More Than Sick of Salt


Parasympathetic and Sympathetic, Nervous System Dysfunction and Monitoring – Introduction

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By Dr. Nicholas DePace and Dr. Joseph Columbo

There are many consequences of Parasympathetic and Sympathetic Dysfunction (P&S Dysfunction; aka., Autonomic Dysfunction or Dysautonomia) 

Major consequences and their effects include:

  • Abnormal cardiovascular control, causing inappropriate peripheral vasoconstriction, inappropriate shifts in blood volume, poor perfusion and distribution, and inefficient cardiac contractility.  The net effects are (1)gravitational pooling of blood volume, usually to the lower half of the body upon or during upright posture; (2) difficulty in returning blood to the heart to produce an adequate cardiac output, which results in inappropriate rapid drops in BP or rapid increases in HR; and (3) an inappropriate distribution of blood flow throughout the various organs of the body, some receiving too much and some too little, resulting in many of the symptoms listed near the end of this Introduction;
  • P&S imbalance, both at rest and in response to challenges, causing abnormal organ function even when the organs themselves are normal and healthy.  Examples include: (1) unequal pupil sizes; (2) abnormal motility and pH of the gastrointestinal (GI) tract; (3) hormone dysregulation; (4) abnormal pain, inflammatory, histaminergic, BP, HR, blood glucose, or affective (g., anxiety or depression, ADD/ADHD, OCD, PTSD) responses; and
  • Compensation, causing many adverse symptoms that may arise when the body attempts to compensate for the P or S dysfunction, such as high resting BP (possibly resulting in secondary hypertension) in response to Orthostatic or Syncopal disorders and auto-immune-like responses resulting from exaggerated inflammatory responses due to Sympathetic Excess secondary to Parasympathetic Excess (see below).
  • Note: In cases where the P&S dysfunctions are relieved and symptoms persist, then the remaining dysfunctions or disorders are true end-organ dysfunctions and should be treated accordingly.

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Signs and Symptoms of Dysautonomia (Autonomic Dysfunction)

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By Dr. Nicholas DePace and Dr. Michael Goldis

Symptoms of Dysautonomia include fainting. drop in blood pressure with getting up, blood pressures that occur without a known cause, flushing of the face, lack of sweating or sweating too much, vomiting, constipation, diarrhea, difficulty swallowing, swelling of the belly, disturbances of urination, difficulties with erections, episodes of stopping breathing and the declining ability to see at night. Quite a lot!

Before the person actually faints, they may experience loss of strength in the muscles that keep us upright, weakness, a generalized feeling of not being well, nausea, headache, sweating, a pale complexion, difficulty seeing and a sense that they are about to lose consciousness. 

Usually low blood pressure and slow heart beat accompany these symptoms. These signs and symptoms can be caused by emotional stress, drops in blood pressure when getting up, vigorous exercise in a hot environment, blockage of blood returning to the heart, sudden onset of pain or its anticipation, and loss of fluids.

There can be a variety of other circumstances involved with these feelings faint one gets before they faint due to dysautonomia.

When a person does faint, they usually limp. Some muscle movement may occur and they may experience fainting and sometimes lose bowel control which can appear like seizure. what is different is that recovery is rapid  once the person is lying flat. After the fainting event, headache, nausea and fatigue. usually persist.


Reference – Current Medical Diagnosis and Treatment, Dysautonomia  2021 page 101


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What is Orthostatic Hypotension

Cracking the Code of Dysautonomia: POTS, Orthostatic Hypotension, and Heart Health

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by Nicholas DePace MD, FACC and Michael Edward Goldis DO, FACOI, MS, BS in Pharm

When venous pooling occurs, the cardiovascular system attempts to maintain cardiac output with activation of the sympathetic nervous system, the so called accelerator of the body.

Adrenalin is released in above normal amounts and that causes the heart to beat faster or compensatory tachycardia. In addition, increased vascular tone occurs with alpha agonist activity.

This maintains blood pressure while there is decreased preload from venous pooling and maintains cardiac output by increasing heart rate with a reduced stroke volume.

This explains how cerebral circulation and thus consciousness is maintained in compensated states like orthostatic hypotension and POTS.

The increased heart rate increased the output of the heart (the cardiac output) while the actual volume the heart puts out each stroke (the stroke volume) falls because of venous pooling.

The heart rate may increase 30, 40 or more above baseline. Therefore, POTS is known as a compensated neuro-cardiovascular dysfunction. One could argue that this is not a well-compensation as the patient has significant symptoms still resulting in orthostatic intolerance.

In contrast, Orthostatic hypotension is thought of as an uncompensated neuro-cardiovascular dysfunction. Here, the patient can become dizzy and lightheaded because the blood pressure is not maintained when there is venous pooling.

