What are the causes of hypokalemia?

Causes of Hypokalemia

Hypokalemia, defined as serum potassium level <3.5 mEq/L, has multiple etiologies that can be categorized into decreased intake, increased losses, and transcellular shifts. 1

Major Causes of Hypokalemia

Medication-Induced Causes

• Diuretic therapy is one of the most common causes of hypokalemia in clinical practice 1, 2
  • Loop diuretics (furosemide) inhibit sodium and chloride reabsorption in the ascending limb of the loop of Henle 3
  • Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubule 3
  • Both can cause significant hypokalemia and metabolic alkalosis 3
• Beta-agonists can cause transcellular shifts of potassium, worsening hypokalemia 4

Gastrointestinal Losses

• Vomiting and diarrhea are common causes of potassium depletion 1, 5
• High-output enterocutaneous fistulas and stomas can lead to significant potassium losses 1
• Biliary tract losses can contribute to hypokalemia 5

Renal Losses

• Primary hyperaldosteronism causes inappropriate renal potassium wasting 1, 6
• Secondary hyperaldosteronism (often due to volume depletion) 1
• Renal tubular disorders:
  • Bartter syndrome 1
  • Gitelman syndrome 1
• Magnesium deficiency causes renal potassium wasting and makes hypokalemia resistant to correction 1, 4

Transcellular Shifts

• Insulin excess can shift potassium intracellularly 2, 7
• Thyrotoxicosis can cause transcellular potassium shifts 4
• Alkalosis promotes potassium movement into cells 7

Other Causes

• Decreased dietary intake (rarely a sole cause but can contribute) 2
• Total parenteral nutrition without adequate potassium supplementation 8

Clinical Significance and Manifestations

Cardiac Manifestations

• ECG changes including T-wave flattening, ST-segment depression, and prominent U waves 1
• Risk of ventricular arrhythmias, especially in patients with heart disease or those on digitalis 1, 4
• Potential progression to ventricular fibrillation, PEA, or asystole if untreated 1

Neuromuscular Symptoms

• Muscle weakness or paralysis in severe cases 1, 8
• Paresthesias and depressed deep tendon reflexes 1
• Respiratory difficulties due to muscle weakness 1

Other System Effects

• Renal: Hypokalemia can cause structural and functional kidney damage 5
• Gastrointestinal: May lead to ileus 9
• Metabolic: Often associated with metabolic alkalosis, especially with diuretic use 3

Special Considerations and Common Pitfalls

Important Clinical Pearls

• Hypomagnesemia frequently coexists with hypokalemia and must be corrected for successful potassium repletion 1, 4
• Serum potassium is an inaccurate marker of total body potassium deficit - mild hypokalemia may represent significant total body depletion 9
• Urinary potassium excretion >20 mEq/day in the presence of hypokalemia suggests inappropriate renal potassium wasting 5

Common Pitfalls to Avoid

• Failing to address magnesium deficiency when treating hypokalemia 1
• Overlooking secondary hyperaldosteronism as a cause in volume-depleted patients 1
• Administering digoxin before correcting hypokalemia, which significantly increases arrhythmia risk 4
• Not monitoring potassium levels regularly after initiating diuretic therapy 4

Management Approach

• Mild hypokalemia (3.0-3.5 mEq/L) often requires oral replacement 4
• Moderate to severe hypokalemia (<3.0 mEq/L) may require more aggressive replacement 1, 4
• For diuretic-induced hypokalemia, consider potassium-sparing diuretics:
  • Spironolactone (25-100 mg daily) 4, 6
  • Amiloride (5-10 mg daily) 4
  • Triamterene (50-100 mg daily) 4, 5