Getting ready for the United States Medical Licensing Examination® (USMLE®) Step 1 is no easy feat, but we’re sharing expert insights to help give you a leg up. Take a look at the exclusive scoop on this month’s most-missed USMLE Step 1 test prep question. Think you have what it takes to rise above your peers? Test your USMLE knowledge, and view an expert video explanation of the answer from Kaplan Medical. View other posts in series.
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This month’s question that stumped most students
An investigational oral contraceptive causes less weight gain than other oral contraceptives because it contains a unique progestin that blocks mineralocorticoid receptors. One hundred consecutive female participants are instructed to take 21 days of active pills, starting at Day 0, containing the progestin and ethinyl estradiol, followed by seven days of placebo. Based on the data shown, which of the following parameters is most likely being measured?
B. Angiotensin II
The correct answer is D.
Kaplan says, here’s why
Since the new investigational combination drug (progestin/ethinyl estradiol) is blocking mineralocorticoid receptors, the actions of aldosterone will be antagonized during the first 21 days of the cycle. Sodium reabsorption and the secretion of potassium and hydrogen ion should be diminished, decreasing potassium and hydrogen ions in the urine. It is important to note that the graph is measuring urine potassium levels, not serum potassium levels. Since many actions of mineralocorticoids are relatively slow and because the progestin will require several days to rise to steady state levels, its effect on urine potassium excretion will not be instantaneous but will gradually increase during the drug treatment.
Why you shouldn’t choose the other answers
Read these explanations to understand the important rationale for each answer to help you prepare with future studying.
Choices A and B: Urinary levels of aldosterone and angiotensin II would be expected to be elevated during the first 21 days because suppression of the response to aldosterone decreases blood pressure. Reduced blood pressure releases the renin-angiotensin-aldosterone system from the normal negative feedback; higher plasma aldosterone causes higher urinary aldosterone excretion. The mechanism of the aldosterone response is increased renin secretion, with increased production of angiotensin II. Angiotensin II has a very short plasma half-life (about 30 seconds); normal urinary excretion is very low, about 20 pmol/24 hours. Increased plasma renin activity and the consequent increased production of angiotensin II would increase rather than decrease urinary angiotensin II levels. Estrogens increase hepatic production of angiotensinogen, leading to an increase in angiotensin II and aldosterone. Also, increased plasma potassium caused by decreased renal excretion is a potent stimulus for aldosterone secretion.
Choice C: Since there are less hydrogen ions in the urine, the urinary pH would increase in the first 21 days of the cycle.
Choice E: Since sodium reabsorption would be impaired, urinary levels of sodium would be expected to increase.
Key points to remember
- An antagonist at mineralocorticoid receptors will block the actions of aldosterone. If administered as a contraceptive, this occurs during the first 21 days of the menstrual cycle.
- Sodium reabsorption and potassium and hydrogen ion secretion would be diminished, decreasing potassium and hydrogen ions in the urine.
- Compensatory responses to aldosterone receptor blockers include increased plasma renin activity, angiotensin II production and aldosterone secretion.