What are the causes of hypokalemia (low potassium levels in the blood)?

Causes of Hypokalemia

Hypokalemia (serum potassium <3.5 mEq/L) is most commonly caused by diuretic use, particularly thiazide and loop diuretics, followed by gastrointestinal losses from vomiting or diarrhea, and renal losses due to various conditions. 1

Classification of Hypokalemia

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

Major Causes of Hypokalemia

1. Decreased Intake

• Inadequate dietary potassium intake (rarely causes hypokalemia alone) 2
• Starvation
• Alcoholism

2. Increased Renal Losses

• Medications:

  • Diuretics (most common cause):
    • Thiazide diuretics 1
    • Loop diuretics 1
  • Amphotericin B
  • High-dose penicillins
  • Aminoglycosides

• Endocrine disorders:

  • Primary aldosteronism (spontaneous or diuretic-induced hypokalaemia) 1
  • Cushing's syndrome
  • Renin-secreting tumors
  • Congenital adrenal hyperplasia

• Renal tubular disorders:

  • Renal tubular acidosis (types 1 and 2)
  • Bartter syndrome
  • Gitelman syndrome
  • Liddle syndrome

3. Increased Gastrointestinal Losses

• Vomiting
• Diarrhea
• Laxative abuse
• Intestinal fistulas
• Villous adenoma

4. Transcellular Shifts (movement of K+ into cells)

• Alkalosis
• Insulin administration
• Beta-adrenergic stimulation
• Periodic paralysis
• Rapid cell proliferation (leukemia treatment)
• Hypothermia

Medication-Induced Hypokalemia

Several medications can cause or worsen hypokalemia:

• Diuretics (thiazides, loop diuretics) 1
• Beta-agonists (albuterol)
• Insulin
• Theophylline
• High-dose penicillins
• Amphotericin B

Clinical Evaluation for Hypokalemia

Key Diagnostic Steps:

1. Measure spot urine potassium and creatinine 2

   • Urinary K+ excretion >20 mEq/day with hypokalemia suggests renal potassium wasting
   • Urinary K+ excretion <20 mEq/day suggests extrarenal losses

2. Evaluate acid-base status to differentiate causes 2

   • Metabolic alkalosis: vomiting, diuretics
   • Metabolic acidosis: diarrhea, RTA

3. Check blood pressure

   • Hypertension may suggest primary aldosteronism 1

4. Screen for primary aldosteronism in patients with:

   • Resistant hypertension
   • Spontaneous or diuretic-induced hypokalemia
   • Incidentally discovered adrenal mass
   • Family history of early-onset hypertension
   • Stroke at young age (<40 years) 1

Clinical Implications of Hypokalemia

Hypokalemia can cause significant complications:

• Cardiovascular: arrhythmias, ECG changes (T-wave flattening, ST depression, U waves), increased risk of sudden cardiac death 1
• Neuromuscular: weakness, paralysis, rhabdomyolysis
• Renal: impaired concentrating ability, increased ammonia production, metabolic alkalosis
• Metabolic: glucose intolerance

Special Considerations

• Heart failure patients should maintain potassium levels of at least 4 mEq/L 1
• Primary aldosteronism is often underdiagnosed (screening rates <4% even in high-risk groups) 1
• Magnesium deficiency often coexists with hypokalemia and must be corrected for successful potassium repletion 3

Pitfalls to Avoid

1. Failing to identify primary aldosteronism - Present in up to 12% of patients with BP >180/110 mmHg 1
2. Overlooking transcellular shifts - Can cause rebound hypokalemia if not addressed 4
3. Neglecting magnesium status - Hypomagnesemia prevents correction of hypokalemia 3
4. Assuming dietary deficiency alone - Rarely the sole cause of hypokalemia 2
5. Missing medication-induced causes - Especially diuretics, which are the most common cause 5

Understanding the underlying cause of hypokalemia is essential for effective treatment and prevention of recurrence, with diuretic therapy and gastrointestinal losses being the most common etiologies in clinical practice.