Acid-Base Review: A Comprehensive Student Guide

The ABC Method for Systematic Blood Gas Interpretation

Clinical Mastery Series Urine Nephrology Now
Index ABG vs VBG RTA Types SGLT2 eDKA Sodium Bicarbonate

Author: Andrew Bland, MD, MBA, MS

1. Introduction

Understanding acid-base disorders is crucial for medical practice. This guide provides a systematic approach to interpreting blood gases and identifying acid-base disturbances.

Key Concepts:
  • Acidemia: Blood pH < 7.40 (acid in the blood)
  • Alkalemia: Blood pH > 7.40 (alkaline blood)
  • Acidosis: The underlying condition causing acidemia
  • Alkalosis: The underlying condition causing alkalemia

Note: You can have acidosis without acidemia if another disorder is compensating.

2. The ABC's of Acid-Base Analysis

A. Initial Assessment

  1. Identify acidemia or alkalemia
    • pH < 7.40 = Acidemia
    • pH > 7.40 = Alkalemia
  2. Identify primary disorder
    • Metabolic: Changes in HCO3¹¯
      • ↑ HCO3¹¯ (> 24 mEq/L) = Metabolic alkalosis
      • ↓ HCO3¹¯ (< 24 mEq/L) = Metabolic acidosis
    • Respiratory: Changes in pCO2
      • ↑ pCO2 (> 40 mmHg) = Respiratory acidosis
      • ↓ pCO2 (< 40 mmHg) = Respiratory alkalosis

B. Assess Compensation

Critical Rules:
  • Compensation is ALWAYS incomplete
  • Overcompensation NEVER occurs
  • If it appears to overcompensate, look for a secondary disorder

C. Calculate Anion Gap

AG = Na⁺ − Cl⁻ − HCO3⁻
Normal AG ≈ 10 mEq/L (range 8–12)

D. Evaluate for Multiple Disorders

Use Potential Bicarbonate or Delta/Delta ratio.

E. For Non-Anion Gap Acidosis

Calculate Urinary Anion Gap (UAG).

3. The Bicarbonate Buffering System

CO2 + H2O ⇌ H2CO3 ⇌ H⁺ + HCO3⁻

4. Step-by-Step Approach

Step 1: pH Assessment

Acidemic (< 7.40) or Alkalemic (> 7.40)?

Step 2: Primary Disorder

Check pCO2 and HCO3¹¯. Which one explains the pH change?

Step 3: Compensation Assessment

Use Winter's Formula for metabolic acidosis:

Expected pCO2 = 1.5 × [HCO3⁻] + 8 ± 2

Step 4: Anion Gap

AG = Na⁺ − Cl⁻ − HCO3⁻

Step 5: Check for Mixed Disorders

Calculate Potential Bicarbonate or Delta/Delta ratio.

5. Compensation Rules

DisorderCompensation Rule
Metabolic Acidosis Winter's Formula: Expected pCO2 = 1.5 × [HCO3⁻] + 8 ± 2
Respiratory compensation occurs within minutes to hours
Metabolic Alkalosis For every 1 mEq/L ↑ in HCO3⁻, pCO2 ↑ by 0.7 mmHg
Respiratory Acidosis (Acute) For every 10 mmHg ↑ in pCO2, HCO3⁻ ↑ by 1 mEq/L
Respiratory Acidosis (Chronic) For every 10 mmHg ↑ in pCO2, HCO3⁻ ↑ by 3.5 mEq/L
Respiratory Alkalosis (Acute) For every 10 mmHg ↓ in pCO2, HCO3⁻ ↓ by 2 mEq/L
Respiratory Alkalosis (Chronic) For every 10 mmHg ↓ in pCO2, HCO3⁻ ↓ by 5 mEq/L

6. Anion Gap

Causes of Elevated Anion Gap — "MUDPILES"

MMethanol
UUremia
DDKA (Diabetic Ketoacidosis) and other ketoses
PPropylene Glycol (from IV Ativan drips)
IINH (Isoniazid), Iron
LLactic acidosis
EEthylene glycol
SSalicylates (ASA)

Causes of Narrow Anion Gap

Albumin Correction:
For every 1 g/dL ↓ in albumin, add 2 mEq/L to calculated AG

7. Non-Anion Gap Acidosis

Causes — "USED CARP"

Kidney function preserved (UAG negative):

UUreterosigmoidostomy
SSmall bowel fistulae
EExtra Cl⁻ (expansion, NS administration)
DDiarrhea

Kidney function NOT preserved (UAG positive):

CCRF (Chronic Renal Failure)
AAcetazolamide, Addison's
RRTA (Renal Tubular Acidosis)
PProtein overfeeding

Urinary Anion Gap (UAG)

UAG = (Urinary Na⁺ + K⁺) − Cl⁻

8. Mixed Disorders

Potential Bicarbonate Method

  1. Calculate Delta AG = Measured AG − Normal AG (10)
  2. Calculate Potential HCO3⁻ = Delta AG + Measured HCO3⁻
  3. Interpret:
    • < 22 mEq/L: Concurrent non-AG acidosis
    • 22–26 mEq/L: Pure AG acidosis
    • > 26 mEq/L: Concurrent metabolic alkalosis

