Diuretics: Potassium imbalance

Loop Diuretics inhibit the Na⁺ K⁺ 2Cl^– transporter in the thick ascending limb of the Loop of Henle. Due to their mechanism of action they may result in hypokalemia. By preventing reabsorption in the Loop of Henle, increased levels of sodium are seen in the collecting duct. The increase in sodium concentration in the collecting duct stimulates action of the sodium pump, (ENaC) which reabsorbs Na⁺ in exchange for K⁺ & H⁺, which are then excreted in the urine. This sodium pump (ENac) is also sensitive to aldosterone. The volume depletion that results from the administration of loop diuretics incites aldosterone release, which then activates these channels and further potentiates the loss of K⁺ in the urine.

Thiazide Diuretics inhibit the Na⁺ Cl^– transporter in the distal convoluted tubule. Similar to the mechanism of the loop diuretic induced hypokalemia, thiazide diuretics increase the concentration of Na⁺ that reaches the collecting tubule. They also activate the renin-angiotensin-aldosterone system. Both of these mechanisms stimulate the collecting duct to reabsorb sodium in exchange for the excretion of K⁺ & H⁺.

Potassium Sparing Diuretics:

Spironolactone is a competitive aldosterone receptor antagonist. It binds aldosterone receptors in the distal tubule and decreases the effect of aldosterone on Na⁺ reabsorption and K⁺ secretion.

Amiloride and Triamterene are direct ENaC blockers. ENaC is the apical epithelial Na⁺ channel that is responsible for cellular reabsorption of Na+ from the collecting duct. When these channels are blocked Na⁺ is not reabsorbed from the collecting duct leading to a limited supply of Na⁺ available for the basolateral Na⁺ K⁺ exchange. Less Na⁺ is reabsorbed and as a result less K⁺ is excreted.