Does anyone else have a problem with vommiting or their colon not working?

[Mya Symons]

Emootje, that is very helpful to see the nerves involved and pathways to various actions.

Question: What would be examples of some norepinephrine reuptake inhibitors?

What I was thinking of is Savella, which I take. I think that Cymbalta and Wellbutrin are two other seritonin and norepinephrine reuptake inhibitors. A lot of antidepressants are. I don't know if "inhibitors" is the correct term, however. I can't remember.

 

[Emootje]

If the NRI meds mentions side effects such as high blood pressure and increased heart rate I think you can assume that they increase plasma norepinephrine levels.

 

[xchocoholic]

Hi Mya,

Sure giving up a favorite food is a pain in the rear but food intolerances can cause a multitude of symptoms which will normally resolve themselves when that food is eliminated ... maybe not all of your symptoms will disappear initially but within time they might. Case in point, it took me a year after eliminating gluten to get over gluten ataxia ...

It may help you to go to this website and see this for yourself ...

http://www.glutenfreeandbeyond.org/forum/

this board is primarily for gluten intolerance but there are plenty of other possible food or chemical intolerances. I just like the format and the people here.

There are other boards specifically for other intolerances if you're interested.

Basically, my attitude is if you have a reaction to a food or chemical eliminate it ... testing is helpful but not always accurate. However, I tested positive for egg white allery and didn't realize I was allergic .. so both methods seem to help us pinpoint the culprits ...

hth .. x

 

[Sing]

If the NRI meds mentions side effects such as high blood pressure and increased heart rate I think you can assume that they increase plasma norepinephrine levels.

Emootje, I am confused because I would think that it is epinephrine which causes those too symptoms rather than its opposite, norepinephrine. Isn't norepinephrine the opposite? If we have too much norepinephrine on board, maybe this causes low blood pressure, lower heart rate, low gut motility and digestive activity--??

Or is it the other way around?

 

[taniaaust1]

I just read a nice article about the autonomic nervous system and the stomach/intestine. http://www.physiologymodels.info/ans/abdominal.htm

Summary:

Stomach
*Vagus nerve (parasympathetic) > acetylcholine > muscarinic 3 (M3) receptors > stimulation of stomach motility
*Vagus nerve (parasympathetic) > acetylcholine > muscarinic 1 (M1) receptors > stimulation of gastric juice
*Celiac ganglion (sympathetic) > (nor)epinephrine > alpha 1 receptors > decreases blood flow to the stomach and decreases the passage of food from the stomach into the small intestine
*Celiac ganglion (sympathetic) > (nor)epinephrine > alpha 2 receptors > reduces acetylcholine secretion
*Celiac ganglion (sympathetic) > (nor)epinephrine > beta 2 receptors > reduces gastric motility

Intestines
*Vagus nerve (parasympathetic) > acetylcholine > muscarinic 3 (M3) receptors > increasing motility
*Mesenteric ganglion (sympathetic) > (nor)epinephrine > alpha 1 receptors > decreases blood flow and constriction of anal sphincter
*Mesenteric ganglion (sympathetic) > (nor)epinephrine > alpha 2 receptors > reduces acetylcholine secretion
*Mesenteric ganglion (sympathetic) > (nor)epinephrine > beta 2 receptors > reduces motility

View attachment 6130

View attachment 6131

@Mya
As you maybe already know, most ME/CFS patients have increased levels of plasma norepinephrine (probably due to low blood volume) These increased levels of plasma norepinephrine lowers gastric motility and can provoke symptoms like nausea and vomiting. If your symptoms are getting worse in (nor)adrenaline situations (stress, exercise, heat, cold) I would definitely recommend you to read more about gastroparesis.
http://en.wikipedia.org/wiki/Gastroparesis
Treatment:
Erythromycin
Metoclopramide
Domperidone

Another thing that can explain your vomiting is bile reflux.
http://www.mayoclinic.com/health/bile-reflux/DS00651
Treatment:
Ursodeoxycholic acid
Proton pump inhibitors

Hope this information was helpful.

Thank you, that was very interesting to me as I do have out of normal range norepinephrine levels (very high..so high that the lab didnt believe the first three tests done and keep redoing them). So maybe if I could get my norepinephrine levels down it would help???? does anyone know? and what would be taken to get norepinephrine down?

