Review of ADH Regulation

00:01 Let's talk a little bit more about ADH and its regulation.

00:04 So again, antidiuretic hormone or ADH is a decapeptide.

00:07 It's synthesized in the supraoptic nucleus of the hypothalamus and it's secreted by the posterior pituitary.

00:14 It's regulated by both osmotic and nonosmotic mechanisms.

00:22 Now, there is two types of ADH receptors that ADH combined to.

00:26 In terms of this top, what's most important is the V2 or Type 2 receptors that are located in the basal lateral surface of the collecting duct.

00:34 That's what mediates water reabsorption.

00:36 So again, we've got ADH, it binds to the basal lateral surface of that V2 receptor.

00:41 It then causes stimulation of aquaporin channels into the apical membrane of the collecting duct to cell.

00:48 ADH can also bind to V1A or Type1 A receptors that are located in the vasculature and help to control vascular tone.

00:56 If you recall in the ICU in the critical care setting, we oftentimes use vasopressin as a vasopressor and our patients.

01:05 so we just talked about before how there's two main mechanisms that stimulate ADH release from that posterior pituitary.

01:12 One is an osmotic mechanism, meaning that our osmolarity gets high, and our body knows that we need to actually drink more water to bring that osmolarity down low.

01:21 So that's our osmotic stimulus.

01:24 The other is a nonosmotic stimulus.

01:27 Stimulated by a decrease in volume.

01:29 So let's go over what that means.

01:31 In the Osmo regulation, things like serum osmolarity, when that gets high, that's sensed our sensors, our hypothalamic, osmoreceptors.

01:41 When they sense an increase in osmolarity they will then produce and release ADH.

01:48 ADH then acts at that kidney in order to insert those aquaporin channels so we reabsorb water.

01:53 And at the same time we get thirsty, so we will drink water.

01:59 In the situation of volume regulation, if we have too little volume, then remember our body wants to preserve that vascular tone in that vascular volume.

02:08 So it wants us to reabsorb water.

02:12 What's actually sensed is the effective tissue perfusion.

02:16 So the actual sensors or our Macula densa our afferent arterial, our atria, and our carotid sinus.

02:24 Our effectors are going to be the Renin Angiotensin Aldosterone System.

02:28 So if I have too little perfusion, RAAS is going to be activated in order to reabsorb sodium.

02:34 Atrial natriuretic peptide, and some of the ANP related peptides are going to be suppressed.

02:39 We want to preserve our sodium.

02:42 And then norepinephrine will be stimulated in order to increase vascular tone.

02:45 And finally, ADH will be released.

02:48 Why? Because ADH will help us reabsorb water and in concert with everything else, sodium, vasoconstriction we can preserve our vascular volume.

03:00 So this is a graphical representation of what I'm talking about and the relationship between ADH release and these two different mechanisms.

03:07 So on the left, what we can see is a graph on the y-axis of plasma ADH.

03:13 The x-axis is plasma osmolality.

03:16 So these were human subjects that basically were restricted from water.

03:20 And as their osmolarity rises, you can see that there is a reliable relationship between ADH release.

03:27 So at about 285 to 290 mOsm/kg, we can see that ADH is released.

03:33 Remember, what happens when ADH is released is not only do we have those aquaporin channels that are inserted to reabsorb water.

03:40 We also get very thirsty.

03:42 So we're going to consume more water.

03:45 Now, on the graphical representation on the right, this was actually an experiment done in rats, where they manipulated the total blood volume of rats.

03:53 So on the y-axis, we have plasma ADH again, and on the x-axis, here we have blood volume depletion.

04:01 And you can see that when rats were depleted by about 10% of their total body volume, that we have an increase in ADH, and this mechanism is so important that it will supersede osmolarity.

04:14 Meaning that if our patients are hyperosmolar, but they have their total body volume is low, ADH will still be released even though they have a low osmolality.

04:25 So it's a very important concept to understand.