Chain reaction

Being a recent member of the LAF squad I have already accepted that in my lifetime there will be no 'silver bullet' to this disease and that I will have to hold it all together via the suppliment route and lifestlye changes until some form of ablation has to take place.

While I'm am waiting for that distant far-off meeting with the catheter equivant of the day and in the absence of any definite single lead from the medical establishment I will obviously take an interest in the condition and try to find that silver bullet. I have already discovered the secrets of Perpetual Motion - not yet proved on the testbed - so this could be easy.

To help me in my quest can anybody answer this question. Can the nervous system break down in just one area or does it deteriate as a full system. I ask because years ago I worked with a bloke who had a trapped??? nerve or something in his back and this made his right shoulder blade protrude out of his back alarmingly. I take it this was damage to the nervous system in a localised area as he was not affected in any other way.The good news for him was that in time, and this was not just a few weeks, the nerves would regenerate and he should return to normal. I never knew the final outcome as one of us moved on as people do.

Now if the nervous system goes down in its entirity then the rest that follows is not worth writing. If there can be weak sections in the system I am off to a flier , here goes.

If the body, and I'm sure it is, is a complex mass completely and totally locked and linked togther as a system then we could consider it as say a chain. I would note that any chemical analysis of supplements, minerals etc tend to use this 'chain' description of the neutrons plutons or whatever they are called.

So now we have this chain and as we all know every chain has a weakest link. A chain will also have a safe working load, max working load and a failure working load. The safe load and the max load are calculated by an authorised testing company. The failure working load is determined by the weakest link. It follows that the human body chain in good condition has a safe working load, a maximum working load and the point of no return load. These loads are given by nature and are definite. All these individual human chains have different safe,max and failure loads.

When a chain is put under load - this could be bricks, cement, steel etc etc. the load description is irrevalent - every single link is under pressure and if the load goes over the max the weakest link will fail. In the human chain the load can be effort, alcohol, reflux etc etc. it is irrevalent the weakest link will fail. In some human chains the weak link may be the migraine link or the gout link or arthritis link and in the most unfortunate the hearts electrical link. In the case of the hearts broken electrical link the link needs welding by a coded welder. The human chains safe working load will then require further investigation and downsized.

So thats Perpetual Motion and LAF sort out whats next.
Have a good weekend

Barry, when I read your post this morning, I asked my husband if he would reply to it. He has spent much of his professional life studying and teaching about the nervous system, and I thought he would enjoy this topic. Kagey

"I suspect Barry has engineering education. When engineers first encounter the human nervous system in any serious attempt to understand it they are always overwhelmed by its complexity. Most never go beyond those initial encounters, because they have other challenges already on their plate, but those who do go beyond somehow never manage to leave the field of study completely because it remains an engagingly intriguing puzzle for the duration of their lives; they quickly recognize it as a puzzle for which no straightforward answers exist for the whole, onlly in one tiny part at a time.

The short reply is that the NS is remarkably discrete. Each of the billions of neurons is a small computer, processing and integrating thousands of chemical and often some electrical inputs, and sending out in turn thousands of branched electrical signals. It is common for one neuron, or one group of neurons, or one functional set of neurons, to be disrupted with minimal disturbance to others. For instance, the results of brain damage, or of genetic or developmental problems in the young nervous system, often are highly specific deficits that do not affect any other parts of the whole conglomeration of neurons, or any other specific functions. Read any of Oliver Sacks' wonderful books for a very human introduction to just how amazing can be the manifestations of peculiarly functioning nervous systems.

But the real issue that is so hard to grapple with is that the nervous system is constantly remaking itself, taking in new information and processing it in different ways. And this is not just at the high levels of verbal skill that we often think of, but at every level. Neurons are highly malleable; the word neuroscientists often use is "plasticity." Depending upon the age at which damage occurs to one part of the system, other parts can adopt its function. When a child is born without visual ability, the parts of the brain that would normally engage with processing of visual information are quite literally taken over by other functions. The older a peson is when such damage occurs, the less likely functions are to shift, but shift they do. The neurologist always says that we won't know how much recovery might occur for at least six months, maybe a year, because the nerve cells are continually rearranging themselves, and we don't know how much capacity is still available to do so in this person.

From the neuroscience perspective the use of the term 'remodelling' in atrial fibrillation is interesting. The conduction of electrical signals within the human heart is done by a series of highly specialized muscle cells, not by nerve cells (nerve cells of the autonomic nervous sytem send signals TO the heart, but do not manage information flow within the heart). These highly specialized muscle cells, which generate and conduct action potentials much as neurons do, have lost their contractile machinery within, and in fact act like neurons in their generation and transmission of signals within the heart. Thus they are also capable of 'remodelling,' that is, of changing the pathways that signals follow, somehow easing - or blocking - the junctions or connection points. And no, we do not really know "how."

I hope that helps. I would encourage anyone who is interested to do some basic reading on any of the many web sites available about the human brain. One has to be prepared for constant ambiguity and lack of explanation, because so very, very little is truly understood. The really interesting phenomena, learning, verbalization, consciousness, are yet a long way from mastery."

