What Exactly is Dysautonomia?

Pyrrhus

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What is Dysautonomia?

For those who may be too afraid to ask, the word "dysautonomia" simply refers to any dysfunction of the autonomic nervous system.

The autonomic nervous system is the part of the body's nervous system that monitors and automatically controls the internal state of the body. In contrast, the "somatic nervous system" is the part of the body's nervous system that monitors and responds to the external environment.

For example, the autonomic nervous system receives input from sensory nerves that sense when there is food in the stomach and then activates motor nerves to push food through the digestive system.

Another example: the somatic nervous system receives input from the sensory nerves that convey vision from the eyes indicating that a big bear is approaching you and then activates motor nerves to make your legs run away from the bear.
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A very important thing to appreciate is that the autonomic nervous system is very large, and there are many many different types of things that can go wrong with it. Since any dysfunction of the autonomic nervous system is referred to as "dysautonomia", the word "dysautonomia" can therefore refer to many many different conditions:

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As you can see in the above diagram, the autonomic nervous system is anatomically divided into a "sympathetic" part and a "parasympathetic" part. The sympathetic part of the autonomic nervous system is often involved in "fight or flight" responses. In contrast, the parasympathetic part of the autonomic nervous system is often involved in "rest and digest" responses.

Hope this helps.
 

Consul

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Is the SNS and PNS working in a all or nothing fashion throughout the whole body, so if one of them is active then the other one is not active? Or can a SNS nerve going to one organ be active at the same time as a PNS nerve going to another organ is active.
 
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Pyrrhus

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Is the SNS and PNS working in a all or nothing fashion throughout the whole body, so if one of them is active then the other one is not active? Or can a SNS nerve going to one organ be active at the same time as a PNS nerve going to another organ is active.
Excellent question.

The division of the autonomic nervous system into "sympathetic" and "parasympathetic" parts is primarily an anatomical division, as the sympathetic signals travel mostly down the spinal cord and the parasympathetic signals travel mostly down non-spinal (cranial) nerves such as the vagus nerve.

In terms of how these two parts function, it is much more complicated. Yes, in the simplest situations, such as in a pure "fight or flight" response to external danger, sympathetic signals might be activated and parasympathetic signals might be suppressed.

But in most other situations, certain sympathetic signals might be activated at the same time as certain parasympathetic signals. For example, in the evolutionarily-programmed autonomic response to excessive heat, the autonomic nervous system might increase the blood flow to the skin to better dissipate heat from the body, which is an effect handled by parasympathetic signals. At the same time, the autonomic nervous system might increase the heart rate in order to pump more blood to the skin and dissipate heat faster, which is an effect handled by sympathetic signals.

So there are many autonomic responses that make use of both sympathetic and parasympathetic signals in order to best respond to the particular internal and external environment that the body finds itself in. Unfortunately, this fact is ignored by some writers who oversimplify situations and try to divide everything into "sympathetic" versus "parasympathetic".

I hope this clarifies.
 

Pyrrhus

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For some examples of the different types of dysautonomia in ME, see the following 7 discussions:

1) The best known type of dysautonomia in ME is orthostatic intolerance (OI). But how exactly is OI a dysfunction of the autonomic nervous system? A 2013 review shows that OI happens when autonomic nerves fail to constrict blood vessels upon standing!
https://forums.phoenixrising.me/thr...sels-low-blood-volume-and-baroreflexes.86445/

2) Do your fingers wrinkle in warm water? Did you know that this is controlled by the autonomic nervous system & isn't simply related to skin moisture? A lack of wrinkling therefore means dysautonomia! (Some people with dysautonomia even get intermittent wrinkling when their fingers are not submerged in water!)
https://forums.phoenixrising.me/thr...reening-test-before-tilt-table-testing.77607/

3) Some patients report dysautonomia of the pupils in their eyes, including unusual dilation in both eyes (mydriasis), in only one eye (anisocoria), or rhythmic contractions (hippus).
https://forums.phoenixrising.me/thr...upils-constricting-dilating-back-forth.82520/

4) ...and let's not forget Erectile Dysfunction...
https://forums.phoenixrising.me/threads/erectile-dysfunction-as-dysautonomia.86583/

