Arterial Blood Gas (ABG) Analysis: Basic to Clinical Application

1. What Is an ABG and Why Does It Matter?

2. Normal ABG Values

pH < 7.35 = acidemia | pH > 7.45 = alkalemia

3. The Henderson-Hasselbalch Equation (The Core Physiology)

• The numerator (HCO3-) is controlled by the kidneys (slow, days)
• The denominator (PaCO2) is controlled by the lungs (fast, minutes)
• Together they maintain pH at 7.40

4. The Four Primary Acid-Base Disorders

5. Compensation Formulas (Memorize These)

Metabolic Acidosis

• Compensation begins within 12-24 hours
• Alternatively: ↓PaCO2 = 1.1 × ↓[HCO3-]

Metabolic Alkalosis

• Compensation within 24-48 hours
• Alternatively: ↑PaCO2 = 0.75 × ↑[HCO3-]

Respiratory Acidosis

• Acute: Δ[HCO3-] = +1 mEq/L per 10 mmHg rise in PaCO2
• Chronic: Δ[HCO3-] = +4 mEq/L per 10 mmHg rise in PaCO2
• Compensation develops over 48-96 hours

Respiratory Alkalosis

• Acute: Δ[HCO3-] = -2 mEq/L per 10 mmHg fall in PaCO2
• Chronic: Δ[HCO3-] = -4 to -5 mEq/L per 10 mmHg fall in PaCO2
• Compensation develops over 48-96 hours

6. Systematic Step-by-Step ABG Interpretation

Step 1: Is the Patient Acidemic or Alkalemic?

• pH < 7.35 → acidemia
• pH > 7.45 → alkalemia
• pH 7.35-7.45 → normal (but a mixed disorder may still exist!)

Step 2: Identify the Primary Disorder

• PaCO2 high + low pH → Respiratory Acidosis
• PaCO2 low + high pH → Respiratory Alkalosis
• HCO3- low + low pH → Metabolic Acidosis
• HCO3- high + high pH → Metabolic Alkalosis

Step 3: Is Compensation Appropriate?

• More acidotic than expected → additional metabolic acidosis
• More alkalotic than expected → additional metabolic alkalosis

Step 4: Calculate the Anion Gap (if metabolic acidosis present)

• Normal: 8-12 mEq/L (or up to 13 with albumin correction)
• Correct for albumin: For every 1 g/dL albumin below 4 g/dL, add 2.5 mEq/L to AG

• Methanol
• Uremia
• DKA (and other ketoacidosis)
• Propylene glycol / Paraldehyde
• Isoniazid / Iron
• Lactic acidosis
• Ethylene glycol
• Salicylates

• Diarrhea (GI bicarbonate loss)
• Renal tubular acidosis (RTA)
• Carbonic anhydrase inhibitors (acetazolamide)
• Saline resuscitation (dilutional)
• Ureteral diversion

Step 5: Delta-Delta Ratio (for High AG Acidosis)

7. Physiologic Consequences of Extreme Derangements

Severe Acidemia (pH < 7.2)

Severe Alkalemia (pH > 7.6)

8. Oxygenation Assessment

A-a Gradient (Alveolar-Arterial Oxygen Difference)

• On room air at sea level: PAO2 = 150 - (PaCO2/0.8)
• A-a gradient = PAO2 - PaO2
• Normal: < 10-15 mmHg (increases with age: ~age/4 + 4)

P/F Ratio (Oxygenation Index)

• Normal: > 400 mmHg
• Mild ARDS: 200-300
• Moderate ARDS: 100-200
• Severe ARDS: < 100

9. Mixed Acid-Base Disorders

1. pH is normal but PaCO2 and HCO3- are both abnormal
2. Compensation exceeds or falls short of expected range
3. Delta-delta ratio is outside 1-2

• ABG: pH 7.47 / PaCO2 25 / PaO2 180
• Step 1: pH 7.47 → alkalemia
• Step 2: PaCO2 25 → respiratory alkalosis
• Step 3: Predicted pH for this PaCO2 = 7.40 + [(40-25)/10 × 0.08] = 7.52
• Measured pH (7.47) is lower than predicted (7.52) → concurrent metabolic acidosis
• Final diagnosis: Mixed respiratory alkalosis + metabolic acidosis

10. Potassium and Acid-Base

• Metabolic acidosis → K+ shifts out of cells → hyperkalemia
• For each ↓0.10 in pH, K+ rises ~0.6 mEq/L
• Metabolic alkalosis → K+ shifts into cells → hypokalemia
• Hypokalemia itself maintains metabolic alkalosis by enhancing H+-K+-ATPase in the collecting duct and increasing NH4+ excretion

DKA and lactic acidosis are exceptions - they often present with low total body K+ despite acidemia due to osmotic diuresis and poor intake.

