Curious if my story rings any bells with others?

[roller]

the pressure, not really the oxygene

 

[LHCTom]

@LHCTom

Still trying to get my head around your medical history. There is no question your metabolism is way out in left field. You do look like a classic case of Naviaux's hypometabolic state. What else is going on is a real question, and unfortunately, there are way too many possible causes.

Yes its a mess! But why is the question.

In terms of infectious agents, I see spirochetes, intestinal bacteria, parasites, fungi and yeast. I did not see mention of toxoplasma gondii, but the association with cats makes that a possibility. I would not be surprised to see high titers of viral antibodies, if your immune system were in good condition, which I doubt considering those multiple infections. I wouldn't be surprised if your immune system has been throttled down to avoid autoimmune disease.

Yes I'm IgG but not IgM positive for toxoplasma Gondii. Just around the time I first began struggling I had been given a feral kitten. Feral kittens being wild are common carriers of Toxoplasma Gondii and Bartonella. Toxoplasma Gondii is a lifelong infection and I've tried to convince a number of doctors including Montoya of Stanford to look harder for Toxo. Montoya is among the world's leading experts in Toxo but my view is expertise makes for lack of creativity. I have leaky gut and its caused about a dozen food allergies including my favorite foods. My total IgE can run over 1000 and my IL4 quite high which creates a Th2 immune system bias at the expense of TH1. I was also treated at least 10 times with Prednisnone and that plus the TH2 bias qualify me as partially immune compromised. My total IgG runs abnormally low. I also see a high EOS on about every third CBC.

I have a pulse oximeter that I run all night and it shows my O2 saturation rarely goes below 90%. Yet when I awake, I feel hypoxic or hypercapnic. I have a brand new CPAP machine which does not help one bit. The CPAP is over-coming any apnea events and reports its working well. So my cells seem to not be getting O2 yet my O2 saturation and CPAP failure suggest its not my respiration alone. That implies my blood is being oxygenated but its not being delivered to my cells while I sleep. When you sleep, your respiration is depressed and the O2 saturation declines but not enough to cause a problem unless something else is interfering like a parasite. When I was tested for Lyme at Fallon's Tick Borne research Center at Columbia and again by 2 integrative doctors via IGenex, I also tested positive for Babesia Duncani. So I was treated with Mepron and Arithromycin.

So I'm very sispicious that something is effecting my blood flow through my capillaries while asleep and my O2 saturation is 90%. On this hypothesis, I switched to my old blood pressure medication Lisinopril ( ACE inhibitor) and Amlodipine ( Calcium Channel Blocker) and away form a beta blocker. I also added a baby aspirin and L-arginine in an attempt to maximize blood flow and minimize blood vessel constriction. That greatly reduced my awakening symptoms. So the question is why? Is it a blood parasite that is further limiting my O2 carriage in my blood or causing something like Rouleaux which is where red blood cells stack due to electric charge which makes them flow less easily and congesting capillaries. I was also IgG positive for Mycoplasma Pn. which is another possibility along with the Toxoplasma, Babesia, 2 fungus's ( Scedosporium apiospermum and Candida guilliermondii), Lyme and I was culture positive for MRSA. I was ALS culture positive for Lyme 3 times, CDC positive by iGenex once, 4/10 IgG by Stony Brook Lab, and Immunetics C6 positive by iGenex, Stony Brook Lab and Quest.

Something on this list is interfering with the delivery of O2 to my cells which cannot be overcome by CPAP and a finger pulse oximeter suggests my saturation is not all that bad.


That foot drop at the onset is a clear sign of some neurological problem, but what? MS?

That was 15 years ago but I believe it was when this all started.

If we are considering unusual infectious agents affecting both nerves and immune response I would wonder about HTLV. I'm sure you've been tested for HIV, but testing for HTLV remains rare, and usually depends on antibody response, which seems to be impaired.

Been tested for HIV 4 times negative but not HTLV.

("We've narrowed things down. It's either an RNA virus, a DNA virus, a retrovirus, a spirochete, a bacillus, a parasite or two, fungi or yeast.")

Some clusters of symptoms and signs you mention go along with mast cell activation disorders, particularly that Imidazoleacetic Acid being way out. Have you had other tests specific to mast cell function? This looks like a case of chronic immune activation firing in many directions.

I probably do have a mast cell activation disorder since certain drugs like Ibuprofen immediately trigger angio-edema.

Other patients I've heard from with that range of gut problems, sleep disorders, etc. have inherited connective tissue disorders. These can range from rare (EDS) to extremely rare (HKPP). That last is connected with a potassium channelopathy. Many have had surgery to reduce apnea, and quite a few of these were not completely successful. Do you have trouble swallowing at present?

I had a sleep study at Stanford and they found mild sleep apnea back in 2003. I had surgery in 2008 and it greatly improved. Its partially come back but the good O2 saturation and the CPAP does not correct for my hypoxic-like awakenning suggesting its not sleep apnea but that could be an aggravating factor for a red blood cell parasite.

You have described a complex case with multiple layers of pathology. If present day medical professionals can't get to the bottom we need a new generation of doctors. Something is obviously wrong.

I've been through every doctor at Kaiser and then multiple Stanford doctors, numerous integrative doctors and now I'm seeing a UCSF Infectious Disease Doctor. I was referred by a UCSF Nephrologist. My creatinine and Ck go up and down together. My creatinine goes as high as 2.1 ( kidney disease) but then falls to 1.1-1.2 after I'm treated with antibiotics. Go figure. When my awkenning with confusion,sever pain, high BP, headache, need for air etc.. was only episodic ( every 3-4 months), I was able to stop it with Bactrim. None of the doctors believed me and others said it couldn't be its antibiotic affect. It turns out Bactrim is a folate synthesis inhibitor and has some effectiveness on Toxoplasma Gondii and Fungus besides bacteria such as Bartonella.


