Correct me if I'm wrong but I think Orthostatic problems are mostly caused by being inactive or bed ridden for long periods of time.........?
There are lots people that have orthostatic intolerance (OI) diseases without having ME/CFS, and these people can be pretty active. Orthostatic intolerance is caused by dysfunction of the autonomic nervous system (ANS). Dysfunction of the ANS is called
dysautonomia. There is a forum for people with dysautonomia here:
www.dinet.org, and if you read that forum, you will see that few of the dysautonomia patients there have ME/CFS.
Very recently, a
groundbreaking study has shown that there are autoantibodies blocking
alpha 1 adrenergic receptors of the autonomic nervous system in OI patients who have POTS (postural orthostatic tachycardia syndrome). There are also
beta 1 adrenergic receptor and
beta 2 adrenergic receptor autoantibodies in POTS.
These autoantibodies would interfere with the nerve signals transmitted along the autonomic nervous system, thereby preventing the the ANS from properly functioning. This means that the ANS cannot adequately respond to the large blood pressure shifts caused by standing up. It is the smooth and healthy functioning of ANS that allows the human body to gracefully shift from lying to standing without a hiccup. The ANS needs to automatically dilate or contract blood vessels by a muscular action in order to compensate for increases in pressure caused by gravity when you stand up. But once the ANS is compromised, it cannot do this effectively, and all sorts of OI symptoms can then manifest upon standing.
If POTS is indeed caused by autoantibodies to the alpha 1 adrenergic receptors as this study indicates, POTS then is in fact an autoimmune disease, and may become treatable by immune therapies.
From the ME/CFS perspective, the fact that POTS, which is often found in ME/CFS, appears to be autoimmune in nature does bolster the view that there are some autoimmune processes going on in ME/CFS patients.
In fact, various studies have found a number of different autoantibodies in ME/CFS patients:
• ME/CFS patients can have autoantibodies to: the
muscarinic cholinergic receptor 1 (50% of patients have autoantibodies to this receptor),
the mu-opioid receptor, and the
serotonin 5-HT1A receptor.
† † One hypothesis suggests that the muscarinic cholinergic receptor autoantibodies may be a significant factor in the disruption of the hypothalamic-pituitary-adrenal axis in ME/CFS.
†
• One study showed ME/CFS patients have autoantibodies to the
neurotransmitter serotonin (5-HT). The incidence of autoimmune activity against serotonin was found in 61.5% of ME/CFS patients, compared to 5.7% of health controls.
†
• ME/CFS patients (and major depression patients) have autoantibodies to
phosphatidylinositol.
† Phosphatidylinositol forms part of the cell membrane, and also plays a role in cell signaling. Interestingly, many viruses up-regulate the body's phosphatidylinositol signaling pathway, because boosting this pathway promotes viral replication.
† So in this case, it occurred to me that the phosphatidylinositol autoantibodies might conceivably be created by the body in order to try to block phosphatidylinositol signaling, and thereby reduce viral replication. But this is just my speculation.
• ME/CFS patients have autoantibodies to
microtubule-associated protein 2 (MAP2).
† † MAP2 is involved with the assembly of microtubules within cells, and one theory
† posits that microtubules play a fundamental role in generating consciousness in the brain.
• ME/CFS patients have autoantibodies to
insoluble cellular antigens. 83%of ME/CFS patients were shown to have antibodies to various insoluble cellular antigens, whereas these antibodies were only found in 17% of health controls.
†
• ME/CFS patients have autoantibodies to
cardiolipin.
† Autoantibodies to cardiolipin are also found in antiphospholipid syndrome.
In my case it's due to low levels of norepinephrine, probably due to overexpression of ADRA2A which has been found to be excessive in ME patients after exertion. ADRA2A inhibits norepinephrine, and taking an ADRA2A antagonist (Yohimbe) or a norepinephrine reuptake inhibitor (Strattera) makes a huge difference for me.
Phoenix Rising @aboutmecfs