The hypokalemic, bowel, bladder, headache relationship; a new syndrome. The role of the potassium ammonia axis.

A conceptual approach that relates vascular headaches, bowel and bladder dysfunction to abnormalities of the "ammonia potassium axis" is presented. Hypokalemia alters smooth muscle function of both the bowel and bladder and results in the elaboration of an alkaline urine. The occurrence of an alkaline urine, along with bladder dysfunction and urinary stasis, predisposes to recurrent urinary tract infections. Hypokalemia and/or alkalosis increases the renal return of ammonia, exposes the brain to chronically higher concentration of ammonia and facilitates its passage into the central nervous system. Increased levels of blood ammonia predispose to hyperventilation which results in a superimposed respiratory alkalosis on a pre-existing hypokalemia and/or alkalosis therefore causing intense cerebral vasoconstriction. Varying degrees of cerebral ischemia and hypoxia occur and give rise to higher brain concentrations of ammonia. Vasodilatation occurs during the headache phase and may be a consequence of the sudden increase of brain ammonia and/or due to the release of other vasoactive mediators. As a consequence of increased blood ammonia, a reduction of protein intake may result in the alterations of amino acid precursors for brain uptake and therefore further interferes with the modulation of cerebral blood flow and brain function.