As always I am not a medical doctor, and the opinions I express are merely my own.

Understood... Ideas welcome!

 

[LHCTom]

The stated range in at least two of the labs I have handy is 22 to 29, and I have been coming in pretty consistently at 21 or 22. I've been flagged as out-of-range low at least three times in the last 18 months.

I don't hyperventilate, and I am amused when ME/CFS experts throw that out there (I've had three solid experts offer that). Imo, it holds about as much merit as my OI is caused by stress.

Thanks for the insights. I will see if I can wrap my head around the math. Doubtful. I do so out of curiosity, not under any illusions you are a doctor, and I also am appreciative of your input with that understanding.

Telling you that its caused by hyperventillation is beyond absurd, its stupid! Where has creativity gone - under a rock!

Is that you Duncan from the LymeNet Forum? Send me the values on some metabolic panels you have had over the year and years. I need the Sodium, Potasium, Chloride and Total CO2

Typical values on my Labcorp Metabolic Panel example

Potassium = 4.6 mmol/L range 3.5-5.2
Sodium = 141 mmol/L range 136-144
Chloride = 101 mmol/L range 97-106
Total CO2 = 25 mmol/L range 18-29

 

[duncan]

Yes, it's me from the Lymenet forum. Still dueling over there with IDSA , NIH and ALDF types. Let me dig around and get you those values.

Hey LHCTom - my C6 is still rising....

 

[taniaaust1]

The stated range in at least two of the labs I have handy is 22 to 29, and I have been coming in pretty consistently at 21 or 22. I've been flagged as out-of-range low at least three times in the last 18 months.

I don't hyperventilate, and I am amused when ME/CFS experts throw that out there (I've had three solid experts offer that). Imo, it holds about as much merit as my OI is caused by stress.

Thanks for the insights. I will see if I can wrap my head around the math. Doubtful. I do so out of curiosity, not under any illusions you are a doctor, and I also am appreciative of your input with that understanding.

Ducan my anion gap on hospital blood tests too has been out of normal range at times

 

[anciendaze]

@LHCTom

I noticed one very curious anomaly. You report multiple specific immunoglobulins up, but overall IGG is low. This could be immune exhaustion from multiple infections, but there is an alternative which raises another wild possibility in my mind. There are a number of autoimmune disorders involving some form of immunoglobulin G. These typically produce a bizarre range of signs and symptoms, including multiple infections. Only the most severe cases have been recognized to date, and that only since 2003. The problem is heritable, but I don't know the status of genetic research.

Sorting out what is going on in all the forms of these diseases is a problem. The term autoimmune normally means a component of the immune system attacking proteins in non-immune cells. It is also possible for different components of immune systems to attack each other, and this is a standard way to select out autoimmune immune cells in healthy people. So we tend to get two opposite conditions lumped together. You can have high levels of particular autoantibodies causing trouble, or you can have low levels of antibodies allowing infectious agents to run wild. The low levels can be caused by fratricide within the immune system, which leads back to high levels of a particular autoantibody and low levels of those attacked.

It is also quite possible for your body to produce defective antibodies which simply don't function well. Common laboratory tests may not distinguish the defective antibodies from good ones, it depends on the defect.

 

[duncan]

Here's two, @LHCTom , one from 2015 and one from 2016.

2015:
CO2 = 19 range: 22-29
Potassium = 4.0 range: 3.3-5.3
Chloride = 101 range: 96-108
Sodium = 138 range: 133-145

2016
CO2 = 20 range:23-32
Potassium = 4.3 range 3.3-5.5
Chloride = 103 range 90-108
Sodium = 142 range 136-146

 

[LHCTom]

Yes, it's me from the Lymenet forum. Still dueling over there with IDSA , NIH and ALDF types. Let me dig around and get you those values.

Hey LHCTom - my C6 is still rising....

 

[LHCTom]

Duncan,

How are you doing? Better - Worse? How high is your C6? Mine was 2.2 ( <.91 = negative) when first checked at Columbia at Stony Brook Labs who used the Immunetics kit. I had follow up tests at Quest and iGenex who both use the Immunetics kit also. It began to fall after my first 2.2 in 2012 to about 1.7 in 2013, 1.5 in 2014 and was barely negative at .9 in early 2015.

I had Bob Lane visit my place and we collected about 100 nyphal ticks. There were 5 with B burgdorferi and 1 with B. miyamotoi which Bob send to Alan Barbour so he could compare Bm genetics between the West Coast and east Coast. Here is an article where Alan Barbour discusses the results of his analysis of my B. miyamotoi infected tick

"We evaluated DNA extracts of B. miyamotoi–infected I. pacificus ticks collected by and stored at 2 laboratories in the San Francisco Bay area of California. Ticks had been collected while questing either on low vegetation or in leaf litter. To confirm B. miyamotoi in candidate extracts and to exclude extracts that also contained B. burgdorferi sensu lato, we used a quantitative PCR, which differentiates relapsing fever and Lyme disease group species (2). Two extracts that met these criteria were Sonom53 from a nymph in Sonoma County, California (38.328758, −122.625286), and SMA107 from an adult male tick in San Mateo County, California (37.466999, −122.283532)."

My property lattitude and longitude in bold underline.

https://wwwnc.cdc.gov/eid/article/22/12/15-2046_article

Can't help but wonder if my positive C6 and mixed Western Blots might be indicative of a Bm infection. I was CDC positive by iGenex once, always positive by iGenex criteria, 4/10 IgG antibodies by Stony Brook in 2012 but 0/10 IgG at Labcorp. I was also positive for Babesia by ELISA at Columbia using MDL labs and again using an IFA at IGenex.

