Causes of POTS/Postural Orthostatic Tachycardia Syndrome

Part of the process of being diagnosed with POTS is wondering what caused it and if you did something to cause it and questioning in general.

The list of things that can go wrong in the body and cause POTS is quite extensive. In addition, there are disorders with symptoms like POTS. The secondary disorders are usually treatable and will in turn, treat your POTS symptoms. I would ideally like to make a separate post for each thing. But it will be more efficient to just make links to information within this post.

Adrenal disorders like Addison's disease is one of those conditions that has POTS-like symptoms, meaning that it mimics POTS. If you have an auto-immune disease, you can have an autoimmune type of Addison's disease. And to complicate that further, autoimmune thyroid disease can put you at risk for the autoimmune form of Addison's disease. Other things associated with it are hypoparathyroidism, hypopituitarism, pernicious anemia, testicular failure in men, diabetes type I, and vitiligo.

One of the problems with adrenal glands can be caused by a form of tumor called a Pheochromocytoma. This causes the adrenal glands to be overactive. This can lead to high blood pressure and cause symptoms such as

• Headaches
• Sweating
• Pounding of the heart
• Being shaky
• Being extremely pale

The hormones produced by the adrenal glands belong to a category called Catecholamines, which are released into the bloodstream in response to physical or emotional stress. The ones specific to the adrenal glands are epinephrine and norepinephrine, also called respectively adrenal and noradrenaline. The other catecholamine is dopamine. But it isn't produced by the adrenal glands. Dopamine is produced in the brain. It is a neurohormone that is released by the hypothalamus. Its action is as a hormone that is an inhibitor or prolactin release from the anterior lobe of the pituitary

Pheocychromatoma and paragangliomas cause an overproduction of these hormones. Blood and urine tests to measure the amounts can help detect a pheochromocytoma.

The urine test is a 24-hour urine collection. The blood test for catecholamines is sometimes done when a person has unexplained hypertension or sudden paroxysmal hypertension.

Anemia

People with Anemia can have symptoms like POTS and if they also have a folic acid deficiency, it will make their anemia and POTS symptoms worse.

Anemia patients sometimes exhibit the symptoms of POTS. Some patients may have a folic acid deficiency, which is contributing to their anemia and POTS symptoms.

Angiotensin II

Some people with POTS have an increased level of Angiotensin II. The renin-angiotensin-aldosterone system (RAAS) helps regulate blood volume by regulating sodium and water retention. Renin and aldosterone can be reduced in POTS patients. But this study found that Angiotensin II was increased. http://www.ncbi.nlm.nih.gov/pubmed/16262605. Angiotensin II is a hormone and it causes blood vessels to constrict.

There may be a gene called the angiotensin II type one receptor gene involved in POTS.

Autoimmune Diseases

Besides anemia and Addison's disease and thyroid disorders, there are several other autoimmune diseases that can cause POTS. See: Lupus, Sjogren's, Guillain-Barre. Sarcoidosis, Crohn's Disease

Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy

Association of small fiber neuropathy with cardiac sympathetic dysfunction in sarcoidosis.

http://ihpotblogspot.blogspot.com/2016/09/slesystemic-lupus-erythematosis.html

http://ihpotblogspot.blogspot.com/2016/09/another-crossover-illness-with-pots.html

There is an antibody to neuronal nicotinic acetylcholine receptors of autonomic ganglia that has been discovered. Some POTS patients have higher levels of this antibody. Some patients that also had anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had even higher levels. And those that had the highest levels of the antibody, had more severe autonomic dysfunction. And levels of the antibody lower when patients symptoms get better. This indicates cause and effect. Meaning that the antibody can cause POTS and POTS can cause an increase in the level of the antibodies. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671239/

Cardiac Problems

Usually, doctors try to rule out cardiac disease before any diagnosis of POTS.

Problems with the electrical conduction of the heart such as atrioventricular conduction and ventricular repolarization can cause POTS in some patients. Sinus node abnormalities and abnormal P-waves can also cause it. Some patients undergo a procedure called ablation to treat these type of problems. But studies show that the long-term benefits were not good. And it really isn't recommended as a treatment.

In addition, if a patient has been misdiagnosed with sinus tachycardia, it will make their POTS worse to go through ablation. Heart rate-dependent electrocardiogram abnormalities in patients with postural tachycardia syndrome.

Spinal Problems

Cervical stenosis is when there is an area of the spinal canal that is too narrow, and it compresses the spinal cord and nerve roots. Some patients have had craniovertebral decompression which resulted in a decrease or cessation of their POTS symptoms. But other patients did not benefit from it.