Because the heart rate generally does not increase significantly for compensation, the patient’s blood pressure drops and may even have overt syncope.

Patients with orthostatic hypotension often do not have an adequate rise in heart rate because of sympathetic nervous system decompensation.

A person can have a 30 or 40 point rise in heart rate, meeting the criteria for POTS, and in another moment, when the neuro-cardiovascular system is not compensated, they can have a blood pressure drop resulting in orthostatic hypotension.

So, while it is rare, both POTS and orthostatic hypotension can coexist. Generally, if someone demonstrates orthostatic hypotension, they rarely have POTS and vice versa.

Vasovagal syncope is a sort of form of orthostatic hypotension which is delayed.

This is whether is an increasing vagal tone that prevents blood vessels from adequate constriction and prevents the heart rate from adequately increasing.

This is an extremely delayed form of orthostatic hypotension which sometimes can be reproduced on Tilt Testing.

POTS oftentimes is due to several mechanisms. There can be hypovolemic, hyperadrenergic, and neuropathic POTS. Mast cell activation is a potential mechanism as well as certain enzyme deficiencies.

When the sympathetic nervous system is extremely overactive the blood pressure may even elevate with a rise in heart rate, which is hyperadrenergic POTS.

Regardless of the mechanism of POTS, the treatment is basically similar. But, for hypovolemic POTS a volume expander makes clinical sense and for hyperadrenergic POTS, a beta blocker makes sense.

Neuropathic POTS occurs when there are diseased small fibers, which can happen with diabetes, rheumatoid arthritis, lupus, and Sjogren’s syndrome and usually has some degree of autoimmunity, but may not necessarily occur in small fiber neuropathy.

While small fiber biopsy is the gold standard to diagnose this form of POTS, we have used psuedomotor testing as an alternative.

The end result, whether the dysautonomia is due to sympathetic overdrive or parasympathetic dysfunction is poor perfusion to the brain, leading to dizziness, syncope, vision and hearing loss, tinnitus, and brain fog.

With Sympathetic overdrive, which is a major compensation mechanism, the patient has a racing heart, insomnia, excessive sweating, high anxiety, and exacerbation of brain fog from reduced cerebral blood flow from hyperventilation. This may also explain the palpitations a person feels with dysautonomia.


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Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome (EDS) and Autonomic Dysfunction

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Autonomic Nervous System Dysfunction in Ehlers-Danlos Syndrome

by Nicholas DePace MD, FACC, and Michael Edward Goldis DO, FACOI, MS, BS in Pharm

The autonomic nervous system (ANS) runs all background bodily functions that do not require a conscious thought process. Major consequences of autonomic dysfunction include abnormal and inappropriate blood volume and flow distribution to the body with gravitational pooling and difficulty returning blood to the heart.

Direct nerve dysfunction can affect pupil size and abnormal motility of the gastrointestinal (GI) tract, compensations which are adaptive mechanisms in the body’s attempt to compensate for autonomic dysfunction, which can cause adverse symptoms. There are 2 components: (1) the sympathetic nervous system, which releases predominantly norepinephrine and is the “accelerator” of the body; (2) the parasympathetic nervous system releases acetylcholine which is the “break” of the body.

The vagus nerve is the main component of the parasympathetic nervous system and is the longest nerve in the body. Because of its long distribution and size, it is susceptible to injury.

Impairment of blood flow to the brain, which is poor perfusion, leads to lightheadedness, tunnel vision, blackout vision, change in hearing, perception, complete loss of consciousness, syncope, presyncope, the need to lie down, giddiness, word-finding difficulties, and short term memory loss.

These occur in the standing position almost always or occasionally sitting, but not lying. These symptoms are known as orthostatic intolerance. Mental cloudiness and brain fog are described.

Lack of perfusion to the brain may precipitate migraines. Light intolerance, photophobia, bothersome sensation to loud noises, anxiety, insomnia, and depression may or may not reflect poor cerebral perfusion.

Ehlers Danlos Syndrome is often associated with GI motility and may be associated with mast cell activation. What the mast cells do is release histamine inflammatory mediators. This accounts for the overlapping features not EDS like abdominal pain and poor GI motility with foggy thinking.

There is an article in the New England Journal of Medicine that feels irritable bowel syndrome (IBS) is the result of a histamine abnormality. What the actual cause is controversial.

While some physicians believe there’s a component of autoimmunity, we believe there is an abnormal connective tissue in the veins precipitating the venous pooling phenomenon, there is poor cerebral perfusion, and Sympathetic overdrive leading to dysautonomia.

There may also be an anatomical component to the autonomic dysfunction when you consider the vagus nerve is a parasympathetic nerve and the most prominent and longest in the parasympathetic nervous system.

