What causes hypokalemia?

Causes of Hypokalemia

Hypokalemia (serum potassium <3.5 mEq/L) is primarily caused by decreased intake, increased renal losses, gastrointestinal losses, or transcellular shifts of potassium from extracellular to intracellular compartments. 1

Major Mechanisms of Hypokalemia

1. Decreased Potassium Intake

• Inadequate dietary intake alone rarely causes hypokalemia since the kidneys can reduce potassium excretion below 15 mmol per day 2
• However, low intake may contribute to hypokalemia when combined with other mechanisms 1

2. Increased Renal Losses

• Medication-induced losses:

  • Potassium-wasting diuretics 3
  • Beta-blockers 3
  • Penicillin G 3
  • Aminoglycosides 4

• Hormonal causes:

  • Primary hyperaldosteronism 4
  • Secondary hyperaldosteronism 5
  • Cushing syndrome 5

• Other renal causes:

  • Magnesium deficiency (impairs potassium reabsorption) 4
  • Renal tubular acidosis 5
  • Salt-wasting nephropathies 5
  • In preterm infants due to immature renal tubular function 3

3. Gastrointestinal Losses

• Vomiting 5
• Diarrhea 5
• Laxative abuse 6
• Intestinal fistulas 6
• Villous adenomas 7

4. Transcellular Shifts

• Alkalosis: Acute alkalosis can produce hypokalemia even without total body potassium deficit 8
• Insulin excess: Drives potassium into cells 6
• Beta-adrenergic stimulation: Catecholamine surge 6
• Early enhanced parenteral nutrition: Increases endogenous insulin production, promoting potassium shift into cells 3
• Refeeding syndrome: When nutrition is reintroduced after prolonged starvation 3
• Periodic paralysis: Genetic disorder causing episodic hypokalemia 7
• Hypothermia: Causes intracellular shift of potassium 7

Diagnostic Approach to Hypokalemia

Initial Assessment

• Measure spot urine potassium and creatinine 2
• Urinary potassium >20 mmol/L suggests renal potassium wasting 4
• Urinary potassium <20 mmol/L suggests extrarenal losses 4
• Evaluate acid-base status to help determine etiology 2

Further Evaluation

• Check blood pressure (hypertension may suggest mineralocorticoid excess) 5
• Measure serum magnesium (coexisting deficiency is common) 4
• Consider measuring plasma renin activity and aldosterone levels in suspected mineralocorticoid excess 5

Clinical Implications and Management

Severity Classification

• Mild: 3.0-3.5 mEq/L 4
• Moderate: 2.5-2.9 mEq/L 4
• Severe: <2.5 mEq/L 4

Treatment Considerations

• Correct underlying cause when possible 1
• Oral replacement is preferred if serum potassium >2.5 mEq/L and patient has functioning GI tract 1
• Intravenous replacement for severe hypokalemia (<2.5 mEq/L) or when oral route not feasible 6
• Always correct coexisting magnesium deficiency for successful potassium repletion 4
• In patients with heart failure, maintain serum potassium ≥4.0 mEq/L 4

Common Pitfalls

• Failure to recognize pseudo-hypokalemia due to improper venipuncture technique or in vitro hemolysis 8
• Overlooking transcellular shifts that may cause rebound hypokalemia after initial correction 6
• Neglecting to correct magnesium deficiency, which can make potassium repletion ineffective 4
• Rapid correction of severe hypokalemia with IV potassium can be dangerous 4

By understanding these mechanisms and following a systematic approach to diagnosis, clinicians can effectively identify and manage hypokalemia, reducing associated morbidity and mortality.