Acid-Base Balance: ABG Analysis, Types of Acidosis and Alkalosis

1. Basic Concepts

• pH = −log[H⁺]. Normal 7.35–7.45 (extracellular); intracellular 7.0–7.2.
• Normal PaCO₂ is 35–45 mm Hg, reflecting alveolar ventilation.
• HCO₃⁻ 22–26 mmol/L is the metabolic component.
• BE (base excess) ± 2 reflects the metabolic component independently of PaCO₂.
• Henderson-Hasselbalch equation: pH = 6.1 + log([HCO₃⁻] / 0.03 × PaCO₂).

2. Buffer Systems

• Bicarbonate-carbonic acid system is the key blood buffer; regulated by lungs and kidneys.
• Hemoglobin is effective in erythrocytes (deoxygenated Hb binds H⁺).
• Phosphates act mainly in the intracellular fluid and urine.
• Plasma proteins bind H⁺ via amino acid side chains.

3. Pulmonary Regulation

• Rapid response (minutes): alteration of alveolar ventilation.
• Acidosis → hyperventilation → ↓ PaCO₂.
• Alkalosis → hypoventilation → ↑ PaCO₂ (limited by hypoxemia).

4. Renal Regulation

• Slow response (hours to days): HCO₃⁻ reabsorption, H⁺ secretion, generation of new HCO₃⁻.
• Proximal tubule reabsorbs 80–90% of HCO₃⁻ via Na⁺-H⁺ exchanger and carbonic anhydrase.
• Distal tubule and collecting duct — α-intercalated cells secrete H⁺ (H⁺-ATPase) and generate new HCO₃⁻.
• Titratable acidity (phosphates) + ammonium (NH₄⁺) are the main routes of H⁺ excretion.

5. Interpretation Algorithm

Step 1. Assessment of pH

• < 7.35 — acidosis; > 7.45 — alkalosis.
• If 7.35–7.45 — normal or compensated/mixed.

Step 2. Primary Disorder

• Acidosis: if ↑ PaCO₂ — respiratory; if ↓ HCO₃⁻ — metabolic.
• Alkalosis: if ↓ PaCO₂ — respiratory; if ↑ HCO₃⁻ — metabolic.

Step 3. Compensation (Winters' formula and others)

• Metabolic acidosis: expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2.
• Metabolic alkalosis: ↑ PaCO₂ by 0.7 mm Hg for every ↑ 1 mmol/L in HCO₃⁻.
• Acute respiratory acidosis: ↑ HCO₃⁻ by 1 mmol/L for every ↑ 10 mm Hg in PaCO₂.
• Chronic respiratory acidosis: ↑ HCO₃⁻ by 4 mmol/L for every ↑ 10 mm Hg.
• Acute respiratory alkalosis: ↓ HCO₃⁻ by 2 mmol/L for every ↓ 10 mm Hg.
• Chronic respiratory alkalosis: ↓ HCO₃⁻ by 5 mmol/L for every ↓ 10 mm Hg.

Step 4. Anion Gap (AG)

• AG = Na⁺ − (Cl⁻ + HCO₃⁻); normal 8–12 mmol/L.
• Albumin correction: AG_corr = AG + 2.5 × (40 − albumin g/L).
• In metabolic acidosis: high AG — accumulation of unmeasured anions; normal — loss of HCO₃⁻ or ↑ Cl⁻.

Step 5. ΔΔ (Delta Gap)

• ΔAG / ΔHCO₃⁻ = (AG − 12) / (24 − HCO₃⁻).
• Normal 1–2 — pure AG acidosis.
• < 1 — combination with normal AG acidosis.
• > 2 — combination with metabolic alkalosis.

6. Metabolic Acidosis

High AG (MUDPILES)

• Methanol (formate).
• Uremia.
• DKA, alcoholic/starvation ketoacidosis.
• Propylene glycol, paracetamol (pyroglutamic acid).
• Isoniazid, iron.
• Lactic acidosis (shock, metformin, reverse transcriptase inhibitors).
• Ethylene glycol (oxalate).
• Salicylates.

