Although, the mechanism is not entirely clear, the likely hypothesis is as follows:
*Hypokalemia causes the movement of potassium out of the cells.
*To maintain electric neutrality, H+ ions move into the cells leading to intracellular acidosis (cellular ph decreases).
*This triggers the conversion of glutamine in the proximal tubule, to NH4+ and bicarbonate.
*Ammonia (NH3+ and NH4+) is selectively, either excreted in the urine or returned to the renal venous circulation (~25-45%).
*Ammonia, that subsequently enters portal circulation, is not metabolized by the cirrhotic liver, therefore likely to precipitate encephalopathy.
Conversely, high potassium levels may be protective by reducing the risk of hepatic encephalopathy. Although, somewhat speculative, this may happen in two ways
- Hyperkalemia may decrease total ammonia production in the proximal tubule by increasing intracellular ph and thereby impairing ammoniagenesis.
- Potassium competes with NH4+ for absorption by the NKCC2 transporter at the thick ascending limb of loop of henle, thereby reducing ammonia accumulation (read ammonia trapping) in the medullary interstitium and hence less ammonia available for absorption in the systemic circulation.
In an interesting study done by Zavagli et al, patients with higher potassium levels (5.4-5.5 meq/l) had a much better survival and less hepatic encephalopathy episodes as compared to patients with lower potassium levels (3.4-3.5meq/l).
While I certainly do not recommend ignoring severe or symptomatic hyperkalemia in liver cirrhosis patients, educating physicians about aggressive correction of hypokalemia, rather than mild hyperkalemia, may serve these patients best.
Viresh Mohanlal, MD