DCS and the immune system redux

[Kevrumbo]

So how does this sound. Nitrogen (or air) bubbles are extremely hydrophobic. It is well known that on very hydrophobic surfaces many physiological proteins can bind and lose their normal structure and expose hydrophobic domains (which are very immunogenic) to the immune system. We will be looking at this in the lab in a few days. This might be particularly important in neonatal ECMO systems (which we make)

Bill

How Bubbles Affect Proteins — Denaturization
A protein molecule is made up of hydrophilic sections which
are attracted to fluid, and hydrophobic sections which are
attracted to gas.

NORMAL: When in blood the protein molecule’s
hydrophobic sections are surrounded by
its hydrophilic sections which are in contact
with the surrounding fluid.

DENATURED: When the protein molecule comes in contact
with a gas bubble it becomes denatured. Its shape and
electrochemical nature is changed: the hydrophobic sections
of the molecule come in contact with the gas whereas
the hydrophilic sections move in the opposite direction to
remain in contact with the fluid.

When this denaturized protein molecule
comes into contact with cell
membranes, it could result in the accumulation
of globules of free fats
and the release of fatty acids from
cell membranes and subsequently
form fat emboli, which could cause
further damage. (see attached pdf file below)

. . .which is I think is the reason why I also had an Emergency Room work-up in Honolulu (stopover, coming home to LA) for Rule Out Pulmonary Embolism and Deep Vein Thrombosis (fat and/or clotting emboli), as well as an additional HBOT Table 6 treatment after my DCS type I episode in Chuuk, Oct 2008. . .

 

[Bubbletrubble]

@kevrumbo: Thanks for sharing the article. I think the author gets bogged down in extraneous details of the immune system. It's an easy thing to do because there are a lot of different types of cells/tissues/organs/molecules involved. For the most part, though, the essay contains a lot of good info. Hopefully, it was well received by the tech diving community.

One thing that's worth mentioning is that the paragraphs you quoted above on how bubbles denature proteins in vivo contain info that is highly, highly speculative. AFAIK, there's not a shred of research that supports that hypothesis. The colored diagrams in the article are also speculative. There's nothing wrong with speculating, but it's important not to be misleading either. I think that many lay people would look at those fancy, shmancy colored diagrams and get confused trying to distinguish what processes actually occur (supported by scientific evidence) and what processes are merely hypothesized.

Regarding why you were worked up for PE and DVTs in the ER...well, that's because it's thought that DCS can produce a local hypercoagulable state and those are conditions that are life-threatening. Moreover, long airplane rides can predispose even normal healthy individuals to developing DVTs. Also, and I don't have any details about your symptoms when you were in Honolulu, perhaps you were complaining of shortness of breath, chest pain, cough, and/or leg swelling/pains.

It's still not understood how DCS induces hypercoagulability. The cause might be a lot more specific than bubbles sticking to denatured proteins and snagging fatty acids along the way. Heck, it could be related to loss-of-function of certain key proteins which regulate clotting cascade/platelets in some way.

 

[Kevrumbo]

@kevrumbo: . . .Regarding why you were worked up for PE and DVTs in the ER...well, that's because it's thought that DCS can produce a local hypercoagulable state and those are conditions that are life-threatening. Moreover, long airplane rides can predispose even normal healthy individuals to developing DVTs. Also, and I don't have any details about your symptoms when you were in Honolulu, perhaps you were complaining of shortness of breath, chest pain, cough, and/or leg swelling/pains.

It's still not understood how DCS induces hypercoagulability. The cause might be a lot more specific than bubbles sticking to denatured proteins and snagging fatty acids along the way. Heck, it could be related to loss-of-function of certain key proteins which regulate clotting cascade/platelets in some way.

Yes!

I was treated last weekend [2008] for a type one bends hit in Truk Lagoon. . . and am now convalescing in Honolulu after a Hospital Emergency Room visit to rule out DVT, PE with history of DCS & HBOT three days earlier in Truk Lagoon. I arrived in Honolulu from Chuuk with complaint of left calf pain and mild shortness-of-breath, status post long transpacific airline flight. (. . . the triage nurse had the ER Doc see me immediately with no waiting upon presenting with these symptoms). . .http://www.scubaboard.com/forums/di...p-vein-thrombosis-status-post-dcs-type-i.html.

see also:
LIFE THREATENING PULMONARY THROMBOEMBOLISM IN NEUROLOGICAL DECOMPRESSION ILLNESS

 

[bvanant]

@kevrumbo: Thanks for sharing the article. I think the author gets bogged down in extraneous details of the immune system. It's an easy thing to do because there are a lot of different types of cells/tissues/organs/molecules involved. For the most part, though, the essay contains a lot of good info. Hopefully, it was well received by the tech diving community.

One thing that's worth mentioning is that the paragraphs you quoted above on how bubbles denature proteins in vivo contain info that is highly, highly speculative. AFAIK, there's not a shred of research that supports that hypothesis. The colored diagrams in the article are also speculative. There's nothing wrong with speculating, but it's important not to be misleading either. I think that many lay people would look at those fancy, shmancy colored diagrams and get confused trying to distinguish what processes actually occur (supported by scientific evidence) and what processes are merely hypothesized.

There are two (or many more, obviously) questions here. I believe that we have lots of experimental evidence both in-vivo and in-vitro that denatured proteins, partially unfolded intermediates and aggregates (particularly of therapeutic proteins) are more immunogenic than properly folded ones. That I think is unambiguous. We also have a variety of data that bubbles can lead to denaturation and unfolding both in-vitro and some limited in-vivo data for blood proteins. What I think no one has is any idea on whether or not these effects are clinically important in DCS. I am still trying to understand all the complement data but it is slow going and I have a day job.
Bill