5) Some studies suggest that Irritable Bowel Syndrome (IBS) might be a dysautonomia of the nerves that tell muscles to move food through the intestines. Too little stimulation: IBS-C. Too much: IBS-D!
https://forums.phoenixrising.me/threads/irritable-bowel-syndrome-ibs-summary-of-discussions.84970/

6) Did you know that there are actually 4 types of gastrointestinal (GI) reflux dysautonomia, which occur when the autonomic nervous system fails to close a GI valve, leading to improper food movement!
https://forums.phoenixrising.me/threads/gastrointestinal-reflux-as-dysautonomia.86644/

7) The vagus nerve tells the pancreas to release digestive enzymes into the intestines after you eat, which help to absorb nutrients. Can dysautonomia of the vagus nerve therefore lead to malnutrition?
https://forums.phoenixrising.me/thr...sible-malnutrition-due-to-dysautonomia.88765/
 
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Pyrrhus

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8) Aerobic Exercise Intolerance can also be a type of dysautonomia:

Exercise Intolerance: Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)
https://forums.phoenixrising.me/thr...patients-with-me-cfs-joseph-et-al-2021.82907/


The authors interpret the findings as clinical evidence for dysautonomia of the nerves that control constriction of the veins that transport blood from the extremities back to the heart, which means that:
  1. The veins that transport blood from the extremities back to the heart remain abnormally dilated while standing,
  2. which means insufficient blood pressure to return the blood from the legs to the heart,
  3. which means the muscles in the legs have impaired circulation (blood pooling) and therefore insufficient oxygen,
  4. which means that the muscles must cross the "anaerobic threshold" and start using anaerobic metabolism which doesn't require oxygen,
  5. which may also mean that the insufficient oxygen in the legs leads to death of the small nerve fibers in the legs. (Small Fiber Neuropathy)
  6. ...Which is exactly what many people have suspected for a while, and is the exact same mechanism behind orthostatic intolerance!
P.S.
For an explanation of the difference between PEM/exertion intolerance and exercise intolerance, see:
Exercise Intolerance vs. PEM/Exertion Intolerance
 

Pyrrhus

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9) Also note that the sympathetic branch of the autonomic nervous system can suppress immune cells.

In the case of Natural Killer (NK) cells, the autonomic nervous system uses the cortisol (glucocorticoid) and β2 adrenergic (epinephrine) receptors to suppress the activity of NK cells:
1650160447267.png


Also note that these Natural Killer (NK) cells appear to be the first line of defense against the re-activation of herpesviruses, so if NK cells are suppressed, then re-activation of herpesviruses might become more likely:
  1. Herpesviruses tend to re-activate in response to pro-inflammatory cytokines.[1]
  2. Exertion is often accompanied by activation of the sympathetic nervous system.
  3. Activation of the sympathetic nervous system decreases the function of NK cells.[2][3]
  4. NK cells are the most potent immune cell for preventing re-activation of herpesviruses, for some reason.[3][4]
  5. So prolonged activation of the sympathetic nervous system by exertion might eventually lead to re-activation of a herpesvirus. One example of this is the outbreak of cold sores that some people experience in response to stressful episodes.

References:
[1] https://pubmed.ncbi.nlm.nih.gov/9475116/
[2] https://content.iospress.com/download/advances-in-neuroimmune-biology/nib006?id=advances-in-neuroimmune-biology/nib006
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144531/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788305/
 

Pyrrhus

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10) Another type of immunological dysautonomia might be mast cell activation syndrome (MCAS).

Generally speaking, mast cells can be degranulated by either biological threats or by the autonomic nervous system. The autonomic nervous system can also increase the sensitivity of mast cells, without degranulation.

The classic example of mast cell degranulation due to dysautonomia is urticaria, commonly known as hives. In this case, dysfunction of the autonomic nervous system leads to degranulation of mast cells throughout the skin, despite the absence of a biological threat in the skin. (although there may be a biological threat elsewhere in the body)

Of course, if the dysautonomia is causing mast cells to degranulate, but you are taking mast cell stabilizing medication, the dysautonomia will fail to degranulate the mast cells, and your symptoms might improve.

