POTS Page 6
The research into deconditioning in POTS, however, is ultimately helpful, in that it shows the importance of cardiovascular reconditioning as an important addition to treatment. However, the problem - in terms of grasping the overall complexity of POTS - is that the deconditioning theory is sometimes presented as being ‘the’ root cause. In a 2011 study, Levine et al., wrote that POTS:
“…patients have often been described as having a “dysautonomia”. However investigations regarding the function of the autonomic nervous system in patients with POTS have not been extensive, with controversial results…We recently found that POTS patients, as a group, had normal autonomic function, while the marked tachycardia during orthostasis appeared to be a physiological compensatory response to a small stroke volume which was attributable to a small heart coupled with reduced blood volume…These results suggest that POTS per se is a consequence of “deconditioning”.”[28]
I note that this claim was made before the dysfunction of the NET protein was established as being a certainty in the POTS patient through other research, and it might well be the case that Levine at al., would no longer be of this view. Indeed, the autonomic nervous system tests they ran did not appear to include either tests for hyperadrenergism or NET deficiency. In any event, I hope that one day deconditioning in POTS will be seen for what it is: one factor of many in understanding the ‘whole elephant’ of POTS and what is required to treat the after-effects of the condition but not something which is the reason for the ‘elephant’ itself.
iii) Renin-Angiotensin-Aldosterone Problems in POTS Patients (and resulting low blood volume / hypovolemia)
Another problem often identified in POTS patients is to be found in the Renin-Angiotensin-Aldosterone (RAA) axis. The actions of this axis are complex. Suffice to say that the correct functioning of this axis is important for maintaining adequate blood volume, the balance of various electrolytes in the blood, and a balanced endocrine system. It has been found that POTS patients often have low levels of renin and aldosterone in their blood stream. One of the functions of both of these substances is to hold onto the body’s salt supply. When both of these are at low levels, the body’s ability to hold onto salt (sodium) is accordingly impaired. It is known that the inability of the body to hold onto salt can lead to low blood volume, as salt raises blood volume. This is an essential point as it is well-known that low-blood volume (hypovolemia) contributes to POTS patients’ symptoms significantly. As Raj writes: ‘These data suggest that abnormalities in the renin-angiotensin-aldosterone axis might have a role in the pathophysiology of POTS by contributing to hypovolemia (low blood volume) and impaired sodium retention.’[29] It is because of low aldosterone levels in POTS patients that they are often given a drug called ‘Flurinef’ which is a synthetic form of aldosterone, so as to boost the levels of aldosterone and thereby increase blood volume. Similarly, POTS patients are usually advised to ‘salt load’ their diets to address their poor sodium retention mechanisms as a result of the low aldosterone and renin.
It might seem that problems with low renin and aldosterone levels are an example of the body ‘just not working properly’, and that the only way to aid the situation is through drugs which ramp up the levels of these substances. But a limbic system in crisis can, again, potentially explain what is really going on with the renin-angiotensin-aldosterone network. For aldosterone is, in fact, secreted from the adrenal gland.[30] Now, if that adrenal gland has been overworked to an unbearable level by being forced to release adrenalin continuously, would it not therefore be less able, logically speaking, to produce adequate amounts of aldosterone? Yes, of course. Push something past its breaking point and it can no longer function properly. Therefore, we immediately see a reason for the fact that there is less aldosterone in the POTS patient than in the healthy person, which thereby explains the resulting low blood volume through poor sodium retention on that count (for poor sodium retention is a direct result of low aldosterone levels). This aspect of hypovolemia in the POTS patient, therefore, might also result from a limbic system in crisis.
But the limbic system link does not stop there. For the entire renin-angiotensin-aldosterone axis also depends for its own functions completely on the state of the autonomic nervous system. As Pratt writes, the RAA axis ‘…interacts with the autonomic nervous system for blood pressure regulation, with angiotensin receptors localized to brain regions involved in modulation of both sympathetic and parasympathetic nervous system activity.’[31] In other words, this axis, like the HPA axis, will also go into overdrive when the sympathetic branch of the nervous system is overactive. Indeed, when angiotensin receptors in the brain become active during sympathetic activity, they: ‘…increase blood pressure, vasoconstriction’ and are ‘pro-inflammation, pro-oxidative, pro-thirst’, and have a role in ‘anxiety, stress, neuronal excitation’ and ‘stimulate aldosterone, norepinephrine…release’.[32] The same old story, in other words. Eventually, the chronic over-activity of the RAA axis will also lead to its malfunction, resulting in low renin and aldosterone levels on that count too. For it too takes its ‘cue’ for how to behave from the signal the limbic system emits.