 

[duncan]

I am doing somewhat worse. I was on heavy abx for many months. Saw my C6 decline to 3.3, and although my ELISA remained positive, my WB dropped to only three bands IgG positive. So I think I was making progress. My IDSA guy wanted to put the final touches by two months IV Rocephin, but insurance would only allow 30 days. Shortly after the IV, my C6 doubled to 6.5, my WB climbed to six bands positive. And I also continue to test positive for bartonella. My brain symptoms worsened as soon as I started IV Rocephin, especially balance and cognitive; they've stayed poor.

I tried getting tested for BM, but couldn't. I think Imugen has a miyamotoi test, and maybe Igenex. There is a God-awfully high portion of ticks testing with BM these days.

Even if you do have miyamotoi, they will claim conventional abx should do the trick, even though it is rightfully classified as a relapsing fever bugger. I think Krause - of babesia fame? - is leading the mainstream efforts into BM.

 

[LHCTom]

Here's two, @LHCTom , one from 2015 and one from 2016.

2015:
CO2 = 19 range: 22-29
Potassium = 4.0 range: 3.3-5.3
Chloride = 101 range: 96-108
Sodium = 138 range: 133-145

2016
CO2 = 20 range:23-32
Potassium = 4.3 range 3.3-5.5
Chloride = 103 range 90-108
Sodium = 142 range 136-146

Anion Gap Calculator without K at http://www.globalrph.com/anion_gap.cgi
Anion Gap Calculator with K at http://www.ebmconsult.com/app/medical-calculators/anion-gap-calculator

2015 - AG = 18
2016 - AG = 19

Increased Anion Gap:

Generally considered to be >12 ± 2 mEq/L or mmol/L and reflect the anions that are not included in the formula (albumin, phosphate, sulfate). Therefore, if the anion gap is > 12 mEq/L this would suggest that additional anions are also present when they should not be. These additional anions that can cause metabolic acidosis where bicarbonate (HCO3) is consumed by negatively charged particles include: ethylene glycol (due to the formation of oxalic acid), ketones, lactate, metabolites of methanol (i.e., formic acid), ketoacids (acetoacetate & β-hydroxybutyrate), and salicylates. In addition, increased albumin (hyperalbuminemia) and uremia can increase anions (or negative charges present) and hypocalcemia or hypomagnesemia can decrease the cations (positive charges present). Alcoholics can also develop an anion gap from lactic acidosis (due to a greater amount of pyruvate being converted to lactate from the excess NADH generated in alcohol metabolism).

The Anion Gap is a techique for verifying the bodies electrolyes are in balance. They call it a "Gap" because by adding the dominant cations Potassium and Sodium and subtracting the dominant Anions Chloride and Bicarbonate ( total CO2), a gap of about 12 corresponds to the normal non-dominant anions such as albumin, sulfate, phosphate etc... But an Anion Gap that is high implies there are other Anions pushing toward acidic that should not be there that the body is trying to balance out to achieve a 7.4 PH. A low Anion gap implies there are cations that shouldn't be there pushing towatd alkalinity.

An Anion Gap of 18 or 19 is high and deserves a deeper look. It could be your albumin or another normal anion is a little high and there is no problem. On the other hand, your gut microbiome could be producing Lactic Acid which is forcing your kidneys to use the stored bicarbonate to balance your PH. It could mean you have a form of acidosis which is a serious condition because a 7.35-7.45 PH is essential or your bodies cells cannot function since almost everything operates on electric charges. As I said before, its like taking a 3V electronic system and connceting its ground to 1.5V.

Many people think they can test body PH by using urine strips. There is nothing further from the truth. Urine is the waste from the kidneys which will dump acids or bases into the urine as part of the body PH balancing. So Urine PH can vary considerably without being an issue. If the blood/cellular PH is outside the 7.35-7.45 range, the body cellular functions begin failing until the body eventually dies. Its amazing the body and especially the kidneys and respiration are able to keep the PH so tightly regulated.

Because I was becoming very ill upon awakenning from sleep ( day or night) with skyrocketing blood pressure, confusion, headache, severe body pain, loss of feeling, tininitus, etc.. but CPAP didn't help an my pulse oximeter said my O2 was 90%+, and my AG was a little high ( less than your 18/19), my doctor ordered the gold standard test known as an Arterial Blood Gas measurement. It must be done in a hospital since they put a needle in your wrist artery ( risky) and immediately run the sample to the hospital lab. My PH was perfect at 7.4 and temperature compensated CO2 was 40.1 mm/Hg = ok and temperature compensated O2 was 90 mm/Hg and O2 saturation was 97.7%

So that showed I do not have an acid-base disorder such as acidosis or alkolosis.

Here is a discussion of the microbiome causing an acidosis disorder due to Lactate being produced by the bacteria due to a dysbiosis condition. The Lactate becomes lactic Acid and the kidneys are forced to use their bicarbonate stores to bring the PH up into the 7.35-7.45 range if they can. Your chronically low bicarbonate could be a result of something like this or a metabolic acidosis or a respiratory acidosis condition.

It downright medical malpractice to blow this off to hyperventilation when there are a variety of serious conditions that could cause the chronically low bicarbonate ( total CO2).This is especially true when you have unexplained symptoms and clear Lyme Disease. The Anion Gap is something thtat has been taught in early medical school since PH balance and electrolytes are essential to physiology and staying alive.

You need to push for the "Arterial Blood Gas" test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936733/


An article on the mirobiome ( gut Flora) producing Lactate or Lactic Acid which pushes your Anion gap high as your kidneys try and neutralize it with bicarbonate. That in turn would exhaust your bicarbonate reserves and might be the reason for the chronically low total CO2 ( bicarbonate). CO2 cannot easily be measured directly since its so fleeting. It changes with every breath and even if it was high at night, by morning or by the time you got to the lab, the CO2 would have normalized and some converted to bicarbonate by your kidneys.

