[AnnieB3]

I'll try to explain about the heat/acetylcholine issue. I may be covering things you already know about but I'm not going to assume you know it.

In MG, antibodies attack the neuromuscular junction. Because of that, we don't get enough acetylcholine and our muscles get weak with activity or sometimes just at rest. The antibodies themselves don't make people with MG heat intolerant. It's what heat does to the chemical reactions between acetylcholine and acetylcholinesterase that is the problem.

Acetylcholine is the "gas" that makes everyone's muscles work well and stay strong. It enters the neuromuscular junction - where the nerves and muscles meet - and goes to work. Acetylcholinesterase is an enzyme whose "job" it is to clean up after acetylcholine once it's "done" doing its job.

Mestinon is a cholinesterase inhibitor. It inhibits that enzyme from cleaning up acetylcholine so that we can use it longer. You may not know that other cholinesterase inhibitors are: caffeine, nightshade foods and organophosphates (pesticides).

The basic science is that extremes of heat and cold will increase acetylcholinesterase in the body, thereby eating up more acetylcholine. People with MG already have too little acetylcholine getting to their muscles due to destruction of the neuromuscular junction muscle receptors. Basically, our muscle gas tank runs low all the time. So heat, and that little enzyme, make us much weaker.

Here is a quote from the abstract I gave you: "Given that acetylcholine is released from cholinergic nerves during whole body heating, . . . " The more acetylcholine that is released, the more acetylcholinesterase is produced. It's the body's checks and balances for making sure "normal" people don't have too much acetylcholine. So the more people are heated up, the more acetylcholine we make and the more that enzyme thinks it needs to get rid of it! That's fine if you don't have MG but if you do, it simply eats up what we can't afford to lose.

The body has so many "signals" and biochemical reactions like this that it is amazing how we stay healthy. There is so much that can go wrong. Probably the one most people know about is water balance and how when we are dehydrated, our bodies retain fluid for us. And when we are overhydrated, it gets rid of the water.

Does that make sense?

Dysautonomia is different than MG. If I were actually awake this morning, I could go into the details of that too! If you look up autonomic nervous system and acetylcholine you may get the info you need on that. Or autonomic nervous system and Mestinon or cholinesterase inhibitor.

I hope you are doing okay and are able to manage your disease well. The autonomic diseases are actually more difficult to treat/manage than MG, although it all depends how bad off you are with either disease!

Annie

[Joanmarie63]

Thank you Annie, once again a great post with a wealth of information. Do you know what the "normal" level of acetylcholine should be? What is high or low?

[AnnieB3]

Most doctors don't measure it, so it's not something there's a lot of info on out there. What I have read is that people with MG have about 1/3 of the receptors (sometimes less) of normal people and, therefore, about that much less of acetylcholine. It depends upon how much of the neuromuscular junction has been destroyed.

Going by how you "feel" or how weak you are is more important than using any kind of measurement. And everyone's "weak" is different.

[Joanmarie63]

Thank you Annie, I couldn't find anything on the internet about it but when I looked at my hosp report it said it was 2.75 I have no idea what it meant..LOL

[maryec]

Thank you for that Annie, I love reading your posts!
Mary

[rach73]

Thanks Annie another excellent post.

Hope the wedding went well and you start to pick up soon.

Love
Rach

[Heat Intolerant]

Your descriptions are terrific. I didn't know about the foods.

Nonetheless, and although your description makes sense -- and your quote revealed half the mystery -- I am now looking for a reference which shows that:

The more acetylcholine that is released, the more acetylcholinesterase is produced.

As far a “basic biology,” from science classes, I have a vague recollection of reaction equilibria and increases in enzymes which catalyze reactions depending on the equilibrium; nonetheless, I can't seem to find any reference to this, either in general or for acetylcholine and acetylcholinesterase.

The best related idea I can find is this one (which would only tend to show just that the acetylcholine gets broken down more quickly in heat and not show why both acetylcholine and acetylcholinesterase appear in greater amount in the heat):

Increases in temperature will speed up the rate of nonenzyme mediated reactions, and so temperature increase speeds up enzyme mediated reactions, but only to a point...