Chiari malformation is when the cerebellar tonsils protrude down into the spinal cord. And it can cause the flow of cerebral spinal fluid to be restricted. Some patients have a procedure to correct the Chiari malformation. But not all of them get better afterward. Some doctors think that Chiari malformation causes all POTS, and some do not. Doctors from the NIH and The Chiari Institue say there is a connection between as well as a connection to EDS/Ehlers-Danlos syndrome. There are lots of links here on Chiari malformation and POTS: http://www.dinet.org/index.php/information-resources/pots-place/pots-useful-links

Syringomyelia is a medical condition caused by a cyst growing in the spinal cord. This sometimes causes POTS. Some people also have Chiari malformation. Many POTS patients also report a worsening of symptoms upon straining. One possible explanation of POTS in syringomyelia patients is partial sympathetic denervation of the legs.

Chemicals

Exposure to some chemicals might cause POTS in some patients. Here is a table of some of the possible chemicals: Chemicals and POTS

Alcohol-related peripheral neuropathy: nutritional, toxic, or both?

Associations between autonomic dysfunction and pain in chemotherapy-induced polyneuropathy.

Ehlers-Danlos Syndrome (EDS), a connective tissue disorder,is found in some POTS patients. Physicians propose that these syndromes occur together due to abnormal connective tissue in dependent blood vessels in those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures (Rowe, Barron, Calkins, Maumenee, Tong & Geraghty, 1999). Simply put, this connective tissue abnormality allows excessive amounts of blood to pool in these patients' lower limbs when they stand up.

There are a variety of types of Ehlers-Danlos syndrome. Classical and type III EDS were originally reported in orthostatic intolerance patients (Rowe et al., 1999). Many POTS patients with EDS have type III (Grubb, 2002).

There can be many symptoms and problems that are associated with the classical and hypermobile types of EDS. Mitral valve prolapse, gastric emptying or motility issues, dilation or rupture of the aorta, hiatal hernia, premature rupture of the membranes during pregnancy, poor wound healing, bruising, joint dislocation, etc.http://ihpotblogspot.blogspot.com/2016/09/joint-hypermobility-syndrome-and-eds.html

Joint Hypermobility Syndrome is a similar disorder. You can read more on them here:

Electrical injury

Electrical injury and being struck by lightning has reportedly occurred prior to the development of POTS in some cases. Lightning strike and autonomic failure -coincidence or causally related?

Liver Disease

A type of liver disease called compensated cirrhosis is when the liver is damaged but is able to compensate for it. This condition causes hypovolemia and vasodilation, POTS and pooling of blood in the lower extremities. Autonomic dysfunction in chronic liver disease

Mast-cell activation disorders

Some people with POTS or other orthostatic intolerance have flushing, palpitations, shortness of breath, chest pain, headache, lightheadedness, hypotension, or hypertension, and syncope

may play a role in the development of POTS in some individuals. Some patients with orthostatic intolerance suffer from episodes of flushing, palpitations, shortness of breath, chest discomfort, headache, lightheadedness, hypotension or hypertension and occasionally syncope, and it is sometimes brought on by an increase in activity. They may also have fatigue, sleepiness, increased urination, and sometimes diarrhea after they have an attack. There are tests for an increase in urinary methylhistamine, which is a marker of mast cell activation, that can be done to find MCAS.

You can read more about MCAS here: A Tale of Two Syndromes – POTS and MCAS

Neuropathy

Some people with neuropathy have POTS. It may be caused by autonomic neuropathy in the cardiovascular system. There may also be sympathetic denervation in the legs. The Neuropathic Postural Tachycardia Syndrome

Nitric Oxide deficit

Nitric Oxide (NO) controls blood vessel size with through changes in blood flow and blood vessels during inflammation and blood vessel leakiness. If you have a deficit of nitric oxide, you may develop POTS. Nitric oxide and regulation of heart rate in patients with postural tachycardia syndrome and healthy subjects

Researchers have found that NO levels can be increased by blocking the most important receptor for angiotensin-II. This may lead to treatments in the future in select groups of POTS patients.

Norepinephrine transporter deficiency

Norepinephrine transporter deficiency causes POTS is some people. These patients have an irregularity in how norepinephrine is used in the body. Under normal conditions, the body recycles norepinephrine. For some people, the protein that causes norepinephrine to be recycled doesn't work properly. And excess norepinephrine is spilled over. They then have depleted levels of norepinephrine if their neurons continue to be stimulated. They go from having excessive amounts of norepinephrine to having no norepinephrine, at which point they crash.Orthostatic Intolerance and Tachycardia Associated with Norepinephrine-Transporter Deficiency

Some patients have hypermethylation of the norepinephrine transporter (NET) gene promoter. When this happens, the gene for the protein that transports norepinephrine (NET) is turned off because its promoter is turned off. 

Nutcracker Phenomenon

This is a condition is which the left renal vein is congested because it is being compressed by the aorta and the superior mesenteric artery. It may cause a disruption in the renin-angiotensin system. And it also may disrupt the sympathetic adrenal system and overproduction of catecholamines.

Nutcracker phenomenon or nutcracker syndrome?

Thyroid disease

Thyroid disease can sometimes cause symptoms that are similar to those of POTS.

