Mechanism of a flare or crash

[MTRJ75]

I've felt much better over the last week. In fact, I had a pretty stressful day the other day where I had to spend 3 hours at the eye doctor, seated in uncomfortable chairs, followed by 2 hours in urgent care while my mother got x-rays after falling down the stairs (she's doing okay). I was actually pretty surprised how I came through the whole issue without any major issues. The last two mornings I've had less pain that usual upon waking and have actually had an appetite in the morning, a very rare thing for me. So, I made swhatome bacon and eggs, sat down to eat, cleaned up and then sat back down to work again...and that's when it hit. Every muscle in my body aching to burning to cramping to nausea, digestive emptying, clammy sweats, mouth and eyes went dry, field of vision started to blur or feel like when you get hit in the head or drink too much. The standard flare up for me with the works after minimal muscle activation and standing on what I thought was a good day. 

I know I've made many of these posts over the last year or two since I've arrived here, but that's because I continue to actually have anxiety, ironically after my system generates all the symptoms of an anxiety attack for an hour or so, because I'm still struggling to understand what exactly is going on in my body and why some things trigger it and others don't. The weather is beautiful today and has been the last few days, so I can't even blame heat or rain.

This is what I currently understand to be potential causes or mechanisms in the body: 

- lack of blood volume 

or 

- lack of proper blood flow (perhaps because I just ate, blood is pooling in my stomach and not getting to my other recently activated muscles or brain? Improper constriction or dilation)

- a chemical reaction in the blood caused by standing or minimal activity that shouldn't happen (too much lactic acid? But why?)

- actual nerve damage (autonomic or peripheral, but if this is the case, shouldn't it be more consistent?)

- dysfunction (the wrong messages are being sent from the brain to the nerves - is it because there is a neural dysfunction or actual damage in pathways? ie...is this something we might be able to fix by rewiring our brains? This would be the best case scenario, right?)

- immune system is attacking and causing actual damage to the pathways (in this case, mental rewiring would have no effect)

Sometimes I can tell when something is likely coming later on in the day if I even try to move off the couch. Sometimes, like today, I think I'm feeling well enough and maybe even have for a few days and I just don't know what I can and can't physically do that day and that's maybe what frustrates me the most. Would I have to have a flare or crash induced as I'm getting blood drawn for some kind of reaction to show up in bloodwork? 

Am I missing anything above or is it a combination of factors and how do I figure out what the exact mechanism actually is (because we can better target it if we know what's actually happening of course). 

[MTRJ75]

Just to add a couple more things I forgot to mention, where I'm going with the brain rewiring stuff I mentioned above and before in this forum is this: 

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These practitioners generally attempt to reduce the unceasing barrage of alarm messages the brain is automatically (and unconsciously) pumping out when it’s in that state. A wide variety of methods – from meditation (to desensitize the system) to visualization (to inculcate peaceful scenarios) to catching negative thoughts (to tame the alarm signals) – just to mention a few – are employed to do this.

https://www.healthrising.org/blog/2021/06/12/amygdala-retraining-program-improves-symptoms-biology-fibromyalgia/

And when I ask the neurologist about most of the above, his general answer seems to be that nobody can predict a dysfunctional autonomic nervous system. 

[Sushi]

And then there is the theory of one or more metabolic “traps” that cause dysfunction in basic metabolic processes like production of energy. This is being actively researched but know answers yet.

[MTRJ75]

You're talking about ATP @Sushi? I read about that in Dan Neuffer's book I think. But in that case, it would simply cause the exhaustion. Would that cause the tightening, burning muscles and all the other symptoms I mentioned at such a severity? Although, I think I remember something being mentioned about lactic acid in that theory too. 

[Sushi]

On 6/18/2021 at 10:58 AM, MTRJ75 said:

You're talking about ATP @Sushi? I read about that in Dan Neuffer's book I think. But in that case, it would simply cause the exhaustion. Would that cause the tightening, burning muscles and all the other symptoms I mentioned at such a severity? Although, I think I remember something being mentioned about lactic acid in that theory too. 

It is much more than ATP, though it would affect one’s ability to produce ATP. The hypothesis of a metabolic trap has a genetic underpinning—damaging mutations that create a “trap” in our metabolic functioning. I don’t have the science background to explain but am just noting that this is a possibility that some researchers are working with.

