Why Does Oxygen Therapy Cause Hypercapnia In COPD?

Ask young physicians why patients with chronic obstructive pulmonary disease (COPD) tend to retain CO(hypercapnia) when given oxygen therapy. I bet the majority will claim that supplemental oxygen depresses one’s “hypoxic drive” to breath. In other words, if our oxygen levels are super high, the body will invest less energy in breathing resulting in hypercapnia. Makes sense? Unfortunately, this is NOT the real reason.

Our lungs do a phenomenal job of matching ventilation (‘V’) to perfusion (‘Q’) at the alveolar level. If areas of the lung are not well ventilated, vasoconstriction will occur in the pulmonary arterioles supplying perfusion to those regions. Blood will instead be shunted to areas of the lung which receive more ventilation. This physiological principle is termed hypoxic pulmonary vasoconstriction (HPV) and is an intrinsic property of the lung. It makes sense – let’s perfuse areas which are ventilated!

Chest x-ray of a patient with COPD (Image: Radiopaedia)

COPD patients have longstanding changes in their lung architecture with resulting HPV to maximize efficiency and gas exchange. Providing supplemental oxygen can, in a sense, reverse the HPV and shunt blood back to poorly ventilated areas (increased shunt fraction). This creates a V/Q mismatch which results in hypercapnia from the increased dead space at well ventilated alveoli.

Additionally, let’s talk about the Haldane effect. Deoxygenated blood picks up CO2 and hydrogen ions which get released when oxygen binds hemoglobin in the alveoli. When supplemental oxygen is provided, imagine the following equilibrium being pushed to the right.

H+Hb + O2 ⇄ H+ + HbO2

The newly released hydrogen ions (H+) will shift the bicarbonate buffer (HCO3) to produce more CO2 resulting in hypercapnia.

CO2 + H2O ⇄ H2CO3H+ + HCO3

V/Q mismatch and the Haldane effect are the two MAJOR reasons why patients with COPD tend to retain CO2 when given oxygen therapy.

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  1. Hi, Rishi. I am a nurse and future CRNA, and love reading the educational information you provide.
    How does an increased dead space with adequate ventilation cause hypercapnia? Am I correct in saying that increased dead space entails less gas exchange at the alveoli?

    • If you’re referring to the vignette outlined in this post (ie, COPD), the whole point is you’re worsening V/Q matching due to the Haldane effect and dysregulation of hypoxic pulmonary vasoconstriction. Just because patients have apparent ventilation doesn’t mean this translates to effective, alveolar ventilation due to newfound shunting from dilating pulmonary capillaries that are associated with poorly ventilated alveoli (ie, what happens when these patients receive oxygen therapy). This can lead to impaired gas exchange.

    • Hypercapnia means higher levels of CO2 in the blood… it is synonymous with hypercarbia.
      Some people use word “hypercapnia” to indicate etCO2 levels but actually means in the blood.


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