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OUWB student question on ammonium production and potassium

How does hyperkalemia or even alkalosis suppress NH3 production?

So the mechanism is not completely worked out but the conventional explanation is…

Hypokalemia causes potassium to shift out of the cells. Hydrogen ions then move on the opposite direction into cells to maintain electroneutrality.

This causes intracellular acidosis. The intracellular acidosis causes the cells of the proximal tubule to erroneously concludes that there is systemic acidosis and so they up regfulate the production of NH4 to increase renal excretion of acid and produce new bicarbonate.

An interesting note about this happens in liver failure. Patients with liver failure are unable to metabolize ammonia and levels build up to high concentrations and can cause hepatic encephalopathy. A known risk factor for this is hypokalemia. The above paragraph provides an explanation for this.

Conclusion from a recent study on this phenomena (Ref)

Hyperkalemia works the same way but in reverse. Potassium shifts into the cells, This causes hydrogen to move out of the cells and causes intracellular alkalosis. The cell mistakes this intracellular alkalosis for systemic alkalosis and the last thing the kidney wants to do in systemic alkalosis is generate additional bicarb, so it down regulates this generation of ammonium.

Slide 97 from Monday’s lecture