DCS and the Immune system

[boulderjohn]

I recently came across this article.

http://atlanticunderwater.com/index.php?option=com_docman&task=doc_download&gid=9&Itemid=91

It is pretty heavy into physiology, and I have to admit I had trouble with some of it. When I read it, I searched for the parts that had practical application for me. What I found troubled me a bit because of some recent incidents.

I would really like it if people with a better understanding of this than I can give a summary of the key ideas that should be taken from it so that I can check my understanding with theirs.

 

[Saturation]

I'll take a stab at this, pending Dr. D's input.

DCI maybe caused by bubbles getting stuck in vessels or tissues and reducing blood flow or initiating pain, spontaneous formation of bubbles within tissue [ uncommon], or causing an immune reaction ... akin to an allergy but much more severe. Depending on how severe the missed decompression is, one, parts or all of the mechanisms can occur. The immune mechanism is the least well studied, but some attempts to intervene by using potent anti-inflammatory drugs during DCI, have been mostly unsuccessful.

In the first two, the treatment is recompression in a chamber. As recompression is very often successful, it suggests these 2 are primary mechanisms in most DCI.

The immune component may play a role in answering why there are roughly 3 tiers of diver response to gas loads once the dive is over: those who bubble a lot, average, and none. This likewise reflects tolerance for inert gas loads in diving, what can bend one diver, doesn't on others. However, there has not yet been a way to use this mechanism as a way to reduce DCI, say among those who are sensitive, by the use of drugs.

 

[cutlass]

My overall impression was that this article echoed a point that micro-bubbles can provoke a response equal to that of "fat embolism syndrome" which has both mechanical (blockage) and immune components. FES is a standard watch item in trauma care. Here's a really tiny nutshell on what it is: FES It might be tough to decipher the jargon, but the "Path" section of this article FES on emedicine reveals the parallels of FES and DCS-immune responses mentioned in the article. In fact, further on the emedicine text, DCS is listed as a possible cause of FES symptoms.

I'd like to know more about the passing blurb on p.6, item #2 under "Inflammation": "... It is interesting to note that hyperbaric oxygen ... also reduces delivery of leukocytes and neutrophils to the area. ..." This seems to have a bearing on the use of hyperbaric treatment for serious burns and infections, something that I wasn't really clear on.

 

[Dr Deco]

Hello: bolderjohn

Biochemical Mechanisms

In the category of DCS and biochemical effects, we are talking about early DCS and late [untreated] DCS. There are different reactions in the body.

Untreated DCS is known to be relatively refractory to hyperbaric therapy after about six hours. This indicates that something has occurred that is not responsive to pressure, i.e., a gas phase is no longer present in the tissue but a DCS problem remains. It is generally thought that some other reaction has progressed, e.g., edema formation.

Human DCS

What is presented in this article [c. 1998] is a concept that grew from experiments in the late 1960s by Philp and Gowdey. Their studies used rats as test subjects and the endpoint of "bends" was death. In diving involving humans, people do not die of the "bends." What was actually studied in rats was right-heart failure from excessive bubble loads. The heart was pumping foam, and the rats expired. Clearly, not what divers refer to as DCS.

While changes were found and drugs to mitigate the decompression problems, the changes were not relevant for humans. Drugs that prevent some deaths had no effect on human joint-pain DCS. What a surprise.

Immune System

When the depress problems are very severe, the human and animal cases begin to merge. Basically, it was a lovely theory that just had to work.

Except for the fact that the drugs did not work in humans, the time course was wrong, and the animal model was flawed, it was terrific.:depressed:

Dr Deco :doctor:

The next class in Decompression Physiology for 2009 is April 4 and 5. This class is on Catalina Island at the USC Marine Laboratory. Contact Karl Huggins at the web site: Advanced Decompression Physiology Seminar Information

 

[boulderjohn]

Thank you very much!

 

[Gene_Hobbs]

Except for the fact that the drugs did not work in humans, the time course was wrong, and the animal model was flawed, it was terrific.

The part that ways got me was that the initial results were never reproducible by other labs under the reported conditions.

Some of the most interesting work I have seen published recently is this paper:
Caviness, J; Montcalm-Smith, E. Stress biomarkers in a rat model of decompression sickness. UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES, BETHESDA MD. MS Thesis. RRR ID: 4781

This ongoing gene expression work in humans should be very interesting to watch. I know Dawn has been working hard and is VERY excited to have her first blood samples in hand. (her work is also funded by the Office of Naval Research)

 

[Dawn_Kernagis]

Excellent points made by Dr. D, Saturation, and Gene.

I wrote a very thorough response full of references, only to lose my internet connection. Since it is late, and I am processing the samples Gene mentioned , I will quickly sum up my previous post...

We talked before (in a previous thread) about the problems with translation from animal models to human pathophysiology in DCS pathophysiology studies.

The biggest thing is, as Saturation pointed out, we don't know what initiates the decompression stress response. The article focused on immune response to the bubbles, but there is a possibility that the snapshots of inflammatory, coagulation, and endothelial pathway activation researchers have observed in previous studies are part of a different response. Endothelial (cells lining the inside of blood vessels) and/or tissue damage by bubbles could initiate a cascade of effects. Similarly, these pathways could be activated as part of an injury mechanism (called ischemia-reperfusion injury) specific to reduction or cessation of blood flow to tissues, which would be caused by a physical obstruction of vessels (for example, in the more severe case of cerebral bubbles). A focus on sublicnical decompression stress response could potentially give us a better idea of initiating mechanisms and subsequent effects, compared to observations made in extreme DCS (as pointed out by Dr. D).

