The Connection Between Mitochondria and Autoimmune Disease in Periodic Paralysis

The Connection Between Mitochondria and Autoimmune Disease

I wrote about the connection between mitochondrial issues and autoimmune dysfunction in the new book, “The Periodic Paralysis Guide And Workbook: Be All You Can Be Naturally.” I did not go into the research and the information that led me to my findings. Although I had written about this for the members in our PPNI Support Group, I felt it was important to add that information to our blog for others to read about and understand.

I am now posting what I wrote last year.

November 3, 2013

Yesterday I spent a great deal of time researching the connections between Periodic Paralysis and lactic acidosis. I did this because of several reasons, but mostly due to the results of a set of tests done a few years ago, that no doctor seems to know what it means or what to do about it. 

           

I posted these a few weeks ago but I am posting it again in order to further explain what I discovered yesterday which may be a major break through for us all !

The following is the results of the Amino Acid Plasma Quantitative Test :

Aspartic Acid (<2, 0-6) and 3 Methylhistidine (<;6, 0-64) were low and Proline Plasma (501, 110-360), Alanine Plasma (744, 230-510), Valine (331, 150-310) Plasma, Tyrosine Plasma (107, 45-74), Homcysteine Plasma (11.9, 4.0-12.0), and Pyruvic Acid (0.146, 0.030-0.107) were all high. Lactic Acid was high also (1.8, .5-1.6)

"The high Alanine Plasma indicates: Primary or Secondary Lactic Acidosis or Hyperammonemic Syndrome. Clinical findings may be episodic. Further workup may be warranted."

"Hyperprolinemia is consistent with Mitochondrial Dysfunction or may indicate Type 1 or Type 2 Hyperprolinemia. Further analysis may be warranted."

"Recommend measurement of blood lactate and repeat of the Plasma Amino Acid Analysis."

These test results indicate "primary or secondary lactic acidosis" and Mitochondrial Dysfunction.

My real eye opener came when I read this:

"Metabolic dysregulation can also cause mitochondrial dysfunction. Vitamins, minerals, and other metabolites act as necessary co-factors..." So, wanting to understand how I could have Periodic Paralysis, over 10 autoimmune condition diagnoses AND Mitochondrial Dysfunction, I set out to find some answers. The discovery I made was unbelievable. Karen Carr has mentioned mitochondrial issues on this board for as long as I can remember. I have read through the complicated articles, etc. and I never quite understood the connection. I will try to put this in an easy to understand format, though it may be a little difficult to follow.

First of all...a biology lesson: There are many mitochondria in a cell. Mitochondria can became damaged for many reasons and then mutate or change. When this happens we can then have "Mitochondrial Dysfunction", leading to things such as lactic acidosis.

There are of course, Mitochondrial Disorders that can be present at birth also which I knew. I had no idea that we can "develop" them.

“…..for the synthesis and function of mitochondrial enzymes and other compounds that support mitochondrial function (see Table 4 ), and diets deficient in micronutrients can accelerate mitochondrial decay and contribute to neurodegeneration (Ames, 2004)"

However, since symptoms vary from case to case, age of onset, and rate of progression, mitochondrial dysfunction can be difficult to diagnose when it first appears. According to Cohen, who wrote a July 2001 article in the Cleveland Clinic Journal of Medicine, “The early phase can be mild and may not resemble any known mitochondrial disease. In addition, symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness”

http://www.nbihealth.com/publications/Mitochondrial_dysfunction.pdf

Periodic Paralysis is a 4th Class Metabolic Dysregulation (Disorder)!!!!!! Periodic Paralysis can cause Mitochondrial Dysfunction!!!!!!!!! Obviously the potassium shifting can cause the damage to the mitochondria in the cells!!!!!! We already know there seems to be an issue with autoimmune issues....Here is the connection!!!!

"…diets deficient in micronutrients can accelerate mitochondrial decay"

THIS IS WHY THE BALANCED DIET IS SO IMPORTANT TO US AND WE SEE DIFFERENCES WHEN WE CUT OUT THE JUNK AND ADD SUPPLEMENTS!!!!!!!

"…symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness”  (MUSCLE PAIN, SHORTNESS OF BREATH, FIBROMYALGIA, CONVERSION DISORDER??????)

"Mitochondrial dysfunction is at the core of a surprising range of very common illnesses and conditions...Even autoimmune diseases such as multiple sclerosis, Sjogrens syndrome, lupus and rheumatoid arthritis appear to have a mitochondrial basis to illness.

Mitochondrial dysfunction has been associated with a wide range of solid tumors, proposed to be central to the aging process, and found to be a common factor in the toxicity of a variety of physical and chemical agents."

http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934637

"EVEN AUTOIMMUNE DISEASES"!!!!!!!!!!!!!