Tumors

When the body tries to get rid of a tumor by producing antibodies to attack it, sometimes they also attack part of the nervous system. This is called Paraneoplastic Syndrome. This is a rare condition. If the autonomic nervous system is attacked, then the result can be POTS or dysautonomia. Some people get better after the tumor is removed. Some people have to have intravenous immunoglobulin or other immune modulating treatments to try and reduce the harmful antibody levels.

Medscape: Paraneoplastic Autonomic Neuropathy

Screening for tumours in paraneoplastic syndromes: report of an EFNS Task Force

Physical Trauma, Surgery, and Pregnancy

Trauma such as surgery, pregnancy, bariatric surgery, and Traumatic Brain Injury, car accidents, etc. have been shown to precipitate POTS

Autonomic dysfunction presenting as postural tachycardia syndrome following traumatic brain injury.

Postural tachycardia syndrome - current experience and concepts

The Neurological Complications of Nutritional Deficiency following Bariatric Surgery

Viruses

It is estimated that 50% of patients with POTS have a recent history of some sort of virus when they become ill. It has been associated with Epstein-Barr virus. It is believed that viruses may affect the autonomic nervous system directly or that they may cause an autoimmune response that results in POTS.Postural Orthostatic Tachycardia Syndrome (POTS): A Diagnostic Dilemma

Vitamin Deficiencies

People with digestive problems, that are common in people with dysautonomia, frequently have B12 deficiency.

University of Chicago Peripheral Neuropathy Center - Vitamin B12 Deficiency

Don't forget to check out the videos at the bottom of the blog. You have to scroll down to the bottom. There is a good one on norepinephrine transporters and one on the sympathetic nervous system. 

Orthostatic HYPERtension As Opposed to HYPOtension

There is a difference between Orthostatic Hypertension and Orthostatic Hypotension. It seems to be more unusual and there isn't much information to be found. I did, however, find some since that seems to be more in line with my personal symptoms. Here are the links to the PDF at two different sites. 
http://www.medscape.com/viewarticle/543590 http://www.nature.com/nrneph/journal/v2/n8/full/ncpneph0228.htmlAt medscape, you have to create a username. But it is free and worth it because they have many medical articles that you can't find elsewhere.  



This is another one, AHA Journals: Orthostatic Hypertension Due to Vascular Adrenergic Hypersensitivity

Orthostatic Hypertension in Patients With Type 2 Diabetes

AHA Journals: Relationship Between Extreme Dippers and Orthostatic Hypertension in Elderly Hypertensive Patients

I am going to try and give a brief overview (well as brief as possible). 
This is a direct quote from the first article: "Orthostatic hypertension—a rise in blood pressure upon assuming upright posture—is an underappreciated and understudied clinical phenomenon. There is currently no widely agreed-upon definition of clinical orthostatic hypertension, the current definitions being operational within the context of particular studies. The underlying pathophysiology is thought to involve activation of the sympathetic nervous system, but the actual etiology is poorly understood. Orthostatic hypertension is observed in association with a variety of other clinical conditions, including essential hypertension, dysautonomias, and type 2 diabetes mellitus. Orthostatic hypertension has been associated with increased occurrence of silent cerebrovascular ischemia and possibly with neuropathy in type 2 diabetes. So, appreciation of the true incidence of orthostatic hypertension, elucidation of the underlying pathophysiology, and an understanding of potentially effective treatment approaches and their associated risks and benefits might all have major clinical significance. Orthostatic hypertension is an aspect of hypertension that is in need of further focused investigation."

Ordinarily, when you change from lying down or sitting up to a standing position, your blood pressure will drop slightly. This is because of  "a redistribution of blood volume into the lower abdomen, buttocks, and legs under the influence of gravity".

For most people, the change is very slight and systems in your body quickly engage and compensate for the change in positions. Usually, baroflex receptors cause some of your arteries like the ones in your neck to stretch so that you can get more blood flow to your brain. And your body senses a decrease in BP in your chest and abdomen and your sympathetic nervous system kicks in and increases activity and there is also a corresponding decrease in the parasympathetic nervous system. Basically, this means that hormones in your body regulate your blood pressure to compensate for your change in position from prone to sitting and from sitting to standing.

Because your blood plasma volume decreases, your systolic blood pressure increases and your diastolic blood pressure drops slightly, as well as having a slight rise in heart rate. There is also an increase in norepinephrine, epinephrine, active plasma renin, aldosterone, and vasopressin. Your sodium reabsorption increases and your potassium excretion are increased by your  kidneys. All of this is controlled by your sympathetic and parasympathetic nervous system, and in turn controlled by the baroflex response.

I have other posts here about orthostatic HYPOtension. That is when your BP drops 20/10 mmHg when you stand up. You also have of cerebral hypoperfusion, including dizziness or lightheadedness, visual changes, discomfort in the head and neck, fatigue, and frank syncope.


The first article above says that POTS frequently presents with no drop in blood pressure, or with a mild orthostatic HYPERtension.

