A 43-year-old man comes to the office due to swelling of the legs and abdomen. The patient has a history of alcohol-induced cirrhosis, and his ascites had been well controlled with furosemide. Over the past week, he has had increasing bilateral lower extremity and abdominal swelling despite taking a diuretic as prescribed. The patient reports no change in dietary sodium or water intake but states he has been taking over-the-counter ibuprofen after injuring his back recently. He stopped drinking alcohol 2 years ago and does not use tobacco or illicit drugs. Physical examination shows 3+ bilateral lower extremity edema and moderate ascites. Which of the following changes most likely contributed to the acute deterioration in this patient's condition?

Question

Quizplus · Accepted Answer

Furosemide is a loop diuretic that binds to Na-K-2Cl symporters in the ascending limb of the loop of Henle and effectively blocks Na and Cl transport, resulting in increased Na, Cl, and fluid excretion. Loop diuretics also stimulate prostaglandin release, which increases renal plasma flow (RPF), leading to increased glomerular filtration rate (GFR) and drug delivery to the loop of Henle. Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen, naproxen, indomethacin) inhibit prostaglandin synthesis (resulting in decreased renal prostaglandin levels). In healthy patients, prostaglandin synthesis is low and NSAID use has minimal effects on renal hemodynamics. However, patients with intravascular volume depletion (eg, cirrhosis, congestive heart failure, dehydration) are dependent on the vasodilatory effects of prostaglandins to maintain adequate RPF and GFR. Therefore, NSAID use in this population leads to markedly decreased GFR and RPF. Reduced fluid and electrolyte delivery to renal tubules reduces the efficacy of loop diuretics, resulting in reduced urinary sodium excretion and fluid retention (eg, ascites, edema, as occurred in this patient). Similar effects can occur in patients with chronic kidney disease; therefore, NSAIDs should generally be avoided in all patients with renal disease or reduced effective arterial volume. (Choices B, C, D, and E) NSAIDs inhibit prostaglandin synthesis, resulting in renal vasoconstriction and decreased GFR. This limits the efficacy of loop diuretics, leading to reduced urinary sodium excretion and fluid retention (promoting the formation of ascites and edema). Educational objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis. Patients with intravascular volume depletion (eg, cirrhosis) are dependent on the vasodilatory effects of prostaglandins to maintain adequate renal plasma flow and glomerular filtration. NSAID use in this population reduces glomerular filtration rates and blunts the effects of loop diuretics, leading to sodium and water retention.

A 43-Year-Old Man Comes to the Office Due to Swelling