What are the causes of hypokalemia (low potassium)?

Causes of Hypokalemia (Low Potassium)

Hypokalemia is most commonly caused by gastrointestinal losses, renal losses (particularly from diuretic use), and transcellular shifts, all of which can lead to potentially life-threatening cardiac arrhythmias if left untreated. 1

Major Categories of Hypokalemia Causes

1. Gastrointestinal Losses

• Vomiting and diarrhea - common causes of potassium depletion 1, 2
• Biliary tract losses - can contribute to significant potassium wasting 3
• Malabsorption syndromes - interfere with potassium absorption 1

2. Renal Losses

• Diuretic therapy - the most common cause of hypokalemia 3, 4
  • Loop diuretics (e.g., furosemide) - cause significant potassium wasting 5
  • Thiazide diuretics - associated with 7%-56% prevalence of hypokalemia 4
• Medications that enhance renal potassium excretion:
  • Corticosteroids and ACTH - intensify electrolyte depletion 5, 6
  • Prolonged use of laxatives 5
  • Antibiotics (e.g., gentamicin, amphotericin B)
  • High-dose penicillins

3. Transcellular Shifts

• Alkalosis - causes potassium to shift into cells 3
• Insulin administration - drives potassium into cells 1
• Beta-adrenergic stimulation - catecholamines promote cellular potassium uptake 1
• Periodic paralysis - rare genetic disorder causing episodic hypokalemia

4. Endocrine Causes

• Primary hyperaldosteronism - excessive aldosterone production 2
• Secondary hyperaldosteronism - from conditions like heart failure, cirrhosis 2
• Cushing's syndrome - excess cortisol promotes potassium excretion
• Renin-producing tumors - activate the renin-angiotensin-aldosterone system

5. Other Causes

• Inadequate dietary intake - rarely the sole cause but can contribute 7
• Magnesium deficiency - often coexists with hypokalemia 1
• Dialysis with low-potassium dialysate - can induce hypokalemia in kidney patients 1
• Severe burns or trauma - cause potassium release followed by losses

Risk Factors and Clinical Significance

Certain populations are at higher risk for developing hypokalemia:

• Patients with heart failure on diuretics 1
• Patients with chronic kidney disease on dialysis 1
• Women and Black individuals (higher risk with thiazide diuretics) 4
• Patients taking digoxin (increased risk of toxicity with hypokalemia) 1, 5

Diagnostic Approach

When evaluating hypokalemia, key diagnostic steps include:

1. Measure urinary potassium excretion - values >20 mEq/day with serum K+ <3.5 mEq/L suggest inappropriate renal potassium wasting 3, 2

2. Assess volume status - helps differentiate between:

   • Primary increase in distal sodium delivery (volume depletion)
   • Primary increase in mineralocorticoid activity (often volume expansion with hypertension) 2

3. Check acid-base status - metabolic alkalosis often accompanies hypokalemia from vomiting or diuretic use 3

4. Measure plasma renin activity and aldosterone levels - when mineralocorticoid excess is suspected 2

Clinical Manifestations

Hypokalemia can affect multiple organ systems:

• Cardiac: ECG changes (U waves, T-wave flattening), arrhythmias (especially with digoxin), and potentially cardiac arrest 1
• Neuromuscular: weakness, paralysis, cramps, and rhabdomyolysis 7, 2
• Renal: impaired urinary concentrating ability, polyuria, and potential acceleration of chronic kidney disease 8
• Metabolic: glucose intolerance and insulin resistance 2

Prevention and Management

Hypokalemia management should focus on:

• Identifying and treating the underlying cause
• Potassium replacement (oral preferred unless severe/symptomatic) 8
• Using potassium-sparing diuretics when appropriate 8
• Monitoring serum potassium levels during treatment 5, 6
• Addressing concurrent magnesium deficiency when present 1

For patients on diuretics, preventive strategies include:

• Lower diuretic doses when possible 4
• Combining with potassium-sparing diuretics or renin-angiotensin system blockers 4
• Increasing dietary potassium intake (fruits and vegetables) 4
• Reducing sodium intake 4

Common Pitfalls

1. Failing to recognize that serum potassium is an inaccurate marker of total body potassium deficit - mild hypokalemia may reflect significant total body depletion 8

2. Overlooking concurrent magnesium deficiency, which can make potassium repletion difficult 1

3. Administering potassium too rapidly, which can cause cardiac arrhythmias 1

4. Not considering transcellular shifts, which can lead to rebound hypokalemia or hyperkalemia during treatment 7