Diagnosing Hypoxemia - Any doctors actually think about a problem - first principles?

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I've suffered with a CFS/ME like problem for over 10 years. Its slowly progressed and I finally understand the cause but not the underlying mechanism. I've been to UCSF, Stanford, Mayo Clinic, John Hopkins and many local doctors. After maybe 40 different doctors, I've yet to hear one try and diagnose based on first principles - Basic Physiology. Maybe they think privately think about it but none really share their process. Has anyone actually seen any Bay Area doctors who might actually "think" rather than pattern match symptoms too a list they have memorized? I'll explain.

I have experienced body-wide and brain hypoxemia that primarily occurs while sleeping but I do experience the beginning of symptoms when very sleepy and my heart rate and O2 saturation are at or near normal minimums ( 52bpm / 92% ). I've come to believe and have good evidence that during my sleep at a minimum heart rate ( below 50bpm), my cells are receiving inadequate oxygen and my muscle begin to have pain and I experience a myriad of neurological symptoms. I've confirmed my Oxygen saturation never drops below 90% and using supplemental O2, I can hold it near 99% with minimal apnea events. I've done this with a home recording pulse oximeter dozens of times.

So with normal O2 saturation, when my heart rate drops to its minimum, hypoxemia begins. So from a physiological point of view:

A---Either my respiratory and circulatory system is somehow producing 97%+ O2 sat at my finger but my cells are not getting enough O2.
OR
B---My cells are getting normal O2 profusion but my mitochondria require more O2 than my circulatory/respiratory system deliver normally at minimum heart rate.

I've had mtDNA sequencing which found 15% of the mitochondria have severely damaged mtDNA with 15% mtDNA 6.3kb deletions damaging 4 complete genes disabling those mitochondria completely - no ATP production. But the mtDNA sequencing was done this year 2021 but it was done at UCSF on a 2017 muscle biopsy sample that was in the freezer. So did freezing damage the sample or was it correct. But that was 2017 and my symptoms are now horrific so has it become far worse. Getting another biopsy is difficult - I think? Does it really require surgery?

Ok that supports B above. But before pressing for another biopsy, is there actually a circulation problem that shows ok O2 sat at my finger but there is not really enough O2 at the cellular levels?

Does anyone know what tests that are simpler might help determine whether A or B is correct and focus looking for a solution?

What would blood CO2 be in these cases. I don't experience any feeling like I need to breath hard upon awakening which suggests my CO2 is normal. No apparent acidosis caused by excess CO2.

What about Lactic Acid or Lactate/pyruvate ratio? Ideas? Doctors who would think like this?
 

hapl808

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I had all the lactate/pyruvate testing and it showed nothing unusual. I declined the muscle biopsy as I was already relatively severe and didn't think I would recover well from the procedure.

I've had some hypoxemia issues, but I guess my question is if A or B that you suggest is correct, what solutions will you try? Rather than focus so much on whether you can prove scientifically the theory, can you just try the solution and see if it works? I feel that we are not researchers trying to prove a theory through peer-review, we are just trying to find the solutions, whether or not they are 'scientifically sound' in any way.

I also think 'proving' a theory (which is always questionable and open to interpretation) is of limited value if there isn't a following intervention.
 

wabi-sabi

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Hypoxemia means too little oxygen in the blood. Are you sure this is you problem based on you 02 sats?

The issue that ME/CFS researchers are looking at is that while we have enough oxygen in our blood, it isn't getting into the cells for some reason. Like the work on endothelial dysfunction, red blood cell deformability, etc.
 

Judee

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Either my respiratory and circulatory system is somehow producing 97%+ O2 sat at my finger but my cells are not getting enough O2.
I think Dr Systom says this. The following article says, "He’s finding that the blood oxygen levels in ME/CFS patients’ veins are simply too high; i.e. not enough oxygen is being taken up by their muscles when they exercise. The oxygen is in the arteries, but the muscles are not taking enough of it up. That’s a big clue."

Here's the link to that article: https://www.healthrising.org/blog/2...ts-chronic-fatigue-fibromyalgia-autoimmunity/

Forgive me if you've already read it.
 

hapl808

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I still wonder about the muscle thing since my PEM is triggered equally by mental or physical activities. The feeling of PEM is the same I think, no matter the trigger.
 

wabi-sabi

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I think Dr Systom says this.
Yes, he's doing some really interesting work on this!

In normal people when blood leaves your lungs it's all topped up and full of oxygen. When blood comes back to the lungs after visiting your toes and brain it's lower(er) on oxygen because it's dropped off the 02 delivery. In us, the blood that comes back to the lungs is still pretty full of oxygen because it hasn't done the delivery properly for some reason. This is what Dr. Systrom's work shows.
 
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I had all the lactate/pyruvate testing and it showed nothing unusual. I declined the muscle biopsy as I was already relatively severe and didn't think I would recover well from the procedure.

I've had some hypoxemia issues, but I guess my question is if A or B that you suggest is correct, what solutions will you try? Rather than focus so much on whether you can prove scientifically the theory, can you just try the solution and see if it works? I feel that we are not researchers trying to prove a theory through peer-review, we are just trying to find the solutions, whether or not they are 'scientifically sound' in any way.