Again, orthostatic HYPERtension is when your BP raises when you stand up. In order for there to be a diagnosis of Orthostatic HYPERtension, there needs to be an increase in systolic BP of 20 mmHg. How this plays out for me personally is very confusing. For instance, sometimes, my BP will raise by the required amount when I sit up from lying down, and then it will gradually drop as I am standing. Other times it has raised dramatically, even higher than the required amount. I do not have high hopes of getting a diagnosis, as I have been hospitalized recently for both low blood pressure and high blood pressure. I think at the very least I have some severe dysregulation.

 My late husband and father both had classic orthostatic HYPOtension and POTS. I would truly like to have a greater understanding of these conditions because I have children and grandchildren who could potentially develop them. Most people think that it any of these disorders are just a condition that you have to live with and they are just annoying. 

According to the article: " orthostatic hypertension might be a symptom of another treatable condition, such as pheochromocytoma or mast-cell activation disorder in the context of POTS.And "orthostatic hypertension resulting from any number of causes might be an important risk factor for silent cerebrovascular ischemia and infarct. 

Published studies from the Shimada laboratory indicate that, at least in populations of elderly Japanese people with essential hypertension, the incidence of silent cerebrovascular infarct detectable by MRI is higher in those patients who have clinically identifiable orthostatic hypertension."Some of these terms like pheochromocytoma are unfamiliar and confusing so I am going to link them to definitions when possible. I should have done that with my earlier posts. That one is basically a non-cancerous tumor on your adrenal gland.

These are the symptoms:

• High blood pressure
• Rapid or forceful heartbeat
• Profound sweating
• Severe headache
• Tremors
• Paleness in the face
• Shortness of breath
• Anxiety or sense of doom
• Abdominal pain
• Constipation
• Weight loss

For some people, the spells last 15-20 minutes and can happen several times a day. Some people's BP is normal between spells and for others it stays elevated.These are some of the triggers:

• Physical exertion
• Anxiety or stress
• Changes in body position
• Bowel movement
• Labor and delivery

Foods high in tyramine, a substance that affects blood pressure, also can trigger a spell. Tyramine is common in foods that are fermented, aged, pickled, cured, overripe or spoiled. 

These foods may include:

Some cheesesSome beers and wines

Dried or smoked meats

Avocados, bananas, and fava beans

Pickled fishSauerkraut or kimchi

Certain medications that can trigger asymptomatic spell include:

Decongestants

Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil), tranylcypromine (Parnate) and isocarboxazid (Marplan)

Stimulants, such as amphetamines or cocaine

It is unknown what causes these tumors. Your body uses the adrenaline/epinephrine and norepinephrine produced by your adrenal glands, in the fight or flight response. Basically, in a stress situation, your body uses adrenaline to raise your BP and norepinephrine to slow down things in your body temporarily, like if a bear attacks you, you don't need to be digesting supper at that moment, so that would slow down in order to shift resources to more important things like running away. A pheochromocytoma causes an excessive release of these hormones. Less common signs or symptoms may include:I found it interesting that the cells that can cause one of these tumors can be found in other areas of the body. When they do, they are called paragangliomas. They can be in your heart, head, neck, bladder, back wall of the abdomen and along the spine. I believe my husband may have had one on his spine. I know he had what they called a benign tumor of some sort there. But doctors didn't connect it to his condition, and I was ignorant. 

There are genetic conditions that predispose you to this condition.

These genetic conditions include the following:

• Multiple endocrine neoplasia, type II (MEN II) is a disorder resulting in tumors in more than one part of the body's hormone-producing (endocrine) system. The locations of other tumors associated with MEN II include the thyroid, parathyroid, lips, tongue and gastrointestinal tract.
• Von Hippel-Lindau disease can result in tumors at multiple sites, including the central nervous system, endocrine system, pancreas and kidneys.
• Neurofibromatosis 1 (NF1) results in multiple tumors in the skin (neurofibromas), pigmented skin spots and tumors of the optic nerve.
• Hereditary paraganglioma syndromes are inherited disorders that result in either pheochromocytomas or paragangliomas.

Interestingly, I have been told I have benign cysts on my liver, my kidneys, and on my thyroid. I also have had problems with my pancreas. My father had a tumor on his pituitary gland. So there may be something here for me. 

Sometimes this requires the removal of the adrenal gland affected and it can be cancerous. I don't know what they do if the tumors are somewhere else in the body.

Mast cell activation syndrome is complicated. Mast cells, if you are familiar at all with them, are associated with allergic responses. They release histamines that cause itching and hives. They also have a role in healing the body and the immune system. Somehow they can also be paired on autonomic nerve fibers. Hence the association with dysautonomia.  

They can release up to 200 different kinds of chemicals, and they produce, histamines, prostaglandins, and leukotrienes. For some people, there may be a malfunction in this system.