[MTRJ75]

Ironic that Dysautonomia International posted this graphic today. But now my question is, which symptoms are each mechanism responsible for: 

[MTRJ75]

Journal article accompanying the diagram with further explanation: 

https://www.sciencedirect.com/science/article/pii/S1566070221000588?fbclid=IwAR143FeT7sMs3VVmdMB-RrGwVkX-YIZnqnDaNZqlvpOlJL21SuGoE3mxR_E

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Fig. 1. Schematic of possible mechanisms leading to orthostatic intolerance and tachycardia in POTS. During upright posture, there is a gravitational shift of plasma volume toward the lower parts of the body which if unopposed would result in reduced cardiac preload and a fall in blood pressure. The autonomic baroreflex serves to prevent orthostatic hypotension and preserve cardiac output through sympathetic activation (peripheral vasoconstriction and increased heart rate). In POTS, excessive orthostatic tachycardia may result from a combination of appropriate autonomic responses to various physiological changes (shown in blue) or an inappropriate exaggeration of the sympathetic response to orthostatic stress (shown in red).

Abnormal cardiovascular physiology could include (1) absolute hypovolemia due to impaired regulation of plasma volume or (2) cardiovascular deconditioning resulting in reduced cardiac mass and low stroke volume. Excessive sympathetic activation may occur in the context of (3) a systemic inflammatory state with increased inflammatory mediators (for example, increased histamine in conditions of mast cell overactivity) or (4) increased sympathetic tone driven by central nervous system (e.g. anxiety or chronic pain). Autoantibodies targeting G-protein coupled autonomic receptors (5) could produce mixed effects by acting as partial agonists that both augment cardiac sympathetic signals and reduce the efficacy of norepinephrine-induced peripheral vasocontriction. Finally, abnormal peripheral vascular function may result from (6) peripheral small fiber neuropathy causing partial denervation in the lower extremities or (7) tissue laxity resulting in increased dependent venous pooling (which might explain an association of POTS with hEDS).

RAAS = renin-angiotensin-aldosterone system; MCAS = mast cell activation syndrome; AAbs = autoantibodies; hEDS = hypermobile form of Ehlers-Danlos syndrome. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

 

[MTRJ75]

More: 

Quote

7. Cardiovascular pathophysiology

A wide variety of cardiovascular pathophysiological mechanisms may lead to an abnormal postural tachycardia response. Importantly, these mechanisms may not be mutually exclusive. The hemodynamic properties of POTS identify closely with those seen in moderate hemorrhage in that central hypovolemia, reduced cardiac output, and increased adrenergic-mediated vasoconstriction occur (Fu et al., 2010; Stewart, 2012), while BP is maintained and may even increase (orthostatic hypertension) (Grubb et al., 1997). Reduced systemic venous return and reduced cardiac output contribute to reduced central blood volume when upright,(Barcroft et al., 1944) and absolute hypovolemia can be found (Fouad et al., 1986; Raj and Robertson, 2007; Raj et al., 2005) similar to bed-rested patients or astronauts with gravitational deconditioning (Montgomery et al., 1993). In others, redistributive central hypovolemia when upright occurs due to decreased lower extremity venous tone (Stewart and Montgomery, 2004), or splanchnic pooling (Stewart et al., 2006a). These cases may correlate with “neuropathic POTS”(Stewart et al., 2006b; Tani et al., 2000), in which local sympathetic noradrenergically-mediated vasoconstriction is impaired because of autonomic denervation or a biochemical milieu that locally reduces vasoconstriction, causing baroreflex unloading, decreased baroreflex-cardiovagal function, increased reflexive sympathetic noradrenergic excitation at other sites (Istvan and Roy, 2004), and augmented reflex tachycardia (Stewart and Weldon, 2001).

While a “hyperadrenergic” state with orthostatic hypertension is defined in some cases, there is scant evidence for enhanced sympathetic outflow from the central nervous system as a primary cause. Most investigations show exaggerated skeletal muscle sympathetic nerve activity while upright (Muenter Swift et al., 2005), consistent with reflexive activation. In addition, cardiac parasympathetic deficits (Jacob et al., 2019; Stewart, 2000) may be found in many individuals with POTS leading to relative excess of “sympatho-vagal balance” based on various measures including power spectral analysis of heart rate variability.

