A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 32-year-old woman with type 1 diabetes mellitus is brought to the emergency department by her husband because of a 2-day history of profound fatigue and generalized weakness. One week ago, she increased her basal insulin dose because of inadequate control of her glucose concentrations. Neurologic examination shows hyporeflexia. An ECG shows T-wave flattening and diffuse ST-segment depression. Which of the following changes are most likely to occur in this patient's kidneys?
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A
Increased activity of H+/K+ antiporter in α-intercalated cellsCorrect. In hypokalemia, alpha-intercalated cells upregulate the apical H+/K+-ATPase to reabsorb K+ while secreting H+, producing metabolic alkalosis and paradoxical aciduria.
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B
Decreased activity of epithelial Na+ channels in principal cellsIncorrect. ENaC in principal cells is regulated by aldosterone and would not be selectively decreased in hypokalemia - and decreasing ENaC would impair Na+ reabsorption rather than conserve K+.
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C
Decreased activity of Na+/H+ antiporter in the proximal convoluted tubuleIncorrect. Na+/H+ antiporter activity in the PCT typically increases in metabolic alkalosis (as compensation) but is not the principal renal response to hypokalemia.
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D
Increased activity of luminal K+ channels in principal cellsIncorrect. Luminal K+ channels (ROMK) in principal cells are DOWN-regulated in hypokalemia to reduce K+ secretion and conserve potassium; the question's option says increased, which is opposite.
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E
Increased activity of Na+/K+-ATPase in principal cellsIncorrect. Basolateral Na+/K+-ATPase activity in principal cells drives K+ secretion; in hypokalemia the kidney downregulates K+ secretion to conserve potassium, so increased activity is the opposite of the expected adaptation.
↑ Tap an answer to reveal the reasoning
Answer: A. A type 1 diabetic with profound weakness, hyporeflexia, and ECG showing T-wave flattening and diffuse ST depression has hypokalemia. The setup is excess basal insulin a week prior, which drives potassium intracellularly (insulin stimulates the Na/K-ATPase on skeletal muscle and adipose). The ECG findings of T-wave flattening, U waves, ST depression, and prolonged QT all reflect potassium depletion. Hyporeflexia is consistent with neuromuscular dysfunction from low extracellular K+.
The kidney's response to hypokalemia centers on the alpha-intercalated cells of the collecting duct. These cells express the H+/K+-ATPase on their apical (luminal) membrane, which reabsorbs filtered K+ in exchange for secreting H+ into the urine. In hypokalemia this antiporter is upregulated, generating a metabolic alkalosis (the classic hypokalemic alkalosis seen with diuretic abuse, vomiting, or hyperaldosteronism) and producing paradoxical aciduria.
The other choices describe responses that would worsen, not correct, hypokalemia. ENaC activity in principal cells is upregulated (not decreased) by aldosterone, but the net K+ effect in principal cells in hypokalemia is to reduce K+ secretion - meaning luminal K+ channels (ROMK) are decreased, not increased. Na+/H+ antiporter activity in the PCT typically increases in alkalosis, not decreases. Therefore alpha-intercalated cell H+/K+-ATPase upregulation is the correct mechanism.
**Why each option:**
**A.** Correct. In hypokalemia, alpha-intercalated cells upregulate the apical H+/K+-ATPase to reabsorb K+ while secreting H+, producing metabolic alkalosis and paradoxical aciduria.
**B.** ENaC in principal cells is regulated by aldosterone and would not be selectively decreased in hypokalemia - and decreasing ENaC would impair Na+ reabsorption rather than conserve K+.
**C.** Na+/H+ antiporter activity in the PCT typically increases in metabolic alkalosis (as compensation) but is not the principal renal response to hypokalemia.
**D.** Luminal K+ channels (ROMK) in principal cells are DOWN-regulated in hypokalemia to reduce K+ secretion and conserve potassium; the question's option says increased, which is opposite.