Mastering Acid-Base Disorders for the USMLE: A High-Yield Review

Acid-base disorders are a high-yield topic frequently tested on the USMLE Step 1 and Step 2. Understanding arterial blood gas (ABG) interpretation, anion gap analysis, and compensation mechanisms is essential for diagnosing and managing metabolic and respiratory disturbances. In this guide, we’ll simplify acid-base disorders, provide a stepwise approach to interpretation, and highlight key concepts to maximize your USMLE score.

1. The Basics of Acid-Base Balance

The body maintains pH balance through three main systems:

• Buffering systems: Bicarbonate (HCO3-), phosphate, and proteins (e.g., hemoglobin)

• Respiratory system: Regulates CO2 elimination via the lungs

• Renal system: Regulates H+ excretion and HCO3- reabsorption

Normal Arterial Blood Gas (ABG) Values:

• pH: 7.35–7.45

• PaCO2: 35–45 mmHg

• HCO3-: 22–26 mEq/L

2. Stepwise Approach to ABG Interpretation

1. Assess the pH:

   • pH < 7.35 → Acidemia

   • pH > 7.45 → Alkalemia

2. Identify the primary disorder:

   • If PaCO2 is the main driver → Respiratory disorder

   • If HCO3- is the main driver → Metabolic disorder

3. Determine Compensation:

   • Respiratory compensation (fast) → Alters PaCO2

   • Metabolic compensation (slow) → Alters HCO3-

4. Calculate the Anion Gap (AG) in Metabolic Acidosis:

   • AG = Na+ – (Cl- + HCO3-)

   • Normal AG: 8–12 mEq/L

   • Increased AG: Ketoacidosis, lactic acidosis, renal failure, toxic ingestions

   • Normal AG: Diarrhea, renal tubular acidosis (RTA)

3. Key Acid-Base Disorders and Their Causes

Metabolic Acidosis (↓ pH, ↓ HCO3-)

• High Anion Gap: MUDPILES mnemonic

  • Methanol

  • Uremia

  • Diabetic ketoacidosis

  • Propylene glycol

  • Isoniazid/Iron

  • Lactic acidosis

  • Ethylene glycol

  • Salicylates (late)

• Normal Anion Gap: HARD-ASS mnemonic

  • Hyperalimentation

  • Addison’s disease

  • Renal tubular acidosis

  • Diarrhea

  • Acetazolamide

  • Spironolactone

  • Saline infusion

Metabolic Alkalosis (↑ pH, ↑ HCO3-)

• Vomiting

• Loop or thiazide diuretics

• Hyperaldosteronism

Respiratory Acidosis (↓ pH, ↑ PaCO2)

• Acute: Opioid overdose, COPD exacerbation, airway obstruction

• Chronic: COPD, neuromuscular disorders

Respiratory Alkalosis (↑ pH, ↓ PaCO2)

• Hyperventilation (anxiety, pain, altitude sickness)

• Salicylate toxicity (early)

4. USMLE Question Approach & High-Yield Tips

• Always check the pH first before determining the disorder.

• Use Winter’s Formula to check expected respiratory compensation in metabolic acidosis:

  • PaCO2 = (1.5 × HCO3-) + 8 ± 2

• Know anion gap causes and differentiate between high and normal AG acidosis.

• Respiratory disorders require time consideration: Acute vs. Chronic.

• In salicylate toxicity, expect a mixed disorder (early respiratory alkalosis + late metabolic acidosis).

5. Conclusion: Mastering Acid-Base for the USMLE

Acid-base disorders are high-yield and require a systematic approach. Use this guide to strengthen your ABG interpretation skills, recognize key patterns, and tackle USMLE-style questions with confidence.

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