In short, this malfunctioning of the RAA axis can also be explained by the fact it becomes ‘overworked’ as a result of taking its ‘cue’ of how to act from a limbic system in crisis. This, in turn, explains to a large extent the low blood volume (hypovolemia) present in many POTS patients, a factor which is not, therefore, due to deconditioning alone, although deconditioning will also explain hypovolemia to a considerable extent.
iv) Mast Cell Activation Subtype
A subset of POTS patients also present with MCAS or ‘Mast Cell Activation Syndrome’ (this is distinct from MCAD, ‘Mast Cell Activation Disorder’, which is a genetic disease). Mast cells are a type of white blood cell important in the allergic response. They are responsible for the release of histamine (you may be familiar with the idea that many who suffer with allergies take ‘anti-histamine’ tablets). When you are stung by a bee, for example, your body releases histamine at the site of the sting. As Raj notes, however, in some patients with POTS, mast cells are likely to be released frequently and for no particularly obvious reason. The symptoms usually involve ‘flushing’, as well as, as Raj writes ‘shortness of breath, headache, light-headedness, excessive diuresis, and gastrointestinal symptoms such as diarrhoea, nausea, and vomiting.’[33] Triggers include, as Raj goes on to say, ‘…long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse.’ The exact reasons for mast cell hyperactivity in POTS patients are currently unknown, although Raj does wonder ‘…if sympathetic activation, through release of norepineprhine…is the cause of mast cell activation’.
This is undoubtedly correct. For, if the limbic system is in crisis, we know that the body is in crisis, and that adrenalin is, put bluntly, everywhere. In this case, more and more things - previously considered benign by the brain - begin to be perceived as ‘dangerous’. It is entirely plausible that, in this way, the signal for mast cells to release histamine is also overactive and that the ‘triggers’ required for this activation become increasingly ‘trivial’. For example, certain foods may start to be detected by the brain and body as ‘dangerous’, leading to the release of histamine after a meal. The ‘crisis state’ in the brain can lead to the creation of all kinds of allergies one would not have otherwise. Indeed, as with the RAA considered above, the release of histamine is very much related to the sympathetic branch of the nervous system. Lipton describes histamine as ‘a local emergency alarm’[34]: histamine is all about protection in response to perceived attack. Now, if the body and brain are stuck in a constant state of ‘perceived attack’, why would not mast cell activity also go haywire? It stands to reason that it would.
v) ‘Neuropathic’ POTS Subtype
Although I argue that all supposed subtypes of POTS, in fact, overlap, it is currently thought that some patients primarily have ‘neuropathic POTS’. In practice, this me
ans that a fraction of POTS patients have ‘denervation of sympathetic nerves…(in)…the lower limbs’.[35] This means in turn that some patients with POTS have ‘…less norepinephrine release (less sympathetic activation) in their lower extremities’.[36]
I admit that I am unsure of the exact connection between limbic system dysfunction and this ‘subtype’, although, on a personal note, I think I remember what it feels like to have this problem (in terms of the ‘shooting pains’ I experienced in the feet, which are a common symptom of this kind of neuropathy). I wonder, however, if the answer to why this happens might be somewhat simpler than one might guess. We know that in those patients with ‘neuropathic POTS’, norepinephrine release is ‘…intact in blood drawn from arm veins but reduced from corresponding leg veins’.[37] In other words, the problem lies in the extremities. Now, could this not be a result of being unable to stand for a while or, at the least, spending most of one’s life supine or sitting down (as the more severe kinds of POTS necessitate)? In such cases, there has been far less circulation to the extremities, which often become cold (indeed, ‘Reynaud’s phenomenon’, which involves extremely cold feet and hands, is common in POTS patients). This in itself tells us that there is not much activity in general going on in the feet, let alone in their nerves: could this reduced blood flow not impact in some adverse way upon the sympathetic nerves in the extremities? In addition, when the brain is in a crisis state, it looks to preserve what is most vital to its survival, and those are the parts of the body closer to the heart. The feet are not vital under such circumstances, as far as the brain is concerned. Its energies are taken inwards to its most vital functions. This might also explain in some way the partial denervation of the feet. In short, my hunch is that this denervation comes about because, in the more severe cases of POTS, the feet are rarely used and, as such, their normal functions (including nerve function) break down to an extent, and also because the brain in crisis prioritises parts of the body which are more vital (and, in this case, the feet also ‘lose out’). If this is correct, then partial denervation in the extremities is not a ‘cause’ or ‘distinct type’ of POTS, but merely another consequence of the initial limbic system crisis state. However, these are just suggestions and the actual link between the neuropathic problems identified in POTS and limbic system malfunction remains to be established.
