[0:08]What's up Ninja Nerds. In this video, we're going to be talking about renal auto regulation. Before we get started, please, if you guys benefit, you like this video, hit that like button, comment down in the comment section and most importantly, subscribe. All right, Ninja Nerds, let's get into it.
[0:22]All right, engineers, so let's start talking about renal auto regulation. What is renal auto regulation? It's just the ability of the kidney to modify its blood flow and modify the way how much blood flow it's getting, modify the urine output in a way.
[0:34]Okay, so how does it do that? There's two particular mechanisms by which the kidney regulates its blood flow, regulates its urine output, so on and so forth.
[0:44]It does it by itself, intrinsically, and there's two particular mechanisms that the kidney does on its own without any assistance, and that is called the first one is called the myogenic mechanism.
[1:07]It's a pretty simple and very effective one. The next one is actually regulated by the kidney tubules, okay? And it's called the tubulo glomerular feedback mechanism.
[1:23]Okay, so we have the first one which is the myogenic mechanism, and the second intrinsic mechanism is called the tubulo glomerular feedback mechanism. So these ones are again, it's the kidney's ability that any blood flow that's coming to the kidney, the kidney will sift through that and it's design is to be able to make urine.
[1:43]Okay? If the blood pressure is too high, you'll end up making too much urine. If the blood pressure is too low, you won't make enough urine.
[1:50]So how does the kidney be able to modulate it where you make an appropriate amount of urine? It can do it intrinsically via these two mechanisms. Now, the extrinsic mechanisms are a little bit different.
[2:00]So the kidney has to, it can do it, but it needs a little assistance from things outside of it. And what are those two things? Those two things, the extrinsic mechanisms, start kicking in whenever the blood pressure really becomes low.
[2:10]These extrinsic mechanisms really, really kick in whenever the blood pressure becomes precipitously low. The first one that we'll talk about is called the sympathetic, okay, your sympathetic nervous system.
[2:32]And then the second one here is called, we're going to abbreviate this one because it's a heck of a thing. I like to call it the Renin Angiotensin Aldosterone ADH system.
[2:45]The RAAS. Okay, so the Renin Angiotensin Aldosterone ADH system or access if you will. And again, these are the different mechanisms that we're going to go into great detail of.
[2:58]So let's start first with the myogenic mechanism and then work our way through understanding how the kidneys regulate its blood flow and then therefore urine output or glomerular filtration. Okay?
[3:09]All right, ninjas, let's start talking about the different intrinsic mechanisms, particularly the myogenic mechanism. So myogenic muscle, so there's going to be some muscle involvement here. It's actually really straightforward, pretty simple process.
[3:21]And so we're going to talk about two scenarios. One is how the muscles of the afferent arterial, kind of giving it away here, modulate blood flow to the kidney of the glomerulus particularly, whenever there's high blood pressure and how they do it whenever there's low blood pressure.
[3:34]So here's the first thing I want you to remember. We talked about this in glomerular filtration, but basically the concept is that blood pressure is kind of a surrogate for glomerular hydrostatic pressure.
[3:45]So whenever the blood pressure is higher, you can say that there is a higher kind of glomerular hydrostatic pressure if you will. And if you remember glomerular hydrostatic pressure is the pressure inside of the capillaries that's exerted to push things like plasma and solute components out of the capillaries and into this thing called the Bowman's capsule.
[4:06]That's what it is. So effectively, the higher the glomerular hydrostatic pressure, assuming all other things remain constant like the oncotic pressure, capsular, all that stuff like that, we would say that there would be an increase in the glomerular filtration rate.
[4:23]All right? Now, that's what would happen, you have a higher glomerular filtration, you'd make more urine. Now, your kidneys try to modulate this a little bit to where it's not too excessive.
[4:30]Well, you're not making too much urine or that the pressure doesn't remain too high that you cause a lot of injury and, you know, exertion of effect on these actual glomerular capillaries. So how does it do this?
[4:45]All right, whenever there's high blood pressure, okay? You know the structures here of this little diagram, this is your afferent arterial. This is the glomerulus, we'll denote this with like a G here. This is the efferent arterial. This green thing here is called the Bowman's capsule and this first part here of the tubules is called the proximal convoluted tubule here, right?
