This question came via e-mail:
A couple of my classmates and I had a question regarding one of your slides (slide 39 on the Potassium, Metabolic Alkalosis presentation). We were unsure of the mechanisms that prevented bicarbonate excretion with hypokalemia, specifically decreased NaK2Cl activity in the loop of Henle and decreased NaCl resorption in the distal convoluted tubule. Could you please give us an explanation for these mechanisms?
So the reason you can’t remember a mechanism is I gave the old “just because” mechanism without much explanation.
The first step of why the the Na-K-2Cl transporter slows own in response to a low K is pretty sraight forward. Tubular potassium will fall as patients get hypokalemia. As the plasma potassium falls, less and potassium is filtered and then less potassium will be available to cycle the Na-K-2Cl pumps. The decreased activity in the loop of Henle results in more distal delivery of sodium and that drives move acid secretion and maintenance of the metabolic alkalosis.
The distal convoluted tubule is a bit more complex. Here is a diagram:
The hypokalemia stimulates the hydrogen-potassium exchanger. This generates intracellular acidosis, even though the patient has alkalosis. In order to correct the acidosis the cell slows sodium-chloride co transport so more sodium washes down stream and stimulates the hydrogen secretion, maintaining the alkalosis.
If you are looking for a deeper dive into metabolic alkalosis I recommend this review by Galla in JASN.