 

[Nin]

I haven't had the burning for ages. Realised I was getting this when my body was reacting to something which was toothpaste with sls in it. It wasn't just the burning, it felt like my body was attacking itself. They got no answer for this. It could be something you're coming into contact with

[yogini]

There are a bunch of different causes for dysautonomia.  What's going on in your body would depend your particular cause, which your doctor can best advise.   Two other things to remember.

Dysautonomia by nature has a lot of ups and downs.  If you did the same exact thing every day, you might have some good days and bad days.  Unfortunately that's just how it is.  It's unpredictable and doesn't always make sense.

Dysautonomia patients - no mater what the cause is - tend to all have similar stressors which do make things worse.  Examples include exercise, menstrual cycle, hot weather, not drinking enough water, not getting enough sleep, overdoing activity, personal stress, travel, etc.

[MTRJ75]

1 hour ago, Nin said:

I haven't had the burning for ages. Realised I was getting this when my body was reacting to something which was toothpaste with sls in it. It wasn't just the burning, it felt like my body was attacking itself. They got no answer for this. It could be something you're coming into contact with

Doesn't feel like that. This more feels like a sunburn on all my muscles. Have never been able to decipher a pattern either. It can come on out of nowhere or it can be lingering all day to the point where I feel it coming. 

33 minutes ago, yogini said:

There are a bunch of different causes for dysautonomia.  What's going on in your body would depend your particular cause, which your doctor can best advise.   Two other things to remember.

Dysautonomia by nature has a lot of ups and downs.  If you did the same exact thing every day, you might have some good days and bad days.  Unfortunately that's just how it is.  It's unpredictable and doesn't always make sense.

Dysautonomia patients - no mater what the cause is - tend to all have similar stressors which do make things worse.  Examples include exercise, menstrual cycle, hot weather, not drinking enough water, not getting enough sleep, overdoing activity, personal stress, travel, etc.

Part of the problem, as I was telling someone yesterday, is that there are no ups. I don't have good days and bad. I can't remember the last day I felt okay and the closest I get (tolerable), I generally ruin it by thinking I can do something. I would LOVE to have good days with my bad. 

I used to think hot weather was a trigger, but now I'm starting to think it's not any specific type of weather (unless extreme), but rather stark changes in weather. 

[MTRJ75]

I wonder if it's easier to just group these things into two sets of two categories: 

1) Things that are caused by actual damage or an actual attack on the body (ie autoimmunity)

or 

Things that are caused by dysfunction, but no actual damage. 

Then

2) Things that can be controlled or influenced by your own thought processes (or brain rewiring). 

or 

Things that can't be controlled or influenced without outside help. 

---

There has to then be some sort of answers once you have this down. As I've heard many say on here, things usually, eventually get better and the proof would seem to be that I don't see many people that have been here for a decade, still suffering at obnoxious levels. Those that have been here a long while are have generally been more stable and are here more to help others (and God bless you). Or aren't here at all anymore and have presumably recovered to the point where they're functional enough they don't need to be here anymore. 

[CJ65]

@MTRJ75 I love your questions and the way you group the possible mechanisms of action. I am an example of actual physical damage leading to POTS. During my cervical spine surgery my 9th cranial nerve -the glossopharyngeal nerve was damaged. This nerve ennervates parts of the throat, posterior tongue and carotid baroreceptors among other things. My efferent (motor) pathway coming from the brain works so I can swallow etc. It took 2 years for me to realize that I had no gag or feeling in my right throat. A scope showed my afferent pathway was damaged. The same pathway that comes from baroreceptors back to the brain. My brain thinks I’m bleeding out so it throws sympathetic NS into overdrive. It’s not baroreflex failure but definitely impairment. So when people tell me I can rewire my brain I want to know: if the nerve is cut and hasn’t started working in the last 5 years how the heck can that be rewired?  I don’t believe it can. And so I slip into the acceptance that this is as good as my health is going to be: limited, chronic and I try to find joy and hope where I can. 

[MTRJ75]

What a positive approach to all this, but that's awful that this happened to you and that the issue is known, but still can't be fixed. I'm hoping there's eventually a way to improve this for you. 

[MTRJ75]

I've found this interesting in perhaps explaining the vasodilation and low blood volume effects of some flare ups. I'll quote what I think are the most pertinent parts, but the entire article is full of pertinent information, starting with "sympathetic nervous system hyperactivity and ß2AdR receptor problems" then "the kallikrein-kinin-system (KKS) which produces bradykinin" and reduced sodium reabsorption into the kidneys. 