*edit*

I understand what you are writing but there is some fundamental assumption underlying it I am not understanding -- which I am sure you know like the back of your hand.
----

With regard to the difference between the conditions, my understanding as of now is that at least the difference in tests (at least in words) is that people on DINET are tested for Ganglionic AChR antibodies and not AChR Antibodies which I guess is a test for defects at neuromuscular junctions.

I imagine there is some similarity in the type of misery people with either disorder experience in the heat -- when I try to understand what happens in MG and the difference between what happens to you guys and what happens to people with dysautonomia, I think I get a better understanding of how the sensations I have in the heat are correlated to acetylcholine defects. I start to understand how the defects are limited to certain body functions or parts because of the type of defect.

Of course, if you are awake at some point, your descriptions and explanations are wonderful to read, so if you feel like writing the details of your understanding of the difference, it would be riveting reading! Thanks so much for your patience and explanations so far.

[AnnieB3]

Hi, Ren. I think what you're talking about is how acetylcholine becomes "denatured" with heat. This issue of acetylcholine sounds simple but it's so complex that you really need a biochemist to explain it all. While I was going to be one, but went into the arts instead, I am not that knowledgeable on all the details.

The bottom line for most people here is that Heat is MG's enemy. That's pretty much all they need or want to know.

Acetylcholine and Acetylcholinesterase are sort of like water and antiduretic hormone (ADH). Too much water in the body and the antidiuretic hormone backs off. Too little and it kicks in. I wish the mechanism was the same for not enough acetylcholine. Our body is set up to protect against getting too much acetylcholine but not when we get too little of it.

Heat does increase production of acetylcholine, thereby increasing production of acetycholinesterase. That little enzyme eats up acetylcholine really fast. Because we don't have a lot of receptors for acetylcholine to go into, we need it to stay in that neuromuscular junction longer to give our muscles the chance to get as much of it as possible. And when that damn enzyme increases, we get even less of it.

There are other drugs too, like Benadryl and Atropine, that do the opposite of Mestinon. There is a list of drugs at www.myasthenia.org that you can look at that are relatively contraindicated in MG. They reduce acetylcholine while things like Mestinon, caffeine and nightshade foods inhibit acetylcholinesterase, thereby increasing acetylcholine.

It's so much more complicated than I'm saying it but, really, all anyone needs to know are the basics. And to get support for this disease.

I'm not sure I have the energy - or desire - right now to go into the differences between MG and autonomic disorders. I really have a lot going on and it takes brain power I don't seem to have lately. I have a lot more than only MG going on. I have an arrhythmia that kicks in while doing the littlest thing that could progress to V-Tach and V-Fib. So my mind is really elsewhere right now. If that changes, I'll post something, okay? Sorry but my life truly sucks right now.

I hope this info at least helped.

Annie

[Heat Intolerant]

Hi Annie,

I'm sorry to hear you are not doing well.

Thanks so much for your time and thought-provoking posts.

I guess I will find what I need by thinking and looking in a bunch of places so don't think strenuously if you don't have time or energy now. I know it can take forever to post a good explanation.

I'll be looking to find out not really how acetylcholine gets denatured (I found explanations for that) but rather where acetycholinesterase is produced and how it's produced in quantity (in response to variable temperature).

I could be doing better as well. Right now, I have bladder and bowel issues. Because I have to worry about changes in blood pressure and odd responses to medications, it is dangerous to have diagnostic procedures without making sure anesthesiologists understand the underlying condition; so now I'm finally getting that investigated (I've been ignored for many years despite horrible exacerbations of all kinds).

Thanks again and I'll be lurking or posting here for a bit inasmuch as some of the issues here give me some perspective...

Feel good.

Ren

[motorhead]

well put!
an interesting factoid i ran across, mestinon is used as a prophyllactic for the nerve agent soman. it was used during the gulf war .