What are the causes of low bicarbonate levels?

Causes of Low Bicarbonate Levels

Low bicarbonate levels are primarily caused by metabolic acidosis, which can result from increased acid production, decreased acid excretion, or direct bicarbonate loss from the body. 1

Metabolic Acidosis Categories

1. Increased Acid Production

• Diabetic Ketoacidosis (DKA)

  • Results from insulin deficiency leading to increased production of ketone bodies (acetoacetate and β-hydroxybutyrate)
  • Characterized by high anion gap acidosis with glucose >250 mg/dl, pH <7.30, and bicarbonate <18 mEq/L 1

• Lactic Acidosis

  • Caused by tissue hypoxia from:
    • Decreased oxygen delivery (hypoxemia)
    • Low cardiac output states
    • Sepsis (where oxygen consumption is impaired despite adequate delivery)
    • Peak exercise in healthy individuals 1

• Drug and Toxin-Induced Acidosis

  • Salicylates, methanol, ethylene glycol, and paraldehyde 1
  • Biguanides, alcohols, polyhydric sugars, cyanide, and carbon monoxide 2

• Starvation Ketosis

  • Distinguished from DKA by clinical history and lower glucose levels
  • Serum bicarbonate usually not lower than 18 mEq/L 1

• Alcoholic Ketoacidosis (AKA)

  • Can result in profound acidosis
  • Glucose ranges from mildly elevated to hypoglycemic 1

2. Decreased Acid Excretion

• Renal Failure (Acute or Chronic)

  • Failure to excrete acid produced by normal metabolic processes 1
  • Common in patients with chronic kidney disease (CKD) 3
  • Particularly problematic in hemodialysis patients, with 73% showing predialysis bicarbonate <22 mEq/L 3

• Type 2 Respiratory Failure

  • Hypercapnia (elevated PaCO2) leads to respiratory acidosis
  • Can become chronic with renal compensation, but acute exacerbations can overwhelm compensatory mechanisms 1

3. Direct Bicarbonate Loss

• Gastrointestinal Losses

  • Severe diarrhea with significant bicarbonate loss 4
  • Chronic diarrhea leading to direct loss of bicarbonate from the gut 1

• Renal Tubular Acidosis

  • Failure of the kidneys to properly reabsorb bicarbonate or excrete acid 5

• Iatrogenic Causes

  • Certain dialysis procedures, such as sorbent system hemodialysis, can induce metabolic acidosis 6

• Medication-Induced Normal Anion Gap Acidosis

  • Carbonic anhydrase inhibitors
  • Hydrochloride salts of amino acids
  • Toluene, amphotericin, spironolactone
  • Non-steroidal anti-inflammatory drugs 2

Clinical Implications

Low bicarbonate levels (metabolic acidosis) are associated with:

• Increased protein degradation and protein-energy wasting
• Inflammation
• Bone disease
• Endocrine dysfunction
• Decreased albumin synthesis
• Increased oxidation of branched-chain amino acids 1

Monitoring and Management

• For patients with chronic kidney disease, especially those on dialysis, serum bicarbonate should be monitored regularly (monthly) 1
• Target serum bicarbonate levels should be maintained at or above 22 mmol/L 1, 3
• In severe metabolic acidosis (pH ≤7.0), bicarbonate therapy may be indicated 5
• For chronic bicarbonate replacement, oral sodium bicarbonate (2-4 g/day or 25-50 mEq/day) can effectively increase serum bicarbonate concentrations 1

Diagnostic Approach

When evaluating low bicarbonate levels:

1. Calculate the anion gap: Na⁺ - (Cl⁻ + HCO₃⁻)
2. Determine if it's a high anion gap acidosis (increased unmeasured anions) or normal anion gap acidosis (hyperchloremic)
3. Consider arterial blood gas analysis to confirm metabolic acidosis and assess for respiratory compensation
4. Evaluate for potential causes based on clinical context and additional laboratory findings

Remember that bicarbonate levels should be interpreted in the context of the overall clinical picture, including pH, PaCO₂, and electrolyte values.