What are the causes of hypokalemia (low potassium levels) in patients, particularly in geriatric individuals or those with a history of gastrointestinal disorders or taking medications such as diuretics?

Causes of Hypokalemia

Renal Potassium Losses (Most Common)

Diuretic therapy is the most frequent cause of hypokalemia in clinical practice. 1, 2, 3, 4

Medications Causing Renal Potassium Wasting

• Loop diuretics (furosemide, bumetanide, torsemide) cause significant urinary potassium losses through increased distal sodium delivery and secondary aldosterone stimulation 1, 2, 5, 4
• Thiazide diuretics (hydrochlorothiazide) block sodium-chloride reabsorption in the distal tubule, triggering compensatory potassium excretion through ROMK2 channels and aldosterone-sensitive ENaC channels 1, 6, 5, 4
• Potassium-sparing diuretics paradoxically cause hyperkalemia, not hypokalemia, when combined with ACE inhibitors or NSAIDs 1, 6
• ACE inhibitors and ARBs reduce renal potassium losses and may eliminate the need for potassium supplementation 1, 2
• Beta-blockers can decrease potassium excretion 1
• NSAIDs affect potassium homeostasis by causing sodium retention and worsening renal function 1, 2
• Corticosteroids (prednisolone, hydrocortisone) cause hypokalemia through mineralocorticoid effects, with hydrocortisone causing more hypokalemia than methylprednisolone at equivalent doses 2
• Certain antibiotics like levofloxacin can cause potassium wasting, though less commonly than diuretics 7

Endocrine and Renal Disorders

• Primary hyperaldosteronism increases renal potassium excretion 1, 8, 4
• Cushing's syndrome and abnormalities of the pituitary-adrenal axis 4
• Renal tubular acidosis causes inappropriate renal potassium wasting 2, 8, 4
• Renal disorders including tumors can lead to potassium deficiency 4

Gastrointestinal Losses

Gastrointestinal potassium wasting is identifiable by increased fluid losses via biliary tract or bowel. 3, 9, 4

• Vomiting and diarrhea are common causes, particularly chronic or frequent episodes 3, 9
• High-output stomas or fistulas require correction of sodium/water depletion first, as hypoaldosteronism from volume depletion paradoxically increases renal potassium losses 2
• Severe colitis can cause significant potassium depletion 2
• Laxative abuse leads to chronic gastrointestinal potassium losses 8

Inadequate Intake

Inadequate dietary potassium intake alone rarely causes hypokalemia since the kidney can lower potassium excretion below 15 mmol per day 8

• Reduced calorie/protein intake in elderly patients with sedentary lifestyle and deconditioning 1
• NPO status and delayed oral intake eliminate dietary potassium while ongoing renal losses continue 2
• Total parenteral nutrition without adequate potassium supplementation 9

Transcellular Shifts (Potassium Moves Into Cells)

Transcellular shifts cause hypokalemia without total body potassium depletion. 2, 3, 8

• Insulin therapy drives potassium into cells, particularly during treatment of diabetic ketoacidosis where total body potassium deficits are 3-5 mEq/kg despite initially normal or elevated serum levels 2, 3, 9
• Beta-agonist therapy (albuterol, other beta-2 agonists) causes intracellular potassium shift 1, 2, 3
• Thyrotoxicosis leads to transcellular potassium redistribution 2
• Metabolic alkalosis shifts potassium intracellularly 1, 2, 4
• Hyperglycemia in diabetic ketoacidosis creates osmotic diuresis with massive potassium losses 2, 3

High-Risk Populations

Elderly patients are particularly susceptible to hypokalemia due to multiple factors 1, 6, 5:

• Reduced glomerular filtration makes thiazides less effective and more likely to cause electrolyte disturbances 1, 6
• Multi-morbidity and polypharmacy increase drug-drug interactions 1
• Altered pharmacokinetic and pharmacodynamic properties of cardiovascular drugs 1
• Reduced skeletal mass and changes in nutritional habits 1

Women are at higher risk for diuretic-induced hypokalemia 5

Patients with edematous states (heart failure, cirrhosis with ascites) require higher diuretic doses, increasing hypokalemia risk 2, 5

Diagnostic Approach

A urinary potassium excretion of 20 mEq or more per day in the presence of serum potassium <3.5 mEq/L suggests inappropriate renal potassium wasting. 4

• Spot urine potassium and creatinine with acid-base status evaluation provides initial diagnostic direction without waiting for 24-hour collection 8
• Check magnesium levels immediately in all hypokalemic patients, as hypomagnesemia (present in ~40% of cases) makes hypokalemia resistant to correction 2
• Measure serum electrolytes including sodium, calcium, glucose, creatinine, and eGFR 2
• Evaluate medications including diuretics, corticosteroids, beta-agonists, insulin, laxatives, and NSAIDs 2, 7

Critical Clinical Caveat

Hypokalemia with concurrent hypomagnesemia will not respond to potassium replacement until magnesium is corrected first, as magnesium deficiency causes dysfunction of potassium transport systems and increases renal potassium excretion 2