How are your catecholamines?

[friday]

Sorry I forgot to mention that that article snippet I just used was from that link that Michelle has posted.

http://en.wikipedia.org/wiki/Norepinephrine

Friday

[Michelle Sawicki]

Beta Blockers can block the direct effects of norepi on your heart. And many of the other medications affect the amount of norepi you release as well. For instance, a medication that helps vasoconstrict will result in your veins constricting more and therefore less norepi being pumped into your system (in an effort to constrict your veins).

Hope that helps!

Michelle

[Nicole's Mom]

Michelle,

Thank you for your last reply. This is exactly the subject that I want to learn about. I just want to clarify what I think I finally understand and ask a question. Because Nicole's norepinephrine was so high I have to assume that it something was or is wrong with her vasoconstriction process. Therefore the norepi shoots out to try and counterbalance this. So something like midodrine would help the veins constrict therefore there is less norepi showing up in the body. So one needs a med to intervene.

And to take it one step back in the process and ask my question am I to understand that what makes the veins dilate instead of constrict is not yet understood- except that all we know is that the autonomic nervous system is malfunctioning?

Bev

[Michelle Sawicki]

Hi Bev,

I wish it were so simple to say that high norepi = problems vasoconstricting, but it's not. This is thought to be true for some people. There are other problems that can affect the veins and cause problems as well. This is from our website:

The following are some abnormalities that can result in reduced venous return:

Abnormal veins that stretch excessively can result in pooling blood (Stewart, 2000).

Altered capillary permeability can affect capillary leakiness and cause excessive fluid collection in the lower body (Stewart, 2000). This may be contributing to orthostatic intolerance in a number of POTS patients.

Blood vessels that don't seem to constrict appropriately have been noted in POTS patients. Some physicians believe this subnormal orthostatic venous constriction, resulting from impaired sympathetic innervation, is the cause of blood pooling excessively in the legs of POTS patients (Streeten, 1999). This loss in the ability to vasoconstrict leads to excessive heart rate increases and contractions (Grubb, 2000).

Denervation occurs in some POTS patients. A number of patients do not sweat in various parts of their bodies. Some patients report losing their ability to sweat altogether. This lack of sweating shows that the nerve supply to the area is damaged (Low, 2000). As a result, the vessels that the nerve supplies lose their tone and become slack. Blood volume is normal but vessel capacity is excessive (Low, 2000). This causes decreased venous return of blood flow to the heart, decreased cardiac output and (probably) orthostatic reduction in cerebral blood flow (Streeten, 1999). Peripheral neuropathy may be present in these patients. This neuropathy seems to be selective, with slight responses in some regions being compensated for by overactivity in other regions (Bush, Wight, Brown & Hainsworth, 2000).

Hypovolemia (low blood volume) sometimes occurs in POTS patients. Reduced plasma renin activity often accompanies the low blood volume. Reduced levels of renin release consequently result in reduced secretion of aldosterone. This would be expected to impair renal sodium conservation thereby contributing to hypovolemia (Streeten, 1999). Findings suggest that the impaired renin release may possibly result from sympathetic denervation (Jacob & Biaggioni, 1999). Physicians believe hypovolemia and inappropriately low levels of plasma renin activity may be important pathophysiological components of orthostatic intolerance (Jacob, Robertson, Mosqueda-Garcia, Ertl, Robertson & Biaggioni, 1997).

Erythropoietin response impairment may be contributing to a patient's hypovolemia. Erythropoietin is a hormone made by the kidneys. It helps stimulate red blood cell production. Impairment of the normal erythropoietin response to low levels of red blood cell mass could contribute to hypovolemia. Physicians postulate that subnormal erythropoietin response may be resulting from a disorder in the normal sympathetic stimulation of erythropoietin release by the kidney (Streeten, 1999). Read more

Paradoxically, POTS can occur because of hypovolemia or hypovolemia can occur because of POTS. This can happen because hypovolemia may lead to a chronic state of adrenergic activation, which may produce POTS symptoms. Chronic adrenergic activation reduces intravascular volume, which may produce hypovolemia (Stewart & Erickson, 2002). Read more

Impaired venous emptying can cause excessive fluid collection in the lower body. This can lead to blood pooling in the lower limbs and consequently, orthostatic intolerance.

Splanchnic pooling is occurring after meals in some POTS patients. Excessive pooling of blood in the abdomen has been shown to occur while the patient is supine and at rest (Tani, Singer, McPhee, Opfer-Gehrking, Haruma, Kajiyama & Low, 2000). The splanchnic vascular bed contains up to 30% of blood volume. Limited autonomic neuropathy causing peripheral denervation may be the cause of increased resting flow and reduced mesenteric resistance in these patients.

Then there are a few out there that have the norepinephrine transporter deficiency. This is from our website re: the norepinephrine transporter deficiency:

Norepinephrine transporter deficiency is thought to cause POTS in some patients. These patients have an abnormality in the clearance of norepinephrine from the synaptic cleft. The body normally recycles norepinephrine. The protein that recycles norepinephrine doesn't work well in people with the norepinephrine transporter deficiency (Grubb, 2002). Excessive amounts of norepinephrine is spilled over. These people soon become depleted of norepinephrine if the neuron is continually stimulated (Grubb, 2002). They go from having excessive amounts of norepinephrine to having no norepinephrine, at which point they crash.

There are probably some (many?) other factors that have yet to be discovered that may be playing a role in increased norepinephrine levels.

Re: your second question....the above mentioned info may apply here as well. There are people like me, Nina, and some others on this board who have Ehlers-Danlos syndrome (joint hypermobility syndrome). We are thought to lack firm enough collagen to hold our veins tight. Our veins stretch excessively and therefore don't constrict appropriately.

I hope this helps!

Michelle

[MightyMouse]

Herdswoman, I'm a science geek at heart, so no problem answering. The original catecholamine blood draws were done shortly after my tilt table test by my renal and hypertension specialist. In addition to abnormal norepi, I also have low blood volume (hypovolvemia). I was on meds during the volume and catech. tests (florinef and midodrine).

I suppose that knowing what type of POTS you've got could affect treatment choices, but I can't say that the tests pointed to anything different than we were already doing. As for NIH (yes, Nat'l Ins. for Health), all the tests were done there as part of a POTS study that I volunteered for several years ago with Dr. David Goldstein.

Nina

[Nicole's Mom]

Thanks Michelle for your answers to my questions. I guess I knew deep in my heart that it couldn't be that simple...the way I stated it. And thank you by the way for explaining about yourself and Nina and others with E.D.

Beverly