Hydration, Salt, and Peeing: The Renin-Angiotensin-Aldosterone System

I guess I should use the technical name for peeing in this title - urination - but it's a catchier to say pee.  Because that's what many of us POTS folks do (and various other forms of Dysautonomia), we pee A LOT.

Why is this?  And why the heck do we have to eat so much salt?  

Well, there is this thing called the

Renin-Angiotensin-Aldosterone System.

 

It's a big deal. It takes place mainly in your kidneys and adrenal cortex, and affects your blood pressure directly.  Lets break down the three components:

 

1. Renin is a protein (enzyme) released by special kidney cells when you have decreased salt (sodium levels) or low blood volume, and stimulates the formation of Angiotensin in blood and tissues. 

2. Angiotensin then undergoes a series of reactions that convert it to Angiotensin II (AII in the diagram below), which in turn stimulates the release of Aldosterone from the adrenal cortex. 

3. Aldosterone is the main mineralocorticoid (steroid hormones that balance electrolytes) hormone secreted by the adrenal cortex, the principal biological activity of which is the regulation of electrolyte and water balance by promoting the retention of sodium (and, therefore, of water) and the excretion of potassium.  In plain English - Aldosterone helps your kidneys retain salt, and therefor retain fluids, helping to keep blood volume and blood pressure up.

Here is a diagram of the entire system.  

•  If you follow the chain of events, you'll see that the production of RENIN is triggered by 3 things: 

1. Sympathetic Stimulation- that is your Sympathetic Nervous System being kicked into gear (and many of us are super sensitive and this is triggered easily)

  

2. Hypotension- LOW blood pressure (caused by systemic, or whole body, hypotension or renal artery stenosi)

3. Decreased Sodium Delivery (to the distal, or the end/faraway, tubules of the kidney)

•  The Renin then stimulates Angiotensin, which then stimulates Angiotensin II.

•  Angiotensin II (AII) then has a bunch of important roles that have an impact of POTS/Dysautonomia:

 

1. Constricts resistance vessels, thereby increasing systemic vascular resistance and arterial pressure (aka VASOCONSTRICTION - squeezing of your veins to circulate blood.  If this is not happening, blood is not being squeezed into the right places properly, and could cause pooling).
   
2. Acts on the adrenal cortex to release aldosterone, which in turn acts on the kidneys to increase sodium and fluid retention (discussed this above).
   
3. Stimulates the release of vasopressin (antidiuretic hormone, ADH) from the posterior pituitary, which increases fluid retention by the kidneys (Some people take DDAVP, which is the synthetic form of ADH, to help retain fluids and salt).
4.  Stimulates thirst centers within the brain (anyone thirsty much???  That's possibly because many of us have too much Angiotensin II).
   
   
5. Facilitates norepinephrine (a type of adrenaline) release from sympathetic nerve endings and inhibits norepinephrine re-uptake by nerve endings (prevents it from being reabsorbed), thereby enhancing sympathetic adrenergic function (again - helps keep your veins squeezing to circulate blood, and keeps levels of adrenalin normal in your system.  So too much Angiotensin II may INCREASE norepinepherine, which the hyperPOTS group, and many POTS people in general have higher levels of).

HOW THIS RELATES TO POTS/DYSAUTONOMIA:

Researchers have found what is termed a paradox in POTS patients.  Studies have shown that some patients with POTS have high levels of AII despite low levels of Renin, and also have low levels of Aldosterone.  This is the opposite of what should happen (shocker!), and is explained in the diagram below from this publication out of Vanderbilt.  Common sense would say that increased AII would mean increased Aldosterone, but this is not the case found in quite a few studies of POTS patients.

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Schematic diagram of the renin-angiotensin-aldosterone (RAAS) system profile in healthy individuals (TOP) and the proposed RAAS profile in patients with POTS (Bottom). Vertical arrows indicate up- or down-regulation of RAAS components. Patients with POTS have high levels of Ang II despite low levels of PRA. The high Ang II might be due to low ACE2 activity with decreased clearance. Despite the high Ang II levels, however, this aldosterone levels are low in the patients with POTS. AGT = angiotensinogen; PRA = plasma renin activity; ACE = angiotensin converting enzyme; ACE2 = angiotensin converting enzyme 2; Ang = angiotensin; AT1R = angiotensin receptor type 1.

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Summary/Discussion: 

In some patients, the Renin-Angiotensin-Aldosterone System (RAAS) is wacky.  It does the opposite (it's paradoxical) of what it should, and therefor patients do not retain fluids.  With increased AII, you would think Aldosterone would increase.  And actually, with lower Renin levels, you would expect LOWER Angiotensin.  But instead, research has shown the opposite.  Hence the paradox.  Yay for POTS bodies doing the opposite of what they should!

Aldosterone specifically helps retain salt, which helps retain fluids.   Patients that are not retaining salt and fluids will pee a lot.  They sometimes have a low blood volume as well, called HYPOVOLEMIA.  Increasing salt helps retain fluids that are taken in by mouth, and therefor increases blood volume.  Florinef is the synthetic form of Aldosterone, which is why it is sometimes the first treatment attempted by many doctors for POTS patients, and even for NCS/NMS and other types of Dysautonomia involving low blood pressure and suspected low blood volume.

This is also why IV fluids work wonders for many.  In studies by Mayo and Vanderbilt researchers, they have found that POTS patients average a 13% - 17% volume deficit. For some reason, drinking fluids and loading up with salt orally doesn't work as well with many, and IV fluids bypass the absorption process in the GI tract and boost blood volume directly - with the added bonus of providing salt as well.

There is some exciting research going on in this field that hopefully will lead to new medications that target abnormalities in both Angiotensin II (POTS patients seem to have too much of this) and Nitric Oxide (NO) deficiencies.   Check out Dr. Julian Stewart's work (link below) for more info.  He has an excellent classification system for POTS based on volume and "flow."

That's it for today people!
--Claire

For your viewing pleasure - here's what I found when I Googled "Toilet" in honor of frequent POTS peeing:

Portable space toilet. Kinda cool.

Obviously the men's room.

CREEPY.

Distinguished.

????

Sourced from an excellent physiology site found here if you are interested in the more technical terms and break down, and other sources below...

• Abnormalities of angiotensin regulation in postural tachycardia syndrome.
• Center for Hypotension, NY College of Medicine (Dr. Julian Stewart)
• NIH Medline Plus Medical Dictionary
• Renin-Aldosterone Paradox and Perturbed Blood Volume Regulation Underlying Postural Tachycardia Syndrome