If you're interested in reading more about this, here are some good papers:

Significance of Conversation between Mast Cells and Nerves (van der Kleij and Bienenstock, 2005)​
The parasympathetic nervous system as a regulator of mast cell function (Forsythe, 2015)​
Mast cell–nerve axis with a focus on the human gut (Buhner and Schemann, 2012)​

P.S.
Since it is common to find one type of dysautonomia alongside other types of dysautonomia, it should not be surprising that MCAS might appear alongside other types of dysautonomia. Here's a new-ish paper that suggests that MCAS and POTS sometimes occur together:

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association (Kohno et al., 2021)​
 

Consul

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@Pyrrhus That MCAS stuff i didnt expect even if i dont know the disease much. It now seems to me like dysautonomia might be a necessary condition to have mecfs? Many if not all of these mecfs associated disorders like MCAS, IBS, POTS etc could all be because of dysatonomia. What about other co-occuring stuff like hypocapnia, FM or connective tissue disorder, do you think they could be explained by dysautonomia as well?

I think Bruce Patterson mentioned in a february youtube talk thought that fixing his Long Covid patients dysautonomia didnt necessarily get rid of the Long Covid. That doesnt fit in very well with this but maybe there could be some issues with it, e.g maybe only parts of the dysautonomia was fixed or something.

Also very nice post on the NK cells and the exercise intolerance study.
 
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Violeta

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@Pyrrhus That MCAS stuff i didnt expect even if i dont know the disease much. It now seems to me like dysautonomia might be a necessary condition to have mecfs? Many if not all of these mecfs associated disorders like MCAS, IBS, POTS etc could all be because of dysatonomia. What about other co-occuring stuff like hypocapnia, FM or connective tissue disorder, do you think they could be explained by dysautonomia as well?

I think Bruce Patterson mentioned in a february youtube talk thought that fixing his Long Covid patients dysautonomia didnt necessarily get rid of the Long Covid. That doesnt fit in very well with this but maybe there could be some issues with it, e.g maybe only parts of the dysautonomia was fixed or something.

Also very nice post on the NK cells and the exercise intolerance study.
Does anyone know how a virus would cause dysautonomia?
 

Pyrrhus

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Many if not all of these mecfs associated disorders like MCAS, IBS, POTS etc could all be because of dysatonomia. What about other co-occuring stuff like hypocapnia, FM or connective tissue disorder, do you think they could be explained by dysautonomia as well?
Yes, dysautonomia does seem to explain many of the symptoms of ME nicely.

But it doesn't explain all the symptoms. It doesn't explain PEM, cognitive dysfunction, swollen glands, or sore throats. So this tells us that there is something bigger behind the dysautonomia. To put it another way, dysautonomia can be seen as one great symptom of the underlying disease that causes ME.

To answer your second question:
  • Connective tissue disorder may be a result of dysautonomic MCAS, since connective tissue, unlike other tissues, is filled with mast cells. If these mast cells in the connective tissue activate inappropriately, it will cause degradation of the connective tissue.
  • Hypocapnia is a type of dysautonomia that might be caused by brainstem problems.
  • Fibromyalgia (FM) is quite another story, however.


Does anyone know how a virus would cause dysautonomia?
Great question. Simple answer.
1) The virus would infect the autonomic nerves.
2) The virus would interfere in some way with signaling along these autonomic nerves.

One way that many such "neurotropic" viruses do this is by using a viral protein called a viroporin. Here is just one hypothesis for how such a viroporin might interfere with signaling along nerves:

 

Consul

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Yes, dysautonomia does seem to explain many of the symptoms of ME nicely.

But it doesn't explain all the symptoms. It doesn't explain PEM, cognitive dysfunction, swollen glands, or sore throats. So this tells us that there is something bigger behind the dysautonomia. To put it another way, dysautonomia can be seen as one great symptom of the underlying disease that causes ME.
Sure, im thinking that autonomic dysfunction could be a necessary condition for mecfs but not a sufficient one. So if all these disorders that appear to be clustered together like IBS, ME/CFS, POTS, MCAS are all caused by their own version of dysautonomia they could all lead to different looking diseases but the core would still be dysautonomia.

