Which condition is most closely associated with causing hyperchloremic metabolic acidosis?

Hyperchloremic Metabolic Acidosis: Causes and Associations

Addison's disease is the condition most closely associated with causing hyperchloremic metabolic acidosis. 1, 2

Pathophysiology of Hyperchloremic Metabolic Acidosis

Hyperchloremic metabolic acidosis is characterized by:

• Bicarbonate loss rather than acid production or retention
• Decreased strong ion difference (SID) due to increased chloride relative to sodium
• Normal anion gap

The mechanism involves:

• Decreased plasma SID leading to lower pH 1
• Calculated as difference between strong cations (Na+, K+, Ca2+, Mg2+) and strong anions (Cl-, lactate) 1

Analysis of Answer Options

A. Vitamin C Deficiency

• Not associated with hyperchloremic metabolic acidosis
• No evidence in the literature linking vitamin C deficiency to this specific acid-base disorder

B. Diabetes Mellitus

• While diabetes can cause metabolic acidosis, it typically presents as high anion gap metabolic acidosis (diabetic ketoacidosis) 3
• DKA is characterized by increased ketone production, not primary bicarbonate loss 3
• The diagnostic criteria for DKA include high anion gap (>10-12) 3

C. Addison's Disease (Correct Answer)

• Addison's disease involves adrenal insufficiency with aldosterone deficiency
• Aldosterone deficiency leads to:
  • Impaired sodium reabsorption and potassium secretion in distal tubule
  • Reduced hydrogen ion secretion in collecting ducts
  • Reduced bicarbonate regeneration
  • Hyperkalemia and hyperchloremic metabolic acidosis 1, 2
• FDA drug labeling for aldosterone specifically mentions "reversible hyperchloremic metabolic acidosis" in association with hyperkalemia 2
• Praxis Medical Insights confirms that adrenal insufficiency is a risk factor for hyperchloremia 1

D. Multiple Sclerosis

• No evidence in the literature linking multiple sclerosis to hyperchloremic metabolic acidosis
• Multiple sclerosis is a demyelinating neurological disorder without direct effects on acid-base balance

Other Important Causes of Hyperchloremic Metabolic Acidosis

1. Renal tubular acidosis (RTA) 4

   • Type 1 (distal) RTA: impaired H+ secretion in collecting ducts
   • Type 2 (proximal) RTA: impaired bicarbonate reabsorption
   • Type 4 RTA: hypoaldosteronism leading to impaired H+ secretion 5

2. Administration of chloride-rich fluids 3, 1

   • 0.9% saline administration can cause hyperchloremic acidosis 3
   • Associated with renal vasoconstriction and AKI risk 3

3. Medications 1, 6

   • Cyclosporine A in renal transplant recipients 6
   • Certain antibiotics with high chloride content 1

4. Diarrhea (bicarbonate loss from GI tract)

Clinical Implications

• Hyperchloremic metabolic acidosis may present with:

  • Weakness
  • Lethargy
  • Gastrointestinal disturbances
  • In severe cases, hemodynamic instability

• Management depends on the underlying cause:

  • For Addison's disease: mineralocorticoid replacement (fludrocortisone) 5
  • For iatrogenic causes: switch to balanced crystalloid solutions 3, 1
  • Address the primary disorder while monitoring electrolytes

In conclusion, among the options presented, Addison's disease (adrenal insufficiency) is the condition most strongly associated with hyperchloremic metabolic acidosis due to the pathophysiological consequences of aldosterone deficiency.