A Practical and Pathophysiologic Approach to Hypokalemia

Hypokalemia is not an isolated disease but an associated finding in a vast number of different diseases; it poses a great challenge in correct diagnosis and proper management. Hypokalemia usually arises from a shift of potassium (K+) into cells and/or a net loss of K+. Besides a detailed history and physical examination, measurement of K+ excretion rate with freshly-voided and/or 24-hour urine and assessment of blood acid-base status can help discriminate between the various causes of hypokalemia. In patients with a low rate of K+ excretion, hypokalemia can be due to an acute shift of K+ into cells, intestinal/sweating K+ loss, or prior renal K+ excretion. In patients with a high rate of K+ excretion, there may be either increased flow rate or increased K+ secretion, seen with fast sodium (Na+) or slow chloride (Cl−) disorders, in the cortical collecting ducts (CCD). An increased flow rate in the CCD arises from increased osmole excretion (whether solutes or electrolytes). Patients with fast Na+ disorders have a high extracellular fluid (ECF) volume and thus high blood pressure associated with a state of high mineralocorticoid activity. Measurement of renin activity, aldosterone, and cortisol levels in plasma helps distinguish between the causes. Patients with slow Cl− disorders usually have low to normal ECF volume and blood pressure and are usually associated with abnormal acid-base states. In patients with metabolic alkalosis, urine Na+ and Cl− excretion rate reveal the basis for renal Na+ wasting and distinguish it from non-renal Na+ loss. In patients with hyperchloremic metabolic acidosis, an assessment of the ammonium excretion rate (NH4+) separates those with renal tubular acidosis (low NH4+ excretion) from those with other causes. The treatment of hypokalemia depends on the degree and timing of hypokalemia, clinical manifestations, underlying causes, and potential risks from associated conditions.