POTS Page 3

  All of this essentially explains why the heart beats faster in the POTS patient upon standing up: the extra adrenalin is, from the point of view of the heart, an ‘external factor’ that forces it to beat faster against its wishes, whilst the widening of the blood vessels is, again from the point of view of the heart, an ‘internal factor’ by which the heart ‘senses’, whenever you stand up, the need to pump faster to keep the blood in full circulation around an expanded overall area. From this, it is clear that, despite what is sometimes thought, POTS is not primarily a cardiac condition. There is nothing intrinsically wrong with your heart that causes the problem (although in some cases, the extra strain on the heart might cause its own problems). Rather the heart is trying to do its best both to keep you conscious and to keep the blood flowing to where it should be. It is hampered, however, by the external factor of the extra presence of adrenalin and the internal factor of widened blood vessels, both of which stem from the NET proteins being unable to do their job.

  These two problem areas also explain several other symptoms felt in the POTS patient. The ‘adrenalin seepage’ explains why POTS patients feel considerable ‘somatic’ anxiety. By this I mean ‘sensations of anxiety in the body’ as opposed to ‘psychological anxiety’. Prof. Raj puts it this way: ‘…much of the (psychological) anxiety attributed to patients with POTS might be due to a misinterpretation of their physical symptoms.’[21] However, I add that the POTS patient may also have ‘associated anxiety’, i.e. understandable anxiety about having such a condition, in addition to feeling anxious because of the extra adrenalin floating around as a result of NET protein deficiency.

  The second feature which NET protein deficiency explains is why there is more adrenalin in the blood stream of the POTS patient upon standing than whilst in the supine position. This is because the NET protein is only really called upon to do its work when someone stands up. When you are supine, your blood vessels do not need to be constricted and, concurrently, the NET protein does not need to do its work. But once the POTS patient stands up, the fact that the NET protein cannot recycle the available adrenalin properly, leading it to spill over into the blood stream, explains why the problems are particularly manifest upon standing. In other words, the POTS patient feels shakier upon standing as the deficient protein in question’s primary work only occurs when someone stands up.

  The third feature which this two-fold dysfunction explains in a sizeable minority of POTS patients is fainting. For, in extreme cases, the NET protein becomes so deficient that it hardly works at all. The blood vessels in these cases become so wide that, upon standing, the heart simply cannot beat fast enough to maintain blood flow to the brain and as a result the patient faints.

  Why does the NET protein become deficient?

  There was, understandably, a high level of excitement amongst medical researchers upon discovering the role of NET deficiency in POTS: at last we have found the main reason why things have gone so wrong! The question which then emerged was: why does the NET protein no longer work properly? Following initial findings at Vanderbilt University, work began there in earnest to find a genetic reason for NET deficiency: perhaps POTS patients were ‘fated’ in their DNA code to have deficient NET proteins. The genetics of hundreds of patients with POTS were studied. Was it found that an aberrant gene could be blamed for POTS?

  In a word: no. With the exception of one family who carried an aberrant gene the other hundreds of patients considered gave no indication of any genetic change whatsoever. As the Vanderbilt website notes: ‘For several years, we looked for this (genetic) mutation in other POTS patients. We have not found any other non-related patients to have this same loss of function mutation.’[22] Whatever the cause of NET deficiency is, therefore, it is not something ‘fated’ to happen to an unlucky few. No other reason for the breakdown in NET deficiency has, as yet, been put forward. We can conclude this section therefore with the simple claim that there must be some reason for NET deficiency, and that that reason is not genetic but environmental. It cannot be the case that the NET protein would just break down ‘of its own accord’, but rather that it breaks down for some other reason entirely. We will consider what this reason might be in the next chapter.

