Renin-Angiotensin-Aldosterone System (RAA System) | Made easy with a step-by-step explanation!

[00:00] The renin-angiotensin-aldosterone system is a homeostatic negative feedback loop system in the body that regulates your blood pressure as well as your blood volume and sodium levels throughout the body. It's going to involve the kidneys and a bunch of other organs. It's going to involve a lot of hormones, a few enzymes, and when you look up a diagram of it it looks something like this.

[00:20] But overwhelming at first. But in this video, we're not going to look at the whole diagram all at once. We're going to take it step by step and build this out, and at the end you have a chance to practice. So by the end of this video, you're going to know the RAA system like the back of your hand. And whenever your blood pressure drops a little bit low and your body has to work to bring that back up to normal levels, you'll know exactly what's going on.

[00:40] throughout the body. So without further ado, let's jump to the whiteboard and get started. One quick thing before we dive in, I'm gonna be referencing the parts of a nephron throughout this video. So if you're not familiar with the nephron and how it works, I've got a video on that that you might wanna check out. So like I said, the RAA system is really a negative feedback loop or homeostasis loop. Anytime we have a homeostasis loop, we're gonna have to look at it in terms of four things. We've got some examples of that.

[01:00] at a stimulus or a change that happens in the body. We're gonna have sensors. Our body has to detect that something is wrong or something value has changed. Then we're gonna have some integration which is where usually we compare that value to a set point but there's some mechanism I'm saying like hey something's wrong let's figure out what to do to change to bring that value back to where it needs to be. And then we'll have a

[01:20] These are going to be the ways in which the body is able to bring that value back to the setpoint. So what are the stimuli that could initiate this RAA system? Well I said this is all about regulating blood pressure and blood volume. So our blood is made mostly of water. And whenever our water levels in the body drop, such as like when we're dehydrated, that's going to be one of the stimuli that kicks the system into place.

[01:40] Another stimulus for the system is going to be blood loss. So let's say we have some hemorrhaging going on, some blood is leaving the body, and so our blood volume is decreasing. That's going to get this system kicking into gear. This system is also going to help regulate the sodium levels in the body, and so whenever we have a sodium deficiency that's going to stimulate the system to become more active as well.

[02:00] dehydration or blood loss that's going to cause a decrease in blood volume, there's just going to be less fluid in the blood or less blood in the body, that's also going to lead to a decrease in blood pressure. So if there's less volume of blood there's going to be a lower pressure of that blood pushing on the artery walls. So first thing our body has to sense that something is not where it's supposed to be. So one of the ways we do that is through Barrow

[02:20] receptors and nephrons. That word baroreceptor means pressure, receptor just means it's going to be a place that's going to sense that. And so these baroreceptors will sense that the blood pressure has decreased. Those are in the nephrons and more specifically those are in the juxtaglomerular cells in the afferent arterial.

[02:40] Fun fact, I had to do like five takes on that because juxtaglomerular is pretty tough to say, I think. So let's break that down. Juxta means right next to like juxtaposition. And glomerular is referring to the glomerulus, which is the site of filtration in the nephron. Here's my diagram of the nephron. This is going to be the afferent arterial. Here is the glomerulus.

[03:00] where fluid from the blood is filtered out, and then here's the efferent arterial. So those juxtaglomerular cells are going to be right in here in this afferent arterial. And here's a more anatomically correct diagram of this. So here are the juxtaglomerular cells. Again, those are in the afferent arterial. Those are going to utilize stretcher

[03:20] receptors. So as the blood is traveling through, if these cells are sort of stretching or pulling apart, that's a way that it detects that the blood pressure is high. And if there's very little stretch happening, that's a way to detect that the blood pressure is low, which is what we're looking at in this case. So when those juxtaglomerular cells detect that the blood pressure is low, they're going to send out something called renin, but we're not to that yet on the diagram.

[03:40] We've got another sensor that we need to look at first. So those baroreceptors will detect what's going on whenever the blood volume and pressure decreases and that's because of dehydration or hemorrhaging or something like that. But what about a sodium deficiency? We have to have a different way to detect that. And so that's going to occur by chemo receptors in the nephron. Chemo means chemical, right? And so the chemical that it's detecting is the blood pressure.

