What is acidity (acidosis), what are its causes, how does bicarbonate (HCO₃⁻) buffer hydrogen ions, and how is diabetic ketoacidosis (DKA) diagnosed?

Understanding Acidity, Bicarbonate Buffering, and DKA Diagnosis

What is Acidity (Acidosis)?

Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO₃⁻) concentration, a compensatory decrease in arterial partial pressure of carbon dioxide (PaCO₂) of approximately 1 mmHg for every 1 mmol/L fall in serum HCO₃⁻, and a reduction in blood pH 1. This represents a fundamental disturbance in the body's acid-base balance where hydrogen ion (H⁺) accumulation exceeds the body's buffering capacity.

Acidosis exists in two temporal forms:

• Acute forms (minutes to days): Most frequently result from overproduction of organic acids such as ketoacids or lactic acid
• Chronic forms (weeks to years): Often reflect bicarbonate wasting and/or impaired renal acidification 1

Causes of Acidosis

The serum anion gap—calculated as [Na⁺] - ([HCO₃⁻] + [Cl⁻])—is the critical tool for categorizing acidosis into two main types 1:

Elevated Anion Gap Acidosis

• Ketoacidosis (diabetic, alcoholic, starvation)
• Lactic acidosis
• Renal failure (accumulation of organic acids)
• Toxic ingestions (salicylates, methanol, ethylene glycol)

Normal (Hyperchloremic) Anion Gap Acidosis

• Bicarbonate loss (diarrhea, renal tubular acidosis)
• Iatrogenic causes (excessive chloride-rich fluid administration) 2

Important caveat: These categories can overlap, particularly in DKA where both elevated anion gap acidosis from ketoacids and hyperchloremic acidosis from fluid resuscitation may coexist 2.

How Bicarbonate (HCO₃⁻) Buffers Hydrogen Ions

The bicarbonate buffer system is the body's primary extracellular buffering mechanism, operating through the following equilibrium:

H⁺ + HCO₃⁻ ⇌ H₂CO₃ ⇌ CO₂ + H₂O

When excess hydrogen ions accumulate:

1. HCO₃⁻ binds to H⁺ to form carbonic acid (H₂CO₃)
2. Carbonic acid rapidly dissociates into CO₂ and water
3. CO₂ is eliminated through increased respiratory rate (respiratory compensation)
4. The result: Serum HCO₃⁻ decreases as it is consumed buffering the acid load, and PaCO₂ decreases through hyperventilation 1

This system is effective because:

• The lungs can rapidly adjust CO₂ elimination
• The kidneys can regenerate HCO₃⁻ (though this takes days)
• The equilibrium can shift in either direction based on physiologic needs

Critical limitation: The buffering capacity is finite—once HCO₃⁻ is depleted below approximately 15-18 mmol/L, the system becomes overwhelmed and pH drops precipitously 1.

How DKA is Diagnosed

DKA is confirmed when all three criteria are present: 'D' (diabetes/hyperglycemia), 'K' (elevated ketoacids), and 'A' (high anion gap metabolic acidosis) 3.

Traditional Diagnostic Criteria 4

• Hyperglycemia: Blood glucose >250 mg/dL (13.9 mmol/L)
• Metabolic acidosis:
  • pH <7.3
  • Serum bicarbonate <18 mEq/L
  • Anion gap >10 mEq/L
• Elevated ketones: Serum (preferred) or urine ketones present

Modern Diagnostic Considerations

Hyperglycemia has been de-emphasized in recent guidelines due to the increasing incidence of euglycemic DKA 4. This is particularly relevant with SGLT2 inhibitor use, which modestly increases DKA risk even with normal glucose levels 5, 4.

Quantitative Ketone Measurement

Serum β-hydroxybutyrate (β-HB) levels ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults, in the presence of uncontrolled diabetes, can be used to diagnose DKA and may be superior to serum HCO₃⁻ for that purpose 6. However:

• A HCO₃⁻ of 18 mmol/L equates to a β-HB of approximately 4.3 mmol/L 7
• Blood glucose correlates poorly with β-HB (r=0.28), pH (r=-0.25), and HCO₃⁻ (r=-0.17) 7
• β-HB itself shows only moderate correlation with pH (r=-0.44) and HCO₃⁻ (r=-0.49) 7

Critical pitfall: Approximately 17% of patients with significant acidosis (HCO₃⁻ <18 mmol/L) may not be hyperglycemic (>13.9 mmol/L) or have β-HB >3 mmol/L 7. Therefore, regardless of glucose or β-HB results, pH and/or HCO₃⁻ should always be tested in any patient suspected of DKA 7.

Essential Laboratory Workup 4

For all patients diagnosed with DKA, evaluate:

• Electrolytes (sodium, potassium, chloride, bicarbonate)
• Phosphate
• Blood urea nitrogen and creatinine
• Urinalysis
• Complete blood count with differential
• A1C
• Electrocardiography

Additional tests to consider based on clinical presentation:

• Amylase, lipase (if abdominal pain)
• Hepatic transaminases
• Troponin, creatine kinase (if chest pain)
• Blood and urine cultures (if infection suspected)
• Chest radiography (if respiratory symptoms)

DKA Severity Classification 8

Based on the degree of acidosis and mental status:

• Mild: pH 7.25-7.30, HCO₃⁻ 15-18 mEq/L
• Moderate: pH 7.00-7.24, HCO₃⁻ 10-14 mEq/L
• Severe: pH <7.00, HCO₃⁻ <10 mEq/L

Bicarbonate Therapy in DKA

Several studies have shown that the use of bicarbonate in people with DKA made no difference in the resolution of acidosis or time to discharge, and its use is generally not recommended 5. However, recent evidence suggests potential protective associations with organ function when used judiciously 9. The current guideline recommendation remains that bicarbonate should only be considered in extreme acidemia (pH <6.9) due to concerns about paradoxical central nervous system acidosis, delayed ketone clearance, and electrolyte imbalances 4, 8.