Causes of Hypoxemia
Hypoxemia is primarily caused by ventilation-perfusion mismatch, intrapulmonary shunting, hypoventilation, diffusion impairment, and low inspired oxygen concentration. 1
Definition and Clinical Significance
Hypoxemia refers to abnormally low partial pressure of oxygen in arterial blood (PaO₂), clinically defined as:
Hypoxemia is associated with 4.84 times higher odds of death compared to non-hypoxemic patients and requires prompt identification and management 1.
Major Causes of Hypoxemia
1. Ventilation-Perfusion (V/Q) Mismatch
- Most common cause of hypoxemia in clinical practice 3
- Results from uneven distribution of ventilation relative to perfusion in different lung regions
- Responds relatively well to supplemental oxygen therapy 1
- Common in:
- COPD
- Asthma
- Bronchiectasis
- Pulmonary edema
2. Intrapulmonary Shunting
- Blood passes from right to left heart without participating in gas exchange
- Relatively refractory to oxygen therapy 1
- Normal shunting is <5% of cardiac output; in ARDS may exceed 25% 1
- Common in:
3. Hypoventilation
- Inadequate alveolar ventilation relative to metabolic demands
- Characterized by increased PaCO₂ (hypercapnia) and decreased PaO₂ 1
- Responds well to oxygen therapy
- Common in:
- CNS depression (sedatives, opioids)
- Neuromuscular disorders
- Chest wall deformities
- Obesity hypoventilation syndrome
- Airway obstruction 1
4. Diffusion Impairment
- Thickened alveolar-capillary membrane impairs oxygen transfer
- Usually only significant during exercise
- Common in:
- Interstitial lung diseases
- Pulmonary fibrosis
- Early stages of pulmonary edema
5. Low Inspired Oxygen (FiO₂)
- Decreased partial pressure of oxygen in inspired air
- Common at high altitude
- Confined spaces with oxygen consumption/inadequate ventilation
Pathophysiological Mechanisms in Specific Conditions
ARDS
- Inflammatory mediators damage alveolar-capillary membrane
- Alveolar flooding with protein-rich edema fluid
- Surfactant dysfunction causing alveolar collapse
- Reduced volume of aeratable lung
- Formation of atelectatic regions, particularly in dependent lung areas 2, 1
- Intrapulmonary shunting may consume >25% of cardiac output 1
COPD
- Primary mechanism is V/Q mismatch
- Alveolar hypoventilation in advanced disease
- Breathing 100% O₂ in COPD patients increases PaO₂ but also increases PaCO₂ due to release of hypoxic pulmonary vasoconstriction 4
- Hypoxemia worsens with disease progression, leading to:
- Pulmonary hypertension
- Secondary polycythemia
- Systemic inflammation
- Skeletal muscle dysfunction 5
Sepsis
- Multiple mechanisms:
- V/Q mismatch
- Increased physiological dead space
- Intrapulmonary shunting
- Cardiocirculatory dysfunction affecting global oxygen delivery
- Shifts in oxyhemoglobin dissociation curve 2
Clinical Pearls
Severity assessment: A fall in SaO₂ of ≥4%, SaO₂ ≤88%, or PaO₂ ≤55 mm Hg during cardiopulmonary exercise testing is considered clinically significant 2.
Oxygen therapy response: The response to oxygen therapy helps identify the underlying mechanism:
- V/Q mismatch: good response
- Shunt: poor response
- Hypoventilation: good response but requires ventilatory support 1
Hypoxemia vs. Hypoxia: Hypoxemia (low blood oxygen) can lead to tissue hypoxia, but hypoxia can also occur with normal PaO₂ in conditions like anemia, circulatory failure, or histotoxic conditions 1.
Types of hypoxia:
- Hypoxemic hypoxia (low PaO₂)
- Anemic hypoxia (reduced oxygen transport capacity)
- Stagnant/circulatory hypoxia (inadequate blood flow)
- Histotoxic/cytopathic hypoxia (inability to utilize oxygen) 1
Acute vs. chronic hypoxemia: Sudden hypoxemia is more dangerous than hypoxemia of gradual onset, as demonstrated by acclimatized individuals at high altitude 2.