"…toxicity of a variety of physical and chemical agents"    (The ISSUES WE HAVE WITH ALLERGIES AND PROBLEMS WITH MEDICATIONS????)

Table 1

Signs, symptoms, and diseases associated with mitochondrial dysfunction

(Cohen and Gold, 2001)

Organ system: Possible symptom or disease

Muscles: Hypotonia, weakness, cramping, muscle pain,

ptosis, opthalmoplegia

Brain: Developmental delay, mental retardation, autism, dementia, seizures, neuropsychiatric disturbances, atypical cerebral palsy, atypical migraines, stroke, and stroke-like events

Nerves: Neuropathic pain and weakness (which may be intermittent), acute and chronic inflammatory demyelinating polyneuropathy, absent deep tendon reflexes, neuropathic
gastrointestinal problems (gastroesophageal reflux, constipation, bowel pseudoobstruction), fainting, absent or excessive sweating, aberrant temperature regulation

Kidneys: Proximal renal tubular dysfunction (Fanconi syndrome); possible loss of protein (amino acids), magnesium, phosphorus, calcium, and other electrolytes

Heart: Cardiac conduction defects {(electrical system)} (heart blocks), cardiomyopathy

Liver: Hypoglycemia, gluconeogenic defects, nonalcoholic

liver failure

Eyes: Optic neuropathy and retinitis pigmentosa

Ears: Sensorineural hearing loss, aminoglycoside sensitivity

Pancreas: Diabetes and exocrine pancreatic failure

Systemic: Failure to gain weight, short stature, fatigue, and respiratory problems including intermittent air hunger

http://www.nbihealth.com/publications/Mitochondrial_dysfunction.pdf

"Exercise intolerance is a well recognized clinical feature of mitochondrial respiratory chain defects due to pathogenic mutations of mitochondrial or nuclear DNA. Severely impaired muscle oxidative phosphorylation results in disabling exercise limitations in which trivial exertion produces muscle fatigue and lactic acidosis. In such patients, low levels of exercise cause prominent tachycardia and dyspnoea (shortness of breath) due to increases in cardiac output and ventilation that exceed the capacity of skeletal muscle to utilize the increase in oxygen delivery mediated by these physiological responses"

".....results in disabling exercise limitations in which trivial exertion produces muscle fatigue and LACTIC ACIDOSIS."

EXERCISE INTOLERANCE and LACTIC ACIDOSIS!!!!! from the Mitochondrial Dysfunction!!!!!

"Oxygen utilization and Lactic Acidosis”

“Latic acidosis has often been used as an indicator of impaired oxidative metabolism and as a clinical marker for mitochondrial disorders…elevated lactate values at rest strengthen the possibility of a mitochondrial disorder."

http://ghr.nlm.nih.gov/mitochondrial-dna

LACTIC ACIDOSIS a cause of low oxygen levels.....

"In such patients, low levels of exercise cause prominent tachycardia and dyspnoea (shortness of breath) due to increases in cardiac output and ventilation that exceed the capacity of skeletal muscle to utilize the increase in oxygen delivery mediated by these physiological responses"...........

So...could this be abortive attacks or what we may be mistaking for PP episodes in normal ranges or it just happens and we wonder why...we cannot figure out a trigger????? We take potassium when we do not need to and it causes side effects, hyperkalemia???

"In conclusion, this study reveals a wide spectrum of oxidative limitations and exercise capacities........It illuminates the relationship between severity of muscle oxidative defects and symptoms of exercise intolerance in MM patients. Furthermore, it provides insight into the regulatory mechanisms responsible for characteristic physiological responses to exercise in these patients,"

http://ghr.nlm.nih.gov/mitochondrial-dna

"oxidative limitations" problems with oxygen...fluctuating oxygen levels....going down upon exertion....... 

Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). The severity of many mitochondrial disorders is thought to be associated with the percentage of mitochondria with a particular genetic change.

http://ghr.nlm.nih.gov/mitochondrial-dna

So there may be varying degrees and severity among us and I suspect that, of course, as we age the symptoms worsen such as the permanent muscle weakness, breathing issues, etc....Thus the importance of stopping the attacks with diet, avoiding triggers, etc as soon as possible when we are young...hopefully avoiding the damage to the mitochondria over a long period of time.....

MY THEORY: Periodic Paralysis, a mineral metabolic disorder, can cause damage to the mitochondria in the cells due to the atypical shifting of potassium. This damage to the DNA of the mitochondria, in turn contributes to the development of autoimmune disorders.

The longer a person with Periodic Paralysis goes with out a diagnosis and without proper treatment and continual atypical potassium shifting, the more chance there is for damage to the mitochondria, which then creates autoimmune diseases.