 

Quote

 

In the first hypothesis paper, the authors proposed that vasodilators (bradykinin, prostaglandins), produced in response to narrowed blood vessels, are causing many of the symptoms of ME/CFS.

That sets up the idea that low blood flows could be causing an ischemia-reperfusion injury in ME/CFS. Ischemia-reperfusion injuries occur when during hypoxic situations where tissue is first deprived of blood and then reperfused with it. Ironically, the injury quickly occurs when the blood is reintroduced back into what’s become a hotbed of oxidative stress.

The authors don’t believe this kind of rapid and devastating situation occurs in ME/CFS but propose that something like it is occurring on a much larger timeframe.

 

It eventually comes down to high sodium levels in the cell, dysfunctional NA+/K+-ATP enzymes 

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It’s the high calcium levels that then whack mitochondrial functioning, mess up blood vessel functioning, and cause insulin resistance in the muscles. The sodium buildup problem, though, comes first.

https://www.healthrising.org/blog/2021/07/09/hypothesis-chronic-fatigue-syndrome-wirth-scheibenbogen/

In sum, I have no idea what I just said and there doesn't seem to be any immediate solution proposed, but it sounded important. 

[MikeO]

On 6/20/2021 at 7:21 PM, MTRJ75 said:

There are a bunch of different causes for dysautonomia

I agree with this statement. As i progress with my issues i am finding out it is not just one cause but a suite that makes up the whole. so i work on what i know helps out to have a better day but is still trial and error. I know that my SNS can go into overdrive "this is bad" especially taking certain meds "lisinopril will trigger it". My reflex responses are all diminished so that would suggest a peripheral neuropathy but this is a blanket term as well so the confusion continues. so until i can get into the clinic all i can do is try stuff.      

[MTRJ75]

Unfortunately, the only thing I know makes me have a better day is not leaving the couch. I've read many people say that it gets better, but I feel like my body keeps getting worse and I'm just becoming more accepting of the fact that I'll live what's left of my life alone on the couch or in bed.

I keep trying to convince my body that things that I know are a trigger aren't because I don't know why they would be a trigger. In a strange way, I guess it's some sick version of exposure therapy. Telling myself it will be fine because it doesn't make sense that it wouldn't be, but it never is. 

Example: Sunshine. Doesn't even matter the temperature. Beautiful 75 degree day with a nice breeze. I go out back with the dog before the shade hits in the evening. I'm out there five minutes, come inside and suffer the rest of the day. I get why sunlight would affect my vision, by why would it cause all the muscles in my body to tighten up and my nervous system to crash? 

[MikeO]

22 minutes ago, MTRJ75 said:

Unfortunately, the only thing I know makes me have a better day is not leaving the couch

I know this feeling as well. but then i crash get blurred vision and life sucks. like said becomes trial and error as to what helps. when i get blurry eyed i can walk it off to some extent but while it helps i am still having a bad day. what i have found is to keep active and upright even if it is a little at a time makes a difference.

[Pistol]

5 hours ago, MTRJ75 said:

Example: Sunshine. Doesn't even matter the temperature. Beautiful 75 degree day with a nice breeze. I go out back with the dog before the shade hits in the evening. I'm out there five minutes, come inside and suffer the rest of the day. I get why sunlight would affect my vision, by why would it cause all the muscles in my body to tighten up and my nervous system to crash?

Sorry @MTRJ75 - the same thing happens to me, and despite the fact that I am much improved since initial onset of my illness: the only way I can avoid having a flare from the sun is by AVOIDING the sun. I do not mean to take the wind out of your sails but honestly - if it makes you feel bad you have to avoid it. I know it isn't fair and it stinks - but the only way you can possibly get in control of these symptoms is by avoiding what makes you feel bad. At least until they come up with a cure. 

[MTRJ75]

But everything makes me feel bad @Pistollol. Waking makes me feel bad. I should probably start avoid that. 

[MTRJ75]

8 hours ago, MikeO said:

I know this feeling as well. but then i crash get blurred vision and life sucks. like said becomes trial and error as to what helps. when i get blurry eyed i can walk it off to some extent but while it helps i am still having a bad day. what i have found is to keep active and upright even if it is a little at a time makes a difference.

