What are the causes of hypokalemia?

Causes of Hypokalemia

Hypokalemia is primarily caused by decreased intake, increased renal losses, gastrointestinal losses, or transcellular shifts of potassium. 1, 2

Classification of Causes

1. Decreased Intake

• Inadequate dietary intake (rarely causes hypokalemia alone as kidneys can reduce potassium excretion below 15 mmol/day) 3
• Starvation
• Eating disorders

2. Increased Renal Losses

• Diuretic therapy (most common cause)
  • Thiazide diuretics 4
  • Loop diuretics 4
• Primary hyperaldosteronism 4, 1
  • Aldosterone-producing adenoma
  • Bilateral adrenal hyperplasia
• Secondary hyperaldosteronism
  • Heart failure
  • Liver cirrhosis
  • Nephrotic syndrome
• Cushing's syndrome 5
• Renal tubular acidosis
• Magnesium deficiency (causes dysfunction of potassium transport systems) 4
• Medications
  • Antibiotics (gentamicin, amphotericin B)
  • Licorice ingestion 5

3. Gastrointestinal Losses

• Vomiting 5
• Diarrhea 5
• Laxative abuse 5
• Intestinal fistulas 5
• Malabsorption 5
• High-output ileostomy/jejunostomy 4

4. Transcellular Shifts

• Alkalosis (metabolic or respiratory)
• Insulin administration
• Beta-adrenergic stimulation
• Periodic paralysis
• Rapid cell growth (leukemia treatment)
• Hypothermia
• Barium poisoning

Diagnostic Approach

When evaluating hypokalemia, consider:

1. Urinary potassium excretion:

   • Urinary K+ >20 mEq/day with hypokalemia suggests renal potassium wasting 6
   • Urinary K+ <20 mEq/day suggests extrarenal losses or transcellular shifts 3

2. Acid-base status:

   • Metabolic alkalosis: suggests vomiting or diuretic use
   • Metabolic acidosis: suggests diarrhea or renal tubular acidosis

3. Blood pressure:

   • Hypertension: consider primary aldosteronism, especially in resistant hypertension 4
   • Normal BP: consider other causes

4. Medication review:

   • Diuretics (most common cause)
   • Sympathomimetics
   • Decongestants 1

Special Considerations

• Hypomagnesemia: Often coexists with hypokalemia and makes it resistant to correction until magnesium is replaced 4, 1

• Severity classification:

  • Mild: 3.0-3.5 mEq/L (often asymptomatic)
  • Moderate: 2.5-3.0 mEq/L (muscle weakness, fatigue)
  • Severe: <2.5 mEq/L (high risk of cardiac arrhythmias) 1

• Short bowel syndrome: Patients with jejunostomy or high-output ileostomy are at high risk for hypokalemia due to excessive fluid and electrolyte losses 4

• Heart failure patients: Often develop hypokalemia due to diuretic therapy and secondary hyperaldosteronism 4

Clinical Pearls

• Low serum potassium is most commonly due to sodium depletion with secondary hyperaldosteronism, causing greater than normal urinary losses of potassium 4

• Hypokalemia in patients with hypertension should prompt screening for primary aldosteronism, especially if resistant to treatment or associated with spontaneous hypokalemia 4

• In patients on diuretics, consider using lower doses or adding potassium-sparing diuretics to prevent hypokalemia 7

• Patients with severe hypokalemia (<2.5 mEq/L) require urgent evaluation and treatment due to risk of cardiac arrhythmias and neuromuscular symptoms 2