Site of Action of Loop Diuretics

Loop diuretics (e.g., furosemide) act on:

Correct Answer: Thick ascending limb of loop of Henle

Loop diuretics (e.g., furosemide, ethacrynic acid, bumetanide) act specifically on the thick ascending limb of the loop of Henle. They inhibit the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) in the luminal membrane of this segment.

Mechanism of Action

• Furosemide blocks NKCC2 → prevents reabsorption of Na⁺, K⁺, and Cl⁻ from the tubular fluid
• This disrupts the medullary osmotic gradient → less water can be reabsorbed in the collecting duct even in the presence of ADH
• Result: Large volume of isotonic/dilute urine is produced → most potent diuretics

Why Thick Ascending Limb is the Target

The thick ascending limb is the main site for creating the medullary concentration gradient via active NaCl reabsorption. Blocking it collapses the entire countercurrent concentration system, producing a dramatic diuretic effect.

Comparison of Diuretic Types

• Loop diuretics (furosemide): Thick ascending limb → Block NKCC2 → Most potent
• Thiazide diuretics (hydrochlorothiazide): DCT → Block Na⁺-Cl⁻ cotransporter
• Osmotic diuretics (mannitol): PCT → Increase tubular fluid osmolarity → inhibit water & solute reabsorption
• Potassium-sparing diuretics (spironolactone): Collecting duct → Block aldosterone