People with mast cell problems can have abdominal pain, cramping, diarrhea, flushing, itching, wheezing, coughing, lightheadedness, brain fog,  and memory problems. Those symptoms can all be caused by other conditions. But there are some people who have these symptoms along with POTS.

There are tests for it. One is for tryptase, which is a protein that is made by mast cells. Elevated levels occur as a result of severe allergic reaction OR if your body makes too many of them, which is called mastocytosis. If you have too many, they will sometimes to a bone marrow biopsy. Mastocytosis is caused by a genetic mutation, that causes a cell to grow and divide uncontrolled. The treatment for it is different than for MCAS
Most people with POTS don't have elevated tryptase or mastocytosis. 

But they can have elevated histamines, prostaglandins and leukotrienes, which can be found in a 24 hour urine test. If they are elevated, then a diagnosis of MCAS, mast cell activation syndrome is usually made. 

Here are the criteria:

       Symptoms consistent with chronic/recurrent mast cell release

• a. Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadedness (usually a combination of some of these symptoms is present)
• Laboratory evidence of mast cell mediator (N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others)
• Improvement in symptoms with the use of medications that block or treat elevations in these mediators

The article I got this information from on dysautonomia international's blog says that the labs need to be sent on ice or they might come back falsely normal. And that they should be done after a flare-up of symptoms is possible. They also say that they are not always 100% accurate and should be interpreted carefully. 

It says that if you have POTS or some other dysautonomia and also have some symptoms that seem allergic, you should ask your doctor about getting tested for MCAS. And it says that an allergist or immunologist is more likely to be familiar with MCAS.MCAS Mast Cell Activation Syndrome

Okay, back to the subject at hand, orthostatic HYPERtension.

Orthostatic hypertension

• Systolic blood pressure increases by at least 20 mmHg upon standing(note:other studies only require a 10 mmHg change)
• No change in diastolic blood pressure has been defined

That is different from Orthostatic HYPOtension, in which

• Systolic blood pressure decreases by at least 20 mmHg upon standing
• Diastolic blood pressure decreases by at least 10 mmHg upon standing

The older criteria for Orthostatic HYPERtension was a diastolic BP that was already 90mmHg and raised even higher when standing. While I am on beta blockers, mine tends to be just under that, at least part of the time. 

People with Orthostatic HYPERtension also have a decrease in cardiac output, more venous pooling in the lower extremities and higher plasma norepinephrine levels when they are standing. I have no idea how they measure that. I assume with blood tests for the norepinephrine and possibly measuring your legs for swelling or just observing changes in color. 

The theory is that the venous pooling in the lower body causes a decrease in cardiac output, which causes sympathetic nervous system response and an increase in diastolic BP. 

Around 11% of older people who already have high blood pressure or hypertension also have orthostatic HYPERtension. And they are more likely to have silent cerebrovascular infarct.

About the same amount of people have orthostatic HYPOtension and they are also at risk of a

silent cerebrovascular infarct. 

There are also people who are what they call an 'extreme dipper'. This means their systolic BP drops during the night. People who do this have a 72% likelihood of having orthostatic HYPERtension compared to the above 11%. They are also 53% more likely to have a silent cerebrovascular infarct. They are also more likely to have a regular stroke and don't recover as well. 

Both people with Orthostatic HYPERtension and HYPOtension are more likely to have lesions on the central nervous system that can be detected by MRI.

The medical article I read said that a recent study showed that people with POTS and MCAS, mast cell activation syndrome, 38% of them had Orthostatic HYPERtension. I feel it necessary here for clarity to define POTS.


Dysautonomia International says that it is "a heart rate increase of 30 beats per minute (bpm) or more, or over 120 bpm, within the first 10 minutes of standing, in the absence of orthostatic hypotension".

So we are discussing BP changes, but POTS is a heart rate change, that can sometimes be concurrent with the orthostatic changes, but is a separate diagnosis.

Some of the patients in the study had orthostatic HYPERtension that was persistent in an upright position or sometimes they had a hypertensive crisis. A hypertensive crisis is a BP that is 180/120 and can go as high as 240/140. They say that it hasn't been observed in patients with POTS bub without MCAS.


People with Baroflex Failure can also have orthostatic HYPERtension.

Baroreflex Failure is a rare disorder characterized by a change of blood pressure with episodes of severe hypertension (high blood pressure). There can be increased heart rate during stress and hypotension (low blood pressure) with normal or reduced heart rate during rest.

Symptoms may include:

• Headache
• Excessive sweating
• Extremely high or volatile blood pressure and heart rate with spikes in blood pressure in response to stress, with periods of normal or even low blood pressure during rest.
• Heart rate that does not respond to medications intended to improve it.

Causes of Baroreflex

Possible causes may include:

• Surgery and radiation for cancer of the throat
• Injury to the glossopharyngeal and vagus nerves (nerves involved in sensing blood pressure)
• Cell loss on both sides in the nuclei of the solitary tract (NTS, a column of cells located in the medulla) in the setting of a degenerative neurologic disease of the brain.
• For many patients, the cause is unknown.

