Mechanisms of Hypokalemia
There are several mechanisms by which thiazide diuretics cause hypokalemia (decreased plasma potassium concentration):
- Increased delivery of sodium to the collecting ducts causes increased cellular uptake of Na from the lumen by apical Epithelial Na Channels (ENaCs). This then causes the basolateral Na/K exchanger to more actively exchange Na for K, which is then passively secreted into the lumen through apical channels, resulting in K loss. (Moreover, the increased delivery of K to the collecting ducts facilitates the exchange of K for H by the H/K exchangers on the intercalated alpha cells, resulting in loss of H .)
- Activation of renin-angiotensin-aldosterone system by the diuretic hypovolemia: body responds to hypovolemia by opposing diuresis, one effect of which is to produce aldosterone which stimulates the Na/K exchanger, resulting in further loss of potassium. For this reason, ACE inhibitors, which inhibit angiotensin II production and therefore aldosterone activation, are frequently used in combination with thiazides to combat hypokalemia.
- Flow rate in nephron is increased under diuresis, reducing potassium concentration in the lumen, thus increasing the potassium gradient. Potassium loss through the many potassium channels, such as ROMK. These are not exchangers; they allow facilitated diffusion, so the increased gradient is directly responsible for increased diffusion.
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