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 due to decreased blood flow to 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. So just to clarify, essentially when you administer oxygen you are causing dilation to the vessels of the poorly ventilated sections of the lung, which are already obstructed due to bronchitis and emphysema. Because there is now increased perfusion to these poor areas of ventilation (Due to O2 administration to someone who has pulmonary hypoxic vasoconstriction), there is a subsequent buildup of CO2 within the blood,(hypercapnia).

    This along with the Haldene effect (which I have been spending the last two days trying to understand the whole bicarbonate buffer system and the haemoglobin disociation curve), is what contributes to hypercapnia in the setting of overoxygenation of the COPD patient. Okay so that’s where I am at there.

    Secondly, I understand there is a V/Q mismatch, however I keep seeing that people are saying “dead space” when referring to this. Am I wrong to say that, when there is increased perfusion to poorly ventilated areas of the lung, it is in fact referred to as “Shunt perfusion”? I understood that dead space perfusion would be areas of well ventilated lung with poor perfusion, from for example a pulmonary embolism.

    As some context I am a 2nd year paramed student and am just trying to see if I have got this right in my head. Thank you for this awesome resource!

    • Hey Joseph! Yes, you understand it! As far as the “dead space” question, yes, you’re right, shunt refers to areas of perfusion without ventilation. By providing supplemental O2, one will undo the effects of HPV thereby restoring some blood flow to alveoli which are poorly ventilated. It depends on the perspective of the alveolus you’re referring to. The well ventilated alveoli are having blood “stolen” from them to now perfuse poorly ventilated alveoli. In short, the good alveoli are experiencing more dead space (since blood is being stolen from them) and the poorly ventilated alveoli are seeing increased blood flow (shunt) due to dysregulation of HPV.

      Hope this helps! Keep up the great work!

      • Hi Rishi,

        Thank you for your response! Yes that completely makes sense, I hadn’t of looked at it from that perspective. The poorly ventilated alveoli are now stealing blood from the well ventilated ones causing a deadspace in those areas. 🙂

        I also finally understand how the haldene effect involving the release of hydrogen ions in the presence of O2 causes the buffer system to release more CO2. It’s funny because I believe most of my teachers still believe in the hypoxic drive thoery. Thanks again!

  2. 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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