Orthostatic Intolerance (OI) Basics: Dysautonomia of Blood Vessels, Low Blood Volume, and Baroreflexes

Pyrrhus

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I just read a good overview article covering all the basics of orthostatic intolerance:


Common Syndromes of Orthostatic Intolerance (Stewart, 2013)
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3639459/pdf/peds.2012-2610.pdf
(or https://dx.doi.org/10.1542/peds.2012-2610)

This paper starts out by explaining that orthostatic intolerance can be caused by either low blood volume or by defective vasoconstriction, a type of dysautonomia of blood vessels. In either case, a drop in regional blood pressure upon standing reduces blood flow to the brain, with blood pooling in the legs.

(Note that the drop in regional blood pressure is often not measurable using standard blood pressure monitors. If the drop in blood pressure is measurable and large enough, the orthostatic intolerance is referred to as orthostatic hypotension.)
Abstract
The autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps are essential components for rapid cardiovascular adjustments to upright posture (orthostasis). Patients lacking sufficient blood volume or having defective sympathetic adrenergic vasoconstriction develop orthostatic hypotension (OH), prohibiting effective upright activities. OH is one form of orthostatic intolerance (OI) defined by signs, such as hypotension, and symptoms, such as lightheadedness, that occur when upright and are relieved by recumbence.
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They mention how blood is normally pulled downward by gravity upon standing, leading to a slightly decreased blood flow to the brain. If there is low blood volume, then this effect becomes much worse:
Standing transfers >500 mL of central blood [downwards], [...] filling veins of the lower extremites. [...] Cerebral blood flow velocity (CBFv) decreases by 3% to 12% partly because of reduced cerebral [blood] pressure by 20 mmHg.

They mention how the autonomic nervous system normally adjusts heart rate (HR) and blood pressure (BP) automatically by using special reflexes called "baroreflexes". These reflexes cause constriction of blood vessels (vasoconstriction) in order to push blood back up towards the heart and brain. Defective vasoconstriction is a type of dysautonomia of blood vessels.
Rapid orthostatic circulatory adjustments depend on the autonomic nervous system (ANS) comprising sympathetic and parasympathetic arms forming a framework for heart rate (HR) and blood pressure (BP) stability. [...] The sympathetic arm acts through its primary vascular neurotransmitter norepinephrine [...] to produce [vasoconstriction], increase [...] HR, [...] and long-term BP control. [...] Autonomic control of HR and BP during [standing] is provided by subsystems designated “baroreflexes” (pressure reflexes), loosely grouped as arterial and cardiopulmonary baroreflexes, which maintain BP under changing conditions such as [standing].
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They also mention when orthostatic intolerance (OI) can be diagnosed as orthostatic hypotension (OH):
True orthostatic hypotension (OH) was defined by consensus in 2011 as sustained reduction of systolic BP >20 mm Hg or of diastolic BP >10 mm Hg within 3 minutes of standing or head-up tilt.

And they mention when orthostatic intolerance can be diagnosed as postural orthostatic tachycardia syndrome (POTS):
POTS is defined by chronic day-to-day symptoms of OI plus excessive increase in HR when upright. Hypotension is not in the definition. [...] HR normally increases with standing. Excessive tachycardia was defined in adults by a sustained increase >30 beats per minute or to a HR >120 beats per minute during a 10-minute tilt. [...] Larger HR increments are observed in healthy young people; the HR increment for POTS has increased to >40 beats per minute in children and teens aged 8 to 19 years.

They go on to mention that temporary orthostatic intolerance (OI) can occur during dehydration or infection. As well, they note that the symptoms of OI include exercise intolerance.
Orthostasis means standing up. OI can be defined by the inability to tolerate the upright posture because of signs and symptoms relieved by lying down. If symptoms initiate while supine, then there is no OI. Transient OI is commonly experienced during dehydration or infectious disease. Typical signs and symptoms include loss of consciousness or lesser cognitive deficits (memory loss, decreased reasoning and concentration), visual difficulties, lightheadedness, headache, fatigue, either increases (hypertension) or decreases (hypotension) of BP, weakness, nausea and abdominal pain, sweating, tremulousness, and exercise intolerance.