Two Unlikely Causes of POTS
In addition to the five possible ‘subsets’ of POTS just discussed, I should also add here two other possible ‘causes’ for POTS which are unlikely to be causal, even though they can co-exist with the condition.
vi) Antibodies
The idea that viral antibodies themselves might be a factor in the origins of POTS is unlikely although, as already explained, a virus may ‘trigger’ the condition. An antibody is a blood protein produced as part of a ‘counteracting response’ to a specific antigen. It is a protein which can bind with substances perceived as alien to the body, including viruses, and it can remain in the blood stream. If evidence of the presence of viral antibodies in POTS patients could be proved consistently, it could indicate a possible cause, illustrating the ‘after-effects’ of the virus. However, this has not been the case. A Mayo clinic trial found only a 7-14% prevalence of a viral antibody in POTS patients. Vanderbilt found none over several years of searching.[38] The idea that antibodies might cause POTS is therefore extremely unlikely. What is more likely is that some patients, for whatever reason, also develop viral antibodies following infection separately to malfunction of their limbic system. Why a small fraction of some patients have antibodies and others do not is unclear. It is equally possible, of course, that someone might have viral antibodies but not have a limbic system in crisis. Therefore, one should not read too much into the antibody theory, the evidence for which is immensely slight in any event.
vii) Ehlers-Danlos Syndrome (EDS) / Joint Hypermobility Syndrome (JHS)
EDS or JHS are sometimes suggested as a ‘cause’ for POTS in those patients who also have those conditions. EDS is a genetic condition which involves malfunction in the production of collagen - the connective tissue which runs throughout the body and which is responsible for placing limits on how much your skin can be stretched. The collagen malfunction problems in those with EDS mean that their skin in particular tends, accordingly, to be stretched very easily. Furthermore, those with EDS tend to be very “hyper-mobile”: their joints can easily dislocate and many parts of their body are overtly flexible. JHS involves the same hyper-flexibility, although usually to a lesser extent, and it is not thought to occur for genetic reasons.
Why should EDS or JHS contribute to the development of POTS? As I understand it, the theory goes something like this. EDS and JHS can cause POTS because the lack of adequate collagen leads in some way to ‘lax’ blood vessels and, by extension, compensative tachycardia. In other words, the general laxity of the skin in the person with EDS impacts, in turn, on the tautness of that person’s blood vessels causing a degree of dysfunction therein. This in turn forces the heart to beat faster to compensate. If this is correct, then POTS would seem to be incurable for those who have EDS/JHS and POTS.