Normal AG (hyperchloremic)

• Diarrhea.
• Renal tubular acidosis (RTA I, II, IV).
• Ureteral diversion to the bowel (ureterosigmoidostomy).
• Carbonic anhydrase inhibitors (acetazolamide).
• Early 0.9% NaCl expansion (hyperchloremic acidosis post-infusion).
• Hypoaldosteronism.

7. Metabolic Alkalosis

• Chloride-responsive (urine chloride < 20 mmol/L): vomiting, nasogastric tube, diuretics (late), cystic fibrosis.
• Chloride-resistant (urine chloride > 20): primary hyperaldosteronism, Cushing's syndrome, Bartter syndrome, Gitelman syndrome, exogenous mineralocorticoids.
• Pathogenesis: H⁺ loss or HCO₃⁻ gain/retention.
• Clinical presentation: tetany, seizures, arrhythmias, hypoventilation.
• Treatment: volume and Cl⁻ replenishment (0.9% NaCl), KCl for hypokalemia; acetazolamide for volume overload; HCl or arginine hydrochloride in severe cases (pH > 7.6).

8. Respiratory Acidosis

• Causes of hypoventilation: CNS depression (opioids, benzodiazepines, stroke), neuromuscular (Guillain-Barré, myasthenia gravis), chest trauma, COPD, severe asthma attack, obstructive sleep apnea, obesity-hypoventilation syndrome.
• Clinical presentation: somnolence, confusion, asterixis, coma.
• Treatment: respiratory support (NIV, mechanical ventilation), address the underlying cause; avoid rapid normalization in chronic compensation.

9. Respiratory Alkalosis

• Causes of hyperventilation: anxiety, panic, pain, fever, hypoxia (PE, pneumonia, ARDS), septic shock, CNS processes, hepatic failure, salicylates (mixed disorder), pregnancy (physiological).
• Clinical presentation: paresthesias, tetany (decreased ionized Ca²⁺), syncope, arrhythmias.
• Treatment — addressing the underlying cause.

10. Mixed Disorders

11. Alternative Approaches

• Stewart approach ( physicochemical): SID (strong ion difference), ATot (weak acids), PCO₂.
• Base excess (BE) according to Van Slyke or Siggaard-Andersen.
• Osmolal gap — suspicion of methanol/ethylene glycol/propylene glycol (measured osmolality − calculated > 10).

12. Correction and Treatment

• Treatment should target the underlying cause.
• Sodium bicarbonate in metabolic acidosis is controversial; indicated at pH < 7.1 combined with cardiac issues, hyperkalemia, TCA overdose, rhabdomyolysis.
• Avoid overcorrection: rapid ↑ pH → hypokalemia, hypocalcemia, sodium overload.
• Monitoring: K⁺, Ca²⁺, Mg²⁺.

13. FAQ

When is the anion gap considered increased?
When > 12 (corrected for albumin). Borderline values require correlation with clinical presentation and the delta gap. Low albumin masks ↑ AG.

Why is a mixed disorder common in sepsis?
Lactic acidosis + respiratory alkalosis (hyperventilation). With AKI — additional metabolic acidosis; with vomiting — metabolic alkalosis.

What is RTA?
Renal tubular acidosis — hyperchloremic metabolic acidosis with normal AG. Type I — distal (H⁺ secretion failure), Type II — proximal (HCO₃⁻ reabsorption failure), Type IV — hypoaldosteronemic (hyperkalemic).

How fast should pH be corrected?
No faster than 0.1 per hour. Rapid correction is dangerous due to shifts in ionized Ca²⁺, K⁺, and CNS disturbances.

Why does pH drop after large-volume resuscitation with 0.9% NaCl?
Chloride load displaces HCO₃⁻ — hyperchloremic metabolic acidosis with normal AG. Alternatives: balanced solutions (Ringer's lactate, Plasmalyte).

See also: Gas exchange · DKA · AKI · Sepsis · Physiology Catalog