There are five basic processes that result in hypoxemia:

1. Ventilation-perfusion (V/Q) mismatch: air isn’t getting to the parts of the lung that the blood is passing through. Causes includes pneumonia, asthma, COPD, ARDS, pulmonary embolism, heart failure, and interstitial lung diseases. V/Q mismatches usually respond well to supplemental oxygen.
2. Right-to-left shunt: blood bypasses the lung altogether. This can happen due to an anatomic shunt in the heart itself as in an ASD, VSD, or PFO or in the lung vasculature through an AVM, or as a physiologic shunt due to severe pneumonia, ARDS, heart failure, or atelectasis. Because blood isn’t getting to the alveoli, supplemental oxygen doesn’t help–all it does it bring O2 to places without blood flow.
3. Hypoventilation: the patient just isn’t moving enough air. It’s associated with an increase in CO2, and causes include CNS causes (sedation, stroke, tumours), neuromuscular disorders, airway obstruction (COPD, asthma, laryngospasm), and dead space ventilation.
4. Diffusion defect: oxygen isn’t getting from the air to the blood. Causes include emphysema, PJP, atypical pneumonias, and pulmonary fibrosis.
5. Low inspired oxygen content: high altitude! And not much else.

Read more in Chapter 49: Hypoxia and Cyanosis in Harrison’s 19e.

Speaking of hypoxemia, an anaesthesia fellow turned me on to an article from a few years back, Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest by Grocott et al. (NEJM 2009), that includes the following table:

Those are some wild ABGs! If I saw those in a patient, I would be calling the ICU.