See the discussion:
https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2014/06/Parrish-September-15.pdf


A pictoral version of how the Anion gap works.

An Arterial Blood Gas report directly from the lab analyzer.

 

[LHCTom]

The fact that hyperbaric oxygen therapy (HBOT) does not help ME/CFS very much seems to indicate that oxygen shortage is not the issue in ME/CFS.

Hyperbaric oxygen therapy (HBOT) uses high ambient pressures of up to 3 atmospheres to dissolve more oxygen into the water component of your blood. HBOT increases the amount of dissolved oxygen by a factor of around 20 times, meaning that with HBOT, up to 30% of the oxygen carried in your blood is oxygen dissolved in the water, and the other 70% is hemoglobin-bound oxygen carried by red blood cells. More info in this post.

Its not as simple as "The fact that hyperbaric oxygen therapy (HBOT) does not help ME/CFS very much seems to indicate that oxygen shortage is not the issue in ME/CFS." HBOT therapy only provides excessive O2 to your lungs but there are a variety of downstream factors that could interfere with the HBOT O2 from reaching your cells. Respiration involves both O2 saturation of red blood cells and the evacuation of CO2 which is your bodies largest waste product. HBOT could actually reduce the CO2 evacuation which could interfere with delivery of O2 to your cells. Your red blood cells hemoglobin must be able to accept the O2 provided by HBOT and if not, HBOT will not help. If your red blood cells accept adequate O2 and your Co2 evacuation is also adequate, your circulation at the capillary level could prevent cell <-> CO2/O2 exchange. Ther are a number of parasites that infect the red blood cells and interfere with delivery of O2 and CO2 exhaust even when HBOT offers excessive O2 at the level of the lungs.

Examples of parasitic diseases that can be bloodborne include African trypanosomiasis, babesiosis, Chagas disease, leishmaniasis, malaria, and toxoplasmosis. In nature, many bloodborne parasites are spread by insects (vectors), so they are also referred to as vector-borne diseases. Toxoplasma gondii is a food borne infection from undercooked meat.

A number of these can be aquired from transfusion in addition to their nornal vectors. Any one of them can block the usefulness of HBOT since they interfere with O2 and CO2 exchange even when HBOT delivers massive O2 at the lungs and body. The cells of your body require an O2/CO2 exchange at the cellular level from capillaries. Some conditions cause Rouleaux (singular is rouleau) which are stacks or aggregations of red blood cells (RBCs) which form because of the unique discoid shape of the cells in vertebrates. The flat surface of the discoid RBCs gives them a large surface area to make contact with and stick to each other; thus forming a rouleau. The Rouleaux looks like stacks of red blood cells somewhat like stacked coins. They stick together due to an innapropriate electric charge that can be a result of infections or other conditions. These stacks essentially congest your capillaries reducing blood flow and O2/CO2 exchange.

Rouleaux congestion in capillaries:

Various blood diorders that can effect O2/CO2gas exchange:

Babesia in Blood.... Similar to Malaria:

So I would not be so sure HBOT eliminates the possibility that your cells are being starved of O2 or are unable to eliminate CO2 adequately. The path of O2/CO2 exchange has many components that HBOT would not overcome.

When you sleep, your respiration becomes naturally depressed. That means while sleeping, the gas exchange between the lungs and blood is reduced. The O2 saturation is somewhat decreased. That would normally not be a problem given there is plenty of margin. But if an infection or other disorder that impacts gas exchange is presnet, sleeping ight be just enough to fall over a cliff and cause inadequate O2 to your cells.

 

[ryan31337]

I don't hyperventilate, and I am amused when ME/CFS experts throw that out there (I've had three solid experts offer that). Imo, it holds about as much merit as my OI is caused by stress.

Telling you that its caused by hyperventillation is beyond absurd, its stupid! Where has creativity gone - under a rock!

I don't think hyperventilation is the whole answer for the reasons you have both alluded to. However, if you have OI there is a good chance you are contributing to the problem by hyperventilating without realising it. It's clearly not hyperventilation as the lay-person would understand it (tachypnea), but a more subtle over-breathing. My POTS expert does ABGs for all patients and says he sees dysfunctional breathing in the majority of them, as a result of the condition, not the cause.

I didn't appreciate that I was doing it until I took a TTT and found myself feeling a lack of oxygen, then automatically drawing lungfuls of air to try and compensate. This goes on in normal life just at a less extreme rate.

If anyone ever tries to insinuate that the dysfunctional breathing is in someway your fault or the cause, show them this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016155/

Edit: key being reduced cerebral blood flow precedes hypocapnia

 

[Hip]

Your red blood cells hemoglobin must be able to accept the O2 provided by HBOT and if not, HBOT will not help.

HBOT dissolves oxygen into the blood, completely bypassing red blood cell hemoglobin, and therefore HBOT is also independent of the effects of CO2 in the blood. Increased CO2 levels make hemoglobin release the oxygen it carries more readily, and so increased CO2 levels in the blood improves tissue oxygenation. But none of this applies to oxygen actually dissolved into the water component of the blood, via HBOT.

If your red blood cells accept adequate O2 and your Co2 evacuation is also adequate, your circulation at the capillary level could prevent cell <-> CO2/O2 exchange. Ther are a number of parasites that infect the red blood cells and interfere with delivery of O2 and CO2 exhaust even when HBOT offers excessive O2 at the level of the lungs.

The idea that altered red blood cell shape might prevent red blood cells from traveling down the narrowest capillaries has been proposed before as a cause of ME/CFS, but I don't think the research got very far.

It has also been proposed that blood may be thickened in ME/CFS.

In any case, since HBOT dissolves oxygen into the blood, HBOT may address this situation (HBOT could deliver oxygen in capillaries too narrow for red blood cells to pass). The only way that HBOT would fail to deliver oxygen to narrow capillaries is if red blood cells or some other factor were somehow blocking the blood flow completely in the narrowest blood vessels.