Re: "The conduction of electrical signals within the human heart is done by a series of highly specialized muscle cells, not by nerve cells... . These highly specialized muscle cells, which generate and conduct action potentials much as neurons do, have lost their contractile machinery within, and in fact act like neurons in their generation and transmission of signals within the heart."

Perhaps atrial myoctes that have lost their contractile machinery become ectopic sites for the generation of atrial fibrillation.

Kagey,

I think you are fantastic. It through people like you and Peggy, Wil, terrible Bob K, George N, Gunther etc. etc and many others that I can't pick out at the moment and not forgetting Hans of course that I can have licence to mock this thing.

I refuse to call LAF a beast, it is something that is frightened to face me face to face and skulkes in the shadows.

If it ever does show its face I will surely knock it out for all of us. I am not frightened of LAF in any way,I have faced what I believed to be imminent death before and the only thing I remember of that episode is that I did not want the embarrasment of dieing in front of all the people in the canteen., another long story. I am angry at it, so it had better keep a low profile.

Given the advice of my unknown friends on this website I am well protected and will not bow to it no matter how many times it tries to knock me down.

LAF is on a loser.We will all beat this blight together.

I have had just a few beers tonight to show this thing who is the boss and as the old saying goes drunks and children tell the truth!!!!!!
Time for bed here in China

Barry - it's all about the gap junctions that allow the potentials or drivers to communicate between the cells. Successful ablation stops the signals from moving from cell-to-cell-to cell via gap junctions.


Connexin Diversity
Discriminating the Message
Mario Delmar
From the Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY.
Correspondence to Mario Delmar, MD, PhD, Department of Pharmacology, SUNY Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210.
[circres.ahajournals.org]


In cardiac electrophysiology, gap junctions are often conceptualized as passive resistors that allow for electrical charge to move between cells. From that standpoint, gap junctions seem like rigid structures that sit idle between cells as small ions traverse across.
Yet, although the importance of gap junctions in electrical synchronization is not questioned, it is generally accepted that these structures are more than electrical elements. Indeed, gap junctions are highly regulable molecular complexes present in the vast majority of cells in the body, including many cell types that are electrically nonexcitable.

In addition to allowing the passage of ions, gap junctions allow the passage of small molecules as well. Hence, gap junctions provide not only electrical coupling to excitable cells but also metabolic coupling to all cell types where they are present.1

Yet, although the nature of the message that carries electrical information is rather well understood (ions carrying charge), the nature of the molecule(s) providing metabolic coupling is mostly unknown. The answer to the obvious question remains elusive: what goes through gap junctions in living cells?


==

WHAT IS A GAP JUNCTION?
N.M. Kumar and N.Gilula, Cell 84:381-388(1996).

Gap junctions are specialized areas of the cell membranes that connects neighboring cells. They are organized collections of protein channels that allow ions and small molecules ( below 1000daltons molecular weight)to traverse between the connected cells in a passive fashion. These allow for the “communicating” cells to equilibrate all of their critical regulatory ions and small molecules (e.g., ca++, C-AMP, glutathione) , as well as macro-molecular substrates ( amino acids; sugars, nucleotides) .

[www.phd.msu.edu]

===

Physiol. Rev. 85: 1205-1253, 2005; doi:10.1152/physrev.00002.2005
0031-9333/05 $18.00

Molecular Physiology of Cardiac Repolarization
Jeanne M. Nerbonne and Robert S. Kass
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri; and Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York

The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next impulse is generated.

Myocardial action potentials reflect the sequential activation and inactivation of inward (Na+ and Ca2+) and outward (K+) current carrying ion channels. In different regions of the heart, action potential waveforms are distinct, owing to differences in Na+, Ca2+, and K+ channel expression, and these differences contribute to the normal, unidirectional propagation of activity and to the generation of normal cardiac rhythms.

Changes in channel functioning, resulting from inherited or acquired disease, affect action potential repolarization and can lead to the generation of life-threatening arrhythmias. There is, therefore, considerable interest in understanding the mechanisms that control cardiac repolarization and rhythm generation. Electrophysiological studies have detailed the properties of the Na+, Ca2+, and K+ currents that generate cardiac action potentials, and molecular cloning has revealed a large number of pore forming () and accessory (, , and ) subunits thought to contribute to the formation of these channels.

Considerable progress has been made in defining the functional roles of the various channels and in identifying the -subunits encoding these channels. Much less is known, however, about the functioning of channel accessory subunits and/or posttranslational processing of the channel proteins. It has also become clear that cardiac ion channels function as components of macromolecular complexes, comprising the -subunits, one or more accessory subunit, and a variety of other regulatory proteins. In addition, these macromolecular channel protein complexes appear to interact with the actin cytoskeleton and/or the extracellular matrix, suggesting important functional links between channel complexes, as well as between cardiac structure and electrical functioning. Important areas of future research will be the identification of (all of) the molecular components of functional cardiac ion channels and delineation of the molecular mechanisms involved in regulating the expression and the functioning of these channels in the normal and the diseased myocardium

===


There is much more online about the function of gap junctions.

