Causes of Hypokalemia
Medication-Induced Causes
Loop diuretics (furosemide, bumetanide, torsemide) are the most common cause of hypokalemia in clinical practice, causing significant urinary potassium losses through increased distal sodium delivery and secondary aldosterone stimulation 1, 2.
- Thiazide diuretics (hydrochlorothiazide) block sodium-chloride reabsorption in the distal tubule, triggering compensatory potassium excretion through ROMK2 channels and aldosterone-sensitive ENaC channels 2.
- Beta-agonist therapy (albuterol, other beta-2 agonists) causes intracellular potassium shift 2.
- Corticosteroids like prednisolone cause hypokalemia through mineralocorticoid effects, with hydrocortisone causing more hypokalemia than methylprednisolone at equivalent doses 1.
- High-dose penicillin can contribute to hypokalemia 2.
- Insulin excess causes transcellular shifts of potassium into cells 1.
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 2.
- Diarrhea and high-output gastrointestinal losses lead to direct potassium depletion 1, 3.
- High-output enterocutaneous fistulas can cause significant potassium losses 2.
- Biliary tract losses contribute to gastrointestinal potassium wasting 4.
Renal Losses
A urinary potassium excretion of 20 mEq or more per day in the presence of serum potassium less than 3.5 mEq/L suggests inappropriate renal potassium wasting 4.
- Primary hyperaldosteronism causes inappropriate aldosterone production, leading to hypertension with hypokalemia in 8-20% of hypertensive patients 2.
- Secondary hyperaldosteronism from volume depletion activates the renin-angiotensin-aldosterone system, promoting sodium retention and potassium excretion 2.
- Bartter syndrome and Gitelman syndrome are genetic tubular disorders causing renal potassium wasting 2.
- Renal tubular acidosis can be a cause of hypokalemia 1.
Transcellular Shifts
Transcellular shift of potassium can occur due to underlying causes such as insulin excess, beta-agonist therapy, or thyrotoxicosis, and potassium may rapidly shift back into extracellular space once the cause is addressed 1.
- Metabolic alkalosis shifts potassium intracellularly 2.
- Thyrotoxicosis leads to transcellular shifts and hypokalemia 1.
- Insulin therapy drives potassium into cells 1.
Inadequate Intake
Inadequate dietary intake of potassium alone rarely causes hypokalemia since the kidney is able to lower potassium excretion below 15 mmol per day 5.
- Reduced calorie/protein intake in elderly patients with sedentary lifestyle can contribute to hypokalemia 2.
- The World Health Organization recommends a potassium intake of at least 3,510 mg per day for optimal cardiovascular health 3.
Magnesium Deficiency
Hypomagnesemia is the most common reason for refractory hypokalemia and must be corrected before potassium levels will normalize, as magnesium depletion causes dysfunction of potassium transport systems and increases renal potassium excretion 1, 2.
- Approximately 40% of hypokalemic patients have concurrent hypomagnesemia 1.
- Hypomagnesemia frequently coexists with hypokalemia and can make potassium repletion difficult until magnesium is corrected 2.
Special Clinical Contexts
- Diabetic ketoacidosis patients typically have total body potassium deficits of 3-5 mEq/kg body weight despite initially normal or even elevated serum levels 1.
- Tissue destruction (catabolism, infection, surgery, chemotherapy) can contribute to hypokalemia 1.
- Constipation can increase colonic potassium losses 1.
High-Risk Populations
Elderly patients are particularly susceptible to hypokalemia due to multiple factors, including reduced glomerular filtration, multi-morbidity, and polypharmacy 2.