What causes hypokalemia?

Common Causes of Hypokalemia

Hypokalemia, defined as serum potassium <3.5 mEq/L, is most commonly caused by diuretic use, gastrointestinal losses, and renal potassium wasting, which can lead to life-threatening cardiac arrhythmias if left untreated. 1, 2

Classification of Hypokalemia

Hypokalemia can be classified by severity:

• Mild: 3.0-3.5 mEq/L
• Moderate: 2.5-2.9 mEq/L
• Severe: <2.5 mEq/L 1

Major Etiologies of Hypokalemia

1. Decreased Potassium Intake

• Inadequate dietary intake (rarely causes hypokalemia alone) 3
• Starvation
• Alcoholism

2. Increased Potassium Loss

Renal Losses (Urinary K+ >20 mEq/day despite hypokalemia)

• Diuretic therapy (most common cause)
  • Loop diuretics
  • Thiazide diuretics 4
• Medications
  • Antibiotics (amphotericin B, aminoglycosides)
  • Caffeine 1
• Endocrine disorders
  • Hyperaldosteronism
  • Cushing's syndrome
  • Renin-secreting tumors 4
• Renal tubular disorders
  • Bartter syndrome
  • Gitelman syndrome
  • Renal tubular acidosis

Gastrointestinal Losses

• Vomiting
• Diarrhea
• Laxative abuse
• Nasogastric suction
• Intestinal fistulas
• Villous adenoma 1, 4

3. Transcellular Shifts (K+ moving from extracellular to intracellular space)

• Insulin administration
• Beta-adrenergic stimulation
• Alkalosis
• Hypokalemic periodic paralysis
• Rapid cell growth (leukemia treatment)
• Hypothermia 2, 5

4. Special Pediatric Considerations

• Immaturity of renal function
• Growth restriction
• Inadequate parenteral or enteral supply
• Early enhanced parenteral nutrition (increased endogenous insulin production) 1

Clinical Manifestations of Hypokalemia

Cardiac Effects

• ECG changes:
  • Broadening of T waves
  • ST-segment depression
  • Prominent U waves 1
• Arrhythmias:
  • First or second-degree atrioventricular block
  • Atrial fibrillation
  • Premature ventricular contractions
  • Ventricular tachycardia
  • Torsades de pointes
  • Ventricular fibrillation
  • Cardiac arrest 1

Neuromuscular Effects

• Muscle weakness
• Paralysis
• Rhabdomyolysis
• Paresthesias
• Depressed deep tendon reflexes 6

Other Effects

• Impaired urinary concentrating ability
• Glucose intolerance
• Metabolic alkalosis (especially with chloride depletion) 4, 6

Diagnostic Approach

1. Measure spot urine potassium and creatinine

   • Urinary K+ <20 mEq/day suggests extrarenal losses
   • Urinary K+ >20 mEq/day suggests renal potassium wasting 3, 6

2. Evaluate acid-base status

   • Metabolic alkalosis often accompanies diuretic use, vomiting
   • Metabolic acidosis may indicate diarrhea or renal tubular acidosis 6

3. Assess volume status

   • Volume depletion suggests primary increase in distal sodium delivery
   • Volume expansion with hypertension suggests primary mineralocorticoid excess 6

4. Additional testing as needed

   • Plasma renin activity and aldosterone levels
   • Cortisol levels
   • Urinary chloride measurement 3, 6

Treatment Considerations

Treatment should address both the underlying cause and potassium replacement:

1. Oral replacement preferred if:

   • Patient has functioning GI tract
   • Serum K+ >2.5 mEq/L
   • No severe symptoms or ECG changes 2

2. Intravenous replacement needed for:

   • Serum K+ ≤2.5 mEq/L
   • ECG abnormalities
   • Neuromuscular symptoms 2

3. Prevention of further losses:

   • Potassium-sparing diuretics (spironolactone, triamterene)
   • Addressing underlying conditions 4

Important Clinical Pitfalls

• Concurrent magnesium deficiency may make hypokalemia resistant to treatment; check and correct magnesium levels 1
• Rapid correction of severe hyponatremia (>10-15 mmol/L/24h) can cause cerebral edema and neurological injury 1
• Bolus administration of potassium for cardiac arrest is ill-advised and potentially dangerous 1
• Rebound hypokalemia can occur after treatment of transcellular shift causes 5
• Chloride deficiency with metabolic alkalosis requires potassium chloride rather than other potassium salts 4

By systematically evaluating the cause of hypokalemia and addressing both the underlying condition and potassium deficit, clinicians can effectively manage this common electrolyte disorder and prevent potentially life-threatening complications.