[04:00] or in this case not detecting, is the sodium. Those receptors are going to be found in something called the macula densa. The macula densa is also really close to the glomerulus. It's actually in the distal convoluted tubule. Here's that diagram from before and this right here is the distal convoluted tubule and these are the macula densa cells. They have receptor

[04:20] receptors for sodium and they'll detect how much sodium is passing through that area. And if that sodium level gets low, they're going to signal actually to the juxtaglomerular cells and tell them, hey, the sodium is low. So if you look at the diagram, I've got an arrow drawn from the chemo receptors down to those baroreceptors or juxtaglomerular cells.

[04:40] the juxtaglomerular cells will do the next part of this process. So again, if there's a sodium deficiency that's detected by chemo receptors in the nephron, specifically the maculodensa, or if the blood volume and blood pressure is low, that's going to be detected directly by the baroreceptors in the nephron. And those juxtaglomerular cells are going to do the next part in this process. But before we get into that, we've got to talk about

[05:00] got a little bit of setup to do in the integration part right here. So this is going to be taking place in the bloodstream and really what we're setting up here is almost like an assembly line to produce a chemical called angiotensin 2. That's going to be the main hormone that's going to travel throughout the body and cause lots of different effectors to work to bring our blood pressure up, but we got to make that first and that's what this part of our diet

[05:20] diagram is all about. We have three organs that are involved in this process. One is the liver, second is the kidney, and then the lungs. The kidney is going to be the main organ in all of this, but the liver and the lungs are going to produce some important chemicals as well. So let's start with this. The liver is going to be producing something called angiotensinogen. So what does angiotensinogen do? Well, it doesn't do much.

[05:40] Hence the fatty face right here. It's an inactive hormone. So it's not going to have any effects, but we need to have it present because we're about to turn it on or convert it into a form that is active. But first let's break down the name. Angio is always referring to blood vessels and then tense right there is going to be talking about tension or pressure. So this is going to be a hormone that's involved.

[06:00] in blood pressure, which makes sense. That's what we're regulating here. And the gen at the end is usually referring to something that's inactive but it's going to become active soon. So this is going to be a blood pressure hormone that's not active but will be active soon. When does the liver produce this? Well it's just sort of always producing this. We've always got an amount of this ready to go. And then the kidneys where the real

[06:20] regulation is going to happen. Whenever those juxtaglomerular cells in the kidney either detect that the blood pressure is low or they've received a signal from the chemo receptors in the macula densa saying that the sodium levels are low, then the kidney is going to release an enzyme, not a hormone, this is an enzyme called renin, and renin is going to work to take the angiotensinogen and

[06:40] convert it into something called angiotensin I. Okay, why is renin not a hormone? Well, a hormone is going to travel somewhere to a target cell and cause some effect to happen, but renin is not doing this. Renin is going to interact with a chemical and cause it to react and become some new chemical. Hence, renin is an enzyme and its job is to convert angiotensin into

[07:00] angiotensin I. That renin is coming from those juxtaglomerular cells. I keep saying the kidney, but the specific cells, if you need to know that, are the juxtaglomerular cells. Great. We have angiotensinin 1 and it's going to do lots of great things throughout... just kidding. It's also pretty inactive and so I've got a saddy face there. Angiotensin 1 isn't going to have much effect throughout

[07:20] body. We've got to do another step and convert this into angiotensin 2, which is going to be the active hormone. So how do we convert angiotensin 1 to angiotensin 2? We're going to use something called the angiotensin converting enzyme, so another enzyme. I abbreviated ACE here, but again that's angiotensin converting enzyme because it converts angiotensin 1 to 2.

[07:40] ACE is going to interact with angiotensin I, converted to angiotensin II, and this time it gets a special little squiggle mark around it as well as a very happy face because this is going to be a very active hormone that's going to cause lots of effects throughout the body. Now the ACE part here might sound a little bit familiar if you've heard of an ACE inhibitor. An ACE inhibitor is a type of blood pressure medication.

