What causes hyponatremia (low sodium), hypokalemia (low potassium), and hypochloremia (low chloride)?

Causes of Low Sodium, Potassium, and Chloride

The most common causes of hyponatremia, hypokalemia, and hypochloremia are gastrointestinal losses (especially from high output stomas/fistulas), diuretic therapy, and renal disorders, with treatment requiring targeted replacement based on the underlying cause. 1

Common Causes by Electrolyte

Hyponatremia (Na < 135 mmol/L)

• Gastrointestinal losses:
  • High output stomas/jejunostomies/ileostomies 1
  • Diarrhea, vomiting, fistulas
  • Rectal villous adenomas (McKittrick-Wheelock syndrome) 2
• Medication-induced:
  • Diuretics (especially thiazides) 3, 4
  • ACE inhibitors, ARBs 1
• Renal causes:
  • Primary sodium depletion in premature infants 1
  • Bartter syndrome 1
  • Salt-wasting nephropathies
• Volume status-related:
  • Hypovolemic hyponatremia (sodium and fluid loss with greater sodium loss) 4
  • SIADH (syndrome of inappropriate antidiuretic hormone)
• Other causes:
  • Adrenal insufficiency
  • Liver cirrhosis with ascites 1
  • Congestive heart failure

Hypokalemia (K < 3.5 mmol/L)

• Gastrointestinal losses:
  • Diarrhea, vomiting
  • High output stomas 1
• Medication-induced:
  • Diuretics (loop diuretics, thiazides) 5, 6
  • Laxative abuse
• Renal causes:
  • Secondary hyperaldosteronism 1
  • Bartter syndrome 1
  • Renal tubular acidosis
• Other causes:
  • Hypomagnesemia (causes dysfunction of potassium transport systems) 1
  • Insulin excess (shifts potassium into cells) 1
  • Enhanced protein synthesis (shifts potassium into cells) 1
  • Inadequate intake 1

Hypochloremia (Cl < normal range)

• Gastrointestinal losses:
  • Vomiting (loss of HCl)
  • Diarrhea
  • High output stomas 1
• Medication-induced:
  • Diuretics (especially loop diuretics)
• Metabolic alkalosis:
  • Often accompanies hypokalemia and hyponatremia
  • Bartter syndrome (characterized by hypochloremic metabolic alkalosis) 1
• Other causes:
  • Excessive sweating
  • Cystic fibrosis (salt loss in sweat) 1

Special Clinical Scenarios with Combined Electrolyte Abnormalities

Short Bowel Syndrome/High Output Stomas

• Effluent from jejunostomy/ileostomy contains high sodium (approximately 100 mmol/L) 1
• Potassium depletion often secondary to sodium depletion with secondary hyperaldosteronism 1
• Management includes:
  • Restricting oral hypotonic fluids to 500 ml/day
  • Providing glucose/saline solution with sodium concentration ≥90 mmol/L
  • Correcting hypomagnesemia to help resolve resistant hypokalemia 1

Bartter Syndrome

• Genetic disorder affecting renal tubular function
• Characterized by hypokalemic, hypochloremic metabolic alkalosis 1
• Different types present at different ages with varying severity
• Diagnosis confirmed by genetic testing 1

Diuretic-Induced Electrolyte Abnormalities

• Loop diuretics more commonly cause hypokalemia 1
• Thiazides more commonly cause hyponatremia 3
• Can lead to hypovolemia, activating renin-angiotensin-aldosterone system
• Adverse effects include acute kidney injury, hyponatremia, hypokalemia 1

Diagnostic Approach

1. Assess volume status:

   • Clinical signs of dehydration or fluid overload
   • Orthostatic vital signs
   • Skin turgor, mucous membranes

2. Laboratory evaluation:

   • Serum electrolytes (Na, K, Cl)
   • Urinary electrolytes (especially Na and K)
   • BUN/creatinine ratio (elevated in hypovolemia)
   • Acid-base status (pH, bicarbonate)
   • Magnesium level (hypomagnesemia can cause refractory hypokalemia) 1

3. Evaluate urinary electrolyte excretion:

   • Urinary sodium <20 mmol/L suggests extrarenal losses 4
   • Urinary sodium >20 mmol/L suggests renal losses 1
   • Urinary potassium >20 mmol/L with hypokalemia suggests inappropriate renal potassium wasting 6

Management Principles

1. Treat the underlying cause:

   • Discontinue offending medications if possible
   • Manage gastrointestinal disorders
   • Treat hormonal imbalances

2. Replace electrolytes appropriately:

   • For hyponatremia: Normal saline for hypovolemic hyponatremia; avoid rapid correction (target 4-6 mEq/L per day, not exceeding 8 mEq/L in 24 hours) 4
   • For hypokalemia: Oral or IV potassium replacement; correct hypomagnesemia if present 1, 6
   • For hypochloremia: Usually corrects with sodium and potassium chloride replacement

3. Special considerations:

   • In short bowel syndrome: Reduce oral hypotonic fluids, provide high-sodium solutions 1
   • In cirrhosis: Avoid NSAIDs, ACE inhibitors, and ARBs 1
   • In severe symptomatic hyponatremia: Consider 3% hypertonic saline 4

Pitfalls and Caveats

• Rapid correction of hyponatremia can lead to osmotic demyelination syndrome 4
• Hypokalemia may be refractory if hypomagnesemia is not corrected 1
• Potassium-sparing diuretics may help in diuretic-induced hypokalemia but can cause hyperkalemia in renal impairment 1
• Imbalances in the potassium/sodium ratio are associated with increased risk for hypertension and cardiovascular disease 1

By systematically evaluating the patient's clinical status, medication history, and laboratory values, the cause of combined electrolyte abnormalities can be determined and appropriate treatment initiated.