Movement cause or worsens my vision. I must be the opposite of you. 

So Cort over at Health Rising wrote more about the RAAS and the hypothesis that high Ang II levels are wreaking havoc. 

https://www.healthrising.org/blog/2021/07/29/long-covid-chronic-fatigue-syndrome-hypothesis-merging/

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They proposed that high ANG II levels are knocking out the mitochondria in endothelial cells lining the blood vessels – reducing nitric oxide (N0) levels (inhibiting the blood vessels from dilating properly), and triggering something they called “vascular aging”.

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High levels of Ang II produce inflammation, fibrosis, inhibit muscle repair, damage the endothelial cells lining the blood vessels, produce vasoconstriction (narrowing) in the blood vessels, jack up oxidative stress levels – producing peroxynitrite, and reducing the levels of nitric oxide – an important vasodilator.

Ang II also inhibits the phagocytosis or swallowing of damaged and dead cells (efferocytosis) – possibly allowing damaged endothelial cells to accumulate – and the intestinal dysbiosis to worsen.

When phagocytic cells such as macrophages fail to cleanly envelop or swallow damaged cells, the contents of those cells (called damage-associated molecular pattern (DAMP)) can leak into the bloodstream, causing an immune response. High DAMP levels have been associated with unexplained fatigue, chronic pain, exhaustion, and muscle dysfunction in other diseases.

So Ang II is directly causing Leaky Gut. I would imagine that trying to heal the gut through diet and supplements wouldn't do much good if high Ang II levels are still blast ing through. 

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The authors noted that several treatments (escitalopram, coenzyme Q10 and nicotinamide adenine dinucleotide (NAD), mildronate) used in ME/CFS can restore endothelial functioning, and suggested that angiotensin receptor blockers (ARBs) might be helpful.

Factors that improve short-chain fatty acids (SCFAs/fermented dietary fiber) may be able improve intestinal integrity. Fat globule membranes (MFGM) and b-glucan have been shown to do the same in mouse studies. B-glucan may also be able to damp down microglial activation in the brain. Fecal transplants haven’t been studied enough, but the early word on them in ME/CFS is pretty good. Metformin may be able to protect the gut barrier.

The authors also believe that a new field of drugs called senotherapeutics (dasatinib, hyperoside, quercetin, fistein, Navitoclax), which target cell death and aging, may present another as yet untested option.

Bolded is what I've tried already with either little effect or was unable to keep up at suggested dosages due to cost. I've read one protocol that called for Ubiquinol (COQ10 precurser) that would have cost me a $60 bottle every two weeks alone. 

Can I ask for Ang II to be tested? Would testing show accurate results or do I have to be particularly symptomatic when tested or need to be tested over a specific period of time? 

[Pistol]

7 hours ago, MTRJ75 said:

Can I ask for Ang II to be tested?

Yes, you can. Early on in my POTS journey my autonomic specialist tested my entire RAAS. Mine was fine. To tell you the truth I am not sure what type of doctor orders this test, maybe a PCP can order it. 

Thank you for posting this very informative article. It explains to a degree one of the mechanisms why auto inflammation is often involved in POTS. I am one of those people that are affected by auto-inflammation and have found relief of both inflammation as well as POTS from hydroxychloroquine. 

8 hours ago, MTRJ75 said:

But everything makes me feel bad @Pistollol. Waking makes me feel bad. I should probably start avoid that. 

I am sorry! That is horrible! I used to be like that too and it took many, many years of relentlessly trying meds until I found some relief. Today I am able to know exactly when I need to stop doing what and to avoid certain activities or triggers all together. I sincerely wish you find some relief!

[MikeO]

10 hours ago, MTRJ75 said:

angiotensin receptor blockers (ARBs)

Have you tried an ARB? I know we are all unique and hope you can sort out what works for you. 

[MTRJ75]

4 hours ago, MikeO said:

Have you tried an ARB? I know we are all unique and hope you can sort out what works for you. 

No, this is going to be my next line of questioning with the neuro. And perhaps testing the entire system like @Pistol said, but also like she said, who knows if it's one of those things that looks fine via testing, but is actually still mess. 

[MikeO]

Keep after it. I know i did not due well with a ARB "got hives" does not mean you won't have better success. what i did feel on the arb was more energy but i just not tolerate the drug well. a ans issue can be tested so push for it.