I also think 'proving' a theory (which is always questionable and open to interpretation) is of limited value if there isn't a following intervention.
My post was going back to simple physiological "break to problem into halves" basics so I could try and find a mechanism so I would know where to focus solutions on, if any - if that makes sense. So far I have done a number of attempts at solutions and further testing with limited results. Its very very difficult to get ANY doctors help at proposing solutions to try, designing "test" solutions to get further evidence toward ideas and justify possible solutions. The problem is I'm not all knowing and without some additional mechanism ideas, I'm not sure what to try. I'm not really trying to "prove" one theory or the others but rather trying to get eveidence that doctors will look at and propose possible solutions that are sensible and based on some reality. So here is a partial list that comes to mind. Its incomplete as my memory sucks:

--- I've tried supplemental Oxygen with does help some. But doesn't help with A or B
--- I've use caffeine, theophylline and pseudoeffedrine to speed up my heart while sleeping and it works - sorta. All definitely reduce my symptoms by 75% + with caffeine and especially long acting theophylline the best. But try living while using caffeine to sleep. Ok it provides strong evidence its my heart rate that is involved - but one doctor says he thinks its the caffeine molecule doing "more" but making suggestions is his best contribution to this. Yes caffeine and theophylline are Adenosine blockers and Adensone pathways are suspicious. But doesn't help with A or B
--- I've tried many other drugs to see if they modify the symptoms with little to no help
--- I've taken iron supplements to see if I can increase red blood cell count or hemoglobin O2 carrying capacity with no real effect. My CBCs show normal hemoglobin and red blood cells
--- Blood smears don't show any red blood cells "shape" issues
--- I have chronic SIBO probably from paralyzed GI motility from lack of O2. I've tried just about every possible GI SIBO and IBS, parasitic, etc.. treatment but I can cure SIBO for weeks but not severe constipation with Rifaximin. Its obvious to me that my GI nervous system and muscles are suffering the most followed by my brain and them large muscles.
--- I've had sleep studies and have gone through 2 CPAP machines with no help what so ever.
--- I've asked about cardiac pacemakers to keep my heart rate above a certain level. Doctors freak out without evidence.
--- I've worn a Zeo-patch ( cardiac monitor) twice for 2 weeks with one showing nothing and the most recent didn't work for all 2 weeks and showed nothing. I'm getting another next week. Three Echocardiograms showed my heart is ok.
--- I've tried the mitochondrial cocktail at least three times for long stretches. I recently restarted a creatine, CoQ10, L-Carnitine, B-Vitamin Complex, good Multiple Vitamin, Alpha Lipoic Acid, NAC DHEA cocktail.
--- I've tried low dose physiological hydrocortisone ( <15mg/day tapered) and various prednisone. Higher dose Prednisone ( >=20mg) made things much worse.
--- I've tried daily 10,000 lux light therapy and nightly melatonin ( my melatonin daily curve is inverted) - makes me curious about Adenosine curve? Caffeine?
--- I had my blood mtDNA sequenced but it did not find the same mtDNA deletions. Blood is made so regularly it might not show the same results as a muscle cell.
--- I've tried just about every supplement cocktail known to man.
--- I've tried getting up and walking around as the hypoxia begins to cause pain and neurological symptoms to increase heart rate and circulation and it works. At least ti I get tired, lie down fall asleep and it all starts again.

That's all I can think of right now ( there are many more) but most of the doctors I've seen are horrified with "tests" ( like my caffeine test), things like pacemakers, biopsies ( to double check the 4 year old frozen biopsy mtDNA sequencing ), etc...

I asked about this but was blown off...
https://rarediseases.org/rare-diseases/mitochondrial-neurogastrointestinal-encephalopathy/

Some solutions are complex and difficult and one needs a rock solid diagnosis from the proper expert to even have it considered... like mitochondrial problem trials

So I've done lost of solution trials and so far caffeine and theophylline show the most results but are unworkable in real life - try sleeping on theophylline every 3 hours as you get hypoxia as it wears off. 2 hours works best but thats dosing every few hours or 5 times a night.
 
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I had all the lactate/pyruvate testing and it showed nothing unusual. I declined the muscle biopsy as I was already relatively severe and didn't think I would recover well from the procedure.

I've had some hypoxemia issues, but I guess my question is if A or B that you suggest is correct, what solutions will you try? Rather than focus so much on whether you can prove scientifically the theory, can you just try the solution and see if it works? I feel that we are not researchers trying to prove a theory through peer-review, we are just trying to find the solutions, whether or not they are 'scientifically sound' in any way.

I also think 'proving' a theory (which is always questionable and open to interpretation) is of limited value if there isn't a following intervention.
My lactate/pyruvate ratio showed an issue but my doctor didn't know what it means.

I'm running out of solution ideas. I've tried dozens based on a variety of speculation ideas for the problem. I listed some above.
 
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Hypoxemia means too little oxygen in the blood. Are you sure this is you problem based on you 02 sats?