Interestingly, the paper notes how leg muscles and abdominal muscles can sometimes help to ensure proper blood flow during orthostatic intolerance:
Upright posture (orthostasis) stresses regulatory capabilities of the circulatory system including [...] intact physical pumps comprising the skeletal muscle pump (leg muscles that compress leg veins) and the respiratory-abdominal muscle pump, which enhances systemic venous return during respiration. Upright stance causes dependent venous pooling. Muscle pumps propel blood back to the heart when upright and during exercise. Enabling the skeletal muscle pump forms an important class of physical countermeasures against orthostatic intolerance (OI).
 

Pyrrhus

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No cures for the defective vasoconstriction aside from drugs like midodrine?
As others have mentioned there may be symptomatic treatments, but ideally we would want to first find out the cause of the dysautonomia that results in defective vasoconstriction and then treat that. (which is easier said than done!)


This paper starts out by explaining that orthostatic intolerance can be caused by [...] defective vasoconstriction, a type of dysautonomia of blood vessels.
It is worth noting that this defective vasoconstriction is also sometimes considered a type of endothelial dysfunction, as described in this discussion:

Endothelial Dysfunction in ME
https://forums.phoenixrising.me/threads/endothelial-dysfunction-in-me.83521/
 
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As others have mentioned there may be symptomatic treatments, but ideally we would want to first find out the cause of the dysautonomia that results in defective vasoconstriction and then treat that. (which is easier said than done!)
Do we know of causes that are separate to just "caused by ME/CFS"?
 
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@Violeta , thanks, I actually just got some Butcher's Broom to try - I'll give it a go soon!

@Learner1 thanks, I have used huperzine A on and off but it doesn't seem to affect my POTS at all, just helps a little bit with brain fog (so maybe it is helping?). The fatigue from being upright and increased HR seem the same though. I think I did 100 ug though, maybe I'd need more.
 

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And here's a 2003 study by Ben Natelson that found an abnormal baroreflex in ME patients:

Baroreceptor Reflex and Integrative Stress Responses in Chronic Fatigue Syndrome. (Peckerman et al., 2003)
https://forums.phoenixrising.me/thr...and-integrative-stress-responses-in-cfs.2174/
(only available to Phoenix Rising members with more than 100 posts)

Excerpt:
Peckerman et al 2003 said:
Objective:
Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning.

Methods:
Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N 21) or less severe (N 22) illness, and in 29 matched control subjects.

Results:
Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task.

Conclusions:
These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.
 

Pyrrhus

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Do we know of causes that are separate to just "caused by ME/CFS"?
Yes, I believe there are a number of non-ME conditions that have orthostatic intolerance as a symptom. But I haven't done any exhaustive search for such conditions.

One complication in searching for such conditions is the tendency for people to talk about orthostatic intolerance and POTS as their own conditions, rather than as symptoms of a condition. I have even heard someone say that ME was a symptom of POTS, instead of saying that POTS was a symptom of ME!
 
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Yes, I believe there are a number of non-ME conditions that have orthostatic intolerance as a symptom. But I haven't done any exhaustive search for such conditions.

One complication in searching for such conditions is the tendency for people to talk about orthostatic intolerance and POTS as their own conditions, rather than as symptoms of a condition. I have even heard someone say that ME was a symptom of POTS, instead of saying that POTS was a symptom of ME!
Ah right ok. Yeah I guess the question really is, what is at the heart of ME POTS/OI, and how well can it be managed outside of just being lucky or improving the ME in general.. If it's just a generic illness response or response to a pathogen I can see it hanging around until someone improves their ME dramatically.

I'll try the Butcher's Broom in the coming weeks at least.
 

