A 62-year-old man comes to the emergency department with severe shortness of breath and orthopnea. His medical history is significant for long-standing hypertension and myocardial infarction a year ago. Physical examination reveals elevated jugular venous pressure, crackles on lung auscultation, and pitting edema of the lower extremities. The patient is given a medication and experiences brisk diuresis with significant symptom relief. The drug most likely used to treat this patient's condition predominantly acts on which of the following nephron segments?
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This patient with dyspnea and volume overload (ie, elevated jugular venous pressure, edema, lung crackles) has acute decompensated heart failure. Patients with heart failure and volume overload are typically treated with loop diuretics due to their potent natriuretic effect, which helps reduce vascular congestion and peripheral edema.
Loop diuretics (eg, furosemide, torsemide, bumetanide) inhibit the Na-K-2Cl symporter in the apical membranes of cells in the thick ascending limb of Henle's loop. Blockade of Na+ and Cl− reabsorption from the tubular lumen decreases the medullary concentration gradient, impairing the kidney's ability to concentrate urine and increasing the overall excretion of Na+, Cl−, and H2O. Adverse effects of loop diuretics include electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) and ototoxicity.
(Choice A) Carbonic anhydrase inhibitors (acetazolamide) block the reabsorption of NaCl and NaHCO3 in the proximal tubule. They are weak diuretic agents typically used to treat glaucoma and altitude sickness.
(Choice B) Mannitol is a nonreabsorbable sugar alcohol that functions as an osmotic diuretic by decreasing sodium and water reabsorption by the proximal tubule and descending limb of the loop of Henle. It is used for treating cerebral edema, but causes initial intravascular volume expansion that can worsen pulmonary edema and heart failure.
(Choice D) Thiazide diuretics act by inhibiting NaCl reabsorption in the distal convoluted tubule. Compared to the loop of Henle, this segment reabsorbs only a small proportion of the filtered NaCl load, leading to a smaller natriuretic effect than loop diuretics. Thiazides are mostly used to treat hypertension and are not as effective as loop diuretics for reducing volume overload in heart failure.
(Choice E) The collecting tubules and ducts are the primary site of action of sodium channel blockers (eg, amiloride, triamterene) and aldosterone receptor antagonists (eg, spironolactone, eplerenone). These are weak diuretics that are not effective for diuresis in patients with decompensated heart failure. However, long-term use of aldosterone receptor antagonists improves survival in patients with severe left ventricular systolic dysfunction.
Educational objective:
Loop diuretics act by inhibiting the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle, increasing Na+, Cl−, and H2O excretion. They are the most potent diuretics and are used as first-line therapy for rapid relief of symptoms in patients with acute decompensated heart failure.