E.g
MCAS is a dysautonomia version that leads to degranulation of mast cells
POTS is a dysautonomia version that leads to reduced blood flow to the brain
IBS is a dysautonomia version that leads to motility problems
Me/cfs is a dysautonomia version that leds to cytokine network dysregulation (just as an example)

Do you think this way of viewing it makes sense?

edit: spelling
 
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Violeta

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Yes, dysautonomia does seem to explain many of the symptoms of ME nicely.

But it doesn't explain all the symptoms. It doesn't explain PEM, cognitive dysfunction, swollen glands, or sore throats. So this tells us that there is something bigger behind the dysautonomia. To put it another way, dysautonomia can be seen as one great symptom of the underlying disease that causes ME.

To answer your second question:
  • Connective tissue disorder may be a result of dysautonomic MCAS, since connective tissue, unlike other tissues, is filled with mast cells. If these mast cells in the connective tissue activate inappropriately, it will cause degradation of the connective tissue.
  • Hypocapnia is a type of dysautonomia that might be caused by brainstem problems.
  • Fibromyalgia (FM) is quite another story, however.




Great question. Simple answer.
1) The virus would infect the autonomic nerves.
2) The virus would interfere in some way with signaling along these autonomic nerves.

One way that many such "neurotropic" viruses do this is by using a viral protein called a viroporin. Here is just one hypothesis for how such a viroporin might interfere with signaling along nerves:

Thank you, Eric. My brain isn't working so great lately and when I come up with something I'm wondering about but don't have the mental energy to find the answer I get anxiety. I appreciate your help.
 

Pyrrhus

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MCAS is a dysautonomia version that leads to degranulation of mast cells
POTS is a dysautonomia version that leads to reduced blood flow to the brain
IBS is a dysautonomia version that leads to motility problems
Me/cfs is a dysautonomia version that leds to cytokine network dysregulation (just as an example)
That's certainly an interesting way of looking at it!

Just remember that one condition can also be a symptom of another condition. Until all these underlying mechanisms are fully elucidated, there simply may not be a clear way to distinguish a condition from a symptom.

Also note that MCAS, POTS, and IBS are all listed as symptoms of ME in various diagnostic criteria for ME.
 

kangaSue

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So there are many autonomic responses that make use of both sympathetic and parasympathetic signals in order to best respond to the particular internal and external environment that the body finds itself in. Unfortunately, this fact is ignored by some writers who oversimplify situations and try to divide everything into "sympathetic" versus "parasympathetic".
There's also the issue that the gut 'has a mind of its own', the enteric nervous system.
Yes, dysautonomia does seem to explain many of the symptoms of ME nicely.

But it doesn't explain all the symptoms. It doesn't explain PEM,
PEM could be explained by dysautomia, where the latter exerts effects on cardiac output, blood pressure regulation, and blood flow regulation (and probably more so at the microvascular level rather than macro flow) - PEM then being the result of a delayed chronic systemic microvascular ischemia-reperfusion response (the mico clots or 'something in the blood' theories).
 

Pyrrhus

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There's also the issue that the gut 'has a mind of its own', the enteric nervous system.
:thumbsup:

PEM then being the result of a delayed chronic systemic microvascular ischemia-reperfusion response
This is indeed a popular theory right now due to interest in the cardiovascular manifestations of a coronaviral infection. However, upon further inspection, this theory falls flat.

Specifically, the symptoms of PEM are nothing like the symptoms of ischemia-reperfusion injuries. Whereas PEM symptoms are generalized and varied, ischemia-reperfusion injuries tend to produce localized, well-defined symptoms.

For example, ischemia-reperfusion injuries in limbs can produce myalgia and paresthesias, which is something like Delayed-Onset Muscle Soreness (DOMS) with Peripheral Neuropathy (PN). PEM, on the other hand, presents with a profound muscle weakness called paresis. Inflammation markers in limb ischemia-reperfusion injuries would likely be elevated, whereas inflammation markers in PEM are not reliably elevated.

An ischemia-reperfusion injury to the brain would produce stroke-like symptoms, as it is essentially a Transient Ischemic Attack (TIA). Although cognitive exertion can trigger PEM, it is not at all clear how cognitive exertion could possibly produce a TIA.

So really, PEM is nothing like ischemia-reperfusion injuries.
 
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