Some conditions cause Rouleaux (singular is rouleau) which are stacks or aggregations of red blood cells (RBCs) which form because of the unique discoid shape of the cells in vertebrates. The flat surface of the discoid RBCs gives them a large surface area to make contact with and stick to each other; thus forming a rouleau. The Rouleaux looks like stacks of red blood cells somewhat like stacked coins. They stick together due to an innapropriate electric charge that can be a result of infections or other conditions. These stacks essentially congest your capillaries reducing blood flow and O2/CO2 exchange.

I recently had a very similar discussion with someone on this forum a few months ago: you might like to look at some of the posts made in the discussion:

This post looks at how increased blood viscosity may be impeding blood flow.

This post looks at erythrocyte aggregation / rouleaux, and includes a microscope picture of my own rouleaux formations.


There is low blood supply to the brainstem and parahippocampal gyrus in ME/CFS:

Brainstem perfusion is impaired in chronic fatigue syndrome
Chronic Fatigue Is Associated with Hypoperfusion of Parahippocampal Gyrus

 

[anciendaze]

Those who experience orthostatic intolerance have measurable problems with hemodynamics while upright. Different ways of measuring can produce different answers but the gold standard is likely to be the invasive CPET which found patients with low fill pressures and preserved ejection fraction whose exercise intolerance and dyspnea were otherwise unexplained.

The hypoxia resulting from this escapes a great deal of medical attention because it is localized and transient. The problem is worst at places and times where it is hard to measure. This is still enough to trigger red blood cells entering an hypoxic region to release not just oxygen, but also ATP, which serves as one signal for vasodilation downstream of the muscle where hypoxia takes place. (There are also pathological processes which release ATP from cells into the bloodstream.) In normal function the temporary hypoxic state at the muscle would then increase the pressure drop across the muscle, since the dilated vein would have lower pressure, which would produce increased flow of oxygenated blood, a process called "functional sympatholysis" in sports medicine.

I'm guessing the problem comes from consistent vasodilation on the path of venous return, all the way to the heart. Normal function has alternating vasoconstriction and dilation which helps to pump blood back to the heart using the check valves in veins. Low fill pressure means the atrium folds in, and the ventricle doesn't achieve full fill. Ejection fraction is not seriously affected because the problem takes place on diastole. This would match Paul Cheney's echocardiogram measurements which show "atrial cavitation" and limited diastolic dysfunction which (usually) stops just short of the point at which there is a sharp increase in mortality.

I'm still having trouble deciding what effect this will have on more convenient measurements. The natural effect of standard medical care for such patients leaves them well equipped to spend the rest of their lives lying down. Many doctors see no problem with this.

 

[anciendaze]

One more thought added to the above post, but posted separately so people won't think they've already read it. We tend to get into all kinds of complicated biochemical arguments about immune function, while overlooking a point so elementary I'm embarrassed to have to explain it.

The effectiveness of your immune system depends on the speed of response to biological insults. It takes time for immune cells throughout the body to be alerted to a problem, and more time for a response to reach the site with the problem. This response depends on the rate of blood flow through the region, and severe conditions like extreme Reynaud's syndrome can result in gangrene and loss of tissues. So can ischemia caused by strangulation of an inguinal hernia. What starts out as sterile cell death need not remain sterile long.

If patients have reduced cardiac output and reduced flow to muscles while upright and active, there will likely be immunological weakness. Immune cells can't do their work if they don't get there quickly or don't get the signals they need. In extreme cases of heart failure there is no question that immune function is poor, but standard evaluation of immune performance is done without any knowledge of output under conditions of exercise required by ordinary life.

Anyone who has dealt with ischemia imposed by trauma, as in "crush syndrome" will recognize that recovery takes much longer than the initial insult. This doesn't have to involve much mechanical force. It can take place in elderly patients who have fallen and can't get up for hours. It can also happen to patients with temporary paralysis who have suffered no impact from a fall.

 

[duncan]

@LHCTom: I frequently have high albumin levels, so there you go.

@ryan31337 : I am sure you are right and there are times hyperventilating is a contributing factor. I don't believe it is the right explanation for me, but that is immaterial. What I have concerns about is that clinicians may foist their diagnostic responsibilities onto a hyperventilating cause. I have had this happen with my occasional hypertension: Doctors, because the hypertension is intermittent, almost to a man declare the occasional elevated BP is due to the stress of going to the doctor's office, or some subconscious stress. I had to go through 4 days of hospital testing before my elevated BP rates were conclusively tied to dysautonomia. I suspect a similar process may be happening sometimes when doctors suggest hyperventilation is behind low CO2 levels

 

[LHCTom]

My history adds additional evidence in support of some kind of underlying normally immune controlled infection being activated. Shortly after my problems began, my blood tests showed elevated muscle enzymes (CK), high creatinine, low testosterone, sporadically high EOS, very positive IgG for Mycoplasma PN, very positive IgG for Toxoplasma Gondii, culture confirmed sinusitis MRSA, plus I was diagnosed with food allergies, frequent angio-edema/hives ( > 100 times over 10+ years) asthma, and chronic sinusitis with a mas in my Maxillary Sinus and of course sleep problems and horrible fatigue.