Delta/Delta Ratio

  1. Delta AG = Measured AG − Normal AG
  2. Delta HCO3⁻ = Normal HCO3⁻ (24) − Measured HCO3⁻
  3. Ratio = Delta AG / Delta HCO3⁻
  4. Interpret:
    • < 1: AG acidosis + Non-AG acidosis
    • 1–2: Pure AG acidosis
    • > 2: AG acidosis + Metabolic alkalosis

9. Clinical Cases

Case 1: Sepsis with NS Resuscitation

55-year-old male, severe sepsis, received 15L NS. On Ativan drip.

pH7.10Na135
pCO219K3.2
HCO3⁻6Cl110
CO27
Analysis:
  1. Acidemic (pH 7.10)
  2. Metabolic acidosis (HCO3⁻ 6)
  3. Appropriate compensation (Expected pCO2 = 17±2, actual 19)
  4. AG = 135 − 110 − 7 = 18 (elevated)
  5. Delta/Delta = 8/17 = 0.47 (< 1)

Diagnosis: AG acidosis (propylene glycol from Ativan) + Non-AG acidosis (NS-induced)

Case 2: DKA with Fungal Sepsis

60-year-old male, DM, fungal sepsis

pH7.01Na140
pCO239K3.0
HCO3⁻10Cl110
CO211
Glucose480β-hydroxybutyrate3
Lactate8
Analysis:
  1. Severe acidemia
  2. Mixed respiratory + metabolic acidosis
  3. AG = 19 (elevated)
  4. Multiple causes: DKA + lactic acidosis

Case 3: C. diff Colitis

67-year-old female, C. diff colitis

pH6.91Na135
pCO240K3.0
HCO3⁻8Cl110
CO28
BUN120Cr2.8
Analysis:
  1. Severe acidemia
  2. Mixed disorder
  3. AG = 17 (elevated from uremia)
  4. UAG = −40 (negative → diarrhea component)

Diagnosis: Uremic acidosis + Diarrhea-induced Non-AG acidosis

10. Quick Reference

Normal Values

pH7.35–7.45
pCO235–45 mmHg
HCO3⁻22–28 mEq/L
Anion Gap8–12 mEq/L

Essential Formulas

Anion Gap: Na⁺ − Cl⁻ − HCO3⁻

Winter's Formula: pCO2 = 1.5 × [HCO3⁻] + 8 ± 2

UAG: (Urinary Na⁺ + K⁺) − Cl⁻

Delta/Delta: (AG − 10) / (24 − HCO3⁻)

Approach Summary

  1. pH → Acidemia or Alkalemia?
  2. Primary disorder → Metabolic or Respiratory?
  3. Compensation → Appropriate?
  4. Anion gap → Elevated or Normal?
  5. Mixed disorders → Check Delta/Delta
  6. If Non-AG acidosis → Check UAG

11. Key Terms

TermDefinition
AcidemiaBlood pH < 7.40
Anion Gap (AG)Difference between measured cations and anions; normal ~10 mEq/L
CompensationBody's attempt to normalize pH; always incomplete
Delta/Delta RatioTool to identify mixed metabolic disorders
Non-Anion Gap Acidosis (NAG)Metabolic acidosis with normal AG, due to HCO3⁻ loss or Cl⁻ gain
Potential BicarbonateCalculation to detect secondary metabolic disorders
Urinary Anion Gap (UAG)Differentiates renal vs non-renal causes of NAG
Winter's FormulaPredicts appropriate respiratory compensation for metabolic acidosis

Practice Questions

  1. A patient has pH 7.32, pCO2 30, HCO3⁻ 15. What is the primary disorder?
  2. Calculate the anion gap: Na 140, Cl 105, HCO3⁻ 20.
  3. A patient with diarrhea has a non-AG acidosis. What would you expect the UAG to be?
  4. Using Winter's formula, what is the expected pCO2 for HCO3⁻ of 12?

Key Takeaways

  • Always approach systematically using the ABC method
  • Compensation is never complete
  • Check for mixed disorders in complex cases
  • UAG differentiates renal from GI causes of NAG acidosis
  • Remember correction factors (especially albumin for AG)

References

  1. Berend K, de Vries AP, Gans RO. Physiological approach to assessment of acid-base disturbances. N Engl J Med. 2014;371(15):1434-1445. PubMed
  2. Seifter JL. Integration of acid-base and electrolyte disorders. N Engl J Med. 2014;371(19):1821-1831. PubMed
  3. Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6(5):274-285. PubMed
  4. Adeva-Andany MM, et al. Sodium bicarbonate therapy in patients with metabolic acidosis. ScientificWorldJournal. 2014;2014:627673. PubMed
  5. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed. McGraw-Hill; 2001. PubMed Search
Index ABG vs VBG RTA Types SGLT2 eDKA Sodium Bicarbonate

© 2025 Andrew Bland, MD, MBA, MS — Urine Nephrology Now