In terms of individual susceptibility, there is a strong interest in the world of anesthesiology in the individual difference of inflammatory response threshold (not immune) to the presence of gas emboli patients can be exposed to during cardiopulmonary bypass. Again, a better understanding of initiating mechanisms (not only of DCS, but also subclinical decompression stress) could help us understand where these individual differences stem from.

 

[boulderjohn]

The biggest thing is, as Saturation pointed out, we don't know what initiates the decompression stress response. The article focused on immune response to the bubbles, but there is a possibility that the snapshots of inflammatory, coagulation, and endothelial pathway activation researchers have observed in previous studies are part of a different response. Endothelial (cells lining the inside of blood vessels) and/or tissue damage by bubbles could initiate a cascade of effects. Similarly, these pathways could be activated as part of an injury mechanism (called ischemia-reperfusion injury) specific to reduction or cessation of blood flow to tissues, which would be caused by a physical obstruction of vessels (for example, in the more severe case of cerebral bubbles).

Please forgive if this next question indicates my degree of ignorance. I am really in over my head here.

DCS symptoms generally occur soon after a dive. Once they occur, they continue.

Is it possible that a "cascade of effects" such as you describe could lead to symptoms, especially symptoms related to the circulatory system, appearing much longer after a dive? Could these symptoms vary from normal symptoms other ways as well?

I have had coversations with divers in which they report that a day or two after diving they felt intermittent numbness in their hands which they are able to shake off each time they occured, like the familiar "my foot went to sleep" experience. These symptoms occured with some frequency in the day they were first noticed, but then diminished over time for about a week before going away altogether. Because of the late onset and the sporadic nature of the symptoms, they dismissed them as DCS symptoms, but the timing of it is sure suspicious, especially since it has happened more than once to more than one person.

 

[Dawn_Kernagis]

Please forgive if this next question indicates my degree of ignorance. I am really in over my head here.

DCS symptoms generally occur soon after a dive. Once they occur, they continue.

Is it possible that a "cascade of effects" such as you describe could lead to symptoms, especially symptoms related to the circulatory system, appearing much longer after a dive? Could these symptoms vary from normal symptoms other ways as well?

I have had coversations with divers in which they report that a day or two after diving they felt intermittent numbness in their hands which they are able to shake off each time they occured, like the familiar "my foot went to sleep" experience. These symptoms occured with some frequency in the day they were first noticed, but then diminished over time for about a week before going away altogether. Because of the late onset and the sporadic nature of the symptoms, they dismissed them as DCS symptoms, but the timing of it is sure suspicious, especially since it has happened more than once to more than one person.

Good morning,

My apologies on the delayed response. The best answer I can give you right now is I don't know, and not being a physician I would be hesitant to make any diagnosis. I will say that when we talk about a cascade of effects, thing like acute inflammatory response typically peak around 4-6 hours post peak-insult in other settings (ie. viral infection initiated in a research setting, insult in the surgical setting, etc.) Now, in other clinical conditions there can be delayed downstream effects (up to days later) that stem from things like direct tissue damage and a vessel that is blocked (for example, delayed injury in stroke), but I do not know how physicians would view these symptoms you've described - would these be treated as DCS?

Maybe one of the diving docs can jump in here?

I know personally I can have similar symptoms in my hand, neck, and right leg after diving, but I chalk these up to carrying heavy equipment and irritating one or both of the herniated disks I have...they typically diminish in a few days or so.

Not ignorant at all, btw, these are excellent questions!

Dawn

 

[Saturation]

What's need is a expert examination to insure the nature of these symptoms. Its also tied to the nature of the dive. Without more expert input, and if symptoms improve without treatment rather than escalate suggests its likely not DCI related. As Dawn mentions, many numbness and peculiar symptoms are often likely to be related to nerve impingement issues from sciatica, tight wrist mounted gear, heavy tanks etc.,

One missing item is an objective, non-symptom related, sign or finding. Without a finding that is reproducible and easily noticed by others such as a segment of numbness or weakness, an abnormal MRI or CT scan, symptoms are difficult to substantiate. One oft missed area are blood studies, even if non-specific. When you put the objective data together, even if such studites alone are not diagnostic, the probability of a disease rises, or drops.

Please forgive if this next question indicates my degree of ignorance. I am really in over my head here.

DCS symptoms generally occur soon after a dive. Once they occur, they continue.

Is it possible that a "cascade of effects" such as you describe could lead to symptoms, especially symptoms related to the circulatory system, appearing much longer after a dive? Could these symptoms vary from normal symptoms other ways as well?

I have had coversations with divers in which they report that a day or two after diving they felt intermittent numbness in their hands which they are able to shake off each time they occured, like the familiar "my foot went to sleep" experience. These symptoms occured with some frequency in the day they were first noticed, but then diminished over time for about a week before going away altogether. Because of the late onset and the sporadic nature of the symptoms, they dismissed them as DCS symptoms, but the timing of it is sure suspicious, especially since it has happened more than once to more than one person.

Good morning,

My apologies on the delayed response. The best answer I can give you right now is I don't know, and not being a physician I would be hesitant to make any diagnosis. I will say that when we talk about a cascade of effects, thing like acute inflammatory response typically peak around 4-6 hours post peak-insult in other settings (ie. viral infection initiated in a research setting, insult in the surgical setting, etc.) Now, in other clinical conditions there can be delayed downstream effects (up to days later) that stem from things like direct tissue damage and a vessel that is blocked (for example, delayed injury in stroke), but I do not know how physicians would view these symptoms you've described - would these be treated as DCS?

Maybe one of the diving docs can jump in here?

I know personally I can have similar symptoms in my hand, neck, and right leg after diving, but I chalk these up to carrying heavy equipment and irritating one or both of the herniated disks I have...they typically diminish in a few days or so.

Not ignorant at all, btw, these are excellent questions!

Dawn