  Conclusion: Two Very Different Theories

  The ‘deconditioning’ argument and the ‘NET protein deficiency’ argument are clearly two very different theories. Indeed, they could not be further apart from each other. For this reason, common sense dictates that, despite the fact that there is strong evidence to support both theories, only one of them can be correct as to the biological cause as rather different mechanisms are indicated in both. For reasons I shall expand upon in the next chapter, I believe the NET protein deficiency argument to be the theory which is along the right lines, whereas the deconditioning theory describes an important clinical feature of POTS patients but is not the cause of the condition.

  Key Points of Chapter One

  In this chapter, we have considered the salient features of POTS, along with why the term ‘POTS’ is, at best, only a temporary descriptor. The term currently only describes some of the condition’s symptoms, but it does not point to its cause, although this fact can sometimes be forgotten. We have also considered the fact that there is a ‘triggering event’ prior to the illness, whether a traumatic psychological or physical event or some kind of illness. With the exception of the deconditioning theory, no other theory has as yet been put forward as to why a triggering event might, in particular, be a catalyst for POTS.

  Finally, we have discussed the two principal theories for POTS, namely that it is a result of profound cardiovascular weakening following a period of bed rest and that it is the result of a faulty NET protein, which causes the blood vessels to stay partially open upon standing and for adrenalin to ‘seep out’ into the blood stream. We have also considered how only one of these theories can point to the biological cause, given the fact that they are so different from each other.

  Further Reading & Viewing:

  1. For an excellent overview of the condition and of pre-existing research on it, see:

  - Raj., S. The Postural Orthostatic Tachycardia Syndrome. Pathophysiology, Diagnosis & Management 2013 - http://circ.ahajournals.org/content/127/23/2336.full (referenced in this book as “Raj (2013)”)

  In addition, Prof. Raj presents another excellent overview of the condition in the following YouTube lecture: Connecting the Dots Between EDS and POTS, - www.YouTube.com/watch?v=srUJRRihvsE .

  The following talk by Prof. Carrie Burdzinski, Postural Orthostatic Tachycardia Syndrome (POTS), Dysautonomia, and the Autonomic Nervous System, is superb in its detail and organisation - www.youtube.com/watch?v=faScrmgKcWg

  For a comprehensive collection of articles on the autonomic nervous system, including several on POTS, see: Primer on the Autonomic Nervous System, Eds. Robertson, Biaggioni, Burnstock, Low and Paton, Academic Press, 2011 (referenced in this book as ANS Primer, chapter no. XX)

  2. For a summary of the Australian NET deficiency paper, see:

  - Lambert, E., et al., Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with postural tachycardia syndrome, Circulation, 2008, - www.ncbi.nlm.nih.gov/pubmed/19808400.

  3. For three papers on the Deconditioning Theory

  Levine et al., Cardiac Origins of the Postural Orthostatic Tachycardia Syndrome, 2010 - www.ncbi.nlm.nih.gov/pmc/articles/PMC2914315/.

  Levine et al., Effects of exercise training on arterial-cardiac baroreflex function in POTS, Springer-Verlag, 2011 - http://link.springer.com/article/10.1007%2Fs10286-010-0091-5 (the article can be purchased at this link)

  Levine, Shibata, Fu, Bivens, Wang, Hastings., Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome, Journal of Physiology, 2012 - www.ncbi.nlm.nih.gov/pmc/articles/PMC3547265/.

  Chapter Two: What is Really Going on in POTS & Why it Happens

  In chapte
r one, we considered two of the most important theories for the physiological problems within POTS. The first concerns the classic signs of deconditioning following a long period of bed rest: POTS patients often have smaller than average hearts and reduced blood volume as a result, both of which lead to the heart having to beat faster in order to compensate for this cardiovascular weakness. The second concerns NET protein deficiency, something which causes simultaneous ‘seeping’ of adrenalin into the blood stream as well as widening of the blood vessels upon standing when really they should constrict, with the ultimate effect of increased heart rate when orthostatic and a wide range of other symptoms. But which theory points us to the cause? The fundamental deconditioning or the aberrant protein?

