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 it's a bit 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 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 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 going to 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 want to 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 a stimulus or a change that happens in the body we're going to have sensors our body has to detect that something is wrong or something value has changed then we're going to 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 effectors these are going to be the ways in which the body is able to bring that value back to the set point 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 another stimulus for 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 the 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 so if there's 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 your body has to sense that something is not where it's supposed to be so one of the ways we do that is through baroreceptors and nephrons that word baroreceptor barrow 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 juxta juxta glomer the juxta glomerular cells in the afferent arterials fun fact I had like five takes on that because juxta glomerular 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 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 juxtagomerular cells again those are in the afferent arterial those are going to utilize stretch receptors so as the blood's 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 we've got a other sensor that we need to look at first so those Barrel receptors 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 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 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 chemoreceptors down to those baroreceptors or juxtaglomerular cells and then those juxical mirror cells will do the next part of this process so again if there's a sodium deficiency that's detected by chemoreceptors in the nephron specifically the macula densa 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 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 II 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 diagram right here is all about we have three organs that are involved in this process one's 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 hence the a saddy 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 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 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 chemoreceptors 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 convert it into thing called Angiotensin one 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's not doing this renin is going to interact with the chemical and cause it to react and become some new chemical hence renin is an enzyme and its job is to convert angiotensinogen into Angiotensin one that renin is coming from those juxtaglomerular cells so I keep saying the kidney but the specific cells if you need to know that are the juxtagomerular cells great so we have angiotensinogen one and it's going to do lots of great things throughout just kidding um it's also pretty inactive and so I've got a saddy face there Angiotensin one isn't going to have much effect throughout the body we've got to do another step and convert this into Angiotensin II which is going to be the active hormone so how do we convert Angiotensin one to Angiotensin II 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 one to two so that Ace is going to interact with Angiotensin one 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 it'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 and Ace inhibitor is a type of blood pressure medication that's going to inhibit or block Ace from doing its thing and converting Angiotensin one to two and if we block that process from happening we block all of these effectors which are going to 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 chronic hypertension then an Ace inhibitor is a common type of blood pressure medication which 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 II do exactly well it does a lot of things and 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 the adrenal gland of course sits on top of the kidney right there and so Angiotensin II 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 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 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 re-uptake or reabsorbing of sodium to keep it in the bloodstream that 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 henle down here and then this is the distal convoluted tubule there's a lot of things happening on 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 as 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 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 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 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 right 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 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 II that's going to Target the adrenal gland the adrenal gland is then going to produce more aldosterone the aldosterone everyone's going to work on the distal convoluted tubule to increase sodium reabsorption and if there's more sodium being reabsorbed there's more water being reabsorbed and that's going to cause an increase in blood volume and increase in blood pressure and of course an increase in the sodium levels in our blood all right 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 II will also just directly act on the nephron sort of bypass the adrenal gland 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 increase that sodium reabsorption so back here in this diagram we have the proximal convoluted tubule right here and Angiotensin II is going to Target that and cause an increase of sodium being released from that proximal convoluted tubule back into the kidney and therefore the bloodstream so aldosterone is working here on the distal convoluted tubule and then Angiotensin II on the proximal convoluted tubule those two things both doing that is going to cause a lot more salt to get reabsorbed into the bloodstream all right what else does Angiotensin to do then next it's going to Target actually a little part of your brain called the pituitary gland more specifically the posterior pituitary that's going to 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 antidiuretic hormone anti-diuretic diuretic means to like produce more urine anti means 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 present for pressure so again regulating 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 tubule and the collecting duct to become more leaky to water and 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 all right that's a lot of things so far let's do a quick recap here of Angiotensin II and what it does remember it's going to Target the adrenal gland to produce aldosterone that's going to increase sodium reabsorption in the distal tubule Angiotensin II is also going to work directly on the nephrons of the kidney to increase sodium reabsorption in the proximal convoluted tubule and Angiotensin II is going to Target the posterior pituitary causing it to release ADH which is going to increase water reabsorption in the distal convoluted tubule on the collecting duct all of 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 all right what else does Angiotensin II 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 and it's going to cause those to constrict if the blood vessels constrict that's going to increase the pressure now 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 arterials and that's going to cause an increase in blood pressure 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 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 to your fight or flight response to work to increase your blood pressure as well all right 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 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 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 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 II is going to cause an increasing glomerular filtration rate and it's going to do that by constricting the afferent arterials and sort of pushing more blood into the glomerulus so let's jump back to our kidney diagram here we've got the afferent arterial as well as the efferent arterial so that's going to cause pressure on these which is 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 all that's going to just 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 II 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 all right 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 of the nephrons will detect the decrease in blood volume or blood pressure that's going to be taking place in the juxtaglomerular cells and the afferent arterioles of nephron we've got chemoreceptors in the nephron which would detect a lack of sodium that's going to be in the macula densa of the distal convoluting tubule and that macula density is going to send a signal to those juxtaper cells now those jux glomerular cells in the kidney are going to release a enzyme called renin meanwhile the liver has produced some angiotensinogen which is an inactive hormone a precursor to Angiotensin II 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 II which is a very active hormone that's going to do all of these other effectors throughout the body and so we'll go through what all those are angiotensinogen 2 will tell the adrenal gland to produce aldosterone that's going to cause an increase in sodium reabsorption and the distal convoluted tubule of the Nephron the angiotensinogen 2 will also just Target the proximal convoluted tubule of the Nephron causing increase in sodium reabsorption both of those things cause an increase in water reabsorption reabsorb more sodium we're going to reabsorb more water and then that increase in water absorption will increase our blood volume and blood pressure counteracting our initial stimulus or change in where that value is Angiotensin 2 also do several other things including targeting the posterior pituitary to release ADH which is going to make the distal convoluted tubule and a collecting duct more permeable to water therefore more watery absorption and raising the blood pressure and blood volume Angiotensin Engine 2 is also going to Target the arterials and cause vasoconstriction or a tightening of those arterials increasing our blood pressure that's also going to cause an increase in our sympathetic nervous system 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 and 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 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 Alana do you want to hear a joke I used to have four kidneys but now two of them are adult knees all right I've got a lot more Anatomy content don't forget to like And subscribe and all that I want to keep making more Anatomy videos and hopefully I'll see you in the next one bye you look confused why I did that