Three Distinct Mechanisms in Postural Orthostatic Tachycardia Syndrome
In this post we will discuss the difference between Neurogenic POTS, Hypovolemic POTS, and Hyperadrenergic POTS.
What is POTS?
POTS stands for Postural Orthostatic Tachycardia Syndrome. This syndrome was first identified as such in 1982. The hallmark diagnostic feature of POTS is an abnormal increase in heart rate of 30 beats per minute or more within ten minutes of remaining in an upright position on a tilt table, and without orthostatic hypotension occurring (meaning there is not also a large decrease in blood pressure while upright). One of the key words in the name POTS is “syndrome”, meaning that the orthostatic tachycardia is repetitive and persistent. In the strictest of POTS diagnostic criteria, the postural orthostatic tachycardia must be present for six months. A POTS diagnosis also means other factors that may trigger orthostatic tachycardia have been ruled out.
Symptoms commonly experienced by people with POTS
· dizziness
· lightheadedness
· heart racing
· chest pain
· air hunger, a sensation like you can’t get enough air
· anxiety
· nausea
· headaches
· blurry vision
· memory problems
· frequent urination
· tremors
· rashes, hives (in the case of POTS+ mast cell activation syndrome)
The Three Distinct Mechanisms of POTS
POTS occurs as either “Primary Idiopathic POTS” or “Secondary POTS”, meaning, it is secondary to another condition. Primary Idiopathic POTS can further be differentiated into three categories that differentiate distinct mechanisms driving the symptoms. These are:
1. Neurogenic POTS
2. Hypovolemic POTS, and
3. Hyperadrenergic POTS
Any one or combination of all of these can be present in an individual, and symptoms are often identical. This is why proper diagnostic testing and evaluation is so important. These three types cannot be distinguished based on symptoms, however, they do matter in regard to treatment.
Neurogenic POTS
The first type, neurogenic POTS is also called neuropathic dysautonomia, in which the autonomic nervous system has inadequate peripheral and splanchnic vasoconstriction in the presence of orthostatic “stress”. This is a super technical way of saying that when a person is standing upright, blood vessels in their legs and blood vessels supplying circulation to the digestive system are not properly constricting. This is due to small fiber neuropathy that can be measured through a skin biopsy test, however these tests are not widely available.
In this test a tiny sample of skin, about the size of a pencil eraser is taken from the leg. The skin sample is then examined under a microscope in a lab to check the condition of the small nerve fibers, which are responsible for sensing pain, temperature, and regulating blood flow. If these small fibers are reduced or damaged, it can confirm small fiber neuropathy, which may be contributing to symptoms of neuropathic POTS.
This failure to control blood circulation can cause a lack of blood supply to the brain, triggering dizziness, lightheadedness and cognitive symptoms like brain fog and difficulty concentrating. Another way to think of this is to consider gravity. When we are upright, our autonomic nervous system has to overcome gravity by increasing blood pressure and heart rate. Increasing blood pressure is done by constricting blood vessels just enough to aid in sending blood upwards to the brain, against gravitational forces that would otherwise send it towards the feet.
What I just described is really important to understand, because it points to a problem with treating all POTS cases similarly, when different mechanisms are at play. If the initial dysfunction in this whole picture is a loss of vasoconstriction, leading to blood pooling in the pelvic floor and legs, then the body is trying to correct this problem by increasing the heart rate to pump more blood. The tachycardia is the body trying to find a solution to the original problem – meaning, the tachycardia is not the root problem, but a reaction to the root problem. This is why simply giving people beta blocker or medications to lower heart rate is not addressing the root cause of POTS, and often just leads to more side effects in the case of neurogenic POTS. The following are beneficial therapies for neurogenic POTS:
· Compression garments
· Compression devices for the legs (Ex: NormaTec compression devices): counteract the lack of proper vasoconstriction by providing an external level of constriction
· Resting with legs inclined above the heart can also help temporarily reduce symptoms
· Mitrodine may be prescribed because of its vasoconstrictive properties
Hypovolemic POTS
Hypovolemic POTS exists when there is dysfunction within the renin-angiotensin-aldosterone system that regulates fluid balance and water metabolism in the body. This system involves actions performed by the kidneys, adrenal glands, liver, and lungs. Problems in this finely-tuned system lead to low plasma volume that can actually be measured by a specific 24-hour urine test. In this test, a special container is given to the patient, all urine over the course of 24 hours is collected in the jar and brought to a lab. The total amount of urine, sodium levels, potassium levels, and creatinine are measured. In hypovolemic POTS, sodium concentrations in this 24-hour collection will be less than 100 mmol/L (millimoles/Liter).
In Hypovolemic POTS interventions that increase the volume of plasma through promoting fluid and sodium retention are helpful. These can include:
· salt tablets
· electrolytes
· increased fluid intake
· exercise
· Licorice root: Licorice root spares sodium in the body thereby increasing fluid retention, and also blood pressure. It can however, increase excretion of potassium, which can be counteracted by taking electrolytes containing potassium.
· Fludrocortisone: Fludrocortisone acts on the kidneys to increase the reabsorption of sodium from the urine back into the bloodstream. As sodium is reabsorbed, water follows it back into the bloodstream, which helps increase blood volume. Fludrocortisone can also cause the body to lose too much potassium through urine, leading to hypokalemia, and potassium supplementation may be needed to counteract this effect.
Hyperadrenergic POTS
Hyperadreneric POTS is the other form of Primary Idiopathic POTS. In this form, there is excessive production and release of the neurotransmitter norepinephrine, or a failure of proper reuptake of norepinephrine, leaving too much in circulation. This leads to orthostatic hypertension and often migraines as part of the clinical presentation. Remember, POTS involves tachycardia without orthostatic hypotension. In hyperadrenergic POTS, both tachycardia and hypertension may be present during tilt table testing. Mainstream treatments for hyperadrenergic POTS include:
· Avoiding drugs that promote norepinephrine such as norepinephrine-serotonin reuptake inhibitors (NSRIs - a class of anti-depressant drugs that include Cymbalta and Effexor).
· Beta-blockers
It is important to note that in many cases, POTS goes undiagnosed for a long time, or can be misdiagnosed as generalized anxiety or some other disorder. When it is diagnosed, medications are often prescribed without taking into account the above categorical distinctions. A breakdown of the different functional tests useful in determining POTS and dysautonomia will be covered in future blog posts.
If you are seeking help for POTS, call to schedule a free 15-minute consultation at 651-323-0005.
References
Angeli, A. M., Salonen, B. R., Ganesh, R., Hurt, R. T., Abdalrhim, A., Mueller, M., . . . Aakre, C. (2024). Symptom presentation by phenotype of postural orthostatic tachycardia syndrome. Sci Rep, 14(1), 205. doi:10.1038/s41598-023-50886-8
Jacob, G., Diedrich, L., Sato, K., Brychta, R. J., Raj, S. R., Robertson, D., . . . Diedrich, A. (2019). Vagal and Sympathetic Function in Neuropathic Postural Tachycardia Syndrome. Hypertension, 73(5), 1087-1096. doi:10.1161/HYPERTENSIONAHA.118.11803
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