Learner1

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@Learner1 thanks, I have used huperzine A on and off but it doesn't seem to affect my POTS at all, just helps a little bit with brain fog (so maybe it is helping?). The fatigue from being upright and increased HR seem the same though. I think I did 100 ug though, maybe I'd need more.
I think there is an effect of the right dose taken consistently over time to gradually increase acetylcholine in the brain. I was successful with a 200mcg dose, some patients might need more, like 400mcg or less. I did a NASA Lean Test (instructions on the Bateman Horne Center website) off of Huperzine A and on it and there was a dramatic difference in the results.
I'll try the Butcher's Broom in the coming weeks at least.
What is the mechanism of Butchers Broom? @Violeta

The Derrick Lonsdale disciple's think POTS is all due to a thiamine deficiency, though I'm not deficient.
 

Violeta

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I think there is an effect of the right dose taken consistently over time to gradually increase acetylcholine in the brain. I was successful with a 200mcg dose, some patients might need more, like 400mcg or less. I did a NASA Lean Test (instructions on the Bateman Horne Center website) off of Huperzine A and on it and there was a dramatic difference in the results.

What is the mechanism of Butchers Broom? @Violeta

The Derrick Lonsdale disciple's think POTS is all due to a thiamine deficiency, though I'm not deficient.
Butcher's broom (Ruscus aculeatus) is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall.
 

Learner1

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Butcher's broom (Ruscus aculeatus) is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall.
Got it! Thanks for explaining. Then, we need to figure out if that's what we need to be doing. In my case, more noradrenaline might be counterproductive. But good to know the tools that are out there.
 

Violeta

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Got it! Thanks for explaining. Then, we need to figure out if that's what we need to be doing. In my case, more noradrenaline might be counterproductive. But good to know the tools that are out there.
I guess it wouldn't be good for people with hypertension.
 

Violeta

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Butcher's broom (Ruscus aculeatus) is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall.
I wonder what the root issue is if butcher's broom helps. Adrenal insufficiency?

"α-Adrenergic receptors α1-Adrenergic receptors are located on postsynaptic effector cells such as those on the smooth muscles of the vascular, genitourinary, intestinal, and cardiac systems. Additionally, in humans these receptors are located within the liver."

And look at this:
Stimulation of α1 adrenergic receptors by norepinephrine results in release of calcium ions from intracellular stores.

And this: Together with other hormones, norepinephrine helps the body respond to stress and exercise.

Conclusion: I am terrible deficient in norephinephrine.

I have to read this:

https://www.drlamcoaching.com/neuroendocrine-stress-adrenal-fatigue/
 
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Learner1

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@Violeta You may find these interesting - they describe the alpha adrenergic and muscarinic receptors affected by antibodies in POTS:


CellTrend test for POTS looks at these antibodies.

My experience is more with adrenal insufficiency, rather than adrenal fatigue. I didn't find the "stages of adrenal fatigue" really happened in my case. It was more Infections that can put a great deal of stress on our systems. I failed an ACTH stimulation test and my aldosterone and cortisol were low, though nowhere near Addison's disease. This did not surprise my ME/CFS specialist, and he and my. naturopathic doctor both thought I should be on hydrocortisone replacement. I started at 30mg a day divided into 3 doses, then, as my infections improved, I gradually was able to cut the hydrocortisone to zero.

Even though Dr. Lan thinks norepinephrine is linked to adrenals, I found my norepinephrine was high when my cortisol was low, for other reasons.
 

Violeta

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I'm still on the first video; it's very interesting. Very eye opening.

What caused the improvement as far as your infections?

Do you know what caused your high norepinephrine?

Did you have antibodies to receptors?

Thanks for the videos.

2nd video not working
 
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Is it possible to have blood pooling only in arms, but not in legs? My arms become more 'reddish' and darker when I let them down. And I feel that they become a little bit heavier when they are down. If I measure BP in arms correctly (hands are at heart level), it is always ~120/80. But if I measure BP when arms are down, it shows ~150/100.
Does it mean that my peripheral autonomic nerves at arms doesn't work properly, but in legs they are normal? Or problem lies somewhere in the brain?