USMLE practice question #131 will test your understanding of the principles of renal physiology.
I’m Paul Ciurysek, MD, founder of The USMLE Guys! This daily newsletter aims to provide super high-yield USMLE concepts commonly tested on exam day. All content is FREE! If you’d like more help with your USMLE preparation, please see the options at the bottom of today’s newsletter. Please share the newsletter with a friend if you’d like to support our efforts!
A 32-year-old woman presents to the clinic with polyuria and nocturia. Laboratory studies reveal hypernatremia and dilute urine with a low osmolality. Her symptoms persist despite adequate water intake. Further evaluation reveals normal serum antidiuretic hormone (ADH) levels. A defect in which segment of the nephron is most likely responsible for her inability to concentrate urine?
A) Proximal tubule
B) Thin descending limb of the loop of Henle
C) Thin ascending limb of the loop of Henle
D) Thick ascending limb of the loop of Henle
E) Collecting duct
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “A defect in which segment of the nephron is most likely responsible for her inability to concentrate urine?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the problem; 2nd: Identify the underlying cause of the diagnosis.
Step 3: Read the vignette carefully and ask yourself: “Based on the presentation, the part of the kidney responsible is most likely the __________________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This 32-year-old woman presents with polyuria, nocturia, hypernatremia, and dilute urine with low osmolality, indicating an inability to concentrate urine. Her symptoms persist despite adequate water intake, and serum antidiuretic hormone levels are normal. These findings suggest a defect in the renal mechanisms responsible for concentrating urine.
ANSWER CHOICES:
CHOICE A: Proximal tubule
Explanation: The proximal tubule is responsible for reabsorbing approximately 65–70% of filtered sodium, water, and other solutes. This process is iso-osmotic, meaning that water reabsorption occurs in proportion to solute reabsorption, and it does not contribute to the generation of a concentration gradient. While the proximal tubule is essential for bulk reabsorption, it does not play a direct role in generating the medullary concentration gradient required for urine concentration.
CHOICE B: Thin descending limb of the loop of Henle
Explanation: The thin descending limb is permeable to water but impermeable to solutes. Water moves out of the tubule into the hypertonic medullary interstitium, concentrating the tubular fluid. While this segment contributes to concentrating tubular fluid, it relies on the medullary concentration gradient established by the thick ascending limb. A defect here would not explain dilute urine with normal ADH levels.
CHOICE C: Thin ascending limb of the loop of Henle
Explanation: The thin ascending limb is impermeable to water but allows passive reabsorption of sodium and chloride into the medullary interstitium. This contributes to maintaining the medullary concentration gradient. This segment plays a minor role compared to the thick ascending limb in generating the medullary concentration gradient. A defect here would not fully account for this patient’s inability to concentrate urine.
CHOICE D: Thick ascending limb of the loop of Henle
Explanation: The thick ascending limb actively reabsorbs sodium, potassium, and chloride via the Na⁺/K⁺/2Cl⁻ cotransporter and is impermeable to water. This process creates a hypertonic medullary interstitium, which is essential for water reabsorption in the collecting duct under the influence of ADH. A defect in this segment disrupts the medullary concentration gradient, impairing urine concentration even when ADH levels are normal. This explains this patient’s inability to concentrate urine.
CHOICE E: Collecting duct
Explanation: The collecting duct is where ADH exerts its effects by increasing water permeability via aquaporin insertion into the apical membrane. If ADH levels are normal but water reabsorption is impaired, a defect in earlier nephron segments (e.g., thick ascending limb) that generate the medullary gradient is more likely responsible. The patient has normal ADH levels, so a primary defect in ADH action (e.g., nephrogenic diabetes insipidus) or aquaporin function is unlikely. The issue lies upstream in generating a hypertonic medullary interstitium.
FINAL VERDICT…
CORRECT ANSWER: D) Thick ascending limb of the loop of Henle
The thick ascending limb actively reabsorbs sodium, potassium, and chloride while being impermeable to water, creating a hypertonic medullary interstitium necessary for concentrating urine. A defect here prevents proper generation of this gradient, leading to dilute urine even when ADH levels are normal.
KEY CONCEPTS:
Role of Nephron Segments in Urine Concentration:
Proximal tubule: Bulk iso-osmotic reabsorption.
Thin descending limb: Water reabsorption driven by medullary hypertonicity.
Thick ascending limb: Active Na⁺/K⁺/2Cl⁻ transport creates a hypertonic medulla (impermeable to water).
Collecting duct: ADH-dependent water reabsorption based on medullary gradient.
Thick Ascending Limb Function:
Active transport via Na⁺/K⁺/2Cl⁻ cotransporter.
Impermeability to water ensures dilution of tubular fluid.
Essential for generating and maintaining the medullary osmotic gradient.
Consequences of Defects in Thick Ascending Limb:
Impaired medullary osmotic gradient disrupts water reabsorption in collecting ducts.
Results in polyuria, nocturia, and dilute urine despite normal or elevated ADH levels.
Seen in conditions such as Bartter syndrome or loop diuretic use.
Differential Diagnosis for Polyuria with Dilute Urine:
Central diabetes insipidus (low ADH production).
Nephrogenic diabetes insipidus (renal resistance to ADH).
Defects in thick ascending limb impairing medullary gradient formation.
1) 1-ON-1 STRATEGY SESSION: CLICK HERE TO SET UP YOUR 1-ON-1 STRATEGY SESSION
2) TEST-TAKING SKILLS & RESIDENCY MASTERCLASSES: LEARN ABOUT THE MASTERCLASSES HERE
3) ASSESSMENT EXAMS: CLICK FOR USMLE STEP 1, STEP 2, & CLINICAL SHELF EXAMS
4) USMLE DRILLS BOOKS: CLICK HERE FOR THE STEP 1 BOOK, OR HERE FOR THE STEP 2 CK BOOK.
See ya tomorrow 👋