It is the 10th cranial nerve and arises from the brain stem located auth the junction between the cranium and the first cervical vertebrae, which is also at the base of the cerebellum.

Any craniocervical instability in this region or compression of the vagus nerve could potentially have profound effects on vagus nerve function. Craniocervical instability is common in EDS and needs flexion and extension radiographic images and proper measurements to clearly characterize it.

The vagus nerve exits from this location along with the ninth cranial nerve, the glossopharyngeal nerve, and the eleventh cranial nerve which is known as the spinal accessory nerve.

The vagus nerve then branches throughout most of the body. The vagus is both afferent sensory and efferent motor. This sensory fiber for the vagus takes information from the GI tract and runs it back to the brain, while the motor activity directs the bodily functions in many organs.

Some physicians describe the enteric nervous system as an organism “second brain” which can function completely in the absence of central nervous system input. The vagus nerve as well as the parasympathetic nervous system in general uses the neurotransmitter acetylcholine to transmit information from the presynaptic nerve termination to the end organ.

There can be abnormalities from the brain to the ganglia or from the end receptors where acetylcholine is released. There are about 30 neurotransmitters within the enteric nervous system which include more than 90% of the body’s serotonin and 50% of the body’s dopamine.

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Chronic Fatigue Syndrome 101

What is Chronic Fatigue Syndrome (CFS) 101

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Dr. DePace, MD, FACC

Symptoms of Chronic Fatigue Syndrome

Chronic diseases usually last for over 6 months. In Chronic Fatigue, we see post-exertional fatigue, unrefreshing sleep, and “Brain Fog” ( memory and cognitive disturbances).

The Autonomic Nervous System (Parasympathetic and Sympathetic balance) is often abnormal in Chronic Fatigue Syndrome (CFS). This affects blood pressure (BP) and heart rate (HR) regulation.

That’s why we see Orthostatic Intolerance in most cases like Postural Orthostatic Tachycardia Syndrome (POTS). In this condition they experience worsening symptoms when are in an upright position and improve when they lie down. Females are more affected than males. As many as 8 million Americans may be affected. Patients are affected at different ages and have different presentations.

What Causes Chronic Fatigue Syndrome?

Chronic Fatigue Syndrome is a group of disorders that consists of many different causes. Let’s take them separately;

  1. Infection (viral or bacterial) that causes autoantibodies and oxidative stress to dysregulate cellular and specifically mitochondrial energetics. This may lead to exercise intolerance.
  2. Disturbed gut microbiota (abnormal bacterial colonization) possibly leading to “leaky-gut” leads to autoimmunity. Irritable Bowel Syndrome is seen in many Chronic Fatigue patients.
  3. Microglial activation of the nervous system, including the Central nervous System (CNS), possibly leading to chronic pain due to allodynia (pain due to stimuli that is usually not painful) and hyperalgesia (abnormally heightened sensitivity to pain).
  4. Neuronal inflammation is important in the pathophysiology of many disabling symptoms.
  5. High levels of pro inflammatory cytokines (chemicals produced by cells) and low level of antioxidants, such as Coenzyme Q-10 (CoQ10) or Glutathione
  6. Abnormalities of the Hypothalamus-Pituitary-Adrenal Axis possibly leading to “delayed cortisol awakening”, possibly leading to unrefreshing sleep. In some cases we see low cortisol levels. Cortisol is a hormone that helps the body handle stress.
  7. Physical or emotional trauma, including form an accident, concussion, immobilization, surgery, trauma, or even emotional stress such as loss of a loved one.
  8. Genetics may contribute, with identical twins having a higher incidence then fraternal twins. There has also been familial aggregations note of CFS.
  9. Environmental factors like mold or toxins may also be a triggers.

While mitochondrial dysfunction is implicated as an immediate cause of CFS, it is not determined what the damage to mitochondrial function is from.

Mitochondria are components of cells that are called organelles and they produce energy in the form of a molecule called ATP. Cellular hypoxia and oxidative stress happen during stressful situations.

Treatments For Chronic Fatigue Syndrome

The end result is disturbing muscle and nerve function. Exercise is the hallmark treatment for improving CFS. “Low and slow” exercise is where patients exercise 2-5 minutes followed by 5 minutes of rest so as not to damage skeletal muscle. Another such exercise is walking slowly, no more than 2 MPH for 40 minutes daily.

Even if biking or rowing, no more than 2 MPH. This may be too stressful for some patients, who on some days cannot lift their heads off the pillow. Supine exercises can be used for them. More work is required to assess the types of exercise programs that are most effective.

Diets high in processed foods and full of chemicals may be a cause of CFS and should be avoided. Cocktails of antioxidants that work on the mitochondria and immune system modulation are current areas of investigation. Currently, we are working on ways to categorize the different patients to determine which treatments work best.

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