Fluid Overload but Intravascularly Depleted: What does this mean?

I often hear people say that the patient, who has fluid overload with significant edema, is intravascularly depleted.
Despite significant reading on the matter I have not been able to find a suitable explanation.
Thankfully, this paper was published a few days ago with the best explanation I’ve read.
Hat tip to the authors, read these data for yourself.
The authors state that there are two key mechanisms to explain this.
“Acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6”.
This is what causes the leaky capillaries.
The other being “nitric oxide-induced inhibition of intrinsic lymphatic pumping”.
This is what causes the fluid to stay in the “third space”.
We have to remember that fluid does not get back into the intravascular space by going in the opposite direction of how it came out in the first place.
For that, our body uses the lymphatic system.
The authors state that forces such as movement and external massage could get the stagnant lymphatic system up and running again.
They do not suggest treatment strategies but quickly addressing what would cause said fluid overload while being intravascularly depleted is the way to go.
Assessing for fluid responsiveness could also help.

Citations for Fluid Overload but Intravascularly Depleted

Dull RO, Hahn RG. Hypovolemia with peripheral edema: What is wrong? Crit Care. 2023 May 27;27(1):206. doi: 10.1186/s13054-023-04496-5. PMID: 37245039.
Link to Article
Link to FULL FREE PDF

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