 

[taniaaust1]

Tania and Mya,

I would be really troubled too if my nerves too weren't working for peristalsis. What are the nerves which govern this? Does the vagus nerve? I wonder what is happening with the signalling for you?

I so wish i could figure it all out. Im yet to talk to a doctor about it (previously saw a gastroenterologist a few years ago but I didnt have this problem back then and only had IBS not like paralysed bowel).. it could get to the point where I end up in hospital in severe pain due to it before I see someone about it.

 

[taniaaust1]

I forgot to add to this that often times after several days or weeks of backup from intestines not moving, I will develop extreme intestinal cramping and diarrhea. It is like suddenly everything starts up again on high speed.

When one gets too constipated one can then start getting diarhear cause of overflow .. maybe at this point, that is then triggering off a full release of the block you had due to the intense irritation etc.

Im fairly familiar with constipation with overflow as I have a disabled daughter who was born lack of muscles (she's also missing a part of her spine) and she had/has severe bowel issues and neuro issues (lacked sensation) due to her spinal issue and deformaties. There was many occassions when she had to have her feaces removed at the hospital (she got a blockage the size of a grapefruit when she was a babe). When she was severely blocked, she got overflow (this was often a sign that I needed to take her to hospital as block was too big at that point for me to be able to clear at home with enemas etc).

(Im just managing to clear my issues with strong enemas just before I get to that point). I probably could try to take on a similar bowel med program to what my daughter used to have but wouldnt want to do that without speaking to a specialist first (as some of what she was on can cause ones bowel to become lazy.. she was on 4 different things). umm im thinking.. one of the things other then fibre didnt need a script (the med other did)... (she was also on senna but that can weaken bowel with time) . She was also lactolose syrup to help (that like oils the bowel.. the correct dose to take was up to the oil was leaking), i dont think that causes bowel weakening and is safe for bowel (not sure thou if it can block vitamins/nutrients being like an oil which is coating everything).

 

[Emootje]

Emootje, I am confused because I would think that it is epinephrine which causes those too symptoms rather than its opposite, norepinephrine. Isn't norepinephrine the opposite? If we have too much norepinephrine on board, maybe this causes low blood pressure, lower heart rate, low gut motility and digestive activity--??

Or is it the other way around?

Hi Sing,

Both epinephrine and norepinephrine activate the alpha and the beta adrenergic receptors. Epinephrine has more affinity with the beta receptor and norepinephrine has more affinity with the alpha receptor.
Alpha 1 = vasoconstriction, reduces gastric motility
Alpha 2 = neurotransmitter inhibition, vasoconstriction
Beta 1 = increases heart muscle contraction and heart rate.
Beta 2 = vasodilation, reduces gastric motility

http://en.wikipedia.org/wiki/Adrenergic_receptor

I hope this clarifies things

 

[Mya Symons]

When one gets too constipated one can then start getting diarhear cause of overflow .. maybe at this point, that is then triggering off a full release of the block you had due to the intense irritation etc.

Im fairly familiar with constipation with overflow as I have a disabled daughter who was born lack of muscles (she's also missing a part of her spine) and she had/has severe bowel issues and neuro issues (lacked sensation) due to her spinal issue and deformaties. There was many occassions when she had to have her feaces removed at the hospital (she got a blockage the size of a grapefruit when she was a babe). When she was severely blocked, she got overflow (this was often a sign that I needed to take her to hospital as block was too big at that point for me to be able to clear at home with enemas etc).

(Im just managing to clear my issues with strong enemas just before I get to that point). I probably could try to take on a similar bowel med program to what my daughter used to have but wouldnt want to do that without speaking to a specialist first (as some of what she was on can cause ones bowel to become lazy.. she was on 4 different things).

Thank you for the information Tania. It explains a lot. This is starting to sound more and more serious. However, I hear you on the waiting until it gets so bad that you have to go to emergency. I am so tired of doctors not believing me that I won't go to the doctor unless I absolutely have to. My FMS doctor just told me that I would not have to see her for a year, but she would keep filling my meds. I was so excited. Actually, I disagreed with her about what causes CFS and FMS and I think she now thinks I am difficult. She also cut my Tramadol dose in half for no apparant reason. My husband sees the same doctor and she prescribes him twice the amount of Tramadol and he also get a prescription for Vicoden. He never acts up.

