Oxygenation and Ventilation Physiology: The Fundamentals

Topic Progress:

Pearls for Oxygenation-Ventilation Physiology

1. Oxygenation is the act of diffusion.
2. Ventilation is the movement of oxygen and carbon dioxide in and out of the lungs.
3. COVID-19 is primarily an oxygenation issue that may or may not progress to an oxygenation and ventilation problem.
Familiarize yourself with this cheat sheet. Click here to download a PDF copy.


The act of oxygen diffusing from high to low concentrations.
Measured by SPO2, pO2.
Eg. Alveolus to capillary. Capillary to cell.


The act of breathing oxygen in and breathing carbon dioxide out.
Measured by CO2, ETCO2.

Short on Time? This is a Quick Summary on Respiratory Failure

These #CritBits episodes are created by the one and only Haney Mallemat. He has many more #CritBits on his Instagram and YouTube channels.

In the following episodes below, Haney gives an overall summary of respiratory failure. We have included specific alterations to respiratory failure secondary to COVID-19 below.

Protip: Haney Mallemat is an amazing educator and has dozens of free lectures online! The only problem is he’s a Philadelphia Sixers fan… but we can forgive him for that.

Part 2: Hypoxemic Respiratory Failure (Oxygenation failure)

Part 3: Hypercarbic Respiratory Failure (Ventilatory failure)

Part 4: V/Q Mismatching

Brought to you by Haney Hallemat. Follow him on Instagram, YouTube and Twitter!

Specific Alterations to Oxygenation due to COVID-19

COVID-19 is thought to attack the lungs, specifically the ACE2 receptors, resulting in shortness of breath, viral pneumonia and can progress to acute respiratory distress syndrome, a devastating lung injury requiring intensive care.

The exact pathophysiology is unknown; however, one working theory is the blood from the right side of the heart is shunted away from areas of hypoxia in the lung and the blood enters the left side of the heart de-oxygenated. PulmCrit has an excellent review.

A Closer Look at Oxygenation (Pink Highlights)

  • Oxygenation is a result of alveolar-capillary gas exchange1
  • Applying or increasing supplemental oxygen (or fraction of inspired oxygen [FiO2]) increases supply of oxygen, increasing diffusion1
  • Increasing the surface area of the alveolus creates more space for oxygen to diffuse into the capillary (positive end expiratory pressure [PEEP])1

Recall the primary problem with oxygen supply and demand in COVID-19 is due to oxygenation problems (shaded in pink). Increasing the ability to oxygenate is vital to maintaining a balance between oxygen supply and demand. This can be primarily done in two different ways:


Increase oxygen that is breathed in, often represented as FiO2 (fraction of inspired oxygen).

You already do this! Can be done via high-flow nasal cannula, non-invasive pressure ventilation and intubation.


Increase the size of the alveolus at the end of a breath to have a longer period of alveolar-capillary diffusion time. This is often described as PEEP.

See the following Tweet; notice how the lungs stay inflated after the breath? That is PEEP. Imagine how much more surface area between the alveoli-and capillaries have to exchange gases.

The Bottom Line

1. We can increase FiO2 to improve oxygenation.
2. We can increase surface area between alevolus and capillary to facilitate oxygenation (PEEP).
3. We ensure the patient’s breath is bringing enough oxygen to the alveoli for gas exchange.

Specific Alterations in Ventilation due to COVID-19

Ventilation is the mechanical movement of gas or air into and out of the lungs and primarily is the removal of CO2 from reverse order of oxygen delivery.

While ventilation is not thought to be the primary problem in the early phases of COVID-19; however, as the disease progresses, ventilation is thought to become impaired due to a storm of cytokines and inflammatory markers2. While there is some debate if the result of this inflammatory state causes acute respiratory distress syndrome, current guidelines suggest to treat it as such with frequent patient reassessments3.

A Closer Look at Ventilation (Blue Highlights)

  • As an overarching thought, ventilation is the product of respiratory rate and volume of air per breath1.
  • Ventilation is gas exchange.
  • Oxygen breathed in, carbon dixoide breathed out.
  • The respiratory rate increases and decreases depending on the amount of CO2 the body wishes to expel.
  • The volume of air expelled is reliant on a number of factors.
  • The less amount of air breathed can contribute to non-ventilated alveoli, causing atelactasis, which decrease oxygenation (V = ventilation / Q = perfusion; VQ mismatch = imbalance of gas exchange with blood perfusion).

The Bottom Line

1. Ventilation is gas exchange.
2. CO2 is a common marker to assess ventilation.
3. Increased CO2 means hypercarbic respiratory failure.
4. Hypercarbic respiratory failure can be treated by changing respiratory rate and volume per breath.


  1. Mora Carpio AL, Mora JI. Ventilator Management. [Updated 2020 Mar 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448186
  2. Driggin E et al. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic JACC 2020
  3. Salim Rezaie, “COVID-19 Hypoxemia: A Better and Still Safe Way”, REBEL EM blog, March 31, 2020. Available at: https://rebelem.com/covid-19-hypoxemia-a-better-and-still-safe-way

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