[08:00] that's gonna inhibit or block ACE from doing its thing and converting angiotensin 1 to 2. And if we block that process from happening, we block all of these effectors, which are gonna work to raise the blood pressure, in this case, back up to where it's supposed to be. But if you have chronic high blood pressure, or chronic hypertension, then an ACE inhibitor is a common type of blood pressure medication,

[08:20] prevents your body from bringing the blood pressure up too high. So that would work by blocking this process right here. So what does angiotensin 2 do exactly? Well, it does a lot of things. In this right side of the diagram is about to get a little bit wild. Let's take it step by step. First we need to add another organ to our diagram and that's going to be the adrenal gland.

[08:40] of the kidney right there. And so angiotensin 2 is going to travel to the adrenal gland and it's going to stimulate the adrenal gland to produce a hormone called aldosterone. That aldosterone is going to travel from the adrenal glands to the kidneys and it's going to cause an increase in sodium reabsorption in the nephrons. So the nephrons are going to filter fluid and things like

[09:00] sodium out of the blood and then that stuff gets, most of that stuff gets reabsorbed back into the bloodstream. Well this is going to cause more and more of that to get reabsorbed back into the bloodstream, therefore conserving the sodium in our blood. Remember one of the things we might be trying to correct is a sodium deficiency in the bloodstream. So this is going to cause there to be an increased

[09:20] reuptake or reabsorbing of sodium to keep it in the bloodstream. Then aldosterone is going to work primarily on the distal convoluted tubule. So let's jump back to our nephron diagram and take a look at where that's going to be. So here we have the glomerulus, the proximal convoluted tubule, we've got the loop of henley down here, and then this is the distal convoluted tubule. There's a lot of things happening

[09:40] all these parts. Let's take a look at that. In the distal convoluted tubule, one of the things taking place here is sodium and chloride is being actively transported out of that distal convoluted tubule back into the medulla where it's very salty and that aldosterone is going to stimulate that to increase. So we have more sodium traveling out of the distal convoluted tubule back into the medulla.

[10:00] the medulla of the kidney. Now that's also really important for water reabsorption. Wherever there's more salt, water is going to move in that direction through the process of osmosis. And if you look throughout this whole nephron here, there's lots of parts where water can leave from the nephron, from the proximal convoluted tubule, the loop of Henle, even

[10:20] If the right hormones are present, the distal convoluted tubule and the collecting duct. So if we've increased the amount of sodium here, that's going to also increase the amount of water that's being pulled out of the nephron and back into the medulla and therefore back into the bloodstream. So as a general rule, if we reabsorb more sodium into the bloodstream,

[10:40] that's going to pull more water back into the bloodstream. So back to this main diagram, I've got that drawn in. If we increase sodium reabsorption, that's also going to increase water reabsorption, which of course is going to work to increase our blood volume. We're pulling more water back into the blood so we have more volume of blood and that's also going to increase our blood pressure. If we have more blood volume, we're going to have more

[11:00] blood pressure pushing on the blood vessel walls. So that's one of the most important effectors of this process. Again, once we've created angiotensin 2, that's going to target the adrenal gland. The adrenal gland is then going to produce more aldosterone. The aldosterone is going to work on the distal convoluted tubule to increase sodium reabsorption. And if there's more sodium being reabsorbed, there's

[11:20] more water being reabsorbed, and that's going to cause an increase in blood volume, an increase in blood pressure, and of course an increase in the sodium levels in our blood. Alright, what else does angiotensin 2 do? Because you know, that's not it. There's a bunch of things. So let's take a look. The second thing is angiotensin 2 will also just directly act on the nephron, sort of bypass the adrenal gland

[11:40] altogether, it's going to increase sodium reabsorption as well, but in a different spot. It's going to work on the proximal convoluted tubule to increase that sodium reabsorption. So back here in this diagram, we have the proximal convoluted tubule right here, and angiotensin 2 is going to target that and cause an increase of sodium being released from that proximal convoluted tubule back into the kidney and the ileus.