Anyway, when I didn't go to the doctor when I had my post op infection until I could not get up off the floor, I did pay for that one. I spent a month in the hospital getting different I.V. antibiotics. Maybe I should suck it up and go.:worried:

 

[taniaaust1]

Emootje, I am confused because I would think that it is epinephrine which causes those too symptoms rather than its opposite, norepinephrine. Isn't norepinephrine the opposite? If we have too much norepinephrine on board, maybe this causes low blood pressure, lower heart rate, low gut motility and digestive activity--??

Or is it the other way around?

Im very confused too as i thought norepinephrine was very stimulating on the nervous system.

 

[Emootje]

Thank you, that was very interesting to me as I do have out of normal range norepinephrine levels (very high..so high that the lab didnt believe the first three tests done and keep redoing them). So maybe if I could get my norepinephrine levels down it would help???? does anyone know? and what would be taken to get norepinephrine down?

The high norepinephrine levels are probably a compensation for a low cardiac output (due to low blood volume) and blocking the norepinephrine effect would make your cardiac output worse.
Hurwitz has found that in ME/CFS, 80% of women and 60% of men have low blood volume [1] which makes it plausible that the increased norepinephrine levels are due to low blood volume in most ME/CFS patients.

My blood results confirm this hypothesis.


Albumin infusion (plasma volume expander) increased my blood volume (and cardiac output) which lowers my plasma norepinephrine level proving that the high norepinephrine level is a secondary phenomenon due to low blood volume/cardiac output. After a couple of hours my extra blood volume disappeared in my urine due to an increase in atrial natriuretic peptide (ANP).
Conclusion: Low blood volume setpoint

I think that norepinephrine is making us very sick (nauseous, constipated, immunodeficient, anxious, agitated, pale) and the best way to lower norepinephrine is to increase your blood volume.

[1] http://aboutmecfs.org.violet.arvixe.com/Rsrch/OIsource.aspx

 

[richvank]

The high norepinephrine levels are probably a compensation for a low cardiac output (due to low blood volume) and blocking the norepinephrine effect would make your cardiac output worse.
Hurwitz has found that in ME/CFS, 80% of women and 60% of men have low blood volume [1] which makes it plausible that the increased norepinephrine levels are due to low blood volume in most ME/CFS patients.

My blood results confirm this hypothesis.
View attachment 6172

Albumin infusion (plasma volume expander) increased my blood volume (and cardiac output) which lowers my plasma norepinephrine level proving that the high norepinephrine level is a secondary phenomenon due to low blood volume/cardiac output. After a couple of hours my extra blood volume disappeared in my urine due to an increase in atrial natriuretic peptide (ANP).
Conclusion: Low blood volume setpoint

I think that norepinephrine is making us very sick (nauseous, constipated, immunodeficient, anxious, agitated, pale) and the best way to lower norepinephrine is to increase your blood volume.

[1] http://aboutmecfs.org.violet.arvixe.com/Rsrch/OIsource.aspx

Hi, emootje.

Very nice data! I think you are correct about the norep. responding to the low blood volume problem. The latter appears to be due to a low rate of production of antidiuretic hormone (vasopressin) in M.E. I think that results in turn from glutathione depletion in the hypothalamus. Antidiuretic hormone is a peptide hormone that contains two cysteine residues in its structure. The synthesis of proteins that contain cysteine depends on having sufficient glutathione and a proper ratio of reduced to oxidized glutathione in the cytosol of the cells where they are made, in order to keep cysteine in its reduced state until the amino acid chain is transported into the endoplasmic reticulum, where the cysteine residues are joined with their appropriate partners to form cystine double bonds, stabilizing the tertiary structure of the protein. When glutathione is depleted in these cells, the cysteine becomes oxidized too early. This results in low production of the protein, recycling of defective proteins to the proteosome, where they are disassembled, or secretion of misfolded proteins. I believe that this same mechanism accounts for problems with other peptide hormones in M.E., including oxytocin, ACTH. CRH, and growth hormone. It think it may also account for low production of perforin by the NK and CD8 T-cells. Perforin contains 20 cysteine residues.