11. Clinical Applications by Setting

ICU / Critical Care

• Serial ABGs guide mechanical ventilation settings (target PaCO2, pH)
• ABG is superior to pulse oximetry alone - SpO2 cannot detect hypercapnia or acid-base disorders
• In septic shock, lactic acidosis drives high-AG metabolic acidosis; pH < 7.2 carries increased mortality
• BICAR-ICU trial: NaHCO3 showed no overall mortality benefit in severe metabolic acidemia but did reduce need for renal replacement therapy in patients with AKI

Respiratory Failure

• ABG distinguishes Type 1 (hypoxemic, PaO2 < 60, normal PaCO2) from Type 2 (hypercapnic, PaCO2 > 45) respiratory failure
• COPD exacerbation: chronic compensated respiratory acidosis with elevated HCO3-; acute decompensation shows pH fall without proportional HCO3- rise
• Use BE + PaCO2 trend to guide NIV/intubation decisions

Metabolic Emergencies

• DKA: High-AG metabolic acidosis, pH can be 6.9-7.2, hyperkalemia, acetone on breath
• HHS: Minimal acidosis (if any), extreme hyperglycemia, severe dehydration
• Lactic acidosis: Sepsis, mesenteric ischemia, metformin overdose, type B causes
• Hyperchloremic acidosis: Aggressive saline resuscitation, diarrhea, RTA

Poisoning/Toxicology

• Salicylates: Mixed respiratory alkalosis + metabolic acidosis (classic)
• Methanol/ethylene glycol: High AG acidosis + elevated osmol gap
• Opioids: Respiratory acidosis with hypoxia
• TCA overdose: Mixed respiratory and metabolic acidosis

Perioperative/Anesthesia

• Goal-directed fluid therapy: Excessive 0.9% saline causes hyperchloremic metabolic acidosis; balanced crystalloids (LR, PlasmaLyte) reduce this risk
• Post-cardiac surgery: Metabolic alkalosis from citrate in blood products, diuretics
• Permissive hypercapnia in laparoscopic surgery (CO2 pneumoperitoneum) → respiratory acidosis

12. Clinical Clues Without ABG

• Elevated AG on chemistry panel → high-AG metabolic acidosis even without blood gas
• Low Cl- + high HCO3- → metabolic alkalosis (vomiting, diuretics)
• Physical exam: tetany (alkalemia), Kussmaul breathing (metabolic acidosis), cyanosis (respiratory failure)
• Drug history: acetazolamide → metabolic acidosis; loop/thiazide diuretics → metabolic alkalosis

13. Three-Step Clinical Algorithm (Quick Reference)

1. Is the patient acidemic or alkalemic?
   ├── pH < 7.35 → Acidemia
   └── pH > 7.45 → Alkalemia

2. Is the primary disorder metabolic or respiratory?
   ├── pH↓ + PaCO2↑ → Respiratory Acidosis
   ├── pH↑ + PaCO2↓ → Respiratory Alkalosis
   ├── pH↓ + HCO3-↓ → Metabolic Acidosis
   └── pH↑ + HCO3-↑ → Metabolic Alkalosis

3. Is compensation appropriate?
   └── If not → Mixed disorder present
       ├── If high-AG acidosis: Calculate delta-delta ratio
       └── Interpret oxygenation: P/F ratio, A-a gradient

Sources

• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e - Chapters 16 (Acid-Base, Fluids, Electrolytes), pp. 1146-1155
• Brenner and Rector's The Kidney - Chapter 16, Stepwise Approach to Acid-Base Disorders, pp. 700-705
• Rosen's Emergency Medicine - Box 113.2, Three-Step ABG Algorithm, p. 2505
• Recent review: Sanagustín MN & Osredkar J, "Blood gas analysis: Clinical applications, interpretation and future directions," Medicine International, 2026 [PMID: 41473681]
• Practice guideline: Habib T et al., "Mastering blood gas interpretation: A practical guide for primary care providers," S Afr Fam Pract, 2025 [PMID: 40336441]