[5:07]Well, you know blood flow it moves through the afferent arterial and then exits out the efferent arterial. Whenever there's high blood pressure, okay? So there's high blood pressure, we already know that it's going to cause higher glomerular hydrostatic pressure, you'll cause more filtration to come out of these glomerular capillaries and more blood to come, more urine to be made via an increased in glomerular filtration.
[5:31]Now, how do we counteract this? Here's what happens. As more higher blood pressures are occurring, there's more blood that's flowing through, there's a higher pressure in the afferent arterial. Imagine we zoom in on one of those smooth muscle cells and look and see what happens here.
[5:46]If there's higher blood pressure, what this is going to do is this high blood pressure is going to exert a lot of force and pressure and stress and stretching on the smooth muscle cells of the afferent arterial. So as a result, these bad boys are going to have an increase in stretch.
[6:03]Well, you know whenever there's stretched a lot, they have these like channels here that are sodium channels that are very sensitive to stretch. So whenever there's an increase in stretch, these sodium channels open and the sodium will flood in.
[6:16]When the sodium floods in, that makes the inside of the cell super positive, which is a stimulator towards it's called the sarcoplasmic reticulum, which is like a calcium storage within smooth muscle cells.
[6:27]When this is stimulated, it starts unloading that calcium into the smooth muscle cell, like it's going out of style. If there's lots of calcium inside of the smooth muscle cell from that increased stretch, what's going to happen? There's going to be more binding of myosin to actin and there'll be increasing contraction as a result of that.
[6:47]When you cause more smooth muscle cells of the afferent arterial to contract, it's going to induce what's called vasoconstriction, okay? So it's going to induce a vasoconstriction type of mechanism.
[7:00]Now, imagine that from that high blood pressure, these afferent arterials just clamp down. If they clamp down, what does that do to the amount of blood, the volume of blood that can run through the afferent arterial?
[7:13]Little hole, less volume. So there's going to be a lower glomerular blood flow, we'll put GBF here, right? That lower glomerular blood flow, if less blood is flowing through here, are you going to be able to make as much of that push as much of that plasma out here into the glomerular capsule? No.
[7:33]So low glomerular blood flow will result in a lower glomerular filtration rate. So as a result, there'll be less filtration here and there'll be a lower glomerular filtration rate as the corrective or compensation or auto regulatory mechanism here.
[7:52]Okay? So with that being said, with low blood pressure, it should be very easy now. It's the exact opposite here. Low blood pressure means an effective lower glomerular hydrostatic pressure, which would mean that there would be a lower GFR.
[8:08]So how do we counteract that? Because if the blood pressure is low, and this is where it's really the problem is when the blood pressure is low. If the blood pressure is low and we're not making urine, that can cause a kidney injury, right? We don't want that.
[8:21]So how does our kidneys try to help prevent that? Well, it's pretty smart actually. Again, to quickly recap here, this is the, this little diagram, this is our afferent arterial. Efferent arterial. This is our glomerulus here. This is our Bowman's capsule, proximal convoluted to be the first part here, right?
[8:37]We have blood flowing through the afferent arterial, exits via the efferent arterial. Now, the blood pressure is low. If there's low blood pressure, that means that there's less force or stress or stretching of the afferent arterial.
[8:50]So come back over here, zooming in on a smooth muscle cell here. If there is less stretch, okay? So there's a lower blood pressure that's less force and stretching on this actual smooth muscle cell.
[9:05]The stretch receptors, I mean the the sodium channels that are very sensitive to stretch, they're not going to be as sensitive now. So now less sodium is going to enter in into these smooth muscle cells.
[9:17]If less sodium enters into the smooth muscle cells, there's less positive charge. The sarcoplasmic reticulum ain't going to respond to no negative, you know, not as much positive charge. So it's going to be like, uh-uh, I'm not pushing calcium out.
[9:34]And so because of that, less calcium is present in the actual sarcoplasma. That means less interaction between actin and myosin and that means less contraction. Another way that I want us to think about this is that there's less contraction that also means that there's kind of more relaxation of the muscle, right?