Best regards,

Rich

 

[Emootje]

Thank you Rich!
Vasopressin (ADH) is definitely low in ME/CFS - I can agree on that - but it's a very mild deficiency and I think it's not the main factor. This mild diabetes insipidus is easy to correct by simply drinking a lot of water or by taking vasopressin. Diabetes insipidus is also associated with hypernatremia which I think is rare in ME/CFS. I also belief that a mild diabetes insipidus is not capable to significantly lower plasma volume. On the other hand, atrial natriuretic peptide (ANP) causes a reduction in blood volume without changing sodium levels. ANP secretion is stimulated by different inflammatory factors like, prostaglandin E2, prostaglandin F2 alfa, F2-isoprostanes, hypoxia and proinflammatory cytokine, all of these factors play a major role in ME/CFS. ANP is capable to significantly lower plasma volume in obstructive jaundice, sleep apnea, COPD and preeclampsia and I believe it is also capable to cause low blood volume in ME/CFS. It fits!
Emootje

Some interesting ANP references:
Mechanisms of atrial natriuretic peptide secretion from the atrium
http://cardiovascres.oxfordjournals.org/content/68/1/8.full.pdf+html
Increased plasma levels of atrial natriuretic peptide and endocrine markers of volume depletion in patients with obstructive jaundice
http://www.ncbi.nlm.nih.gov/pubmed/9462378
Regulation of plasma volume during obstructive sleep apnoa
http://www.ncbi.nlm.nih.gov/pubmed/10607185
Plasma Concentrations of Atrial, Brain, and C-type Natriuretic Peptides and Endothelin-1 in Patients With Chronic Respiratory Diseases*
http://chestjournal.chestpubs.org/content/110/2/462.full.pdf
Increased atrial and brain natriuretic peptides in adults with cyanotic congenital heart disease: enhanced understanding of the relationship between hypoxia and natriuretic peptide secretion
http://circ.ahajournals.org/cgi/reprint/109/23/2872
Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide
http://content.karger.com/produktedb/produkte.asp?DOI=29380&typ=pdf
Interaction of platelet-activating factor, spleen and atrial natriuretic peptide in plasma volume regulation during endotoxaemia in rats
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231185/pdf/tjp0512-0227.pdf
Low plasma volume in the pathophysiology of preeclampsia
http://arno.unimaas.nl/show.cgi?fid=9379

 

[richvank]

Thank you Rich!
Vasopressin (ADH) is definitely low in ME/CFS - I can agree on that - but it's a very mild deficiency and I think it's not the main factor. This mild diabetes insipidus is easy to correct by simply drinking a lot of water or by taking vasopressin. Diabetes insipidus is also associated with hypernatremia which I think is rare in ME/CFS. I also belief that a mild diabetes insipidus is not capable to significantly lower plasma volume. On the other hand, atrial natriuretic peptide (ANP) causes a reduction in blood volume without changing sodium levels. ANP secretion is stimulated by different inflammatory factors like, prostaglandin E2, prostaglandin F2 alfa, F2-isoprostanes, hypoxia and proinflammatory cytokine, all of these factors play a major role in ME/CFS. ANP is capable to significantly lower plasma volume in obstructive jaundice, sleep apnea, COPD and preeclampsia and I believe it is also capable to cause low blood volume in ME/CFS. It fits!
Emootje

Some interesting ANP references:
Mechanisms of atrial natriuretic peptide secretion from the atrium
http://cardiovascres.oxfordjournals.org/content/68/1/8.full.pdf+html
Increased plasma levels of atrial natriuretic peptide and endocrine markers of volume depletion in patients with obstructive jaundice
http://www.ncbi.nlm.nih.gov/pubmed/9462378
Regulation of plasma volume during obstructive sleep apnoa
http://www.ncbi.nlm.nih.gov/pubmed/10607185
Plasma Concentrations of Atrial, Brain, and C-type Natriuretic Peptides and Endothelin-1 in Patients With Chronic Respiratory Diseases*
http://chestjournal.chestpubs.org/content/110/2/462.full.pdf
Increased atrial and brain natriuretic peptides in adults with cyanotic congenital heart disease: enhanced understanding of the relationship between hypoxia and natriuretic peptide secretion
http://circ.ahajournals.org/cgi/reprint/109/23/2872
Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide
http://content.karger.com/produktedb/produkte.asp?DOI=29380&typ=pdf
Interaction of platelet-activating factor, spleen and atrial natriuretic peptide in plasma volume regulation during endotoxaemia in rats
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231185/pdf/tjp0512-0227.pdf
Low plasma volume in the pathophysiology of preeclampsia
http://arno.unimaas.nl/show.cgi?fid=9379

Hi, Emootje.

