1) Acidaemia or alkalaemia? 2) Primary process (look at PaCO2 and HCO3-). 3) Is compensation appropriate? 4) Anion gap (correct for albumin). 5) If HAGMA, the delta ratio reveals hidden disorders. Then the clinical story.
At the bedside
Timed steps- 1
pH
Step 1< 7.35 acidaemia, > 7.45 alkalaemia. A normal pH does not exclude a mixed disorder.
- 2
Primary process
Step 2pH low + HCO3- low = metabolic acidosis; pH low + PaCO2 high = respiratory acidosis; pH high + HCO3- high = metabolic alkalosis; pH high + PaCO2 low = respiratory alkalosis.
- 3
Compensation
Step 3Metabolic acidosis: expected PaCO2 = 1.5 × HCO3- + 8 (± 2) (Winters). Metabolic alkalosis: PaCO2 rises ~0.7 per 1 mmol/L HCO3- rise. Respiratory: see the compensation table. Outside range = second disorder.
- 4
Anion gap
Step 4AG = Na+ − (Cl- + HCO3-); normal ≈ 8-12 (analyser-dependent). Corrected AG = AG + 2.5 × (40 − albumin g/L)/10, i.e. + 2.5 per 10 g/L fall in albumin.
- 5
Delta ratio
Step 5(AG − 12) ÷ (24 − HCO3-). < 0.4 = NAGMA; 0.4-0.8 = mixed HAGMA + NAGMA; 0.8-2 = pure HAGMA; > 2 = HAGMA + metabolic alkalosis (or pre-existing high HCO3-).
- 6
Oxygenation
ThenA-a gradient = PAO2 − PaO2, where PAO2 = FiO2 × (760 − 47) − PaCO2/0.8. Normal ≈ age/4 + 4 on room air.
Expected compensation
| Disorder | Rule |
|---|---|
| Metabolic acidosis | PaCO2 = 1.5 × HCO3- + 8 (± 2) |
| Metabolic alkalosis | PaCO2 rises 0.7 mmHg per 1 mmol/L HCO3- rise |
| Acute respiratory acidosis | HCO3- rises 1 per 10 mmHg PaCO2 rise |
| Chronic respiratory acidosis | HCO3- rises 3.5-4 per 10 mmHg PaCO2 rise |
| Acute respiratory alkalosis | HCO3- falls 2 per 10 mmHg PaCO2 fall |
| Chronic respiratory alkalosis | HCO3- falls 4-5 per 10 mmHg PaCO2 fall |
Calculators for this topic
Anion gap
Na⁺ − (Cl⁻ + HCO₃⁻). Correct for albumin.
Albumin-corrected anion gap
AG + 2.5 × (4.0 − albumin g/dL).
Delta ratio
(AG − 12) ÷ (24 − HCO₃⁻). Detects a second metabolic process in a high-AG acidosis.
Expected PaCO₂ (Winter's formula)
Expected PaCO₂ = 1.5 × HCO₃⁻ + 8 (± 2) in metabolic acidosis.
Alveolar-arterial O₂ gradient
PAO₂ = FiO₂ × (Patm − 47) − PaCO₂/0.8; A-a = PAO₂ − PaO₂.
Five-step gas
Step 1 of ~4
Decision: pH?
Based on Berend K, de Vries APJ, Gans ROB. Educational use; follow local protocol.
Pathophysiology
The bicarbonate-CO2 buffer system follows Henderson-Hasselbalch: pH = 6.1 + log(HCO3- / 0.03 × PaCO2). The Stewart approach (strong ion difference, weak acids, PaCO2) explains chloride and albumin effects and is complementary.
Evidence
- Berend 2014: physiological (bicarbonate-based) approach with compensation rules, anion gap and delta ratio.
- Figge 1998: each 10 g/L fall in albumin lowers the anion gap by ~2.5 mmol/L.
Controversies
- Physiological vs Stewart vs base-excess approaches give similar bedside conclusions when applied correctly.
🇮🇳 India notes
- Hypoalbuminaemia (malnutrition, chronic liver disease, sepsis) is very common in Indian ICUs; always correct the anion gap.
References
Test yourself
Module quiz · score 70% to complete the module
Educational reference for trained clinicians. Check doses against your hospital protocol and the patient in front of you.