Jackie

Interesting, in my last Chemesty blood test it shows my Anion Gap is low: 2.0, Normal 3.0 - 16.0 mmo1/L. I have no idea what that means and Doc said not to worry about it. Now I wonder ?? Anyone have an answer?

Ella

Ella, I googled anion gap and found some info.

1. The normal range for the anion gap is 8-16 mmol/L . I found this range in all four websites that I googled. It's not clear why the normal range on your blood test is different.

2. Anion gap is a measure of how acidic your blood is. In your case, your blood isn't acidic enough.

3. A low anion gap is relatively rare and can mean multiple myeloma ( a cancer of the bone marrow) or other possibilities such as low sodium and these possibilities varied from website to website. One thing all these websites had in common was the possibility of multiple myeloma. One of the websites said that, "Additional testing needs to be done to find out the reason for the anion gap level being too low."
___________________________________________________________
[www.medfriendly.com]
- "If the anion gap level is too low, this can mean that the person has hyponatremia (a decreased level of sodium in the blood). It can also mean that the person has multiple myeloma, which is cancer of the bone marrow. Bone marrow is a tissue that fills the center of long bones. Additional testing needs to be done to find out the reason for the anion gap level being too low."

[en.wikipedia.org]
-"A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma, or in the setting of a low albumin level."

[physioweb.med.uvm.edu]
[www.medterms.com]

Ella, I did some googling for low anion gap and I found the following:

1) one place says the chance of myeloma is small,
"97% of patients with a low anion gap do not have myeloma"
[www.pubmedcentral.nih.gov]

2) another place says the most common cause is low albumin,
"A low anion gap can also occur; this is most commonly seen when albumin (an anion as well as a protein) is low, while immunoglobulins (cations as well as proteins) are increased."
[www.labtestsonline.org]

3) and one place had a different reference range and suggests that 2 mmol/L is only borderline low,
"Normal Values: 5-14 mmol/L (Only values < 2 and > 17 mmol/L are likely to be clinically significant)."
[www.webhealthcentre.com]

Bob K
I thank you for doing all that research, I will print it out and take to my Doctor and see if she wants more tests done.
My other flag was for Bicarbonate being high: 32, normal shows: 20-30mmo1/L.
Maybe I should quit brushing my teeth with Baking Soda and I also use it as underarm deodorant as I am chemical sensitive.

Thanks again,

Ella

"I refuse to call LAF a beast, it is something that is frightened to face me face to face and skulks in the shadows."

Gee, that sounds like a BEAST of the worst sort, the ones who want to be sneaky and devious..... KG

Ella, It looks like your low anion gap can be explained by the high bicarbonate level so it looks like we don't have to worry about multiple myeloma.

According to the info at [www.lakesidepress.com], one way of calculating the anion gap is by taking the amount of sodium (Na+) in your blood and subtracting the amounts of chloride (Cl-) and bicarbonate (HCO3-). The typical value of bicarbonate is 24 and yours is 32. So if your bicarbonate had the typical value of 24 instead of 32 (i.e. 32-24=8 higher), your anion gap would be 2+8=10 instead of your value of 2. Thus, your low anion gap can be explained by the high bicarbonate level and multiple myeloma is not a concern.

Also, "...some clinical labs use a method that gives a lower normal range (e.g., 3-11 mEq/L; Winter 1990)." So this explains the low normal range for your lab's anion gap measurement.

Bob

Ella, Here's some details,

anion gap = sodium - chloride - bicarbonate

So if anion gap is 2, and bicarbonate is 32 we have,

2 = sodium - chloride - 32

Now if we change your high bicarbonate level of 32 to the typical value of 24, the anion gap goes up and we have,

10 = sodium - chloride - 24

In other words, the anion gap would be 10 if the bicarbonate level had the typical value of 24 instead of the high value of 32.

Ella, I continued to look into your anion gap and bicarbonate situation, since I started thinking about the possibility that the low anion gap and high bicarbonate level might still be related to multiple myeloma. I found the following,

"It has been suggested that a small anion gap noticed in some patients with myeloma is caused by the presence of positively charged, i.e. cationic, myeloma proteins3 causing the retention of chloride and bicarbonate.
[www.pubmedcentral.nih.gov]

One thing I have realized about this subject is that it has surprising twists and turns that are not easy to sort out for someone like me whose only knowledge about the subject is from googling. Perhaps asking your doctor about these issues is the best course.

Bob

P.S. Just in case the above wasn't clear about the bicarbonate, the article was saying that people with myeloma can have "retention of chloride and bicarbonate", in other words high chloride and bicarbonate levels. Ella, What was your chloride level?

If you look in the Klaubunde book there is a little passage about the change of non pacemaker cells to pacemaker cells creating ectopics.

Transformation of non-pacemaker into pacemaker cells
[cvphysiology.com]