I had a sleep study at Stanford and was diagnosed with mild sleep apnea and put on a CPAP. It didn't help much but did reduce events as measured on the pulse oximeter I purchased and would download to a PC in the morning. I was then tested for Lyme given I live on 30 acres of tick infected oaks and grasslands. I'd been bitten many times before learning of the tick borne disease nightmare. I was positive by iGenex by their standards and once to the 5/10 CDC standard. I was also positive by iGenex IFA for Babesia Duncani. I didn't trust iGenex so I went to Fallon's Tick Borne research center at Columbia for a second opinion. The concluded I had Lyme since my C6 was positive and my stony brook lab WB was 4/10 IgG antibodies. Their MDL lab Babesia ELISA showed a positive IgM. So I was a believer and undertook a one year oral antibiotic treatment in around 2012. As a triple check I had the ALS Lyme culture 3 times over a year and was positive each time albeit controversial. ALS is involved in what appears to be a decent clinical trial to test their culture again.

https://clinicaltrials.gov/ct2/show/NCT02741609

After my one year antibiotic treatment, both my asthma and angio-edema and sinusitis were cured to this day. As far as I know, antibiotics can't cure "real" asthma unless its actually a bacterial infection like mycoplasma PN. I was treated for Babesia with Mepron and arithromycin for about 6 months. I was gain treated for H. pylori, Babesia and Lyme yet again after my C6 refused to decline. So all together I was treated about 2 years with ABx cocktails and Mepron/arithromycin.

My symptoms began to become more acute in the 2013/14 timeframe where I would awake with severe body pain mostly in my large muscles in my hips/shoulders/back and in my arms and legs to a lesser degree. It would definely begin while sleeping. My Kaiser doctor gave me Prednisone many times over a few years after receiving Prednisone and steroids for a back facet joint problem and the earlier sinusitis and generalized pain. The prednisone and my allergies and the high total IgE ( 900-110) and IL4 would have biased my immune system toward TH2 and an IgE cellular response at the expense of all else. So that would qualify as partially immune compromised. That in turn could give the toxoplasmosis, Babesia, Mycoplasma PN and the mycobacterium TB which I was exposed to in 2001. Any one of those could lead to a parasitic reduction in O2 carriage in the blood and O2/CO2 exchange. An integrative doctor I saw worried about the Prednisone impact on my immune system if my problem was an underlying infection. So he prescribed Bactrim after learning I had a feral kitten during the time this all began. Feral cats can carry Bartonella as can ticks. In Sonoma, almost half the feral cats are infected by Bartonella.

The Bactrim stopped the episodic sleeping pain attack after 3-4 days. Was it die to an infection, its supression of my gut microbiome or some other metabolic effect due to its folate synthesis inhibition. A mystery but it worked 4-5 times up trough 2015. In 2016, I left Kaiser sine they were useless with complex problems and seemed to test the same thing over and over again. In the meantime, I noticed and then graphed my creatinine and CK rise and fall multiple times over the years. I also notices the bot roughly tracked and both came down after antibiotic treatments. A coincidence??? Most doctors from local to Stanford simply dismissed it. My new non-Kaiser PCP switched my blood pressure medicine to a beat blocker and away from a calcium channel blocker and ACE inhibitor which both reduce any blood vessel constriction easing blood flow versus a beta blocker.

Them my sleeping trigger of confusion, very high blood pressure, sever burning pain in my hips and shoulders and lesser in my arms and legs plus a headache and need for air. It sure felt like I was hypoxic ( O2 starvation in my cells) and or hypercapnia ( excess CO2). But my pulseoximeter claimed my O2 saturation rarely droped below 90% and my CPAP made no difference yet it claimed it was doing well. So why would I feel hypoxic if my CPAP was providing adequate O2 and my O saturation was ok. My arterial blood gases were checked and I din't have respiratory acidosis or any form of acid base disorder. So what would prevent my cells from receiving the O2 in my red blood cells. Maybe blood flow/circulation problems compounded by my reduced respiration while asleep and lower saturation at 92-95%. But why. In this period I also was diagnosed by fingernail and toenail culture for 2 unusual pathogenic fungus's.

So as a hail Mary, I switched to my old blood pressure medication to improve circulation. I also began a baby aspirin and L-arginine also to ease blood flow. My severe awakening symptoms almost immediately stopped or were reduced to just feeling ill in the morning similar to my 10 years of history. But why? There must be some kind of underlying pathology causing either poor flow, poor O2/CO2 exchange with my cells or something along these lines. Certainly Babesia, Toxoplasma Gondii, Mycoplasma, Mycobacteria, or even Lyme, fungus or MRSA could be involved. Or maybe something else!

Any ideas appreciated. Its sure seems like the recent sleeping trigger with all the things eliminated combined with the blood pressure medication change impact with the various infections in the background creates some very focused evidence.

 

[gregh286]

I was diagnosed with Chronic Fatigue by multiple doctors including one at Stanford, OMI, multiple integrative clinics, Kaiser among others. But even though my symptoms match the criteria, other symptoms do not. I was one of the patients in Dr. Naviaux’s recent metabolomics CFS study and helped fund it. It can be found at http://www.pnas.org/content/113/37/E5472.full . My metabolic abnormalities fell inside the identified biomarker signature including the following abnormalities:

I had a total of 28 metabolic abnormalities defined by outside 2 SD above or below normal. A common theme seen in some of my symptoms and abnormalities is a gut microbiome dysbiosis and a leaky gut epithelium.

1) L-Carnitine was 2.1 SD below the mean and several acyl-carnitines were increased 1.7-2,5 above the mean suggesting decrease fatty acid oxidation in mitochondria is decreased.

2) Phosphatidyl Choline lipids were 2-2.3 SD below normal

3) Sphingomyelin lipids were decreased 2.2-2.8 SD below normal

4) Homoserine was 2.0 SD below the mean

5) Betaine was 3.0 SD below the mean

6) DHEA Sulfate was 2.5 SD below the mean

7) CoQ10H2 and CoQ9H2 were decreased 1.5 to 4.0 SD below the mean suggestive of CoQ10 deficiency

8) Imidazoleacetic Acid ( IZA) was 3.7 SD below the mean. Consitent with chronic histamine release and consitent with chronic basophil and mast cell histamine release and allergic activation – Consistent with my having at least a dozen testing confirmed IgE mediated food allergies

9) Lathosterol was 2.1 SD below the mean. Consistent with decrease in de novo cholesterol synthesis.

