Thread by @nickmmark

Lots of talk about funny hemoglobin and ‘happy hypoxic’ people with #COVID19. I think we can explain everything using plain old pulmonary physiology. Let’s dive into hypoxic pulmonary vasoconstriction (HPV) and hypoxic ventilatory drive (HVD) and try to make sense of this...
1/

Normally, different areas of the lung receive different amounts of ventilation. The lungs are able to sense oxygen levels and adjust smooth muscle tone to modulate blood flow. This process is hypoxic pulmonary vasoconstriction (HPV), reviewed here: ncbi.nlm.nih.gov/pmc/articles/P…
2/

To understand why HPV is important, imagine a simple two alveoli model of the lung. Normally oxygen content (CaO2) and saturation (SpO2) increase as blood crosses the alveolar capillaries. This brings the oxygen level from venous SpO2 of 70% up to an arterial SpO2 of 100%.
3/

What happens if one alveolus is filled with fluid? Deoxygenated blood would go through the pulmonary vasculature without picking up any oxygen. This is Shunt.
4/

One of the hallmarks of shunt physiology is that it only partially improves with supplemental O2. Even by giving 100% FiO2 we can’t quite get that SpO2 back to normal because of the shunt.
5/

This is where Hypoxic Pulmonary Vasoconstriction (HPV) comes in. Under normal conditions, HPV reduces pulmonary blood flow to areas of the lung that are poorly oxygenated. This helps bring up the SpO2 closer to normal. 6/

Clinical Pearl 🦪: HPV is important because several common medications can mess it up, including CCBs, nitrates, and hydralazine. Occasionally we see someone in the ICU with persistent hypoxia on these meds whose hypoxia gets better almost immediately when the med is stopped.
7/

BUT it turns out we don’t all have the same degree of HPV. This was a study of healthy volunteers exposed to hypoxia for 4 hrs. About half the people (black lines) had in increase in PA pressure due to HPV while the other half (dashing lines) did not.
➡️liebertpub.com/doi/full/10.10…
8/

Clinical Pearl 🦪: This baseline variation in the strength of the HPV response helps explain why some ICU patients with #ARDS avoid severe hypoxia but develop RV failure, whereas other have normal RV pressures but become hypoxic.
9/

The last piece of the #COVID 🧩is hypoxic ventilatory drive (HVD). For most of us, PaCO2 (and resulting pH) affects respiratory drive. Low O2 also stimulate breathing, but only when we are hypoxic. The relationship b/w drive and PCO2 looks like this:
thorax.bmj.com/content/63/Sup…
11/

But just like HPV, there is also variation in hypoxic ventilatory drive (HVD). Let’s turn to some old school physiology: in this golden oldie they subjected volunteers to hypoxia and observed change in ventilation (VE); look how much variation!
12/
➡️bit.ly/3dYo2Xn

To summarize so far:
* HPV determines how much shunt we get when we have a patchy pulmonary process. This varies widely from person to person.
* HVD determines how much shortness of breath we feel and how much we increase our ventilation w/ hypoxia. This also varies a lot.
12/

This brings us back to #COVID19. We are seeing wide variation our patients' hypoxia and their tolerance for it. This CT shows just how patchy #COVID19 can be. Putting together the known variation in HPV and HVD we can perhaps explains this variation in clinical presentations. 13/

Bottom line: We can explain the magnitude of hypoxemia and varied responses to it in terms of HPV and HVD (without invoking any crazy viral hemoglobinopathies, porphyrias, or other novel pathologies). All we need is some good ol’ physiology.
fin/