[9:47]It's kind of like the the, you know, the the associated kind of opposite effect here. Less contraction meaning it's probably going to relax a lot more. If the smooth muscles relax within this vessel, we call this effectively vasodilation, okay?
[10:00]So we're going to effectively call this vasodilation. Now, vasodilation, imagine these blood vessels, the efferent arterial kind of plumping up, opening up really wide and allowing for larger volume of blood, more flow to run within that blood vessel.
[10:24]As a result here, now I'm going to have an increase, right, in the glomerular blood flow. If I have an increase in the glomerular blood flow, then I technically am going to have more filtration.
[10:41]And if that's the case, I should have an increase in GFR or an attempt to increase the GFR through this mechanism when the blood pressure is low. An easy way to summate all of this is what?
[10:58]When the blood pressure is high, it causes the GFR to go up. How do we counteract that? How do our kidneys do that? They undergo vasoconstriction.
[11:06]So high blood pressure triggers vasoconstriction, causing low GFR. Summating the low blood pressure, which is the more important thing. Low blood pressure leads to low GFR. That's a problem because then the kidneys can't make urine. That can lead to a kidney injury.
[11:21]How does our kidneys protect? That leads to vasodilation of the afferent arterial and an increase in the effective GFR. That covers the myogenic. Now let's cover tubulo glomerular feedback mechanism.
[11:35]All right, so we talked about the myogenic mechanism. Now let's talk about the tubulo glomerular feedback mechanism. So this one's a very cool one, okay? It can get it kind of complicated, but we're going to break it down to the simplest explanation.
[11:47]All right, so we have to talk about two scenarios, what happens in this mechanism when the blood pressure is too high, what happens when the blood pressure is too low. It's kind of the same thing we talked about with the the myogenic mechanism, that the same concept here if we get to it, is that a high BP, increased in glomerular hydrostatic pressure, effectively and ultimately, it results in an increase in the glomerular filtration.
[12:10]Low blood pressure, low glomerular hydrostatic pressure eventually, uh, it'll lead to a low glomerular filtration rate. Okay? So that's kind of the end result here, right?
[12:21]So we can kind of effectively kind of follow this out here that again, with our diagram here, this is our afferent arterial, this is our efferent arterial here, blood flows through here, through here, exits. And then there should be some filtration process here in the middle. Now, if you have low blood pressure, okay? You know, these JG cells respond to that. They say, man, there's some low blood pressure.
[12:40]That's not good. I need to try to get the blood pressure up. So what I'm going to do is, is I'm going to release a molecule called Renin. Because again, what was the issue? That low BP was resulting in lower glomerular hydrostatic pressure, it was resulting in low glomerular filtration, right?
[13:05]So we have to try to be able to fix this in some way, as well as increase the blood pressure so that we can try to perfuse the kidney a little bit more. We're going to try some mechanisms here, right?
[13:14]So when the Renin is released, Renin is kind of like a really cool enzyme. Your liver makes a very particular type of protein here. It's one heck of a name, but this protein that the liver makes is called angiotensinogen. And what happens is Renin is going to act like an enzyme.
[13:34]And it's going to actually kind of cleave a couple amino acids off of angiotensinogen. When it cleaves angiotensinogen, it converts it into a molecule called Angiotensin 1. Angiotensin 1 will then move to a capillaries within the lungs.
[13:58]And you know within the lungs, there's a very special enzyme that the lungs, uh, the capillary endothelium within the lungs have, which is called ACE, Angiotensin Converting Enzyme. And what this enzyme does is is it stimulates the conversion, it cleaves off a couple amino acids of Angiotensin 1 and converts him effectively into what's called Angiotensin 2.
[14:23]Now, this is our money maker here. This is where all of it starts to really just happen. Angiotensin 2 does so many different things. What are some of the things that he does?
[14:34]Okay, first one, let's kind of drag him over here. So the first thing is we're going to kind of see what it does here to your central nervous system. The central nervous system has a very particular structure in this area, the hypothalamus, and then it has a structure that hangs here called the pituitary gland, right?
[14:52]When this stimulates the hypothalamus, it stimulates the posterior pituitary and triggers the release of a very special type of hormone called ADH. There's going to be an effective increase in this hormone.
