What are the causes of low CO₂ (bicarbonate) in arterial blood?

What Causes Low CO₂ in Blood

Low blood CO₂ (bicarbonate) is primarily caused by metabolic acidosis, where bicarbonate is either lost directly from the body or consumed buffering excess acid, or by chronic respiratory alkalosis from hyperventilation. 1

Primary Mechanisms of Low Bicarbonate

Metabolic Acidosis (Most Common)

In all forms of metabolic acidosis, there is a low blood bicarbonate level, occurring through two distinct pathways 1:

Direct Bicarbonate Loss

• Gastrointestinal losses: Chronic diarrhea causes direct bicarbonate wasting
• Renal losses: Kidney dysfunction leading to bicarbonate excretion

Bicarbonate Consumption (Buffering Excess Acid)

The bicarbonate is consumed buffering excess hydrogen ions and then excreted as CO₂:

Common causes include:

• Lactic acidosis from tissue hypoxia - the most frequent cause in acute settings, resulting from:

  • Hypoxemia (low oxygen delivery)
  • Low cardiac output states
  • Sepsis (impaired oxygen consumption despite adequate delivery)
  • Peak exercise in healthy individuals 1

• Diabetic ketoacidosis - abnormal metabolic acid production 1, 2

• Renal failure - inability to excrete acid from normal metabolic processes 1

Chronic Respiratory Alkalosis

Sustained hyperventilation lowers CO₂ levels, and over time the kidneys compensate by reducing bicarbonate retention, resulting in low bicarbonate with elevated pH (>7.45) 1, 3. This is commonly misdiagnosed as metabolic acidosis.

Critical Diagnostic Distinction

You must obtain arterial blood gas analysis to differentiate true metabolic acidosis from chronic respiratory alkalosis 3. Both present with low serum bicarbonate, but:

• Metabolic acidosis: pH <7.35, low bicarbonate
• Chronic respiratory alkalosis: pH >7.45, low bicarbonate, low PaCO₂

Important Pitfall: Pseudohypobicarbonatemia

Severe hypertriglyceridemia (>3,500 mg/dL) can cause falsely low bicarbonate readings on enzymatic autoanalyzers through lipid interference 4, 5, 6. The arterial blood gas will show normal bicarbonate despite the chemistry panel suggesting metabolic acidosis. Always check:

• Lipid panel if unexplained high anion gap
• Arterial blood gas to confirm true bicarbonate level
• Sample appearance (lipemic/milky)

This prevents unnecessary workup and inappropriate alkali therapy.

Clinical Algorithm for Evaluation

1. Measure arterial pH and PaCO₂ to determine if acidosis or alkalosis
2. Calculate anion gap: [Na⁺] - ([HCO₃⁻] + [Cl⁻]) 7
   • Normal (8-12): hyperchloremic metabolic acidosis
   • Elevated (>12): suggests organic acid accumulation
3. Check for lipemia if high anion gap with no clear cause
4. Assess urine anion gap to evaluate renal acidification 3