However, I seriously doubt the credibility of this theory. For a start, if it were true, then everyone with EDS would also have POTS. In other words, if a lack of collagen somehow produced the malfunctioning blood vessels we see in POTS, then for those with EDS this should be true across the board. Rather, only a small fraction of those with EDS also have POTS. Evidence from one study, by Jacob and Grubb, on the co-presence of POTS and EDS supports my view. They write:
“…The mean increase in heart rate after standing for at least 3 minutes was higher in (EDS) patients compared to controls (22 vs 15 bpm). Fifteen percent of hypermobile patients and none of the controls fulfilled the stringent criteria of postural tachycardia syndrome.”[39]
In this study, therefore, only 15% of the EDS group had POTS. That number is simply too small to suggest that EDS somehow causes POTS - the percentage would need to be much higher before one could suggest that with any confidence. Furthermore, the mean increase in heart rate from supine to standing in the EDS group was only 22 beats, which is only slightly higher than the normal increase (10-20 BPM) in the healthy person, and the fact that it is slightly higher can probably be explained by the 15% of EDS patients in the study who did, in fact, have POTS (i.e. their presence in the study slightly ‘skewed’ the results). Furthermore, if there is something specific about EDS which contributes to POTS then why is it that there are so many people with POTS who don’t have EDS? This last fact points to the root cause being something else entirely. Furthermore, if someone has EDS from birth and if EDS causes POTS, then that person should also have POTS from birth. But neither of these are true: only a tiny fraction of those with EDS have POTS and those who do have EDS from birth, do not also have POTS from birth - rather they develop POTS later. Indeed, I have not come across any case of POTS existing from birth.
It is my strong feeling that those who have both EDS and POTS have the latter for the same reason everyone else has it: due to a crisis in their brain after some kind of ‘traumatic’ event, broadly understood, including a ‘humdinger’ of a viral illness. If you are reading this and you have EDS as well as POTS, ask yourself whether there is more evidence for your POTS having been caused by a specific event which your brain might have perceived as ‘traumatic’ or whether you have had POTS for ‘as long as you can remember’, due to a genetic malfunction in collagen production. I suspect the former.
Other Limbic System Related Conditions Which Overlap with POTS
In going through the various parts of the “POTS elephant” above, my aim was to suggest how each one of them can, in theory, be traced back to a limbic system in crisis. However, in addition to there being ‘subsets’ of POTS, it is also commonly noted that there are limbic system conditions with which POTS often ‘overlaps’. I will now consider each of these in turn so as to illustrate how, in fact, these condi
tions too should probably not be thought of as ‘wholly separate’ conditions, but as stemming from the same root cause.
viii) Irritable Bowel Syndrome (IBS)
IBS need only be discussed briefly, as its causes, in light of limbic system malfunction, are obvious. They are the following: if the limbic system is in crisis, the autonomic nervous system is in crisis, and the sympathetic branch of the nervous system is favoured over the parasympathetic. It is the latter which is required for digestion. When the former is active, blood is drawn away from the internal organs, blood which is needed for efficient digestion and elimination. When this happens, all kinds of digestive problems emerge, as the body is simply not in a position to digest food effectively. Over time, coupled with increasing allergic responses (cf. the mast cell discussion above) the body becomes sensitive to various kinds of foods which previously would not have caused any problems. It is not uncommon for the POTS patient to have a highly restricted diet, and problems with nausea, vomiting, constipation and diarrhoea. All of these symptoms can be explained by the fact that the autonomic nervous system’s efforts are engaged in primarily non-parasympathetic activities, and that, therefore, the body’s ‘rest and digest’ function is compromised.
ix) Multiple Chemical Sensitivity (MCS) / Environmental Illness (EI)[40]
The limbic system is the part of the brain which, of course, processes smell. MCS, in its severest forms, is caused initially by an exposure to noxious chemicals. Following this initial poisoning, the limbic system ‘rewires’ itself (as part of a maladaptive neuroplastic response) to detect all chemicals as threatening. In addition, the sense of smell of the person with MCS becomes increasingly hypersensitive and they are able to detect smells that others cannot and at a level of intensity that others cannot. Exposure even to small levels of chemicals can lead to various physical reactions, including loss of voice, flu-like symptoms, migraines, nausea and, in extreme cases, anaphylaxis. We shall discuss MCS in more detail in the next chapter. For now, it is important to note that it is also possible to become sensitive to chemicals without having had an initial chemical poisoning. This is because the limbic system’s various parts all inter-relate. The initial trauma - such as a virus - may be the cause for the limbic system crisis but, over time, that crisis becomes more and more severe as stress builds upon stress. The result is that the cingulate cortex, which processes smell in the limbic system, may eventually become adversely affected. At this point, chemicals might seem more overpowering than before and might lead to adverse reactions. Indeed, those with POTS often report this increased sensitivity to smell (and also to sound and light), a further indication that there is a problem in the part of their brain which processes sensory experience, i.e. the limbic system.