I didn't know anything about atrial natriuretic peptide, so I looked it up in my new physiology book (Guyton and Hall Textbook of Medical Physiology, twelfth edition, 2011). Here's what it says on page 376: "Changes in ANP levels probably help to minimize changes in blood volume during various disturbances, such as increased salt and water intake. However, excessive production of ANP or even complete lack of ANP does not cause major changes in blood volume because these effects can easily be overcome by small changes in blood pressure, acting through pressure natriuresis. For example, infusions of large amount of ANP initially raise urine output of salt and water and cause slight decreases in blood volume. In less than 24 hours, this effect is overcome by a slight decrease in blood pressure that returns urine output toward normal, despite continued excess of ANP."

By contrast, here's what they say about antidiuretic hormone, on the same page: "In patients who have lost their ability to secrete ADH because of destruction of the supraoptic nucei, the urine volume may become 5 to 10 times normal. This is almost always compensated for by ingestion of enough water to maintain fluid balance. If free access to water is prevented, the inability to secrete ADH may lead to marked reduction in blood volume and arterial pressure."

Best regards,

Rich

 

[Emootje]

Hi, Emootje.

I didn't know anything about atrial natriuretic peptide, so I looked it up in my new physiology book (Guyton and Hall Textbook of Medical Physiology, twelfth edition, 2011). Here's what it says on page 376: "Changes in ANP levels probably help to minimize changes in blood volume during various disturbances, such as increased salt and water intake. However, excessive production of ANP or even complete lack of ANP does not cause major changes in blood volume because these effects can easily be overcome by small changes in blood pressure, acting through pressure natriuresis. For example, infusions of large amount of ANP initially raise urine output of salt and water and cause slight decreases in blood volume. In less than 24 hours, this effect is overcome by a slight decrease in blood pressure that returns urine output toward normal, despite continued excess of ANP."

By contrast, here's what they say about antidiuretic hormone, on the same page: "In patients who have lost their ability to secrete ADH because of destruction of the supraoptic nucei, the urine volume may become 5 to 10 times normal. This is almost always compensated for by ingestion of enough water to maintain fluid balance. If free access to water is prevented, the inability to secrete ADH may lead to marked reduction in blood volume and arterial pressure."

Best regards,

Rich

Hi Rich,

I didn't know that the natriuresis caused by infusions of large amount of ANP is compensated by a decrease in pressure natriuresis. This makes me think critical about ANP as a cause of the hypovolemia and for that I thank you. However I think it could be explained.
In the previously mentioned diseases (obstructive jaundice, sleep apnoa, hypoxic COPD, preeclampsia) the hypovolemia is caused by vasoconstrictors (i.e. endothelins, F2-isoprostanes) in combination with ANP. I think that these vasoconstrictors abolish the decrease in pressure natriuresis caused by ANP resulting in hypovolemia in these diseases. I expect in ME/CFS a similar mechanism. (vasoconstrictor + ANP = hypovolemia) Dr. Bell also believes that low blood volume is caused by increased systemic vasoconstriction. The most likely candidate: isoprostanes Unfortunately he never mentioned ANP
http://vimeo.com/9261929 (9 min - 18 min)

Emootje

 

[Marco]

Chronic intestinal 'pseudo-obstruction' and 'neurogenic bladder' are both symptoms of mitochondrial disease.

http://maciej.bioinfo.pl/meid:263431

Not that I'm suggesting that you have a genetic mitochondrial disease per se but may reflect our underlying 'low energy state'.

That aside, I presume your gastro problems have been fully investigated?

 

[taniaaust1]

The high norepinephrine levels are probably a compensation for a low cardiac output (due to low blood volume) and blocking the norepinephrine effect would make your cardiac output worse.

Thanks for pointing that out to me.