Clinical meaning
Potassium is the primary intracellular cation, with 98% of total body potassium (~3,500 mEq) residing inside cells and only 2% (~70 mEq) in the extracellular fluid, maintaining a normal serum concentration of 3.5-5.0 mEq/L. This steep concentration gradient across cell membranes (intracellular K+ ~150 mEq/L vs extracellular ~4 mEq/L) is maintained by the Na+/K+-ATPase pump, which actively transports 3 Na+ out and 2 K+ into cells with each cycle, and is essential for establishing the resting membrane potential (-70 to -90 mV) that governs cardiac, neural, and skeletal muscle excitability. Potassium homeostasis is regulated through two mechanisms: internal balance (transcellular shifting) and external balance (renal excretion). Internal balance is modulated by insulin (drives K+ into cells via Na+/K+-ATPase stimulation), beta-2 adrenergic catecholamines (shift K+ intracellularly), aldosterone (promotes both renal excretion and cellular uptake), and acid-base status (acidosis causes H+/K+ exchange pushing K+ out of cells, raising serum K+; alkalosis does the opposite). External balance is predominantly renal: 90% of daily potassium excretion occurs through the kidneys, primarily via secretion in the cortical collecting duct principal cells regulated by aldosterone. Aldosterone binds mineralocorticoid receptors, upregulating epithelial sodium channels (ENaC) and Na+/K+-ATPase activity, thereby increasing K+ secretion into the tubular lumen. Hypokalemia (K+ <3.5 mEq/L) hyperpolarizes cell membranes, making them less excitable, manifesting as skeletal muscle weakness, ileus, and cardiac conduction abnormalities (U waves, flattened T waves, ST depression, prolonged QT interval, predisposition to torsades de pointes and digitalis toxicity). Hyperkalemia (K+ >5.0 mEq/L) partially depolarizes cell membranes, initially increasing excitability (peaked T waves, shortened QT) but progressively impairing conduction (widened QRS, loss of P waves, sine wave pattern) and ultimately causing ventricular fibrillation or asystole. The cardiac toxicity of hyperkalemia is the primary clinical emergency because the ratio of intracellular to extracellular potassium determines cardiac membrane potential — rapid changes in serum K+ are more dangerous than chronically elevated levels.