specific action of loop diuretics helps appreciate their role in conditions such as heart failure, where rapid fluid removal is essential, and explains why they are a first-line treatment in such scenarios.