The causes of hypoxemia !

Mechanism
Exam priority: high

There are only a few ways to end up with too little oxygen in the blood. The A–a gradient and the response to oxygen tell you which.

Updated 2026-11-01

Also called: Mechanisms of hypoxemia, Hypoxemia vs. hypoxia

What it is

Hypoxemia is a low PaO₂; hypoxia is too little oxygen in the tissues, which can happen with a normal PaO₂ (anemia, CO, cyanide, low cardiac output). There are five mechanisms of hypoxemia: low inspired PO₂, hypoventilation, diffusion impairment, V/Q mismatch and shunt. The first two have a normal A–a gradient.

How it works, step by step

Calculate PAO₂ with the local barometric pressure and compare it with PaO₂.
If the gradient is normal, look at PaCO₂: high means hypoventilation; normal or low with a low PB means altitude.
If the gradient is wide, think about the O₂ response: a big rise in PaO₂ means V/Q or diffusion; almost none means shunt.
On 100% O₂, low-V/Q alveoli fill with O₂ over time; shunt units never receive air.

Oxygen–hemoglobin dissociation curve

P50 27.7 mmHgArterial blood 97 %Mixed venous blood 73 %O₂ given up to the tissues 24 %

Right shift (P50 27.7 mmHg): Hb has less affinity and gives up more O₂ in the tissues. Acid, CO₂, heat and 2,3-BPG cause it.

Current curve
Normal curve (pH 7.40 · 37 °C)
Arterial blood (PO₂ 100)
Mixed venous blood (PO₂ 40)
O₂ given up to the tissues

At altitude PaO₂ falls, but saturation holds on the flat part of the curve.

The five mechanisms

Mechanism	A–a gradient	Improves with O₂	Example
Low inspired PO₂	Normal	Yes	Altitude (Bogotá, páramo)
Hypoventilation	Normal	Yes	Opioids, neuromuscular disease
Diffusion impairment	Wide	Yes	Interstitial fibrosis (especially on exercise)
V/Q mismatch	Wide	Yes	COPD, asthma, pulmonary embolism
Shunt	Wide	Little	ARDS, lobar pneumonia, right-to-left cardiac shunt

Clinical notes

ARDS: large shunt with O₂-refractory hypoxemia; alveoli must be recruited.
COPD: V/Q mismatch dominates; in advanced disease hypoventilation with hypercapnia is added.
CO poisoning: tissue hypoxia with a normal PaO₂ and a misleadingly normal pulse oximeter.

Test yourself

Think of the answer, then tap the question to see it.

Hypoxemia barely improves on 100% O₂. Which mechanism dominates?

Shunt: blood crosses unventilated regions and is never exposed to the added O₂.

Opioid overdose: PaCO₂ 70 mmHg, low PaO₂. What will the A–a gradient be?

Normal: hypoventilation explains the hypoxemia (more alveolar CO₂ displaces O₂), with no exchange defect.

Why does a patient with pulmonary fibrosis desaturate when walking but not at rest?

Exercise raises cardiac output and shortens red cell transit through the capillary; across a thickened membrane there is no longer time to equilibrate.

Why doesn't severe anemia lower PaO₂?

PaO₂ reflects dissolved O₂, set by alveolar exchange; what falls in anemia is the O₂ content bound to hemoglobin.

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 22.4 Gas Exchange (OpenStax (Rice University), 2022); Acute Respiratory Distress Syndrome (StatPearls (NCBI Bookshelf), 2024); Interstitial Lung Disease (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 43). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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