Causes of Hypokalemia
Hypokalemia results from three primary mechanisms: inadequate intake, excessive losses (renal or extrarenal), or transcellular shifts of potassium from extracellular to intracellular compartments 1, 2.
Inadequate Intake
Dietary potassium deficiency alone rarely causes hypokalemia because the kidneys can reduce potassium excretion to below 15 mmol per day 1. However, inadequate intake becomes clinically significant when combined with other factors such as diuretic use or gastrointestinal losses 2.
Excessive Losses
Renal Losses
Diuretic therapy is the most frequent cause of hypokalemia in clinical practice 3, 4. Loop diuretics (furosemide, bumetanide, torsemide) and thiazide diuretics (hydrochlorothiazide) cause significant urinary potassium losses through increased distal sodium delivery and secondary aldosterone stimulation 3.
Other renal causes include:
- Primary hyperaldosteronism, which increases mineralocorticoid activity and promotes renal potassium wasting 5, 6
- Medications including beta-agonists, corticosteroids, and certain antibiotics 3, 5
- Renal tubular disorders such as Bartter syndrome or Gitelman syndrome 3
- Hypomagnesemia, which causes dysfunction of potassium transport systems and increases renal potassium excretion 3
Extrarenal Losses
Gastrointestinal losses are common causes of hypokalemia 2, 7. These include:
- Vomiting and nasogastric suction 5, 6
- Diarrhea from any cause 1, 2
- High-output ileostomy or colostomy 3
- Laxative abuse 6
Excessive sweating can contribute to potassium loss, though it is rarely the sole cause 5.
Transcellular Shifts
Potassium shifts from extracellular to intracellular compartments can cause hypokalemia without total body potassium depletion 1, 2. Common causes include:
- Insulin excess, which drives potassium into cells 3, 2
- Beta-agonist therapy (albuterol, other beta-2 agonists) 3, 5
- Metabolic alkalosis, which shifts potassium intracellularly 3
- Thyrotoxicosis 3
- Refeeding syndrome, particularly in malnourished patients receiving enhanced parenteral nutrition 5
Special Populations
Neonates and Preterm Infants
Immature renal tubular function in preterm infants (especially those <34 weeks gestation) results in physiologic renal potassium wasting 5. Enhanced parenteral nutrition can increase endogenous insulin production, promoting potassium shift into cells 5.
Patients with Cardiovascular Disease
Even mild or moderate hypokalemia increases mortality and morbidity in patients with cardiovascular disease 4. Both hypokalemia and hyperkalemia adversely affect cardiac excitability and conduction, potentially leading to sudden death 8, 3.
Diagnostic Approach
Measurement of spot urine potassium and creatinine, along with acid-base status evaluation, serves as the initial diagnostic step 1. Urinary potassium >20 mmol/L suggests renal potassium wasting, while <20 mmol/L suggests extrarenal losses 5.
A common pitfall is failing to check and correct magnesium levels first, as hypomagnesemia is the most common reason for refractory hypokalemia and must be corrected before potassium levels will normalize 3, 9.