About a year ago, I became debilitated for a few months due to a condition that is known as Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (Hyper POTS). The definition of POTS is an increase in heart rate of more than 30 beats per minute when standing up versus lying down - typically resulting from a lack of blood flow to the brain. The hyperadrenergic subtype indicates that the tachycardia corresponds to high levels of adrenaline (norepinephrine to be specific). There are many different underlying conditions that can cause POTS, but this post is going to focus on the one that has affected me.
I am nearly positive that the underlying cause of my POTS is from an ACE2 deficiency. For some background, the system that regulates blood volume is called the renin-angiotensin-aldosterone system (RAAS). When the kidneys detect low blood flow (for example, when you are dehydrated), the kidneys release renin into the bloodstream. Renin causes the release of a hormone called angiotensin I. Angiotensin I then gets converted to Angiotensin II through an enzyme called the Angiotensin Converting Enzyme (ACE). Angiotensin II then triggers a variety of activity in the body. It is a very potent vasoconstrictor that causes your blood pressure to rise. It also triggers the release of aldosterone from the adrenal glands, and the aldosterone is responsible for making you feel thirsty and it also causes the kidneys to retain sodium, thereby increasing blood volume. Most of the angiotensin II in your system gets catabolized to lesser forms of angiotensin (angiotensin 1-7) through another enzyme called the ACE2. The other interesting thing about this system is that when the kidneys detect a certain level of angiotensin II in the blood stream, it will stop producing any more renin even if the blood flow is low. It does this because if it didn't, your body could kill itself by overproducing angiotensin II thereby raising your blood pressure too high. Wikipedia's article on RAAS is very informative (https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system)
Julian Stewart has published some articles on a version of POTS that he calls "low flow pots" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511483). He found a defect in the ACE2 that results in elevated levels of angiotensin II. The high levels of angiotensin II cause havoc on your system. One affect is low blood volume (aka hypovolemia) since your kidneys aren't releasing enough renin due to the inhibitory feedback loop of the high angiotensin II levels. Low blood volume makes it so that you aren't getting enough blood flow to your brain when you are upright. Julian Stewart states that angiotensin II can exaccerbate the release of norepinephrine as well. Norepinephrine is typically released as part of the fight or flight system (sympathetic nervous system) in order to provide blood and oxygen to the parts of your body that are required for immediate survival by inhibiting to the areas that are less important. Since a sufficient supply of blood to the brain is critical, the brain activates the sympathetic nervous system for the same survival reasons. My experience is that a relatively low amount of anxiety when blood volume is low can trigger a vicious norepinephrine attack that when combined with the already high levels of angiotensin II can lead to dangerously high blood pressure - even while lying down. Basically, I think that my body was releasing way more norepinephrine than it normally would have for the amount of anxiety that I was experiencing. Another problem that high levels of angiotensin II can cause is oxidative stress which can also lead to fatigue, brain fog, vision problems, etc. There is also research to suggest that high levels of angiotensin II can cause low levels of testosterone in males (http://www.sciencedirect.com/science/article/pii/S0018506X12001377). Basically, the leydig cells in the testes have angiotensin II receptors
that when activated stops the production of testosterone.
The symptoms that I personally have experienced are a dizzy-like feeling that felt like I was on the verge of passing out when upright, constant brain fog, tachycardia when standing or when anxious, chest pressure, high blood pressure when standing or when anxious, skin that turned noticeably pale, cold / tingly feet hands and face, pressure in the back of my eyes, slightly blurry vision, low testosterone, high norepinephrine levels when standing vs lying down, severe fear and anxiety (presumably from the activation of the sympathetic nervous system), frequent urination, and occasional flushing of my ears when especially symptomatic. The symptoms were so intense that I was practically bed ridden for 10 weeks. Before I understood what was happening to me, I spent nearly every day feeling fear that I was about to die at any moment. I visited about 10 different doctors including a couple of trips to the ER, had an MRI, 2 echocardiograms, 2 cardio stress tests, wore a 2 week event monitor, had a renal ultrasound, and had tons of lab work done. I was even told multiple times that it was probably just anxiety, which I knew couldn't be true because I had never had a problem with anxiety previously. The key to unlocking the mystery though was that I got lucky and happened to visit a doctor who was experienced treating POTS. He ran a test where he drew my blood after lying down for 10 minutes, then again after standing for 10 mintues to check my catecholamines in both positions. My lying down norepinephrine was 225, but was 849 when standing. This large difference between the two positions indicated that I had the hyperadrenergic subtype of POTS.
There are a few things that I do to keep myself functional. The most important thing is to prevent my body from being in a dehydrated state. This helps prevent the release of renin and the subsequent conversion to angiotensin II. I take one or two 1 gram sodium chloride tablets a day and I drink 3-6 Propels a day in addition to a few glasses of water to keep my blood volume high enough to keep a sufficient supply of blood flowing to the brain. Those with the hyperadrenergic subtype like myself have to be extremely careful with the intake of sodium though because an increase of blood volume can lead to dangerously high blood pressure if a norepinephrine attack happens. Manually balancing blood volume and blood pressure is a delicate task. When my anxiety is higher, I will consume less sodium to keep my blood pressure in check. The most important medication that I take is Losartan. Losartan is an angiotensin II receptor blocker (ARB) which lessens its effects. Second, I take Clondidine because it suppresses the release of norepinephrine. I actually carry with me Clonidine everywhere I go just in case I get another norepinephrine attack where my blood pressure nears 180/120. Third, I take a low dosage of Zoloft (SSRI) to help keep my anxiety in check since like I mentioned above, anxiety with high levels of angiotensin II have the potential to trigger norepinephrine attacks that exceeds what my dosage of Clonidine suppresses. I actually tried an SNRI for a week or two before switching to an Zoloft, but that made things much worse for me since SNRIs increase norepinephrine. I also take a daily multivitamin primarily for the antioxidant effects from the vitamin C. Since the angiotensin II leads to oxidative stress, antioxidants like vitamin C are extremely important (http://www.prohealth.com/library/showarticle.cfm?libid=17890)
Unfortunately for those that suffer with this condition, the medical world struggles understanding and treating POTS. There just aren't many doctors that are familiar with it or have experience treating it. POTS is often misdiagnosed as anxiety because both can activate the sympathetic nervous system. POTS should really be thought of as more of a symptom of an underlying cause instead of a stand alone condition in the same way a cough is a symptom of a cold, influenza, asthma, etc. Another common point of confusion is that the underlying condition that is causing the symptoms of POTS has the possibility to lead to other symptoms even while supine. Sometimes doctors will discount a diagnosis of POTS because all symptoms are not isolated to standing up.
Please note that I am not a doctor so it is possible that some of this information is incorrect. Please take it with a grain of salt and do not view it as authoritative. My hope though is that this information may help someone that is struggling to find answers to this same condition.
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