What causes hypokalemia (low potassium)?

Causes of Low Potassium (Hypokalemia)

Hypokalemia is primarily caused by decreased potassium intake, increased potassium excretion, or transcellular shifts, with medication use (especially diuretics) being the most common cause in clinical practice. 1

Medication-Related Causes

Diuretics

• Thiazide and loop diuretics are the most common causes of hypokalemia 2
• Hydrochlorothiazide can cause hypokalemia, especially with:
  • Brisk diuresis
  • Concomitant severe cirrhosis
  • Prolonged therapy 3
  • High salt diets and large urine volumes 2

Other Medications

• Potassium-wasting medications 4:
  • Corticosteroids and ACTH
  • Laxatives (bisacodyl, Milk of Magnesia)
  • Beta-agonists
  • Amphotericin B
  • Aminoglycosides
  • Penicillin derivatives
  • Insulin (acute effect)

Gastrointestinal Losses

• Vomiting
• Diarrhea
• Nasogastric suction
• Laxative abuse
• Fistulas
• Villous adenoma 5

Renal Causes

• Primary hyperaldosteronism
• Cushing's syndrome
• Bartter syndrome
• Gitelman syndrome
• Renal tubular acidosis (types 1 and 2)
• Magnesium deficiency 6

Transcellular Shifts

• Alkalosis (metabolic or respiratory)
• Insulin administration
• Beta-adrenergic stimulation
• Periodic paralysis
• Hypothermia
• Barium poisoning 7

Inadequate Intake

• Malnutrition
• Alcoholism
• Anorexia nervosa 1

Clinical Implications of Hypokalemia

Cardiovascular Effects

• Cardiac arrhythmias
• ECG changes (U waves, flattened T waves, ST depression)
• Increased risk of digitalis toxicity 4
• Increased mortality in heart failure patients 4

Neuromuscular Effects

• Muscle weakness
• Cramps
• Rhabdomyolysis
• Paralysis in severe cases 6

Other Effects

• Glucose intolerance
• Increased ammonia production
• Nephropathy
• Exacerbation of hepatic encephalopathy 2
• Impaired urinary concentrating ability 6

Risk Factors for Developing Hypokalemia

• Concurrent use of multiple diuretics
• High sodium intake
• Metabolic alkalosis
• Increased aldosterone production
• Magnesium deficiency 2
• Heart failure
• Cirrhosis
• Nephrotic syndrome 1

Diagnostic Approach

When evaluating hypokalemia, assess:

1. Urinary potassium excretion:

   • 20 mEq/day with hypokalemia suggests renal potassium wasting

   • <20 mEq/day suggests extrarenal losses 5

2. Acid-base status:

   • Metabolic alkalosis often accompanies diuretic-induced hypokalemia
   • Metabolic acidosis may suggest diarrhea or renal tubular acidosis 7

3. Medication review:

   • Especially diuretics, laxatives, steroids 3

4. Blood pressure:

   • Hypertension with hypokalemia suggests hyperaldosteronism 1

Prevention and Management

• For diuretic-induced hypokalemia:

  • Use lowest effective dose of diuretic
  • Consider potassium-sparing diuretics in high-risk patients
  • Monitor serum potassium regularly, especially after medication changes 1

• For patients at high risk (e.g., on digoxin, with heart disease):

  • Maintain serum potassium ≥4.0 mmol/L 1
  • Consider prophylactic potassium supplementation 8

• Correction of hypomagnesemia is essential in refractory hypokalemia 1

Common Pitfalls

• Failing to recognize transcellular shifts as a cause of hypokalemia
• Not addressing underlying magnesium deficiency
• Overlooking laxative abuse as a cause of chronic hypokalemia
• Assuming serum potassium accurately reflects total body potassium (it doesn't) 6
• Not recognizing that mild hypokalemia can be associated with significant total-body potassium deficits 6

Remember that hypokalemia can be multifactorial, and multiple mechanisms may be present simultaneously in a single patient. Identifying and addressing all contributing factors is essential for effective management.