What are the causes of hypokalemia (low potassium levels)?

Causes of Hypokalemia

Hypokalemia (serum potassium <3.5 mEq/L) results from four primary mechanisms: inadequate intake, excessive renal losses, gastrointestinal losses, or transcellular shifts—with diuretic therapy being the single most common cause in clinical practice. 1

Major Etiologic Categories

Renal Potassium Losses

Medications are the predominant cause of renal potassium wasting:

• Loop diuretics (furosemide, bumetanide, torsemide) inhibit sodium and chloride reabsorption in the ascending limb of the loop of Henle, causing significant hypokalemia and metabolic alkalosis 1
• Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubule, leading to potassium depletion 1
• Diuretic therapy represents the most frequent cause of potassium deficiency in clinical practice, with deficits typically ranging 200-300 mEq 1, 2

Endocrine disorders causing inappropriate aldosterone activity:

• Primary hyperaldosteronism causes inappropriate aldosterone production, leading to hypertension with hypokalemia in 8-20% of hypertensive patients 1
• Secondary hyperaldosteronism occurs in volume-depleted states, including patients with high-output stomas or fistulas 1
• Bartter syndrome and Gitelman syndrome are genetic tubular disorders causing renal potassium wasting 1

Magnesium deficiency causes renal potassium wasting through dysfunction of potassium transport systems, making hypokalemia resistant to correction until magnesium is restored 1, 3

Gastrointestinal Losses

• Vomiting causes hypokalemia primarily through renal losses driven by metabolic alkalosis and secondary hyperaldosteronism, not through direct gastric fluid loss 1
• Diarrhea results in direct potassium losses from intestinal secretions 1, 4
• High-output fistulas, particularly enterocutaneous fistulas, can cause substantial potassium depletion 1

Transcellular Shifts

Potassium moves from extracellular to intracellular compartments without total body depletion:

• Insulin excess drives potassium into cells 1, 4
• Beta-agonist therapy (albuterol, terbutaline) promotes intracellular potassium shift 1, 4
• Thyrotoxicosis causes transcellular redistribution 1
• Metabolic alkalosis enhances potassium movement into cells 1

Inadequate Intake

• Dietary insufficiency rarely causes hypokalemia alone but contributes when combined with other factors 1, 5
• The WHO recommends potassium intake of at least 3,510 mg per day for optimal cardiovascular health 5

Critical Diagnostic Considerations

A urinary potassium excretion ≥20 mEq/day in the presence of serum potassium <3.5 mEq/L indicates inappropriate renal potassium wasting 3. This distinguishes renal from extrarenal losses and guides further evaluation.

Hypomagnesemia coexists in approximately 40% of hypokalemic patients and represents the most common reason for refractory hypokalemia 1, 6. Magnesium levels must be checked and corrected (target >0.6 mmol/L) before potassium repletion will be effective 1, 6.

Common Clinical Pitfalls

• Failing to address magnesium deficiency when treating hypokalemia is the single most common reason for treatment failure 1, 6
• Overlooking secondary hyperaldosteronism in volume-depleted patients (vomiting, diarrhea, high-output stomas) leads to persistent potassium wasting despite supplementation 1
• Not recognizing concealed diuretic use or hidden medications containing licorice (causing mineralocorticoid effects) delays appropriate diagnosis 1
• Administering potassium supplements to patients on ACE inhibitors or ARBs without careful monitoring risks dangerous hyperkalemia, as these medications reduce renal potassium excretion 6