10) Elevated plasma sucrose, phenyllactate and a decrease in several bile acids ( glycocholic and taurocholic ) which is consistent with a relatively leaky gut epithelium. This is consistent with the extensive food allergies due to the leaky gut.

11) Homovanillic Acid was decreased 1.9 SD suggesting a mild dopamine deficiency.


One of the problems I see in all people with Chronic Fatigue Syndrome is the vague symptoms which overlap with a multitude of conditions. Fatigue is among the most common symptoms from nearly a hundred different conditions. This suggests there may be many underlying pathologies to CFS/ME yet most people receive one diagnosis which has no known cause and no reliable treatment. Different people and studies have seen improvements due to a variety of treatment but they typically do not apply widely. This is the frustration of CFS/ME.

I’ve pursued a diagnosis of an underlying pathology irrespective of how a CFS/ME diagnosis discourages many doctors from pursuing a deeper analysis. I have recently had my symptoms reach an acute stage that I believe has now presented me with a “lead” that is a solid as finding DNA at a crime scene. Most of the “leads” in the past have been analogous to an eye witness without their glasses in the dark. I’m curious if I’m alone as there have been “hints” that this now acute problem has been there from the beginning over 10 years ago. I'm telling this story in hopes it triggers ideas in other.

From the very beginning in the late 90's, I always knew that my fatigue and a raft of other symptoms all seem aggravated while asleep. I would awake feeling the worst and it would take until around noon before I felt well enough to function. Then this cycle would repeat the next night and on and on for more than a dozen years. I experienced bouts of pain, sweats, nausea, low grade night fevers ( 99-100.5), swelling, numbness, etc.. but the pattern kept evolving and changing. Only the sleep trigger, fatigue, felling ill and pain in the morning were truly constant. It all started with a bout of foot drop followed by numbness up my legs, the discovery I produced no testosterone, had high CK=250-700, high total IgE=400-1100, and wildly varying creatinine (1.1->1.4->1.2->1.6->1.3 2.1->1.6->1.4->1.12) seemingly going down after antibiotic treatment. Very suspicious.

I had a sleep study at Stanford which found mild sleep apnea. I used CPAP for 2 years followed by surgery at Stanford which seemed to stop all O2 desaturations. I then went on to be diagnosed with Lyme and Babesia as I live one 35 acres which are infected with ticks. I Helped fund a few studies by Dr. Bob Lane of UCB and we collected about 100 nymphal ticks on my property within 100 feet of my home and found both B burgdorferi and B. miyamotoi described here: http://wwwnc.cdc.gov/eid/article/22/12/15-2046_article . I have been bitten numerous times by ticks over 20 years and was CDC and IGenex positive on the WB plus C6 positive. A Babesia IFA was both IgG and IgM positive. I wasn’t sure what to believe so I went to Dr Fallon’s Tick Borne Research Center at Columbia for a second opinion.

They confirmed the positive C6 ELISA at Stony Brook Lab and I had 4/10 antibodies on the WB which fell short of the CDC 5/10. They said it was likely I had Lyme due to the positive C6 and 4/10 near CDC positive that was consistent with the IGenex testing. I also had a positive Babesia Microti IgM positive ELISA by Medical Diagnostics Laboratories while at Columbia. I returned and was treated with antibiotics orally for 1 year followed by Mepron plus arythromycin for Babesia for about 6 months. I felt better but not great. I remained C6 ELISA positive until early 2015 after being tested each year until it became negative.

I noticed that every time I was given extensive antibiotic treatment, my creatinine and CK would decline to either normal or near normal. When I told doctors, they would dismiss this even though I graphed every creatinine and CK test from 2003 through 2016 and their correlation and antibiotic driven decline was obvious. Still not one doctor took this pattern seriously until recently. When they saw my creatinine drop, they were happy my kidneys were ok but never asked why my creatinine wildly fluctuated between about 1.1 and 2.1 in mysterious near synch with my CK muscle enzymes. I then investigated whether a fungal infection could be involved.

During the 2013 to 2015 timeframe, I had episodes of body pain focused in my hips and shoulders but also back and legs/arms where I could barely walk and felt like I had run a marathon in my sleep and awoke in this state. I was given prednisone by Kaiser which helped but worried me it could suppress my immune system should an infection be the real cause. One doctor believed it could be Bartonella due to my feral kitten and tick bites and we discovered Bactrim would stop the pain episode cold after about 4 days.

I then asked for both a fingernail and toenail culture and arranged multiple mycotoxin ELISAs. Bactrim is a folate synthsisis inhibitor and does have fungal effectiveness. The mycotoxin ELISAs came back positive 3 times. My fingernail culture came back with a “Scedosporium apiospermum” infection

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223844/

and my toenails had a “Candida guilliermondii” infection. Its difficult to test for a disseminated fungal infection since once it reaches the blood, sepsis is not far away. Until a fungus breaks through the skin where it can be cultured, its hard to get at it if for example its in your muscles or kidneys.

So recently things have come to an acute “head” which puts the cause very closely related to my sleep as always suspected. But now when I fall asleep day or night, when I awake 30 minutes to 3 hours later, I feel confused, hypoxic in need of air, a severe headache, severe pain in my hips and shoulders and lesser pain throughout my large muscles. It was so bad I went to the ER where I was turned away since my most basic vitals were ok. So that points at respiration and or circulation. I utilized an overnight pulse oximeter which suggested my O2 saturation was rarely dropping below 90%. That would not explain such severe symptoms upon awakening. A sleep specialist suggested I use a snoring monitor APP on my phone which also indicated only mild snoring. I then tried CPAP and it too had NO effect. So that leaves excess CO2 due to failure to exhaust or circulation. My total CO2 or bicarbonate on metabolic panels was often near the top of the range and occasionally over. So was it an Acid/Base problem like respiratory Acidosis? My doctor arranged an Arterial Blood Gas test in the hospital and my PH was dead on normal and no blood gas abnormalities. CO2 is fleeting but it had no caused something like a Acid/Base disorder like Acidosis. The mystery deepens.