  To find out the answer we need to look somewhere hitherto unconsidered: the brain. And, in particular, a part of the brain which is utterly essential to nearly every aspect of our lives, namely the ‘limbic system’, the primitive, yet crucial, mammalian part of our brain, whose job it is to keep us safe, to tell us to fight, freeze or flee, and which connects down into the rest of our body via the entire nervous system. The central claim of this book is that when this part of the brain becomes impaired, for reasons that shall become clear, then it can lead to what we call ‘POTS’. The brain is, in other words, ‘the missing link’ which can explain the central aspects of pre-existing research into POTS. I note the importance of understanding at this point that I am not - in any way - suggesting POTS is psychosomatic or ‘all in your head’, which are ludicrous ideas that a number of POTS patients, before they finally received a correct diagnosis, have had to put up with. Rather, I am discussing a very serious, physical impairment that can occur to the limbic system and the knock-on health effects this impairment can have on the body as a whole. POTS is a very real neurological condition.

  In order to state the case for this claim, in this chapter I shall consider, first of all, how the limbic system operates under normal circumstances so as to provide important background information. Then, I shall discuss how the limbic system can, under certain circumstances, enter a state of crisis with direct neurological consequences but also with knock-on consequences on the health of the body. With both of these aspects in place, I shall then consider how these negative changes to the limbic system and knock-on health effects can explain the key findings discussed in the last chapter, thereby showing that limbic system impairment is the ‘missing link’ in understanding the condition’s origins.

  The Limbic System Under Normal Circumstances

  Before I begin this section, I note here that I owe much of my understanding of the limbic system to Annie Hopper, who works in the field of limbic system dysfunction and rehabilitation, and who herself had a form of limbic system dysfunction called Multiple Chemical Sensitivity (a condition which we shall consider more closely later in the book). I also note that the limbic system is far more complicated than the briefest of sketches I am able to provide here. Rather, my aim in this section is just to focus on the most important functions of the limbic system so that you can best understand later in this chapter how its malfunctioning can lead to POTS.

  How can we best describe the limbic system in a general way? Hopper’s description of it as follows is a good place to start. The limbic system is:

  “…the part of the brain that is responsible for interpreting, categorizing, and sorting sensory input. It filters the billion bits of information that we experience at any given moment, and determines how we code, remember, and respond to them. It stores memories, regulates hormones, and is also involved in motor function. The limbic system is a large part of our primitive defense mechanism.”[23]

  Indeed, the word ‘limbic’ itself comes from the Latin ‘limbus’, which means ‘protection’. It is the part of the brain entirely responsible for keeping us safe and for ensuring - in many different ways - that we stay alive. It interprets what we experience and, based on this reading, sends a ‘myriad’ of signals to the rest of our body.

  Let us now consider the function of four crucial parts of the limbic system under normal circumstances: the amygdala, hippocampus, cingulate cortex and hypothalamus.

  The amygdala is classically understood as the ‘survival’ centre of the brain. It is able to send quick protective messages in response to immediate danger. If you have ever unthinkingly walked onto a road only to see a car fast approaching, you don’t have to think twice about getting out of the way: your amygdala has sent your body the message to get out of the way without any ‘conscious’ decision to do so on your part. (Although, sometimes, the amygdala will also send a message to ‘freeze’ on the spot - note the way animals can ‘freeze’ in the headlights of oncoming cars at night). The healthy amygdala only senses what danger is present when it actually is present. When danger is not present, the fear centres of the amygdala prefer to take a back seat, stay calm and thereby allow the body to be in a peaceful and restorative state.

  The hippocampus stores memories. For our purposes, it is important to note that it stores the messages sent out by the amygdala as specific memories, which can be recalled at a later date, when needed. To use a (hopefully) unlikely example, if you have been chased by a tiger and happen to see a real tiger again in the flesh - even if it is behind bars in the zoo - the hippocampus will almost certainly replay the images in your mind of your previous encounter with a tiger. These memories are not accompanied by neutral feelings. A sense of value, importance and meaning is also attached to each memory by the hippocampus. A negative memory of something which caused fear will be stored with ‘high importance’, and will carry extra weight in your brain. The hippocampus does this for your survival, and it is an essential function. Having said that, when danger is not present, the fear centres in the hippocampus should not be active.