[15:05]It actually stimulates particular cells within the hypothalamus that trigger the release of ADH from the posterior pituitary. ADH is a very special hormone, it's also called vasopressin, anti-diuretic hormone, but what it does is is it acts on cells in the collecting duct.
[15:29]You know the cells within the collecting duct, uh, they're very, very impermeable to water. But what happens is when ADH is present, it puts these little aquaporins present inside of the actual tubular membrane. And then what happens is water can actually funnel into these actual tubular cells and into the actual bloodstream.
[15:43]So effectively, we get an increase in water reabsorption in the blood. And if there's an increase of water in the blood, that's going to increase your blood volume. And if you increase your blood volume, you increase your blood pressure.
[15:53]What was the issue? Low BP. If we increase the BP, we can actually get more blood flow to go to the kidney so that the kidney can increase its GFR effectively. Man, that's pretty cool, right? All right, what else?
[16:18]Another thing that the Angiotensin 2 does is it acts on the kidneys itself, right? And it works in a very particular way, two particular ways. So here we're going to have again, the afferent arterial on this end, the efferent arterial on this end. Now, remember, blood flows through the afferent arterial and likes to exit through the efferent arterial.
[16:26]Imagine that the efferent arterial is really small. So less blood can escape from the glomerulus, more blood will stay in the glomerulus. If more blood stays in the glomerulus, then more of it can be filtered out. There's a longer transit time.
[16:47]And so because of that, you are going to increase the glomerular filtration rate. It's kind of like a nice little protective mechanism that Angiotensin 2 has. Pretty cool, right? All right, what else?
[17:10]Angiotensin 2 can also, you know, another thing it also can do with the hypothalamus if you really want to remember here. It can also just make you thirsty. And if you have a, you have an increase in thirst, you'll drink more water. You drink more water, you increase your blood volume, you increase your blood pressure, and increase the GFR, right?
[17:19]But anyway, it also can act on the adrenal cortex, okay? So we'll put here the adrenal cortex, particularly what's called the Zona Glomerulosa. You know the cells that make up a particular hormone called Aldosterone.
[17:39]Now, Aldosterone likes to work on a very particular area, which is also relatively impermeable to sodium and water naturally. And this is the distal convoluted tubule, right? This was the collecting duct, okay? The collecting tubule, the collecting duct, this is the distal convoluted tubule, this portion here.
[18:00]Aldosterone acts on these distal convoluted tubule cells and makes them permeable to sodium and makes them permeable to water. So then you reabsorb sodium and you reabsorb water into the bloodstream. So if I reabsorb more sodium and water into the bloodstream, I increase sodium. I increase water. I increase blood volume. I increase blood pressure.
[18:14]Again, if I increase blood pressure, I increase perfusion to the kidney, and increase GFR. Woo. That's all of the effects here. The only other thing that we have to think about now, is something very interesting.
[18:49]Okay, the opposite effect. When there's high BP, when there's high BP, this entire thing here, it just doesn't work. We don't release Renin. We don't cause Angiotensinogen to be converted into Angiotensin 1, Angiotensin 2. And all the effects of Angiotensin 2 don't occur here.
[19:05]Okay? And if that doesn't happen, then we're not going to have all of the things that we just talked about occur. It's a pretty straightforward kind of process here. The only other thing that I do want you to remember, is that when there is an increase in blood pressure, it can cause the heart to release a very particular type of molecule from the atria.
[19:27]And it's called atrial natriuretic peptide. And atrial natriuretic peptide will just basically, here's what I want you to remember, oppose or block any function of Angiotensin 2. So watch this. Angiotensin 2 is going to block each part here.
[19:40]It is going to block Renin release. If it blocks Renin release, it blocks Angiotensin 1 being formed, Angiotensin 2 being formed. And so all the effects of Angiotensin 2 don't occur here. Secondly, it also can directly affect the blood vessels. Atrial natriuretic peptide will cause vasodilation of the blood vessels, lower your systemic vascular resistance, and lower your blood pressure. Man, we good.
[20:00]All right, Ninja Nerds, that covers renal auto regulation.