I'm leaning towards this for my own problems because I have had both low blood pressure and high blood pressure and the rise in heart rate. Also, my urine test didn't indicate Pheochromocytoma.

The treatment for Baroreflex Failure is medication to control blood pressure and heart rate and to reduce stress. 

The purpose of Baroflexes is to buffer changes in arterial pressure so that excessive fluctuations of blood pressure are avoided. Baroreceptors are mechanoreptors in each carotid sinus brain stem and the aortic arch, and their function is to sense pressure changes caused by distention of the blood vessel walls send information about distention of the vessel wall by the glossopharyngeal nerves to the brain stem. There are baroceptors in the aortic arch and the large vessels of the thorax that transmit information through the vagal nerves to the same area of the brain stem. The blood volume in the thorax is sensed by low-pressure receptors that are linked to the vagal nerves and the brain stem. 

Problems in the baroceptors, the glossopharyngeal or the vagus nerves or the brain stem all could cause baroflex failure. Sometimes the terms baroflex failure and autonomic failure are used interchangeably. But usually, autonomic failure caused orthostatic HYPOtension and baroflex failure and the accompanying anatomical lesions usually cause volatile hypertension. 

Baroflex failure usually causes a loss of the buffering of blood pressure and  volatility of BP and heart rate. 

Baroflex failure can be  documented by the inability of infusions of pressor and depressor drugs to cause reflex bradycardia and tachycardia.25 mmHg or higher. If you have a heart rate drop of 25 mmHg it indicates baroflex control of heart rate.

They can put you in a supine position(laying down) and inject you with phenylephrine and increase the dose until your systolic BP raises 25 mmHg or higher. If you have a heart rate drop of 25 mmHg it indicates baroflex control of heart rate.

They have also injected people with nitroprusside until your systolic BP drops by 25mmHg and causes a change in HR. 

Apparently, there can be several causes of Baroflex failure. Some of the people in the study had previously had surgical damage of the glossopharyngeal nerve because of a neck injury. And some had radiation of the pharynx that caused problems and some other people had familial paraganglioma syndrome, which is a genetic problem that causes benign non-catecholamine producing tumors of the carotid body and glomus jugulare and glomus vagale. The tumors damage the glossopharyngeal and vagus nerves. One person also had cell loss in the nuclei of the solitary tracts of the brain stem that had been caused by a degenerative neurologic disorder. But some of the patients they coudn't find a cause for their baroflex failure. 

I certainly hope there is some other way to find out if you have it besides being injected with stuff.

After they did the injection part of the test, the patients were monitored. In contrast to the 24-hour urine test I had, during the study they measured catecholamines were measured every so often. And the BP was taken every 4 hours in supine and upright positions and anytime they had symptoms. 

They also did cold pressor tests. This is when they have you to put your right hand in a basin filled half with ice and half with water and keep it there for 1 minute. They measure your heart rate before and after. They did math tests by having people count backward from 200 by sevens. And they measured BP before and after this. And there is also a test called the isometric handgrip. 

They also gave patients propranolol and atropine in order to measure sympathetic and parasympathetic responses that control heart rate. They gave them Clonidine and monitored BP afterward to see how it affected reduced the sympathetic response. 

The patients BP would rise dramatically due to the cold pressor and math tests, which basically caused some mental stress.Some patients had increased nervousness or depression after they became ill. And it was worse with the patients with the worst BP elevation. When their BP was up, they had a sensation of flushing and were pale. They had palpitations and headache and sweating pheochromocytoma. But they had previously had this ruled out by urine and blood tests and radiographic tests and also by the improvement, or at least the absence of an increase, in hypertensive episodes during follow-up.

These patients had higher systolic BP than normal people. But they also had lower than normal BP at night, that "extreme dipper" thing. Their heart rates were also abnormal. Some of them had HR of 90 beats a minute, which could be from loss of parasympathetic control of the heart rate, caused by damage to the right vagal nerve. 

When they were measuring the norepinephrine during the tests, they were much higher than normal. And they raised in some patients  to more than 200 pg per milliliter (1.1 nmol per liter). Urinary excretion of epinephrine plus norepinephrine averaged 118 μg per 24 hours (697 nmol per 24 hours), more than twice normal (P = 0.015).

The cold pressor test caused a hypertensive paroxysm in some of the patients and lasted for a long time after they removed their hand from the cold water. That means their BP raised to a volatile level. 

They were able to show a greater drop in BP during bouts of hypertension with Clonidine, more so than when their BP was at normal levels. Their norepinephrine levels decreased substantially too. 

I would think that indicates that Clonidine is a pretty good treatment for it. 

Propanolol didn't do much when the BP and heart rate was low in patients. But when they had tachycardia it would decrease the HR by about 12 beats a minute. 

The study says that most of the patients could be treated with Clonidine and that many of them could eventually decrease the dosage after 2-4 years, and go onto diazepam 5mg three times a day.

