From the Guidelines
Chronic hypoxia is primarily caused by conditions that impair oxygen delivery to tissues over extended periods, including chronic obstructive pulmonary disease (COPD), interstitial lung diseases, pulmonary hypertension, congestive heart failure, severe anemia, sleep apnea, high-altitude exposure, and certain congenital heart defects. These conditions lead to chronic hypoxia through different mechanisms:
- Ventilation-perfusion mismatch, as seen in COPD and interstitial lung diseases, where damaged airways and thickened lung tissue impair gas exchange 1
- Diffusion impairment, which can occur in interstitial lung diseases, where the thickened lung tissue reduces the ability of oxygen to diffuse into the bloodstream
- Hypoventilation, which can be caused by sleep apnea, where intermittent breathing cessation leads to reduced oxygen levels
- Right-to-left shunting, which can occur in certain congenital heart defects, where deoxygenated blood bypasses the lungs
- Reduced oxygen-carrying capacity, which can be caused by severe anemia, where the decreased red blood cell count or hemoglobin level reduces the ability of the blood to carry oxygen 1. The body compensates through increased respiratory rate, cardiac output, and erythropoiesis (red blood cell production), but these adaptations may eventually become insufficient, leading to tissue damage, organ dysfunction, and potentially life-threatening complications if the underlying cause remains untreated, as noted in the British Thoracic Society guidelines for home oxygen use in adults 1.
From the Research
Causes of Chronic Hypoxia
- Chronic obstructive pulmonary disease (COPD) is a leading cause of chronic hypoxia, with alveolar hypoxia and consequent hypoxemia increasing in prevalence as disease severity increases 2.
- Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of hypoxia in COPD patients, which may be exacerbated by sleep and exercise 2.
- Residing at high altitudes can also expose individuals to hypoxemia, with potential adverse consequences on their health 3.
- Systemic inflammation, renal impairment, malnutrition, low testosterone levels, growth hormone level abnormalities, oxygen supplementation, theophylline treatment, inhibition of angiotensin-converting enzyme, and aging itself are additional factors that could be associated with the development of anemia, which can contribute to chronic hypoxia 4, 5.
- Chronic heart failure can also lead to chronic breathlessness, which may be related to chronic hypoxia, although the role of oxygen therapy in relieving chronic breathlessness in heart failure is not well described 6.
Underlying Mechanisms
- Hypoxia-inducible factor-1-alpha (HIF-1α) plays a crucial role in responding to hypoxia, with increased levels of HIF-1α stabilizing the transcription factor and transactivating genes that govern angiogenesis and metabolic pathways 3.
- Erythropoietin (EPO) levels are increased in hypoxemic patients, which can respond to oxygen therapy 3.
- Vascular endothelial growth factor (VEGF) levels are heterogeneous in hypoxemic patients, with varying responses to oxygen therapy depending on the underlying disease 3.