1. Clinical Manifestations and Initial Evaluation

Early recognition of neurologic, cardiovascular, and respiratory signs drives timely arterial blood gas (ABG) sampling and acid–base assessment.

Neurologic

• Acidemia: Manifests as a spectrum from confusion to lethargy, and ultimately to stupor or coma.
• Alkalemia: Can cause paresthesias, tetany (due to decreased ionized calcium), and hyperreflexia.

Cardiovascular

• Acidemia: Leads to decreased myocardial contractility, hypotension, and hyperkalemia, which increases the risk for arrhythmias.
• Alkalemia: Associated with hypokalemia and hypomagnesemia, which can prolong the QT interval and precipitate torsades de pointes.

Respiratory

• Metabolic acidosis: Characterized by Kussmaul respirations (deep, rapid breathing) as a compensatory mechanism.
• Respiratory acidosis: Results from hypoventilation, causing dyspnea.
• Respiratory alkalosis: Presents with tachypnea and may cause lightheadedness.

Initial Workup

A comprehensive initial evaluation includes an ABG with a basic metabolic panel (Na⁺, Cl⁻, HCO₃⁻, albumin) and a thorough history focusing on volume status, drug exposures, and underlying chronic diseases.

2. Arterial Blood Gas Interpretation

A stepwise ABG approach—assessing pH first, then determining the primary respiratory (PaCO₂) versus metabolic (HCO₃⁻) disturbance—is crucial. This framework is based on the Henderson–Hasselbalch equation: pH = pKa + log([HCO₃⁻] / (0.03 × PaCO₂)).

Normal Laboratory Ranges

• pH: 7.35–7.45
• PaCO₂: 35–45 mm Hg
• HCO₃⁻: 22–26 mEq/L

3. Anion Gap and Delta-Ratio Analysis

The anion gap (AG) is used to identify the presence of unmeasured anions, while the delta ratio helps to unmask mixed metabolic acidoses.

Anion Gap (AG) Calculation

• Formula: AG = [Na⁺] – ([Cl⁻] + [HCO₃⁻])
• Normal Range: 8–12 mEq/L
• Albumin Correction: Since albumin is the primary unmeasured anion, the AG must be corrected for hypoalbuminemia. A common formula is: Corrected AG = Measured AG + 2.5 × (4.0 – measured albumin [g/dL]).

Delta Ratio

The delta ratio assesses the relationship between the increase in the anion gap (ΔAG) and the decrease in bicarbonate (ΔHCO₃⁻).

• Calculation: Δ Ratio = (AGmeasured – 12) / (24 – HCO₃⁻measured)
• Interpretation:
  • 1 to 2: Suggests a pure high-AG metabolic acidosis (HAGMA).
  • <1: Suggests a mixed HAGMA and normal-AG metabolic acidosis (NAGMA), as HCO₃⁻ has decreased more than the AG has increased.
  • >2: Suggests a concurrent metabolic alkalosis, as HCO₃⁻ is higher than expected for the degree of AG elevation.

4. Compensatory Mechanisms and Expected Limits

Calculating the expected physiologic compensation is a critical step to distinguish simple acid-base disorders from more complex mixed disturbances. A mixed disorder is suspected whenever the actual measured values fall outside the predicted ranges.

5. Classification Systems and Severity Scores

Algorithms and severity metrics, such as base excess and the anion gap, help differentiate simple versus mixed disorders and inform the urgency of intervention.

Simple vs. Mixed Disorders

• Simple Disorder: Consists of one primary disturbance with the appropriate physiologic compensation.
• Mixed Disorder: Defined by the presence of more than one primary disorder. Compensation rules are violated.

Severity Thresholds and Metrics

• Base Excess (BE): A BE less than –5 mEq/L indicates significant metabolic acidosis, while a BE greater than +5 mEq/L indicates significant metabolic alkalosis.
• pH and Bicarbonate: A pH ≤7.20 or HCO₃⁻ ≤12 mEq/L is considered severe metabolic acidosis and warrants urgent attention.
• Anion Gap: An AG >16 mEq/L is an independent predictor of higher mortality in critically ill patients.

Risk Stratification

Clinical risk is best assessed by combining pH, base excess, anion gap, and evidence of end-organ dysfunction (e.g., acute kidney injury). These scores guide escalation of care, such as consideration for bicarbonate therapy or early renal replacement therapy (RRT).