[12:00] there for the bloodstream. So aldosterone is working here on the distal convoluted tubule and then angiotensin 2 on the proximal convoluted tubule. And those two things, both doing that is going to cause a lot more salt to get reabsorbed into the bloodstream. Alright, what else does angiotensin 2 do? Then next it's going to target actually a little part of your brain called the pituitary gland, more specifically the posterior pituitary.

[12:20] That's gonna be the little homeostatic regulation center that's hanging off sort of the front part of the brain. It's connected right there to the hypothalamus. There's the anterior pituitary and the posterior pituitary. That's going to stimulate the posterior pituitary to release something called ADH or anti-diuretic hormone. Anti-diuretic. Diuretic means to like produce more urine. Anti means

[12:40] to not do that. So antidiuretic hormone causes you to produce less urine, which is therefore going to keep more of that fluid not in your urine, but in your bloodstream, working to raise your blood pressure and blood volume. Basically the same thing that all of these effectors have been doing. Another name for ADH is vasopressin, which vaso is referring to your blood vessels, pressin for pressure. So again, regulate.

[13:00] your blood pressure here. The ADH is going to regulate the reabsorption of water in the nephron. So let's jump back to the nephron again. Water will leave the distal convoluted tubule as well as the collecting duct, but only if ADH is present. So when the pituitary gland produces the ADH, it travels down here, it's going to interact with receptors here and cause the distal convoluted

[13:20] tubule and the collecting duct to become more leaky to water or more porous to water. More water is going to leave and go back into the bloodstream which of course is going to raise our blood pressure back up. And again that's happening in the distal convoluted tubule and the collecting duct. Alright that's a lot of things so far. Let's do a quick recap here of angiotensin 2 and what it does. Remember it's going to target the adrenal gland to produce aldosterone.

[13:40] That's going to increase sodium reabsorption in the distal tubule. Angiotensin 2 is also going to work directly on the nephrons of the kidney to increase sodium reabsorption in the proximal convoluted tubule. And angiotensin 2 is going to target the posterior pituitary, causing it to release ADH, which is going to increase water reabsorption in the distal convoluted tubule and the collecting duct.

[14:00] that's going to cause more water reabsorption, therefore an increase in blood volume and blood pressure, bringing those variables back to where they're supposed to be. Alright, what else does angiotensin 2 do? The next thing is it's going to cause vasoconstriction. So the angiotensin 2 is going to travel throughout the body and it's going to target receptors on the muscles of the blood vessels.

[14:20] muscles and it's going to cause those to constrict. If the blood vessels constrict, that's going to increase the pressure. Now in this case, this doesn't really help the blood volume. It's not causing more fluid to be in the blood, but it is causing an increase in the pressure because the arteries are constricting a little bit. So it's going to cause vasoconstriction in the arterioles and that's going to cause an increase in blood pressure.

[14:40] Notice I didn't say an increase in blood volume, just an increase in blood pressure from that particular effector. What else does it do? It's also going to target the brain and cause an increase in your sympathetic nervous system. Your sympathetic nervous system is your fight-or-flight system. So this causes a bunch of changes throughout the body, things like your heart beating faster and harder, you becoming more alert and aware. A bunch of things that are

[15:00] all going to cause an increase in your blood pressure. So that's going to circle back up to there as well, increasing your sympathetic nervous system response, your fight or flight response to work to increase your blood pressure as well. Alright, those are all of the effectors that are going to work to increase your blood pressure, your blood volume, and your sodium levels back to where they're supposed to be. There's one more effector I want to talk about, but it's actually one that's not

[15:20] going to help regulate this blood volume, blood pressure, and sodium levels back to where they're supposed to be. This is going to cause a different effect. So let's think about this. If you are dehydrated or if you have lost a lot of blood and your blood pressure has dropped, in the glomerulus in your kidney, you still need to be filtering waste out. So even though your blood pressure is low, you still need to be filtering waste out. But the problem is

[15:40] if your blood pressure is dropped the filtration rate drops way down as well. So we need a way to cause the filtration rate to stay high even if you've lost blood. We still need to be filtering out waste and other chemicals that we want to get rid of. So how can we make sure that glomerular filtration rate stays high? Well the angiotensin 2 is going to cause an increase in glomerular filtration rate and it's going to

[16:00] do that by constricting the afferent arterioles and sort of pushing more blood into the glomerulus. So let's jump back to our kidney diagram here. We've got the afferent arteriole as well as the efferent arteriole. So that's going to cause pressure on these, which is going to push more blood into the glomerulus, as well as putting more pressure right there, which is going to prevent blood from leaving the glomerulus.