It refers to an earlier study that concluded that baroflex failure could be differentiated from pheochromocytoma because pheochromocytoma doesn't respond to clonidine treatment. 

They concluded the paper by saying that baroflex failure symptoms range from patients that have an acute hypertensive crisis to patients that have what they called habitual volatility of blood pressure and with heart rate and high BP surges in response to stress. But they could be punctuated by periods of normal or even low BP during rest. And that it is important to differentiate baroflex failure from other causes in order to treat the orthostatic HYPERtension properly. 

I've done the best I can to condense this study. If you want to read it yourself here is a link to it. New England Journal of Medicine: The Diagnosis and Treatment of Baroreflex Failure

Here is some information about people who are "extreme dippers" This medical journal article says that  these extreme drops in BP at night are closely related to the abnormalities of autonomic nervous activity.

They defined orthostatic HYPERtension slightly differently than other places. They said it was a systolic BP rise of 10 mmHg when in the upright or standing position after 6-10 minutes. Whereas the above definitions required a 20 mmHg raise. 

It also says that orthostatic HYPERtension isn't well known and that it hasn't been well defined. Some places define it as a rise from 90mmHg to above 90 mmHg. And that the older patients had higher systolic BP and lower diastolic BP. 

I would assume this study would be a good one to point out to your doctor if you have a tilt table test and they say it was negative. American Heart Association: Relationship Between Extreme Dippers and Orthostatic Hypertension in Elderly Hypertensive Patients  (72%) of the 14 extreme dippers had orthostatic hypertension, and (27%) of the 11 extreme dippers had orthostatic hypotension. 

This study concluded that: Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension. American Diabetes Association: Orthostatic Hypertension in Patients With Type 2 Diabetes

"Although orthostatic hypotension is well recognized and commonly encountered, there are only a few reports of orthostatic hypertension. Most of the reported cases of orthostatic hypertension were related to excessive venous pooling, with an initial drop in cardiac output followed by overcompensation with an excessive release of catecholamines, or to nephroptosis, (also called floating kidney or renal ptosis is an abnormal condition in which the kidney drops down into the pelvis when the patient stands up.) with orthostatic activation of the renin-angiotensin system."

In this study, again from the American Heart Association, the patient had normal plasma and urinary catecholamines and renin release. Pharmacological tests of autonomic nervous system function showed an increased pressor sensitivity to norepinephrine (11 to 14 times normal), normal sensitivity to isoproterenol, diminished baroreceptor reflex sensitivity, and exquisite sensitivity to alpha blockers. This unusual case of orthostatic hypertension appears to be secondary to vascular adrenergic hypersensitivity. It also goes with the rise from 90 mmHg to above 90 mmHg on upright position. And refers to a man who had previously had orthostatic HYPOtension that was followed by HYPERtension. That is precisely what happened to me. 

"Autonomic evaluation demonstrated diminished baroreflex sensitivity and an exaggerated pressor response to the cold pressor test and Valsalva phase 2. Combined autonomic blockade with propranolol and atropine abolished the postural BP changes. These data suggested that the exaggerated pressor response was due to an increase in systemic vascular resistance in excess of the demands arising from a transient postural fall in cardiac output."

They used the Valsalva maneuver to indicate baroflex failure. It is the action of attempting to exhale with the nostrils and mouth, or the glottis, closed. This increases pressure in the middle ear and the chest, as when bracing to lift heavy objects, and is used as a means of equalizing pressure in the ears. When you do that your pulse is supposed to drop when you let your breath out. 

Just out of curiosity, I did this and my heart rate actually went up instead of down after I let my breath back out. I have one of those wristbands that measures your heart rate and steps and how many hours you are sleeping. It made my ears pop a lot. I repeated it and got the same response. (not a picture of me)

 "Orthostatic hypertension is also associated with morning blood pressure surge and extreme nocturnal blood pressure dipping, both of which increase the pulsatile haemodynamic stress of central arterial pressure and blood flow in patients with systemic haemodynamic atherothrombotic syndrome."Orthostatic hypertension—a new haemodynamic cardiovascular risk factor

There is still a lot of information here to absorb, even after I attempted to condense it. But I hope it is helpful to someone. I will be rereading it myself to try and get a grip on it. 

I appologize for some of the weird formatting of this post. I don't know if it is something wrong with blogger or is related to the photos I included or what. I attempted to fix it about six times.

Don't forget to watch the POTS videos at the bottom of the blog. You have to scroll down for them. 

Catecholamines

                                                                                         

Right now the thing on my mind is catecholamines. I just did a 24-hour urine study to check my catecholamine levels. So, I've been trying to understand them.

As part of our ability to survive as a species, the human body needs to be able to change internal things from one minute to the next, rather quickly and without our involvement, and regardless of what is happening in the environment outside the body, but also in response to it.

