Potassium homeostasis - Physiology and pharmacology in a clinical context

Membrane voltage controls the function of excitable cells and is mainly a consequence of the ratio between the extra- and intracellular potassium concentration. Potassium homeostasis is safeguarded by balancing the extra-/intracellular distribution and systemic elimination of potassium to the dietary potassium intake. These processes adjust the plasma potassium concentration between 3.5 and 4.5 mmol/L. Several genetic and acquired diseases but also pharmacological interventions cause dyskalemias that are associated with increased morbidity and mortality. The thresholds at which serum K⁺ not only associates but also causes increased mortality are hotly debated. We discuss physiologic, pathophysiologic, and pharmacologic aspects of potassium regulation and provide informative case vignettes. Our aim is to help clinicians, epidemiologists, and pharmacologists to understand the complexity of the potassium homeostasis in health and disease and to initiate appropriate treatment strategies in dyskalemic patients.