Causes of Hypokalemia
Hypokalemia results from three primary mechanisms: inadequate intake, excessive losses (renal or gastrointestinal), or transcellular shifts of potassium from extracellular to intracellular compartments. 1, 2, 3
Inadequate Dietary Intake
- Inadequate dietary potassium intake alone rarely causes hypokalemia because the kidneys can reduce potassium excretion to below 15 mmol per day 2
- Low serum potassium secondary to low potassium ingestion typically occurs only after an extended period of inadequate oral intake 4
- Reduced calorie/protein intake in elderly patients with sedentary lifestyle and deconditioning can contribute to hypokalemia 5
Excessive Renal Losses
Medication-Induced Renal Losses
- Loop diuretics (furosemide, bumetanide, torsemide) are the most frequent cause of hypokalemia in clinical practice, inhibiting sodium and chloride reabsorption in the ascending limb of the loop of Henle and causing significant potassium wasting through increased distal sodium delivery and secondary aldosterone stimulation 5, 6, 3
- Thiazide diuretics (hydrochlorothiazide) block sodium-chloride reabsorption in the distal tubule, triggering compensatory potassium excretion through ROMK2 channels and aldosterone-sensitive ENaC channels 5, 6
- The risk of diuretic-induced hypokalemia is markedly enhanced when two diuretics are used in combination 5
Hormonal Causes of Renal Losses
- Primary aldosteronism causes inappropriate aldosterone production, leading to hypertension with hypokalemia in 8-20% of hypertensive patients, and should be screened when hypertension coexists with spontaneous or substantial diuretic-induced hypokalemia, resistant hypertension, adrenal mass, or family history of early-onset hypertension 6
- Secondary hyperaldosteronism from volume depletion (high-output stomas, fistulas, vomiting) paradoxically increases renal potassium losses 5, 6
- Bartter syndrome and Gitelman syndrome cause renal potassium wasting 6
Other Renal Causes
- Hypomagnesemia causes dysfunction of potassium transport systems and increases renal potassium excretion, making it the most common reason for refractory hypokalemia 5, 6, 4
- Magnesium deficiency frequently coexists with hypokalemia (approximately 40% of hypokalemic patients) and must be corrected before potassium levels will normalize 5, 6
Gastrointestinal Losses
- Vomiting causes hypokalemia primarily through renal potassium losses driven by metabolic alkalosis and secondary hyperaldosteronism, not through direct loss of potassium in gastric fluid 6
- Diarrhea and high-output gastrointestinal losses (enterocutaneous fistulas, high-output stomas) cause significant potassium depletion 6, 3, 7
- Metabolic alkalosis from gastric acid loss upregulates ENaC activity in the cortical collecting duct, creating a self-perpetuating cycle of potassium loss 6
Transcellular Shifts
- Beta-agonist therapy (albuterol, other beta-2 agonists) causes intracellular potassium shift without actual total body potassium depletion 5, 1, 3
- Insulin excess drives potassium into cells, particularly during treatment of diabetic ketoacidosis or hyperglycemia 5, 1, 3
- Metabolic alkalosis shifts potassium intracellularly 5
- Thyrotoxicosis can lead to transcellular shifts and hypokalemia 5
Special Clinical Contexts
- Peritoneal dialysis patients are at increased risk of hypokalemia because of greater filtration of potassium compared to hemodialysis 4
- Patients on total parenteral nutrition may develop hypokalemia due to inadequate potassium supplementation 7
- Tissue destruction (catabolism, infection, surgery, chemotherapy) can contribute to potassium disturbances 5
- Constipation can increase colonic potassium losses 5
High-Risk Populations
- Elderly patients are particularly susceptible to hypokalemia due to reduced glomerular filtration, multi-morbidity, polypharmacy, and reduced dietary intake 5
- Patients with chronic lung disease on chronic diuretic therapy require adequate potassium supplementation to prevent hypokalemia and metabolic alkalosis that can exacerbate CO2 retention 5