  The cingulate cortex is concerned with many of the same aspects as the amygdala and hippocampus, including memory, emotional processing and learning. But it is also, interestingly, concerned with ascertaining how ‘safe’ stimuli are, both the stimuli from within our own body (e.g. ‘Am I too close to the fire?’ or ‘The pebble in my shoe is hurting my foot!’) and sensory stimuli in the external world. Accordingly, it is also the part of the brain particularly associated with processing smell, and in particular smells that are perceived to be dangerous (such as the smell of gas). For example, if you would be unlucky enough to be overexposed to chemicals, your cingulate cortex would fire up into overdrive, sending alarm signals to get away from the noxious smell.

  Onto the final - and most important part for understanding POTS as we shall see - part of the limbic system under discussion, the hypothalamus. For in the hypothalamus we come to see how what is going on in the limbic system really matters to the rest of the body. For the hypothalamus’ main job is to take the messages and signals it receives from the other aspects of the limbic system we have just discussed, and repackage them in turn into a collection of messages and signals which the body can understand. In this way, the hypothalamus is constantly sending out a ‘signal’ or ‘collection of messages’ directly to the rest of the body. It does this by sending the signal via the nervous system. As Hopper puts it:

  “It (the hypothalamus) is the control center of all autonomic regulatory activities of the body. It is like having an internal chemist as it produces powerful brain hormones which relay information and instructions to all parts of the brain and body. It is responsible for maintaining homeostasis in the body through the cardiovascular system, temperature regulation, and abdominal visceral regulation. It manages endocrine hormonal levels, sensory processing, body metabolism, eating and drinking behaviours.”[24]

  The signal that the hypothalamus emits is sent via the ‘HPA axis’, or the ‘Hypothalamus-Pituitary-Adrenal Gland Axis’ (this can also be understood as the signal the limbic system sends to the entire nervous system). If the signal is one of fear (‘flight or fight’), then the signal along the entire nervous system via the HPA axis will instruct the body to prepare
for danger. If the signal is one of calm, then the signal the body receives from the brain will be one of rest and restoration. These two kinds of signal (put here in a very general way) are also referred to as the ‘sympathetic branch of the nervous system’ (the flight or fight system) and the ‘parasympathetic branch of the nervous system’ (the rest and digest system). These branches do not act ‘of their own accord’. Rather, they act depending on the signal they receive from the limbic system via the HPA axis. Therefore, what is happening in the limbic system is a matter of utmost importance to the body as a whole.

  The way I have described the limbic system so far has been very ‘top-down’, but, crucially, it also works in another way, i.e. ‘bottom-up’. For the limbic system does not just emit signals to the nervous system but also receives signals, in turn, from the nervous system itself (notice how you can sense the signals from your own body right now in this moment). This is the ‘body-mind’ connection (as opposed to ‘mind-body’). In this way, what matters to the body also really matters to the brain. Things work two ways, therefore. This is an absolutely essential point and one which explains why, as we shall see shortly, traumatic illnesses (such as viruses) which affect the body can also affect the limbic system adversely.

  Limbic System Malfunction and Disorganisation

  So much for the limbic system as it should operate under normal circumstances: what about the possibility of limbic system malfunction?

  The limbic system is a vulnerable and sensitive part of the brain, and it is particularly sensitive to events. This is already well-known with the case of PTSD or Post-Traumatic Stress Disorder, where the limbic system becomes damaged as a result of a psychological trauma. PTSD is a very serious kind of limbic system dysfunction and it occurs primarily as a result of a traumatic external experience (although this could also involve internal elements, i.e. if the traumatic event also leads to physical injury such as might occur in a car accident).