Loop diuretics achieve their diuretic effect by blocking which ion transporter in the thick ascending limb of the loop of Henle?

Explanation

## Loop Diuretics: Mechanism of Action **Key Point:** Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid) inhibit the **Na⁺-K⁺-2Cl⁻ cotransporter** (NKCC2) in the thick ascending limb of the loop of Henle. ### Why the Thick Ascending Limb? The thick ascending limb is responsible for: - Reabsorption of ~25% of filtered sodium (the highest single-segment reabsorption) - Generation of the positive electrical potential that drives paracellular calcium and magnesium reabsorption - Creation of the osmotic gradient for the countercurrent multiplier system **High-Yield:** Blocking this transporter causes the **greatest diuretic effect** of any drug class — loop diuretics are the most potent diuretics available. ### Comparison of Transporter Targets | Diuretic Class | Transporter | Nephron Segment | % Na⁺ Reabsorbed | | --- | --- | --- | --- | | Loop diuretics | Na⁺-K⁺-2Cl⁻ cotransporter | Thick ascending limb | ~25% | | Thiazides | Na⁺-Cl⁻ cotransporter | Distal convoluted tubule | ~5% | | K⁺-sparing | Epithelial Na⁺ channel (ENaC) | Collecting duct | ~2% | **Mnemonic:** **THICK LOOP = MOST REABSORPTION** — The thick ascending limb reabsorbs the most sodium, so blocking it causes the most diuresis. **Clinical Pearl:** Loop diuretics are the only diuretics effective in severe renal impairment (GFR <30 mL/min) because they are secreted into the tubular lumen via organic anion transporters, independent of glomerular filtration.