Whatever the mechanism(s), the clinical ramifications of these physiological observations have not been explored fully. Testing a panel of known gut or pituitary peptide hormones did not reveal a likely culprit. It has been hypothesized to be a peptide hormone or a centrally mediated reflex, but one cannot discount the possibility that there is no mystery factor and instead the error signal driving kaliuresis is a small increase in the potassium concentration in the renal peritubular capillaries, not readily detectable by venous sampling. The gut-responsive ‘kaliuretic factor’ has not been identified. Enteral loads elicited a kaliuretic response of greater magnitude. In one particularly meticulous study, potassium loads were administered to rats via an enteral or intravenous route in such a way as to induce identical increases in plasma. This provides evidence for an aldosterone-independent, gut-to-kidney feedforward kaliuretic signal (Prong 3).Īlthough only recently confirmed in humans, this mode of feedforward control has been known about for several decades in sheep and has been studied in some detail in rodents. Despite there being no change in venous plasma, there was an increase in renal potassium excretion, which was not prevented by treatment with the mineraolocorticoid receptor (MR) antagonist eplerenone. When the same potassium load was administered as part of a complex meal, there was no change in plasma, probably reflecting insulin-mediated transcellular potassium shifts (Prong 2). When subjects were administered 35 mmol K +, plasma rose by ∼0.5 mM and was accompanied by increases in plasma and renal K + excretion (Prong 1: the classic aldosterone-dependent negative feedback loop). ![]() Recent studies in healthy human subjects have helped to delineate three prongs to the response to a dietary potassium load. Thus the large intracellular potassium store constitutes a potential threat but is also a lifesaving buffer. We survive the banana smoothie because of a rapid response that shifts potassium into cells and into the urine. Without this defence, we would rarely make it past breakfast: a banana smoothie delivering 35 mmol of potassium to an extracellular fluid volume of 12 L would induce a potentially fatal e increase of ∼3 mM. Ĭonsequently we have evolved robust mechanisms to defend against potassium influx into the extracellular space (reviewed in McDonough and Youn ). A modern Western diet contains ∼120 mmol potassium per day and throughout most of our evolutionary history this was a great deal more (∼300 mmol per day in the palaeolithic diet). The second is external: our potassium-rich diet. ![]() The first is internal: 98% of total body potassium (3–4 mol) is stored within cells, predominantly skeletal muscle. This control is under continual threat from two sources of potassium influx. ![]() The extracellular potassium concentration, e, is kept under tight control to maintain the resting membrane potential (RP) of excitable cells. The three-pronged response to an acute potassium load The newer potassium binders could play a role in attempts to minimize reduced prescribing of renin–angiotensin inhibitors and mineraolocorticoid antagonists in this context. Hyperkalemia-or the fear of hyperkalemia-contributes to the underprescription of potentially beneficial medications, particularly in heart failure. ![]() In addition to its well-established effects on cardiac excitability, hyperkalemia could also contribute to peripheral neuropathy and cause renal tubular acidosis. Hyperkalemia is associated with an increased risk of death, and this is only in part explicable by hyperkalemia-induced cardiac arrhythmia. Accordingly, the major risk factors for hyperkalemia are renal failure, diabetes mellitus, adrenal disease and the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or potassium-sparing diuretics. Hyperkalemia occurs when renal potassium excretion is limited by reductions in glomerular filtration rate, tubular flow, distal sodium delivery or the expression of aldosterone-sensitive ion transporters in the distal nephron. We highlight aspects that are of particular relevance for clinical practice. In this article we discuss these advances within a concise review of the pathophysiology, risk factors and consequences of hyperkalemia. There have been significant recent advances in our understanding of the mechanisms that maintain potassium homoeostasis and the clinical consequences of hyperkalemia.
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