A Physiologic-Based Approach to the Evaluation of a Patient With Hyperkalemia

The renin-angiotensin-aldosterone system and regulation of renal potassium (K⁺) excretion. Aldosterone binds to a cytosolic receptor in the principal cell and stimulates sodium (Na⁺) reabsorption across the luminal membrane through a well-defined sodium channel. As sodium is reabsorbed, the electronegativity of the lumen increases, thereby providing a more favorable driving force for potassium secretion through an apically located potassium channel. The permeability of the anion that accompanies sodium also influences potassium secretion, with less permeable anions having a greater stimulatory effect on potassium secretion. Disease states or drugs that interfere at any point along this system can impair renal potassium secretion and increase the risk of hyperkalemia. In many patients, this risk is magnified because of disturbances at multiple sites along this system. Abbreviation: NSAID, nonsteroidal anti-inflammatory drug.