I saw a UCSF nephrologist since when I awoke, my BP was skyrocketing plus the unusual creatinine and CK behavior. My kidney was ok by ultrasound as was my kidney artery. He felt that since my creatinine comes down to normal regularly and my urine shows no protein and my ultrasounds were solid, it must be some underlying pathology such as an infection. He has referred me to a UCSF ID doctor and now my pattern and creatinine behavior is so specific, I believe we are closing in on the culprit. My personal suspicion at this point is I am experiencing a hypoxic condition while sleeping but its not due to respiration as much as the inability of my blood to accept “enough” O2 and flow through my capillaries while sleeping. This could also cause elevated CO2 since its removal from cells would also be affected by a combined oxygenation/blood flow problem. Now that I’m this focused, can I get a doctor to dig in properly.

To support this conjecture, I switched my blood pressure medication from metopronol ( a beta blocker ) back to my previous Lisinopril ( an ACE inhibitor) and Amlodipine ( a calcium channel blocker) plus a baby aspirin and L-arginine to ease blood flow and prevent my blood vessels from contracting thereby allowing O2 saturated red blood cells to flow. This has now reduced my night awakenings in a panic and in pain with HBP to almost nothing. But I still feel lousy in the morning so its not a full solution. But now I have the ability to manipulate the symptoms based on a hypothesis that was left after eliminating sleep apnea and an acid base disorder such as respiratory acidosis.

So why did I tell this story? I’m curious if any of this rings any bells with anyone else diagnosed with CFS? Failure to deliver adequate O2 to one's cells is a sure fire way to cause fatigue and a myriad of othre symptoms. I also wanted to show my example of where CFS does map to the metabolomics biomarker recently found in Dr Naviaux's study yet the underlying mechanism has to do with delivering inadequate O2 and or removing adequate CO2 from cells. No doubt failure to deliver adequate O2 to one cells and mitochondria would badly disrupt metabolism.

In my case, suspect this will be tracked to some kind of infection or autoimmune condition that is affecting my blood vessels and or capillaries and circulation - something like a vasculitis or similar condition. But my awake respiration and O2 delivery and CO2 removal are probably at an acceptable albeit marginal level. Only when I’m sleeping and my respiration depresses naturally and O2 saturation declines to the mid 90% range and when combined with some apnea events does my O2 delivery to cells fall over some cliff and become inadequate. I suspect I have had this going on chronically for a dozen years and something like the Prednisone treatment unleashed an infection or something similar happened that pushed it to an acute phase which may be understood by doctors. I hope.

Does this ring any bells or am I alone in this pattern?

Hi @LHCTom
Great piece and very comprehensive.
This story is very similar to mine, especially the later half, with the O2 delivery to cells etc. I have a long thread on the use of NO2 black (an AAKG) to relieve symptoms of CFS, very very useful in my case.
Also, I notice you can do directly with Glutamine, but takes around 6 hours to work. I imagine this is how long the body take to convert the glutamine to keto gluatmate and push it in the krebs cycle.

Personally, I dont think its an O2 delivery issue. Reason being i have used an O2 meter on my fingers many a night, have woken up, pinky finger pure numb, frozen almost and curled up, 02 still at 95%+, there is 02 in the blood, but cells not uptaking,
So, AKG one of my main weapons, combined with 1500mg X 2 of niacin a day. (another large vasodilator)
Certainly, consider it more of an uptake issue than circulation,
The recent comments from research about a possible PDH blockage (pyruvate dehydrogenase) would certainly make more sense, as this would stop the krebs cycle uptaking from glycosis, leaving krebs cycle totally stranded. It would also make sense to me personally, as I am feeding krebs cycle directly with AAKG and bypassing PDH Complex, so krebs can function better with direct AAKG.
Davies team have noticed the cells pooping out in CFS serum,,,,autoimmune indicative.
Whatever the root cause of CFS, it certainly knows how to disconnect the krebs cycle from uptaking from our blood, whether it nutrient or o2.

Hyperventilation, a very annoying symptom that I assume you guys are referring to air hunger? The need to take a deep and satisfying breath?
I think that just effect of lung cells not uptaking o2 fully, same problem, different body part.
Same with appetite loss, gut cells not uptaking.

 

[anciendaze]

Just want to comment that we have seen patients with tests reporting zero alphaketoglutarate (AKG).

I am not suggesting patients have low O2sat either, I've done the same test you mention. This is quite different from a transient localized hypoxia that appears near muscles during exercise. In healthy people this is normally the trigger for increased blood flow to relieve the problem via "functional sympatholysis". This appears to be broken in ME/CFS patients, and I have a very strong suspicion we are dealing with a problem of biochemical signalling, particularly after recent reports that our cells behave fine in healthy blood, and cells from healthy people behave poorly in our blood.

I'm less thrilled with glutamates because a high percentage of us show excess sympathetic activation, and some even show antibodies to GAD65. This looks like an adaptation in response to a pathology. There are definite limits to how far this can go without itself becoming pathological. Some of us are already close to that point. In my case I was having so much trouble with sleep I got an implanted vagus nerve stimulator to shift activity back toward the parasympathetic nervous system.

Sleep deprivation alone is capable of inducing psychotic symptoms in healthy people. Of course healthy people will usually recover when allowed to sleep. Misunderstand the shift toward sympathetic activation long enough and the patient definitely will become psychotic.