# Acid-Base Review: A Comprehensive Student Guide

[Index](https://urinenephrology.org/mastery/acid-base/index.html) [ABG vs VBG](https://urinenephrology.org/mastery/acid-base/abg-vs-vbg.html) [RTA Types](https://urinenephrology.org/mastery/acid-base/rta-types.html) [SGLT2 eDKA](https://urinenephrology.org/mastery/acid-base/sglt2-edka.html) [Sodium Bicarbonate](https://urinenephrology.org/mastery/acid-base/sodium-bicarbonate.html)

**Author:** Andrew Bland, MD, FACP, FAAP

## 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

- It is an "open system" — CO2 can be expelled by lungs
- CO2 is the respiratory component (acid)
- HCO3¹¯ is the metabolic component (base)
- When the system becomes "closed" (e.g., respiratory failure), severe acidosis occurs

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

[TABLE]

## 6. Anion Gap

### Causes of Elevated Anion Gap — "MUDPILES"

|       |                                               |
|-------|-----------------------------------------------|
| **M** | Methanol                                      |
| **U** | Uremia                                        |
| **D** | DKA (Diabetic Ketoacidosis) and other ketoses |
| **P** | Propylene Glycol (from IV Ativan drips)       |
| **I** | INH (Isoniazid), Iron                         |
| **L** | Lactic acidosis                               |
| **E** | Ethylene glycol                               |
| **S** | Salicylates (ASA)                             |

### Causes of Narrow Anion Gap

- Hypoalbuminemia (most common)
- Hypercalcemia
- Lithium toxicity
- Multiple myeloma (cationic proteins)

**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):**

|       |                                          |
|-------|------------------------------------------|
| **U** | Ureterosigmoidostomy                     |
| **S** | Small bowel fistulae                     |
| **E** | Extra Cl⁻ (expansion, NS administration) |
| **D** | Diarrhea                                 |

\

**Kidney function NOT preserved (UAG positive):**

|       |                              |
|-------|------------------------------|
| **C** | CRF (Chronic Renal Failure)  |
| **A** | Acetazolamide, Addison's     |
| **R** | RTA (Renal Tubular Acidosis) |
| **P** | Protein overfeeding          |

### Urinary Anion Gap (UAG)

UAG = (Urinary Na⁺ + K⁺) − Cl⁻

- **Negative UAG:** Appropriate NH4⁺ production → Non-renal cause
- **Positive UAG:** Inappropriate NH4⁺ production → Renal cause

## 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.**

|       |      |     |     |
|-------|------|-----|-----|
| pH    | 7.10 | Na  | 135 |
| pCO2  | 19   | K   | 3.2 |
| HCO3⁻ | 6    | Cl  | 110 |
|       |      | CO2 | 7   |

**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**

|         |      |                   |     |
|---------|------|-------------------|-----|
| pH      | 7.01 | Na                | 140 |
| pCO2    | 39   | K                 | 3.0 |
| HCO3⁻   | 10   | Cl                | 110 |
|         |      | CO2               | 11  |
| Glucose | 480  | β-hydroxybutyrate | 3   |
| Lactate | 8    |                   |     |

**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**

|       |      |     |     |
|-------|------|-----|-----|
| pH    | 6.91 | Na  | 135 |
| pCO2  | 40   | K   | 3.0 |
| HCO3⁻ | 8    | Cl  | 110 |
|       |      | CO2 | 8   |
| BUN   | 120  | Cr  | 2.8 |

**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

|           |             |
|-----------|-------------|
| pH        | 7.35–7.45   |
| pCO2      | 35–45 mmHg  |
| HCO3⁻     | 22–28 mEq/L |
| Anion Gap | 8–12 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

| Term | Definition |
|----|----|
| **Acidemia** | Blood pH \< 7.40 |
| **Anion Gap (AG)** | Difference between measured cations and anions; normal ~10 mEq/L |
| **Compensation** | Body's attempt to normalize pH; always incomplete |
| **Delta/Delta Ratio** | Tool to identify mixed metabolic disorders |
| **Non-Anion Gap Acidosis (NAG)** | Metabolic acidosis with normal AG, due to HCO3⁻ loss or Cl⁻ gain |
| **Potential Bicarbonate** | Calculation to detect secondary metabolic disorders |
| **Urinary Anion Gap (UAG)** | Differentiates renal vs non-renal causes of NAG |
| **Winter's Formula** | Predicts 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](https://pubmed.ncbi.nlm.nih.gov/25295502/)
2.  Seifter JL. Integration of acid-base and electrolyte disorders. *N Engl J Med*. 2014;371(19):1821-1831. [PubMed](https://pubmed.ncbi.nlm.nih.gov/25372090/)
3.  Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. *Nat Rev Nephrol*. 2010;6(5):274-285. [PubMed](https://pubmed.ncbi.nlm.nih.gov/20308999/)
4.  Adeva-Andany MM, et al. Sodium bicarbonate therapy in patients with metabolic acidosis. *ScientificWorldJournal*. 2014;2014:627673. [PubMed](https://pubmed.ncbi.nlm.nih.gov/25405229/)
5.  Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed. McGraw-Hill; 2001. [Publisher textbook](https://www.mheducation.com/highered/mhp/product/clinical-physiology-acid-base-electrolyte-disorders.html)

[Index](https://urinenephrology.org/mastery/acid-base/index.html) [ABG vs VBG](https://urinenephrology.org/mastery/acid-base/abg-vs-vbg.html) [RTA Types](https://urinenephrology.org/mastery/acid-base/rta-types.html) [SGLT2 eDKA](https://urinenephrology.org/mastery/acid-base/sglt2-edka.html) [Sodium Bicarbonate](https://urinenephrology.org/mastery/acid-base/sodium-bicarbonate.html)

© 2025 Andrew Bland, MD, FACP, FAAP — Urine Nephrology Now

### Also on this topic

The same subject at other levels of depth.

- **Primer chapter:** [Chapter 16: Acid-Base Disorders In-Depth](https://urinenephrology.org/nephrology-textbook/chapters/chapter-13-acid-base-review.html)
- **Student handout:** [Acid-Base Disorders: Student Handout](https://urinenephrology.org/student-resources/electrolyte-acid-base/acid-base-student-handout.html)


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