The issue that ME/CFS researchers are looking at is that while we have enough oxygen in our blood, it isn't getting into the cells for some reason. Like the work on endothelial dysfunction, red blood cell deformability, etc.
You have the right idea. My O2 sats are normal after dozens of checks. My breathing looks normal on video and audio suggests no snoring or breathing noise.

This is what led to the mtDNA sequencing. But you are right. Does simple O2 sat at my finger mean there are enough red blood cells passing through my capillaries resulting in proper profusion to my cells. Are there any red blood cell physiologic mechanisms that would show good O2 sat at finger but inadequate profusion to cells? Is there an endothelial issue at my capillaries preventing the O2 from properly reaching cells? Does CO2 look ok? I don't awaken needing "air" suggesting my chemo-sensors are not detecting high CO2.

If the 2017 15% mtDNA deletions are throughout my body ( but not in my blood) but has increased to well over 15% in 2021, that would explain my problem.

Blood smears and CBC do not show any problems except chronically high MCH "mean corpuscular hemoglobin." It's the average amount in each of your red blood cells of the O2 carrying protein called hemoglobin - suspicious its a bit high... not much 34 or so.

If say 50% of my cells have 50% "dead" mitochondria, the remaining 50% would need to support 100% ATP production. But if my circulation only delivers the original 100% Oxygen at low a heart rate ( minimum O2 delivery) during sleep and 50% ATP ( and other stuff) production by my mitochondria is not enough, it would explain everything. But the mito cocktail isn't helping. Other ideas?
 
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I think Dr Systom says this. The following article says, "He’s finding that the blood oxygen levels in ME/CFS patients’ veins are simply too high; i.e. not enough oxygen is being taken up by their muscles when they exercise. The oxygen is in the arteries, but the muscles are not taking enough of it up. That’s a big clue."

Here's the link to that article: https://www.healthrising.org/blog/2...ts-chronic-fatigue-fibromyalgia-autoimmunity/

Forgive me if you've already read it.
No I haven't. Thanks... I will.
 
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No I haven't. Thanks... I will.
Just read it. is this doctor accessible and still pursuing this? Mestinon - Pyridostigmine Bromide sounds interesting. Heard any reports on it?

Others listed in article inside that blog/post below:

A bevy of drugs, many of which have not been tried ME/CFS or FM, can improve parasympathetic nervous system functioning. They do so either by blocking aceytlcholine from being degraded (e.g. Mestinon), or by increasing acetylcholine release, or by inhibiting sympathetic nervous system activity.

Reversible parasympathomimetic drugs include Donepezil, Edrophonium, Neostigmine, Physostigmine, Pyridostigmine, Rivastigmine, Tacrine, Caffeine (non-competitive) and Huperzine A.
 
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Just read it. is this doctor accessible and still pursuing this? Mestinon - Pyridostigmine Bromide sounds interesting. Heard any reports on it?

Others listed in article inside that blog/post below:

A bevy of drugs, many of which have not been tried ME/CFS or FM, can improve parasympathetic nervous system functioning. They do so either by blocking aceytlcholine from being degraded (e.g. Mestinon), or by increasing acetylcholine release, or by inhibiting sympathetic nervous system activity.

Reversible parasympathomimetic drugs include Donepezil, Edrophonium, Neostigmine, Physostigmine, Pyridostigmine, Rivastigmine, Tacrine, Caffeine (non-competitive) and Huperzine A.
Funny... caffeine is listed here.. Interesting
 
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Until we get more research I think it comes down to good pacing. Don't spend more energy than your mitos can make.
My severe problems occur during sleep when my heart rate is at a minimum. So not spending more energy than my mito can make doesn't help much.
 
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Its somewhat described in my first post. When my heart rate gets low <50bpm during sleep, I believe my large muscles and brain are getting too little O2. As I get sleepy or I am asleep and my heart rate dips into the low 50's while my O2 sat remains at >97%, I begin to feel increasing bodywide pain, especially in shoulders and hips at first and especially those I'm laying on and neurological symptoms begin. If I get up right away and walk or have only slept briefly, the increase in circulation due to getting up and walking stops all pain and symptoms in minutes. If I've been asleep a few hours, getting up helps but not completely.

If I sleep too long, I awaken in total severe pain, cannot walk, cannot think, I'm dizzy, pins and needles all over, a severe headache etc.. like someone hit me with a 4x4. If I take caffeine, theophylllline or pseudofed to boost my heart rate a little to about 60bpm, these symptoms dramatically reduce. I have an Oura ring and a recording all night pulse oximeter with heart rate monitor and if I can keep my heart above 60 its much better. If it dips into the low 50's for any time, they are back but how bad is dependent on well I kept my heart rate up. The caffeine and theophylllline might have some additional help since they effect the adenosine system. Its not terribly clear if its a circulatory problem or a mitochondrial problem. Could be both.
 
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Yes fluids are ok..Done that. It's quite horrible. I'm exhausted and if I begin to doze off, it all begins in the day. Every night I take either Caffeine or theophylline at bedtime and again every few hours. If not it's a nightmare.But I cannot get good sleep which just magnifies things. And I just cannot get help anywhere. It's like the the doctors dont care, yet it seems like some of it is basic physiology but they dont even get that far. I guess everyone here has that problem.