Periodic Paralysis is difficult to diagnose. Mitochondrial dysfunction is difficult to diagnose. Symptoms of both appear similar to "conversion disorders".  More time passes. Autoimmune diseases develop further clouding the picture of the basic disease...Periodic Paralysis. Damage is irreversible and becomes progressive causing permanent muscle weakness, oxygen issues, cardiac issues...etc.

November 5, 2013
Good Morning Everyone!

This is about Exercise Intolerance......

When I wrote about my discovery yesterday, I forgot to mention how our exercise intolerance may play into this. So, today I will discuss that connection with:

"MY THEORY: Periodic Paralysis, a mineral metabolic disorder, can cause damage to the mitochondria in the cells due to the atypical shifting of potassium. This damage to the DNA of the mitochondria, in turn contributes to the development of autoimmune disorders."

This is based on the fact that metabolic disorders and other issues can cause damage to the mitochondria in cells (probably due to the atypical shifting of potassium). The DNA of the mitochondria gets damaged. Damaged mitochondria then may begin to develop autoimmune disorders. This is all factual except what is in the parentheses...I am not sure of the process for the damage.

This is all related to how the complicated oxygen cycle works in our cells and bodies. That being said, this is the part forgot:

"Exercise intolerance is a well recognized clinical feature of mitochondrial respiratory chain defects due to pathogenic mutations of mitochondrial or nuclear DNA. Severely impaired muscle oxidative phosphorylation results in disabling exercise limitations in which trivial exertion produces muscle fatigue and lactic acidosis. In such patients, low levels of exercise cause prominent tachycardia and dyspnoea due to increases in cardiac output and ventilation that exceed the capacity of skeletal muscle to utilize the increase in oxygen delivery mediated by these physiological responses (Haller and Bertocci, 1994). "

This says that exercise intolerance is related to mutations of the mitochondria. The oxygen cycle does not work properly and then we are unable to do anything in which we must exert ourselves, even the smallest amount of exertion causes muscle weakness and lactic acidosis and then tachycardia and shortness of breath set in. This is because the heart must work harder to try to keep up with a lack of oxygen the muscles are receiving and (our body is not expelling the carbon dioxide as it should).

 
"......in patients .......peak oxygen uptake and mitochondrial capacity for oxidative phosphorylation decreased in proportion to increasing mutation load in muscle. "

"This study is the first to relate the severity of the skeletal muscle oxidative defect to the severity of mismatch between the exercise increase in cardiac output and oxygen uptake."

As we exert ourselves and need more oxygen, we do not get it. The more exertion, the less amount of oxygen.

"This study demonstrates for the first time that exaggerated ventilation relative to oxygen utilization ........ is related to the degree of oxidative impairment. Hyperventilation was more pronounced in patients with more severe oxidative defects, consistent with symptoms of exertional dyspnoea experienced by many patients. The mechanism underlying this hyperventilatory exercise response may relate to excess carbon dioxide production due to lactate buffering, as suggested by the finding of a correspondingly exaggerated respiratory exchange ratio..."

http://brain.oxfordjournals.org/content/126/2/413.long

The more we exert ourselves the more carbon dioxide builds up.

This may be the reason for our exercise intolerance.

This may be why also, when you go to the doctor and they take your blood oxygen level with the finger oximeter it is just fine, because you are sitting and have been for awhile, but you know you are having problems with your breathing, etc they do not think you need oxygen. They need to test you with an overnight or 24 hour recording oximeter. It should show oxygen level decreases during exercise and episodes of paralysis, etc....any exertion.

I am on oxygen 24/7 because my oxygen drops any time I exert myself, even talking on the telephone, going to the bathroom, etc at the same time, my heart rate increases and breathing gets difficult. This is happening even with my oxygen. I can only imagine how bad it would be without my oxygen.

Before I was on it, I could not even sit up to a meal at the table. It was too much exertion. Even now, sitting up straight for any length of time is too taxing...why I have a reclining feature on my power wheelchair.

I hope this information is helpful to you. It explains a lot of what we are all experiencing everyday and not fully understanding it or how it relates to Periodic Paralysis.

I do not know if anyone has put this together like this. I did it quite accidentally. It does seem to make sense. I forgot to mention that the lactic acidosis thing is also something that would be intermittent and may not show up on tests each time. It also needs to be tested using a very rare test: Amino Acid Plasma Quantitative Test it is only interpreted at a few places in the country. One is: Duke Children's Hospital and Health Center in North Carolina

A thought.....If our body is in stress from the lack of appropriate oxygen to the muscles and build up of lactic acidosis and carbon dioxide...would the STRESS be the CAUSE of the paralysis from exercise or exertion and why it happens after we begin to rest after our running around, walking, shopping, cooking dinner, doing dishes, etc?? As we begin to rest, the adrenaline will be released from the stress?? The adrenaline causes paralysis for most of us. 

Until later...