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Hypoxemia Mechanisms and Diagnosis

Jun 28, 2025

Overview

This lecture explains the five basic mechanisms of hypoxemia, how to distinguish between them, and the main causes and diagnostic strategies for low blood oxygen.

Mechanisms of Hypoxemia

  • Hypoxemia is defined as low partial pressure of oxygen in arterial blood (PaO2).
  • Five mechanisms: low inspired oxygen (high altitude), hypoventilation (high PaCO2), impaired diffusion, ventilation-perfusion (VQ) mismatch, and shunt.
  • Only right-to-left intracardiac shunts are linked to a single mechanism; most causes involve multiple mechanisms.

Key Equations and Concepts

  • The alveolar-arterial (A-a) gradient measures difficulty in oxygen exchange; a high gradient suggests pathology.
  • Alveolar gas equation estimates alveolar oxygen pressure (PAO2).
  • Fixed law describes gas diffusion: rate = diffusion coefficient × surface area × pressure gradient / membrane thickness.

Impaired Diffusion

  • Usually caused by increased alveolar-capillary membrane thickness (e.g., pulmonary fibrosis).
  • Exacerbated by high altitude or high cardiac output (less diffusion time).
  • CO2 diffusion is less affected due to its higher solubility.

Ventilation-Perfusion (VQ) Mismatch

  • Optimal gas exchange requires matched alveolar ventilation and blood perfusion; normal lung VQ ≈ 0.8.
  • Causes include pulmonary edema, airway obstruction (atelectasis), or pulmonary embolism (dead space).
  • Adaptive hypoxic vasoconstriction diverts blood from poorly ventilated areas.
  • Supplemental oxygen often corrects hypoxemia unless the underlying disease is severe.

Shunt

  • Right-to-left shunt: blood bypasses lungs (e.g., tetralogy of Fallot), leading to hypoxemia unresponsive to oxygen.
  • Shunt fraction ≥30%: little improvement in PaO2 with supplemental oxygen.

Diagnostic Approach

  • Step 1: Check A-a gradient; normal suggests hypoventilation or low inspired O2.
  • Step 2: Assess correction with 100% oxygen; incomplete correction indicates shunt.
  • Step 3: Combine history, physical exam, chest X-ray, and possibly echocardiogram with bubble study to localize shunt.

Radiographic Patterns in Hypoxemia

  • Normal X-ray: COPD/asthma, PE, hypoventilation, intracardiac shunt, AVM.
  • Single lobe abnormal: pneumonia, infarct, collapse.
  • Unilateral diffuse: large effusion, collapse, severe pneumonia, re-expansion edema, selective intubation.
  • Bilateral diffuse: pulmonary edema, ARDS, interstitial disease, viral/fungal pneumonia.

Key Terms & Definitions

  • A-a Gradient — difference between alveolar and arterial O2 pressures, indicates oxygenation efficiency.
  • VQ Mismatch — regions with uneven ventilation and perfusion, impairing gas exchange.
  • Shunt — blood bypasses alveolar gas exchange, resistant to supplemental oxygen.
  • Hypoventilation — inadequate ventilation, leads to increased PaCO2 and hypoxemia.
  • Fixed Law — law describing diffusion rate of gases across membranes.
  • Dead Space — ventilated lung regions not participating in gas exchange.

Action Items / Next Steps

  • Review lectures 16 and 17 for background on ABGs if needed.
  • Read up on Fixed law and alveolar gas equation for full understanding.
  • Next lecture: study carbon monoxide poisoning and methemoglobinemia.