USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

How do loop diuretics impact Tubuloglomerular Feedback?

1. They increase GFR by stimulating vasoconstriction

2. They decrease urine production by blocking tubular feedback

3. They blunt tubuloglomerular feedback, maintaining GFR despite increased NaCl traffic

4. They enhance tubular reabsorption, reducing GFR

The correct answer is: They blunt tubuloglomerular feedback, maintaining GFR despite increased NaCl traffic

Loop diuretics primarily act on the thick ascending limb of the loop of Henle, where they inhibit the Na⁺-K⁺-2Cl⁻ co-transporter. This results in decreased reabsorption of sodium and chloride, leading to an increase in their concentration in the distal convoluted tubule and a higher load likely reaching the macula densa. In this context, tubuloglomerular feedback refers to the mechanism by which the composition and flow of fluid in the nephron influence the glomerular filtration rate (GFR). When sodium chloride concentration increases in the distal tubular fluid, the macula densa cells sense this change and send signals (such as adenosine production) that lead to afferent arteriolar constriction. This, in turn, helps to maintain GFR by reducing renal blood flow. However, loop diuretics can blunt this feedback mechanism. They increase the delivery of sodium chloride to the macula densa, but instead of triggering the normal compensatory response (i.e., arteriolar constriction and GFR adjustment), the pre-existing increase in sodium and chloride leads to a less responsive feedback effect in maintaining GFR. Thus, GFR may remain elevated despite this increased