Changes in temperature, the humidity, and barometer or any danger we may find ourselves in, require the body to react quickly in order to maintain homeostasis (the body being in a stable state, normal operation). The hypothalamus does this through the Autonomic Nervous System and the endocrine glands.

The Autonomic Nervous System or ANS is one of the systems in our body that responds to changes in position. Around 25% to 30% of our blood volume is in the upper chest when we are laying down. But when we stand up between 300 and 800 mL of the blood moves to the lower body and extremities, helped along by gravity. This is a 25% to 30% drop in volume. Half of this happens during the first few minutes after we stand up.This causes a drop in the blood flow going back to the heart. That in turn, cause a drop in arterial pressure.

In order for you to remain standing and maintain adequate blood flow to the brain, several systems in your body have to be regulated.One of which is your blood pressure. Your blood pressure as to stabilize within about a minute after you stand up.

In Hyperadrenergic POTS, there is an abnormally large increase in plasma norepinephrine and a RISE of blood pressure instead of a drop when you stand up. The criteria for Hyperadrenergic POTS is an increase in systolic blood pressure >10 mmHg during 10 minutes of head-up tilt(HUT), as well as an increase of plasma norepinephrine, >600 pg/mL.

Patients usually have a rise in heart rate like other POTS patients, but also have symptoms like palpitations,anxiety, tachycardia and tremulousness. When a ganglionic blockade called trimethaphan is administered, they have a larger drop in BP than other patients, and their upright plasma norepinephrine levels are higher than non-hyperadrenergic POTS patients. When upright, individuals may experience a sense of anxiety, tremor, and cold sweaty hands and feet. Also, in a good portion of individuals, there is a significant urge to pass urine after even a short period of time upright (I wonder if this is why I have to run to the bathroom as soon as I stand up?). True migraine headaches are also common.

NMH or Orthostatic Tachycardia  is most likely to occur if you have a decrease in norepinephrine and an increase in epinephrine. POTS is the opposite, it is most likely to result from an increase in norepinephrine and a decrease in epinephrine.


An interesting article I read on Medscape.com said that people with Hyperadrenergic POTS have exaggerated pressor and sometimes tachycardia response to both orthostatic and other types of stress. It said it's important for them to minimize the reduction of blood flow back to the heart and pulse pressure. This can be helped by volume expansion, i.e. staying hydrated, and wearing an abdominal binder, which reduces vein capacity. Physical counter-maneuvers help too. Counter maneuvers are when you contract certain muscles in order to help blood flow back to the heart.

One really interesting thing the article said was that Inderal(propranolol0, which is a non-β-selective lipophilic agent, at about 10mg a day may work better than atenolol, which is a β-selective lipophilic agent. I happen to be on atenolol right now. Some people have such high BP jumps when they stand, (as much as 250/150 mmHg), that they have to be given phenobarbital. Sometimes they are helped
by clonidine or drugs in the same class.

I found the following on a Vanderbilt University website: "Some studies have labeled patients with “Hyperadrenergic POTS” if the patient’s upright plasma norepinephrine level is >600 pg/ml.  Other studies label patients with “Neuropathic POTS”if the QSART sweat test is abnormal.  Someone in the first study might say “I have hyperadrenergic POTS”, while the person in the second study might say “I have neuropathic POTS”.  The truth is that at least some (if not many) of those patients will have both abnormalities.  Often, these terms are not used to describe mutually exclusive subtypes, but to describe specific findings."

One related condition is pheochromocytoma (a norepinephrine producing tumor) and tests may be needed to differentiate between pheochromocytoma and hyperadrenergic POTS.

Another condition that is similar to Hyperadrenergic POTS is Norepinephrine Transporter (NET) Deficiency. It is thought to be an abnormality in a gene that leads to too much norepinephrine circulating in the body. It can be treated with a class of antidepressants called SNRIs, which will block these transporters. However, some people experience an increase in HR and can't take them.

Inappropriate sinus tachycardia or IST has similar symptoms to Hyperadrenergic POTS. IST patients have a high HR when they are laying down (around 90-100bpm), and slight exertion or emotional stress will cause rapid acceleration. Both conditions can overlap and may have the same underlying causes. Treatment options are similar.

I found an excellent explanation of what adrenergic receptors are at Dysautonomia International. "Think of adrenergic receptors like a TV antenna (if you are old enough to remember when TVs had antennas!). If the TV antenna picks up a signal, it transmits a message across the screen. In adrenergic receptors, the “signals” are chemicals present in the body called catecholamines (primarily epinephrine and norepinephrine). The “message” is what the catecholamine tells the receptor to do. For example, constrict a blood vessel or make the heart beat faster."

Some people have been found to have auto-antibodies called adrenergic receptor auto=antibodies. So instead of only fighting off a virus or something, their bodies have made auto-antibodies that have  attacked and damaged important sites on certain cell membrane proteins and altered their normal cell function. There are two kinds of adrenergic receptor auto-antibodies. One affects the blood pressure and causes it to drop and the other effects the HR and causes it to raise.