Acid-Base Balance: How to Interpret Any Blood Gas in 3 Minutes
Acid-base physiology is one of the most clinically important and reliably tested topics in all of medicine. Every critically ill patient has an acid-base disturbance. Every MCAT, USMLE Step 1, and AP Biology/Chemistry exam tests it. This guide gives you the systematic approach used by experienced clinicians to interpret any blood gas — in under 3 minutes.
AI-generated content. This guide was written by MedAI's AI and is intended as a study aid. Always cross-reference with your official course materials, textbooks, and instructor guidance before your exam.
The Core Chemistry: What Is pH?
pH = −log[H⁺]. Physiological blood pH is tightly maintained between 7.35 and 7.45. Below 7.35 is acidosis; above 7.45 is alkalosis. Small changes in pH represent large changes in H⁺ concentration due to the logarithmic relationship.
Key Normal Values
Memorize these: pH 7.40 (7.35–7.45) | PaCO₂ 40 mmHg (35–45) | HCO₃⁻ 24 mEq/L (22–26) | PaO₂ 95 mmHg. These are the reference points for every blood gas interpretation.
The Henderson-Hasselbalch Equation
pH = pKa + log([A⁻]/[HA]). For the bicarbonate buffer system (the most important in blood): pH = 6.1 + log([HCO₃⁻] / [0.03 × PaCO₂]). This shows that pH depends on the ratio of bicarbonate (metabolic component, controlled by kidneys) to CO₂ (respiratory component, controlled by lungs).
The Two Axes: Respiratory vs. Metabolic
Every acid-base disorder is either respiratory (problem with CO₂ elimination by lungs) or metabolic (problem with HCO₃⁻ by kidneys). This gives 4 primary disturbances:
| Disorder | Primary Change | pH | Cause Examples |
|---|---|---|---|
| Metabolic Acidosis | ↓ HCO₃⁻ | ↓ (acidic) | Diarrhea, DKA, lactic acidosis, renal failure, aspirin OD |
| Metabolic Alkalosis | ↑ HCO₃⁻ | ↑ (alkaline) | Vomiting, diuretics (loop/thiazide), hyperaldosteronism |
| Respiratory Acidosis | ↑ PaCO₂ (hypoventilation) | ↓ (acidic) | COPD, opioid OD, neuromuscular disease, obesity hypoventilation |
| Respiratory Alkalosis | ↓ PaCO₂ (hyperventilation) | ↑ (alkaline) | Anxiety, pain, pulmonary embolism, altitude, salicylate toxicity (early) |
The 5-Step Blood Gas Interpretation Framework
- 1Step 1 — Check pH: Is it acidic (<7.35), normal (7.35–7.45), or alkaline (>7.45)?
- 2Step 2 — Identify the primary disorder: If pH is acidic, look for ↓HCO₃⁻ (metabolic acidosis) or ↑PaCO₂ (respiratory acidosis). If alkaline, look for ↑HCO₃⁻ or ↓PaCO₂.
- 3Step 3 — Check for compensation: Compensation never fully normalizes pH. Metabolic acidosis compensates with hyperventilation (↓PaCO₂). Respiratory acidosis compensates with bicarbonate retention (↑HCO₃⁻).
- 4Step 4 — Is compensation appropriate? Use expected compensation equations (below). If actual compensation ≠ expected, there is a MIXED disorder.
- 5Step 5 — If metabolic acidosis: calculate the Anion Gap to identify the cause.
Compensation Formulas (High-Yield)
| Primary Disorder | Expected Compensation | Formula |
|---|---|---|
| Metabolic Acidosis | Respiratory (↓PaCO₂) | PaCO₂ = 1.5 × [HCO₃⁻] + 8 ± 2 (Winters' formula) |
| Metabolic Alkalosis | Respiratory (↑PaCO₂) | PaCO₂ = 0.7 × [HCO₃⁻] + 21 ± 2 |
| Respiratory Acidosis (acute) | Metabolic (↑HCO₃⁻) | ↑HCO₃⁻ by 1 mEq/L per 10 mmHg ↑PaCO₂ |
| Respiratory Acidosis (chronic) | Metabolic (↑HCO₃⁻) | ↑HCO₃⁻ by 3.5 mEq/L per 10 mmHg ↑PaCO₂ |
| Respiratory Alkalosis (acute) | Metabolic (↓HCO₃⁻) | ↓HCO₃⁻ by 2 mEq/L per 10 mmHg ↓PaCO₂ |
| Respiratory Alkalosis (chronic) | Metabolic (↓HCO₃⁻) | ↓HCO₃⁻ by 5 mEq/L per 10 mmHg ↓PaCO₂ |
The Anion Gap: Finding the Cause of Metabolic Acidosis
Anion Gap (AG) = Na⁺ − (Cl⁻ + HCO₃⁻). Normal AG = 8–12 mEq/L (mainly albumin). The anion gap tells you whether an unmeasured acid is accumulating.
| AG Type | Value | Causes — Mnemonic |
|---|---|---|
| High Anion Gap Metabolic Acidosis (HAGMA) | >12 | MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates |
| Normal Anion Gap Metabolic Acidosis (NAGMA) | 8–12 | HARDUPS: Hyperalimentation, Addison's, Renal tubular acidosis, Diarrhea, Ureteroenteric fistula, Pancreatic fistula, Saline infusion |
Delta-Delta Ratio for Mixed Disorders
If AG is elevated, calculate the delta-delta: Δ AG / Δ HCO₃⁻. Ratio 1–2: pure HAGMA. Ratio >2: HAGMA + concurrent metabolic alkalosis (e.g., DKA + vomiting). Ratio <1: HAGMA + concurrent NAGMA.
Clinical Presentation Clues
- Kussmaul breathing (deep, rapid): classic sign of metabolic acidosis — the body hyperventilating to blow off CO₂
- Carpopedal spasm / Chvostek sign: alkalosis → ↑ protein binding of Ca²⁺ → hypocalcemia symptoms
- Confusion/arrhythmias: severe acidosis or alkalosis both disrupt cardiac and neural ion channels
- DKA triad: Kussmaul breathing + fruity breath (acetone) + polyuria/polydipsia; pH often 7.1–7.2
- Hyperchloremic NAGMA after massive saline infusion: common post-surgical complication
Buffer Systems in the Body
| Buffer System | Location | pKa | Importance |
|---|---|---|---|
| Bicarbonate/CO₂ | Blood (extracellular) | 6.1 | Most important physiological buffer; linked to respiratory and renal regulation |
| Phosphate (H₂PO₄⁻/HPO₄²⁻) | Intracellular, urine | 6.8 | Important for urinary acid excretion; urinary buffer |
| Proteins (histidine residues) | Intracellular, blood (hemoglobin) | ~6.0 | Hemoglobin is a major blood buffer; tissues |
| Ammonia (NH₃/NH₄⁺) | Renal tubule | 9.0 | Renal ammoniagenesis: major route for chronic acid excretion; impaired in renal failure |
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