Thread by @Thind888

1/ **How does pleural pressure (Ppl) affect alveolar capillary transmural pressure?**

This was brought up recently-

https://twitter.com/ArgaizR/status/1254838818412335106

Although it's impossible to do justice to this topic in a #tweetorial, I'll give it a shot

This is important to understand for 2 reasons:

2/ (i). If the transmural capillary pressure (pressure distending the capillaries) is highly positive - it will favor pulmonary edema.

(ii). If the transmural capillary pressure is highly negative - it will favor capillary collapse --> West zone 1 condition --> increased PVR.

3/ Considering oncotic pressures constant, the pressure gradient for fluid exudation from alveolar capillaries = Pc - Palv.

In normal lung, the net gradient of Starling forces is outward (mildly positive transmural pressure) --> mild transudation of fluid --> interstitial edema.

4/ This is being consistently cleared by lymphatic drainage. Alveolar edema occurs when lymphatic drainage is overwhelmed.

Although the "ambient" pressure of alveolar vessels is Palv, that of extra-alveolar vessels (including small pre- and post- capillary vessels) is *Ppl*.

5/Now let's compare effects of Ppl "swings" on pulmonary circulation with the assumption that vascular volume (and hence transmural vascular pressure) remains the same:

1. NPV = negative Ppl:
(a)Extra-alveolar vessels: Ambient pressure (Ppl) reduced -->⬇️ intravascular  pressure

6/(b)Alveolar vessels: Palv is reduced in NPV (which would tend to cause more transudation)

However, the reduced pre- and post-capillary pressures also reduces Pc proportional to reduction in Ppl

So you can see that Ppl tends to oppose the effect of Palv on alveolar capillaries

7/ In other words, if Ppl = 0, then (Pc - Palv) is the transcapillary pressure. However, in the presence of a non-zero Ppl, the relationship can be roughly designated as -

Capillary transmural pressure (Ptm) = Pc - (Palv - Ppl) = Pc - PL, where PL is transpulmonary pressure.

8/
2.Similarly, in PPV:
(a)Extra-alveolar vessels: ⬆️ Ambient pressure (Ppl) --> ⬆️intravascular pressure
(b)Alveolar vessels: ⬆️Palv opposes transudation

However, the increased pre- and post-capillary pressures also ⬆️Pc proportional to Ppl

Again, Ptm = Pc-(Palv - Ppl) = Pc-PL

9/ If stressed volume & lung elastance are constant, both NPV and PPV would require identical PL for a given tidal volume. So does that mean there's no difference in NPV and PPV for a given TV?

Actually, there is. The key here is the effect of Ppl on pulmonary vascular volume.

10/ In NPV, negative Ppl ⬆️ venous return --> more volume in pulmonary circulation --> higher transmural vascular pressures and vice-versa.

So in NPV, Pc would be higher for the same "pleural pressure swing" for a given TV. Extremely negative Ppl can exacerbate pulmonary edema.

11/ Let's take another example to drive this point home:
Consider an obese patient receiving PPV. Their end-exp PPl = 25, PEEP applied = 25, so PL = 0. (These are realistic numbers)
One may think that such high PEEP (Palv) would "crush" the capillaries causing increase in PVR?

12/ But remember, the transmural alveolar capillary pressure = Pc - PL (PL is key, not Palv). As long as PL is reasonable, we should be fine.

It was extremely difficult to find a clinical study exploring this idea until I finally found one from Vieillard-Baron: PMID: 10562603

13/ ***Summary***

1. Transmural capillary pressure (roughly) proportional to Palv - PL.

2. For same TV and lung elastance, both NPV and PPV generate the same PL.

3. However, for the same end-exp pulmonary vascular volume, NPV and PPV will have opposing effects on venous return

14/
E.g.: NPV --> negative Ppl --> ⬆️ venous return --> ⬆️pulmonary vascular volume --> ⬆️transmural vascular pressures.

4. Due to point 3, NPV would result in a higher transmural capillary pressure (for the same PL)  --> higher chance of pulmonary edema. And vice versa.

/END

15/ P.S.:

For extra credits: I'll briefly mention how alveolar volume relates to PVR. There are, in fact, 2 individual mechanical factors that affect PVR
(i) Transmural capillary pressure: which is proportional to PL
(ii) Alveolar volume (for purely geometric reasons) - ....

16/ (Alveolar overinflation can physically "stretch" alveolar vessels --> ⬇️capillary diameter --> ⬆️PVR)

Both of these have synergistic effects (⬆️PL also ⬆️alveolar volume). However, if lung elastance is high, same PL would generate a lower alveolar volume, and hence lower PVR