[16:20] All of that is going to cause more blood to be right here and therefore more blood plasma to be filtered out of the glomerulus into that Bowman's capsule and through the rest of the nephron. So that angiotensin 2 is causing that increase in pressure in these arterioles, therefore increasing the glomerular filtration rate and trying to keep it back where it needs to be, even more dehydrated or losing blood.

[16:40] blood. Alright, pretty simple right? You got it? Not yet? I'm going to do two things now. One is I'm going to go back through this whole process and re-explain it again and then I'm going to give you a blank diagram where you can practice it. Let's do a quick recap. This whole process starts by detecting a change in blood pressure, blood volume, or sodium levels. And so baroreceptors in the nephrons will detect the decrease in blood volume or blood blood.

[17:00] pressure that's going to be taking place in the juxtaglomerular cells and the afferent arterioles of the nephron. We've got chemo receptors in the nephron which would detect a lack of sodium that's going to be in the macula densa of the distal convoluted tubule and that macula densa is going to send a signal to those juxtaglomerular cells. Now those juxtaglomerular cells in the kidney are going to release an enzyme called renin.

[17:20] Meanwhile, the liver has produced some angiotensinogen, which is an inactive hormone, a precursor to angiotensin 2. The renin is going to convert that angiotensinogen into angiotensin 1, which is still an inactive hormone. And then angiotensin-converting enzyme, which is made by the lungs, is going to convert angiotensin 1 into angiotensin 2, which is a very

[17:40] active hormone that's going to do all of these other effectors throughout the body and so we'll go through what all of those are. angiotensin-2 will tell the adrenal gland to produce aldosterone that's going to cause an increase in sodium reabsorption in the distal convoluted tubule of the nephron. The angiotensin-2 will also just target the proximal convoluted tubule of the nephron causing increase in sodium reabsorption.

[18:00] Both of those things cause an increase in water reabsorption, reabsorbed more sodium, reabsorbed more water, and then that increase in water reabsorption will increase our blood volume and blood pressure, counteracting our initial stimulus or change in where that value is. angiotensin 2 will also do several other things, including targeting the posterior pituitary to release an increase in water reabsorption.

[18:20] ADH, which is going to make the distal convoluted tubule and the collecting duct more permeable to water, therefore more water absorption and raising the blood pressure and blood volume. Angiotensin engine 2 is also going to target the arterioles and cause vasoconstriction or a tightening of those arterioles, increasing our blood pressure. That's also going to cause an increase in our sympathetic nervous system.

[18:40] our fight-or-flight response. Both of those things are going to cause an increase in blood pressure, bringing our blood pressure back up to where it should be. And angiotensinogen 2 is also going to work to increase our glomerular filtration rate back to where it's supposed to be so that we're still filtering fluid and waste and stuff out of our bloodstream and getting rid of that waste, even as our blood pressure

[19:00] blood volume is lower than we want it to be. Now there's two things I recommend doing to study and to learn this stuff really well. One is to pause the video right now on this image where I've got everything written out and go through and see if you can explain what's happening in every stage of the process here. Do that a few times until you know that really really well and you feel pretty confident with it. Then I've got a blank diagram. See if you can see.

[19:20] can go through and explain everything that's going on without everything just written out like that. And maybe a third thing for a third challenge is get rid of a diagram altogether and see if you can draw it out yourself from memory. If you can do that then you know this stuff really, really well. Alon, did you want to hear a joke? I used to have four kidneys, but now two of them are adult knees.

[19:40] Alright, I've got a lot more anatomy content. Don't forget to like and subscribe and all that. I'm going to keep making more anatomy videos and hopefully I'll see you in the next one. Bye. You look confused why I did that.